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Real-World Ocrelizumab Data Mirrors MS Trials

DALLAS — Ocrelizumab (Ocrevus) showed safety and effectiveness for relapsing-remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS) patients over 6 months of real-world clinical practice, researchers reported here.

In a prospective longitudinal cohort study, ocrelizumab showed good clinical efficacy and fewer adverse events than expected, according to Brandon Moss, MD, of the Cleveland Clinic Mellen Center, and colleagues, in a presentation at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) forum.

“Clinical trials are not always representative of the patients you see in clinic, and that’s the case here,” Moss told MedPage Today. “In our clinical practice, people who were started on the drug were older, had longer disease duration, and had lower disease activity when they started the medication, all of which can decrease the effectiveness of the drug.”

Ocrelizumab, a monoclonal antibody that depletes CD20+ B-cells, was approved by the FDA to treat RRMS and PPMS in 2017 based on three clinical trials: OPERA I, OPERA II, and ORATORIO. The trials showed annualized lower relapse rates in RRMS of 46% (OPERA I) and 47% (OPERA II) over interferon, and a 24% reduction in risk of 12-week confirmed disability progression in PPMS (ORATORIO) relative to placebo.

Infections, mostly minor, were common side effects seen in the trials. The FDA also noted in its approval announcement that the drug “may increase the risk for malignancies, particularly breast cancer.”

At ACTRIMS, researchers reported 6-month results of 351 patients — 274 with RRMS and 76 with PPMS — who had been treated with ocrelizumab at the Cleveland Clinic. Patients, ages 18-75, who started ocrelizumab after regulatory approval, and who had been followed clinically for at least 6 months before starting ocrelizumab were included.

Patients had many similar characteristics as OPERA and ORATORIO participants, but longer disease duration and fewer brain lesions at baseline.

They also were older: RRMS patients were a median age of 45, compared with an average age of 37 in the OPERA trials; PPMS patients were a median age of 57, compared with an average age of 45 in ORATORIO. Nearly all (95%) of relapsing patients and 68% of progressive patients had been on at least one high-efficacy therapy before starting ocrelizumab.

Over 6 months, 10 patients (2.8%) were treated for a clinical relapse, including six cases corroborated by MRI or exam findings. Most relapses occurred in the first 3 months after starting ocrelizumab.

At 6 months, about 5% of patients had a normal CD19 B-cell count. Only age showed a significant link to CD19 counts (P=0.04) with a correlation coefficient of -0.13. Baseline white blood cell count (P=0.41) and absolute lymphocyte count (P=0.66) were not significantly associated with 6-month CD19 B-cell counts.

About one-third (31%) of patients experienced adverse events, substantially lower than 80% to 95% adverse event figures reported in the phase III trials. Part of this finding was driven by infusion-related reactions, which occurred in 31% to 40% of trial participants, but only 13% of Cleveland Clinic patients.

“We found that to be a little surprising,” Moss noted. “We are using the same infusion protocol that was used for the clinical trials, but maybe some of the differences lie within how we administer that protocol.”

In the Cleveland Clinic cohort, 12% of patients had infections, primarily urinary tract and upper respiratory tract infections. Four patients had serious infections (1%), similar to reports from the OPERA trials, but lower than the 6% of serious infections reported in ORATORIO.

A total of nine (3%) serious adverse events occurred in the Cleveland Clinic study — suicidal ideation, depression resulting in hospitalization, Crohn’s colitis, septic abortion, urosepsis, hepatic failure, abdominal pain, infective endocarditis, and basal cell carcinoma. One patient developed atypical ductal hyperplasia (0.3%) and one developed basal cell carcinoma (0.3%). In contrast, serious adverse events were 7% in OPERA I and OPERA II and 20% in ORATORIO.

Longer-term outcomes in clinical practice are yet to be seen. “We are in the process of collecting 12-month data now,” Moss said.

The study was supported by Genentech.

Moss disclosed relevant relationships with Genentech and Genzyme.