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.
Summary. This article reviews the evidence that adhesion molecules are critical in leukocyte recirculation and pathogenesis of diseases affecting the closely related tissues of the liver and gut, which offer novel opportunities for treatment.
For anatomical reasons apparently related to the vasculature of the human and rodent small bowel, specific sites along the mesenteric margin are susceptible to Crohn's disease ulceration and NSAID damage, respectively.
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