Use of anti-ICAM-1 therapy in ischemic stroke - Results of the Enlimomab Acute Stroke Trial

Background: There has been recent interest in the possible role of reperfus ion-induced inflammation with neuronal injury after stroke. Enlimomab, a mu rine intercellular adhesion molecule-1 (ICAM-1) antibody, reduces leukocyte adhesion and infarct size in experimental stroke studies. The purpose of t he current clinical trial was to evaluate the use of enlimomab after ischem ic stroke. Methods: A total of 625 patients with ischemic stroke were rando mized to receive either enlimomab (n = 317) or placebo (n = 308) within 6 h ours of stroke onset. Treatment was given over 5 days. Patients were evalua ted at baseline and on days 5 and 90 after initiation of treatment; long-te rm assessments were carried out after 6 and 12 months. The primary efficacy endpoint was the response to therapy at 90 days on the Modified Rankin Sca le; other endpoints included Barthel Index (BI) and NIH Stroke Scale and su rvival. Results: At day 90, the Modified Rankin Scale score was worse in pa tients treated with enlimomab than with placebo (p = 0.004). Fewer patients had symptom-free recovery on enlimomab than placebo (p = 0.004), and more died (22.2 versus 16.2%). The negative effect of enlimomab was apparent on days 5, 30, and 90 of treatment (p = 0.005). There were significantly more adverse events with enlimomab treatment than placebo, primarily infections and fever. Patients experiencing fever were more likely to have a poor outc ome or die. Conclusions: The authors conclude that anti-ICAM therapy with e nlimomab is not an effective treatment for ischemic stroke in the model stu died and, indeed, may significantly worsen stroke outcome.