Emolientes y humectantes para el eczema
Información
- DOI:
- https://doi.org/10.1002/14651858.CD012119.pub2Copiar DOI
- Base de datos:
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- Cochrane Database of Systematic Reviews
- Versión publicada:
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- 06 febrero 2017see what's new
- Tipo:
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- Intervention
- Etapa:
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- Review
- Grupo Editorial Cochrane:
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Grupo Cochrane de Piel
- Copyright:
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- Copyright © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Cifras del artículo
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Autores
Contributions of authors
EvZ was the contact person with the editorial base.
EvZ co‐ordinated contributions from co‐authors and wrote the final draft of the review.
EvZ and ZF screened papers against eligibility criteria.
EvZ and ZF obtained data on ongoing and unpublished studies.
EvZ translated German and French studies.
EvZ and ZF assessed 'Risk of bias' of the studies.
EvZ and ZF extracted data for the review and sought additional information about papers.
EvZ and ZF entered data into RevMan 5.
EvZ, ZF and RC analysed and interpreted data.
EvZ, ZF and RC worked on the methods sections.
EvZ, ZF, AL and BA drafted the clinical sections of the background and responded to the clinical comments of the referees.
EvZ, ZF, and RC responded to the methodology and statistics comments of the referees.
BA was the consumer co‐author and checked the review for readability and clarity, as well as ensuring outcomes are relevant to consumers.
EvZ is the guarantor of the update.
Disclaimer
This project was supported by the National Institute for Health Research (NIHR), via Cochrane Infrastructure funding and Cochrane Incentive funding to the Cochrane Skin Group. The views and opinions expressed herein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, National Health Service or the Department of Health.
Sources of support
Internal sources
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No sources of support supplied
External sources
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Oak Foundation, Denmark
The Parker Institute (RC) is supported by grants from the Oak Foundation, a philantropic/non‐profit organisation.
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The National Institute for Health Research (NIHR), UK
The NIHR, UK, is the largest single funder of the Cochrane Skin Group.
Declarations of interest
Esther J van Zuuren: nothing to declare.
Zbys Fedorowicz: nothing to declare.
Adriana Lavrijsen: nothing to declare.
Robin Christensen: nothing to declare.
Bernd Arents: nothing to declare.
Matthew Ridd (referee of the protocol): "I am chief investigator on a feasibility trial comparing four commonly used emollients in children with eczema (not yet published but likely to be included in this review). I have recently submitted an application for funding to take this study to a full trial."
Sandra Lawton (referee of the protocol): "I have received an honorarium for speaking at meetings from Genus, Almirall, and Thornton & Ross Ltd, and for reviewing an educational programme for Bayer."
Acknowledgements
We would like to thank Masaki Futamura from the Department of Pediatrics Nagoya Medical Center, Nagoya Japan for his translation of Hamada 2008 from Japanese into English.
We thank Kyung‐Hwa Seo, Senior Researcher, Research Institute for Healthcare Policy of Korean Medical Association, and Doctorate student, Department of Medical Sciences, Ewha Woman's University, Seoul, South Korea, for his translation of Noh 2011 from Korean into English.
We would like to thank Professor Ching‐Chi Chi from the Department of Dermatology & Centre for Evidence Based Medicine, Ms Yu‐Shiun Tsai, Department of Medical Education, and Dr Yu‐Jung Chen, Department of Traditional Chinese Medicine all from Chang Gung Memorial Hospital, Chiayi, Taiwan for the translation of Wu 2014; Yang 2010 from Chinese into English.
We would like to thank all principal investigators as well as pharmaceutical companies who were so helpful in addressing our questions and clarifying missing study details (see Table 2).
The editorial base of the Cochrane Skin Group wish to thank Hywel Williams, the Cochrane Dermatology Editor for this review; Thomas Chu, the statistical editor; Ching‐Chi Chi, the methods editor; the clinical referees, Sandra Lawton and Miriam Santer; and the consumer referee, Amanda Roberts, as well as Megan Prictor, who copy‐edited the protocol for the review, and Elizabeth Royle who copy‐edited the review.
Version history
| Published | Title | Stage | Authors | Version |
| 2017 Feb 06 | Emollients and moisturisers for eczema | Review | Esther J Zuuren, Zbys Fedorowicz, Robin Christensen, Adriana PM Lavrijsen, Bernd WM Arents | |
| 2016 Mar 11 | Emollients and moisturisers for eczema | Protocol | Esther J van Zuuren, Zbys Fedorowicz, Adriana Lavrijsen, Robin Christensen, Bernd Arents | |
Differences between protocol and review
We have added 'vehicle' as comparator under Types of interventions. For clarity, under Effects of interventions we added: "To ensure consistency with the terminology used by the investigators, we used the wording for placebo or vehicle accordingly. It is important to know that a placebo is also a moisturiser, but with a different composition and without the assumed effective ingredient; a vehicle has the same composition as the moisturiser it is compared with, but without the assumed effective ingredient. As both placebo and vehicle have moisturising properties they might have a beneficial effect on the skin barrier and thus might decrease disease severity."
The text under Measures of treatment effect, Unit of analysis issues (within‐participant studies), Assessment of heterogeneity and Assessment of reporting biases has been amended slightly to provide improved clarification, but without and substantive change made to the content.
We removed the last sentence Dealing with missing data "Whenever possible, we used results based on an ITT analysis" as this was already mentioned in first paragraph.
In the protocol we stated under Assessment of heterogeneity "However, based on the GRADE Working Group approach (GRADE) we will rate down for very serious inconsistency if the I² is above 75%". Rating down the quality of evidence also depends on how much other items have been downgraded. The GRADE Handbook states "Reviewers should grade the quality of the evidence by considering both the individual factors in the context of other judgments they made about the quality of evidence for the same outcome. In such a case, you should pick one or two categories of limitations which you would offer as reasons for downgrading and explain your choice in the footnote. You should also provide a footnote next to the other factor, you decided not to downgrade, explaining that there was some uncertainty, but you already downgraded for the other factor and further lowering the quality of evidence for this outcome would seem inappropriate" (Schünemann 2013). Therefore, we have made the following post hoc changes to the protocol; "However, based on the recommendations of the Grading of Recommendations Assessment, Development and Evaluation working group (GRADE) we considered rating down for serious inconsistency if the I² was above 50%, taking into account other considerations for rating down the quality of evidence."
The text under Data synthesis has changed slightly as although we planned to undertake meta‐analyses using Mantel‐Haenszel risk differences, this was not applicable. In future updates when we can perform meta‐analyses we will report results including 95% confidence intervals and forest plots for both Peto OR and Mantel‐Haenszel risk differences so that findings can be compared.
In the Subgroup analysis and investigation of heterogeneity we were not able to conduct our planned stratified analyses, as we had no studies that addressed disease severity (mild versus severe eczema), atopic versus non‐atopic eczema, or presence of filaggrin gene mutations versus no filaggrin gene mutations and, although some studies were conducted only in children and others only in adults, none of the comparisons allowed stratified analyses for age for the primary outcomes.
In the Sensitivity analysis section we planned to assess the influence of small‐study effects on the results of a meta‐analysis, but this was only applicable in Comparison 1 for the outcome 'amount of active topical treatment used' (Analysis 1.4). Also in this section we were not able to perform a stratified analysis to compare study results from preregistered trials (e.g. available on Clinicaltrials.gov) with those without an available prespecified protocol as planned because none of the studies included in meta‐analyses were preregistered.
Keywords
MeSH
Medical Subject Headings (MeSH) Keywords
Medical Subject Headings Check Words
Humans;
PICO
Study flow diagram
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
Risk of bias summary: review authors' judgements about each risk of bias item for each included study
Funnel plot of comparison 5: All moisturisers versus vehicle, placebo or no treatment (no moisturiser), outcome: 5.5 Change in disease severity as assessed by the investigators
Comparison 1: Moisturisers versus no treatment (i.e. no moisturiser), Outcome 1: Change from baseline in SCORAD
Comparison 1: Moisturisers versus no treatment (i.e. no moisturiser), Outcome 2: Number of participants experiencing a flare
Comparison 1: Moisturisers versus no treatment (i.e. no moisturiser), Outcome 3: Rate of flare
Comparison 1: Moisturisers versus no treatment (i.e. no moisturiser), Outcome 4: Amount of topical steroids used
Comparison 1: Moisturisers versus no treatment (i.e. no moisturiser), Outcome 5: Change from baseline in quality of life
Comparison 2: Atopiclair versus vehicle, Outcome 1: Number of participants who experienced good improvement to total resolution
Comparison 2: Atopiclair versus vehicle, Outcome 2: Change from baseline in itch measured on a VAS
Comparison 2: Atopiclair versus vehicle, Outcome 3: Number of participants reporting an adverse event
Comparison 2: Atopiclair versus vehicle, Outcome 4: Change from baseline in EASI
Comparison 2: Atopiclair versus vehicle, Outcome 5: Number of participants experiencing a flare
Comparison 3: Urea‐containing moisturiser versus vehicle, Outcome 1: Change from baseline in skin capacitance
Comparison 4: Glycerin cream versus placebo cream, Outcome 1: Number of participants reporting an adverse event
Comparison 5: Oat‐containing cream versus vehicle or no treatment, Outcome 1: Change in disease severity as assessed by the investigators (SCORAD and EASI)
Comparison 5: Oat‐containing cream versus vehicle or no treatment, Outcome 2: Change from baseline in quality of life
Comparison 6: All moisturisers versus vehicle, placebo or no treatment (no moisturiser), Outcome 1: Number of participants who experienced improvement
Comparison 6: All moisturisers versus vehicle, placebo or no treatment (no moisturiser), Outcome 2: Change from baseline in itch
Comparison 6: All moisturisers versus vehicle, placebo or no treatment (no moisturiser), Outcome 3: Number of participants who expressed treatment satisfaction
Comparison 6: All moisturisers versus vehicle, placebo or no treatment (no moisturiser), Outcome 4: Number of participants reporting an adverse event
Comparison 6: All moisturisers versus vehicle, placebo or no treatment (no moisturiser), Outcome 5: Change in disease severity as assessed by the investigators
Comparison 6: All moisturisers versus vehicle, placebo or no treatment (no moisturiser), Outcome 6: Number of participants experiencing a flare
Comparison 6: All moisturisers versus vehicle, placebo or no treatment (no moisturiser), Outcome 7: Change from baseline in quality of life
Comparison 7: Evening primrose oil versus placebo oil, Outcome 1: Change from baseline in TEWL
Comparison 7: Evening primrose oil versus placebo oil, Outcome 2: Change from baseline in skin hydration
Comparison 8: Licochalcone versus hydrocortisone acetate (HCA) 1%, Outcome 1: Change from baseline in itch (VAS)
Comparison 8: Licochalcone versus hydrocortisone acetate (HCA) 1%, Outcome 2: Change from baseline in SCORAD
Comparison 8: Licochalcone versus hydrocortisone acetate (HCA) 1%, Outcome 3: Change from baseline in TEWL
Comparison 9: Advabase versus MPA cream twice weekly and emollient, Outcome 1: Rate of flare
Comparison 10: Vehicle + daily moisturiser versus fluticasone propionate (FP) + daily moisturiser, Outcome 1: Number of participants reporting an adverse event
Comparison 10: Vehicle + daily moisturiser versus fluticasone propionate (FP) + daily moisturiser, Outcome 2: Number of participants experiencing a flare
Comparison 10: Vehicle + daily moisturiser versus fluticasone propionate (FP) + daily moisturiser, Outcome 3: Rate of flare
Comparison 11: Active treatment in combination with a moisturiser versus active treatment only, Outcome 1: Change in disease severity as assessed by the investigators
Comparison 11: Active treatment in combination with a moisturiser versus active treatment only, Outcome 2: Change in quality of life IDQOL
Comparison 11: Active treatment in combination with a moisturiser versus active treatment only, Outcome 3: Change in quality of life DFI
| Moisturisers versus no moisturiser for eczema | ||||||
| Patient or population: people with eczema | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with no moisturiser | Risk with moisturisers | |||||
| Change from baseline in disease severity according to participants ‐ not measured | ‐ | ‐ | ‐ | ‐ | ‐ | This outcome was not assessed in any of the studies. |
| Participant satisfaction ‐ not measured | ‐ | ‐ | ‐ | ‐ | ‐ | This outcome was not assessed in any of the studies. |
| Number of participants reporting an adverse event | Study population | RR15.34 | 173 | ⊕⊕⊝⊝ | 8/91 versus 0/82 reported an adverse event. Peto OR 7.26 (95% CI 1.76 to 29.92). 3 adverse events were reported to be mild, 3 moderate, and 2 were severe leading to treatment discontinuation. No adverse events were reported in the study of Simpson 2013 (within‐participant). | |
| 1 per 100 (0.5/82)a | 9 per 100 (1 to100) | |||||
| Change from baseline in disease severity as assessed by the investigators | The mean change from baseline in disease severity as assessed by the investigators ranged from ‐2.4 to ‐19.5 | The mean change from baseline in disease severity as assessed by the investigators in the intervention group was 2.42 lower (4.55 lower to 0.28 lower) | ‐ | 276 | ⊕⊕⊝⊝ | Reductions from baseline in Giordano‐Labadie 2006 and Grimalt 2007 met MID (= 8.7 Schram 2012) in both treatment arms. There was greater severity of disease in these studies than in Patrizi 2014. A MD of ‐2.42, although statistically significant, is not clinically important. |
| Number of participants who experienced a flare | Study population | RR 0.40 | 87 | ⊕⊕⊝⊝ | There were fewer flares in the moisturiser groups. The rate of flare in the control group was 3.74 times the rate in the moisturiser group (hazard ratio (HR) 3.74, 95% CI 1.86 to 7.50; P = 0.0002). | |
| 67 per 100 | 27 per 100 | |||||
| Amount of corticosteroids used | The mean amount of corticosteroids used ranged from 22.73 g to 62.1 g | The mean amount of corticosteroids used in the intervention group was 9.30 g less (15.30 g less to 3.27 g less) | ‐ | 222 | ⊕⊕⊝⊝ | P = 0.003. There was a statistically significant difference showing that the use of moisturisers decreased the use of topical corticosteroids to achieve similar reductions in SCORAD. |
| Change from baseline in health‐related quality of life | ‐ | The mean change from baseline in health‐related quality of life in the intervention group calculated as the SMD was 0.15 lower (0.55 lower to 0.24 higher) | ‐ | 177 | ⊕⊕⊝⊝ | There was no statistically significant difference in change from baseline of quality of life between the 2 treatment arms. |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| aWe had to put a value other than 0 in GRADEproGDT to calculate the risk with no moisturiser in relation to the RR, and we chose 0.5 (after discussion with the GRADE working Group). GRADEproGDT then calculates the risk with moisturiser. 2Downgraded one level due to high risk of bias because of performance and detection bias. 3Downgraded one level due to serious imprecision (wide confidence interval, low occurrence of events). 4Giordano‐Labadie 2006, Grimalt 2007, Patrizi 2014. 5Downgraded one level for serious inconsistency (I² = 68%), caused by Grimalt 2007. 7Downgraded one level for serious imprecision (small sample size). 8Giordano‐Labadie 2006, Grimalt 2007. 9Downgraded one level for serious inconsistency (I² = 68%). In the study of Giordano‐Labadie 2006, far more topical corticosteroids were used and the difference between the two arms was much larger. 10Downgraded one level for serious imprecision (wide confidence interval). | ||||||
