SEATTLE — Dimethyl fumarate (Tecfidera) was effective and safe for African-American and black patients with relapsing-remitting multiple sclerosis (MS), an interim analysis of the real-world ESTEEM study showed.
African-American and black patients experienced significantly lower relapse rates in the 24 months after starting dimethyl fumarate treatment than in the year before treatment and had safety results consistent with the known profile of the drug, reported Mitzi Williams, MD, of Morehouse School of Medicine in Atlanta, at the Consortium of Multiple Sclerosis Centers (CMSC) annual meeting.
“The rationale for this study is that our clinical trials do not have large cohorts of African Americans,” Williams said in a CMSC platform session. Although an integrated analysis of the DEFINE and CONFIRM studies showed fewer relapses and reduced disability progression in African-American patients, the sample size was too small to draw definitive conclusions, she explained.
Evidence has suggested MS has a more severe course in African-American patients than in white patients, Williams added. “Progression of disease may be significantly faster in African Americans with multiple sclerosis,” she said. Recent MRI findings have shown that whole-brain gray and white matter atrophy may occur twice as fast in African Americans, as well as faster thalamic atrophy.
ESTEEM is an ongoing, 5-year, prospective study evaluating real-world, long-term safety and effectiveness of dimethyl fumarate in 5,000 patients at 380 sites globally. Interim data presented at the CMSC meeting reflected 3,975 participants, including 149 African-American and black patients. In her presentation, Williams looked at the overall subgroup of African-American and black patients, and cohorts within this subgroup who switched therapy from interferon or glatiramer acetate (Copaxone) to dimethyl fumarate at any time from diagnosis.
Patients in the ESTEEM study had a diagnosis of relapsing-remitting MS and were newly prescribed dimethyl fumarate under routine clinical care. The subgroup of African-American and black patients had a mean age of 43 and 81% were female. Most (97%) came from the U.S.; the rest were from Western Europe, Canada, New Zealand, and Australia. Many had tried other MS treatments before the study: 58% had used glatiramer acetate, 42% had used intramuscular interferon beta-1a, and 27% had used subcutaneous interferon beta-1a.
The interim analysis showed the annualized relapse rate was 73% lower (P<0.0001) in the overall African-American and black population and 79% lower (P<0.0001) in the interferon or glatiramer acetate switch subgroup in the 24 months after starting dimethyl fumarate, compared with the 12 months before starting the drug.
A total of 22 African-American and black patients (15%) reported any adverse event leading to discontinuation, with gastrointestinal disorders mentioned most commonly (6%), consistent with the rest of the ESTEEM population. The majority of GI-related discontinuations occurred within the first month of treatment.
These results mirror data found in the phase III DEFINE and CONFIRM studies, said Robert Fox, MD, of the Cleveland Clinic, who was not involved with ESTEEM.
“In a combined post-hoc analysis of the two phase III trials, dimethyl fumarate appeared to have similar efficacy, safety, and tolerability in black patients as the overall study population,” Fox told MedPage Today. “However, that analysis was limited by including only 29 black patients.”
“The ESTEEM study extends these observations into a much larger cohort and a more heterogeneous population,” he continued. “Compared with the pre-treatment period, there was a robust decline in annualized relapse rate, with similar safety and tolerability to that seen in the phase III trials. This study provides reassuring data regarding dimethyl fumarate’s efficacy in black and African-American patients.”
ESTEEM has several limitations, Williams noted: it is an observational study and is open-label. In addition, it lacks MRI baseline data to characterize disease severity in the African-American and black population accurately, she added.
The study was funded by Biogen.
Williams disclosed relevant relationship with Biogen, Celgene, EMD Serono, Genentech, Teva Neuroscience, Sanofi Genzyme, and Genentech.