TY - JOUR
T1 - Safety of Topical Non-steroidal Anti-Inflammatory Drugs in Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis
AU - Honvo, Germain
AU - Leclercq, Victoria
AU - Geerinck, Anton
AU - Thomas, Thierry
AU - Veronese, Nicola
AU - Charles, Alexia
AU - Rabenda, Véronique
AU - Beaudart, Charlotte
AU - Cooper, Cyrus
AU - Reginster, Jean Yves
AU - Bruyère, Olivier
N1 - Funding Information:
Acknowledgements This paper was written on behalf of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) Working Group on the safety of anti-OA medications: Nasser Al-Daghri, Nigel Arden, Bernard Avouac, Olivier Bruyère, Roland Chapurlat, Philip Conaghan, Cyrus Cooper, Elizabeth Curtis, Elaine Dennison, Nicholas Fuggle, Gabriel Herrero-Beaumont, Germain Honvo, Margreet Kloppenburg, Stefania Maggi, Tim McAlindon, Alberto Migliore, Ouafa Mkinsi, François Rannou, Jean-Yves Reginster, René Rizzoli, Roland Roth, Thierry Thomas, Daniel Uebelhart, and Nicola Veronese. The authors of this article are grateful to the authors of the articles included in the meta-analysis and to the pharmaceutical companies who kindly accepted to collaborate with this project by sharing the raw safety data from these studies. The authors would also like to express their sincere gratitude to Laboratoires Genevrier (France) and GlaxoSmithKline (GSK, Switzerland), as well as to Doctor Ian Burnett (from Novartis Consumer Health SA—a GSK Consumer Healthcare company, Switzerland). They also thank Drs. Herbert S.B. Baraf, Stefano Rovati, Pius Brühlmann, Daniele Pavone, Alessandro Allegrini, Hakan Ergün, Gyula Varadi and Noboru Otsuka, as well as the sponsors of their studies, for having accepted to share their raw data with us. The authors acknowledge the assistance and advice of Nancy Durieux and Frédéric de Lemos Esteves from the Library of Life Sciences, University of Liège, Liège, Belgium, in the preparation of the search strategies for the systematic review, and thank them very sincerely for their contribution to one of the most important parts of this research. Finally, the authors would like to express their most sincere gratitude to Dr Lisa Buttle, PhD, of Medscript Ltd, for her invaluable assistance with the manuscript preparation. Dr Lisa Buttle was entirely funded by the ESCEO asbl, Belgium.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/4/1
Y1 - 2019/4/1
N2 - 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; I 2 = 0.0%) and more withdrawals due to AEs (OR 1.49, 95% CI 1.15–1.92; I 2 = 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.
AB - 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; I 2 = 0.0%) and more withdrawals due to AEs (OR 1.49, 95% CI 1.15–1.92; I 2 = 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.
UR - http://www.scopus.com/inward/record.url?scp=85065676402&partnerID=8YFLogxK
U2 - 10.1007/s40266-019-00661-0
DO - 10.1007/s40266-019-00661-0
M3 - Review article
C2 - 31073923
AN - SCOPUS:85065676402
SN - 1170-229X
VL - 36
SP - 45
EP - 64
JO - Drugs and Aging
JF - Drugs and Aging
ER -