| Atopiclair versus vehicle for eczema | ||||||
| Patient or population: people with eczema | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with vehicle | Risk with Atopiclair | |||||
| Change from baseline in disease severity according to participants (number of participants who considered their skin to have improved) | Study population | RR 4.51 | 390 | ⊕⊕⊕⊝ | Participants considered Atopiclair more effective than its vehicle. NNTB = 2, 95% CI 1 to 2 | |
| 17 per 100 | 77 per 100 | |||||
| Participant satisfaction | Study population | Not estimable | 248 | ⊕⊕⊕⊝ | Abramovits 2008: 119/145 (Atopiclair) vs 28/73 (vehicle) wished to continue (RR 2.14, 95% CI 1.58 to 2.89; P < 0.00001; NNTB = 2; 95% CI 2 to 3). Belloni 2005: 5/15 vs 0/15 would use again (Peto OR 10.18, 95% CI 1.54 to 67.23; P = 0.02) | |
| Not pooled | Not pooled | |||||
| Number of participants reporting an adverse event | Study population | RR 1.03 | 430 | ⊕⊕⊕⊝ | The number of participants reporting adverse events was not statistically different between the 2 groups. | |
| 33 per 100 | 34 per 100 | |||||
| Change from baseline in disease severity according to the investigators | The mean change from baseline in disease severity according to the investigators ranged from ‐1.7 to 0.84 | The mean change from baseline in disease severity according to the investigators in the intervention group was 4 lower (5.42 lower to 2.57 lower) | ‐ | 426 | ⊕⊕⊕⊝ | Although there is a statistically significant difference in favour of Atopiclair, the difference between the treatment group is not clinically important (MID EASI is 6.6 (Schram 2012)). |
| Number of participants who experienced a flare | Study population | RR 0.18 | 397 | ⊕⊕⊕⊝ | Participants in the Atopiclair group experienced fewer flares than the vehicle group (NNTB 3, 95% CI 3 to 5). | |
| 35 per 100 | 6 per 100 | |||||
| Change in use of topical active treatment ‐ not measured | ‐ | ‐ | ‐ | ‐ | ‐ | This outcome was not assessed in any of the studies. |
| Change from baseline in health‐related quality of life ‐ not measured | ‐ | ‐ | ‐ | ‐ | ‐ | This outcome was not assessed in any of the studies. |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Abramovits 2008, Belloni 2005, Boguniewicz 2008. 2Downgraded one level for serious imprecision (wide confidence interval). 3Abramovits 2008, Belloni 2005. 4Downgraded one level for serious indirectness, as outcomes did not exactly match participant satisfaction. 5Abramovits 2008, Belloni 2005, Boguniewicz 2008, Patrizi 2008. 6Downgraded one level for serious imprecision (small sample size and CI includes no difference (1) and appreciable harm (1.25)). 7Downgraded one level for serious inconsistency (I² = 51%), caused by Boguniewicz 2008, which showed a larger effect size. 8Abramovits 2008, Boguniewicz 2008, Patrizi 2008. 9Downgraded one level for risk of bias (Abramovits 2008: high risk for attrition bias, Boguniewicz 2008: unclear risk of bias for allocation concealment blinding and incomplete outcome data, and Patrizi 2008: at unclear risk of bias due to incomplete outcome data). | ||||||
| Urea‐containing moisturiser versus vehicle, placebo or no moisturiser for eczema | ||||||
| Patient or population: people with eczema | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with vehicle, placebo or no moisturiser | Risk with urea‐ containing moisturiser | |||||
| Change from baseline in disease severity according to the participants (number of participants who considered their skin to have improved) | Study population | RR 1.28 | 129 | ⊕⊕⊝⊝ | P = 0.0009. NNTB = 5 (95% CI 3 to 18). Participants considered that urea‐containing moisturiser provided more improvement than placebo cream without urea. In Wilhelm 1998 (n = 77, within‐participant design), 61% considered that the side treated with urea cream showed moderate to very good improvement, and 48.1% felt the vehicle‐treated side showed moderate to very good improvement. | |
| 70 per 100 | 89 per 100 | |||||
| Participant satisfaction Assessed with: Likert scale Follow‐up: mean 4 weeks | ‐ | 38 (1 RCT) 4, 5 | ⊕⊕⊝⊝ | Smell, spreadability, penetration into the skin, and skin feel were assessed. None of these features were assessed as being better on the urea‐treated side than on the vehicle‐treated side. For details, see comparison 2b under Effects of interventions. | ||
| Number of participants reporting an adverse event | Study population | RR 1.65 | 129 | ⊕⊕⊕⊝ | P = 0.005; NNTH = 4, 95% CI 2 to 11.There were fewer adverse events in the group treated with placebo cream. | |
| 39 per 100 | 65 per 100 | |||||
| Change from baseline in disease severity according to the investigators (number of participants who improved according to the investigators) | Study population | RR 1.40 | 129 | ⊕⊕⊕⊝ | The assessments of the investigators were in line with the assessments of the participants. P = 0.001; NNTB = 4, 95% CI 3 to 9. The within‐participant study of Wilhelm 1998 demonstrated a mean of the paired differences of ‐0.57 (95% CI ‐1.14 to 0.0) in favour of urea moisturiser (lower score being better), and is more or less in line with the parallel‐design study of Lodén 2002. | |
| 64 per 100 | 89 per 100 | |||||
| Number of participants who experienced a flare | Study population | RR 0.47 | 44 | ⊕⊕⊝⊝ | P = 0.03; NNTB = 3, 95% CI 2 to 11 The rate of flare in the group that did not use a moisturiser was 3.2 times the rate in the group treated with urea cream (HR 3.2, 95% CI 1.3 to 7.8; P < 0.01). | |
| 68 per 100 | 32 per 100 | |||||
| Change in use of topical active treatment ‐ not measured | ‐ | ‐ | ‐ | ‐ | ‐ | This outcome was not assessed in any of the studies. |
| Change from baseline in health‐related quality of life ‐ not measured | ‐ | ‐ | ‐ | ‐ | ‐ | This outcome was not assessed in any of the studies. |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 2Downgraded one level for serious indirectness, the study of Lodén 2002 had a parallel study design and the study of Wilhelm 1998 had a within‐participant design. 3Downgraded one level for serious imprecision (small sample size). 5Within‐participant design. 6Downgraded two levels for very serious imprecision (very small sample size). 8Downgraded one level for risk of bias as Wirén 2009 was assessed as at high risk of bias as the study was not blinded. | ||||||
| Glycerin/glycerol‐containing moisturiser versus vehicle or placebo for eczema | ||||||
| Patient or population: people with eczema | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with vehicle or placebo | Risk with glycerol‐containing moisturiser | |||||
| Change from baseline in disease severity as assessed by the participants | Study population | RR 1.22 | 134 | ⊕⊕⊕⊝ | Participants considered glycerol‐containing moisturiser more effective for improving dry skin than placebo cream (P = 0.03; NNTB = 6, 95% CI 3 to 60) | |
| 70 per 100 | 85 per 100 | |||||
| Participant satisfaction ‐ not measured | ‐ | ‐ | ‐ | ‐ | ‐ | This outcome was not assessed in any of the studies. |
| Number of participants reporting an adverse event | Study population | RR 0.90 | 385 | ⊕⊕⊕⊝ | The adverse events were mild to moderate and consisted of smarting, erythema, pruritus, or burning. | |
| 35 per 100 | 32 per 100 | |||||
| Change from baseline in disease severity as assessed by the investigators | The mean change from baseline in disease severity as assessed by the investigators was ‐3.1 | The mean change from baseline in disease severity as assessed by the investigators in the intervention group was 2.2 lower (3.44 lower to 0.96 lower) | ‐ | 249 | ⊕⊕⊕⊕ | P = 0.0005, but does not meet the MID (which is 8.2 for objective SCORAD (Schram 2012)). The study of Breternitz 2008 had a within‐participant design and confirmed these data. The mean of the paired differences was ‐1.10, CI 95% ‐1.63 to ‐0.57. In Lodén 2002, in the glycerol group 58/68 showed improvement in 'dryness' of the skin versus 42/66 in the vehicle group (RR 1.34, 95% CI 1.09 to 1.65; P = 0.0006, NNTB 5, 95% CI 3 to 14) |
| Number of participants who experienced a flare ‐ not measured | ‐ | ‐ | ‐ | ‐ | ‐ | This outcome was not assessed in any of the studies. |
| Change in use of topical active treatment ‐ not measured | ‐ | ‐ | ‐ | ‐ | ‐ | This outcome was not assessed in any of the studies. |
| Change from baseline in health‐related quality of life ‐ not measured | ‐ | ‐ | ‐ | ‐ | ‐ | This outcome was not assessed in any of the studies. |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 2Downgraded one level for serious imprecision (lower bound of CI approaches 1). 3Lodén 2002 and Boralevi 2014. 4Downgraded one level for serious imprecision (small sample size and CI includes appreciable benefit (0.75) and no difference (1)). | ||||||
| Oat‐containing moisturiser versus vehicle or no moisturiser | ||||||
| Patient or population: people with eczema | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with vehicle or no moisturiser | Risk with oat‐containing moisturiser | |||||
| Change from baseline in disease severity as assessed by the participants (number of participants who considered their skin to have improved) | Study population | RR 1.11 | 50 | ⊕⊕⊝⊝ | P = 0.45. Participants did not consider that the oat‐containing moisturiser was more effective than the control treatment (occlusive vehicle). | |
| 76 per 100 | 84 per 100 | |||||
| Participant satisfaction | Study population | RR 1.06 | 50 | ⊕⊝⊝⊝ | P = 0.76. Participants were not more satisfied with oat‐containing moisturiser than with the occlusive vehicle. | |
| 68 per 100 | 72 per 100 | |||||
| Number of participants reporting an adverse event | Study population | RR 15.34 | 173 | ⊕⊕⊝⊝ | 8/91 versus 0/82 reported an adverse event. | |
| 1 per 100 | 9 per 100 | |||||
| Change from baseline in disease severity as assessed by the investigators | ‐ | The mean change from baseline in disease severity in the intervention group calculated as the SMD was 0.23 lower (0.66 lower to 0.21 higher) | ‐ | 272 | ⊕⊕⊝⊝ | P = 0.30. There was no statistically significant difference according to the investigators between the 2 treatment arms. |
| Number of participants who experienced a flare | Study population | RR 0.31 | 43 | ⊕⊕⊝⊝ | P = 0.01; NNTB = 2, 95% CI 1 to 5. The HR for rate of flare was 4.74 (95% CI 1.57 to 14.34; P = 0.006) in favour of the oat‐containing cream. | |
| 65 per 100 | 20 per 100 | |||||
| Total amount of topical corticosteroids used | The mean total amount of topical corticosteroids used ranged from 22.73 g to 62.1 g | The mean total amount of topical corticosteroids used in the intervention group was 9.3 g lower (15.3 g less to 3.27 g less) | ‐ | 222 | ⊕⊕⊝⊝ | P = 0.003. There is a statistically significant difference showing that the use of moisturisers decreased the use of topical corticosteroids to achieve similar reductions in disease severity. |
| Change from baseline in health‐related quality of life | ‐ | The mean change from baseline in health‐related quality of life in the intervention group calculated as the SMD was 0.09 lower (0.37 lower to 0.19 higher) | ‐ | 226 | ⊕⊕⊝⊝ | There was no statistically significant difference in change from baseline in quality of life between the 2 treatment arms. |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| aWe had to put a value other than 0 in GRADEproGDT to calculate the risk with no moisturiser in relation to the RR, and we chose 0.5 (after discussion with the GRADE working Group). GRADEproGDT then calculates the risk with moisturiser. 2Downgraded two levels level for very serious imprecision (small sample size and CI includes no effect (1) and appreciable benefit (1.25)). 3Downgraded one level for serious indirectness as the outcome was more about soothing and calming of the skin and not really participant satisfaction. 4Downgraded two levels for very serious imprecision as the CI includes both no effect, and benefit of both oat‐containing cream as well as of the vehicle. 5Downgraded one level for risk of bias because of performance and detection bias. 6Downgraded one level for serious imprecision (wide confidence interval, low occurrence of events). 8Giordano‐Labadie 2006, Grimalt 2007, Nebus 2009. 9Downgraded one level for serious inconsistency (I² = 65%), caused by Giordano‐Labadie 2006, which was the study showing a favourable result for the oat‐containing creams whilst the other studies showed no difference between the treatment arms. 10Downgraded one level for serious imprecision; the CI creates uncertainty with the effect, ranging from moderate effect to small harmful effect. 11Weber 2015. 12Downgraded one level for serious imprecision (small sample size). 13Giordano‐Labadie 2006 and Grimalt 2007. 14Downgraded one level for serious inconsistency (I² = 68%). In the study of Giordano‐Labadie 2006, far more topical corticosteroids were used and the difference between the two arms was much larger. 15Downgraded one level for serious imprecision (wide confidence interval). 16Downgraded one level for serious risk of bias because of performance, detection, and attrition bias. 17Downgraded one level for serious imprecision (the CI creates uncertainty with the effect, ranging from small effect to small harmful effect). | ||||||
| All moisturisers compared to vehicle, placebo or no moisturiser for eczema | ||||||
| Patient or population: people with eczema | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with vehicle, placebo or no moisturiser | Risk with all moisturisers | |||||
| Change from baseline in disease severity as assessed by the participants (number of participants who considered their skin to have improved) | Study population | RR 2.46 | 572 | ⊕⊕⊝⊝ | Participants considered the use of a moisturiser to be more effective than vehicle/placebo or no moisturiser. P = 0.02, NNTB = 2, 95% CI 2 to 3 | |
| 37 per 100 | 91 per 100 | |||||
| Participant satisfaction | Study population | RR 1.35 | 298 | ⊕⊕⊝⊝ | P = 0.29. According to the participants, there was no difference between the 2 treatment arms for this outcome. Results are supported by the within‐participant study (Bohnsack 1997). | |
| 48 per 100 | 65 per 100 | |||||
| Number of participants reporting an adverse event | Study population | RR 1.03 | 1275 | ⊕⊕⊕⊝ | There was no statistically significant difference in number of participants experiencing an adverse event. | |
| 23 per 100 | 24 per 100 | |||||
| Change from baseline in disease severity as assessed by the investigators | ‐ | The mean change from baseline in disease severity as assessed by the investigators in the intervention group calculated as the SMD was 1.04 lower (1.57 lower to 0.51 lower) | ‐ | 1281 | ⊕⊕⊕⊕ | P < 0.0001 The investigators considered the use of moisturisers to be more beneficial than the vehicle, placebo, or no moisturiser. However, clinical impact was unclear. |
| Number of participants who experienced a flare | Study population | RR 0.33 | 607 | ⊕⊕⊕⊝ | P = 0.006; NNTB = 4, 95% CI 3 to 5. The rate of flare in the control group was 3.74 times the rate in the moisturiser group based on Weber 2015 and Wirén 2009 (HR 3.74, 95% CI 1.86 to 7.50; P = 0.0002 in favour of moisturiser). | |
| 41 per 100 | 13 per 100 | |||||
| Total amount of topical corticosteroids used | The mean amount of corticosteroids used ranged from 22.73 g to 62.1 g | The mean amount of corticosteroids used in the intervention group was 9.30 g less (15.30 g less to 3.27 g less) | ‐ | 222 | ⊕⊕⊝⊝ | P = 0.003. There was a statistically significant difference showing that the use of moisturisers decreased the use of topical corticosteroids to achieve similar reductions in eczema severity. |
