NASHVILLE—The benefits of ocrelizumab on 24-week confirmed disability improvement, which were demonstrated in two-year, double-blind, controlled trials, were maintained for two years in an open-label extension study in patients with relapsing-remitting multiple sclerosis (MS), according to data described at the 2018 CMSC Annual Meeting.
The 96-week, double-blind, controlled periods of the OPERA I and II trials demonstrated the efficacy and safety of ocrelizumab in relapsing-remitting MS. Upon completion of the controlled treatment periods, all patients were eligible to enter an open-label extension phase during which they would receive ocrelizumab. Robert T. Naismith, MD, Associate Professor of Neurology at Washington University School of Medicine in St. Louis, and colleagues reviewed data from this extension phase to assess the effect of switching to ocrelizumab or maintaining ocrelizumab therapy on the proportion of patients experiencing disability improvement.
Difference Between Groups Endured
During the controlled treatment period, patients received IV ocrelizumab (600 mg) every 24 weeks or subcutaneous interferon beta-1a (44 μg) three times weekly for 96 weeks. At the start of the open-label extension period, patients continued ocrelizumab or were switched from interferon beta-1a to ocrelizumab. Disability improvement compared with baseline was defined as a reduction in Expanded Disability Status Scale (EDSS) score of 1.0 or more points for patients with a baseline EDSS score from 2.0 to 5.5, or a reduction of 0.5 or more points for patients with a baseline EDSS score greater than 5.5. Time to onset of 24-week confirmed disability improvement was analyzed in patients with a baseline EDSS score of 2.0 or greater.
More than 89% of patients who entered the open-label extension period completed two years of the open-label extension. The group that started and continued ocrelizumab (n = 454), compared with the group that switched from interferon beta-1a to ocrelizumab (n = 419), had a higher proportion of patients with 24-week confirmed disability improvement in the year before the switch (16.8% vs 13.3%). At year 1 of the extension, the group that started and continued ocrelizumab included 399 participants, and 20.6% had 24-week confirmed disability improvement, compared with 16.6% of the group that switched from interferon beta-1a to ocrelizumab, which included 366 participants. At year 2, the former group included 363 patients, and 23.7% had 24-week confirmed disability improvement. The latter group included 339 participants, and 18.9% of them achieved this outcome.
Analyzing Four Years of Treatment
When the investigators examined data for four years of treatment (ie, the double-blind and extension phases), they observed that between 20% and 25% of patients with an EDSS score of 2 or more who received ocrelizumab had improvement in EDSS score. When they examined patients with EDSS scores lower than 2, the results were similar. “This [finding] parallels some of the effects that we see in clinical efficacy, based upon a reduction in MRI parameters such as T1 and T2 lesions,” said Dr. Naismith.
“What we are seeing, especially with some of our high-efficacy therapies, is that patients come back and report that they are feeling better in subsequent visits. I admit, I never tell patients that this is an expectation they should have…. But it is always nice to hear from a patient that they are doing better in some tangible way in their lives,” Dr. Naismith concluded.