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Meta-Analysis
. 2015 Oct 22;2015(10):CD005328.
doi: 10.1002/14651858.CD005328.pub3.

Intra-articular corticosteroid for knee osteoarthritis

Peter Jüni  1 , Roman Hari, Anne W S Rutjes, Roland Fischer, Maria G Silletta, Stephan Reichenbach, Bruno R da Costa
Affiliations
Meta-Analysis

Intra-articular corticosteroid for knee osteoarthritis

Peter Jüni et al. Cochrane Database Syst Rev. .

Abstract

Background: Knee osteoarthritis is a leading cause of chronic pain, disability, and decreased quality of life. Despite the long-standing use of intra-articular corticosteroids, there is an ongoing debate about their benefits and safety. This is an update of a Cochrane review first published in 2005.

Objectives: To determine the benefits and harms of intra-articular corticosteroids compared with sham or no intervention in people with knee osteoarthritis in terms of pain, physical function, quality of life, and safety.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE (from inception to 3 February 2015), checked trial registers, conference proceedings, reference lists, and contacted authors.

Selection criteria: We included randomised or quasi-randomised controlled trials that compared intra-articular corticosteroids with sham injection or no treatment in people with knee osteoarthritis. We applied no language restrictions.

Data collection and analysis: We calculated standardised mean differences (SMDs) and 95% confidence intervals (CI) for pain, function, quality of life, joint space narrowing, and risk ratios (RRs) for safety outcomes. We combined trials using an inverse-variance random-effects meta-analysis.

Main results: We identified 27 trials (13 new studies) with 1767 participants in this update. We graded the quality of the evidence as 'low' for all outcomes because treatment effect estimates were inconsistent with great variation across trials, pooled estimates were imprecise and did not rule out relevant or irrelevant clinical effects, and because most trials had a high or unclear risk of bias. Intra-articular corticosteroids appeared to be more beneficial in pain reduction than control interventions (SMD -0.40, 95% CI -0.58 to -0.22), which corresponds to a difference in pain scores of 1.0 cm on a 10-cm visual analogue scale between corticosteroids and sham injection and translates into a number needed to treat for an additional beneficial outcome (NNTB) of 8 (95% CI 6 to 13). An I(2) statistic of 68% indicated considerable between-trial heterogeneity. A visual inspection of the funnel plot suggested some asymmetry (asymmetry coefficient -1.21, 95%CI -3.58 to 1.17). When stratifying results according to length of follow-up, benefits were moderate at 1 to 2 weeks after end of treatment (SMD -0.48, 95% CI -0.70 to -0.27), small to moderate at 4 to 6 weeks (SMD -0.41, 95% CI -0.61 to -0.21), small at 13 weeks (SMD -0.22, 95% CI -0.44 to 0.00), and no evidence of an effect at 26 weeks (SMD -0.07, 95% CI -0.25 to 0.11). An I(2) statistic of ≥ 63% indicated a moderate to large degree of between-trial heterogeneity up to 13 weeks after end of treatment (P for heterogeneity≤0.001), and an I(2) of 0% indicated low heterogeneity at 26 weeks (P=0.43). There was evidence of lower treatment effects in trials that randomised on average at least 50 participants per group (P=0.05) or at least 100 participants per group (P=0.013), in trials that used concomittant viscosupplementation (P=0.08), and in trials that used concomitant joint lavage (P≤0.001).Corticosteroids appeared to be more effective in function improvement than control interventions (SMD -0.33, 95% CI -0.56 to -0.09), which corresponds to a difference in functions scores of -0.7 units on standardised Western Ontario and McMaster Universities Arthritis Index (WOMAC) disability scale ranging from 0 to 10 and translates into a NNTB of 10 (95% CI 7 to 33). An I(2) statistic of 69% indicated a moderate to large degree of between-trial heterogeneity. A visual inspection of the funnel plot suggested asymmetry (asymmetry coefficient -4.07, 95% CI -8.08 to -0.05). When stratifying results according to length of follow-up, benefits were small to moderate at 1 to 2 weeks after end of treatment (SMD -0.43, 95% CI -0.72 to -0.14), small to moderate at 4 to 6 weeks (SMD -0.36, 95% CI -0.63 to -0.09), and no evidence of an effect at 13 weeks (SMD -0.13, 95% CI -0.37 to 0.10) or at 26 weeks (SMD 0.06, 95% CI -0.16 to 0.28). An I(2) statistic of ≥ 62% indicated a moderate to large degree of between-trial heterogeneity up to 13 weeks after end of treatment (P for heterogeneity≤0.004), and an I(2) of 0% indicated low heterogeneity at 26 weeks (P=0.52). We found evidence of lower treatment effects in trials that randomised on average at least 50 participants per group (P=0.023), in unpublished trials (P=0.023), in trials that used non-intervention controls (P=0.031), and in trials that used concomitant viscosupplementation (P=0.06).Participants on corticosteroids were 11% less likely to experience adverse events, but confidence intervals included the null effect (RR 0.89, 95% CI 0.64 to 1.23, I(2)=0%). Participants on corticosteroids were 67% less likely to withdraw because of adverse events, but confidence intervals were wide and included the null effect (RR 0.33, 95% CI 0.05 to 2.07, I(2)=0%). Participants on corticosteroids were 27% less likely to experience any serious adverse event, but confidence intervals were wide and included the null effect (RR 0.63, 95% CI 0.15 to 2.67, I(2)=0%).We found no evidence of an effect of corticosteroids on quality of life compared to control (SMD -0.01, 95% CI -0.30 to 0.28, I(2)=0%). There was also no evidence of an effect of corticosteroids on joint space narrowing compared to control interventions (SMD -0.02, 95% CI -0.49 to 0.46).