| Change from baseline in health‐related quality of life | ‐ | The mean change from baseline in health‐related quality of life in the intervention group calculated as the SMD was 0.39 lower (0.9 lower to 0.12 higher) | ‐ | 300 | ⊕⊕⊝⊝ | The effect on quality of life ranges from a moderate effect on quality of life in favour of moisturisers to no difference between the groups. |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Abramovits 2008, Belloni 2005, Boguniewicz 2008, Lodén 2002, Nebus 2009. 2Downgraded one level for inconsistency (I² = 95%), which was in part caused studies by studies at risk for attrition bias (Abramovits 2008 and Boguniewicz 2008). 3Downgraded one level for serious imprecision (wide confidence interval). 4Abramovits 2008, Belloni 2005, Nebus 2009. 5Downgraded one level for serious inconsistency (I² = 83%). All heterogeneity was removed when a study at high risk of bias was excluded (Abramovits 2008); we did not double count for risk of bias. 6Downgraded one level for serious imprecision (CI interval includes no effect (1) and appreciable benefit (1.25)). 7Abramovits 2008, Belloni 2005, Boguniewicz 2008, Boralevi 2014, Gayraud 2015, Grimalt 2007, Korting 2010, Lodén 2002, Patrizi 2008, Tan 2010. 8Downgraded one level for imprecision (CI interval included no difference (1) and appreciable harm (1.25)). 9Abramovits 2008, Belloni 2005, Boguniewicz 2008, Boralevi 2014, Gayraud 2015, Giordano‐Labadie 2006, Grimalt 2007, Korting 2010, Nebus 2009, Patrizi 2008, Patrizi 2014, Tan 2010. 10We did not downgrade for inconsistency as all sensitivity analyses show a clear positive effect of moisturisers. 11Abramovits 2008, Boguniewicz 2008, Gayraud 2015, Patrizi 2008, Weber 2015, Wirén 2009. 12Downgraded one level for serious inconsistency (I² = 73%), which was caused by the studies at unclear to high risk of bias showing better results. 13Giordano‐Labadie 2006, Grimalt 2007. 14Downgraded one level for serious inconsistency (I² = 68%). In the study of Giordano‐Labadie 2006, far more topical corticosteroids were used and the difference between the two arms was much larger. 15Gayraud 2015, Giordano‐Labadie 2006, Grimalt 2007. 16We did not downgrade for risk of bias, as, although there was attrition bias in Grimalt 2007, it did not impact the overall result, and even reduced the direction of effect. 17Downgraded one level for serious inconsistency (I² = 79%), it might have no effect at all, signal around 0. 18Downgraded one level for serious imprecision (CI includes moderate effect in favour of moisturisers as well as no difference). | ||||||
| Licochalcone‐containing moisturiser versus hydrocortisone acetate1% cream for eczema | ||||||
| Patient or population: people with eczema | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with hydrocortisone acetate 1% cream | Risk with licochalcone‐containing moisturiser | |||||
| Change from baseline in disease severity according to participants ‐ not measured | ‐ | ‐ | ‐ | ‐ | ‐ | This outcome was not assessed in any of the studies. |
| Number of participants who rated treatment satisfaction as good to excellent | ‐ | ‐ | ‐ | 30 | ⊕⊕⊝⊝ | On both treatment sides, 22/30 participants rated their satisfaction good to excellent with no difference between either side. |
| Number of participants reporting an adverse event | ‐ | ‐ | ‐ | 18 | ⊕⊕⊝⊝ | Both Udompataikul 2011 and Wanakul 2013 reported no adverse events on any side during the study. Side effects in Angelova‐Fischer 2014 (within‐participant study) were skin tightness, itch, and scaling on both sides. 9 side effects were reported on each forearm (n = 18). |
| Change from baseline in disease severityas assessed by the investigators | The mean disease severity as assessed by the investigators ranged from ‐3.50 to ‐21.29 | The mean disease severity as assessed by the investigators in the intervention group was 0.08 higher (1.96 lower to 2.13 higher) | ‐ | 96 | ⊕⊕⊝⊝ | There was no statistically significant difference between the 2 treatments, which is in accordance with the data for participant satisfaction. |
| Number of participants who experienced a flare | ‐ | ‐ | ‐ | 30 | ⊕⊕⊝⊝ | 3/30 experienced a flare on the side treated with licochalcone and 6/30 on the contralateral side treated with hydrocortisone acetate 1%. |
| Change in use of active topical treatment ‐ not measured | ‐ | ‐ | ‐ | ‐ | ‐ | This outcome was not assessed in any of the studies. |
| Change from baseline in quality of life ‐ not measured | ‐ | ‐ | ‐ | ‐ | ‐ | This outcome was not assessed in any of the studies. |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Within‐participant study Udompataikul 2011. 2We did not downgrade for detection bias as the participants were not blinded, but they considered treatments equally satisfactory. 3Downgraded two levels for serious imprecision (very small sample size). 4Within‐participant study Angelova‐Fischer 2014. 5Not downgraded for risk of bias (participants in Angelova‐Fischer 2014 and Udompataikul 2011 were not blinded) as there was no difference between the both treatment arms regarding reporting adverse events. 6Downgraded two levels for very serious imprecision (very small sample size). 7We did not downgrade for detection bias as investigators were blinded. 8Downgraded two levels for very serious inconsistency (I² = 85%); it could benefit both treatments. We therefore did not downgrade further for imprecision. Differences in study duration, and, in Angelova‐Fischer 2014, only forearms were treated. 9Downgraded one level for serious imprecision (small sample size and as we downgraded for risk of bias, we only downgraded once for imprecision for this outcome). 10Downgraded one level for risk of bias (no blinding of participants). | ||||||
| Vehicle treatment + daily moisturiser compared to fluticasone propionate twice weekly + daily moisturiser for eczema | ||||||
| Patient or population: people with eczema | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with fluticasone propionate twice weekly + moisturiser | Risk with vehicle treatment + moisturiser | |||||
| Change from baseline in disease severity as assessed by the participants (number of participants reporting good to excellent result) | Study population | RR 0.45 | 348 | ⊕⊕⊕⊕ | NNTB = 3, 95% CI 2 to 3, in favour of fluticasone propionate twice weekly + daily moisturiser | |
| 71 per 100 | 32 per 100 | |||||
| Participant satisfaction ‐ not measured | ‐ | ‐ | ‐ | ‐ | ‐ | This outcome was not assessed in any of the studies. |
| Number of participants reporting an adverse event | Study population | RR 0.51 | 718 | ⊕⊕⊝⊝ | Although there was a trend favouring the vehicle treatment + daily moisturiser, the 2 comparisons of Berth‐Jones 2003 implied that they might be equally safe (no adverse events in either group). | |
| 22 per 100 | 11 per 100 | |||||
| Change from baseline in disease severityas assessed by the investigators | 75 (1 RCT)5 | ⊕⊕⊕⊝ | There were reporting inconsistencies in the paper between the data table and text regarding the increase in SCORAD in the twice‐weekly fluticasone propionate + daily moisturiser group. These were reported as 7.1 in the table and as 3.8 in the text. In the vehicle + daily moisturiser group, the increase was 12.2 in both table and text. | |||
| Number of participants who experienced a flare | Study population | RR 2.17 | 718 | ⊕⊕⊕⊝ | NNTB = 3, 95% CI 2 to 3. Twice‐weekly fluticasone propionate combined with moisturiser resulted in fewer flares than moisturiser alone. HR of rate of flare 3.69, 95% CI 1.80 to 7.55 in favour of fluticasone propionate twice weekly + daily moisturiser | |
| 28 per 100 | 61 per 100 | |||||
| Change in use of topical active treatment ‐ not measured | ‐ | ‐ | ‐ | ‐ | ‐ | This outcome was not assessed in any of the studies. |
| Change from baseline in quality of life ‐ not measured | ‐ | ‐ | ‐ | ‐ | ‐ | This outcome was not assessed in any of the studies. |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 2Berth‐Jones 2003 (two comparisons), Glazenburg 2009, Hanifin 2002. 3Downgraded one level for serious inconsistency (I² = 67%); as there were no adverse events in both comparisons in Berth‐Jones 2003 in both treatment arms, they could be equally safe. 4Downgraded one level for serious imprecision (CI includes appreciable benefit and no difference). 5Glazenburg 2009 (See 'Comments'). 6Downgraded one level for serious imprecision (small sample size). 7Downgraded one level for serious inconsistency (I² = 72%). | ||||||
| Topical active treatment in combination with moisturiser compared to topical active treatment alone for eczema | ||||||
| Patient or population: people with eczema | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with active treatment alone | Risk with active treatment in combination with moisturiser | |||||
| Change from baseline in disease severity according to participants ‐ not measured | ‐ | ‐ | ‐ | ‐ | ‐ | This outcome was not assessed in any of the studies. |
| Participant satisfaction | ‐ | ‐ | 201 | ⊕⊕⊝⊝ | Hanifin 1998: 96% of 78 preferred the combination treatment and just 4% the active treatment 'only'. Simpson 2011: 84.3% to 96.7% of 123 felt that the addition of the RestoraDerm to the routine use of their topical steroids "reduces inflammation, relieves dry and itchy skin, provides long lasting hydration, leaves skin protected and maintains healthy skin". | |
| Number of participants reporting an adverse event Follow‐up: mean 3 weeks | Study population | RR 0.39 | 125 | ⊕⊝⊝⊝ | Draelos 2008: no adverse events. Hanifin 1998 (within‐participant): 10 participants reported burning and stinging on the side treated with desonide 0.05% combined with moisturiser versus 11 on the other side treated with only desonide 0.05%. | |
| 16 per 100 | 6 per 100 | |||||
| Change from baseline in disease severity as assessed by the investigators | ‐ | The mean change from baseline in disease severity as assessed by the investigators in the intervention group calculated as the SMD0.87 lower (1.17 lower to 0.57 lower) | ‐ | 192 | ⊕⊕⊕⊝ | According to the assessments of the investigators, adding a moisturiser to topical active treatment is more effective than topical active treatment alone. |
| Number of participants who experienced a flare | Study population | RR 0.43 | 105 | ⊕⊕⊝⊝ | Adding a moisturiser to active treatment reduced the number of flares (NNTB = 6, 95% CI 3 to 57). | |
| 31 per 100 | 13 per 100 | |||||
| Change in amount of use topical active treatment ‐ not measured | ‐ | ‐ | ‐ | ‐ | ‐ | This outcome was not assessed in any of the studies. |
| Change from baseline in health‐related quality of life | The mean change from baseline in health‐related quality of life ranged from ‐2.07 to ‐3.17 | The mean change from baseline in health‐related quality of life in the intervention group was 1.31 lower (2.7 lower to 0.09 higher) | ‐ | 67 | ⊕⊕⊝⊝ | The study duration of 3 weeks was short; there was no difference in changes from baseline in quality of life between the 2 treatment groups. Results of DFI confirmed this (MD ‐1.03, 95% CI ‐2.47 to 0.42) |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Within‐participant design. 3Downgraded one level for serious risk of detection bias (no blinding of participants). 4Downgraded one level for serious indirectness as in both studies satisfaction was not really assessed. 5Wu 2014. 6Downgraded one level for risk of bias. Hanifin 1998 and Wu 2014 were assessed as being at a high risk of bias. 7Downgraded one level for serious indirectness for different reporting on adverse events including outcome definitions. 8Downgraded one level for serious imprecision (small sample size, too few adverse events, and wide CI). 9Msika 2008 (2 comparisons), Wu 2014. 10Downgraded one level for risk of bias (no blinding of outcome assessors). 11Downgraded one level for risk of bias (attrition bias (17/62) in the control group). 12Downgraded one level for serious imprecision (small sample size). 13Msika 2008 (2 comparisons). 14Downgraded one level for risk of bias (no blinding of participants). | ||||||
| Term | Definition |
|---|---|
| Adverse events | Unwanted side effects of using medication |
| Allergic contact dermatitis | A form of eczema after contact with a substance (an allergen) that produces (elicits) an immune‐mediated response in the skin |
| Allergic rhinitis | 'Hay fever': inflammation of the nose caused by allergens such as house dust mite, animals, pollen. Symptoms include sneezing, itchiness in the nose, watery eyes, runny or blocked nose |
| Ameliorate | Improve, to make something (such as a problem) better |
| Atopy | The individual's genetic predisposition to develop allergic reactions such as eczema, allergic rhinitis and asthma. Atopy often involves production of IgE antibodies against allergens such as, for example, house dust mite, animals, grass and tree pollen, and food proteins. |
| Bacteria | Also referred to as germs, bacteria are tiny micro‐organisms that are invisible to the eye. They are found everywhere and can be harmful, e.g. causing infections, or helpful, e.g. aiding digestion of food |
| Ceramides | Lipid (fatty) molecules found in the lipid bilayer of the intercellular matrix (see `Intercellular lipid matrix' below) |
| Colonisation | The point at which an Infection begins, when an organism successfully enters the body, grows and multiplies |
| Control | The alternative treatment, placebo, or absence of treatment against which the intervention of interest in the review is compared |
| Corneodesmosomes | Any of a class of proteins that hold corneocytes (cells in the epidermis, or outer layers of the skin) together; their degradation leads to desquamation (see 'Desquamation' below) |
| DASI | Dry skin area and severity index: a tool used to evaluate dryness and severity of dry skin (Serup 1995) |
| Desquamation | Skin peeling |
| Dizygotic | Non‐identical twins, i.e. twins formed from two different eggs fertilised by separate sperm cells, are referred to as dizygotic. |
| DLQI | Dermatology Life Quality Index: an assessment tool to evaluate the impact of eczema and its treatment on quality of life (Finlay 1994) |
| EASI | Eczema Area and Severity Index: a tool used to measure the extent (area) and severity of eczema (Hanifin 2001) |
| Emollients | The terms `emollients' and `moisturisers' are often used interchangeably. But, since 'emollient' sometimes refers to a specific ingredient that soothes the skin, it is more appropriate to use the term 'moisturiser'. Emollients are included within ointments, creams, lotions, gels, bath oils and sprays, and are used to keep the skin soft and supple and reduce scaling. Application to the skin reduces water loss by covering it with a protective film. They can be used frequently and might ease itching |
| Epidermis | The outermost layers of cells in the skin which consist mainly of keratinocytes that mature to become corneocytes |
| Exacerbation | Periods of worsening the symptoms and signs of eczema |
| Excoriation | Abrasion, scratched skin |
| Extensor | The opposite site of a flexure point, i.e. the outer side of, for example elbow, knee or wrist |
| Filaggrin | An epidermal barrier protein |
| Flare | Periods of worsening of eczema symptoms and signs, or escalation in use of medication (Thomas 2015) |
| Flexural dermatitis | Eczema at the flexure points (inner sides) of elbow, knees, wrists, groin and armpits |
| Gene | Part of DNA that encodes a protein involved in body function |
| Genome‐wide linkage study | An established tool to map inherited diseases |
| Humectant | Substance or product that is 'water loving' and draws water towards it |
| Hygroscopic | Absorbing water |
| Hypersensitivity | An exaggerated immune response toward an allergen (for example pollen, house dust mite, but also for contact allergens such as nickel and fragrances) |
| IgE (immunoglobulin E) | A class of antibody that is important in defence against parasitic disease, and plays a key role in the disease process of allergic diseases. People with eczema often have an increased level of IgE in their blood |
| Immune response | The process through which the body identifies and defends itself against bacteria, viruses and other harmful agents |
| Intercellular lipid matrix | Space surrounding corneocytes with stacked layers of lipids |
| Lesion | A region or area of damaged skin |
| Lesional | Concerning lesions, or accompanied by lesions |
| Lichenification | Skin thickening |
| Moisturisers | Ointments, creams, lotions, gels, bath oils and sprays that are used to keep the skin soft and supple and reduce scaling. Application to the skin reduces water loss and covers it with a protective film. Moisturisers can be used frequently and might ease itching. |
