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Cochrane Database of Systematic Reviews

Topical tacrolimus for atopic dermatitis

Information

DOI:
https://doi.org/10.1002/14651858.CD009864.pub2Copy DOI
Database:
  1. Cochrane Database of Systematic Reviews
Version published:
  1. 01 July 2015see what's new
Type:
  1. Intervention
Stage:
  1. Review
Cochrane Editorial Group:
  1. Cochrane Skin Group

Copyright:
  1. Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Authors

  • Jade Cury Martins

    Correspondence to: Department of Dermatology, Universidade Federal de São Paulo, São Paulo, Brazil

    [email protected]

  • Ciro Martins

    Department of Dermatology, Belecara Premium Multispecialty Center, Baltimore, USA

  • Valeria Aoki

    Department of Dermatology, University of Sao Paulo Medical School Hospital das Clinicas, São Paulo, Brazil

  • Aecio FT Gois

    Brazilian Cochrane Centre, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil

  • Henrique A Ishii

    c/o Cochrane Skin Group, The University of Nottingham, Nottingham, UK

  • Edina MK da Silva

    Emergency Medicine and Evidence Based Medicine, Universidade Federal de São Paulo, São Paulo, Brazil

Contributions of authors

JCM was the contact person with the editorial base, co‐ordinated contributions from the co‐authors, and wrote the final draft of the review.
JCM and EMKS screened papers against eligibility criteria.
JCM obtained data on ongoing and unpublished studies.
JCM and EMKS appraised the quality of papers.
JCM and EMKS extracted data for the review, and JCM sought additional information about papers.
JCM entered data into RevMan.
JCM analysed and interpreted data.
JCM and EMKS worked on the methods sections.
JCM drafted the clinical sections of the background and responded to the clinical comments of the referees.
EMKS looked at the methodology and statistics of the final version of the review and comments of the referees.
HAI was the consumer co‐author and checked the review for readability and clarity, as well as ensuring that outcomes were relevant to consumers.
JCM is the guarantor of the update.
CM checked the review for English language translation problems.
VA, CM, EMKS, and AFTG reviewed the final paper.

Disclaimer

This project was supported by the National Institute for Health Research, via Cochrane Infrastructure funding to the Cochrane Skin Group. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, NHS or the Department of Health.

Sources of support

Internal sources

  • No sources of support supplied

External sources

  • The National Institute for Health Research (NIHR), UK.

    The NIHR, UK, is the largest single funder of the Cochrane Skin Group.

Declarations of interest

Jade Cury Martins: nothing to declare.
Ciro Martins: nothing to declare.
Valeria Aoki: nothing to declare.
Aecio FT Gois: nothing to declare.
Henrique Akira Ishii: nothing to declare.
Edina MK da Silva: nothing to declare.

Acknowledgements

The authors wish to thank Finola M Delamere, Elizabeth Doney, Jun Xia, and all other members of the Cochrane Skin Group editorial base for all of their the support in the review process.

The Cochrane Skin Group editorial base wishes to thank Hywel Williams who was the Dermatology Editor for this review; Matthew Grainge and Ching‐Chi Chi who were the Statistical and Methods Editors, respectively; the clinical referees, Åke Svensson and Sherman Gu; and the consumer referee, Amanda Roberts.

Version history

Published

Title

Stage

Authors

Version

2015 Jul 01

Topical tacrolimus for atopic dermatitis

Review

Jade Cury Martins, Ciro Martins, Valeria Aoki, Aecio FT Gois, Henrique A Ishii, Edina MK da Silva

https://doi.org/10.1002/14651858.CD009864.pub2

2012 May 16

Topical tacrolimus for atopic dermatitis

Protocol

Jade Cury Martins, Ciro Martins, Valeria Aoki, Jo Leonardi‐Bee, Aecio FT Gois, Henrique Akira Ishii, Edina MK da Silva

https://doi.org/10.1002/14651858.CD009864

Differences between protocol and review

We updated the Description of the condition section by adding two recent references for systemic treatments: Roekevisch 2014 and Simon 2014.

Within the Objectives section in the published protocol, we stated that we were going to compare topical tacrolimus with "other available topical treatments"; we decided to expand the search to any active treatments, topical or systemic, and therefore, there was a change to "other active treatments". In the same section, we changed the term "effectiveness" to "efficacy", as the latter relates to the circumstances of a randomised controlled trial that might be more ideal than the usual circumstances of healthcare practice.

In the Types of outcome measures section, with regard to 'Timing of outcome assessment', we considered the longer‐term data the primary end point, since these are clinically more important as atopic dermatitis is a chronic inflammatory skin condition with a relapsing course. As most of the included studies reported short‐term data, we analysed only the rapid onset of improvement and included this comment in this section so that readers can understand the reasons. In the same section, we changed timing for longer‐term benefit for "one year or longer", instead of ± 2 years, as we originally planned in the protocol. We added SCORing Atopic Dermatitis (SCORAD) to our secondary outcome measures as another validated or objective measure.

We excluded studies where only a limited area of the body, such as the face or neck, were the subject of the clinical trial because the aim of this review was to look at studies where the whole person was treated and evaluated. Additionally, we also excluded studies where dropout rate was greater than 40%, as we feel the data had lost credibility because of the high degree of dropout.

Dealing with missing data/Sensitivity analysis: we could not impute missing data or perform the planned analyses because of lack of studies.

We amended the thresholds for interpretation of the I² statistic in line with Higgins 2011.

We used GRADE to assess the evidence and added 'Summary of findings' tables for the primary outcomes of our review. We did not plan this at the time of publication of the protocol.

Notes

A search of MEDLINE, PubMed, and Embase in October 2016 found only two relevant studies, which our Co‐ordinating Editor and the lead author decided did not merit an update at this time. Thus, an update of this review has been postponed. Our Information Specialist will run a new search in October 2017 to re‐assess whether an update is needed.

