New long-term follow-up data from a pair of phase 3 trials confirm early and ongoing treatment with monoclonal antibodies continue to offer clinical benefits after 10 years.
The 10-year data from the OPERA I and II open-label extension have been released, reiterating the importance of starting effective treatment as soon as possible in relapsing MS.
The OPERA trials saw over 1600 patients with relapsing multiple sclerosis receive either ocrelizumab, an anti-CD20 monoclonal antibody, or interferon beta-1a over a two-year period. Patients were subsequently invited to participate in an eight-year open-label extensions study, where 1300 participants were treated with ocrelizumab. Additional follow-ups were undertaken at five, and now 10, years as part of the OLE.
“The current analysis provides robust evidence of the significant and durable benefit of ocrelizumab in patients with RMS, 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 in JAMA Neurology.
Eight hundred and fifty-three patients completed the eight-year OLE, with more of these patients receiving ocrelizumab initially (438) than interferon (415). Both groups had been treated for a similar time (median 10.1 years in each group), were of a similar age at their last follow-up (mean 47.4 years versus 48.2 years), and had a similar proportion of female participants (62.3% versus 62.2%).
Initial treatment with ocrelizumab decreased the likelihood of a 48-week confirmed disability progression by 24% (hazard ratio and 95% confidence interval 0.76, 0.61-0.95) at the 10-year follow-up compared to starting on interferon and later switching. There was no association between ocrelizumab and the time to first progression independent of relapse activity event in the OLE phase, nor was there an association to the first time to an Expanded Disability Status scale score ≥4. However, receiving ocrelizumab throughout the entire 10 years decreased the likelihood of reaching an EDSS score ≥6 by 43% (HR 0.57, 0.40-0.82) compared to only receiving it during the OLE.
Treatment with ocrelizumab in both the double-blind and OLE phase also reduced the likelihood of experiencing a relapse by 38% compared to patients treated with both interferon and ocrelizumab (HR 0.62, 0.52-0.74).
“In the 8-year OLE period, 564 patients (80%) were relapse free regardless of the treatment allocation during the DBP. The number of relapses decreased consistently over time, and in year 10, only approximately 1 out of 100 patients experienced a relapse,” said the researchers.
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Similarly, over half of the patients treated with ocrelizumab in both phases of the trials showed no evidence of disease activity (NEDA-3) over the 10-year follow-up period compared to roughly a third of the patients initially treated with interferon (58.6% versus 38.0%), corresponding to a 52% reduction in the likelihood of displaying disease activity (HR 0.48, 0.41-0.55).
Differences in whole-brain volume were also observed between patients who received ocrelizumab from the outset compared to those who only initiated it during the OLE.
“Whole-brain volume loss from baseline to year 10 was numerically lower in the OCR-OCR group (−3.38%; 95% CI, −3.59% to −3.18%) compared with the IFN-OCR group (−3.62%; 95% CI, −3.82% to −3.41%); this difference was significant up to year eight (difference in adjusted means, 0.24%),” the researchers said.
Adverse events occurred at a rate of 194/100 person-years and did not increase throughout the follow-up period. Serious adverse events also remained stable across the OLE, occurring at a rate of 6.3/100 person-years. Around 1% of patients discontinued ocrelizumab treatment each year as a result of adverse events, with infusion-related reactions and urinary tract infections the most common reasons for discontinuing treatment.
The latest findings underscore the importance of starting treatment early, according to the researchers.
“Patients with a two-year delay in ocrelizumab initiation (initially randomised to IFN) exhibited worse cumulative disability and NEDA-3 outcomes,” they said. “Despite receiving ocrelizumab for at least eight years, significant differences in disability accumulation persisted, supporting existing evidence that early initiation of high-efficacy CMTs is crucial to delaying long-term disability.”
The post hoc nature of the analysis and the lack of a control arm during the open-label extension phase were highlighted as potential limitations of the new research.