| Monozygotic | Identical twins, i.e. twins who develop from a single fertilised egg (zygote) that splits to form two identical embryos, are referred to as monozygotic (in contrast to dizygotic twins (see above)). |
| Objective | Something observed and verified by physician or investigator by visible physical signs or laboratory tests (i.e. based on facts, not emotions or feelings) |
| Objective‐ SCORAD | Objective ‐ SCORing Atopic Dermatitis is a clinical scoring system, that uses the SCORAD system and excludes subjective symptoms, which cannot be measured accurately, such as daytime itching (pruritus) and sleep loss (Kunz 1997) |
| Occlusive | Describes an agent or process that seals something off |
| Over‐the‐counter (OTC) medicines | Medicines that can be bought without a prescription |
| Papulovesicular | Relating to an eruption of papules (clearly defined (circumscribed), solid elevations of skin with no visible fluid) and vesicles (small fluid‐filled sacs on the skin) |
| Pathogenesis | Origin of disease and how it develops |
| Pathognomonic biomarker | A specific indicator for a disease |
| Photochemotherapy (PUVA) | PUVA is a combination treatment of a drug (psoralen) with ultraviolet A (UVA) light. The psoralen makes the skin temporarily more sensitive to the ultraviolet light |
| Phototherapy | Treatment with ultraviolet light (UVB or UVA) |
| Placebo | A 'dummy' or fake medicine that has no expected benefit. In this review placebo means, in accordance with the terminology used by the investigators, a moisturiser without the ingredient considered to be the most beneficial, and so, of a different composition than the moisturiser being studied. Use of placebo treatments allows patients and staff to be blinded, as the placebo and active treatments appear the same, so it is impossible to tell which has been used. |
| POEM | The Patient Oriented Eczema Measure is a self‐assessment tool for monitoring eczema severity, based on signs and symptoms (Charman 2004) |
| PO‐SCORAD | The Patient‐Oriented SCORing Atopic Dermatitis (PO‐SCORAD) index is a self‐assessment score for patients to evaluate their eczema, based on subjective and objective criteria from the SCORAD (see also SCORAD below) (Stalder 2011) |
| Preservative | A natural or synthetic ingredient added to products such as foods, pharmaceuticals, paints, biological samples, wood, etc. which help to prevent decomposition caused by microbial growth or by undesirable chemical changes |
| Propylene glycol | Propylene glycols attract water and by enhancing skin penetration they behave as moisturisers to improve the appearance of the skin |
| Protease | An enzyme that breaks down proteins (via proteolysis) |
| Pruritus | Itch |
| Quality of life | The general well‐being of individuals and societies. Health‐Related Quality of Life (HRQoL) looks at quality of life in relation to health |
| QoLIAD | Quality of Life Index for Atopic Dermatitis (QoLIAD). An assessment tool to evaluate the impact of eczema and its treatment on quality of life (Whalley 2004) |
| Remission | A temporary or permanent decrease or absence of the symptoms and signs of disease activity |
| Sensitisation | Exposure to an allergen that results in the development of hypersensitivity, i.e. an increased or disproportionate response to the allergen |
| SCORAD‐index | An assessment tool used by clinicians to evaluate the extent and severity of eczema (SCORing Atopic Dermatitis) (European Task Force on Atopic Dermatitis 1993) |
| Staphyloccocus aureus | A type of bacterium that is often found on the skin |
| Subjective | Something experienced by the participant not perceived by the investigator or physician |
| TEWL | Trans‐epidermal water loss (TWL or TEWL) is the quantity of water that diffuses through and evaporates from the epidermis |
| Topical corticosteroid | Corticosteroids applied to the skin; these are effective in controlling inflammation and used to treat eczema and many other skin conditions |
| Urea | Urea absorbs water, helps to reduce the amount of water lost though the skin and increases skin penetration of other substances. It softens the horny layer and also has anti‐itch (anti‐pruritic) properties. |
| Vehicle | In this review 'vehicle' means a moisturiser that has the same composition as the studied moisturiser, but lacks the ingredient that is considered to be the most beneficial |
| Volar | The inside surface of the forearm, i.e. the same side as the palm of the hand |
| Xerosis | Dry skin |
| Study ID | Response | Additional | Comment |
|---|---|---|---|
| Emails sent: 26 June 2014, 7 February 2016, 12 February 2016, 26 February 2016, 12 March 2016, 19 March 2016, to [email protected] Regarding allocation concealment and method of blinding Replies received: 24 March 2016 with responses; 29 March 2016 with additional information | Yes | ‐ | |
| Emails sent: 13 February 2016, 26 February 2016, to irena.angelova‐fischer@uk‐sh.de Regarding sequence generation and allocation concealment Reply received: 1 March 2016 with response to sequence generation Several emails sent regarding allocation concealment, but this remains unclear | Yes | ‐ | |
| [email protected] no need to contact, but this is recent email for future update of the review | Not applicable | ‐ | |
| Email sent: 13 February 2016, to [email protected] Regarding sequence generation and allocation concealment Email received: 15 February 2016 with responses | Yes | ‐ | |
| Emails sent: 13 February 2016, 26 February 2016, to [email protected] Regarding method of blinding Email received: 27 February 2016 with responses | Yes | ‐ | |
| Emails sent: 12 May 2014, 14 June 2014, 21 January 2016, to [email protected] and [email protected] Regarding sequence generation, allocation concealment and method of blinding Replies received: 2 February 2015 and 15 February 2016; received all responses and additional material | Yes | ‐ | |
| Emails sent: 14 February 2016, 26 February 2016, 12 March 2016, 19 March 2016, to [email protected]. Also did not reply to questions about the Abramovits 2008 study Regarding allocation concealment and method of blinding, EASI scores at day 43 and subjects/care givers assessment of global response at day 43 in vehicle group No reply received | Not applicable | ‐ | |
| Emails sent: 15 February 2016, 26 February 2016, 12 March 2016, 26 March 2016, to franck.boralevi@chu‐bordeaux.fr Regarding P‐VAS scores, SCORAD, Objective SCORAD, and HI at day 28 as well as SDs Replies received: 31 March 2016 and 5 April 2016 responses and additional information | Yes | ‐ | |
| Emails sent: May 2014, 15 February 2016, to elsner@derma‐jena.de and [email protected] Regarding sequence generation, allocation concealment and method of blinding, mean SCORAD, TEWL, capacitance and SDs Replies received: 16 May 2014 and 15 February 2016, received responses and additional information | Yes | ‐ | |
| Emails sent: 15 February 2016, 26 February 2016, 15 March 2016, 19 March 2016, to [email protected] Regarding sequence generation, allocation concealment, method of blinding, TEWL values and SDs after 2 weeks, number of dropouts, numbers of male/female and age of participants Reply received: 22 March 2016 with responses to our questions | Yes | ‐ | |
| Email sent: 16 February 2016 to [email protected] and clarence.de‐[email protected] Regarding allocation concealment and method of blinding Replies received: 24 February 2016 and 12 March 2016 from [email protected] and [email protected], with responses to our questions | Yes | ‐ | |
| Emails sent: 16 February 2016, 12 March 2016, 19 March 2016, 26 March 2016, to [email protected] Regarding allocation concealment and method of blinding No reply received | Not applicable | ‐ | |
| Emails sent: 19 February 2016, 12 March 2016, 19 March 2016, 26 March 2016, to [email protected] Regarding allocation concealment and method of blinding, more precise baseline data and data at end of study means and SDs No reply received | Not applicable | ‐ | |
| Emails sent: 19 February 2016, 12 March 2016, 19 March 2016, 26 March 2016, to [email protected] Regarding sequence generation, allocation concealment, method of blinding, precise baseline data and data at end of study, means and SDs, Participant assessments of target site skin appearance for redness, peeling, dryness, stinging/burning, and overall skin irritation, sponsoring and declaration of interest No reply received | Not applicable | ‐ | |
| Emails sent: 5 March 2016, 12 March 2016, 19 March 2016, 26 March 2016 to Jason Emer (email not current anymore), with last 2 emails to A Frankel ([email protected]) Regarding sequence generation, allocation concealment, method of blinding, colour version of pdf and SDs at week 4 No reply received | Not applicable | ‐ | |
| Emails sent: 7 March 2016, 12 March 2016, to [email protected] Regarding sequence generation, allocation concealment, method of blinding, more precise data Reply received: 12 March 2015 "it is so long time ago that I performed this study so I do not remember. I retired last November 2015 and I do not have assess to any data now." | No | ‐ | |
| Email sent 9 March 2016 to [email protected] Regarding sequence generation, allocation concealment, method of blinding and incomplete data Reply received: 14 March 2014 with responses to our questions | Yes | ‐ | |
| Email sent: 13 May 2014 to giordano.labadie.f@chu‐toulouse.fr, frederic.cambazard@chu‐st‐etienne.fr, gerard.guillet@chu‐poitiers.fr, [email protected], and valerie.mengeaud@pierre‐fabre.com Regarding sequence generation and allocation concealment Reply received: 26 May 2014 with responses to our questions | Yes | ‐ | |
| Emails sent:14 March 2016, 19 March 2016, 26 March 2016, 3 April 2016, to [email protected] Regarding allocation concealment, method of blinding and inconsistencies in text page 64 and table 1 No reply received | Not applicable | ‐ | |
| Email sent: 13 April 2014, to [email protected], frederic.cambazard@chu‐st‐etienne.fr, valerie.mengeaud@pierre‐fabre.com Regarding sequence generation and allocation concealment Reply received: 24 June 2015, after several emails we received responses to everything we asked for | Yes | ‐ | |
| Email sent: 17 April 2016, to [email protected] (no longer correct, no more recent email, so sent again to [email protected], but this is also no longer correct) Regarding sequence generation, allocation concealment and baseline data for TEWL and corneometry No recent email addresses could be found | Not applicable | ‐ | |
| We could not find a current email address of any of the authors listed | Not applicable | ‐ | |
| Emails sent: 18 March 2016, 26 March 2016, 3‐4 February 2016,10 April 2016, to [email protected] Regarding sequence generation and allocation concealment, frequency of use, precise data after 3 months (means and SDs), more data on adverse events No reply received | Not applicable | ‐ | |
| Emails sent: 19 March 2016, 26 March 2016, 3 April 2016, to [email protected] Regarding allocation concealment, method of blinding, exact data for POEM and quality of life at baseline, and SCORAD, POEM and quality of life at day 28 | Not applicable | ‐ | |
| Emails sent: 8 January 2016, 24 January 2016, 12 February 2016, 8 April 2016, 18 April 2016, to [email protected] Regarding sequence generation and allocation concealment No reply received | Not applicable | ‐ | |
| Email sent: 19 March 2015, to [email protected] Regarding full text publication Reply received: 21 March 2015, Principal investigator could not remember anymore | No | ‐ | |
| Email sent: 19 March 2015, to [email protected] Regarding sequence generation, allocation concealment, method of blinding, exact TEWL values and corneometry with SDs at week 4 Reply received: 21 March 2016 with responses to some of our questions, the rest was no longer accessible | Yes and No | We did not receive exact data | |
| Email sent: 20 March 2016, to [email protected]‐muenchen.de Regarding allocation concealment and blinding Email address is no longer correct, and further searches showed that he died in 2012. None of the other authors could be contacted | Not applicable | ‐ | |
| Emails sent: 20 March 2016, 26 March 2016, to a‐[email protected], [email protected] [email protected] Regarding sequence generation, allocation concealment, method of blinding and precise study data Reply received: 26 March 2016 with responses to our questions | Yes | ‐ | |
| Emails sent: 15 April 2016, 19 April 2016, 23 April 2016, 30 April 2016, to [email protected] Regarding allocation concealment and blinding Reply received: 2 May 2016 with responses to our questions | Yes | ‐ | |
| Email sent: 14 May 2014, to [email protected]. Latest email address is [email protected] (since October 2015) Regarding sequence generation and allocation concealment Reply received: 14 May 2014 with responses to our questions | Yes | ‐ | |
| Email sent: 15 May 2014, to [email protected], clarence.de‐[email protected], [email protected] Regarding sequence generation, stratifying, allocation concealment, means and SDs for some outcomes and clarification about data losses for the following outcomes in particular IDQOL, DFI, IGE Reply received: 30 June 2014 with additional information | Yes | ‐ | |
| Email sent: 30 June 2014, to [email protected] and [email protected] Regarding clarification of correct citation i.e. author string/journal page numbers to the 2 citations listed in Included studies, plus sequence generation, allocation concealment and method of blinding Reply received: 30 June 2014 and 5 July 2014, with responses to our questions | Yes | ‐ | |
| Emails sent: 2 January 2016, 5 January 2016, 15 January 2016, 20 January 2016, to [email protected], [email protected], [email protected] Regarding missing data of control, and clarification regarding study design, and data regarding EASI, IGA Repy received: 20 January 2016 from Dr Nebus with responses to our questions and additional documents | Yes | ‐ | |
| Email sent: 7 January 2016, to [email protected] Regarding sequence generation and allocation concealment Reply received: 18 January 2016, from [email protected], with responses to our questions | Yes | ‐ | |
| Email sent: 26 March 2016, to [email protected] Regarding sequence generation, allocation concealment, method of blinding, dropouts, EASI, VAS scores at baseline and day 21 and additional study details Replies received: 26 March 2016, and 30 March 2016 with responses to our questions | Yes | ‐ | |
| Emails sent: 26 March 2016, 3 April 2016, 10 April 2016, 16 April 2016, to Dr Seo: [email protected] Regarding sequence generation, allocation concealment, method of blinding and precise data of IGA, VAS, TEWL and corneometry with SD at 4 weeks No reply received | Not applicable | ‐ | |
| Emails sent: 27 March 2016, 3 April 2016, 10 April 2016, to [email protected] Regarding sequence generation, allocation concealment, method of blinding and precise data of EASI at day 43, and data of appraisal patients Reply received: 12 April 2016, with responses regarding sequence generation, allocation concealment and blinding, but not the rest. 14 April 2016 we sent mails to the sponsor at [email protected] (no longer working) and [email protected] No further details retrieved | In part | ‐ | |
| Email sent 27 March 2016, 3 April 2016 jennifer.theunis@pierre‐fabre.com. Regarding sequence generation, allocation concealment, and precise data of TEWL at day 43, and to which group drop‐out was randomised Response 7 April 2016 we received responses to our questions | Yes | ‐ | |
| Email sent 28 March 2016, 3 April 2016, 10 April 2016, 16 April 2016 [email protected] Regarding allocation concealment, precise data at baseline,day 10 and 28 for TEWL, PGA, EASI, adverse events in Cis UCA group and in vehicle No reply received | Not applicable | ‐ | |
| Email sent: 29 March 2016, to [email protected]‐bonn.de Regarding sequence generation, allocation concealment, method of blinding as one group had two different tubes, precise data at baseline and week 16 for VAS, EASI, DLQI and CDLQI Reply received: 30 March 2016, saying that cannot help us, the study was too long ago, and Schering Dermatology does not exist anymore. Intendis (the pharmaceutical company) did not reply | No | ‐ | |
| Email sent: 2 April 2016, to [email protected], [email protected] Regarding sequence generation, allocation concealment, differences between publication and protocol and exact baseline values for data after 15, 30 and 60 minutes for TEWL, and corneometry Reply received: 12 April 2016, with responses to our questions | Yes | ‐ | |
