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03-11-2011 | Immunology | Article

Ocrelizumab reduces disease activity in multiple sclerosis


Free abstract

MedWire News: B-cell depletion with the recombinant humanized antibody ocrelizumab effectively reduces magnetic resonance imaging (MRI)-detected lesions and clinical disease activity in patients with multiple sclerosis (MS), study findings indicate.

The reductions occurred irrespective of whether patients received 600 mg or 2000 mg of the drug, which is designed to selectively target CD20 B cells, report Ludwig Kappos (University Hospital, Basel, Switzerland) and colleagues in The Lancet.

The researchers explain that B lymphocytes are implicated in the pathogenesis of MS through antibody-dependent and antibody-independent mechanisms.

Therefore, targeting of these cells might disrupt disease progression, they add.

To test this hypothesis, Kappos and team randomly assigned 200 patients aged 18-55 years with relapsing-remitting MS to receive either placebo, low-dose (600 mg), or high-dose (2000 mg) ocrelizumab given in two doses on days 1 and 15, or intramuscular interferon beta-1a 30 µg once a week.

At week 24, patients in the initial placebo, 600 mg ocrelizumab, and interferon beta-1a groups received ocrelizumab 600 mg, while those in the ocrelizumab 2000 mg group received 1000 mg.

The researchers assessed the total number of gadolinium-enhancing T1 lesions (GEL) observed on brain MRI scans at weeks 12, 16, 20, and 24.

They found that there were highly significant differences in both ocrelizumab groups compared with placebo for the total number of GEL at all time points.

At week 24, the number of GEL was 89% lower in the 600 mg ocrelizumab group and 96% lower in the 2000 mg group than in the placebo group.

Annualized relapse rates were also significantly lower in the ocrelizumab treatment groups (by 80% in the 600 mg group and 73% in the 2000 mg group) than in the placebo group.

Furthermore, an exploratory comparison with interferon beta-1a showed 91% and 97% reductions in GEL among patients treated with ocrelizumab 600 mg and 2000 mg, respectively.

Of note, patients in the placebo and interferon beta-1a groups reached a disease activity level similar to that of the ocrelizumab-treated patients after one treatment cycle with ocrelizumab at 24 weeks.

Serious adverse events were rare in all four groups, at rates of 4%, 2%, 5%, and 4% for placebo, ocrelizumab 600 mg, ocrelizumab 2000 mg, and interferon beta-1a, respectively. There were no opportunistic infections recorded and no differences in immunoglobulin levels over time.

Kappos and co-authors say that the rapid reduction in disease activity with ocrelizumab adds to the increasing body of evidence that B-cell-directed therapies have potential for treatment of MS.

"With caution needed when results are compared between different trials, the effect size in our study on MRI and relapse activity compares favorably with established treatments, and to most of the other compounds in development," they add.

The team concludes by calling for further assessment of ocrelizumab in large, long-term trials.

By Laura Dean

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