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; 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.

Efficacy of Chondroitin Sulfate in Patients with Knee Osteoarthritis: A Comprehensive Meta-Analysis Exploring Inconsistencies in Randomized, Placebo-Controlled Trials.

INTRODUCTION: There are some controversies about treatment modalities in osteoarthritis (OA), including chondroitin sulfate (CS). The objective of this study was to determine whether CS is effective at alleviating pain and improving function in patients with knee OA and to identify the factors that explain inconsistencies in clinical trial results. METHODS: We conducted a systematic review of randomized, placebo-controlled trials, searching the databases Medline, Cochrane central register for controlled trials and Scopus. Random effects meta-analysis was then performed, using tau2 and I2 statistics to assess heterogeneity. The pain and Lequesne index (LI) scores were expressed as standardized mean differences (SMDs), with a 95% confidence interval (CI). Heterogeneity was explored by stratifying the analyses according to pre-specified study-level characteristics and assessing the sources of funnel plot asymmetry. RESULTS: The inclusion criteria yielded 18 trials. Overall, CS significantly but inconsistently reduced pain (SMD: - 0.63; 95% CI: - 0.91, - 0.35; I2 = 94%) and improved function (SMD: - 0.82; 95% CI: - 1.31, - 0.33; I2 = 95%). When limiting the analysis to studies with a low risk of bias, the pharmaceutical grade CS of IBSA origin showed a greater reduction in pain (SMD: - 0.25; 95% CI: - 0.34, - 0.16; I2 = 75%) and function (SMD: - 0.33; 95% CI: - 0.47, - 0.20; I2 = 53%, p = 0.07) compared with the other preparations (SMDPain: - 0.08; 95% CI: - 0.19, + 0.02; I2 = 20%; SMDFunction: - 0.18; 95% CI: - 0.36, +0.01; I2 = 0%). Assessing funnel plot asymmetry in the studies with a low risk of bias, we found strong correlations between the treatment effects and study size (pain: rS = 0.93; LI: rS = 0.86; p < 0.05). Ultimately, there was no residual heterogeneity in the CS effects when the smallest studies were removed from the analyses. CONCLUSION: This new meta-analysis suggests that CS provides a moderate benefit for pain and has a large effect on function in knee OA, however with large inconsistency. The risks of bias, brand and study size were the factors explaining heterogeneity among the clinical trial results.

Adverse Health Events Related to Self-Medication Practices Among Elderly: A Systematic Review.

BACKGROUND: Older adults often resort to self-medication to relieve symptoms of their current illnesses; however, the risks of this practice are multiplied in old age. In particular, this age group is more vulnerable to adverse drug events because of the physiological changes that occur due to senescence. OBJECTIVE: The aim of the study was to obtain an overview of the adverse health events related to self-medication among subjects aged 60 years and over through a systematic review of the literature. METHODS: A study of relevant articles was conducted among databases (MEDLINE, PsycINFO, and EBM Reviews-Cochrane Database of Systematic Reviews). Eligibility criteria were established and applied by two investigators to include suitable studies. The results and outcomes of interest were detailed in a descriptive report. RESULTS: The electronic search identified 4096 references, and the full texts of 74 were reviewed, of which four were retained in the analysis: three had a cross-sectional design and one prospectively followed elderly subjects. The first study showed a 26.7% prevalence of adverse drug reactions (ADRs) among elders, the second study found a 75% prevalence of side effects, and, finally, a prospective study showed an ADR incidence of 4.5% among self-medicated elders. These studies showed that adverse health events related to self-medication are relatively frequently reported. They also highlighted that analgesics and anti-inflammatory drugs are the most self-medicated products, while vitamins and dietary supplements also appear to be frequently self-administered, but by older individuals. CONCLUSIONS: Studies on self-medication in the elderly and its adverse health effects are clearly lacking. There is a need to perform prospective studies on this topic to gain a clear understanding of the extent of this problem and to enhance the awareness of health professionals to better inform seniors.