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.


OBJECTIVE
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 < or = 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.
Gordon
F H
FH
Centre for Gastroenterology, Royal Free and University College Medical School, London, UK. fionagorgon@ownhomeline.freeserve.co.uk
Hamilton
M I
MI
Donoghue
S
S
Greenlees
C
C
Palmer
T
T
Rowley-Jones
D
D
Dhillon
A P
AP
Amlot
P L
PL
Pounder
R E
RE
D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology*; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D039441:Integrin alpha4; D008297:Male; D010865:Pilot Projects; D011788:Quality of Life; D012812:Sigmoidoscopy; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D039441:Integrin alpha4