| Email sent: 18 May 2014, to [email protected], SOTIRIOS‐[email protected] Regarding sequence generation and allocation concealment, mean reduction in EASI and corresponding standard deviations at day 28, and dropouts Reply received: 18 July 2014, with responses to our questions | Yes | ‐ | |
| Emails sent: 2 April 2016, 10 April 2016, 16 April 2016, 23 April 2016, to [email protected], [email protected], [email protected] Regarding exact baseline values (and SD) at day 28 for dryness scale, TEWL, and corneometry Reply received: 2 May 2016, with responses to our questions and additional information | Yes | ‐ | |
| Email sent: 3 April 2016, to [email protected] Regarding sequence generation, allocation concealment, method of blinding, precise data at baseline and day 28 for IGA and patient/family self‐assessments Reply received: 4 April 2016, with responses to our questions and additional information | Yes | ‐ | |
| Email sent: 14 May 2014, to [email protected], Adam Reich Regarding sequence generation and allocation concealment | Yes | Quasi randomised, exclude | |
| Emails sent: 3 April 2016, 10 April 2016, 16 April 2016, 23 April 2016, 30 April 2016, to [email protected]‐u.ac.jp Regarding sequence generation and allocation concealment, and SCORAD (mean and SD) at start maintenance phase and at day 28 No reply received | Not applicable | ‐ | |
| Emails sent: 3 April 2016, 10 April 2016, to [email protected] Regarding allocation concealment Reply received: 11 April 2016, with response to our question | Yes | ‐ | |
| Email sent: 8 April 2016, to [email protected] Regarding allocation concealment Reply received: 8 April 2016, with response to our question | Yes | ‐ | |
| Emails sent: 2 July 2014, 7 July 2014, 24 January 2016, 12 February 2016, 8 April 2016, 18 April 2016, to [email protected] ([email protected] is no longer in use) Regarding sequence generation, allocation concealment and standard deviations (or SEM) of the SCORAD at baseline, week 2, week 4 and week 6? Reply received: 18 April 2016, with some data but no information regarding sequence generation, or allocation concealment and there were no data for week 6 | In part | ‐ | |
| Email sent: 10 April 2016, to tweberQbdfusa.com Regarding sequence generation and allocation concealment | Yes | ‐ | |
| Email sent: 15 April 2016, to [email protected], karin.wiren@omega‐pharma.se Regarding sequence generation and allocation concealment | Yes | ‐ | |
| Emails sent: 5 January 2016, 15 January 2016, 31 January 2016, 12 February 2016, 10 April 2016, to [email protected] Regarding sequence generation and allocation concealment No reply received | Not applicable | ‐ | |
| Emails sent: 10 April 2016, 16 April 2016, to [email protected] Regarding allocation concealment, method of blinding, SCORAD values at start maintenance phase and follow‐up, item EQ‐5D Reply received: 18 April 2016, with responses to our questions | Yes | ‐ | |
| Abbreviations CDLQI: Children’s Dermatology Life Quality Index | |||
| MOISTURISER VERSUS VEHICLE, PLACEBO OR NO TREATMENT | ||||
|---|---|---|---|---|
| Moisturisers versus no treatment (i.e. no moisturiser) | ||||
| Study | Intervention | Comparator | Within‐participant? | Active treatment allowed? |
| Exomega lotion (oat) twice daily 6 weeks | No treatment for 6 weeks | No | Moderate‐ and high‐potency corticosteroids allowed | |
| Exomega moisturising milk (oat) twice daily for 2 months | No treatment for 2 months | No | Moderate‐ and high‐potency corticosteroids allowed | |
| Eucerin Eczema Relief body cream (oat and licochalcone) once a day for 6 months + cleanser | Only cleanser for 6 months | No | Eucerin Eczema Relief Instant Therapy allowed for active lesions, | |
| Canoderm (urea 5%) twice daily 6 months | No treatment 6 months | No | Permitted only at areas other than target lesion | |
| Cethaphil Restoraderm Body moisturiser (ceramide precursors etc) twice daily 27 days | No treatment 27 days | Yes | No | |
| Emollient balm twice daily for 28 days | Hygiene product for 28 days | No | Not mentioned | |
| Atopiclairversus vehicle | ||||
| Study | Intervention | Comparator | Within‐participant? | Active treatment allowed? |
| Atopiclair three times daily for 50 days | Vehicle three times daily for 50 days | No | No | |
| Atopiclair three times daily for 21 days | Vehicle three times daily for 21 days | No | Oral medication continued | |
| Atopiclair three times daily for 43 days | Vehicle three times daily for 43 days | No | If really needed, low‐potency topical corticosteroids allowed | |
| Patrizi 20083‐arm (1st comparison) As Atopiclair 'light' is not marketed and clearly less effective, it is not included in the comparison Atopiclair versus vehicle. The comparison Atopiclair 'light' versus vehicle (2nd comparison) will therefore not be further discussed | Atopiclair three times daily for 43 days | Vehicle three times daily for 43 days | No | If really needed, low‐potency topical corticosteroid allowed |
| Other moisturisers versus vehicle or placebo | ||||
| Urea‐containing moisturisers | ||||
| Study | Intervention | Comparator | Within‐participant? | Active treatment allowed? |
| Laceran (10% urea) twice daily for 4 weeks | Vehicle twice daily for 4 weeks | Yes | No | |
| Canoderm (urea 5%) twice daily for 6 months | No treatment for 6 months | No | Only at other areas than target lesion | |
| Laceran (10% urea) twice daily for 4 weeks | Vehicle twice daily for 4 weeks | Yes | No | |
| Lodén 20023 arm (1st comparison) | Urea saline 4% cream once daily for 30 days | Placebo (cream base) cream once daily for 30 days | No | Topical steroids allowed |
| Glycerol‐containing moisturisers | ||||
| Lodén 20023 arm (2nd comparison) | Glycerol 20% once daily for 30 days | Placebo (cream base) once daily for 30 days | No | Topical steroids allowed |
| Dexeryl (glycerol 15%) twice daily for 4 weeks | Vehicle without glycerol twice daily for 4 weeks | No | If really needed, moderate‐potency topical corticosteroid allowed | |
| Glycerol 20% twice daily for 4 weeks | Vehicle without glycerol twice daily for 4 weeks | Yes | No | |
| Oat‐containing moisturisers | ||||
| Exomega lotion (oat) twice daily for 6 weeks | No treatment for 6 weeks | No | Moderate‐ and high‐potency corticosteroids allowed | |
| Exomega moisturising milk (oat) twice daily for 2 months | No treatment for 2 months | No | Moderate‐ and high‐potency corticosteroids allowed | |
| Oatmeal based occlusive cream twice daily for 8 weeks | Occlusive vehicle for 8 weeks | No | Topical medications allowed | |
| Eucerin Eczema Relief body cream (oat and licochalcone) once a day for 6 months + cleanser | Cleanser only for 6 months | No | Eucerin Eczema Relief Instant Therapy was allowed for active lesions | |
| Remaining moisturisers versus vehicle or placebo | ||||
| Ammonium lactate 6% in water‐in‐oil emulsion twice daily for 4 weeks | Vehicle twice daily for 4 weeks | Yes | No | |
| Pale sulfonated 4% shale oil cream three times daily for 4 weeks | Vehicle three times daily for 4 weeks | No | No | |
| Atoderm Intensive cream twice daily for 6 months | Moisturiser base twice daily for 6 months | No | Topical corticosteroid and immunomodulators could be continued | |
| Triclosan 1% moisturiser twice daily for 41 days | Vehicle cream twice daily for 41 days | No | Low‐potency corticosteroid allowed | |
| Thumm 20003 arm (1st comparison) | Hippophae rhamnoides 10% cream for 4 weeks | Placebo cream for 4 weeks | No | No |
| Thumm 20003 arm (2nd comparison) | Hippophae rhamnoides 20% cream for 4 weeks | Placebo cream for 4 weeks | No | No |
| Oils versus placebo | ||||
| Gehring 1999study 1 | Primrose oil amphilic o/w emulsion twice daily for 4 weeks | Placebo oil twice daily for 4 weeks | Yes | No |
| Gehring 1999study 2 | Primrose oil amphilic w/o emulsion twice daily for 4 weeks | Placebo oil twice daily for 4 weeks | Yes | No |
| Camellia oil spray for 2 weeks | Purified water spray for 2 weeks | No | All allowed without changing | |
| ONE MOISTURISER VERSUS ANOTHER MOISTURISER | ||||
| Study | Intervention | Comparator | Within‐participant? | Active treatment allowed? |
| Patrizi 20083 arm (3rd comparison) | Atopiclair three times daily for 43 days | Atopiclair 'light' three times daily for 43 days | No | If really needed, low‐potency topical corticosteroid allowed |
| Miller 20113 arm (1st comparison) | Atopiclair three times daily for 3 weeks | EpiCeram three times daily for 3 weeks | No | No |
| Miller 20113 arm (2nd comparison) | Atopiclair three times daily for 3 weeks | Aquaphor (petrolatum 41%, glycerol, lanolin etc.), three times daily for 3 weeks | No | No |
| Miller 20113 arm (3rd comparison) | EpiCeram (high ceramides) three times daily for 3 weeks | Aquaphor three times daily for 3 weeks | No | No |
| EpiCeram twice daily for 4 weeks | Hyalotopic (hyaluronic acid, glycerol, propylene glycol etc) twice daily for 4 weeks | Yes | No | |
| EpiCeram twice daily for 3 weeks | Oatmeal‐containing cream twice daily for 3 weeks | No | No | |
| EpiCeram for 4 weeks | Eucerin for 4 weeks | Yes | No | |
| MimyX + Eucerin twice daily for 12 weeks | Eucerin cream twice daily for 12 weeks | Yes | If really needed, low‐potency topical corticosteroid allowed | |
| Albolene twice daily for 4 weeks | MimyX twice daily for 4 weeks | Yes | Low‐potency topical corticosteroid allowed | |
| Fredriksson 1975(2 studies) | Aquacare twice daily for 4 weeks | Calmurid twice daily for 4 weeks | Yes | No |
| Locobase repair twice daily for a year | Atoderma twice daily for a year | No | Moderate‐potency topical corticosteroid allowed | |
| Canoderm (urea 5%) twice daily for 6 months | Miniderm (no urea) twice daily for 6 months | No | No | |
| Urea 5% moisturiser twice daily for 6 weeks | Urea 10% lotion for 6 weeks | No | Topical steroids allowed | |
| Urea 4% + NaCl in o/w twice daily for 2 weeks | Urea 4% in o/w twice daily for 2 weeks | Yes | No | |
| Lodén 20023 arm (3rd comparison) | Glycerol 20% once daily for 30 days | Urea saline 4% cream once daily for 30 days | No | Topical corticosteroids allowed |
| Propyless (20% propylene glycol) twice daily for 2 weeks | Fenuril (urea 4% and NaCl 4%) twice daily for 2 weeks | Yes | No | |
| Ceramide‐containing moisturiser twice daily for 6 weeks | Control moisturiser (?) twice daily for 6 weeks | No | Topical corticosteroids allowed | |
| Furfuryl palmitate‐enriched moisturiser twice daily for 2 weeks | Moisturiser twice daily for 2 weeks | No | No | |
| Pro‐AMP cream (rhamnosoft ceramides) twice daily for 4 weeks | Hydrating cream (glycerol, vaseline, paraffin twice daily for 4 weeks | No | No | |
| Thumm 20003 arm (3rd comparison) | Hippophae rhamnoides 10% cream for 4 weeks | Hipophae rhamnoides 20% cream for 4 weeks | No | No |
| Lactobacillus sakei‐containing moisturiser twice daily for 4 weeks | Control moisturiser for 4 weeks | Yes | Topical corticosteroids allowed | |
| Virgin coconut oil twice daily for 8 weeks | Mineral oil twice daily for 8 weeks | No | No | |
| Virgin coconut oil twice daily for 4 weeks | Virgin olive oil twice daily for 4 weeks | No | No | |
| Bleach bath with moisturiser on one occasion | Water bath with moisturiser on one occasion | No | No | |
| MOISTURISERS VERSUS ACTIVE TREATMENT | ||||
| Moisturisers versus topical corticosteroids | ||||
| Study | Intervention | Comparator | Within‐participant? | Active treatment allowed? |
| Within‐participant studies comparing licochalcone containing moisturiser versus hydrocortisone | ||||
| O/W formulation containing licochalcone A (Glycyrrhiza Inflata root extract) twice daily for 1 week | Hydrocortisone cream twice daily for 1 week | Yes | No | |
| Licochalcone twice daily for 6 weeks | Hydrocortisone cream twice daily for 6 weeks | Yes | No | |
| Licochalcone twice daily for 4 weeks | Hydrocortisone cream twice daily for 4 weeks | Yes | No | |
| Parallel studies comparing moisturisers versus topical corticosteroids | ||||
| Stelatopia (2% sunflower oil distillate, fatty acids, ceramides) twice daily for 3 weeks | Hydrocortisone butyric propionate twice daily for 3 weeks | No | No | |
| EpiCeram twice daily for 4 weeks | Fluticasone 0.5% cream twice a day for 4 weeks | No | No (Cetaphil lotion applied to uninvolved lesions) | |
| 20% petrolatum in cetomacrogol + wet wrap for 4 weeks | Mometasone furoate 0.1% + wet wrap for 4 weeks | No | No | |
| w/o emulsion Excipial twice a day for 1 week | Hydrocortisone 1% in w/o emulsion (Excipial) twice daily for 1 week | No | No | |
| Moisturiser containing spent grain wax, spinose kernel oil, etc. twice a day for 4 weeks | Hydrocortisone 1% cream twice a day for 4 weeks | Yes | No | |
| Moisturiser (Advabase) twice a day for 16 weeks | Methylprednisolone aceponate cream 2 days a week, on other days used moisturiser twice a day for 16 weeks | No | No | |
| Moisturiser versus topical immunomodulators | ||||
| Eletone (high lipid) three times daily for 4 weeks | Pimecrolimus three times daily for 4 weeks | Yes | No | |
| Moisturiser therapy (?) for 4 weeks | Tacrolimus for 4 weeks | No | No | |
| Hyalotopic (ceramide) three times daily for 4 weeks | Pimecrolimus twice a day for 4 weeks | Yes | No | |
| VEHICLE + MOISTURISER VERSUS TOPICAL CORTICOSTEROID + MOISTURISER | ||||
| Berth‐Jones 20034 arm (1st comparison) | Vehicle cream twice weekly + moisturiser for 16 weeks | Fluticasone propionate 0.05% cream twice weekly + moisturiser for 16 weeks | No | No |
| Berth‐Jones 20034 arm (2nd comparison) We did not consider other possible comparisons of the 4 arms important for this review | Vehicle ointment twice weekly + moisturiser for 16 weeks | Fluticasone propionate 0.005% ointment twice weekly + moisturiser for 16 weeks | No | No |
| Vehicle twice a week + moisturiser for 20 weeks | Fluticasone propionate 0.05% cream twice weekly + moisturiser for 20 weeks | No | No | |
| Placebo ointment twice weekly + moisturiser for 16 weeks | Fluticasone propionate 0.005% ointment twice weekly + moisturiser for 16 weeks | No | No | |
| TOPICAL ACTIVE TREATMENT + MOISTURISER VERSUS TOPICAL ACTIVE TREATMENT ALONE | ||||
| Study | Intervention | Comparator | Within‐participant? | Active treatment allowed? |
| Draelos 20083 arm (1st comparison) | Fluocinonide 0.05% twice a day + ceramide cleanser+ moisturising cream for 4 weeks | Fluocinonide 0.05% twice a day plus cleansing bar for 4 weeks | No | No |
| Draelos 20083 arm (2nd comparison) 3rd possible comparison did not include moisturiser i.e. fluocinonide + cleansing bar vs fluocinonide + ceramide cleanser | Fluocinonide 0.05% twice a day + ceramide cleanser+ moisturising cream for 4 weeks | Fluocinonide 0.05% twice a day plus ceramide cleanser for 4 weeks | No | No |
| Moisturising and softening cream + flumethasone ointment twice a day for 3 weeks | Flumethasone ointment twice a day for 3 weeks | No | No | |
| Simpson 2011 study D | Restoraderm moisturiser twice a day + topical corticosteroids for 4 weeks | Routine use of topical corticosteroids for 4 weeks | Yes | No |
| Desonide 0.05% twice a day + three times daily moisturiser for 3 weeks | Desonide 0.05% cream twice a day for 3 weeks | Yes | No | |
| Msika 20085 arm (1st comparison) | Desonide 0.05% twice a day plus moisturiser + sunflower oil 2% twice a day for 21 days | Desonide 0.05% twice a day for 21 days | No | No |
| Msika 20085 arm (2nd comparison) We did not consider other possible comparisons of the 5 arms to be important for this review | Desonide 0.05% once daily plus moisturiser + sunflower oil 2% twice a day for 21 days | Desonide 0.05% once daily for 21 days | No | No |
| BoPao cream + 10% urea ointment once a day or twice a day for 2 weeks | BoPao cream only (antifungal/anti‐inflammatory cream) | No | No | |
| o/w: oil in water w/o: water in oil | ||||
| Study ID | Interventions & comparisons | N | Comments |
|---|---|---|---|
| 5% urea as active substance versus 4% urea and 4% NaCl | 50 | The data were reported in box‐and‐whisker plots, and no precise data were provided, too much estimation | |
| Emollient + fresh expressed milk versus moisturiser only | 9 | None of our outcomes were assessed | |
| Aqueous cream BP versus Oilatum Junior Bath additive | 38 | Poster with limited information. The principal investigator said, "The study itself was a purely mechanistic study, and not meant to provide clinical evidence" | |
| Nioleol (10% primrose oil, 8%‐9% γ‐linolenic acid) versus Uriage (borage oil and 24% γ‐linolenic acid) versus Atopic (35%‐40% γ‐linolenic acid) versus Atoderm control moisturiser once daily for 12 weeks | 23 | Unclear how many participants were randomised to each arm | |
