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Cochrane Database of Systematic Reviews

Intra‐articular corticosteroid for knee osteoarthritis

Información

DOI:
https://doi.org/10.1002/14651858.CD005328.pub3Copiar DOI
Base de datos:
  1. Cochrane Database of Systematic Reviews
Versión publicada:
  1. 22 octubre 2015see what's new
Tipo:
  1. Intervention
Etapa:
  1. Review
Grupo Editorial Cochrane:
  1. Grupo Cochrane de Salud musculoesquelética

Copyright:
  1. Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Autores

  • Peter Jüni

    Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland

  • Roman Hari

    Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland

  • Anne WS Rutjes

    Centre for Systematic Reviews, Fondazione "Università G. D'Annunzio", Chieti, Italy

    Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland

  • Roland Fischer

    Department of General Internal Medicine, Inselspital Bern, Bern, Switzerland

  • Maria G Silletta

    Centre for Systematic Reviews, Fondazione "Università G. D'Annunzio", Chieti, Italy

  • Stephan Reichenbach

    Department for Rheumatology, Clinical Immunology, and Allergology, University Hospital, Bern, Switzerland

  • Bruno R da Costa

    Correspondencia a: Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland

    [email protected]

Contributions of authors

Protocol completion: Jüni, Rutjes, Reichenbach, da Costa.
Acquisition of data: Hari, Rutjes, Fischer, Silletta, da Costa.
Analysis and interpretation of data: Jüni, Hari, Reichenbach, da Costa.
Manuscript preparation: Jüni, Hari, da Costa.
Statistical analysis: Jüni, da Costa.

Sources of support

Internal sources

  • No sources of support supplied

External sources

  • NIHR Cochrane Direct Commmission Incentive Award, UK.

    This review was supported by a grant from the NIHR, UK (NIHR Cochrane Direct Commmission Incentive Award)

Declarations of interest

Peter Jüni: none
Roman Hari: none
Anne WS Rutjes: none
Roland Fischer: none
Maria G Silletta: none
Stephan Reichenbach: none
Bruno R da Costa: none

Acknowledgements

We acknowledge Dr. med. Marcello Di Nisio for his contribution with reference screening. We are grateful to Dr. Janne Estill and Elena Jüni for their translation of the Popov 1989 trial. We would also like to acknowledge the authors of the original version of this review: Nicholas Bellamy, Jane Campbell, Vivian Welch, Travis L Gee, Robert Bourne, and George A Wells.

Version history

Published

Title

Stage

Authors

Version

2015 Oct 22

Intra‐articular corticosteroid for knee osteoarthritis

Review

Peter Jüni, Roman Hari, Anne WS Rutjes, Roland Fischer, Maria G Silletta, Stephan Reichenbach, Bruno R da Costa

https://doi.org/10.1002/14651858.CD005328.pub3

2006 Apr 19

Intraarticular corticosteroid for treatment of osteoarthritis of the knee

Review

Nicholas Bellamy, Jane Campbell, Vivian Welch, Travis L Gee, Robert Bourne, George A Wells

https://doi.org/10.1002/14651858.CD005328.pub2

2005 Apr 20

Intraarticular corticosteroid for treatment of osteoarthritis of the knee

Review

Nicholas Bellamy, Jane Campbell, Vivian A Robinson, T Gee, Robert Bourne, George Wells

https://doi.org/10.1002/14651858.CD005328

Differences between protocol and review

Types of studies

In the previous version of this Cochrane Review, only RCTs were eligible for inclusion, while in the present review update both RCTs and quasi‐RCTs were eligible.

Types of interventions

In the previous review version, control interventions were both sham intra‐articular corticosteroid and active interventions (joint lavage, intra‐articular hyaluronan/hylan, and other intra‐articular corticosteroids). In the present review update, the prespecified control interventions were sham intra‐articular corticosteroid and no intervention.

Types of outcome measures

In the previous review version there were eight outcomes: pain, physical function, patient global assessment, joint imaging, adverse reaction caused by procedure, adverse reaction caused by corticosteroid, adverse reaction caused by toxicity‐related withdrawals, total number of withdrawals and dropouts. In the review update, there were two prespecified primary outcomes and six prespecified secondary outcomes. Primary outcomes were pain and physical function, and secondary outcomes were quality of life, joint imaging, and the number of participants who experienced any adverse event, withdrew because of adverse events, and experienced any serious adverse events.

