Annualized Relapse Rate of First-Line Treatments for Multiple Sclerosis: A Meta-Analysis, Including Indirect Comparisons Versus Fingolimod (P01.136)

Objective: To conduct an indirect comparison of annualized relapse rates (ARR) for fingolimod, interferon beta, and glatiramer acetate in relapsing-remitting multiple sclerosis (RRMS) using evidence from both placebo-controlled and head-to-head studies. Background Previous systematic reviews and meta-analyses of treatments in RRMS derived their findings from either placebo-controlled studies only or separately from head-to-head and comparative studies. Design/Methods: A systematic literature review was conducted by searching MEDLINE, EMBASE, and the Cochrane Library. Included studies were randomized controlled trials evaluating one or more of fingolimod, interferon beta-1a, interferon beta-1b, or glatiramer acetate in RRMS populations. The quality of all trials included in the meta-analysis was assessed using the criteria recommended by the Centre for Reviews and Dissemination. Primary outcome was ARR. The evidence synthesis was performed within a mixed-treatment comparison framework and ARR was analyzed as a Poisson outcome. Results: The relative ARRs estimated from our meta-analyses were 1.43, 1.51, 1.55, 1.67, 1.93, and 2.32 for the comparisons of glatiramer acetate 20 mg, interferon beta-1b 250 mcg, interferon beta-1a 44 mcg, interferon beta-1a 22 mcg, interferon beta-1a 30 mcg, and placebo, respectively, versus fingolimod. None of the 95% confidence intervals for these estimates overlapped unity, implying statistical significance of these findings. The key limitations of this study are heterogeneity even after adjusting for population-level baseline characteristics and the variability in outcome definition across the included trials. Conclusions: The MTC results suggest that fingolimod significantly reduces relapse frequency in patients with RRMS compared with all current first-line disease-modifying therapies. The results for interferon beta and glatiramer acetate disease-modifying therapies were consistent with the relapse reduction findings from earlier systematic reviews, comparative trials, and real-world studies. Disclosure: Dr. Tyas has received personal compensation for activities with Novartis as an employee. Mr. Roskell has received personal compensation for activities with RTI Health Solutions as an employee. Ms. Zimovetz has received personal compensation for activities with RTI Healh Solutions. Ms. Rycroft has received personal compensation for activities with RTI Health Solutions as an employee. Dr. Eckert has received personal compensation for activities with Novartisas an employee.