| Proderm versus no treatment | 24 | No baseline data nor end value data were reported. The data were reported in box‐and‐whisker plots, and were not interpretable | |
| Oilatum Plus versus Oilatum Emollient | 30 | Unclear how many participants were randomised to each arm, inconsistencies in reporting of data | |
| Study 1 Emulsifying ointment with aqueous cream versus emulsifying ointment with baby oil Study 2 Cetomacrogol versus emulsifying ointment versus glycerol/petrolatum versus petroleum jelly | 120 | Frequency of use during day or week were not reported. There were quite some inconsistencies in text and figures. Study 2 reported no end data, just that all scores tended to decline. We mailed investigators numerous times to clarify study details, but received no response. | |
| Midpotency corticosteroid cream versus midpotency corticosteroid cream combined with a hydrolipid cream | 6 | Poster with limited information, principal investigator was not able to provide missing study details | |
| Glycerol 20% cream versus 4% urea and 4% NaCl | 110 | Unclear how many participants were randomised to each arm. The data all need to be estimated from box‐and‐whisker plots, too much estimation | |
| PPARα activator and ceramide versus moisturiser without these ingredients | 31 | Only 5 participants with eczema included, no individual patient data, not our prespecified outcomes | |
| Cis‐urocanic acid 5% emulsion cream versus control vehicle | 14 | Data provided need to be estimated from figures (for transepidermal water loss (TEWL)), or no precise data were provided other than that there were no significant differences. We mailed investigators numerous times to clarify study details, but received no response | |
| Cream containing 10% urea versus control cream | 70 | Unclear how many were randomised to each treatment arm, no separate data for healthy subjects and atopic subjects | |
| Two different formulations of polidocanol‐ and urea‐containing creams against each other | 54 | Unclear how many were randomised to each treatment arm, no separate data for healthy subjects and atopic subjects | |
| Urea 10% ointment versus base OR versus urea 20% ointment | 552 | The data were confusingly reported in this study and did not lend themselves to further analysis. As the study was 39 years old we have not contacted the investigators for data |
| Analysis | Comparison | MD/RR/HR/SMD | 95% confidence interval | P value |
|---|---|---|---|---|
| Change from baseline in SCORAD | Moisturisers versus no treatment Pooled data | MD ‐2.51 | ‐3.66 to ‐1.37 | P < 0.0001 |
| Number of participants experiencing a flare | Moisturisers versus no treatment Pooled data | RR 0.39 | 0.22 to 0.68 | P = 0.0008 |
| Amount of topical steroids used | Moisturisers versus no treatment Pooled data for the first 3 to 4 weeks | MD ‐5.34 | ‐7.79 to ‐2.89 | P < 0.0001 |
| Moisturisers versus no treatment Single study data last 3 to 4 weeks | MD 0.50 | ‐4.70 to 5.70 | P = 0.85 | |
| Moisturisers versus no treatment Pooled data for 6 to 8 weeks | MD ‐8.11 | ‐11.00 to ‐5.22 | P < 0.00001 | |
| Change from baseline in quality of life | Moisturisers versus no treatment Pooled data | SMD ‐0.14 | ‐0.44 to 0.16 | P = 0.35 |
| Number of participants who experienced good improvement to total resolution | Atopiclair versus vehicle Pooled data | RR 4.16 | 2.96 to 5.86 | P < 0.00001 |
| Change from baseline itch measured on a VAS | Atopiclair versus vehicle Pooled data | MD ‐2.08 | ‐2.35 to ‐1.81 | P < 0.00001 |
| Number of participants reporting an adverse event | Atopiclair versus vehicle Pooled data | RR 1.04 | 0.80 to 1.35 | P = 0.78 |
| Change from baseline in EASI | Atopiclair versus vehicle Pooled data | MD ‐4.05 | ‐5.00 to ‐3.10 | P < 0.00001 |
| Number of participants experiencing a flare | Atopiclair versus vehicle Pooled data | RR 0.18 | 0.11 to 0.31 | P < 0.00001 |
| Change from baseline in skin capacitance | Urea‐containing versus vehicle | MD 3.13 | 2.13 to 4.13 | P < 0.00001 |
| Numbers of participants reporting an adverse event | Glycerol versus placebo cream Pooled data | RR 0.89 | 0.67 to 1.18 | P = 0.46 |
| Change in disease severity as assessed by the investigators | Oat‐containing cream versus vehicle or no treatment Pooled data | SMD ‐0.19 | ‐0.43 to 0.05 | P = 0.12 |
| Change from baseline in quality of life | Oat‐containing cream versus vehicle or no treatment Pooled data | SMD ‐0.09 | ‐0.35 to 0.17 | P = 0.51 |
| Number of participants that experienced improvement | All moisturisers versus vehicle, placebo or no treatment Pooled data | RR 2.20 | 1.84 to 2.62 | P < 0.00001 |
| Change from baseline in itch | All moisturisers versus vehicle, placebo or no treatment Pooled data | SMD ‐0.88 | ‐1.04 to ‐0.72 | P < 0.00001 |
| Number of participants that expressed treatment satisfaction | All moisturisers versus vehicle, placebo or no treatment Pooled data | RR 1.69 | 1.35 to 2.11 | P < 0.00001 |
| Number of participants reporting an adverse event | All moisturisers versus vehicle, placebo or no treatment Pooled data | RR 1.06 | 0.88 to 1.27 | P = 0.56 |
| Change in disease severity as assessed by the investigators | All moisturisers versus vehicle, placebo or no treatment Pooled data | SMD ‐0.62 | ‐0.73 to ‐0.51 | P < 0.00001 |
| Number of participants experiencing a flare | All moisturisers versus vehicle, placebo or no treatment Pooled data | RR 0.35 | 0.26 to 0.47 | P < 0.00001 |
| Change from baseline in quality of life | All moisturisers versus vehicle, placebo or no treatment Pooled data | SMD ‐0.40 | ‐0.64 to ‐0.17 | P = 0.0006 |
| Change from baseline in TEWL | Primrose oil versus placebo oil Pooled data | MD ‐0.34 | ‐1.44 to 0.76 | P = 0.55 |
| Change from baseline in skin hydration | Primrose oil versus placebo oil Pooled data | MD 0.34 | ‐2.54 to 3.21 | P = 0.82 |
| Change from baseline in itch (VAS) | Licochalcone versus hydrocortisone Pooled data | MD ‐0.37 | ‐0.75 to ‐0.00 | P = 0.05 |
| Change from baseline in SCORAD | Licochalcone versus hydrocortisone Pooled data | MD ‐0.12 | ‐0.77 to 0.54 | P = 0.73 |
| Change from baseline in TEWL | Licochalcone versus hydrocortisone Pooled data | MD ‐2.04 | ‐3.60 to ‐0.49 | P = 0.010 |
| Number of participants reporting an adverse event | Vehicle plus moisturiser versus fluticasone propionate plus moisturiser Pooled data | RR 0.60 | 0.42 to 0.85 | P = 0.004 |
| Number of participants experiencing a flare | Vehicle plus moisturiser versus fluticasone propionate plus moisturiser Pooled data | RR 2.27 | 1.91 to 2.71 | P < 0.00001 |
| Hazard ratio for rate of flare | Vehicle plus moisturiser versus fluticasone propionate plus moisturiser Pooled data | HR 3.67 | 2.78 to 4.84 | P < 0.00001 |
| Change in disease severity as assessed by the investigators | Active treatment in combination with a moisturiser versus active treatment only Pooled data | SMD ‐0.87 | ‐1.17 to ‐0.57 | P = 0.00001 |
| Change in quality of life IDQOL | Active treatment in combination with a moisturiser versus active treatment only Pooled data | MD ‐1.31 | ‐2.70 to 0.09 | P = 0.07 |
| Change of quality of life DFI | Active treatment in combination with a moisturiser versus active treatment only Pooled data | MD ‐1.03 | ‐2.47 to 0.42 | P = 0.17 |
| Abbreviations DFI: dermatitis family impact | ||||
| MOISURISER VERSUS NO MOISTURISER | ||||||
|---|---|---|---|---|---|---|
| Change from baseline in SCORAD | ||||||
| Variable | Number of studies | Number of participants in moisturiser group | Number of participants in control group | MD (95% CI) | Heterogeneity I² | P value |
| All trials (Giordano‐Labadie 2006; Grimalt 2007; Patrizi 2014) | 3 | 141 | 135 | ‐2.42 (‐4.55 to ‐0.28) | 68% | P = 0.03 |
| Sequence generation | ||||||
| Low risk (all trials) | 3 | 141 | 135 | ‐2.42 (‐4.55 to ‐0.28) | 68% | P = 0.03 |
| Allocation concealment | ||||||
| Low risk (all trials) | 3 | 141 | 135 | ‐2.42 (‐4.55 to ‐0.28) | 68% | P = 0.03 |
| Blinding of participants and personnel | ||||||
| High risk (all trials) | 3 | 141 | 135 | ‐2.42 (‐4.55 to ‐0.28) | 68% | P = 0.03 |
| Blinding of outcome assessment | ||||||
| High risk (all trials) | 3 | 141 | 135 | ‐2.42 (‐4.55 to ‐0.28) | 68% | P = 0.03 |
| Incomplete outcome data | ||||||
| Low risk (Giordano‐Labadie 2006; Patrizi 2014) | 2 | 63 | 65 | ‐3.39 (‐4.73 to ‐2.05) | 0% | P < 0.00001 |
| High risk (Grimalt 2007) | 1 | 78 | 70 | ‐0.16 (‐2.36 to 2.04) | NA | P = 0.89 |
| Selective reporting | ||||||
| Low risk (all trials) | 3 | 141 | 135 | ‐2.42 (‐4.55 to ‐0.28) | 68% | P = 0.03 |
| Other bias | ||||||
| Low risk (all trials) | 3 | 141 | 135 | ‐2.42 (‐4.55 to ‐0.28) | 68% | P = 0.03 |
| ATOPICLAIR VERSUS VEHICLE | ||||||
| Number of participants who considered their skin to have improved | ||||||
| Variable | Number of studies | Number of participants in Atopiclair group | Number of participants in vehicle group | RR (95% CI) | Heterogeneity I² | P value |
| All trials (Abramovits 2008; Belloni 2005; Boguniewicz 2008) | 3 | 232 | 158 | 4.51 (2.19 to 9.29) | 64% | P < 0.0001 |
| Sequence generation | ||||||
| Low risk (all trials) | 3 | 232 | 158 | 4.51 (2.19 to 9.29) | 64% | P < 0.0001 |
| Allocation concealment | ||||||
| Low risk (Abramovits 2008; Belloni 2005) | 2 | 160 | 88 | 3.09 (2.08 to 4.59) | 0% | P < 0.00001 |
| Unclear risk (Boguniewicz 2008) | 1 | 72 | 70 | 8.06 (3.95 to 16.42) | NA | P < 0.00001 |
| Blinding of participants and personnel | ||||||
| Low risk (Abramovits 2008; Belloni 2005) | 2 | 160 | 88 | 3.09 (2.08 to 4.59) | 0% | P < 0.00001 |
| Unclear risk (Boguniewicz 2008) | 1 | 72 | 70 | 8.06 (3.95 to 16.42) | NA | P < 0.00001 |
| Blinding of outcome assessment | ||||||
| Low risk (Abramovits 2008; Belloni 2005) | 2 | 160 | 88 | 3.09 (2.08 to 4.59) | 0% | P < 0.00001 |
| Unclear risk (Boguniewicz 2008) | 1 | 72 | 70 | 8.06 (3.95 to 16.42) | NA | P < 0.00001 |
| Incomplete outcome data | ||||||
| Low risk (Belloni 2005; Boguniewicz 2008) | 2 | 87 | 85 | 6.95 (3.69 to 13.07) | 0% | P < 0.00001 |
| High risk (Abramovits 2008) | 1 | 145 | 73 | 3.02 (2.00 to 4.56) | NA | P < 0.00001 |
| Selective reporting | ||||||
| Low risk (all trials) | 3 | 232 | 158 | 4.51 (2.19 to 9.29) | 64% | P < 0.0001 |
| Other bias | ||||||
| Low risk (all trials) | 3 | 232 | 158 | 4.51 (2.19 to 9.29) | 64% | P < 0.0001 |
| Change from baseline in itch measured on a VAS | ||||||
| Variable | Number of studies | Number of participants in Atopiclair group | Number of participants in vehicle group | MD (95% CI) | Heterogeneity I² | P value |
| All trials (Abramovits 2008; Belloni 2005; Boguniewicz 2008; Patrizi 2008) | 4 | 235 | 161 | ‐2.65 (‐4.21 to ‐1.09) | 97% | P = 0.0008 |
| Sequence generation | ||||||
| Low risk (all trials) | 4 | 235 | 161 | ‐2.65 (‐4.21 to ‐1.09) | 97% | P = 0.0008 |
| Allocation concealment | ||||||
| Low risk (Abramovits 2008; Belloni 2005; Patrizi 2008) | 3 | 163 | 91 | ‐2.25 (‐3.83 to ‐0.68) | 95% | P = 0.005 |
| Unclear risk (Boguniewicz 2008) | 1 | 72 | 70 | ‐3.80 (‐4.36 to ‐3.24) | NA | P < 0.00001 |
| Blinding of participants and personnel | ||||||
| Low risk (Abramovits 2008; Belloni 2005; Patrizi 2008) | 3 | 163 | 91 | ‐2.25 (‐3.83 to ‐0.68) | 95% | P = 0.005 |
| Unclear risk (Boguniewicz 2008) | 1 | 72 | 70 | ‐3.80 (‐4.36 to ‐3.24) | NA | P < 0.00001 |
| Blinding of outcome assessment | ||||||
| Low risk (Abramovits 2008; Belloni 2005; Patrizi 2008) | 3 | 163 | 91 | ‐2.25 (‐3.83 to ‐0.68) | 95% | P = 0.005 |
| Unclear risk (Boguniewicz 2008) | 1 | 72 | 70 | ‐3.80 (‐4.36 to ‐3.24) | NA | P < 0.00001 |
| Incomplete outcome data | ||||||
| Low risk (Belloni 2005; Boguniewicz 2008; Patrizi 2008) | 3 | 106 | 104 | ‐2.33 (‐4.13 to ‐0.52) | 97% | P = 0.01 |
| High risk ((Abramovits 2008) | 1 | 129 | 57 | ‐3.70 (‐4.66 to ‐2.74) | NA | P < 0.00001 |
| Selective reporting | ||||||
| Low risk (all trials) | 4 | 235 | 161 | ‐2.65 (‐4.21 to ‐1.09) | 97% | P = 0.0008 |
| Other bias | ||||||
| Low risk (all trials) | 4 | 235 | 161 | ‐2.65 (‐4.21 to ‐1.09) | 97% | P = 0.0008 |
| Change from baseline in EASI | ||||||
| Variable | Number of studies | Number of participants in Atopiclair group | Number of participants in vehicle group | MD (95% CI) | Heterogeneity I² | P value |
| All trials (Abramovits 2008; Belloni 2005; Boguniewicz 2008; Patrizi 2008) | 4 | 251 | 175 | ‐4.00 (‐5.42 to ‐2.57) | 51% | P < 0.00001 |
| Sequence generation | ||||||
| Low risk (all trials) | 4 | 251 | 175 | ‐4.00 (‐5.42 to ‐2.57) | 51% | P < 0.00001 |
| Allocation concealment | ||||||
| Low risk Abramovits 2008; Belloni 2005; Patrizi 2008) | 3 | 179 | 105 | ‐3.36 (‐4.47 to ‐2.25) | 0% | P < 0.00001 |
| Unclear risk (Boguniewicz 2008) | 1 | 72 | 70 | ‐5.99 (‐7.85 to ‐4.13) | NA | P < 0.00001 |
| Blinding of participants and personnel | ||||||
| Low risk Abramovits 2008; Belloni 2005; Patrizi 2008) | 3 | 179 | 105 | ‐3.36 (‐4.47 to ‐2.25) | 0% | P < 0.00001 |
| Unclear risk (Boguniewicz 2008) | 1 | 72 | 70 | ‐5.99 (‐7.85 to ‐4.13) | NA | P < 0.00001 |
| Blinding of outcome assessment | ||||||
| Low risk Abramovits 2008; Belloni 2005; Patrizi 2008) | 3 | 179 | 105 | ‐3.36 (‐4.47 to ‐2.25) | 0% | P < 0.00001 |
| Unclear risk (Boguniewicz 2008) | 1 | 72 | 70 | ‐5.99 (‐7.85 to ‐4.13) | NA | P < 0.00001 |
| Incomplete outcome data | ||||||
| Low risk (Belloni 2005) | 1 | 15 | 15 | ‐3.30 (‐5.67 to ‐0.93) | NA | P = 0.006 |
| Unclear risk (Boguniewicz 2008; Patrizi 2008) | 2 | 91 | 89 | ‐4.42 (‐7.73 to ‐1.10) | 77% | P = 0.009 |
| High risk (Abramovits 2008) | 1 | 145 | 71 | ‐3.62 (‐5.06 to ‐2.18) | NA | P < 0.0001 |
| Selective reporting | ||||||
| Low risk (all trials) | 4 | 251 | 175 | ‐4.00 (‐5.42 to ‐2.57) | 51% | P < 0.00001 |
| Other bias | ||||||
| Low risk (all trials) | 4 | 251 | 175 | ‐4.00 (‐5.42 to ‐2.57) | 51% | P < 0.00001 |
| OAT‐CONTAINING MOISTURISERS VERSUS VEHICLE OR NO TREATMENT (NO MOISTURISER) | ||||||
| Change from baseline in disease severity as assessed by the investigators (EASI and SCORAD) | ||||||
| Variable | Number of studies | Number of participants in oat‐containing moisturiser group | Number of participants in control group | SMD (95% CI) | Heterogeneity I² | P value |
| All trials (Giordano‐Labadie 2006; Grimalt 2007; Nebus 2009) | 3 | 138 | 134 | ‐0.23 (‐0.66 to 0.21) | 65% | P = 0.30 |
| Sequence generation | ||||||
| Low risk (all trials) | 3 | 138 | 134 | ‐0.23 (‐0.66 to 0.21) | 65% | P = 0.30 |
| Allocation concealment | ||||||
| Low risk (all trials) | 3 | 138 | 134 | ‐0.23 (‐0.66 to 0.21) | 65% | P = 0.30 |
| Blinding of participants and personnel | ||||||
| Low risk (Nebus 2009) | 1 | 25 | 25 | 0.01 (‐0.55 to 0.56) | NA | P = 0.98 |
| High risk (Giordano‐Labadie 2006; Grimalt 2007) | 2 | 113 | 109 | ‐0.33 (‐0.98 to 0.32) | 81% | P = 0.32 |
| Blinding of outcome assessment | ||||||
| Low risk (Nebus 2009) | 1 | 25 | 25 | 0.01 (‐0.55 to 0.56) | NA | P = 0.98 |
| High risk (Giordano‐Labadie 2006; Grimalt 2007) | 2 | 113 | 109 | ‐0.33 (‐0.98 to 0.32) | 81% | P = 0.32 |
| Incomplete outcome data | ||||||
| Low risk (Giordano‐Labadie 2006; Nebus 2009) | 2 | 60 | 64 | ‐0.36 (‐1.03 to 0.32) | 71% | P = 0.30 |
| High risk (Grimalt 2007) | 1 | 78 | 70 | ‐0.02 (‐0.35 to 0.30) | NA | P = 0.98 |
| Selective reporting | ||||||
| Low risk (all trials) | 3 | 138 | 134 | ‐0.23 (‐0.66 to 0.21) | 65% | P = 0.30 |
| Other bias | ||||||
| Low risk (all trials) | 3 | 138 | 134 | ‐0.23 (‐0.66 to 0.21) | 65% | P = 0.30 |
| Effect | ||||||
| No difference (Grimalt 2007; Nebus 2009) | 2 | 103 | 95 | ‐0.02 (‐0.29 to 0.26) | 0% | P = 0.91 |
| Difference in favour of oat‐containing moisturiser (Giordano‐Labadie 2006) | 1 | 35 | 39 | ‐0.69 (‐1.16 to ‐0.22) | NA | P = 0.004 |
| Change from baseline in quality of life | ||||||
| Variable | Number of studies | Number of participants in oat‐containing moisturiser group | Number of participants in control group | SMD (95% CI) | Heterogeneity I² | P value |
| All trials (Giordano‐Labadie 2006; Grimalt 2007; Nebus 2009) | 3 | 110 | 116 | ‐0.09 (‐0.37 to 0.19) | 12% | P = 0.53 |
| Sequence generation | ||||||
| Low risk (all trials) | 3 | 110 | 116 | ‐0.09 (‐0.37 to 0.19) | 12% | P = 0.53 |
| Allocation concealment | ||||||
| Low risk (all trials) | 3 | 110 | 116 | ‐0.09 (‐0.37 to 0.19) | 12% | P = 0.53 |
| Blinding of participants and personnel | ||||||
| Low risk (Nebus 2009) | 1 | 25 | 25 | 0.10 (‐0.46 to 0.65) | NA | P = 0.74 |
| High risk (Giordano‐Labadie 2006; Grimalt 2007) | 2 | 85 | 91 | ‐0.16 (‐0.55 to 0.24) | 42% | P = 0.44 |