Keywords

MeSH

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Study flow diagram
Figures and Tables -
Figure 1

Study flow diagram

'Risk of bias' graph: review authors' judgements about each 'Risk of bias' item presented as percentages across all included studies
Figures and Tables -
Figure 2

'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
Figures and Tables -
Figure 3

'Risk of bias' summary: review authors' judgements about each 'Risk of bias' item for each included study

Forest plot of comparison: 2 Tacrolimus 0.1% versus pimecrolimus 1%, outcome: 2.1 Physician's assessment of global response of improvement, clear or excellent
Figures and Tables -
Figure 4

Forest plot of comparison: 2 Tacrolimus 0.1% versus pimecrolimus 1%, outcome: 2.1 Physician's assessment of global response of improvement, clear or excellent

Forest plot of comparison: 3 Tacrolimus 0.03% versus corticosteroids, outcome: 3.1 Physician's assessment of global response of improvement, clear or excellent
Figures and Tables -
Figure 5

Forest plot of comparison: 3 Tacrolimus 0.03% versus corticosteroids, outcome: 3.1 Physician's assessment of global response of improvement, clear or excellent

Forest plot of comparison: 4 Tacrolimus 0.03% versus tacrolimus 0.1%, outcome: 4.1 Physician's assessment of global response of improvement, clear or excellent
Figures and Tables -
Figure 6

Forest plot of comparison: 4 Tacrolimus 0.03% versus tacrolimus 0.1%, outcome: 4.1 Physician's assessment of global response of improvement, clear or excellent

Comparison 1 Tacrolimus 0.1% versus steroids, Outcome 1 Physician's assessment of global response of improvement, clear or excellent.
Figures and Tables -
Analysis 1.1

Comparison 1 Tacrolimus 0.1% versus steroids, Outcome 1 Physician's assessment of global response of improvement, clear or excellent.

Comparison 1 Tacrolimus 0.1% versus steroids, Outcome 2 Adverse effects: burning.
Figures and Tables -
Analysis 1.2

Comparison 1 Tacrolimus 0.1% versus steroids, Outcome 2 Adverse effects: burning.

Comparison 1 Tacrolimus 0.1% versus steroids, Outcome 3 Adverse effects: pruritus.
Figures and Tables -
Analysis 1.3

Comparison 1 Tacrolimus 0.1% versus steroids, Outcome 3 Adverse effects: pruritus.

Comparison 1 Tacrolimus 0.1% versus steroids, Outcome 4 Adverse effects: skin infection.
Figures and Tables -
Analysis 1.4

Comparison 1 Tacrolimus 0.1% versus steroids, Outcome 4 Adverse effects: skin infection.

Comparison 1 Tacrolimus 0.1% versus steroids, Outcome 5 SCORAD: 3 weeks.
Figures and Tables -
Analysis 1.5

Comparison 1 Tacrolimus 0.1% versus steroids, Outcome 5 SCORAD: 3 weeks.

Comparison 2 Tacrolimus 0.1% versus pimecrolimus 1%, Outcome 1 Physician's assessment of global response of improvement, clear or excellent.
Figures and Tables -
Analysis 2.1

Comparison 2 Tacrolimus 0.1% versus pimecrolimus 1%, Outcome 1 Physician's assessment of global response of improvement, clear or excellent.

Comparison 2 Tacrolimus 0.1% versus pimecrolimus 1%, Outcome 2 Adverse effects ‐ 6 weeks.
Figures and Tables -
Analysis 2.2

Comparison 2 Tacrolimus 0.1% versus pimecrolimus 1%, Outcome 2 Adverse effects ‐ 6 weeks.

Comparison 3 Tacrolimus 0.03% versus steroids, Outcome 1 Physician's assessment of global response of improvement, clear or excellent.
Figures and Tables -
Analysis 3.1

Comparison 3 Tacrolimus 0.03% versus steroids, Outcome 1 Physician's assessment of global response of improvement, clear or excellent.

Comparison 3 Tacrolimus 0.03% versus steroids, Outcome 2 Participants's assessment of global response of improvement better or much better.
Figures and Tables -
Analysis 3.2

Comparison 3 Tacrolimus 0.03% versus steroids, Outcome 2 Participants's assessment of global response of improvement better or much better.

Comparison 3 Tacrolimus 0.03% versus steroids, Outcome 3 Adverse effects: burning.
Figures and Tables -
Analysis 3.3

Comparison 3 Tacrolimus 0.03% versus steroids, Outcome 3 Adverse effects: burning.

Comparison 3 Tacrolimus 0.03% versus steroids, Outcome 4 Adverse effects: pruritus.
Figures and Tables -
Analysis 3.4

Comparison 3 Tacrolimus 0.03% versus steroids, Outcome 4 Adverse effects: pruritus.

Comparison 3 Tacrolimus 0.03% versus steroids, Outcome 5 Adverse effects: skin infection.
Figures and Tables -
Analysis 3.5

Comparison 3 Tacrolimus 0.03% versus steroids, Outcome 5 Adverse effects: skin infection.

Comparison 4 Tacrolimus 0.03% versus tacrolimus 0.1%, Outcome 1 Physician's assessment of global response of improvement, clear or excellent.
Figures and Tables -
Analysis 4.1

Comparison 4 Tacrolimus 0.03% versus tacrolimus 0.1%, Outcome 1 Physician's assessment of global response of improvement, clear or excellent.

Comparison 4 Tacrolimus 0.03% versus tacrolimus 0.1%, Outcome 2 Adverse effects.
Figures and Tables -
Analysis 4.2

Comparison 4 Tacrolimus 0.03% versus tacrolimus 0.1%, Outcome 2 Adverse effects.

Comparison 5 Tacrolimus 0.03% versus pimecrolimus 1%, Outcome 1 Physician's assessment of global response of improvement.
Figures and Tables -
Analysis 5.1

Comparison 5 Tacrolimus 0.03% versus pimecrolimus 1%, Outcome 1 Physician's assessment of global response of improvement.

Comparison 5 Tacrolimus 0.03% versus pimecrolimus 1%, Outcome 2 Adverse effects.
Figures and Tables -
Analysis 5.2

Comparison 5 Tacrolimus 0.03% versus pimecrolimus 1%, Outcome 2 Adverse effects.

Comparison 6 Tacrolimus 0.1% versus ciclosporin, Outcome 1 Adverse effects.
Figures and Tables -
Analysis 6.1

Comparison 6 Tacrolimus 0.1% versus ciclosporin, Outcome 1 Adverse effects.

