PMID- 31073923 OWN - NLM STAT- MEDLINE DCOM- 20190708 LR - 20210109 IS - 1179-1969 (Electronic) IS - 1170-229X (Print) IS - 1170-229X (Linking) VI - 36 IP - Suppl 1 DP - 2019 Apr TI - Safety of Topical Non-steroidal Anti-Inflammatory Drugs in Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis. PG - 45-64 LID - 10.1007/s40266-019-00661-0 [doi] 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. FAU - Honvo, Germain AU - Honvo G AUID- ORCID: 0000-0002-6992-6712 AD - Department of Public Health, Epidemiology and Health Economics, University of Liege, Liege, Belgium. germain.honvo@uliege.be. AD - WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and Aging, Liege, Belgium. germain.honvo@uliege.be. FAU - Leclercq, Victoria AU - Leclercq V AD - Department of Public Health, Epidemiology and Health Economics, University of Liege, Liege, Belgium. AD - WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and Aging, Liege, Belgium. FAU - Geerinck, Anton AU - Geerinck A AD - Department of Public Health, Epidemiology and Health Economics, University of Liege, Liege, Belgium. AD - WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and Aging, Liege, Belgium. FAU - Thomas, Thierry AU - Thomas T AD - Department of Rheumatology, Hopital Nord, CHU de St-Etienne and INSERM 1059, Universite de Lyon, Saint-Etienne, France. FAU - Veronese, Nicola AU - Veronese N AD - National Research Council, Neuroscience Institute, Aging Branch, Padua, Italy. FAU - Charles, Alexia AU - Charles A AD - Department of Public Health, Epidemiology and Health Economics, University of Liege, Liege, Belgium. AD - WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and Aging, Liege, Belgium. FAU - Rabenda, Veronique AU - Rabenda V AD - Department of Public Health, Epidemiology and Health Economics, University of Liege, Liege, Belgium. AD - WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and Aging, Liege, Belgium. FAU - Beaudart, Charlotte AU - Beaudart C AD - Department of Public Health, Epidemiology and Health Economics, University of Liege, Liege, Belgium. AD - WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and Aging, Liege, Belgium. FAU - Cooper, Cyrus AU - Cooper C AD - WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and Aging, Liege, Belgium. AD - MRC Lifecourse Epidemiology Unit, Southampton General Hospital, University of Southampton, Southampton, UK. AD - Musculoskeletal Biomedical Research Unit, National Institute for Health Research (NIHR), University of Oxford, Oxford, UK. FAU - Reginster, Jean-Yves AU - Reginster JY AUID- ORCID: 0000-0001-6290-752X AD - Department of Public Health, Epidemiology and Health Economics, University of Liege, Liege, Belgium. AD - WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and Aging, Liege, Belgium. AD - Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia. FAU - Bruyere, Olivier AU - Bruyere O AUID- ORCID: 0000-0003-4269-9393 AD - Department of Public Health, Epidemiology and Health Economics, University of Liege, Liege, Belgium. AD - WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and Aging, Liege, Belgium. LA - eng GR - MC_U147585819/MRC_/Medical Research Council/United Kingdom GR - MC_UP_A620_1014/MRC_/Medical Research Council/United Kingdom GR - MC_UU_12011/1/MRC_/Medical Research Council/United Kingdom GR - G0400491/MRC_/Medical Research Council/United Kingdom GR - MC_U147585824/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review PL - New Zealand TA - Drugs Aging JT - Drugs & aging JID - 9102074 RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 144O8QL0L1 (Diclofenac) SB - IM MH - Administration, Cutaneous MH - Anti-Inflammatory Agents, Non-Steroidal/*administration & dosage/*adverse effects/therapeutic use MH - Diclofenac/*administration & dosage/*adverse effects/therapeutic use MH - Drug-Related Side Effects and Adverse Reactions/epidemiology/*etiology MH - Humans MH - Osteoarthritis/*drug therapy MH - Randomized Controlled Trials as Topic MH - Treatment Outcome PMC - PMC6509095 COIS- Olivier Bruyere 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 Veronique Rabenda have no disclosures to report. EDAT- 2019/05/11 06:00 MHDA- 2019/07/10 06:00 PMCR- 2019/05/09 CRDT- 2019/05/11 06:00 PHST- 2019/05/11 06:00 [entrez] PHST- 2019/05/11 06:00 [pubmed] PHST- 2019/07/10 06:00 [medline] PHST- 2019/05/09 00:00 [pmc-release] AID - 10.1007/s40266-019-00661-0 [pii] AID - 661 [pii] AID - 10.1007/s40266-019-00661-0 [doi] PST - ppublish SO - Drugs Aging. 2019 Apr;36(Suppl 1):45-64. doi: 10.1007/s40266-019-00661-0.