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Abstract
Purpose/Aim of the Study: Trials of dimethyl fumarate (DMF) and teriflunomide, two new oral therapies for relapsing-remitting multiple sclerosis (RRMS) were recently published [Citation1, 2, Citation3]. A comparison of their safety against glatiramer acetate–a prevalent injectable treatment–is relevant to inform therapy-switching decisions. The study objective was to conduct a systematic review and mixed treatment comparison of total AEs in RCTs of dimethyl fumarate 240 mg bid (DMF2) or tid (DMF3), glatiramer acetate 20 mg injectable daily (GA), and teriflunomide 7 mg (TERI7) or 14 mg (TERI14) daily in RRMS patients. Materials and Methods: Articles were selected following Cochrane guidelines. A network meta-analysis was used to compare the odds of patients experiencing at least one AE between drugs, using placebo as baseline. Drugs were compared using the odds ratio (OR), credible interval (CrI), and confidence in OR ≥1 (PrOR). The mean rank (best = 1) and corresponding Surface-Under-Cumulative-Ranking (SUCRA) (best = 100%) were reported. Results: 3737 patients from three RCTs were included for analysis. Patients receiving GA exhibited the lowest AEs (DMF2 [OR = 2.67, PrOR = 98.7%], DMF3 [OR = 1.92, PrOR = 95.3%], Teri7 [OR = 2.74, PrOR = 95.2%], Teri14 [OR = 3.03, PrOR = 96.4%]), and equivalent to PB (OR = 1.60; PrOR = 94.3%). No other significant differences were found. GA also ranked with the lowest AEs (rank = 1.2, SUCRA = 96.0%), whereas DMF2 and Teri14 ranked highest (rank = 4.8). Conclusions: RRMS patients treated with glatiramer have the lowest odds of experiencing AEs, while patients taking DMF or teriflunomide have similar, higher odds of developing AEs, suggesting that patients treated with glatiramer may have higher QoL than patients under DMF or teriflunomide.