番茄社区

NASHVILLE -- Patients with relapsing multiple sclerosis (MS) who switched from interferon beta (IFNβ)-1a to ocrelizumab (Ocrevus) showed rapid improvement in disease activity and progression on magnetic resonance imaging (MRI) in an open-label extension of the OPERA I and II trials.

Patients initially randomized to receive ocrelizumab in the two clinical trials maintained lower whole brain, white matter, and cortical grey matter tissue loss after 4 years of continuous treatment, compared with patients initiating ocrelizumab after 2 years of IFNβ-1a while enrolled in the study.

But switching from IFNβ-1a to ocrelizumab at the start of the open-label extension period was associated with rapid and robust reductions in MRI disease activity.

Initial findings from the open-label extension of the pooled OPERA trials were reported in a poster session of the Annual Meeting of the Consortium of Multiple Sclerosis Centers, held here May 30-June 2. The results were also reported in late April at the 2018 American Academy of Neurology annual meeting.

Ocrelizumab was approved by the FDA in March 2017 for the treatment of relapsing MS, based on the OPERA results. The drug also became the first and only disease-modifying therapy to be approved for the most aggressive form of the disease, primary progressive MS (PPMS), based on findings from a third clinical trial.

Upon completion of the controlled, 96-week OPERA trials, all patients were eligible to enter the ocrelizumab open-label extension phase of the trials. The main objective of the extension was to assess the efficacy of ocrelizumab in patients switching and continuing on the treatment during the 2-year open-label period, the researchers explained.

During the double-blind controlled treatment period, patients received intravenous ocrelizumab, 600 mg, every 24 weeks or subcutaneous IFNβ-1a, 44 μg, three times weekly for 96 weeks.

MRI lesion activity (T1 gadolinium-enhancing [T1Gd+] lesions, new/enlarging T2 [N/ET2] lesions) and percentage change in whole brain volume, cortical grey matter volume, and white matter volume were analyzed.

The analysis revealed the following:

• Among patients switching from IFNβ-1a to ocrelizumab, the adjusted number of T1Gd+ lesions was 0.48 lesion/scan before switching, decreasing to 0.00 at years 1 and 2 of the open-label extension
• Similar reductions in the adjusted number of N/ET2 lesions were seen from 2.16 lesions/scan in the year pre-switch to 0.33 and 0.08 at years 1 and 2 of the open-label extension
• Patients treated with ocrelizumab throughout the trial maintained low numbers of T1Gd+ and N/ET2 lesions through 2 years of the open-label extension period
• Compared with the patients who switched, those on ocrelizumab during the clinical trial had lower brain atrophy from the core study baseline to the end of years 1 and 2 of the open-label extension period as measured by whole brain volume change (–1.31%/–1.51% and –1.57%/–1.88%; P<0.01 for both); cortical grey matter volume change (–1.47%/–1.56% and –1.72%/–1.91%; P=0.16 and P<0.01) and white matter volume change (–0.94%/–1.23% and –1.11%/–1.46%; P<0.01 for both

Patricia Coyle, MD, of Stony Brook University in New York, who was not involved in the extension trials, said that lingering questions about the use of ocrelizumab center more around patients with primary progressive MS with relapsing MS.

That is because, she explained, the clinical trial that confirmed the drug's efficacy in these patients excluded patients over age 55, those with a PPMS diagnosis of 15 years or more, those who were non-ambulatory, those with prior relapses, and those with abnormal prior cerebrospinal fluid results. In addition, a post-hoc analysis of the raised new questions about the drug's efficacy in female patients with PPMS.

It raises the question, Coyle said, of whether ocrelizumab be offered to women with primary progressive MS. "I think the answer is yes. I'm doing it. But I'm telling them about the post-hoc analysis. Should it be offered to non-ambulatory primary progressive MS patients or those over age 55? Well, of course, our clinical trials are rigid. You try to get a pristine, pure population. But that is not real life."