Patients with multiple sclerosis (MS) who began treatment on ocrelizumab had less disability after 8.5 years than patients who began on interferon beta-1a and then switched to ocrelizumab, according to a study presented in April at the AAN Annual Meeting in Boston.
The study is a secondary analysis from the pivotal OPERA I and II trials, which led to the approval of the B cell-targeting therapy.
“Early intervention using high-efficacy therapies to prevent disease progression is an increasingly adopted therapeutic strategy in multiple sclerosis," as reaching disability milestones is associated with increased patient and societal burden, said the researchers led by Martin Weber, MD, of the Institute of Neuropathology and department of neurology at University Medical Centre and Fraunhofer-Institute for Translational Medicine and Pharmacology ITMP in Göttingen, Germany.
The OPERA trials compared ocrelizumab with interferon beta-1a including 1,656 patients with relapsing MS over 96 weeks and showed that the annualized relapse rate for patients receiving ocrelizumab was 46 to 47 percent lower than those receiving interferon beta-1a. Functional composite scores favored ocrelizumab in the second trial but not the first.
At the end of the trial, an open-label extension began, and those receiving interferon beta-1a could cross over to ocrelizumab. The new study compared the risk of reaching disability milestones between those who had begun the double-blind trial on ocrelizumab and thus received it for the full 8.5 years, and those who started on interferon and thus received two years of interferon followed by 6.5 years of ocrelizumab.
Key metrics were time to onset of 24-week confirmed disability progression, walking impairment, and need for a walking aid.
The authors found that each metric favored those who received ocrelizumab longer. The hazard ratio for ocrelizumab only was 0.42 for onset of confirmed disability compared with interferon/ocrelizumab treatment (p=0.0303), 0.69 for walking impairment (p=0.0486), and 0.67 for requiring a walking aid (p=0.0207).
Over 8.5 years, 85 percent of ocrelizumab-only patients had not progressed to a score of 2 or more on the Expanded Disability Status Scale (EDSS), and 92.6 percent had not progressed to EDSS score of 6 or more.
The authors concluded that “early institution of high-efficacy therapy can preserve function that is not regained when the same treatment is initiated later."
"This study adds to the growing body of information that indicates that persons with MS will have better long-term outcomes if high-efficacy therapy is initiated early in the disease process, rather than switching to a higher-efficacy agent from a less efficacious one after damage has occurred," said Barbara Giesser, MD, FAAN, staff physician at the Pacific Neuroscience Institute in Santa Monica, CA, and professor emeritus of clinical neurology at the David Geffen University of California, Los Angeles School of Medicine.
The rationale for early treatment with a B cell-targeting therapy is based on recent developments in understanding of progressive MS, said Dina Jacobs, MD, associate professor of neurology and clinical director of the Multiple Sclerosis and Related Disorders Center at the University of Pennsylvania. “We now believe that the progressive disease process starts at the onset of the disease, not later in the course of MS," as a consequence of immune cells taking up residence within the central nervous system. To prevent disability progression, it is critical to prevent those cells from doing so as early as possible.
“Early treatment is absolutely critical in preventing disability," Dr. Jacobs said. “B cell-targeting therapies are highly effective and well-tolerated with limited toxicity. These exciting results are further proof that they should be started early in the disease course to limit disability progression before it starts."
Dr. Weber had no disclosures.
