Nondisabling relapses that occur early in the course of relapsing-remitting multiple sclerosis (RRMS) signal faster accumulation of disability relative to no early relapses, new research suggests. However, in the large registry study, this association was not found in patients treated with high-efficacy, disease-modifying therapies (DMTs) early on.
The results suggest that ,” said lead author Cyrus Daruwalla, MD, department of clinical neurosciences at the University of Cambridge, and Addenbrooke’s Hospital, Cambridge, England.
Dr. Daruwalla presented the findings at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
Questioning EMA restrictions
“We designed this project because regulators, including EMA [European Medicines Agency], restrict the use of certain DMTs to only those with disabling relapses. In particular, natalizumab [Tysabri] and fingolimod [Gilenya] can only be used as the first-line therapy for people with rapidly evolving, severe MS – which includes having two disabling relapses in a year,” Dr. Daruwalla noted.
“In clinic, when we see somebody who has a nondisabling relapse, we’re left with the question of what is the prognostic significance of that relapse, and how should it influence treatment decisions,” he added.
Using prospectively collected data from the MSBase international registry, the researchers examined data on individuals with RRMS and complete early relapse severity information.
They compared patients with exclusively nondisabling relapses in the 2 years after definitive RRMS diagnosis with peers with no relapses within this time frame.
To mitigate the confounding effect of DMT use, the investigators performed analyses in participants untreated during follow-up, and then in those who received only older or “platform” therapies (interferon-beta, glatiramer acetate, dimethyl fumarate, or teriflunomide) during follow-up.
In the untreated cohort, 285 patients had nondisabling relapses and 4,717 had no relapses during the 2 years after diagnosis. Those with early nondisabling relapses had a significantly increased risk for disability accumulation (adjusted hazard ratio [aHR], 1.29; 95% confidence interval [CI], 1.00-1.68).
In the treated cohort, 1,074 patients had nondisabling early relapses and 7,262 did not.
In this cohort, those treated with “platform” DMTs who had nondisabling relapses showed a significantly increased risk for disability accumulation compared with treated peers who had no relapses (aHR, 1.33; 95% CI, 1.15-1.54).
Notably, said Dr. Daruwalla, in patients treated at any point during follow-up with high-efficacy DMTs, including monoclonal antibodies, sphingosphine-1 phosphate modulators, and hematopoietic stem cell transplantation, there was no difference in disability accumulation between patients who did and did not experience nondisabling relapses (aHR, 0.90; 95% CI, 0.71-1.13).
The data clearly show that early nondisabling relapses are associated with a higher risk of disability accumulation than no early relapses in people with relapsing remitting MS,” Dr. Daruwalla said.
However, he noted, treatment with high-efficacy DMTs offers protection against disability accumulations.
“Therefore, contrary to EMA guidance, nondisabling relapses should be considered in decisions to initiate or escalate treatment, including with high-efficacy therapies,” he added.
Valuable, confirmatory data
Patricia Coyle, MD, professor of neurology and director of the MS Comprehensive Care Center at Stony Brook (N.Y.) University, called the study “valuable.”
“It confirms prior data that having relapses is bad in MS even if they are mild, and provides additional modest data in support of high-efficacy versus moderate-efficacy DMT,” said Dr. Coyle, who was not involved with the research.
“Although certainly not definitive, it adds to data supporting high-efficacy as preferred treatment [and] addresses a completely arbitrary governmental limitation to DMT use in Europe,” she added.
The study had no commercial funding. Dr. Daruwalla has reported no relevant financial relationships. Dr. Coyle reports having received consulting fees from Accordant, Biogen, Bristol-Myers Squibb, Celgene, Genentech/Roche, GlaxoSmithKline, Horizon, Janssen, Novartis, Sanofi Genzyme, and Viela Bio; and grant funding from Actelion, Alkermes, Bristol-Myers Squibb, CorEvitas, Genentech/Roche, Sanofi Genzyme, MedDay, and Novartis.
A version of this article first appeared on Medscape.com.