Comparison 6 Tacrolimus 0.1% versus ciclosporin, Outcome 2 SCORAD.
Figures and Tables -
Analysis 6.2

Comparison 6 Tacrolimus 0.1% versus ciclosporin, Outcome 2 SCORAD.

Summary of findings for the main comparison. Tacrolimus 0.1% compared with corticosteroids for atopic dermatitis

Tacrolimus 0.1% compared with corticosteroids for atopic dermatitis

Patient or population: people with atopic dermatitis
Settings: outpatients, Europe and Canada

Intervention: tacrolimus 0.1%
Comparison: corticosteroids

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

Number of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Corticosteroids

Tacrolimus 0.1%

Physician's assessment of global response of improvement, clear or excellent ‐ tacrolimus 0.1% versus hydrocortisone acetate 0.1%: 3 weeks
Follow‐up: mean 3 weeks

Study population

RR 3.09
(2.14 to 4.45)

371
(1 study)

⊕⊕⊕⊝
moderate¹

157 per 1000

484 per 1000
(335 to 698)

Moderate

157 per 1000

485 per 1000
(336 to 699)

Physician's assessment of global response of improvement, clear or excellent ‐ tacrolimus 0.1% versus hydrocortisone butyrate: 3 weeks
Follow‐up: mean 3 weeks

Study population

RR 0.95
(0.78 to 1.16)

377
(1 study)

⊕⊕⊝⊝
low¹, ²

516 per 1000

490 per 1000
(403 to 599)

Moderate

516 per 1000

490 per 1000
(402 to 599)

Physician's assessment of global response of improvement, clear or excellent ‐ tacrolimus 0.1% versus hydrocortisone acetate and butyrate 0.1%: short term (6 months)
Follow‐up: 6 months

Study population

RR 1.32
(1.17 to 1.49)

972
(1 study)

⊕⊕⊝⊝
moderate¹

464 per 1000

612 per 1000
(543 to 691)

Moderate

464 per 1000

612 per 1000
(543 to 691)

Adverse effects: burning ‐ tacrolimus 0.1% versus hydrocortisone acetate 0.1%: 3 weeks
Follow‐up: mean 3 weeks

Study population

RR 2.91
(1.6 to 5.28)

371
(1 study)

⊕⊕⊕⊝
moderate¹

70 per 1000

204 per 1000
(112 to 371)

Moderate

70 per 1000

204 per 1000
(112 to 370)

Adverse effects: burning ‐ tacrolimus 0.1% versus hydrocortisone butyrate: 3 weeks
Follow‐up: mean 3 weeks

Study population

RR 4.59
(3.1 to 6.78)

377
(1 study)

⊕⊕⊕⊝
moderate¹

129 per 1000

592 per 1000
(400 to 875)

Moderate

129 per 1000

592 per 1000
(400 to 875)

Adverse effects: burning ‐ tacrolimus 0.1% versus hydrocortisone acetate and butyrate 0.1%: 6 months

Follow‐up: 6 months

Study population

RR 3.79

(2.99 to 4.81)

972

(1 study)

⊕⊕⊕⊝
moderate¹

138 per 1000

524 per 1000

(413 to 664)

Moderate

138 per 1000

524 per 1000

(413 to 664)

Participant's self‐assessment of global response of improvement

Follow‐up: mean 6 months

Study population

RR 1.21

(1.13 to 1.29)

974

(1 study)

⊕⊕⊝⊝
low¹, ³

718 per 1000

868 per 1000

(811 to 926)

Moderate

718 per 1000

869 per 1000

(811 to 926)

*The basis for the assumed risk (e.g., the median control group risk across studies) is provided in footnotes. The corresponding risk (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).
CI: confidence interval; RR: risk ratio.

GRADE Working Group grades of evidence
High quality: further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: we are very uncertain about the estimate.

¹Downgraded one level due to publication bias because only one study was identified and publication bias was strongly suspected.
²Downgraded one level due to Imprecision: sample size falls below the optimal information size; 95% CI of the estimated effect includes both no effect and appreciable benefit.
³Downgraded one level due to Imprecision: sample size falls below the optimal information size.

Figures and Tables -
Summary of findings for the main comparison. Tacrolimus 0.1% compared with corticosteroids for atopic dermatitis
Summary of findings 2. Tacrolimus 0.1% compared with pimecrolimus 1% for atopic dermatitis

Tacrolimus 0.1% compared with pimecrolimus 1% for atopic dermatitis

Patient or population: people with atopic dermatitis
Settings: outpatients, USA
Intervention: tacrolimus 0.1%
Comparison: pimecrolimus 1%

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

Number of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Pimecrolimus 1%

Tacrolimus 0.1%

Physician's assessment of global response of improvement, clear or excellent ‐ 6 weeks
Follow‐up: mean 6 weeks

Study population

RR 1.8
(1.34 to 2.42)

506
(2 studies)

⊕⊕⊕⊝
moderate¹

202 per 1000

363 per 1000
(270 to 488)

Moderate

199 per 1000

358 per 1000
(267 to 482)

Adverse effects ‐ 6 weeks
Follow‐up: mean 6 weeks

Study population

RR 0.89
(0.47 to 1.71)

506
(2 studies)

⊕⊝⊝⊝
very low¹, ², ³

229 per 1000

204 per 1000
(108 to 392)

Moderate

227 per 1000

202 per 1000
(107 to 388)

*The basis for the assumed risk (e.g., the median control group risk across studies) is provided in footnotes. The corresponding risk (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).
CI: confidence interval; RR: risk ratio.

GRADE Working Group grades of evidence
High quality: further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: we are very uncertain about the estimate.

¹Downgraded one level due to publication bias because only one study was identified and publication bias was strongly suspected.
²Downgraded one level due to inconsistency: there is moderate level of heterogeneity between studies: I² value of 69%.
³Downgraded one level due to imprecision: 95% CI of the estimate of summary effect includes both no effect and appreciable harm.