Search methods for identification of studies

In the previous review version, the following four databases were searched: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (including PreMEDLINE), EMBASE, and Current Contents. The electronic searches were supplemented by handsearches of bibliographic references and abstracts published in conference proceedings or in special issues of specialised journals, and industry representatives were contacted to request additional studies of their product that could meet eligibility criteria. In the present review update, we searched the following three databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid and PubMed platforms, and EMBASE. The electronic searches were supplemented by handsearches of bibliographic references, abstracts published in conference proceedings, and search of clinical trial registers to identify ongoing or recently concluded trials.

Keywords

MeSH

PICO

Population
Intervention
Comparison
Outcome

El uso y la enseñanza del modelo PICO están muy extendidos en el ámbito de la atención sanitaria basada en la evidencia para formular preguntas y estrategias de búsqueda y para caracterizar estudios o metanálisis clínicos. PICO son las siglas en inglés de cuatro posibles componentes de una pregunta de investigación: paciente, población o problema; intervención; comparación; desenlace (outcome).

Para saber más sobre el uso del modelo PICO, puede consultar el Manual Cochrane.

Study flow chart. *records with the exact same bibliographic information of another already‐screened record.
Figuras y tablas -
Figure 1

Study flow chart. *records with the exact same bibliographic information of another already‐screened record.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figuras y tablas -
Figure 2

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

Forest plot of comparison: 1 Pain, outcome: 1.1 Pain ‐ Main.
Figuras y tablas -
Figure 3

Forest plot of comparison: 1 Pain, outcome: 1.1 Pain ‐ Main.

Contour‐enhanced funnel plot for effects on knee pain. Numbers on x axis refer to standardised mean differences (SMDs), on y axis to standard errors of SMDs
Figuras y tablas -
Figure 4

Contour‐enhanced funnel plot for effects on knee pain. Numbers on x axis refer to standardised mean differences (SMDs), on y axis to standard errors of SMDs

Forest plot of comparison: 1 Pain, outcome: 1.2 Pain ‐ Time points. P for trend = 0.001
Figuras y tablas -
Figure 5

Forest plot of comparison: 1 Pain, outcome: 1.2 Pain ‐ Time points. P for trend = 0.001

Forest plot of comparison: 2 Function, outcome: 2.1 Function ‐ Main.
Figuras y tablas -
Figure 6

Forest plot of comparison: 2 Function, outcome: 2.1 Function ‐ Main.

Contour‐enhanced funnel plot for effects on knee function. Numbers on x axis refer to standardised mean differences (SMDs), on y axis to standard errors of SMDs
Figuras y tablas -
Figure 7

Contour‐enhanced funnel plot for effects on knee function. Numbers on x axis refer to standardised mean differences (SMDs), on y axis to standard errors of SMDs

Forest plot of comparison: 2 Function, outcome: 2.2 Function ‐ Time points. P for trend = 0.011
Figuras y tablas -
Figure 8

Forest plot of comparison: 2 Function, outcome: 2.2 Function ‐ Time points. P for trend = 0.011

Forest plot of comparison: 3 Quality of life, outcome: 3.1 Quality of life ‐ Main.
Figuras y tablas -
Figure 9

Forest plot of comparison: 3 Quality of life, outcome: 3.1 Quality of life ‐ Main.

Forest plot of comparison: 7 Joint space narrowing, outcome: 7.1 Joint space narrowing ‐ Main.
Figuras y tablas -
Figure 10

Forest plot of comparison: 7 Joint space narrowing, outcome: 7.1 Joint space narrowing ‐ Main.

Forest plot of comparison: 4 Number of participants experiencing any adverse event, outcome: 4.1 Number of participants experiencing any adverse event ‐ Main.
Figuras y tablas -
Figure 11

Forest plot of comparison: 4 Number of participants experiencing any adverse event, outcome: 4.1 Number of participants experiencing any adverse event ‐ Main.

Forest plot of comparison: 5 Number of participants who withdraw because of adverse events, outcome: 5.1 Number of participants who withdraw because of adverse events ‐Main.
Figuras y tablas -
Figure 12

Forest plot of comparison: 5 Number of participants who withdraw because of adverse events, outcome: 5.1 Number of participants who withdraw because of adverse events ‐Main.

Forest plot of comparison: 6 Number of participants experiencing any serious adverse event, outcome: 6.1 Number of participants experiencing any serious adverse event ‐ Main.
Figuras y tablas -
Figure 13

Forest plot of comparison: 6 Number of participants experiencing any serious adverse event, outcome: 6.1 Number of participants experiencing any serious adverse event ‐ Main.

