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.

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.

Cost-effectiveness of vitamin D and calcium supplementation in the treatment of elderly women and men with osteoporosis.

BACKGROUND: The supplementation with vitamin D and calcium has been recommended for elderly, specifically those with increased risk of fractures older than 65 years. This study aims to assess the cost-effectiveness of vitamin D and calcium supplementation in elderly women and men with osteoporosis and therefore to assess if this recommendation is justified in terms of cost-effectiveness. METHODS: A validated model for economic evaluations in osteoporosis was used to estimate the cost per quality-adjusted life-year (QALY) gained of vitamin D/calcium supplementation compared with no treatment. The model was populated with cost and epidemiological data from a Belgian health-care perspective. Analyses were conducted in women and men with a diagnosis of osteoporosis (i.e. bone mineral density T-score ≤-2.5). A literature search was conducted to describe the efficacy of vitamin D and calcium in terms of fracture risk reduction. RESULTS: The cost per QALY gained of vitamin D/calcium supplementation was estimated at €40 578 and €23 477 in women and men aged 60 years, respectively. These values decreased to €7912 and €10 250 at the age of 70 years and vitamin D and calcium supplementation was cost-saving at the age of 80 years, meaning that treatment cost was less than the costs of treating osteoporotic fractures of the no-treatment group. CONCLUSION: This study suggests that vitamin D and calcium supplementation is cost-effective for women and men with osteoporosis aged over 60 years. From an economic perspective, vitamin D and calcium should therefore be administrated in these populations including those also taking other osteoporotic treatments.

The effects of vitamin D on skeletal muscle strength, muscle mass, and muscle power: a systematic review and meta-analysis of randomized controlled trials.

CONTEXT: There is growing evidence that vitamin D plays a role on several tissues including skeletal muscle. OBJECTIVE: The aim was to summarize with a meta-analysis, the effects of vitamin D supplementation on muscle function. DATA SOURCES: A systematic research of randomized controlled trials, performed between 1966 and January 2014 has been conducted on Medline, Cochrane Database of Systematics Reviews, Cochrane Central Register of Controlled and completed by a manual review of the literature and congressional abstracts. STUDY SELECTION: All forms and doses of vitamin D supplementation, with or without calcium supplementation, compared with placebo or control were included. Out of the 225 potentially relevant articles, 30 randomized controlled trials involving 5615 individuals (mean age: 61.1 years) met the inclusion criteria. DATA EXTRACTION: Data were extracted by two independent reviewers. DATA SYNTHESIS: Results revealed a small but significant positive effect of vitamin D supplementation on global muscle strength with a standardized mean difference (SMD) of 0.17 (P = .02). No significant effect was found on muscle mass (SMD 0.058; P = .52) or muscle power (SMD 0.057; P = .657). Results on muscle strength were significantly more important with people who presented a 25-hydroxyvitamin D level <30 nmol/L. Supplementation seems also more effective on people aged 65 years or older compared to younger subjects (SMD 0.25; 95% CI 0.01 to 0.48 vs SMD 0.03; 95% CI -0.08 to 0.14). CONCLUSIONS: Vitamin D supplementation has a small positive impact on muscle strength, but additional studies are needed to define optimal treatment modalities, including dose, mode of administration, and duration.

Potential clinical and economic impact of nonadherence with osteoporosis medications.

This study aims to estimate the potential clinical and economic implications of therapeutic adherence to bisphosphonate therapy. A validated Markov microsimulation model was used to estimate the impact of varying adherence to bisphosphonate therapy on outcomes (the number of fractures and the quality-adjusted life-years [QALYs]), health-care costs, and the cost-effectiveness of therapy compared with no treatment. Adherence was divided into persistence and compliance, and multiple scenarios were considered for both concepts. Analyses were performed for women aged 65 years with a bone mineral density T-score of -2.5. Health outcomes and the cost-effectiveness of therapy improved significantly with increasing compliance and/or persistence. In the case of real-world persistence and with a medical possession ratio (MPR; i.e., the number of doses taken divided by the number of doses prescribed) of 100%, the QALY gain and the number of fractures prevented represented only 48 and 42% of the values estimated assuming full persistence, respectively. These proportions fell to 27 and 23% with an MPR value of 80%. The costs per QALY gained, for branded bisphosphonates (and generic alendronate), were estimated at 19,069 euros (4,871 euros), 32,278 euros (11,985 euros), and 64,052 euros (30,181 euros) for MPR values of 100, 80, and 60%, respectively, assuming real-world persistence. These values were 16,997 euros (2,215 euros), 24,401 euros (6,179 eruos), and 51,750 euros (20,569 euros), respectively, assuming full persistence. In conclusion, poor compliance and failure to persist with osteoporosis medications results not only in deteriorating health outcomes, but also in a decreased cost-effectiveness of drug therapy. Adherence therefore remains an important challenge for health-care professionals treating osteoporosis.