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Meta-Analysis
. 2020 May;72(5):641-651.
doi: 10.1002/acr.23884. Epub 2020 Apr 14.

Duration of Symptom Relief and Early Trajectory of Adverse Events for Oral Nonsteroidal Antiinflammatory Drugs in Knee Osteoarthritis: A Systematic Review and Meta-Analysis

Mikala C Osani  1 , Elizaveta E Vaysbrot  1 , Mengyu Zhou  1 , Timothy E McAlindon  1 , Raveendhara R Bannuru  1
Affiliations
Meta-Analysis

Duration of Symptom Relief and Early Trajectory of Adverse Events for Oral Nonsteroidal Antiinflammatory Drugs in Knee Osteoarthritis: A Systematic Review and Meta-Analysis

Mikala C Osani et al. Arthritis Care Res (Hoboken). 2020 May.

Abstract

Objective: Despite an extensive body of research on nonsteroidal antiinflammatory drugs (NSAIDs) in osteoarthritis, the duration of their efficacy and timeline of adverse event (AE) onset have been understudied. We conducted a systematic review and meta-analyses from 2 to 26 weeks to characterize the efficacy and AE trajectories of oral NSAIDs in knee osteoarthritis.

Methods: We searched MEDLINE, Embase, Web of Science, Google Scholar, and the Cochrane Database from inception to May 2018. Randomized controlled trials assessing the efficacy and/or safety of Federal Drug Administration-approved NSAIDs in knee osteoarthritis patients were included. Two independent reviewers assessed quality and extracted data. We calculated standardized mean differences (SMDs) and risk ratios (RRs) with 95% confidence intervals (95% CIs).

Results: We included 72 randomized controlled trials (26,424 participants). NSAIDs demonstrated moderate, statistically significant effects on pain that peaked at 2 weeks (SMD -0.43 [95% CI -0.48, -0.38]), but the magnitude of the effects decreased over time. The results for function were similar. The incidence of gastrointestinal (GI) AEs was significantly higher in NSAID users than placebo users as early as 4 weeks (RR 1.38 [95% CI 1.21, 1.57]). The incidence of cardiovascular (CV) AEs in NSAID users was not significantly different from placebo. Most GI and CV AEs were transient and of minor severity.

Conclusion: NSAIDs produced significant pain and function improvements that peaked at 2 weeks but decreased over time. The incidence of minor GI and CV AEs consistently rose, reaching significance as early as 4 weeks. Clinicians should weigh the durability of efficacy with the early onset of minor AEs along with patient tolerability and preferences when formulating an NSAID regimen.

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Conflict of interest statement

Conflicts of interest:

Dr. McAlindon has reported consulting activities for Flexion, Astellas Pharma, Pfizer, Samumed, Seikugaku, and Regeneron Pharma outside the submitted work. Dr. Bannuru has reported consulting activities for Fidia Pharma outside the submitted work. All other authors declare that they have no conflicts of interest.

Figures

Figure 1:
Figure 1:
Trajectory of Overall Effects of NSAIDs on Pain (A) and Function (B)
Figure 2:
Figure 2:
Trajectories of the Gastrointestinal (A) and Cardiovascular (B) Safety of NSAIDs
Figure 3:
Figure 3:
Trajectory of Effects of Different Classes of NSAIDs on Pain (A) and Function (B)
See this image and copyright information in PMC

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