VANCOUVER, BC—Natalizumab, a treatment indicated for multiple sclerosis and Crohn’s disease, failed to affect infarct volume growth or neurologic findings when administered up to nine hours after acute ischemic stroke (AIS), according to findings from a randomized, double-blind, placebo-controlled trial, reported by Biogen at the 68th AAN Annual Meeting.
“However, at Days 30 and 90, natalizumab showed some surprising benefits over placebo” for functional outcomes, noted coauthor Lahar Mehta, MD, of Biogen in Cambridge, MA. “This was quite unexpected and suggests other doses might be considered.”
No safety issues were reported. Smaller strokes showed better benefits, Dr. Mehta noted.
Natalizumab is a humanized monoclonal antibody against α4 integrin with a well-defined pharmacokinetic/pharmacodynamic profile. “Anti-α4 integrin reduces infarct volume and improves outcome in some, but not all, experimental models of acute ischemic stroke,” Dr. Mehta said.
A total of 159 patients were randomized in a double-blind Phase 2 study: 77 were administered 300mg intravenous natalizumab and 82 were assigned placebo. All study participants were treated within the first 9 hours from symptom onset.
No difference was displayed in MRI-assessed infarct growth volume in the natalizumab over placebo study groups, at Day 5 (ratio of relative growth: 1.09; P=0.779) or Day 30 (ratio of relative growth: 1.05; P=0.684), Dr. Mehta reported.
However, at Days 30 and 90, Barthel Index (BI) scores (a measure of independent function and mobility) were superior among patients treated with natalizumab (Day 30: BI ≥95: 8.6% placebo vs. 18.1% natalizumab patients; odds ratio [OR] 2.88; 90% CI: 1.2–6.9; Day 90: BI ≥95: 32.5% vs. 44.2%; OR 1.91; 90% CI: 1.1–3.4), he added.
The study was funded by Biogen, and Dr. Mehta and other coauthors are employed by, and own stock options in, Biogen, he disclosed.