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

Gordon, F. H
Hamilton, M. I
Donoghue, S
Greenlees, C
Palmer, T
Rowley-Jones, D
Dhillon, A. P
Amlot, P. L
Pounder, R. E

¹Centre for Gastroenterology, Royal Free and University College Medical School, London, UK,
²Elan Pharmaceuticals Europe Ltd, Stevenage, Hertfordshire, UK,
³Department of Histopathology, Royal Free and University College Medical School, London, UK,
⁴Department of Clinical Immunology, Royal Free and University College Medical School, London, UK

Correspondence to: Dr F. H. Gordon, Centre for Gastroenterology, 10th Floor, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, UK. E-mail: [email protected]

Alimentary Pharmacology & Therapeutics 16(4):p 699-705, April 2002.

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.