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Meta-Analysis
. 2019 Apr;36(Suppl 1):45-64.
doi: 10.1007/s40266-019-00661-0.

Safety of Topical Non-steroidal Anti-Inflammatory Drugs in Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis

Germain Honvo  1   2 , Victoria Leclercq  3   4 , Anton Geerinck  3   4 , Thierry Thomas  5 , Nicola Veronese  6 , Alexia Charles  3   4 , Véronique Rabenda  3   4 , Charlotte Beaudart  3   4 , Cyrus Cooper  4   7   8 , Jean-Yves Reginster  3   4   9 , Olivier Bruyère  3   4
Affiliations
Meta-Analysis

Safety of Topical Non-steroidal Anti-Inflammatory Drugs in Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis

Germain Honvo et al. Drugs Aging. 2019 Apr.

Abstract

Objective: We aimed to assess the safety of topical non-steroidal anti-inflammatory drugs (NSAIDs) in the management of osteoarthritis (OA) in a systematic review and meta-analysis of randomized, placebo-controlled trials.

Methods: A comprehensive literature search was undertaken in the MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Scopus electronic databases. Randomized, double-blind, placebo-controlled, parallel-group trials that assessed adverse events (AEs) with topical NSAIDs in patients with OA were eligible for inclusion. Authors and/or study sponsors were contacted to obtain the full report of AEs. The primary outcomes were overall severe and serious AEs, as well as the following MedDRA System Organ Class (SOC)-related AEs: gastrointestinal, vascular, cardiac, nervous system, skin and subcutaneous tissue, musculoskeletal and connective tissue.

Results: The search strategy identified 1209 records, from which 25 papers were included in the qualitative synthesis and 19 were included in the meta-analysis, after exclusions. Overall, more total AEs (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.04-1.29; I2 = 0.0%) and more withdrawals due to AEs (OR 1.49, 95% CI 1.15-1.92; I2 = 0.0%) were observed with topical NSAIDs compared with placebo. The same results were achieved with topical diclofenac, largely driven by an increase in skin and subcutaneous tissue disorders (OR 1.73, 95% CI 0.96-3.10), although the difference was not statistically significant compared with placebo. No significant difference in the odds for gastrointestinal disorders was observed between topical NSAIDs and placebo (OR 0.96, 95% CI 0.73-1.27).

Conclusions: Topical NSAIDs may be considered safe in the management of OA, especially with regard to low gastrointestinal toxicity. The use of topical NSAIDs in OA should be considered, taking into account their risk: benefit profile in comparison with other anti-OA treatments.

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Conflict of interest statement

Olivier Bruyère reports grants from Biophytis, IBSA, MEDA, Servier, SMB and Theramex, outside of the submitted work. Cyrus Cooper reports personal fees from Alliance for Better Bone Health, Amgen, Eli Lilly, GlaxoSmithKline, Medtronic, Merck, Novartis, Pfizer, Roche, Servier, Takeda and UCB, outside of the submitted work. Jean-Yves Reginster reports grants from IBSA-Genevrier, Mylan, CNIEL and Radius Health (through institution); consulting fees from IBSA-Genevrier, Mylan, CNIEL, Radius Health and Pierre Fabre; fees for participation in review activities from IBSA-Genevrier, MYLAN, CNIEL, Radius Health and Teva; and payment for lectures from AgNovos, CERIN, CNIEL, Dairy Research Council (DRC), Echolight, IBSA-Genevrier, Mylan, Pfizer Consumer Health, Teva and Theramex, outside of the submitted work. Thierry Thomas reports personal fees from Abbvie, Amgen, Arrow, BMS, Chugai, Expanscience, Gilead, HAC-Pharma, LCA, Lilly, Medac, MSD, Pfizer, Thuasne, TEVA and UCB, and grants from Amgen, Bone Therapeutics, Chugai, HAC-Pharma, MSD, Novartis, Pfizer and UCB, outside of the submitted work. Germain Honvo, Nicola Veronese, Victoria Leclercq, Anton Geerinck, Alexia Charles, Charlotte Beaudart and Véronique Rabenda have no disclosures to report.

Figures

Fig. 1
Fig. 1
Study selection process
Fig. 2
Fig. 2
Risk of bias summary: review authors’ judgements about each risk of bias item for each study included in the qualitative synthesis. Note: This figure does not include the two diclofenac NCT studies, as explained in Sect. 3
Fig. 3
Fig. 3
Risk of bias graph: review authors’ judgements about each risk of bias item presented as percentages across all studies included in the qualitative synthesis. Note: This figure does not include information on risk of bias for the two diclofenac NCT studies, as explained in Sect. 3; thus, the summaries made here are based on data from 23 studies
Fig. 4
Fig. 4
Forest plot displaying the results of the meta-analysis comparing gastrointestinal disorders for all topical NSAIDs versus placebo in patients with osteoarthritis. NSAIDs non-steroidal anti-inflammatory drugs, CI confidence interval
Fig. 5
Fig. 5
Forest plot displaying the results of the meta-analysis comparing gastrointestinal disorders with topical diclofenac versus placebo in patients with osteoarthritis, CI confidence interval
Fig. 6
Fig. 6
Assessment of publication bias: funnel plots for total adverse events with a all topical NSAIDs, b topical diclofenac, and c topical ketoprofen. (These funnel plots are based on the data used for the meta-analyses of ‘any AEs’ for each single NSAID or for all topical NSAIDs; these analyses were those including as much data as possible). NSAIDs non-steroidal anti-inflammatory drugs, AEs adverse events, OR odds ratio
See this image and copyright information in PMC

References

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