Switching From Injectable to Oral Therapy for Relapsing-Remitting MS

A team of researchers conducted a cohort study to provide clinicians more evidence about treatment decisions affecting patients with relapsing-remitting multiple sclerosis.

Switching from injectable platform therapies to the oral first-line therapies dimethyl fumarate (DMF) or teriflunomide (TFL) did not increase the risk of Expanded Disability Status Scale (EDSS) worsening in patients with clinically stable relapsing-remitting multiple sclerosis (RRMS), according to research published in the Journal of Neurology, Neurosurgery and Psychiatry.

Although patients with multiple sclerosis (MS) often switch therapies for reasons other than disease activity, evidence on the effect of this switching is limited. The study researchers sought to provide physicians more evidence for treatment decisions by conducting a cohort study.

They included 3206 patients (1543 in the DMF analysis and 1663 in the TFL analysis) with data from the Danish Multiple Sclerosis Registry. Patients had clinically stable RRMS on an injectable-platform therapy for at least 1 year prior to baseline, which was either the date previous therapy was stopped for patients who switched to another treatment (“switchers”) or the date of the first recorded EDSS score in 2014 for those who stayed on initial treatment (“stayers”).

Patients were observed until death, emigration, or the date of their last valid EDSS score. The study researchers adjusted the groups to ensure similarity at baseline across all analyses in the covariates.

They found no change in risk of 6-month confirmed EDSS score worsening in patients switching to DMF. The hazard ratios (HRs) for switchers compared with stayers were 1.15 (95% CI, 0.88-1.50; P =.31) for DMF and 1.16 (95% CI, 0.92-1.46; P =.21) for TFL. The HRs for relapses during follow-up for switchers compared with stayers were 0.73 (95% CI, 0.51-1.04) for DMF and 1.25 (95% CI, 0.96-1.63) for TFL.

During the first year after baseline, the annualized relapse rates (ARRs) for switchers were 0.01 (95% CI, 0.01-0.02) for DMF and 0.04 (95% CI, 0.03-0.07) for TFL. During the entire treatment periods on DMF and TFL, their ARRs were 0.05 (95% CI, 0.03-0.06) and 0.08 (95% CI, 0.06-0.1), respectively.

The cohort of patients younger than 40 years of age experienced a similar risk of 6-month confirmed EDSS worsening in switchers compared with stayers and a more pronounced decline in the risk of a first relapse (HR, 0.52; 95% CI, 0.28-0.95) for DMF. For TFL, the risk of 6-month confirmed EDSS worsening tended to increase in switchers (HR, 1.54; 95% CI, 0.99-2.40) and the risk of a first relapse was comparable to the main analysis.

Patients who switched to DMF during follow-up had a lower risk of a first relapse (HR, 0.50; 95% CI, 0.30-0.85) and a similar risk of EDSS worsening compared with staying on injectable therapy. Switching to TFL did not produce a difference in the risk of a first relapse or EDSS worsening.

Limitations of the study included the scarcity of MRI data and the inability to precisely quantify the causal effect of the decision to switch therapy and differences in effectiveness and pharmacokinetics of therapies patients switched between.

The study researchers concluded that “Overall, in patients treated with injectable MS therapies and no recent evidence of MS activity, switching to first-line oral DMTs for convenience can be viewed as a safe strategy.” But as they noted, “Special consideration in younger patients is warranted.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Buron MD, Kalincik T, Sellebjerg F, Sørensen PS, Magyari M. Effect of lateral therapy switches to oral moderate-efficacy drugs in multiple sclerosis: a nationwide cohort study. J Neurol Neurosurg Psychiatry. Published online January 12, 2021. doi:10.1136/jnnp-2020-324869