Conference Coverage

Ibudilast’s efficacy differs in primary and secondary progressive MS


 

REPORTING FROM AAN 2019

Ibudilast’s treatment effect in a phase 2 trial for progressive multiple sclerosis (MS) primarily was driven by patients with primary progressive MS, and not by patients with secondary progressive disease, researchers reported at the annual meeting of the American Academy of Neurology.

The difference may be related to faster atrophy rates among patients with primary progressive MS who received placebo, compared with those with secondary progressive MS who received placebo.

The finding was surprising, said Andrew Goodman, MD, professor of neurology, chief of the neuroimmunology unit, and director of the multiple sclerosis center at the University of Rochester (N.Y.). “Going into the trial, it was my bias and expectation that both primary and secondary progressive MS would behave more similarly than different.”

The trial, SPRINT-MS, included more than 250 patients with progressive MS at 28 sites. Patients were aged 18-65 years and were followed for 96 weeks. Patients had primary progressive MS (n = 134) or secondary progressive MS (n = 121) and were randomized 1:1 to ibudilast or placebo.

Ibudilast is an orally administered small molecule that has been used in Japan for approximately 30 years for asthma and other indications, Dr. Goodman said. Preclinical models suggested that the drug may have neuroprotective effects.

The trial’s primary result – a 48% slowing in the rate of whole brain atrophy as measured by brain parenchymal fraction with ibudilast – was reported last year (N Engl J Med. 2018 Aug 30;379[9]:846-55).

The present study examined whether the treatment effect of ibudilast was similar by progressive disease type using a linear mixed model analytic approach.

The group with primary progressive MS included a smaller percentage of women. Patients with secondary progressive MS had longer disease duration and more brain atrophy at baseline.

“The overall benefit which we previously reported appears to be driven by subjects with primary progressive rather than secondary progressive MS,” Dr. Goodman said. Accounting for baseline covariates did not affect this result.

Among patients who received placebo, brain atrophy in those with secondary progressive MS was 57% slower than in those with primary progressive MS. The rate of atrophy for untreated patients with primary progressive MS “was roughly twice as fast as that in the secondary progressive MS group, which we think may explain in part the differential in efficacy,” Dr. Goodman said. “These findings may impact future trial design for progressive MS.”

The SPRINT-MS trial was funded by the National Institute of Neurological Disorders and Stroke. The National Multiple Sclerosis Society and MediciNova also supported the study. Dr. Goodman reported receiving research support from pharmaceutical companies, as well as personal compensation from companies for consulting, serving on a scientific advisory board, and speaking.

SOURCE: Goodman A et al. AAN 2019, Abstract S12.007.

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