Fingolimod Easier to Swallow Than Dimethyl Fumarate?

Megan Brooks

April 20, 2016

VANCOUVER — Fingolimod (Gilenya, Novartis) was better tolerated than dimethyl fumarate (Tecfidera, Biogen) in a 2-year comparison of the oral multiple sclerosis (MS) drugs.

Patients receiving dimethyl fumarate had greater than 1.5 times the odds of discontinuation at 2 years or less than patients receiving fingolimod.

Discontinuation rates over the 2 years were driven by tolerability issues, and there were fewer discontinuations with fingolimod than with dimethyl fumarate, reported Brandi Vollmer, from the Rocky Mountain MS Center at the University of Colorado in Aurora.

She presented these data in an emerging science platform session here at the American Academy of Neurology (AAN) 2016 Annual Meeting.

Fingolimod and dimethyl fumarate are the two most common oral treatments for MS, but there are "limited" comparative effectiveness data over 2 years, Vollmer noted. "This is what provoked us to do this study; we wanted to compare the 2-year real-world experience of fingolimod and dimethyl fumarate in the treatment of MS," she said.

The study included 271 patients who initiated fingolimod and 342 who initiated dimethyl fumarate at the Rocky Mountain MS Center and were followed for 2 years.

Clinician-reported data, including relapse history, adverse events, medications, MRI outcomes, disease history, and patient characteristics, were retrospectively collected. Patients in both groups were predominantly women (72% fingolimod, 70% dimethyl fumarate) in their mid-40s, with a mean MS disease duration of 11 years.

Compared with patients starting dimethyl fumarate, those starting fingolimod had a greater proportion of relapsing-remitting MS and greater disease severity and were more apt to have baseline gadolinium enhancement on MRI; 42% of patients taking fingolimod had previously received natalizumab compared with 19% of those taking dimethyl fumarate.

During the 24-month study period, fewer patients receiving fingolimod than those receiving dimethyl fumarate had a clinical relapse (24 patients [8.9%] vs 44 patients [12.9%]).

At 24 months (or earlier), discontinuation rates were lower with fingolimod (93 patients [34.3%]) than dimethyl fumarate (161 patients [47.1%]), with an unadjusted odds ratio (OR) of 1.70 (95% confidence interval [CI], 1.23 - 2.37; P = .002) and an adjusted OR of 1.78 (95% CI, 1.16 - 2.73; P = .009).

The chief reason for discontinuation was tolerability, with more patients receiving dimethyl fumarate than those receiving fingolimod discontinuing treatment because of adverse events (82 patients [24%] vs 46 patients [17%]), yielding an OR of 1.54 (95% CI, 1.03 - 2.31; P = .034).

In both groups, gastrointestinal (GI) issues topped the list of adverse events leading to discontinuation; 23.9% of fingolimod recipients discontinued because of GI problems compared with 80.5% of dimethyl fumarate recipients. Thirty percent of patients receiving dimethyl fumarate discontinued treatment because of flushing, rash, or hot flashes. One patient taking fingolimod experienced alveolar hemorrhage.

Disease activity (relapses and/or new MRI lesions) was a reason for discontinuation in 27 fingolimod recipients (10.0%) and 38 (11.1%) dimethyl fumarate recipients (OR, 1.13; 95% CI, 0.67 - 1.90; P = .647). The median time to discontinuation was 12 months for both groups. Vollmer cautioned that "further results are needed to assess efficacy outcomes."

This "real-world" study, she concluded, shows that patients taking dimethyl fumarate have greater odds of discontinuing the drug than those taking fingolimod.

A Tough Decision

Asked for comment on the study, Raghav Govindarajan, MD, from the University of Missouri, Columbia, told Medscape Medical News that with more than 10 US Food and Drug Administration–approved disease-modifying therapies (DMTs), "it is a complicated decision for both MS specialists and patients to choose the right DMT as there is a lack of comparative effectiveness data. This is an important study towards that end as it compares the efficacy and adverse effect profiles between fingolimod and dimethyl fumarate, albeit retrospectively."

He added, "As a neurologist taking care of MS patients, I find this study intriguing. Many of my patients have tended to choose dimethyl fumarate over fingolimod as it is cumbersome to start fingolimod with the eye testing, EKGs [electrocardiograms], tuberculosis/varicella testing, and the fact that you have to bring your patient to the hospital for observation after the first dose."

"But this study shows that long-term fingolimod is better tolerated than dimethyl fumarate, and that is something I will start emphasizing with my patients when I discuss different DMTs," Dr Govindarajan said.

He noted that changing DMTs is "a hassle as it involves a lot of paper work that goes along with it. I have even had patients who have developed MS flare-up during this transition, and these factors will play a bigger role as years go by and we have even more DMTs to choose from."

"Clinically and certain studies including this one have shown fingolimod to be more efficacious than dimethyl fumarate, but I will take that with a pinch of salt until there are clear head-to-head studies comparing the two," Dr Govindarajan said.

The study had no funding. Brandi Vollmer has disclosed no relevant financial relationships. Several authors reported financial relationships with Biogen Idec, Novartis, and other pharmaceutical companies. Dr Govindarajan has disclosed no relevant financial relationships.

American Academy of Neurology (AAN) 2016 Annual Meeting. Abstract S24.004. Presented April 18, 2016.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.