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First Drug Success In Slowing Untreatable Form Of Multiple Sclerosis

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A trial of the drug ocrelizumab has demonstrated a measurable slowing of the primary progressive form of multiple sclerosis (MS). The effect is not very large, but for a disease that has proven so resistant to treatment in the past, any benefits mark a big step forward. In a separate trial, ocrelizumab outperformed existing drugs for patients with the more common relapsing remitting MS.

All forms of MS occur when the immune system malfunctions, attacking the myelin sheaths that protect nerves and interfering with the transmission of impulses in the neural system. Patients with primary progressive MS almost always get continuously worse, while, as the name suggests, the relapsing remitting form can give sufferers some relief between attacks.

Immunotherapy has been shown to reduce the frequency and severity of attacks for people with relapsing remitting MS, but it is not generally recommended for people with the primary progressive form of the disease.

A paper in the New England Journal of Medicine reports a trial of ocrelizumab given to almost 500 people with primary progressive MS. Ocrelizumab depletes CD20-expressing B cells, which represent at least part of the immune system’s attack on myelin. Although this potentially leaves the body less able to fend off the infections B cells are meant to fight, that may be a price worth paying for people with MS.

Of the 488 primary progressive MS patients given ocrelizumab, 101 died or withdrew before the end of the trial, but this was still a significantly lower proportion than among the 244 given a placebo, a third of whom did not finish the trial. Those on the drug did better on a number of tests for the progression of the disease than those in the control group.

Nevertheless, the benefits were far from a dramatic cure. For example, it took those on the placebo 55.1 percent longer to walk 7.6 meters (25 feet) after 120 weeks in the trial. Those on the drug took 38.9 percent longer – a significant difference, but still a substantial increase in disability in just over two years.

Although some patients had adverse reactions to the ocrelizumab infusions, changes to the rate at which the drug was administered appeared to resolve these in most cases, and other side effects were limited.

Another paper in the same edition reveals that among 1,656 people with relapsing remitting MS, those given ocrelizumab were just over half as likely to suffer an attack during a 12-week period as those given interferon beta-1a, a common existing drug for the condition. Those on the newer drug also scored better on tests of both physical and mental MS symptoms.

The work was inspired by a previous study on a different CD20 antibody. While that failed to benefit patients over all, it did delay the progression of the disease among younger sufferers, making the authors think that an approach along similar lines might be worthwhile.

Earlier this year, more dramatic results were seen for patients with aggressive MS. The treatment in that case was not only exceptionally risky, but the sample size was also much smaller, making this the first success with such a large trial.

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