Comparison 1 Pain, Outcome 1 Pain ‐ Main.
Figuras y tablas -
Analysis 1.1

Comparison 1 Pain, Outcome 1 Pain ‐ Main.

Comparison 1 Pain, Outcome 2 Pain ‐ Timepoints.
Figuras y tablas -
Analysis 1.2

Comparison 1 Pain, Outcome 2 Pain ‐ Timepoints.

Comparison 2 Function, Outcome 1 Function ‐ Main.
Figuras y tablas -
Analysis 2.1

Comparison 2 Function, Outcome 1 Function ‐ Main.

Comparison 2 Function, Outcome 2 Function ‐ Timepoints.
Figuras y tablas -
Analysis 2.2

Comparison 2 Function, Outcome 2 Function ‐ Timepoints.

Comparison 3 Quality of life, Outcome 1 Quality of life ‐ Main.
Figuras y tablas -
Analysis 3.1

Comparison 3 Quality of life, Outcome 1 Quality of life ‐ Main.

Comparison 4 Number of participants experiencing any adverse event, Outcome 1 Number of participants experiencing any adverse event ‐ Main.
Figuras y tablas -
Analysis 4.1

Comparison 4 Number of participants experiencing any adverse event, Outcome 1 Number of participants experiencing any adverse event ‐ Main.

Comparison 5 Number of participants who withdraw because of adverse events, Outcome 1 Number of participants who with draw because of adverse events ‐Main.
Figuras y tablas -
Analysis 5.1

Comparison 5 Number of participants who withdraw because of adverse events, Outcome 1 Number of participants who with draw because of adverse events ‐Main.

Comparison 6 Number of participants experiencing any serious adverse event, Outcome 1 Number of participants experiencing any serious adverse event ‐ Main.
Figuras y tablas -
Analysis 6.1

Comparison 6 Number of participants experiencing any serious adverse event, Outcome 1 Number of participants experiencing any serious adverse event ‐ Main.

Comparison 7 Joint space narrowing, Outcome 1 Joint space narrowing ‐ Main.
Figuras y tablas -
Analysis 7.1

Comparison 7 Joint space narrowing, Outcome 1 Joint space narrowing ‐ Main.

Intra‐articular corticosteroid compared with sham injection for osteoarthritis of the knee

Patient or population: participants with osteoarthritis of the knee

Settings: various orthopaedic or rheumatology clinics

Intervention: intra‐articular corticosteroid

Comparison: sham injection

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Sham injection

Intra‐articular corticosteroid

Pain intensity

Various pain scales.

(median follow‐up: 12 weeks)

‐1.8 cm change on 10‐cm VAS1
29% improvement

‐2.8 cm change
(Δ ‐1.0 cm, ‐1.5 to ‐0.6)2

46% improvement
(Δ 17%, 10% to 25%)3

SMD ‐0.40 (‐0.58 to ‐0.22)

Predictive interval (‐1.20 to 0.40)

1749

(26)

⊕⊕⊝⊝
low9

NNTB 8 (95% CI 6 to 13)4

Function

Various function scales.

(median follow‐up: 12 weeks)

‐1.2 units on WOMAC (range 0 to 10)1
21% improvement

‐1.9 units on WOMAC
(Δ ‐0.7, ‐1.2 to ‐0.2)5

34% improvement
(Δ 13%, 4% to 22%)6

SMD ‐0.33 (‐0.56 to ‐0.09)

Predictive interval (‐1.19 to 0.54)

1014

(15)

⊕⊕⊝⊝
low9

NNTB 10 (95% CI 7 to 33)7

Number of participants experiencing any adverse event

(median follow‐up: 17 weeks)

150 per 1000 participant‐years8

134 per 1000 participant‐years
(96 to 185)

RR 0.89 (0.64 to 1.23)

84

(2)

⊕⊕⊝⊝
low10

Little evidence of harmful effect (NNTB not statistically significant)

Number of participants who withdraw because of adverse events

(median follow‐up: 25 weeks)

17 per 1000 participant‐years8

6 per 1000 participant‐years
(1 to 35)

RR 0.33 (0.05 to 2.07)

204

(2)

⊕⊕⊝⊝
low10

Little evidence of harmful effect (NNTB not statistically significant)

Number of participants experiencing any serious adverse event

(median follow‐up: 26 weeks)

4 per 1000 participant‐years8

3 per 1000 participant‐years
(1 to 11)

RR 0.63 (0.15 to 2.67)

331

(5)

⊕⊕⊝⊝
low10

Little evidence of harmful effect (NNTB not statistically significant)

*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; NNTB: number needed to treat for an additional beneficial outcome; RR: risk ratio; SMD: standardised mean difference; VAS: visual analogue scale; WOMAC: Western Ontario and McMaster Universities Arthritis Index

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.