| Blinding of outcome assessment | ||||||
| Low risk (Nebus 2009) | 1 | 25 | 25 | 0.10 (‐0.46 to 0.65) | NA | P = 0.74 |
| High risk (Giordano‐Labadie 2006; Grimalt 2007) | 2 | 85 | 91 | ‐0.16 (‐0.55 to 0.24) | 42% | P = 0.44 |
| Incomplete outcome data | ||||||
| Low risk (Giordano‐Labadie 2006; Nebus 2009) | 2 | 60 | 64 | ‐0.17 (‐0.63 to 0.29) | 39% | P = 0.48 |
| High risk (Grimalt 2007) | 1 | 50 | 52 | 0.03 (‐0.36 to 0.41) | NA | P = 0.89 |
| Selective reporting | ||||||
| Low risk (all trials) | 3 | 110 | 116 | ‐0.09 (‐0.37 to 0.19) | 12% | P = 0.53 |
| Other bias | ||||||
| Low risk (all trials) | 3 | 110 | 116 | ‐0.09 (‐0.37 to 0.19) | 12% | P = 0.53 |
| ALL MOISTURISERS VERSUS VEHICLE TO PLACEBO OR NO MOISTURISER | ||||||
| Number of participants who considered their skin to have improved | ||||||
| Variable | Number of studies | Number of participants in moisturiser group | Number of participants in control group | RR (95% CI) | Heterogeneity I² | P value |
| All studies (Abramovits 2008; Belloni 2005; Boguniewicz 2008; Lodén 2002; Nebus 2009) | 5 | 323 | 249 | 2.46 (1.16 to 5.23) | 95% | P = 0.02 |
| Sequence generation | ||||||
| Low risk (Abramovits 2008; Belloni 2005; Boguniewicz 2008; Nebus 2009 | 4 | 257 | 183 | 3.10 (0.98 to 9.82) | 95% | P = 0.05 |
| Unclear risk (Lodén 2002) | 1 | 66 | 66 | 1.24 (1.03 to 1.49) | NA | P = 0.02 |
| Allocation concealment | ||||||
| Low risk (Abramovits 2008; Belloni 2005; Nebus 2009) | 3 | 185 | 113 | 2.19 (0.75 to 6.39) | 95% | P = 0.15 |
| Unclear risk (Boguniewicz 2008; Lodén 2002) | 2 | 138 | 136 | 3.11 (0.25 to 38.71) | 98% | P = 0.98 |
| Blinding of participants and personnel | ||||||
| Low risk (Abramovits 2008; Belloni 2005; Nebus 2009) | 3 | 185 | 113 | 2.19 (0.75 to 6.39) | 95% | P = 0.15 |
| Unclear risk (Boguniewicz 2008; Lodén 2002) | 2 | 138 | 136 | 3.11 (0.25 to 38.71) | 98% | P = 0.98 |
| Blinding of outcome assessment | ||||||
| Low risk (Abramovits 2008; Belloni 2005; Nebus 2009) | 3 | 185 | 113 | 2.19 (0.75 to 6.39) | 95% | P = 0.15 |
| Unclear risk (Boguniewicz 2008; Lodén 2002) | 2 | 138 | 136 | 3.11 (0.25 to 38.71) | 98% | P = 0.98 |
| Incomplete outcome data | ||||||
| Low risk (Belloni 2005; Lodén 2002; Nebus 2009) | 3 | 106 | 106 | 1.23 (0.94 to 1.62) | 48% | P = 0.13 |
| Unclear risk (Boguniewicz 2008) | 1 | 72 | 70 | 8.06 (3.95 to 16.42) | NA | P < 0.00001 |
| High risk (Abramovits 2008) | 1 | 145 | 73 | 3.02 (2.00 to 4.56) | NA | P < 0.00001 |
| Selective reporting | ||||||
| Low risk (all trials) | 5 | 323 | 249 | 2.46 (1.16 to 5.23) | 95% | P = 0.02 |
| Other bias | ||||||
| Low risk (all trials) | 5 | 323 | 249 | 2.46 (1.16 to 5.23) | 95% | P = 0.02 |
| Change from baseline in itch | ||||||
| Variable | Number of studies | Number of participants in moisturiser group | Number of participants in control group | SMD (95% CI) | Heterogeneity I² | P value |
| All studies (Abramovits 2008; Belloni 2005; Boguniewicz 2008; Boralevi 2014; Nebus 2009; Patrizi 2008; Patrizi 2014) | 7 | 412 | 337 | ‐1.10 (‐1.83 to ‐0.38) | 94% | P = 0.003 |
| Sequence generation | ||||||
| Low risk (all trials) | 7 | 412 | 337 | ‐1.10 (‐1.83 to ‐0.38) | 94% | P = 0.003 |
| Allocation concealment | ||||||
| Low risk (Abramovits 2008; Belloni 2005; Boralevi 2014; Nebus 2009; Patrizi 2008; Patrizi 2014) | 6 | 340 | 267 | ‐0.89 (‐1.56 to ‐0.23) | 91% | P = 0.009 |
| Unclear risk (Boguniewicz 2008) | 1 | 72 | 70 | ‐2.22 (‐2.64 to ‐1.80) | NA | P < 0.00001 |
| Blinding of participants and personnel | ||||||
| Low risk (Abramovits 2008; Belloni 2005; Boralevi 2014; Nebus 2009; Patrizi 2008) | 5 | 312 | 241 | ‐0.98 (‐1.79 to ‐0.18) | 93% | P < 0.00001 |
| Unclear risk (Boguniewicz 2008) | 1 | 72 | 70 | ‐2.22 (‐2.64 to ‐1.80) | NA | P < 0.00001 |
| High risk (Patrizi 2014) | 1 | 28 | 26 | ‐0.52 (‐1.06 to 0.03) | NA | P = 0.06 |
| Blinding of outcome assessment | ||||||
| Low risk (Abramovits 2008; Belloni 2005; Boralevi 2014; Nebus 2009; Patrizi 2008) | 5 | 312 | 241 | ‐0.98 (‐1.79 to ‐0.18) | 93% | P < 0.00001 |
| Unclear risk (Boguniewicz 2008) | 1 | 72 | 70 | ‐2.22 (‐2.64 to ‐1.80) | NA | P < 0.00001 |
| High risk (Patrizi 2014) | 1 | 28 | 26 | ‐0.52 (‐1.06 to 0.03) | NA | P = 0.06 |
| Incomplete outcome data | ||||||
| Low risk (Belloni 2005; Boralevi 2014; Nebus 2009; Patrizi 2014) | 4 | 192 | 191 | ‐0.38 (‐0.94 to 0.17) | 80% | P = 0.18 |
| Unclear risk (Boguniewicz 2008; Patrizi 2008) | 2 | 91 | 89 | ‐2.29 (‐2.67 to ‐1.91) | 0% | P < 0.00001 |
| High risk (Abramovits 2008) | 1 | 129 | 57 | ‐1.33 (‐1.67 to ‐0.99) | NA | P < 0.00001 |
| Selective reporting | ||||||
| Low risk (all trials) | 7 | 412 | 337 | ‐1.10 (‐1.83 to ‐0.38) | 94% | P = 0.003 |
| Other bias | ||||||
| Low risk (all trials) | 7 | 412 | 337 | ‐1.10 (‐1.83 to ‐0.38) | 94% | P = 0.003 |
| Number of participants who expressed treatment satisfaction | ||||||
| Variable | Number of studies | Number of participants in moisturiser group | Number of participants in control group | RR (95% CI) | Heterogeneity I² | P value |
| All trials (Abramovits 2008; Belloni 2005; Nebus 2009) | 3 | 185 | 113 | 1.35 (0.77 to 2.36) | 83% | P = 0.29 |
| Sequence generation | ||||||
| Low risk (all trials) | 3 | 185 | 113 | 1.35 (0.77 to 2.36) | 83% | P = 0.29 |
| Allocation concealment | ||||||
| Low risk (all trials) | 3 | 185 | 113 | 1.35 (0.77 to 2.36) | 83% | P = 0.29 |
| Blinding of participants and personnel | ||||||
| Low risk (all trials) | 3 | 185 | 113 | 1.35 (0.77 to 2.36) | 83% | P = 0.29 |
| Blinding of outcome assessment | ||||||
| Low risk (all trials) | 3 | 185 | 113 | 1.35 (0.77 to 2.36) | 83% | P = 0.29 |
| Incomplete outcome data | ||||||
| Low risk (Belloni 2005; Nebus 2009) | 2 | 40 | 40 | 1.04 (0.77 to 1.42) | 0% | P = 0.79 |
| High risk (Abramovits 2008) | 1 | 145 | 73 | 2.14 (1.58 to 2.89) | NA | P < 0.00001 |
| Selective reporting | ||||||
| Low risk (all trials) | 3 | 185 | 113 | 1.35 (0.77 to 2.36) | 83% | P = 0.29 |
| Other bias | ||||||
| Low risk (all trials) | 3 | 185 | 113 | 1.35 (0.77 to 2.36) | 83% | P = 0.29 |
| Number of participants who reported an adverse event | ||||||
| Variable | Number of studies | Number of participants in moisturiser group | Number of participants in control group | RR (95% CI) | Heterogeneity I² | P value |
| All trials (Abramovits 2008; Belloni 2005; Boguniewicz 2008; Boralevi 2014; Gayraud 2015; Grimalt 2007; Korting 2010; Lodén 2002; Patrizi 2008; Tan 2010) | 10 | 680 | 595 | 1.03 (0.82 to 1.30) | 21% | P = 0.80 |
| Sequence generation | ||||||
| Low risk (Abramovits 2008; Belloni 2005; Boguniewicz 2008; Boralevi 2014; Gayraud 2015; Grimalt 2007; Korting 2010; Patrizi 2008; Tan 2010) | 9 | 614 | 529 | 0.96 (0.74 to 1.24) | 16% | P = 0.76 |
| Unclear risk (Lodén 2002) | 1 | 66 | 66 | 1.31 (0.89 to 1.91) | NA | P = 0.17 |
| Allocation concealment | ||||||
| Low risk ((Abramovits 2008; Belloni 2005; Boralevi 2014; Gayraud 2015; Grimalt 2007; Korting 2010; Patrizi 2008; Tan 2010) | 7 | 491 | 411 | 1.00 (0.65 to 1.55) | 35% | P = 0.99 |
| Unclear risk (Boguniewicz 2008; Korting 2010; Lodén 2002) | 3 | 189 | 184 | 1.08 (0.82 to 1.43) | 15% | P = 0.59 |
| Blinding of participants and personnel | ||||||
| Low risk (Abramovits 2008; Belloni 2005; Boralevi 2014; Gayraud 2015; Patrizi 2008; Tan 2010) | 6 | 400 | 329 | 0.94 (0.72 to 1.24) | 0% | P = 0.67 |
| Unclear risk (Boguniewicz 2008; Lodén 2002) | 2 | 138 | 136 | 1.11 (0.83 to 1.48) | 26% | P = 0.49 |
| High risk (Grimalt 2007; Korting 2010) | 2 | 142 | 130 | 2.27 (0.06 to 90.70) | 80% | P = 0.66 |
| Blinding of outcome assessment | ||||||
| Low risk (Abramovits 2008; Belloni 2005; Boralevi 2014; Gayraud 2015; Patrizi 2008; Tan 2010) | 6 | 400 | 329 | 0.94 (0.72 to 1.24) | 0% | P = 0.67 |
| Unclear risk (Boguniewicz 2008; Lodén 2002) | 2 | 138 | 136 | 1.11 (0.83 to 1.48) | 26% | P = 0.49 |
| High risk (Grimalt 2007; Korting 2010) | 2 | 142 | 130 | 2.27 (0.06 to 90.70) | 80% | P = 0.66 |
| Incomplete outcome data | ||||||
| Low risk (Belloni 2005; Boralevi 2014; Gayraud 2015; Korting 2010; Lodén 2002; Tan 2010) | 6 | 352 | 350 | 0.99 (0.70 to 1.40) | 23% | P = 0.96 |
| Unclear risk (Boguniewicz 2008; Patrizi 2008) | 2 | 92 | 90 | 0.95 (0.69 to 1.30) | 0% | P = 0.73 |
| High risk (Abramovits 2008; Grimalt 2007) | 2 | 236 | 155 | 3.04 (0.24 to 38.72) | 71% | P = 0.39 |
| Selective reporting | ||||||
| Low risk (all trials) | 10 | 680 | 595 | 1.03 (0.82 to 1.30) | 21% | P = 0.80 |
| Other bias | ||||||
| Low risk (all trials) | 10 | 680 | 595 | 1.03 (0.82 to 1.30) | 21% | P = 0.80 |
| Change in disease severity as assessed by the investigators | ||||||
| Variable | Number of studies | Number of participants in moisturiser group | Number of participants in control group | SMD (95% CI) | Heterogeneity I² | P value |
| All studies (Abramovits 2008; Belloni 2005; Boguniewicz 2008; Boralevi 2014; Gayraud 2015; Giordano‐Labadie 2006; Grimalt 2007; Korting 2010; Nebus 2009; Patrizi 2008; Patrizi 2014; Tan 2010) | 12 | 683 | 598 | ‐0.65 (‐0.89 to ‐0.41) | 75% | P < 0.00001 |
| Sequence generation | ||||||
| Low risk (all trials) | 12 | 683 | 598 | ‐0.65 (‐0.89 to ‐0.41) | 75% | P < 0.00001 |
| Allocation concealment | ||||||
| Low risk (Abramovits 2008; Belloni 2005; Boralevi 2014; Gayraud 2015; Giordano‐Labadie 2006; Grimalt 2007; Nebus 2009; Patrizi 2008; Patrizi 2014; Tan 2010) | 10 | 561 | 481 | ‐0.53 (‐0.76 to ‐0.30) | 66% | P = 0.009 |
| Unclear risk (Boguniewicz 2008; Korting 2010) | 2 | 122 | 117 | ‐1.15 (‐1.43 to ‐0.88) | 0% | P < 0.00001 |
| Blinding of participants and personnel | ||||||
| Low risk (Abramovits 2008; Belloni 2005; Boralevi 2014; Gayraud 2015; Nebus 2009; Patrizi 2008; Tan 2010) | 7 | 420 | 346 | ‐0.53 (‐0.77 to ‐0.30) | 52% | P < 0.00001 |
| Unclear risk (Boguniewicz 2008) | 1 | 72 | 70 | ‐1.04 (‐1.39 to ‐0.69) | NA | P < 0.00001 |
| High risk ( Giordano‐Labadie 2006; Grimalt 2007; Korting 2010; Patrizi 2014) | 4 | 191 | 182 | ‐0.77 (‐1.41 to ‐0.12) | 88% | P = 0.02 |
| Blinding of outcome assessment | ||||||
| Low risk (Abramovits 2008; Belloni 2005; Boralevi 2014; Gayraud 2015; Nebus 2009; Patrizi 2008; Tan 2010) | 7 | 420 | 346 | ‐0.53 (‐0.77 to ‐0.30) | 52% | P < 0.00001 |
| Unclear risk (Boguniewicz 2008) | 1 | 72 | 70 | ‐1.04 (‐1.39 to ‐0.69) | NA | P < 0.00001 |
| High risk (Giordano‐Labadie 2006; Grimalt 2007; Korting 2010; Patrizi 2014) | 4 | 191 | 182 | ‐0.77 (‐1.41 to ‐0.12) | 88% | P = 0.02 |
| Incomplete outcome data | ||||||
| Low risk (Belloni 2005; Boralevi 2014; Gayraud 2015; Giordano‐Labadie 2006; Korting 2010; Nebus 2009; Patrizi 2014; Tan 2010 | 8 | 369 | 368 | ‐0.66 (‐0.96 to ‐0.36) | 71% | P < 0.0001 |
| Unclear risk (Boguniewicz 2008; Patrizi 2008) | 2 | 91 | 89 | ‐0.93 (‐1.29 to ‐0.57) | 17% | P < 0.00001 |
| High risk (Abramovits 2008; Grimalt 2007) | 2 | 223 | 141 | ‐0.41 (‐1.17 to 0.35) | 92% | P = 0.29 |
| Selective reporting | ||||||
| Low risk (all trials) | 12 | 683 | 598 | ‐0.65 (‐0.89 to ‐0.41) | 75% | P < 0.00001 |
| Other bias | ||||||
| Low risk (all trials) | 12 | 683 | 598 | ‐0.65 (‐0.89 to ‐0.41) | 75% | P < 0.00001 |
| Number of participants who experienced a flare | ||||||
| Variable | Number of studies | Number of participants in moisturiser group | Number of participants in control group | RR (95% CI) | Heterogeneity I² | P value |
| All studies (Abramovits 2008; Boguniewicz 2008; Gayraud 2015; Patrizi 2008; Weber 2015; Wirén 2009) | 6 | 341 | 266 | 0.33 (0.17 to 0.62) | 73% | P = 0.0006 |
| Sequence generation | ||||||
| Low risk (all trials) | 6 | 341 | 266 | 0.33 (0.17 to 0.62) | 73% | P = 0.0006 |
| Allocation concealment | ||||||
| Low risk (Abramovits 2008; Gayraud 2015; Patrizi 2008; Weber 2015; Wirén 2009) | 5 | 269 | 196 | 0.33 (0.15 to 0.71) | 78% | P = 0.005 |
| Unclear risk (Boguniewicz 2008) | 1 | 72 | 70 | 0.29 (0.12 to 0.68) | NA | P = 0.005 |
| Blinding of participants and personnel | ||||||
| Low risk (Abramovits 2008; Gayraud 2015; Patrizi 2008) | 3 | 227 | 151 | 0.27 (0.06 to 1.20) | 89% | P = 0.09 |
| Unclear risk (Boguniewicz 2008) | 1 | 72 | 70 | 0.29 (0.12 to 0.68) | NA | P = 0.005 |
| High risk (Weber 2015; Wirén 2009) | 2 | 42 | 45 | 0.40 (0.23 to 0.70) | 0% | P = 0.001 |
| Blinding of outcome assessment | ||||||
| Low risk (Abramovits 2008; Gayraud 2015; Patrizi 2008) | 3 | 227 | 151 | 0.27 (0.06 to 1.20) | 89% | P = 0.09 |
| Unclear risk (Boguniewicz 2008) | 1 | 72 | 70 | 0.29 (0.12 to 0.68) | NA | P = 0.005 |
| High risk (Weber 2015; Wirén 2009) | 2 | 42 | 45 | 0.40 (0.23 to 0.70) | 0% | P = 0.001 |
| Incomplete outcome data | ||||||
| Low risk (Gayraud 2015; Weber 2015; Wirén 2009) | 3 | 104 | 106 | 0.54 (0.31 to 0.92) | 47% | P = 0.02 |
| Unclear risk (Boguniewicz 2008; Patrizi 2008) | 2 | 92 | 89 | 0.26 (0.12 to 0.57) | 0% | P = 0.0007 |
| High risk (Abramovits 2008) | 1 | 145 | 71 | 0.14 (0.07 to 0.28) | NA | P < 0.00001 |
| Selective reporting | ||||||
| Low risk (all trials) | 6 | 341 | 266 | 0.33 (0.17 to 0.62) | 73% | P = 0.0006 |
| Other bias | ||||||
| Low risk (all trials) | 6 | 341 | 266 | 0.33 (0.17 to 0.62) | 73% | P = 0.0006 |
| Change from baseline in quality of life | ||||||
| Variable | Number of studies | Number of participants in moisturiser group | Number of participants in control group | SMD (95% CI) | Heterogeneity I² | P value |
| All trials (Gayraud 2015; Giordano‐Labadie 2006; Grimalt 2007) | 3 | 146 | 154 | ‐0.39 (‐0.90 to 0.12) | 79% | P = 0.13 |
| Sequence generation | ||||||
| Low risk (all trials) | 3 | 146 | 154 | ‐0.39 (‐0.90 to 0.12) | 79% | P = 0.13 |
| Allocation concealment | ||||||
| Low risk (all trials) | 3 | 146 | 154 | ‐0.39 (‐0.90 to 0.12) | 79% | P = 0.13 |
| Blinding of participants and personnel | ||||||
| Low risk (Gayraud 2015) | 1 | 62 | 61 | ‐0.81 (‐1.18 to ‐0.44) | NA | P < 0.0001 |
| High risk (Giordano‐Labadie 2006; Grimalt 2007) | 2 | 84 | 93 | ‐0.15 (‐0.55 to 0.24) | 42% | P = 0.44 |
| Blinding of outcome assessment | ||||||
| Low risk (Gayraud 2015) | 1 | 62 | 61 | ‐0.81 (‐1.18 to ‐0.44) | NA | P < 0.0001 |
| High risk (Giordano‐Labadie 2006; Grimalt 2007) | 2 | 84 | 93 | ‐0.15 (‐0.55 to 0.24) | 42% | P = 0.44 |
| Incomplete outcome data | ||||||
| Low risk (Gayraud 2015; Giordano‐Labadie 2006) | 2 | 97 | 100 | ‐0.62 (‐1.04 to ‐0.19) | 52% | P = 0.004 |
| High risk (Grimalt 2007) | 1 | 49 | 54 | 0.03 (‐0.36 to 0.41) | NA | P = 0.89 |
| Selective reporting | ||||||
| Low risk (all trials) | 3 | 146 | 154 | ‐0.39 (‐0.90 to 0.12) | 79% | P = 0.13 |
| Other bias | ||||||
| Low risk (all trials) | 3 | 146 | 154 | ‐0.39 (‐0.90 to 0.12) | 79% | P = 0.13 |
| LICOCHALCONE‐CONTAINING MOISTURISERS VERSUS HYDROCORTISONE ACETATE 1% CREAM | ||||||
| Change from baseline in disease severity as assessed by the investigators (SCORAD) | ||||||
| Variable | Number of studies | Number of participants in licochalcone group | Number of participants in hydrocortisone group | MD (95% CI) | Heterogeneity I² | P value |
| All trials (Angelova‐Fischer 2014; Udompataikul 2011; Wanakul 2013) | 3 | 96 (within‐participant) | 96 (within‐participant) | 0.08 (‐1.96 to 2.13) | 85% | P = 0.94 |
| Sequence generation | ||||||
| Low risk (Angelova‐Fischer 2014; Wanakul 2013) | 2 | 70 (within‐participant) | 70 (within‐participant) | ‐0.90 (‐2.85 to 1.05) | 82% | P = 0.32 |
| Unclear risk (Udompataikul 2011) | 1 | 26 (within‐participant) | 26 (within‐participant) | 2.57 (0.59 to 4.55) | NA | P = 0.01 |
| Blinding of participants and personnel | ||||||
| Low risk (Wanakul 2013) | 1 | 52 (within‐participant) | 52 (within‐participant) | ‐2.00 (‐3.47 to ‐0.53) | NA | P = 0.008 |
| Unclear risk (Angelova‐Fischer 2014; Udompataikul 2011) | 2 | 44 (within‐participant) | 44 (within‐participant) | 1.12 (‐1.38 to 3.61) | 82% | P = 0.38 |
| Blinding of outcome assessment | ||||||
| Low risk (Wanakul 2013) | 1 | 52 (within‐participant) | 52 (within‐participant) | ‐2.00 (‐3.47 to ‐0.53) | NA | P = 0.008 |
| High risk (Angelova‐Fischer 2014; Udompataikul 2011) | 2 | 44 (within‐participant) | 44 (within‐participant) | 1.12 (‐1.38 to 3.61) | 82% | P = 0.38 |
| Incomplete outcome data | ||||||
| Low risk (Angelova‐Fischer 2014; Wanakul 2013) | 2 | 70 (within‐participant) | 70 (within‐participant) | ‐0.90 (‐2.85 to 1.05) | 82% | P = 0.32 |
| Unclear risk (Udompataikul 2011) | 1 | 26 (within‐participant) | 26 (within‐participant) | 2.57 (0.59 to 4.55) | NA | P = 0.01 |
| Selective reporting | ||||||
| All studies | 3 | 96 (within‐participant) | 96 (within‐participant) | 0.08 (‐1.96 to 2.13) | 85% | P = 0.94 |
| Other bias | ||||||
| All studies | 3 | 96 (within‐participant) | 96 (within‐participant) | 0.08 (‐1.96 to 2.13) | 85% | P = 0.94 |
