AT THE AAN 2016 ANNUAL MEETING
VANCOUVER (FRONTLINE MEDICAL NEWS) – Multiple sclerosis patients discontinued treatment and relapsed earlier with dimethyl fumarate (Tecfidera) than with fingolimod (Gilenya), and had more gadolinium-enhancing lesions at 12 months, in a propensity score matching analysis involving 775 patients at the Cleveland Clinic.
“Based on these data, I now [favor] Gilenya over Tecfidera; Gilenya works a little bit better,” lead investigator and staff neurologist Carrie Hersh said at the annual meeting of the American Academy of Neurology.
The two drugs performed about equally in clinical trials, but Dr. Hersh and her colleagues said fingolimod seems to have the edge in clinical practice; they wanted to see if that hunch held up to scrutiny.
In the single-center cohort study , about 30% of the 458 dimethyl fumarate patients discontinued the drug after an average of 4 months, and about 14% relapsed within a year of starting it. About a quarter of the 317 fingolimod patients discontinued at an average of 6.5 months, and 11% relapsed. About 9% of dimethyl fumarate patients, but 6% of fingolimod patients, had new gadolinium-enhancing (GdE) brain lesions at 12 months.
A propensity score analysis was performed to control for confounders; patients were matched one to one for baseline demographics and clinical and MRI characteristics. Dimethyl fumarate patients were almost three times more likely than fingolimod patients to have new GdE lesions after a year (odds ratio, 2.90; 95% confidence interval, 1.24-6.57). They also had an earlier time to discontinuation (OR, 1.35; 95% CI, 1.05-1.74) and clinical relapse (OR, 1.64; 95% CI, 1.10-2.46). The study included patients with secondary progressive disease. Results were the same when the analysis was limited to relapsing-remitting multiple sclerosis.
The investigators concluded that “dimethyl fumarate and fingolimod have comparable annualized relapse rates, overall brain MRI activity, and discontinuation at 12 months.” However, “dimethyl fumarate may have greater GdE lesions and side effects early after treatment initiation, leading to early discontinuation and relapses.
“This makes sense from what we are seeing in the clinic. We know Tecfidera patients have tolerability issues,” especially with gastrointestinal and flushing events, “so they discontinue earlier or might not be as adherent, and so they relapse earlier. The new enhancing lesions might be a difference in efficacy,” Dr. Hersh said.
Patients treated with fingolimod were more likely to be white (91% vs. 83%), have a longer disease duration (16 vs. 14 years), have a higher proportion of relapsing-remitting disease (82% vs. 74%), and have more severe baseline brain lesion burden (15% vs. 8%). The subjects had tried interferon, glatiramer acetate (Copaxone), natalizumab (Tysabri), or other options before being switched to the study medications because of disease activity or intolerability. Patients were in their 40s, on average, and about 70% were women.
Data are now being collected for a 2-year analysis.
There was no industry funding for the work, and Dr. Hersh had no disclosures. Other investigators reported ties to both Novartis, the maker of Gilenya, and Biogen, the maker of Tecfidera.