1 Median reduction as observed across placebo groups in large osteoarthritis trials (see methods section, Nüesch 2009).
2 SMDs were back‐transformed onto a 10‐cm visual analogue scale (VAS) on the basis of a typical pooled standard deviation (SD) of 2.5 cm in large trials that assessed pain using a VAS and expressed as change based on an assumed standardised reduction of 0.72 SD units in the control group.
3 Percentage of improvement was calculated based on median observed pain at baseline across control groups of large osteoarthritis trials of 6.1 cm on 10‐cm VAS (Nüesch 2009).
4 Absolute response risks for pain in the control groups were assumed 31% (see methods section).

5 SMDs were back‐transformed onto a standardised Western Ontario and McMaster Universities Arthritis Index (WOMAC) disability score ranging from 0 to 10 on the basis of a typical pooled SD of 2.1 in trials that assessed function using WOMAC disability scores and expressed as change based on an assumed standardised reduction of 0.58 SD units in the control group.
6 Percentage of improvement was calculated based on median observed WOMAC function scores at baseline across control groups of large osteoarthritis trials of 5.6 units (Nüesch 2009).
7 Absolute response risks for function in the control groups were assumed 26% (see methods section).
8 Median control risk across placebo groups in large osteoarthritis trials (see methods section, Nüesch 2009).

9 Downgraded (2 levels) because: Most studies that reported this outcome are of high or unclear risk of bias, and statistical heterogeneity is large.

10 Downgraded (3 levels) because: 50% or more of the studies that reported this outcome are of high or unclear risk of bias, and the confidence interval of the pooled estimate is wide and includes the null effect.

Figuras y tablas -
Table 1. Stratified analyses: Pain

Variable

Number of studies

N of participants corticosteroids

N of participants control

Pain intensity SMD (95% CI)

Heterogeneity I2 (%)

P value*

All trials

26

922

827

‐0.40 (‐0.58 to ‐0.22)

68%

Allocation concealment

0.15

Adequate

2

88

83

‐0.16 (‐0.46 to 0.14)

0%

Inadequate or unclear

24

834

744

‐0.42 (‐0.62 to ‐0.22)

69%

Blinding of participants

0.64

Adequate

6

220

218

‐0.34 (‐0.61 to ‐0.06)

49%

Inadequate or unclear

20

702

609

‐0.42 (‐0.65 to ‐0.19)

72%

Blinding of therapists

0.45

Adequate

3

92

92

‐0.24 (‐0.66 to 0.17)

44%

Inadequate or unclear

23

830

735

‐0.42 (‐0.62 to ‐0.22)

70%

Intention‐to‐treat analysis

0.29

Yes

9

236

233

‐0.26 (‐0.57 to 0.06)

59%

No or unclear

17

686

594

‐0.47 (‐0.69 to ‐0.24)

71%

Type of control intervention

0.08

Sham injection

19

614

526

‐0.50 (‐0.72 to ‐0.28)

65%

No intervention

7

284

280

‐0.18 (‐0.47 to 0.11)

63%

Funding independent of industry

0.80

Yes

11

341

333

‐0.37 (‐0.55 to ‐0.18)

26%

No or unclear

15

581

494

‐0.41 (‐0.70 to ‐0.12)

78%

Trial size

0.05

≥ 50 per trial group

3

205

204

‐0.13 (‐0.37 to 0.12)

34%

< 50 per trial group

23

717

623

‐0.44 (‐0.65 to ‐0.24)

67%

Trial size

0.013

≥ 100 per trial group

1

103

103

0.00 (‐0.27 to 0.27)

N/A

< 100 per trial group

25

819

724

‐0.42 (‐0.61 to ‐0.23)

66%

Publication type

0.93

Full journal article

22

785

706

‐0.40 (‐0.61 to ‐0.20)

70%

Other type or unpublished material

4

137

121

‐0.38 (‐0.84 to ‐0.08)

