Reuters Health – 05/11/2020 – Primary progressive multiple sclerosis (MS) patients treated with ocrelizumab show sustained long-term benefit, a post-hoc analysis of the phase-3 ORATORIO trial’s open-label extension period shows.
Those initially randomized to ocrelizumab had less disease progression based on disability measures and imaging studies than those who started the study on placebo, Dr. Jerry S. Wolinsky of McGovern Medical School at The University of Texas Health Science Center at Houston and colleagues found.
“To me the beauty of this study was at the same time the drug ocrelizumab was being tried in classic relapsing-remitting disease, we were doing this study in primary progressive disease, so that we could have enough common elements in those studies as to begin to understand how similar or how different relapsing and primary progressive disease really are,” Dr. Wolinsky noted.
“The benefits that we’re seeing were maintained in the group that was randomized on the drug originally,” he added. But as seen in trials of the drug for relapsing-remitting disease, patients for whom treatment is delayed “never look quite the same” as those who started earlier.
In the ORATORIO trial, 732 patients with primary progressive MS aged 18 to 55 were randomly assigned 2:1 to receive two 300 mg infusions of ocrelizumab two weeks apart every 24 weeks for at least 120 weeks, or placebo, until 253 disability events occurred.
A total of 544 patients completed the double-blind period of the trial up to week 144, 527 (97%) of whom joined the open-label extension phase. Of these patients, 451 (86%) are continuing to participate in the study, which the authors plan to continue to the end of 2022.
During follow-up of at least 6.5 years, 51.7% of the patients initially on active treatment had disease progression based on Expanded Disability Status Scale scores, versus 64.8% of those who started on placebo (P=0.0018).
Thirty percent of patients started on ocrelizumab had a 20% or greater increase in the time it took them to perform the Nine-Hole Peg Test, compared to 43.1% of the patients initially on placebo, while 63.2% and 70.7%, respectively, showed disease progression based on the Timed 25-Foot Walk – both significant differences.
Composite progression, defined as the first occurrence of increased disability based on any of these measures, occurred in 73.2% of the earlier-treatment group and 83.3% of the initial-placebo group (P=0.0023). Time-to-requiring a wheelchair (EDSS of 7.0 or higher) was 11.5% and 18.9%, respectively (P=0.0274).
The patients on continuous active treatment had almost complete suppression of T1 gadolinium-enhancing lesions and new or growing T2 lesions at the end of the double-blind phase of the study, which continued through the open-label extension period.
For the placebo group, new MRI-lesion disease activity was suppressed almost completely once they switched to ocrelizumab, and suppression was maintained through the follow-up.
“We think there’s a better level of containment of what we think is the driving force of the disease, which are these microscopic and sometimes larger lesions that we can visualize with our more advanced imaging,” Dr. Wolinsky said. “This seems to be occurring across this whole spectrum of presentations of multiple sclerosis, and amenable across the whole spectrum to treatment.”
Dr. Jeffrey A. Cohen of the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic, who co-authored a linked comment on the study, said, “This long-term follow-up study provides no big surprises, but the information that it provides is valuable. It showed that ocrelizumab has continued effectiveness in patients with primary progressive MS. It’s the first approved medication for that indication.”
“The safety profile with long-term follow-up was largely what was seen not only in the shorter core trial, but also what was seen in the trials with relapsing-remitting MS,” he told Reuters Health by phone.
While informative censoring is an issue with all open-label extension studies, he added, “one of the positive aspects of this study is that the retention rate was good, so that makes it easier to interpret.”
By Anne Harding
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