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A randomized placebo-controlled trial of a humanized monoclonal antibody to alpha4 integrin in active Crohn's disease.
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BACKGROUND & AIMS: alpha4 integrins are important mediators of leukocyte migration across vascular endothelium. This pilot placebo- controlled study aimed to assess the safety and efficacy of natalizumab, a recombinant humanized monoclonal antibody to alpha4 integrin, in patients with mild to moderately active Crohn's disease. METHODS: Thirty patients with active Crohn's disease (Crohn's Disease Activity Index [CDAI] > or =151 and < or =450) received a 3-mg/kg infusion of natalizumab (n = 18) or placebo (n = 12) by double-blind randomization. The study's primary endpoint was change in CDAI at week 2. RESULTS: At week 2, the CDAI decreased significantly from baseline after infusion of natalizumab (mean 45 points) but not placebo (mean 11 points). Seven (39%) natalizumab-treated patients achieved remission at week 2, compared with 1 (8%) treated with placebo. In contrast, 4 (33%) of the placebo-treated patients required rescue medication by week 2, compared with 2 (11%) natalizumab-treated patients. Significant increases in circulating B and T lymphocytes were detected only after natalizumab administration. The frequency of commonly reported adverse events did not differ significantly between groups. CONCLUSIONS: A single 3-mg/kg natalizumab infusion was well tolerated by Crohn's disease patients, although the dose used may have been suboptimal. Elevated circulating lymphocyte levels after natalizumab suggest interrupted lymphocyte trafficking. Natalizumab therapy in active Crohn's disease merits further investigation
|Title:||A randomized placebo-controlled trial of a humanized monoclonal antibody to alpha4 integrin in active Crohn's disease|
|Additional information:||UI - 21379973 LA - eng RN - 0 (Antibodies, Monoclonal) RN - 0 (Antigens, CD) RN - 0 (Biological Markers) RN - 143198-26-9 (alpha4 integrin) PT - Clinical Trial PT - Journal Article PT - Randomized Controlled Trial DA - 20010806 IS - 0016-5085 SB - AIM SB - IM CY - United States|
|Keywords:||activity, Administration, ADVERSE, adverse events, ALPHA, ALPHA(4)BETA(7), antibodies, Antibody, circulating, CO, colitis, COTTON-TOP TAMARIN, Crohn's disease, disease, DISEASE-ACTIVITY, dose, DOUBLE BLIND, DOUBLE-BLIND, EFFICACY, Endothelium, English, EVENTS, expression, FREQUENCIES, FREQUENCY, gastroenterology, groups, GUT-HOMING INTEGRIN, INCREASE, INCREASES, INDEX, INFLAMMATORY BOWEL-DISEASE, INFUSION, Integrin, Integrins, LESS, leukocyte, LEVEL, LYMPHOCYTE, Lymphocytes, LYMPHOID-TISSUE, May, MEDIATOR, Medication, Methods, migration, MONOCLONAL ANTIBODIES, MONOCLONAL ANTIBODY, MONOCLONAL-ANTIBODIES, MONOCLONAL-ANTIBODY, N, natalizumab, Patient, patients, pilot, PLACEBO, PLACEBO CONTROLLED TRIAL, placebo-controlled, PLACEBO-CONTROLLED TRIAL, randomized, recombinant, REMISSION, RESCUE, Result, Safety, SINGLE, T lymphocyte, T lymphocytes, T-CELLS, T-Lymphocytes, THERAPIES, therapy, TREATED PATIENTS, TRIAL, USA, vascular, vascular endothelium, VLA-4, Wales, WEST, Antibodies, Monoclonal, Antigens, CD, Biological Markers, controlled study, Crohn Disease, Double-Blind Method, immunology, Pharmacokinetics, administration & dosage, adult, adverse effects, ANTIGEN, clinical, Clinical trial, CLINICAL-TRIAL, CONTROLLED TRIAL, Female, IM, LA, Male, MARKER, Markers, Middle Age, Quality of Life, RANDOMIZED CONTROLLED TRIAL, STATE, STATES, Support, Non-U.S.Gov't, Treatment Outcome, united, United States, UNITED-STATES|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)|
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