Polypharmacy is associated with treatment response and serious adverse events: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis

Abstract

Objective To evaluate whether polypharmacy is associated with treatment response and serious adverse events (SAEs) in patients with RA using data from the British Society for Rheumatology Biologics Register (BSRBR-RA). Methods The BSRBR-RA is a prospective observational cohort study of biologic therapy starters and a DMARD comparator arm. A logistic regression model was used to calculate the odds of a EULAR ‘good response’ after 12 months of biologic therapy by medication count. Cox proportional hazards models were used to identify risk of SAEs. The utility of the models were compared with the Rheumatic Disease Comorbidity Index using Receiver Operator Characteristic and Harrell’s C statistic. Results The analysis included 22 005 patients, of which 83% were initiated on biologics. Each additional medication reduced the odds of a EULAR good response by 8% [odds ratios 0.92 (95% CI 0.91, 0.93) P < 0.001] and 3% in the adjusted model [adjusted odds ratios 0.97 (95% CI 0.95, 0.98) P < 0.001]. The Receiver Operator Characteristic demonstrated significantly greater areas under the curve with the polypharmacy model than the Rheumatic Disease Comorbidity Index. There were 12 547 SAEs reported in 7286 patients. Each additional medication equated to a 13% increased risk of an SAE [hazard ratio 1.13 (95% CI 1.12, 1.13) P < 0.001] and 6% in the adjusted model [adjusted hazard ratio 1.06 (95% CI 1.05, 1.07) P < 0.001]. Predictive values for SAEs were comparable between the polypharmacy and Rheumatic Disease Comorbidity Index model. Conclusion Polypharmacy is a simple but valuable predictor of clinical outcomes in patients with RA. This study supports medication count as a valid measure for use in epidemiologic analyses.

Polypharmacy in Middle-European Rheumatoid Arthritis-Patients: A Retrospective Longitudinal Cohort Analysis With Systematic Literature Review

“…Whereas, at the first visit women took more medications than men, both women and men had more medications at the last visit. Also in the SLR, polypharmacy is reported to be associated with age, whereas results are inconclusive for the gender association (6,20,23).…”

“…The question, how much the intake of multiple medications with possible interactions harms the patient more than provides a benefit, and reduces the patients' compliance, is still unanswered. Bechman et al (23) addressed two aspects of polypharmacy in his paper. The aspect of serious adverse events (SAE) could not be assessed in the Innsbruck cohort, as SAEs did not occur within the observational period.…”

“…Overall, polypharmacy is common and considerable in RA-patients (6). Polypharmacy has been associated with age, female gender, multimorbidity, disease activity, disease duration, and functional impairment, resulting in a higher risk of hospital admissions (20,23). In 24.446 RA-patients from these studies, treatment included an average of 5.3 medications ( Table 2).…”

“…An increased rate of SAEs was reported together with an increased number of medications, with infection as the most common SAE. The authors' calculation provides an Hazard ratio (HR) of 1.13 as additional risk for SAEs per drug (23).…”

Special Considerations in Geriatric Populations

“…Studies in rheumatoid arthritis cohorts show that patients with rheumatoid arthritis tend to have polypharmacy (median number of drugs approximately 5) and, further, that older age tends to increase the risk for polypharmacy (65,66). Other studies have also shown polypharmacy to be a predictor of adverse outcomes in rheumatoid arthritis (67). For example, higher use of corticosteroids, irrespective of disease activity, has been associated with poor outcomes in rheumatoid arthritis (68–71).…”