Early start on now-approved MS drug seen to limit progression over 10 years
Greater disability found in analysis among those starting med 2 years into trial
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An analyis of clinical trial data showed that an early start in taking the approved MS drug Ocrevus was linked to less disability after 10 years. (Image from iStock)
- A trial analysis found less disability over 10 years for those immediately taking the now-approved MS therapy Ocrevus compared with starting it after two years.
- Still, for all trial participants, lower relapse rates were being seen a decade later for those continuously taking Ocrevus.
- The two large clinical trials analyzed had compared the drug against an earlier approved medication for treating relapsing MS.
In the large, late-stage clinical trials that led to the approval of the multiple sclerosis (MS) drug Ocrevus (ocrelizumab), participants with relapsing forms of MS who were initially assigned to — and remained on the infusion therapy for as long as 10 years — had less disability progression after a decade than those who began treatment two years later.
That’s the key finding of a new post hoc analysis — one planned and conducted after a trial is completed — of the two Phase 3 studies, which together enrolled more than 1,600 people with relapsing MS. In fact, the analysis found that, among other measures, the risk of reaching a disability level associated with needing a walking aid was reduced by more than 40% with early and continuous use of Ocrevus.
According to the researchers, the data “reinforce the importance of early initiation of high-efficacy treatment in patients with [relapsing MS],” in which flare-ups occur despite treatment.
The results showed that, compared with starting on an older, less effective drug and switching to Ocrevus later, beginning with and staying on the now-approved treatment significantly lowered the risk of confirmed disability progression among participants, by 24%. The team noted that “continuous [Ocrevus] treatment over 10 years provided greater benefit in preserving function than a 2-year delay in initiating [the therapy].”
Overall, these findings “confirm the long-term clinical benefits and manageable safety profile of [Ocrevus],” the researchers wrote, noting that “preventing irreversible disability accumulation is a primary treatment goal in [MS].”
The study, “Ten Years of Ocrelizumab in Relapsing Multiple Sclerosis: The OPERA I and II Randomized Clinical Trials,” was published in the journal JAMA Neurology by a team of scientists in North America and Europe. Funding and editorial support for the study were provided by Roche, which owns Genentech, the company that markets Ocrevus.
Ocrevus is an antibody-based therapy that targets immune B-cells, which are involved in MS-driving inflammation. The therapy is now widely approved for use by those with relapsing forms of MS, including relapsing-remitting MS, as well as clinically isolated syndrome, primary progressive MS (PPMS), and active secondary progressive MS.
Its approval for relapsing MS types was based on data from OPERA I (NCT01247324) and OPERA II (NCT01412333), two Phase 3 trials that each enrolled more than 800 patients. Participants were randomly assigned to receive Ocrevus or Rebif (interferon beta-1a), an older MS medication, for about two years. After completing the trial’s main phase, participants could enter an open-label extension, in which all received Ocrevus for as long as eight years.
In trials, Ocrevus worked better than earlier MS med
In the main trials, Ocrevus significantly reduced relapse rates by nearly 50%, and was also associated with a 40% lower risk of disability worsening compared with Rebif. While patients on Rebif eventually transitioned to Ocrevus in the extension portion, analyses over the years have indicated that those who started Ocrevus earlier continued to have better outcomes.
Now, researchers launched a post hoc analysis to assess the long-term safety and effectiveness of Ocrevus over a decade based on pooled data from OPERA I and II.
The team found that, over 10 years, 82% of continuously treated patients remained free from 48-week confirmed disability progression, meaning they did not experience an increase in disability that persisted for at least 48 weeks, or almost one year.
[The data] reinforce the importance of early initiation of high-efficacy treatment in patients with [relapsing MS].
That shows that starting Ocrevus at the beginning of the trials was associated with a 24% lower risk of confirmed disability progression compared with a two-year delay in treatment initiation, according to the team. Importantly, this benefit was largely established in the randomized part of the OPERA trials, as no difference in disability progression was observed in the extension periods, during which time all patients were taking Ocrevus.
The data also showed that 86% of patients always on Ocrevus remained free from progression independent of relapse activity (PIRA), meaning disability worsening that is not associated with a recent relapse. Compared with those who started Ocrevus after two years, the continuously treated group had an estimated 14% lower risk of PIRA; however, this difference was not statistically significant, meaning it could potentially be due to chance.
Need for walking aid cut by over 40% with treatment’s use
The researchers also examined the risk for patients of transitioning to certain disability milestones. In their analyses, the risk of reaching a disability level on the Expanded Disability Status Scale (EDSS) of 6, consistent with needing a walking aid, was significantly reduced, by 43%.
Relapse control also remained “robust,” according to the researchers. About 73% of continuously treated patients remained relapse-free over 10 years, compared with 63% of participants in the delayed treatment group — corresponding to a 38% reduction in the risk of relapses.
However, relapse rates decreased consistently in both groups over time and, by year 10, about one relapse occurred for every 100 patients treated, the data showed.
MRI signs of new inflammatory activity were rapidly suppressed and remained near zero throughout the follow-up period, the researchers noted. Also, Ocrevus continued to show a manageable long-term safety profile, with no new or unexpected safety findings reported and fewer than 1% of patients discontinuing treatment each year.
“The current analysis provides robust evidence of the significant and durable benefit of [Ocrevus] in patients with [relapsing] MS, shown by the near-complete and sustained suppression of acute activity, the low levels of disability accrual, and a manageable long-term safety profile,” the researchers wrote.
Overall, the team concluded, these findings “[confirm] a favorable long-term benefit-risk profile with [Ocrevus] in the management of patients with [relapsing MS].”
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