Figures and Tables -
Summary of findings 2. Tacrolimus 0.1% compared with pimecrolimus 1% for atopic dermatitis
Summary of findings 3. Tacrolimus 0.03% compared with corticosteroids for atopic dermatitis

Tacrolimus 0.03% compared with corticosteroids for atopic dermatitis

Patient or population: people with atopic dermatitis
Settings: outpatients, Europe, Tunisia, Pakistan, Morocco, Taiwan
Intervention: tacrolimus 0.03%
Comparison: corticosteroids

Outcomes

Ilustrative comparative risks* (95% CI)

Relative effect
(95% CI)

Number of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Corticosteroids

Tacrolimus 0.03%

Physician's assessment of global response of improvement, clear or excellent ‐ tacrolimus 0.03% 1x/day versus hydrocortisone acetate 1% 2x/day
Follow‐up: mean 3 weeks

Study population

RR 2.05
(1.36 to 3.08)

411
(1 study)

⊕⊕⊕⊝
moderate¹

136 per 1000

279 per 1000
(185 to 419)

Moderate

136 per 1000

279 per 1000
(185 to 419)

Physician's assessment of global response of improvement, clear or excellent ‐ tacrolimus 0.03% 2x/day versus hydrocortisone acetate 1% 2x/day
Follow‐up: mean 3 weeks

Study population

RR 2.58
(1.96 to 3.38)

790
(2 studies)

⊕⊕⊕⊝
moderate¹

146 per 1000

376 per 1000
(286 to 493)

Moderate

146 per 1000

377 per 1000
(286 to 493)

Physician's assessment of global response of improvement, clear or excellent ‐ tacrolimus 0.03% 2x/day versus corticosteroids moderate‐potency 2x/day
Follow‐up: 3 to 4 weeks

Study population

RR 0.45
(0.13 to 1.57)

409
(2 studies)

⊕⊝⊝⊝
very low¹, ², ³

527 per 1000

237 per 1000
(69 to 828)

Moderate

591 per 1000

266 per 1000
(77 to 928)

Physician's assessment of global response of improvement, clear or excellent ‐ tacrolimus 0.03% 2x/day versus methylprednisolone 0.03% 1x/day
Follow‐up: mean 3 weeks

Study population

RR 1
(0.85 to 1.19)

265
(1 study)

⊕⊕⊝⊝
low¹, ³

667 per 1000

667 per 1000
(567 to 793)

Moderate

667 per 1000

667 per 1000
(567 to 794)

Adverse effects: burning ‐ tacrolimus 0.03% versus steroids

Study population

RR2.48
(1.96 to 3.14)

1883
(5 studies)

⊕⊕⊕⊕
high

89 per 1000

221 per 1000
(174 to 279)

Moderate

70 per 1000

174 per 1000
(137 to 220)

Participant's self‐assessment of global response of improvement: tacrolimus 0.03% 2x/day versus hydrocortisone acetate 1% 2x/day

Follow‐up: 3 weeks

Study population

RR 1.64

(1.41 to 1.90)

416

(1 study)

⊕⊕⊕⊝
moderate¹

505 per 1000

828 per 1000

(712 to 959)

Moderate

505 per 1000

828 per 1000

(712 to 959)

*The basis for the assumed risk (e.g., the median control group risk across studies) is provided in footnotes. The corresponding risk (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).
CI: confidence interval; RR: risk ratio.

GRADE Working Group grades of evidence
High quality: further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: we are very uncertain about the estimate.

¹Downgraded one level due to publication bias because only very small number of studies were identified and publication bias was strongly suspected.
²Downgraded one level due to inconsistency: there is moderate level of heterogeneity between studies: I² value of 79%.
³Downgraded one level due to imprecision: 95% CI of estimated summary effect includes both no effect and appreciable harm.

Figures and Tables -
Summary of findings 3. Tacrolimus 0.03% compared with corticosteroids for atopic dermatitis
Summary of findings 4. Tacrolimus 0.03% compared with tacrolimus 0.1% for atopic dermatitis

Tacrolimus 0.03% compared with tacrolimus 0.1% for atopic dermatitis

Patient or population: people with atopic dermatitis
Settings: outpatients, USA, Japan, China
Intervention: tacrolimus 0.03%
Comparison: tacrolimus 0.1%

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

Number of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Tacrolimus 0.1%

Tacrolimus 0.03%

Physician's assessment of global response of improvement, clear or excellent
Follow‐up: 3 to 12 weeks

Study population

RR 0.82
(0.72 to 0.92)

1640
(6 studies)

⊕⊕⊕⊕
high

430 per 1000

353 per 1000
(310 to 396)

Moderate

445 per 1000

365 per 1000
(320 to 409)

Adverse effects
Follow‐up: mean 3 weeks

Study population

RR 0.95
(0.86 to 1.06)

986
(4 studies)

⊕⊕⊕⊝
moderate¹

573 per 1000

544 per 1000
(492 to 607)

Moderate

448 per 1000

426 per 1000
(385 to 475)

*The basis for the assumed risk (e.g., the median control group risk across studies) is provided in footnotes. The corresponding risk (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).
CI: confidence interval; RR: risk ratio.

GRADE Working Group grades of evidence
High quality: further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: we are very uncertain about the estimate.

¹Downgraded one level due to imprecision: sample size is below the optimal information size.

Figures and Tables -
Summary of findings 4. Tacrolimus 0.03% compared with tacrolimus 0.1% for atopic dermatitis
Summary of findings 5. Tacrolimus 0.03% versus pimecrolimus 1% for atopic dermatitis

Tacrolimus 0.03% versus pimecrolimus 1% for atopic dermatitis

Patient or population: people with atopic dermatitis
Settings: outpatients, USA
Intervention: tacrolimus 0.03% versus pimecrolimus 1%

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

Number of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Control

Tacrolimus 0.03% versus pimecrolimus 1%

Physician's assessment of global response of improvement
Follow‐up: mean 6 weeks

Study population

RR 1.42
(1.02 to 1.98)

139
(1 study)

⊕⊕⊝⊝
low¹, ²

429 per 1000

609 per 1000
(437 to 849)

Moderate

429 per 1000

609 per 1000
(438 to 849)

Adverse effects ‐ application site reaction
Follow‐up: mean 6 weeks

Study population

RR 1.07
(0.6 to 1.91)

141
(1 study)

⊕⊕⊝⊝
low², ³

239 per 1000

256 per 1000
(144 to 457)

Moderate

239 per 1000

256 per 1000
(143 to 456)

Adverse effects ‐ burning
Follow‐up: mean 6 weeks

Study population

RR 0.87
(0.43 to 1.75)