Authors' conclusions: Whether there are clinically important benefits of intra-articular corticosteroids after one to six weeks remains unclear in view of the overall quality of the evidence, considerable heterogeneity between trials, and evidence of small-study effects. A single trial included in this review described adequate measures to minimise biases and did not find any benefit of intra-articular corticosteroids.In this update of the systematic review and meta-analysis, we found most of the identified trials that compared intra-articular corticosteroids with sham or non-intervention control small and hampered by low methodological quality. An analysis of multiple time points suggested that effects decrease over time, and our analysis provided no evidence that an effect remains six months after a corticosteroid injection.

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Conflict of interest statement

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

Figures

1
1
Study flow chart. *records with the exact same bibliographic information of another already‐screened record.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Forest plot of comparison: 1 Pain, outcome: 1.1 Pain ‐ Main.
4
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
5
5
Forest plot of comparison: 1 Pain, outcome: 1.2 Pain ‐ Time points. P for trend = 0.001
6
6
Forest plot of comparison: 2 Function, outcome: 2.1 Function ‐ Main.
7
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
8
8
Forest plot of comparison: 2 Function, outcome: 2.2 Function ‐ Time points. P for trend = 0.011
9
9
Forest plot of comparison: 3 Quality of life, outcome: 3.1 Quality of life ‐ Main.
10
10
Forest plot of comparison: 7 Joint space narrowing, outcome: 7.1 Joint space narrowing ‐ Main.
11
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Forest plot of comparison: 4 Number of participants experiencing any adverse event, outcome: 4.1 Number of participants experiencing any adverse event ‐ Main.
12
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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.
13
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.
1.1
1.1. Analysis
Comparison 1 Pain, Outcome 1 Pain ‐ Main.
1.2
1.2. Analysis
Comparison 1 Pain, Outcome 2 Pain ‐ Timepoints.
2.1
2.1. Analysis
Comparison 2 Function, Outcome 1 Function ‐ Main.
2.2
2.2. Analysis
Comparison 2 Function, Outcome 2 Function ‐ Timepoints.
3.1
3.1. Analysis
Comparison 3 Quality of life, Outcome 1 Quality of life ‐ Main.
4.1
4.1. Analysis
Comparison 4 Number of participants experiencing any adverse event, Outcome 1 Number of participants experiencing any adverse event ‐ Main.
5.1
5.1. Analysis
Comparison 5 Number of participants who withdraw because of adverse events, Outcome 1 Number of participants who with draw because of adverse events ‐Main.
6.1
6.1. Analysis
Comparison 6 Number of participants experiencing any serious adverse event, Outcome 1 Number of participants experiencing any serious adverse event ‐ Main.
7.1
7.1. Analysis
Comparison 7 Joint space narrowing, Outcome 1 Joint space narrowing ‐ Main.
See this image and copyright information in PMC

