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Safety of symptomatic slow-acting drugs for osteoarthritis: Outcomes of a systematic review and meta-analysis

Safety of symptomatic slow-acting drugs for osteoarthritis: Outcomes of a systematic review and meta-analysis
Safety of symptomatic slow-acting drugs for osteoarthritis: Outcomes of a systematic review and meta-analysis

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; I 2 = 52.8%), gastrointestinal disorders (OR 2.85; 95% CI 2.02–4.04; I 2 = 62.8%) and renal and urinary disorders (OR 3.42; 95% CI 2.36–4.96; I 2 = 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; I 2 = 0%) and more dropouts due to AEs (OR 3.18; 95% CI 1.85–5.47; I 2 = 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.

1170-229X
65-99
Honvo, Germain
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Reginster, Jean Yves
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Rabenda, Véronique
cc81b2c5-82bc-490a-ae8b-94d251b7b5ed
Geerinck, Anton
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Mkinsi, Ouafa
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Charles, Alexia
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Rizzoli, Rene
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Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Avouac, Bernard
bb50a1a0-f315-4ff1-a311-61744a4e1088
Bruyère, Olivier
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Honvo, Germain
b028bd1a-b0a7-444f-bde5-32b5b611b9af
Reginster, Jean Yves
08b05e27-73dd-4ce9-90e5-d64ec922147a
Rabenda, Véronique
cc81b2c5-82bc-490a-ae8b-94d251b7b5ed
Geerinck, Anton
06bb9a12-8354-4567-814f-743a14a6b881
Mkinsi, Ouafa
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Charles, Alexia
00074b06-5e9c-4793-a3b4-243ae6d2405a
Rizzoli, Rene
e02c0d92-6da1-430c-a669-0c20e94a850a
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Avouac, Bernard
bb50a1a0-f315-4ff1-a311-61744a4e1088
Bruyère, Olivier
ba727e54-ca17-4fa8-be3d-4729fb4b8c0d

Honvo, Germain, Reginster, Jean Yves, Rabenda, Véronique, Geerinck, Anton, Mkinsi, Ouafa, Charles, Alexia, Rizzoli, Rene, Cooper, Cyrus, Avouac, Bernard and Bruyère, Olivier (2019) Safety of symptomatic slow-acting drugs for osteoarthritis: Outcomes of a systematic review and meta-analysis. Drugs and Aging, 36, 65-99. (doi:10.1007/s40266-019-00662-z).

Record type: Review

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; I 2 = 52.8%), gastrointestinal disorders (OR 2.85; 95% CI 2.02–4.04; I 2 = 62.8%) and renal and urinary disorders (OR 3.42; 95% CI 2.36–4.96; I 2 = 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; I 2 = 0%) and more dropouts due to AEs (OR 3.18; 95% CI 1.85–5.47; I 2 = 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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e-pub ahead of print date: 9 May 2019

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Local EPrints ID: 431436
URI: http://eprints.soton.ac.uk/id/eprint/431436
ISSN: 1170-229X
PURE UUID: 92f74980-79ee-4cd8-a4ec-ea8171a1222b
ORCID for Cyrus Cooper: ORCID iD orcid.org/0000-0003-3510-0709

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Date deposited: 03 Jun 2019 16:30
Last modified: 18 Mar 2024 02:46

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Contributors

Author: Germain Honvo
Author: Jean Yves Reginster
Author: Véronique Rabenda
Author: Anton Geerinck
Author: Ouafa Mkinsi
Author: Alexia Charles
Author: Rene Rizzoli
Author: Cyrus Cooper ORCID iD
Author: Bernard Avouac
Author: Olivier Bruyère

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