Dimethyl Fumarate Better than Teriflunomide and as Good as Fingolimod in MS

Background

The existing real-world comparative data on the disease modifying treatments (DMTs) for multiple sclerosis (MS) suggests that dimethyl fumarate (DMF) is comparable to fingolimod (FTY) and even more efficacious than teriflunomide (TERI) in reducing relapses in MS patients. Nevertheless, there is not much comparative evidence in patients switching from injectable platform DMTs to oral DMTs.

Aim

To compare the annual relapse rate (ARR) and risk of relapse in MS patients switching from an injectable platform therapy to DMF, FTY, or TERI.

Patient Population

• MS patients (18–65 years old) who were switched from an injectable platform DMT (interferons or glatiramer acetate) to a single oral DMT between June 31, 2013 and March 31, 2015 (n=3906)
• The study subjects were required to have:
  • Continuous enrollment in the database for 12 months pre-index date and at least 3 months post-index date (The date of first oral DMT fill was considered as the index date)
  • At least 1 MS diagnosis over the pre-index period
  • Discontinuation of a platform DMT with no evidence of oral or infusion DMTs (natalizumab, novantrone, or alemtuzumab) over the pre-index period
  • Adherence to the index drug for at least 90 days

Method

Study Design

• Retrospective analysis

Treatment

• DMF cohort: (n=3092)
• FTY cohort: (n=535)
• TERI: (n=279)
• Patients treated with DMF were propensity-score matched (PSM) 3:1 to those treated with FTY and TERI, based on age, gender, region, a claims-based MS severity measure, ARR, and number of hospitalizations over the pre-index period.

Follow-Up

• Patients were followed until they dropped out of the database or until the end of the study period (March 31, 2016) whichever occurred earlier.

Outcome

• Post-index relapse rate [calculated as annualized relapse rate (ARR)]
• Time to relapse (the number of days from the index date to the date of the earliest relapse that occurred during the post-index period)

Results

• MS relapse was defined as a hospitalization with a primary diagnosis of MS or an outpatient visit with a diagnosis of MS and one of the following treatments within 30 days of the visit: intravenous steroid treatment, adrenocorticotropic hormone (ACTH) use, ≥500 mg/day prednisone use, or total plasma exchange.
• Application of the study criteria yielded 1602:534 switch patients for the DMF–FTY PSM 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).
• The PSM analysis yielded 833:279 switch patients for the DMF–TERI match. DMF–TERI patients were also 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).
• Patients in the DMF-FTY cohort 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), irrespective of the current treatment status.
• In contrast, patients treated with DMF had a significant 33% lower post-index ARR (RR=0.667; 95%CI: 0.486, 0.914) and a significant 32% lower risk of relapse (HR=0.679; 95% CI: 0.503, 0.917]) as compared to those treated with TERI.
• Analysis of time to relapse among DMF–TERI cohort who were on treatment revealed that patients treated with DMF rather than TERI had a significantly lower risk of relapse (HR=0.543; 95% CI: 0.391, 0.754], p=0.0003).

Conclusions

• Amongst MS patients switched from injectable platform DMT to oral DMTs, DMF was as effective as FTY and superior to TERI in terms of reducing the ARR and risk of relapse.
• These findings not only provide additional real-world data on the efficacy of oral DMTs but also strengthen the decision making related to their use in routine clinical practice to achieve optimal therapeutic benefits in MS patients.

Mult Scler Relat Disord. 2019; 27: 101-11.