A pilot study of treatment of active ulcerative colitis with natalizumab, a humanized monoclonal antibody to alpha-4 integrin

Background: Alpha-4 integrins facilitate leucocyte migration across vascular endothelium. Aim: To assess the safety and efficacy of natalizumab (Antegren), a humanized antibody to alpha-4 integrin, in patients with active ulcerative colitis. Methods: Ten patients with active ulcerative colitis, defined by a Powell-Tuck activity score > 4, received a single 3 mg/kg natalizumab infusion. The primary end-point was the change in Powell-Tuck score at 2 weeks post-infusion. Results: Significant decreases in the median Powell-Tuck score were observed at 2 and 4 weeks post-infusion (7.5 and 6, respectively) compared to the median baseline score (10). Five of 10 patients achieved a good clinical response at 2 weeks and one more patient by 4 weeks, defined by a Powell-Tuck score of less than or equal to 5. Significant improvements in quality of life scores were found at week 4. Rescue medication was required by two (20%). three (30%) and eight (80%) patients by weeks 2, 4 and 8. respectively (median, 34 days; range, 8-43 days). One patient remained in remission at 12 weeks. The median C-reactive protein at 2 weeks (6 mg/L) was lower than that pre-treatment (16 mg/L). Conclusions: A single 3 mg/kg infusion of natalizumab was well tolerated by ulcerative colitis patients. The positive efficacy demonstrated in this study merits further investigation by randomized, placebo-controlled trials.