65%

Ultrasound guidance of injections

0.71

Yes

2

70

70

‐0.62 (‐1.83 to 0.58)

89%

No or unclear

24

852

757

‐0.39 (‐0.57 to ‐0.20)

67%

Use of local anaesthetic

0.41

Yes

5

172

157

‐0.55 (‐0.93 to ‐0.16)

62%

No or unclear

21

750

670

‐0.36 (‐0.57 to ‐0.15)

70%

Concomitant viscosupplementation

0.08

Yes

4

129

127

‐0.16 (‐0.42 to 0.09)

4%

No or unclear

22

793

700

‐0.46 (‐0.67 to ‐0.25)

71%

Concomitant joint lavage

≤ 0.001

Yes

4

197

187

‐0.06 (‐0.26 to 0.15)

0%

No or unclear

26

725

640

‐0.57 (‐0.78 to ‐0.35)

72%

Use of crystalline preparation

0.82

Yes

18

623

562

‐0.47 (‐0.69 to ‐0.24)

72%

No or unclear

12

299

265

‐0.52 (‐0.90 to ‐0.14)

76%

Prednisolone equivalence dose

0.53

≥ 50 mg

17

520

470

‐0.55 (‐0.85 to ‐0.25)

80%

< 50 mg

13

402

357

‐0.43 (‐0.66 to ‐0.20)

56%

Number of randomised comparisons are shown in "number of studies" for stratified analyses according to use of lavage as co‐intervention, crystalline preparation, prednisolone equivalence. *P value for interaction. N/A: not available.

CI: confidence interval
SMD: standardised mean difference

Figuras y tablas -
Table 1. Stratified analyses: Pain
Table 2. Stratified analyses: Function

Variable

Number of studies

N of participants corticosteroids

N of participants control

Function SMD (95% CI)

Heterogeneity I2 (%)

P value*

All trials

15

546

468

‐0.33 (‐0.56 to ‐0.09)

69%

Allocation concealment

0.25

Adequate

2

88

83

‐0.09 (‐0.49 to 0.32)

43%

Inadequate or unclear

13

458

385

‐0.37 (‐0.64 to ‐0.10)

72%

Blinding of participants

0.97

Adequate

5

201

199

‐0.32 (‐0.82 to 0.18)

83%

Inadequate or unclear

10

345

269

‐0.33 (‐0.59 to ‐0.07)

58%

Blinding of therapists

0.78

Adequate

2

75

75

‐0.48 (‐1.65 to 0.70)

91%

Inadequate or unclear

13

471

393

‐0.31 (‐0.55 to ‐0.06)

66%

Intention‐to‐treat analysis

0.49

Yes

5

161

159

‐0.21 (‐0.59 to 0.17)

62%

No or unclear

10

385

309

‐0.38 (‐0.69 to ‐0.07)

73%

Type of control intervention

0.031

Sham injection

11

409

334

‐0.45 (‐0.74 to ‐0.15)

73%

No intervention

4

137

134

‐0.01 (‐0.27 to 0.25)

13%

Funding independent of industry

0.73

Yes

9

310

302

‐0.36 (‐0.66 to ‐0.07)

68%

No or unclear

6

236

166

‐0.27 (‐0.71 to 0.16)

76%

Trial size

0.023

≥ 50 per trial group

2

102

101

0.05 (‐0.23 to 0.32)

0%

< 50 per trial group

13

444

367

‐0.40 (‐0.67 to ‐0.13)

70%

Trial size

N/A

≥ 100 per trial group

0

0

0

N/A

N/A

< 100 per trial group

15

546

468

‐0.33 (‐0.56 to ‐0.09)

69%

Publication type

0.023

Full journal article

14

514

438

‐0.37 (‐0.61 to ‐0.13)

68%

Other type or unpublished material

1

32

30

0.28 (‐0.22 to 0.78)

N/A

Ultrasound guidance of injections

0.49

Yes

2

70

70

‐0.14 (‐0.70 to 0.43)

58%

No or unclear

13

476

398

‐0.36 (‐0.62 to ‐0.09)

71%

Use of local anaesthetic

0.34

Yes

4

105

105

‐0.60 (‐1.25 to 0.05)

78%

No or unclear

11

441

363

‐0.25 (‐0.51 to 0.00)

68%

Concomitant viscosupplementation

0.06

Yes

2

85

84

‐0.00 (‐0.30 to 0.30)

0%

No or unclear

13

461

384

‐0.39 (‐0.66 to ‐0.12)

