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Efficacy and Tolerability of Oral Versus Injectable Disease-Modifying Therapies for Multiple Sclerosis in Clinical Practice


Efficacy and Tolerability of Oral Versus Injectable Disease-Modifying Therapies for Multiple Sclerosis in Clinical Practice

Erin E Longbrake et al. Mult Scler J Exp Transl Clin.


Background: The advent of oral disease-modifying therapies fundamentally changed the treatment of multiple sclerosis. Nevertheless, impressions of their relative efficacy and tolerability are primarily founded on expert opinion.

Objective: The purpose of this study was to determine whether oral disease-modifying therapies were better tolerated and/or more effective for controlling multiple sclerosis compared to injectable therapies in clinical practice.

Methods: Single-center, retrospective cohort study. 480 patients initiated oral (fingolimod, teriflunomide, or dimethyl fumarate) or injectable therapy between March 2013-March 2015 and follow-up data was collected for 5-31 months. Outcomes included on-drug multiple sclerosis activity and drug discontinuation. Cox proportional hazards models were used to control for baseline differences and sensitivity analyses using propensity-weighted matching were performed.

Results: A higher proportion of teriflunomide-treated patients experienced multiple sclerosis activity compared to those treated with injectable therapies (p = 0.0053) in the adjusted model. Breakthrough multiple sclerosis was equally prevalent among fingolimod and dimethyl fumarate-treated compared to injectable therapy-treated patients. Of patients initiating a disease-modifying therapy, 32-46% discontinued or switched treatments during the study. After controlling for baseline differences, discontinuation rates were comparable across treatment groups.

Conclusions: In this cohort, oral and injectable disease-modifying therapies were equally well tolerated, but teriflunomide appeared less effective for controlling multiple sclerosis activity than injectable therapies. Further study is needed.

Keywords: Multiple sclerosis; dimethyl fumarate; disease modifying therapy; fingolimod; teriflunomide; tolerability.


Figure 1.
Figure 1.
Forest plots of hazard ratios (HRs) for multiple sclerosis (MS) activity (a) and treatment discontinuation (b) after controlling for measured baseline variables. CI: confidence interval; EDSS: estimated disability status score.
Figure 2.
Figure 2.
Multiple sclerosis (MS) activity and persistence on therapy for oral (blue lines) versus injectable (red lines) disease modifying therapies (DMTs). After propensity weighted matching, 82 dimethyl fumarate (DMF)-treated patients, 48 teriflunomide (TER)-treated patients and 57 fingolimod (FGD)-treated patients were matched with comparable injectable (INJ)-treated patients. On-drug MS activity (a)–(c) and persistence on drug (d)–(f) were evaluated. Kaplan-Meier time to event analyses are shown.
Figure 3.
Figure 3.
Factors contributing to multiple sclerosis (MS) disease-modifying therapy discontinuation. Primary reasons for drug discontinuation (a). Side effects precipitating discontinuation (b). Number (n) of discontinuation events (a) or discontinuations due to drug side effects (b).

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