141
(1 study)

⊕⊕⊝⊝
low², ³

197 per 1000

172 per 1000
(85 to 345)

Moderate

197 per 1000

171 per 1000
(85 to 345)

Adverse effects ‐ itching
Follow‐up: mean 6 weeks

Study population

RR 2.37
(0.96 to 5.81)

141
(1 study)

⊕⊕⊝⊝
low², ³

85 per 1000

200 per 1000
(81 to 491)

Moderate

85 per 1000

201 per 1000
(82 to 494)

Adverse effects ‐ erythema
Follow‐up: mean 6 weeks

Study population

RR 2.2
(0.89 to 5.46)

141
(1 study)

⊕⊕⊝⊝
low², ³

85 per 1000

186 per 1000
(75 to 461)

Moderate

85 per 1000

187 per 1000
(76 to 464)

*The basis for the assumed risk (e.g., the median control group risk across studies) is provided in footnotes. The corresponding risk (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).
CI: confidence interval; RR: risk ratio.

GRADE Working Group grades of evidence
High quality: further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: we are very uncertain about the estimate.

¹Downgraded one level due to imprecision: sample size is smaller than the optimal information size.
²Downgraded one level due to publication bias because only one study was identified and publication bias was strongly suspected.
³Downgraded one level due to imprecision: 95% CI of the estimate of summary effect includes both no effect and appreciable harm.

Figures and Tables -
Summary of findings 5. Tacrolimus 0.03% versus pimecrolimus 1% for atopic dermatitis
Summary of findings 6. Tacrolimus 0.1% versus ciclosporin for atopic dermatitis

Tacrolimus 0.1% versus ciclosporin for atopic dermatitis

Patient or population: people with atopic dermatitis
Settings: outpatients, Italy
Intervention: tacrolimus 0.1% versus ciclosporin

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

Number of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Control

Tacrolimus 0.1% versus ciclosporin

Adverse effects
Follow‐up: mean 6 weeks

Study population

RR 1
(0.31 to 3.28)

30
(1 study)

⊕⊝⊝⊝
very low¹, ², ³

267 per 1000

267 per 1000
(83 to 875)

Moderate

267 per 1000

267 per 1000
(83 to 876)

*The basis for the assumed risk (e.g., the median control group risk across studies) is provided in footnotes. The corresponding risk (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).
CI: confidence interval; RR: risk ratio.

GRADE Working Group grades of evidence
High quality: further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: we are very uncertain about the estimate.

¹Downgraded one level due to risk of bias: randomisation and allocation concealment procedures were unclear.
²Downgraded one level due to imprecision: sample size is smaller than optimal information size; 95% CI of the estimate of summary effect includes both no effect and appreciable benefit and harm.
³Downgraded one level due to publication bias because only one study was identified and publication bias was strongly suspected.

Figures and Tables -
Summary of findings 6. Tacrolimus 0.1% versus ciclosporin for atopic dermatitis
Table 1. Characteristics of treatment and participants in included studies

Study

Number of participants

(n = 5885)

Age

Intervention

Follow up

Classification of AD

Antiga 2010

24

Adults (21 to 65 years)

Tacrolimus 0.1% ointment vs hydrocortisone butyrate 0.1% ointment (BID)

3 weeks

Moderate to severe (SCORAD)

Bieber 2007

265

Children

(2 to 15 years)

Tacrolimus 0.03% ointment (BID) vs methylprednisolone aceponate 0.1% ointment (evening) and vehicle ointment (morning)

2 to 3 weeks

Severe flare (IGA > 4) history of moderate to severe AD

Boguniewicz 1998

169

Older children

(7 to 16 years)

Tacrolimus 0.03% ointment vs tacrolimus 0.1% ointment vs tacrolimus 0.3% ointment vs vehicle ointment (BID)

3 weeks

Moderate to severe (Rajka and Langeland (Rajka 1989))

Caproni 2007

16

Adults

Tacrolimus 0.1% ointment vs hydrocortisone butyrate 0.1% ointment (BID)

3 weeks

Moderate to severe (SCORAD)

Doss 2010

473

Children

(2 to 15 years)

Tacrolimus 0.03% ointment vs fluticasone 0.005% ointment (BID)

3 weeks

Moderate to severe (Rajka and Langeland (Rajka 1989)) and with prior inadequate response to topical corticosteroids

Dou 2006

202

Adults (> 18 years)

Tacrolimus 0.03% ointment vs tacrolimus 0.1% ointment vs vehicle ointment (BID)

3 weeks

Moderate to severe

Draelos 2005

37

Adults

Tacrolimus 0.1% ointment vs pimecrolimus 1% cream (BID)

2 weeks

Moderate to severe (IGA)

Fleischer 2007

281

Adults (> = 16 years)

Tacrolimus 0.1% ointment vs pimecrolimus 1% cream (BID)

6 weeks

Moderate to severe (IGA)

Hanifin 2001

632

Adults (> = 16 years)

Tacrolimus 0.1% ointment vs tacrolimus 0.03% ointment vs vehicle ointment (BID)

3 months

Moderate to severe (Rajka and Langeland (Rajka 1989))

Hung 2007

60

Adults and

children

(9 months to 33 years)

Tacrolimus 0.03% ointment (BID) alone or with fusidic acid 2% cream vs fluticasone propionate 0.05% cream (BID) alone or with fusidic acid 2% cream

6 months

Moderate to severe (Rajka and Langeland (Rajka 1989))

Kempers 2004

141 (for safety)

139 (for efficacy)

Children (2 to 17 years)

Tacrolimus 0.03% ointment vs pimecrolimus 1% cream (BID)

6 weeks

Moderate (IGA)

Otsuki 2003

213

Children (2 to 15 years)

Tacrolimus 0.03% ointment vs tacrolimus 0.1% ointment vs vehicle ointment (BID)

3 weeks

Moderate to severe (Rajka and Langeland (Rajka 1989))

Pacor 2004

30

Adults and

children (13 to 45 years)

Tacrolimus 0.1% ointment (BID) vs ciclosporin 3 mg/kg orally

6 weeks

Moderate to severe (Rajka and Langeland (Rajka 1989))

Paller 2001

351

Children (2 to 15 years)

Tacrolimus 0.03% ointment vs tacrolimus 0.1% ointment vs vehicle ointment (BID)

