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

Abstract

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 ≤ 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.

Long-term treatment with anti-α4 integrin antibodies aggravates colitis in Gαi2-deficient mice

“…In animal and human studies in which a4 integrin was neutralized for a short time, intestinal inflammation was attenuated [10][11][12][13][14]. Similar results were obtained after blocking MadCAM-1, the ligand for the intestinal homing receptor, a4b7 integrin [15,16].…”

Natalizumab for Active Crohn's Disease

“…13,14 Natalizumab (Antegren, Elan Pharmaceuticals and Biogen), a recombinant, humanized monoclonal antibody against a 4 integrin, improved the signs and symptoms of patients with Crohn's disease or ulcerative colitis in two pilot studies. 15,16 We conducted a large, randomized, placebo-controlled trial of this selective adhesion-molecule inhibitor in patients with moderate-to-severe Crohn's disease.…”

Current and Future Biological Treatments in Inflammatory Bowel Disease

“…Three hundred and thirty-nine patients with CD who responded to natalizumab were followed by 12 months (ENACT-2), natalizumab demonstrated a significant superiority over the placebo in its ability to sustain both the response and remission at all consecutive time points over a 6 months period and enabled patients to be successfully withdrawn from steroids [17]. In an uncontrolled short term pilot study in 10 patients with active UC, a single 3 mg/kg intravenous infusion of natalizumab showed a short-term benefit [18]. Natalizumab is efficacious in multiple sclerosis (MS) as well [19,20].…”