Comparative effectiveness of dimethyl fumarate versus fingolimod and teriflunomide among MS patients switching from first-generation platform therapies in the US

Abstract

Background: Previous real-world comparative research of MS disease modifying therapies (DMTs) in the overall population has suggested dimethyl fumarate (DMF) to be comparable to fingolimod (FTY) and more efficacious than teriflunomide (TERI) in reducing relapses. However, there is limited comparative evidence in patients switching from platform DMTs in the US. The objective of the study was to compare the annualized relapse rate (ARR) and risk of relapse in MS patients who have switched from a platform therapy to DMF, FTY, or TERI. Methods: MS patients (18-65 years old) initiating an oral DMT from June 2013 to March 2015 were identified from the Truven MarketScan ® Commercial Claims Database. The index date was the date of first oral DMT fill. Patients were required to have: continuous enrollment in the database for 12 months pre-index date and ≥3 months post-index date; ≥1 MS diagnosis over the pre-index period; discontinuation of a platform DMT with no evidence of oral or infusion DMTs over the pre-index period; and adherence to the index drug for ≥90 days. DMF patients were propensity-score matched (PSM) 3:1 to FTY and to TERI based on age, gender, region, a claims-based MS severity measure, ARR, and number of hospitalizations over the pre-index period. Patients were censored when they dropped out of the database or at the end of the study period (March 31, 2016). Post-index relapses were annualized. Results: The database included 20,311 oral DMT users. After applying the study criteria, the PSM yielded 1602:534 switch patients for the DMF-FTY matched cohort. DMF-FTY patients were well-matched on all covariates: age (mean = 44 for both), gender (28% vs. 26% male, respectively), MS severity measure (0.99 vs. 1.08), and baseline ARR (0.40 vs. 0.44). PSM yielded 833:279 switch patients for the DMF-TERI match. DMF-TERI patients were well-matched on all covariates: age (mean = 50), gender (24% vs. 25% male), MS severity measure (0.86 vs. 0.99), and baseline ARR (0.23 vs. 0.30). The standardized differences confirmed balance across all covariates for matched cohorts. The matched DMF-FTY cohorts had comparable post-index ARR (Rate Ratio [RR] = 1.07 [95% Cl: 0.861, 1.328]) and risk of relapse (Hazard Ratio [HR ]= 0.996 [95% CI: 0.803, 1.236]). Post-index ARR was significantly lower with DMF in comparison to TERI (RR = 0.667 [0.486, 0.914]). The risk of relapse was also significantly lower when switching to DMF than TERI (HR = 0.679 [0.503, 0.917]). Conclusion:In this analysis, the effectiveness profiles for those oral DMT users specifically switching from platform therapies are consistent with findings from previous research conducted among all oral DMT users, regardless of prior therapy.

Oral therapies for treatment of relapsing–remitting multiple sclerosis in Austria: a 2-year comparison using an inverse probability weighting method

“…Ontaneda et al, analysed patients from a commercial claims database, switching from platform disease-modifying therapies (DMTs) to DMF, FTY and TERI and staying on treatment for at least 3 months. Comparable post-index ARR were observed between DMF and FTY, but were significantly lower with DMF versus TERI [16]. In contrast, Kalincik et al [17] showed a lower ARR on FTY compared with DMF and TERI analysing 614 (TERI), 782 (DMF) or 2332 (FTY) patients from the global MSBase cohort, staying at least 3 months on treatment.…”

“…The longer observation period on treatment (at least 24 months) produced more robust data especially in regards to disease progression and regression. patients Two previous studies also compared between these oral MS drugs [16,17]. Ontaneda et al, analysed patients from a commercial claims database, switching from platform disease-modifying therapies (DMTs) to DMF, FTY and TERI and staying on treatment for at least 3 months.…”

“…Studies matching the clinical efficacy provided conflicting results [9][10][11][12][13][14][15][16][17][18][19][20]. These discrepancies ask for further investigations to confirm or rebut the published findings, especially by real-life experiences.…”

Comparative effectiveness of teriflunomide vs dimethyl fumarate in multiple sclerosis

“…Recent observational studies have reported inconsistent results regarding clinical MS activity at 1 year (annualized relapse rate, time to first relapse) but none has compared clinical efficacy, MRI disease activity, and treatment withdrawals at 1 and 2 years in a large population of patients. [8][9][10][11][12] Such a study has the advantage of being more representative of real-life practices and effects, even if the treated patients are often noncomparable directly due to indication biases. In this context, taking advantage of the French Multiple Sclerosis Registry (Observatoire Français de la Sclérose En Plaques [OFSEP]), we propose to compare the real-life effectiveness and tolerance of DMF and TRF, using weighted propensity scores to deal with possible confounders.…”

Expert consensus from the Arabian Gulf on selecting disease-modifying treatment for people with multiple sclerosis according to disease activity

“…'First-line' or 'platform' agents usually refer to interferons, glatiramer acetate, and teriflunomide, while 'highefficacy' agents usually include fingolimod, alemtuzumab, natalizumab, ocrelizumab, and cladribine tablets [5,12]. Dimethyl fumarate may be intermediate between these categories, as there is some evidence that the efficacy of this agent is similar to that of fingolimod [33,34].…”