3 months

Moderate to severe (Rajka and Langeland (Rajka 1989))

Paller 2005

225

Children (2 to 15 years)

Tacrolimus 0.1% ointment vs pimecrolimus 1% cream (BID)

6 weeks

Moderate to severe (IGA)

Reitamo 2002a

570

Adults (16 to 70 years)

Tacrolimus 0.1% ointment vs tacrolimus 0.03% ointment vs hydrocortisone butyrate 0.1% ointment (BID)

3 weeks

Moderate to severe (Rajka and Langeland (Rajka 1989))

Reitamo 2002b

560

Children (2 to 15 years)

Tacrolimus 0.1% ointment vs tacrolimus 0.03% ointment vs hydrocortisone acetate 1% ointment (BID)

3 weeks

Moderate to severe (Rajka and Langeland (Rajka 1989))

Reitamo 2004

621

Children (2 to 15 years)

Tacrolimus 0.03% ointment (OD) vs tacrolimus 0.03% ointment (BID) vs hydrocortisone acetate 1% ointment (BID)

3 weeks

Moderate to severe (Rajka and Langeland (Rajka 1989))

Reitamo 2005

972

Adults (> = 18 years)

Tacrolimus 0.1% ointment vs hydrocortisone butyrate 0.1% ointment (on trunk and extremities) and hydrocortisone acetate 1% ointment (on face and neck) (BID)

Up to 6 months

Moderate to severe (Rajka and Langeland (Rajka 1989))

Sikder 2005

45

Older children (7 to 15 years)

Tacrolimus 0.03% ointment (BID) vs clobetasone butyrate 0.05% cream (BID) vs clobetasone butyrate 0.05% cream (morning) and tacrolimus 0.03% ointment (evening)

4 weeks

Moderate to severe (Rajka and Langeland (Rajka 1989))

AD: atopic dermatitis.
BID: twice a day.
IGA: Investigators' Global Assessment.
OD: once daily.
SCORAD: SCORing Atopic Dermatitis.
vs: versus.

Figures and Tables -
Table 1. Characteristics of treatment and participants in included studies
Table 2. Spontaneous reported malignancies in association with topical tacrolimus use

Malignancy

Age (years)

Application site

Occurence site

Comment

Exposure to onset (days)

B‐cell lymphoma, EBV‐associated, and primary lung carcinoma

49

Face

Kidney

730

Cutaneous Kaposi sarcoma

28

Axilla, groin

Axilla, groin

HIV patient on HAART, treated for inverse psoriasis, developed KS at these sites, which metastasised, and the patient died

30

Hepatoblastoma

5

Liver

Considered unrelated

455

Lymphadenopathy – possible
lymphoma

40

Application site

Application site

Pre‐existing lymphoma lesions 'looked like' lymphoma and resolved spontaneously*

Lymphoma or Sézary syndrome

16

Face

Lymph nodes

Participant also had been on systemic ciclosporin

730

Metastatic angiosarcoma

16

Face/neck

Clavicle

Present before treatment but increased rapidly in size

105

Metastatic melanoma

39

Generalised

Metastatic disease newly detected from primary 3 years early

21 to 28

Metastatic sweat gland carcinoma

43

Not axilla

Axilla

4 years

Nodular follicular lymphoma

60

Lower limbs, face

May be associated with EBV

504

Non‐Hodgkin lymphoma

52

Used tacrolimus for 6 months. Insufficient evidence

365

Non‐Hodgkin lymphoma

54

Used tacrolimus on extensive areas: 50% of body. Died from lymphoma. Insufficient evidence

Oesophageal cancer with metastases

49

Oesophagus

122

Panniculitis‐like T‐cell lymphoma

53

Trunk, limbs

Trunk, limbs

Also used pimecrolimus

240

Squamous cell carcinoma

34

Face

Face

UV therapy, outdoor sports

Squamous cell carcinoma

57

Penis

Penis

Treated for balanitis considered to be lichen sclerosus et atrophicus; non‐specific biopsy

70

Squamous cell carcinoma

51

Mouth

Long history of pipe smoking

Squamous cell carcinoma recurrence

75

Vulva

Vulva

Treated for lichen sclerosus et atrophicus

42

T‐cell lymphoma, anaplastic large cell

50

Right hip

Right hip

Insufficient evidence

EBV: Epstein–Barr virus.
HIV: human immunodeficiency virus.
HAART: highly active antiretroviral therapy.
KS: Kaposi sarcoma.
UV: ultraviolet.
*Questionable if this should be classed as malignant.
Data shown in Ormerod 2005.

Figures and Tables -
Table 2. Spontaneous reported malignancies in association with topical tacrolimus use
Table 3. Lymphoma risk

Study

Study population

Follow‐up

Comparisons

Results related to lymphoma risks

Arellano 2007

294 cases/293,000 controls

TCIs and TCS in participants with AD

‐ Increased risk in AD participants (related to severity)

‐ No evidence of increased risk with any of the topical treatments

Arellano 2009

> 3,000,000 (cohort)

1992 to 2006

AD, treatment with topical immunosuppressants, or both

‐ Increase risk in AD participants (related to severity)

‐ Increased risk with topical corticosteroids (related to potency)

‐ Insufficient data to assess TCI‐related risks

Hui 2009

953,064 (cohort) (96% unexposed, 4% exposed)

Median 2.4 years

AD or eczema participants exposed or not to TCI

‐ Increased risk in the exposed group**

Schneeweiss 2009

‐ 118,863 for pimecrolimus

‐ 38,757 for tacrolimus

‐ 1,043,025 mid to potent corticosteroid

‐ 118,825 untreated dermatitis

‐ 118,863 for general population

2002 to 2006

(median 1.3 years)

See study population

‐ Increased risk compared with general population*

‐ No risk differences between the 3 treatments

*pre‐existing lymphomas misdiagnosed as AD.
**proportion of people who had diagnosis of AD was 2 times higher in the exposed group (i.e., there was a higher prevalence of AD than eczema in the exposed group). See Summary of main results (Risk of malignancies).
AD: atopic dermatitis.
TCI: topical calcineurin inhibitor.
TCS: topical corticosteroids.

