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Open Access 01-04-2019 | Osteoarthrosis | Systematic Review

Safety of Symptomatic Slow-Acting Drugs for Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis

Authors: Germain Honvo, Jean-Yves Reginster, Véronique Rabenda, Anton Geerinck, Ouafa Mkinsi, Alexia Charles, Rene Rizzoli, Cyrus Cooper, Bernard Avouac, Olivier Bruyère

Published in: Drugs & Aging | Special Issue 1/2019

Abstract

Background

Symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) are an important drug class in the treatment armamentarium for osteoarthritis (OA).

Objective

We aimed to re-assess the safety of various SYSADOAs in a comprehensive meta-analysis of randomized placebo-controlled trials, using, as much as possible, data from full safety reports.

Methods

We performed a systematic review and random-effects meta-analyses of randomized, double-blind, placebo-controlled trials that assessed adverse events (AEs) with various SYSADOAs in patients with OA. The databases MEDLINE, Cochrane Central Register of Controlled Trials (Ovid CENTRAL) and Scopus were searched. The primary outcomes were overall severe and serious AEs, as well as AEs involving the following Medical Dictionary for Regulatory Activities (MedDRA) system organ classes (SOCs): gastrointestinal, cardiac, vascular, nervous system, skin and subcutaneous tissue, musculoskeletal and connective tissue, renal and urinary system.

Results

Database searches initially identified 3815 records. After exclusions according to the selection criteria, 25 studies on various SYSADOAs were included in the qualitative synthesis, and 13 studies with adequate data were included in the meta-analyses. Next, from the studies previously excluded according to the protocol, 37 with mainly oral nonsteroidal anti-inflammatory drugs (NSAIDs) permitted as concomitant medication were included in a parallel qualitative synthesis, from which 18 studies on various SYSADOAs were included in parallel meta-analyses. This post hoc parallel inclusion was conducted because of the high number of studies allowing concomitant anti-OA medications. Indeed, primarily excluding studies with concomitant anti-OA medications was crucial for a meta-analysis on safety. The decision for parallel inclusion was made for the purpose of comparative analyses. Glucosamine sulfate (GS), chondroitin sulfate (CS) and avocado soybean unsaponifiables (ASU; Piascledine^®) were not associated with increased odds for any type of AEs compared with placebo. Overall, with/without concomitant OA medication, diacerein was associated with significantly increased odds of total AEs (odds ratio [OR] 2.22; 95% confidence interval [CI] 1.58–3.13; I² = 52.8%), gastrointestinal disorders (OR 2.85; 95% CI 2.02–4.04; I² = 62.8%) and renal and urinary disorders (OR 3.42; 95% CI 2.36–4.96; I² = 17.0%) compared with placebo. In studies that allowed concomitant OA medications, diacerein was associated with significantly more dermatological disorders (OR 2.47; 95% CI 1.42–4.31; I² = 0%) and more dropouts due to AEs (OR 3.18; 95% CI 1.85–5.47; I² = 13.4%) than was placebo. No significant increase in serious or severe AEs was found with diacerein versus placebo.

Conclusions

GS and CS can be considered safe treatments for patients with OA. All eligible studies on ASU included in our analysis used the proprietary product Piascledine^® and allowed other anti-OA medications; thus, the safety of ASU must be confirmed in future studies without concomitant anti-OA medications. Given the safety concerns with diacerein, its usefulness in patients with OA should be assessed, taking into account individual patient characteristics.

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Title: Safety of Symptomatic Slow-Acting Drugs for Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis
Authors: Germain Honvo
Jean-Yves Reginster
Véronique Rabenda
Anton Geerinck
Ouafa Mkinsi
Alexia Charles
Rene Rizzoli
Cyrus Cooper
Bernard Avouac
Olivier Bruyère
Publication date: 01-04-2019
Publisher: Springer International Publishing
Keywords: Osteoarthrosis
Osteoarthrosis
Published in: Drugs & Aging / Issue Special Issue 1/2019
Print ISSN: 1170-229X
Electronic ISSN: 1179-1969
DOI: https://doi.org/10.1007/s40266-019-00662-z

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