| VEHICLE TREATMENT + MOISTURISER VERSUS FLUTICASONE TREATMENT TWICE WEEKLY + MOISTURISER | ||||||
| Number of participants reporting an adverse event | ||||||
| Variable | Number of studies | Number of participants in vehicle + moisturiser group | Number of participants in fluticasone propionate + moisturiser group | RR (95% CI) | Heterogeneity I² | P value |
| All studies (Berth‐Jones 2003 (2 studies); Glazenburg 2009; Hanifin 2002) | 4 | 312 | 406 | 0.51 (0.22 to 1.14) | 67% | P = 0.10 |
| Sequence generation | ||||||
| Low risk (Berth‐Jones 2003 (2 studies); Glazenburg 2009) | 3 | 193 | 177 | 0.30 (0.12 to 0.73) | NA | P = 0.008 |
| Unclear risk (Hanifin 2002) | 1 | 119 | 229 | 0.70 (0.48 to 1.04) | NA | P = 0.08 |
| Allocation concealment | ||||||
| Low risk (Berth‐Jones 2003 (2 studies)) | 2 | 157 | 138 | Not estimable | NA | NA |
| Unclear risk (Glazenburg 2009; Hanifin 2002) | 2 | 155 | 268 | 0.51 (0.22 to 1.14) | 67% | P = 0.10 |
| Blinding of participants and personnel | ||||||
| Low risk (Berth‐Jones 2003 (2 studies)) | 2 | 157 | 138 | Not estimable | NA | NA |
| Unclear risk (Glazenburg 2009; Hanifin 2002) | 2 | 155 | 268 | 0.51 (0.22 to 1.14) | 67% | P = 0.10 |
| Blinding of outcome assessment | ||||||
| Low risk (Berth‐Jones 2003 (2 studies)) | 2 | 157 | 138 | Not estimable | NA | NA |
| Unclear risk (Glazenburg 2009; Hanifin 2002) | 2 | 155 | 268 | 0.51 (0.22 to 1.14) | 67% | P = 0.10 |
| Incomplete outcome data | ||||||
| Unclear risk (all studies) | 4 | 312 | 406 | 0.51 (0.22 to 1.14) | 67% | P = 0.10 |
| Selective reporting | ||||||
| Low risk (all studies) | 4 | 312 | 406 | 0.51 (0.22 to 1.14) | 67% | P = 0.10 |
| Other bias | ||||||
| Low risk (all studies) | 4 | 312 | 406 | 0.51 (0.22 to 1.14) | 67% | P = 0.10 |
| Number of participants experiencing a flare | ||||||
| Variable | Number of studies | Number of participants in vehicle + moisturiser group | Number of participants in fluticasone propionate + moisturiser group | RR (95% CI) | Heterogeneity I² | P value |
| All studies (Berth‐Jones 2003 (2 studies); Glazenburg 2009; Hanifin 2002) | 4 | 312 | 406 | 2.17 (1.51 to 3.11) | 74% | P < 0.0001 |
| Sequence generation | ||||||
| Low risk (Berth‐Jones 2003 (2 studies); Glazenburg 2009) | 3 | 193 | 177 | 2.02 (1.24 to 3.30) | 76% | P = 0.005 |
| Unclear risk (Hanifin 2002) | 1 | 119 | 229 | 2.62 (2.03 to 3.39) | NA | P < 0.00001 |
| Allocation concealment | ||||||
| Low risk (Berth‐Jones 2003 (2 studies)) | 2 | 157 | 138 | 2.17 (0.88 to 5.37) | 88% | P = 0.09 |
| Unclear risk (Glazenburg 2009; Hanifin 2002) | 2 | 155 | 268 | 2.27 (1.62 to 3.19) | 54% | P < 0.00001 |
| Blinding of participants and personnel | ||||||
| Low risk (Berth‐Jones 2003 (2 studies)) | 2 | 157 | 138 | 2.17 (0.88 to 5.37) | 88% | P = 0.09 |
| Unclear risk (Glazenburg 2009; Hanifin 2002) | 2 | 155 | 268 | 2.27 (1.62 to 3.19) | 54% | P < 0.00001 |
| Blinding of outcome assessment | ||||||
| Low risk (Berth‐Jones 2003 (2 studies)) | 2 | 157 | 138 | 2.17 (0.88 to 5.37) | 88% | P = 0.09 |
| Unclear risk (Glazenburg 2009; Hanifin 2002) | 2 | 155 | 268 | 2.27 (1.62 to 3.19) | 54% | P < 0.00001 |
| Incomplete outcome data | ||||||
| Unclear risk (all studies) | 4 | 312 | 406 | 2.17 (1.51 to 3.11) | 74% | P < 0.0001 |
| Selective reporting | ||||||
| Low risk (all studies) | 4 | 312 | 406 | 2.17 (1.51 to 3.11) | 74% | P < 0.0001 |
| Other bias | ||||||
| Low risk (all studies) | 4 | 312 | 406 | 2.17 (1.51 to 3.11) | 74% | P < 0.0001 |
| Hazard ratio for rate of flare | ||||||
| Variable | Number of studies | Number of participants in fluticasone propionate + moisturiser group | Number of participants in vehicle + moisturiser group | HR (95% CI) | Heterogeneity I² | P value |
| All studies (Berth‐Jones 2003 (2 studies); Glazenburg 2009; Hanifin 2002) | 4 | 406 | 312 | 3.69 (1.80 to 7.55) | 85% | P = 0.0004 |
| Sequence generation | ||||||
| Low risk (Berth‐Jones 2003 (2 studies); Glazenburg 2009) | 3 | 177 | 193 | 2.84 (1.44 to 5.61) | 76% | P = 0.003 |
| Unclear risk (Hanifin 2002) | 1 | 229 | 119 | 7.70 (4.62 to 12.84) | NA | P < 0.00001 |
| Allocation concealment | ||||||
| Low risk (Berth‐Jones 2003 (2 studies)) | 2 | 138 | 157 | 3.26 (1.09 to 9.74) | 87% | P = 0.03 |
| Unclear risk (Glazenburg 2009; Hanifin 2002) | 2 | 268 | 155 | 4.16 (1.21 to 14.31) | 89% | P = 0.02 |
| Blinding of participants and personnel | ||||||
| Low risk (Berth‐Jones 2003 (2 studies)) | 2 | 138 | 157 | 3.26 (1.09 to 9.74) | 87% | P = 0.03 |
| Unclear risk (Glazenburg 2009; Hanifin 2002) | 2 | 268 | 155 | 4.16 (1.21 to 14.31) | 89% | P = 0.02 |
| Blinding of outcome assessment | ||||||
| Low risk (Berth‐Jones 2003 (2 studies)) | 2 | 138 | 157 | 3.26 (1.09 to 9.74) | 87% | P = 0.03 |
| Unclear risk (Glazenburg 2009; Hanifin 2002) | 2 | 268 | 155 | 4.16 (1.21 to 14.31) | 89% | P = 0.02 |
| Incomplete outcome data | ||||||
| Unclear risk (all studies ) | 4 | 406 | 312 | 3.69 (1.80 to 7.55) | 85% | P = 0.0004 |
| Selective reporting | ||||||
| Low risk (all studies) | 4 | 406 | 312 | 3.69 (1.80 to 7.55) | 85% | P = 0.0004 |
| Other bias | ||||||
| Low risk (all studies) | 4 | 406 | 312 | 3.69 (1.80 to 7.55) | 85% | P = 0.0004 |
| NA not applicable; MD mean difference; SMD standardised mean difference; RR risk ratio; HR hazard ratio | ||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 Change from baseline in SCORAD Show forest plot | 3 | 276 | Mean Difference (IV, Random, 95% CI) | ‐2.42 [‐4.55, ‐0.28] |
| 1.2 Number of participants experiencing a flare Show forest plot | 2 | 87 | Risk Ratio (M‐H, Random, 95% CI) | 0.40 [0.23, 0.70] |
| 1.3 Rate of flare Show forest plot | 2 | 87 | Hazard Ratio (IV, Random, 95% CI) | 3.74 [1.86, 7.50] |
| 1.4 Amount of topical steroids used Show forest plot | 2 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 1.4.1 Amount of topical corticosteroids first 3‐4 weeks | 2 | 222 | Mean Difference (IV, Random, 95% CI) | ‐8.25 [‐17.22, 0.72] |
| 1.4.2 Amount of topical corticosteroids used last 3‐4 weeks | 1 | 74 | Mean Difference (IV, Random, 95% CI) | 0.50 [‐4.70, 5.70] |
| 1.4.3 Total amount of topical corticosteroids used in 6 to 8 weeks | 2 | 222 | Mean Difference (IV, Random, 95% CI) | ‐9.30 [‐15.33, ‐3.27] |
| 1.5 Change from baseline in quality of life Show forest plot | 2 | 177 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.15 [‐0.55, 0.24] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 2.1 Number of participants who experienced good improvement to total resolution Show forest plot | 3 | 390 | Risk Ratio (M‐H, Random, 95% CI) | 4.51 [2.19, 9.29] |
| 2.1.1 Number of participants who experienced good improvement to total resolution (low risk of bias) | 1 | 30 | Risk Ratio (M‐H, Random, 95% CI) | 4.00 [1.01, 15.81] |
| 2.1.2 Number of participants who experienced good improvement to total resolution (unclear risk of bias) | 1 | 142 | Risk Ratio (M‐H, Random, 95% CI) | 8.06 [3.95, 16.42] |
| 2.1.3 Number of participants who experienced good improvement to total resolution (high risk of bias) | 1 | 218 | Risk Ratio (M‐H, Random, 95% CI) | 3.02 [2.00, 4.56] |
| 2.2 Change from baseline in itch measured on a VAS Show forest plot | 4 | 396 | Mean Difference (IV, Random, 95% CI) | ‐2.65 [‐4.21, ‐1.09] |
| 2.2.1 Change from baseline in itch measured on a VAS (low risk of bias) | 1 | 30 | Mean Difference (IV, Random, 95% CI) | ‐0.80 [‐1.20, ‐0.40] |
| 2.2.2 Change from baseline in itch measured on a VAS (unclear risk of bias) | 2 | 180 | Mean Difference (IV, Random, 95% CI) | ‐3.10 [‐4.47, ‐1.73] |
| 2.2.3 Change from baseline in itch measured on a VAS (high risk of bias) | 1 | 186 | Mean Difference (IV, Random, 95% CI) | ‐3.70 [‐4.66, ‐2.74] |
| 2.3 Number of participants reporting an adverse event Show forest plot | 4 | 430 | Risk Ratio (M‐H, Random, 95% CI) | 1.03 [0.79, 1.33] |
| 2.4 Change from baseline in EASI Show forest plot | 4 | 426 | Mean Difference (IV, Random, 95% CI) | ‐4.00 [‐5.42, ‐2.57] |
| 2.4.1 Change from baseline in EASI (low risk of bias) | 1 | 30 | Mean Difference (IV, Random, 95% CI) | ‐3.30 [‐5.67, ‐0.93] |
| 2.4.2 Change from baseline in EASI (unclear risk of bias) | 2 | 180 | Mean Difference (IV, Random, 95% CI) | ‐4.42 [‐7.73, ‐1.10] |
| 2.4.3 Change from baseline in EASI (high risk of bias) | 1 | 216 | Mean Difference (IV, Random, 95% CI) | ‐3.62 [‐5.06, ‐2.18] |
| 2.5 Number of participants experiencing a flare Show forest plot | 3 | 397 | Risk Ratio (M‐H, Random, 95% CI) | 0.18 [0.11, 0.31] |
| 2.5.1 Number of participants experiencing a flare (unclear risk of bias) | 2 | 181 | Risk Ratio (M‐H, Random, 95% CI) | 0.26 [0.12, 0.57] |
| 2.5.2 Number of participants experiencing a flare (high risk of bias) | 1 | 216 | Risk Ratio (M‐H, Random, 95% CI) | 0.14 [0.07, 0.28] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 3.1 Change from baseline in skin capacitance Show forest plot | 2 | Mean Difference (IV, Random, 95% CI) | 1.23 [‐7.39, 9.86] | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 4.1 Number of participants reporting an adverse event Show forest plot | 2 | 385 | Risk Ratio (M‐H, Random, 95% CI) | 0.90 [0.68, 1.19] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 5.1 Change in disease severity as assessed by the investigators (SCORAD and EASI) Show forest plot | 3 | 272 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.23 [‐0.66, 0.21] |
| 5.1.1 Change in disease severity as assessed by the investigator (EASI) (low risk of bias) | 1 | 50 | Std. Mean Difference (IV, Random, 95% CI) | 0.01 [‐0.55, 0.56] |
| 5.1.2 Change in disease severity as assessed by the investigators (SCORAD) (high risk of bias) | 2 | 222 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.33 [‐0.98, 0.32] |
| 5.2 Change from baseline in quality of life Show forest plot | 3 | 226 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.09 [‐0.37, 0.19] |
| 5.2.1 Change from baseline in quality of life (low risk of bias) | 1 | 50 | Std. Mean Difference (IV, Random, 95% CI) | 0.10 [‐0.46, 0.65] |
| 5.2.2 Change from baseline in quality of life (high risk of bias) | 2 | 176 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.16 [‐0.55, 0.24] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 6.1 Number of participants who experienced improvement Show forest plot | 5 | 572 | Risk Ratio (M‐H, Random, 95% CI) | 2.46 [1.16, 5.23] |
| 6.1.1 Number of participants who experienced improvement (low risk of bias) | 2 | 80 | Risk Ratio (M‐H, Random, 95% CI) | 1.86 [0.41, 8.31] |
| 6.1.2 Number of participants who experienced improvement (unclear risk of bias) | 2 | 274 | Risk Ratio (M‐H, Random, 95% CI) | 3.11 [0.25, 38.71] |
| 6.1.3 Number of participants who experienced improvement (high risk of bias) | 1 | 218 | Risk Ratio (M‐H, Random, 95% CI) | 3.02 [2.00, 4.56] |
| 6.2 Change from baseline in itch Show forest plot | 7 | 749 | Std. Mean Difference (IV, Random, 95% CI) | ‐1.10 [‐1.83, ‐0.38] |
| 6.2.1 Change from baseline in itch (low risk of bias) | 3 | 329 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.36 [‐1.16, 0.43] |
| 6.2.2 Change from baseline in itch (unclear risk of bias) | 2 | 180 | Std. Mean Difference (IV, Random, 95% CI) | ‐2.29 [‐2.67, ‐1.91] |
| 6.2.3 Change from baseline in itch (high risk of bias) | 2 | 240 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.95 [‐1.75, ‐0.16] |
| 6.3 Number of participants who expressed treatment satisfaction Show forest plot | 3 | 298 | Risk Ratio (M‐H, Random, 95% CI) | 1.35 [0.77, 2.36] |
| 6.3.1 Number of participants who expressed treatment satisfaction (low risk of bias) | 2 | 80 | Risk Ratio (M‐H, Random, 95% CI) | 1.04 [0.77, 1.42] |
| 6.3.2 Number of participants who expressed treatment satisfaction (high risk of bias) | 1 | 218 | Risk Ratio (M‐H, Random, 95% CI) | 2.14 [1.58, 2.89] |
| 6.4 Number of participants reporting an adverse event Show forest plot | 10 | 1275 | Risk Ratio (M‐H, Random, 95% CI) | 1.03 [0.82, 1.30] |
| 6.4.1 Number of participants reporting an adverse event (low risk of bias) | 4 | 471 | Risk Ratio (M‐H, Random, 95% CI) | 0.83 [0.58, 1.18] |
| 6.4.2 Number of participants reporting an adverse events (unclear risk of bias) | 3 | 314 | Risk Ratio (M‐H, Random, 95% CI) | 1.08 [0.82, 1.42] |
| 6.4.3 Number of participants reporting an adverse events (high risk of bias) | 3 | 490 | Risk Ratio (M‐H, Random, 95% CI) | 1.35 [0.37, 4.96] |
| 6.5 Change in disease severity as assessed by the investigators Show forest plot | 12 | 1281 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.65 [‐0.89, ‐0.41] |
| 6.5.1 Change in disease severity as assessed by the investigators (low risk of bias) | 5 | 512 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.45 [‐0.74, ‐0.15] |
| 6.5.2 Change in disease severity as assessed by the investigators (unclear risk of bias) | 2 | 180 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.93 [‐1.29, ‐0.57] |
| 6.5.3 Change in disease severity as assessed by the investigators (high risk of bias) | 5 | 589 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.77 [‐1.23, ‐0.30] |
| 6.6 Number of participants experiencing a flare Show forest plot | 6 | 607 | Risk Ratio (M‐H, Random, 95% CI) | 0.33 [0.17, 0.62] |
| 6.6.1 Number of participants experiencing a flare (low risk of bias) | 1 | 123 | Risk Ratio (M‐H, Random, 95% CI) | 0.80 [0.48, 1.34] |
| 6.6.2 Number of participants experiencing a flare (unclear risk of bias) | 2 | 181 | Risk Ratio (M‐H, Random, 95% CI) | 0.26 [0.12, 0.57] |
| 6.6.3 Number of participants experiencing a flare (high risk of bias) | 3 | 303 | Risk Ratio (M‐H, Random, 95% CI) | 0.27 [0.12, 0.59] |
| 6.7 Change from baseline in quality of life Show forest plot | 3 | 300 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.39 [‐0.90, 0.12] |
| 6.7.1 Change from baseline in quality of life (low risk of bias) | 1 | 123 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.81 [‐1.18, ‐0.44] |
| 6.7.2 Change from baseline in quality of life (high risk of bias) | 2 | 177 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.15 [‐0.55, 0.24] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 7.1 Change from baseline in TEWL Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | ‐0.34 [‐1.44, 0.76] | |
| 7.2 Change from baseline in skin hydration Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | 0.34 [‐2.54, 3.21] | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 8.1 Change from baseline in itch (VAS) Show forest plot | 2 | Mean Difference (IV, Random, 95% CI) | ‐0.48 [‐1.46, 0.50] | |
| 8.1.1 Change from baseline in itch (VAS) (unclear risk of bias) | 1 | Mean Difference (IV, Random, 95% CI) | 0.00 [‐0.47, 0.47] | |
| 8.1.2 Change from baseline in itch (VAS) (high risk of bias) | 1 | Mean Difference (IV, Random, 95% CI) | ‐1.00 [‐1.61, ‐0.39] | |
| 8.2 Change from baseline in SCORAD Show forest plot | 3 | Mean Difference (IV, Random, 95% CI) | 0.08 [‐1.96, 2.13] | |
| 8.2.1 Change from baseline in SCORAD (unclear risk of bias) | 1 | Mean Difference (IV, Random, 95% CI) | ‐2.00 [‐3.47, ‐0.53] | |
| 8.2.2 Change from baseline in SCORAD (high risk of bias) | 2 | Mean Difference (IV, Random, 95% CI) | 1.12 [‐1.38, 3.61] | |
| 8.3 Change from baseline in TEWL Show forest plot | 2 | Mean Difference (IV, Random, 95% CI) | ‐0.50 [‐5.88, 4.87] | |
| 8.3.1 Change from baseline in TEWL (unclear risk of bias) | 1 | Mean Difference (IV, Random, 95% CI) | ‐3.00 [‐4.71, ‐1.29] | |
| 8.3.2 Change from baseline in TEWL (high risk of bias) | 1 | Mean Difference (IV, Random, 95% CI) | 2.51 [‐1.21, 6.23] | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 9.1 Rate of flare Show forest plot | 1 | Hazard Ratio (IV, Random, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 10.1 Number of participants reporting an adverse event Show forest plot | 3 | 718 | Risk Ratio (M‐H, Random, 95% CI) | 0.51 [0.22, 1.14] |
| 10.2 Number of participants experiencing a flare Show forest plot | 3 | 718 | Risk Ratio (M‐H, Random, 95% CI) | 2.17 [1.51, 3.11] |
| 10.3 Rate of flare Show forest plot | 3 | 723 | Hazard Ratio (IV, Random, 95% CI) | 3.69 [1.80, 7.55] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 11.1 Change in disease severity as assessed by the investigators Show forest plot | 2 | 192 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.87 [‐1.17, ‐0.57] |
| 11.2 Change in quality of life IDQOL Show forest plot | 1 | 67 | Mean Difference (IV, Random, 95% CI) | ‐1.31 [‐2.70, 0.09] |
| 11.3 Change in quality of life DFI Show forest plot | 1 | 67 | Mean Difference (IV, Random, 95% CI) | ‐1.03 [‐2.47, 0.42] |