Figures and Tables -
Table 3. Lymphoma risk
Table 4. Non‐melanoma skin cancer (NMSC) and melanoma (MM) skin cancer risk

Study

Study population

Follow up

Comparisons

Results related to skin cancer risks

Hui 2009

953,064 (cohort) (96% unexposed, 4% exposed)

Median 2.4 years

AD participants exposed or not to TCI

‐ Similar risks for NMSC

‐ Lower risks for MM

Margolis 2007

875 cases

1946 controls

Dermatitis participants (AD, seborrhoeic dermatitis, rosacea, other dermatitis) with or without use of TCI

‐ No increased risk of NMSC in TCI‐treated participants

‐ MM risk not evaluated

Naylor 2005

9813 tacrolimus‐treated participants

3 months to 4 years

AD participants with tacrolimus use compared with an aged cohort in the US

‐ No increased risk of NMSC in tacrolimus treated participants

‐ MM risk not evaluated

AD: atopic dermatitis.
TCI: topical calcineurin inhibitor.
MM: melanoma.
NMSC: non‐melanoma skin cancer.

Figures and Tables -
Table 4. Non‐melanoma skin cancer (NMSC) and melanoma (MM) skin cancer risk
Table 5. Observational non‐comparative studies

Study

1. Population

2. Age group

3. Follow‐up

Tacrolimus formulation

Common local effects

Systemic effects

Laboratory values

Malignancies

Others (number of events)

Detectable blood concentration

Gontijo 2008

1. n = 174

2. Paediatric
3. 6 weeks

0.03%

‐ Burning

‐ Pruritus

‐ Asthma (2)

‐ Pneumonia (2)

‐ Pyodermitis (1)

Koo 2005

1. n = 7923

2. Adult/paediatric

3. Median: 210 days

0.1% (92.7%)

0.03% (7.3%)

‐ Burning

‐ Pruritus

‐ Flu‐like symptoms

‐ Headache

(frequency similar to that expected of the general population)

‐ 13 cases of NMSC (no risk with calculated incidence)

‐ Alcohol intolerance 3.7%

Mandelin 2012

1. n = 50

2. Paediatric (< 2 years)

3. 2 years

0.03%

‐ Pruritus

‐ Local infection

‐ Non‐serious respiratory

infection and

gastroenteritis

< 1 ng/ml (in 98%)

Reitamo 2000

1. n = 316

2. Adults

3. 6 to 12 months

0.1%

‐ Burning

‐ Pruritus

‐ Erythema

Normal

(only 1 transient

increase in

liver enzymes)

‐ Alcohol intolerance

5 serious events:

‐ Eczema herpeticum (1)

‐ Cellulitis (1)

‐ Varicella (1)

‐ AD flare‐up (1)

Staphylococcus aureus

superinfection (1)

Minimal < 1 ng/dl in 76% of participants

Reitamo 2007

1. n = 672

2. Adults

3. 2 years

0.1%

‐ Burning

‐ Pruritus

‐ 2 cases (Bowen and prostate carcinoma) not related

‐ Benign neoplasm (7)

‐ Herpes (7%) (expected in AD participants)

‐ Eczema herpeticum (1)

‐ Erythroderma (1)

‐ AD exacerbation (1)

Reitamo 2008

1. n = 782

2. Adult/paediatric

3. 4 years (median: 1422 days)

0.1%

‐ Burning

‐ Pruritus

‐ Skin infection

‐ Flu‐like symptoms

(more in children)

6 cases

‐ Cervical carcinoma (1)

‐ Acute leukaemia (1)

‐ Chronic leukaemia (1)

‐ Basal cell carcinoma (2 to 3 on the same participant)

‐ 34 benign neoplasms

Remitz 2007

1. n = 466

2. Paediatric

3. 29.5 months (mean: 16.3 months)

0.03%

0.1%

‐ Burning

‐ Pruritus

‐ Seasonal infection

(flu‐syndrome)

‐ No growth

retardation

Normal

‐ Leukopenia (1)*

‐ Herpes (4.9%)/eczema herpeticum (0.9%)

‐ Molluscum 3%)

‐ Warts (3.6%)

Saple 2003

1. n = 125

2. 12 to 69 years

3. 5 weeks

0.03%

‐ Burning

‐ Pruritus

‐ Erythema

Normal

Won 2004

1. n = 18

2. Adult/paediatric

3. 4 weeks

0.03%

‐ Burning

‐ Pruritus

Normal

Serious events (3):

‐ Flu‐syndrome (1)

‐ Severe skin rash (1)

‐ Eczema herpeticum (1)

Wong 2003

1. n = 30

2. Adult/paediatric

3. 4 weeks

0.1% adults

0.03% paediatric

‐ Burning

‐ Pruritus

Normal

2 participants

< 5 ng/ml

* 6‐year‐old participant, at month 6, resolution after withdrawn.
AD: atopic dermatitis.
NMSC: non‐melanoma skin cancer.

Figures and Tables -
Table 5. Observational non‐comparative studies
Comparison 1. Tacrolimus 0.1% versus steroids

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Physician's assessment of global response of improvement, clear or excellent Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

1.1 Tacrolimus 0.1% versus hydrocortisone acetate 0.1%: 3 weeks

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.2 Tacrolimus 0.1% versus hydrocortisone butyrate: 3 weeks

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.3 Tacrolimus 0.1% versus hydrocortisone acetate and butyrate 0.1%: short‐term (6 months)

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.4 Tacrolimus 0.1% versus hydrocortisone acetate and butyrate 0.1%: long‐term (12 months)

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2 Adverse effects: burning Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2.1 Tacrolimus 0.1% versus hydrocortisone acetate 0.1%: 3 weeks

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.2 Tacrolimus 0.1% versus hydrocortisone butyrate: 3 weeks

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.3 Tacrolimus 0.1% versus hydrocortisone acetate and butyrate 0.1%: short‐term (6 months)

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.4 Tacrolimus 0.1% versus hydrocortisone acetate and butyrate 0.1%: long‐term (12 months)

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3 Adverse effects: pruritus Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

3.1 Tacrolimus 0.1% versus hydrocortisone acetate 0.1%: 3 weeks

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.2 Tacrolimus 0.1% versus hydrocortisone butyrate: 3 weeks