72%

Concomitant joint lavage

0.18

Yes

3

94

84

‐0.13 (‐0.55 to 0.28)

48%

No or unclear

16

452

384

‐0.46 (‐0.71 to ‐0.21)

70%

Use of crystalline preparation

0.66

Yes

12

365

319

‐0.37 (‐0.66 to ‐0.08)

73%

No or unclear

7

181

149

‐0.47 (‐0.83 to ‐0.11)

61%

Prednisolone equivalence dose

0.16

≥ 50 mg

12

328

277

‐0.52 (‐0.83 to ‐0.20)

74%

< 50 mg

7

218

191

‐0.22 (‐0.48 to 0.05)

47%

Number of randomised comparisons are shown in "number of studies" for stratified analyses according to use of lavage as co‐intervention, crystalline preparation, prednisolone equivalence. *P value for interaction. N/A: not available.

CI: confidence interval
SMD: standardised mean difference

Figuras y tablas -
Table 2. Stratified analyses: Function
Comparison 1. Pain

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Pain ‐ Main Show forest plot

26

1749

Std. Mean Difference (Random, 95% CI)

‐0.40 [‐0.58, ‐0.22]

2 Pain ‐ Timepoints Show forest plot

26

Std. Mean Difference (Random, 95% CI)

Subtotals only

2.1 Pain‐ 1‐2 week

16

1041

Std. Mean Difference (Random, 95% CI)

‐0.48 [‐0.70, ‐0.27]

2.2 Pain‐ 4‐6 week

22

1529

Std. Mean Difference (Random, 95% CI)

‐0.41 [‐0.61, ‐0.21]

2.3 Pain‐ 3 months

18

1233

Std. Mean Difference (Random, 95% CI)

‐0.22 [‐0.44, 0.00]

2.4 Pain‐ 6 months

7

526

Std. Mean Difference (Random, 95% CI)

‐0.07 [‐0.25, 0.11]

Figuras y tablas -
Comparison 1. Pain
Comparison 2. Function

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Function ‐ Main Show forest plot

15

1014

Std. Mean Difference (Random, 95% CI)

‐0.33 [‐0.56, ‐0.09]

2 Function ‐ Timepoints Show forest plot

15

Std. Mean Difference (Random, 95% CI)

Subtotals only

2.1 Function ‐ 1‐2 weeks

10

763

Std. Mean Difference (Random, 95% CI)

‐0.43 [‐0.72, ‐0.14]

2.2 Function ‐ 4‐6 weeks

12

818

Std. Mean Difference (Random, 95% CI)

‐0.36 [‐0.63, ‐0.09]

2.3 Function ‐ 3 months

11

800

Std. Mean Difference (Random, 95% CI)

‐0.13 [‐0.37, 0.10]

2.4 Function ‐ 6 months

4

328

Std. Mean Difference (Random, 95% CI)

0.06 [‐0.16, 0.28]

Figuras y tablas -
Comparison 2. Function
Comparison 3. Quality of life

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Quality of life ‐ Main Show forest plot

2

184

Std. Mean Difference (Random, 95% CI)

‐0.01 [‐0.30, 0.28]

Figuras y tablas -
Comparison 3. Quality of life
Comparison 4. Number of participants experiencing any adverse event

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Number of participants experiencing any adverse event ‐ Main Show forest plot

2

84

Risk Ratio (IV, Random, 95% CI)

0.89 [0.64, 1.23]

Figuras y tablas -
Comparison 4. Number of participants experiencing any adverse event
Comparison 5. Number of participants who withdraw because of adverse events

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Number of participants who with draw because of adverse events ‐Main Show forest plot

2

204

Risk Ratio (IV, Random, 95% CI)

0.33 [0.05, 2.07]

Figuras y tablas -
Comparison 5. Number of participants who withdraw because of adverse events
Comparison 6. Number of participants experiencing any serious adverse event

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Number of participants experiencing any serious adverse event ‐ Main Show forest plot

5

331

Risk Ratio (IV, Random, 95% CI)

0.63 [0.15, 2.67]

Figuras y tablas -
Comparison 6. Number of participants experiencing any serious adverse event
Comparison 7. Joint space narrowing

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Joint space narrowing ‐ Main Show forest plot

1

68

Std. Mean Difference (Random, 95% CI)

‐0.02 [‐0.49, 0.46]

Figuras y tablas -
Comparison 7. Joint space narrowing