Does flare trial design affect the effect size of non-steroidal anti-inflammatory drugs in symptomatic osteoarthritis? A systematic review and meta-analysis

Smith, Toby O.; Zou, Kun; Abdullah, Natasya; Chen, Xi; Kingsbury, Sarah R.; Doherty, Michael; Zhang, Weiya; Conaghan, Philip G.

Abstract

Objectives: It is thought that the clinical trial benefits of oral non-steroidal anti-inflammatory drugs (NSAIDs) may relate to flare designs. The aim of this study was to examine the difference in NSAID (including cyclooxygenase-2 (COX-2) inhibitors) response in osteoarthritis (OA) trials based on different designs.

Methods: Systematic review was undertaken of the databases MEDLINE, EMBASE, AMED, CINAHL and the Cochrane library till February 2015. Randomised controlled trials assessing pain, function and/or stiffness following commencement of NSAIDs in flare and non-flare designs were eligible. Trials were assessed using the Cochrane Risk of Bias tool. Meta-analyses were conducted to assess the effect sizes (ES) of NSAIDs for OA with flare versus non-flare trial designs.

Results: Fifty-seven studies including 33 263 participants assessing 26 NSAIDs were included. Twenty-two (39%) were flare design, 24 (42%) were non-flare designs, 11 (19%) were possible flare designs. On meta-analysis, there was no statistically significant difference in ES of NSAIDs versus placebo between flare and non-flare trial designs for absolute pain and function or stiffness at immediate-term (1 week), short-term (2–4 week) or longer-term (12–13 week) follow-up periods (p>0.05). However there was a lower ES for mean change in pain in flare and possible flare trials compared with non-flare trials at short-term follow-up (0.36 vs 0.69; p=0.05).

Conclusions: Contrary to previous understanding, flare trial designs do not result in an increased treatment effect for NSAIDs in people with OA compared with non-flare design. Whether flare design influences other outcomes such as joint effusion remains unknown.

• Journal Article Type: Article
• Acceptance Date: Jan 23, 2016
• Publication Date: Feb 18, 2016
• Deposit Date: Apr 17, 2018
• Print ISSN: 0003-4967
• Electronic ISSN: 1468-2060
• Publisher: BMJ Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 75
• Issue: 11
• DOI: https://doi.org/10.1136/annrheumdis-2015-208823
• Public URL: https://nottingham-repository.worktribe.com/output/1126433
• Publisher URL: https://ard.bmj.com/content/75/11/1971
• PMID: 26882928