Update of

Comment in

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Lequesne 1970 {published data only}
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Maricar 2013c {published data only}
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McAlindon 2014 {published data only}
    1. McAlindon T E, Bannuru R R, Sullivan M C, Arden N K, Berenbaum F, Bierma‐Zeinstra S M, et al. OARSI guidelines for the non‐surgical management of knee osteoarthritis. Osteoarthritis and Cartilage 2014;22:363‐88. - PubMed
Murdoch 1959 {published data only}
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Murdoch 1959a {published data only}
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Nicol 1972 {published data only}
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No named author {published data only}
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Parmigiani 2010 {published data only}
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Pendleton 2008 {published data only}
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Punzi 2001 {published data only}
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Rasmussen 1998 {published data only}
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Rasmussen 1998a {published data only}
    1. Rasmussen S, Larsen A S, Thomsen S T, Kehlet H. Intraarticular glucocorticoid, morphine and bupivacaine reduces pain, inflammatory response and convalescence after arthroscopic meniscectomy [abstract]. Acta Orthopaedica Scandinavica 1998;69(Suppl 280):45.
Rasmussen 1998b {published data only}
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Van Middelkoop 2013 {published data only}
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Van Middelkoop 2013a {published data only}
    1. Middelkoop M, Dziedzic K, Doherty M, Zhang W, Bijlsma J W, McAlindon T, et al. The OA trial bank: Individual patient data meta‐analysis of trials investigating the effectiveness of intra‐articular corticosteroid injections in patients with knee or hip oa. Annals of the Rheumatic Diseases. 2013; Vol. 72. - PMC - PubMed
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Van Middelkoop 2014 {published data only}
    1. Middelkoop M, Arden N, Atchia I, Birrell F, Chao J, Lambert R, et al. The OA trial bank: Meta‐analysis of individual patient data show that patients with severe pain or with inflammatory signs detected by ultrasound especially benefit from intra‐articular glucocorticoids for knee or hip OA. Annals of the Rheumatic Diseases 2014;73:749.
Van Middelkoop 2014a {published data only}
    1. Middelkoop M, Arden N, Atchia I, Birrell F, Chao J, Lambert R G, et al. The OA trial bank: Meta‐analysis of individual patient data show that patients with severe pain or with inflammatory signs detected by ultrasound especially benefit from intra‐articular glucocorticoids for knee or hip OA. Osteoarthritis and Cartilage 2014;22:S474‐5.
Wang 1998 {published data only}
    1. Wang J J, Ho S T, Lee S C, Tang J J S, Liaw W J. Intraarticular triamcinolone acetonide for pain control after arthroscopic knee surgery. Anesthesia and Analgesia 1998;87(5):1113‐6. - PubMed
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Yamamoto 1970 {published data only}
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Zuckner 1958 {published data only}
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References to studies awaiting assessment

Ellis 2011 {published data only}
    1. Ellis M E, Lun V M Y, Preston Wiley J. Combination treatment for knee osteoarthritis. Clinical Journal of Sport Medicine 2011;21(4):374‐5.
Friedman 1978 {published data only}
    1. Friedman D M, Moore M F. The efficacy of intraarticular corticosteroid for osteoarthritis of the knee. Arthritis and Rheumatism 1978;21:556.
Hall 2013 {published data only}
    1. Hall M, Courtney P, Doherty S, Latief K, Zhang W, Doherty M. Ultrasound response following intra‐articular corticosteroid and a placebo injection in symptomatic osteoarthritic knees: A pilot study. Annals of the Rheumatic Diseases 2013;72:54. - PubMed
Hall 2014 {published data only}
    1. Hall M, Doherty S, Courtney P, Latief K, Zhang W, Doherty M. Ultrasound detected synovial change and pain response following intra‐articular injection of corticosteroid and a placebo in symptomatic osteoarthritic knees: A pilot study. Annals of the Rheumatic Diseases 2014;73:1590‐1. - PubMed
Motyl 2013 {published data only}
    1. Motyl J M, Driban J B, McAdams E, McAlindon T E. Reliability and sensitivity of the 20‐meter walk test among patients with knee osteoarthritis. Osteoarthritis and Cartilage 2013;21:S137. - PMC - PubMed
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    1. Motyl J M, Driban J B, McAdams E, Price L L, McAlindon T E. Test‐retest reliability and sensitivity of the 20‐meter walk test among patients with knee osteoarthritis. BMC Musculoskeletal Disorders 2013;14:166. - PMC - PubMed
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    1. O'Neill T W, Parkes M J, Maricar N, Gait A D, Cootes T F, Marjanovic E J, et al. Bone marrow lesions may not respond to anti‐inflammatory treatments in knee osteoarthritis (OA). Osteoarthritis and Cartilage 2014;22:S475.
Raynauld 1999 {published data only}
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Singh 1996 {published data only}
    1. Singh G K, Jain S, Das S K, Sharma V. Conservative treatment of osteoarthritis (OA) of the knee vs add on intra‐articular (IA) steroid injection [abstract]. Journal of Clinical Epidemiology 1996;49 Suppl 1:8s.

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