A French prospective study of efficacy in active relapsing-remitting multiple sclerosis (RRMS) favored natalizumab (Tysabri) over fingolimod (Gilenya), researchers for the BEST-MS study reported.
At 12 months, BEST-MS showed that 47.8% of natalizumab-treated patients reached the primary outcome of No Evidence of Disease Activity (NEDA), compared with 30.4% of fingolimod-treated patients, said Mikael Cohen, MD, of Centre Hospitalier Universitaire de Nice in France.
Of 94 patients treated with natalizumab in the study, 98.4% had no new gadolinium-enhancing (Gd+) lesions, 70% had no new T2 lesions, 82.7% were relapse-free, and 75.3% had stable scores on the Expanded Disability Status Scale (EDSS). Of 92 patients treated with fingolimod, 86.2% had no new Gd+ lesions, 61.6% had no new T2 lesions, 76% were relapse-free, and 69.8% had stable EDSS scores.
“BEST-MS is the first prospective and standardized study that compared the efficacy of those two drugs,” Cohen said.
“So far, most publicized studies relied on retrospective data analysis,” he pointed out. “Head-to-head comparison studies between different disease-modifying treatments in MS are very relevant to optimize therapeutic strategy.”
Cohen presented the findings online as part the 2020 American Academy of Neurology (AAN) Science Highlights, which featured research from the AAN annual meeting, which was cancelled because of the Covid-19 pandemic.
Helmut Butzkueven, MBBS, PhD, of Monash University in Australia, who was not involved with the study, observed that the BEST-MS results were similar to findings from the randomized REVEAL trial, which Butzkueven presented at an earlier MS meeting.
“In our study, patients randomized to natalizumab had less clinical and radiological disease activity than patients randomized to fingolimod,” Butzkueven said. “MRI differences favoring natalizumab were already apparent by week 4 and were significant by week 16.”
Fingolimod, the first approved oral MS treatment, is a sphingosine-1-phosphate (S1P) receptor modulator which sequesters lymphocytes in lymph nodes, reducing autoimmune involvement. It was approved in the U.S. for relapsing forms of MS in 2010. Generic forms of the drug were approved by the FDA in 2019.
Natalizumab is a humanized monoclonal antibody to cell adhesion molecule α4-integrin that reduces the entry of inflammatory cells to the brain via the blood-brain barrier. It is given by intravenous infusion every 28 days. Natalizumab was approved for relapsing forms of MS in 2004. It has been linked with progressive multifocal leukoencephalopathy (PML), a serious adverse effect of anti-immune treatment, which led it to be withdrawn from the market, then re-introduced, in the United States. PML has also been a concern with fingolimod.
Prior work has shown that natalizumab may be more effective in reducing relapse rate and slowing disability progression. A 2018 study of 547 Swiss patients with RRMS switching from either interferon beta or glatiramer acetate (Copaxone) to either fingolimod or natalizumab with median follow-up of 1.8 years showed a lower risk of relapse in the natalizumab group (incidence rate ratio 0.5, 95% CI 0.3-0.8, P = 0.001).
A 2020 study of imaging parameters in RRMS compared the findings for natalizumab (n=30) or fingolimod (n=25) versus healthy controls (n=15) after 2 years of treatment and found that both drugs reduced relapse rate, stabilized disability, and improved cognitive function, but natalizumab had an edge in proportion of freedom from MRI activity (67% versus 36%).
BEST-MS began in 10 MS clinics in France in 2013, when the two most common treatments for active RRMS were natalizumab and fingolimod, Cohen said. Participants were considered to have active disease if they had at least one relapse in the last 12 months on first-line line therapy and 9 or more T2 hyperintensities on MRI, or two relapses in the last 12 months and evidence of active disease on MRI on two consecutive exams. Participants had no previous treatment with mitixantrone, natalizumab, or fingolimod.
The treating physician decided whether natalizumab or fingolimod would be used, and patients were assessed at baseline and at 12 months for relapses, EDSS, and MRI. MRI analysis was by a senior neuroradiologist blinded to treatment arm.
Both groups were similar in baseline clinical and radiological characteristics. Mean age was 38.2 years, and three-quarters of the participants were women. Baseline EDSS was 2.6 in the natalizumab group and 2.3 in the fingolimod group.
Secondary outcomes showed that annualized relapse rates were 0.2 in the natalizumab group at 0.27 in the fingolimod group. Most relapses occurred early in the study, within the first 6 months of beginning either treatment.
Limitations of the study included the fact that it was non-randomized and unblinded. Unmeasured confounders also may have influenced results.
The French prospective BEST-MS study of efficacy in active relapsing-remitting multiple sclerosis (RRMS) favored natalizumab (Tysabri) over fingolimod (Gilenya). Note that this study was unblinded and non-randomized.
Findings are based on analyses prepared for the American Academy of Neurology annual meeting and have not been peer-reviewed.
Paul Smyth, MD, Contributing Writer, BreakingMED™
This study had European public funding and was independent from industry.
Cohen disclosed relationships with Biogen, Roche, Merck, and Ad Scientiam.
Butzkueven disclosed relationships with Novartis and Biogen.
Cat ID: 167
Topic ID: 98,167,730,131,36,192,167