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.3 Tacrolimus 0.1% versus hydrocortisone acetate and butyrate 0.1%: short‐term (6 months)

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4 Adverse effects: skin infection Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

4.1 Tacrolimus 0.1% versus hydrocortisone acetate 0.1%: 3 weeks

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.2 Tacrolimus 0.1% versus hydrocortisone butyrate: 3 weeks

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.3 Tacrolimus 0.1% versus hydrocortisone acetate and butyrate 0.1%: short‐term (6 months)

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

5 SCORAD: 3 weeks Show forest plot

2

37

Mean Difference (IV, Fixed, 95% CI)

‐8.82 [‐15.36, ‐2.27]

Figures and Tables -
Comparison 1. Tacrolimus 0.1% versus steroids
Comparison 2. Tacrolimus 0.1% versus pimecrolimus 1%

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Physician's assessment of global response of improvement, clear or excellent Show forest plot

3

543

Risk Ratio (M‐H, Fixed, 95% CI)

1.80 [1.35, 2.42]

1.1 13 days

1

37

Risk Ratio (M‐H, Fixed, 95% CI)

1.89 [0.19, 19.13]

1.2 6 weeks

2

506

Risk Ratio (M‐H, Fixed, 95% CI)

1.80 [1.34, 2.42]

2 Adverse effects ‐ 6 weeks Show forest plot

2

506

Risk Ratio (M‐H, Random, 95% CI)

0.89 [0.47, 1.71]

Figures and Tables -
Comparison 2. Tacrolimus 0.1% versus pimecrolimus 1%
Comparison 3. Tacrolimus 0.03% versus steroids

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Physician's assessment of global response of improvement, clear or excellent Show forest plot

5

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

1.1 Tacrolimus 0.03% 1x/day versus hydrocortisone acetate 1% 2x/day

1

411

Risk Ratio (M‐H, Random, 95% CI)

2.05 [1.36, 3.08]

1.2 Tacrolimus 0.03% 2x/day versus hydrocortisone acetate 1% 2x/day

2

790

Risk Ratio (M‐H, Random, 95% CI)

2.58 [1.96, 3.38]

1.3 Tacrolimus 0.03% 2x/day versus steroids moderate potency 2x/day

2

409

Risk Ratio (M‐H, Random, 95% CI)

0.45 [0.13, 1.57]

1.4 Tacrolimus 0.03% 2x/day versus methylprednisolone 0.03% 1x/day

1

265

Risk Ratio (M‐H, Random, 95% CI)

1.00 [0.85, 1.19]

2 Participants's assessment of global response of improvement better or much better Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2.1 Tacrolimus 0.03 1x/day versus hydrocortisone acetate 1% 2x/day

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.2 Tacrolimus 0.03% 2x/day versus hydrocortisone acetate 1% 2x/day

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.3 Tacrolimus 0.03% 2x/day versus fluticasone 0.005% 2x/day

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3 Adverse effects: burning Show forest plot

5

1883

Risk Ratio (M‐H, Fixed, 95% CI)

2.48 [1.96, 3.14]

3.1 Tacrolimus 0.03% versus hydrocortisone acetate 1%

2

998

Risk Ratio (M‐H, Fixed, 95% CI)

1.87 [1.36, 2.57]

3.2 Tacrolimus 0.03% versus steroids moderate potency

3

885

Risk Ratio (M‐H, Fixed, 95% CI)

3.52 [2.45, 5.06]

4 Adverse effects: pruritus Show forest plot

5

1883

Risk Ratio (M‐H, Fixed, 95% CI)

1.51 [1.17, 1.95]

4.1 Tacrolimus 0.03% versus hydrocortisone acetate 1%

2

998

Risk Ratio (M‐H, Fixed, 95% CI)

1.37 [1.00, 1.88]

4.2 Tacrolimus 0.03% versus steroids of moderate potency

3

885

Risk Ratio (M‐H, Fixed, 95% CI)

1.81 [1.18, 2.80]

5 Adverse effects: skin infection Show forest plot

4

1643

Risk Ratio (M‐H, Fixed, 95% CI)

1.07 [0.69, 1.66]

5.1 Tacrolimus 0.03% versus hydrocortisone acetate 1%

2

788

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.49, 1.79]

5.2 Tacrolimus 0.03% versus steroids of moderate potency

2

855

Risk Ratio (M‐H, Fixed, 95% CI)

1.19 [0.65, 2.18]

Figures and Tables -
Comparison 3. Tacrolimus 0.03% versus steroids
Comparison 4. Tacrolimus 0.03% versus tacrolimus 0.1%

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Physician's assessment of global response of improvement, clear or excellent Show forest plot

6

1640

Risk Ratio (M‐H, Fixed, 95% CI)

0.82 [0.72, 0.92]

1.1 3 weeks

4

985

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.71, 0.96]

1.2 12 weeks

2

655

Risk Ratio (M‐H, Fixed, 95% CI)

0.80 [0.64, 0.99]

2 Adverse effects Show forest plot

4

986

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.86, 1.06]

Figures and Tables -
Comparison 4. Tacrolimus 0.03% versus tacrolimus 0.1%
Comparison 5. Tacrolimus 0.03% versus pimecrolimus 1%

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Physician's assessment of global response of improvement Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2 Adverse effects Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2.1 Application site reaction

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.2 Burning

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.3 Itching

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.4 Erythema

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

Figures and Tables -
Comparison 5. Tacrolimus 0.03% versus pimecrolimus 1%
Comparison 6. Tacrolimus 0.1% versus ciclosporin

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Adverse effects Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2 SCORAD Show forest plot

1

Mean Difference (Fixed, 95% CI)

Totals not selected

2.1 14 days

1

Mean Difference (Fixed, 95% CI)

0.0 [0.0, 0.0]

2.2 21 days

1

Mean Difference (Fixed, 95% CI)

0.0 [0.0, 0.0]

2.3 28 days

1

Mean Difference (Fixed, 95% CI)

0.0 [0.0, 0.0]

2.4 35 days

1

Mean Difference (Fixed, 95% CI)

0.0 [0.0, 0.0]

2.5 42 days

1

Mean Difference (Fixed, 95% CI)

0.0 [0.0, 0.0]

Figures and Tables -
Comparison 6. Tacrolimus 0.1% versus ciclosporin