Basiliximab does not increase efficacy of corticosteroids in patients with steroid-refractory ulcerative colitis.

Abstract

BACKGROUND & AIMS:

Basiliximab is a chimeric monoclonal antibody that binds CD25 and thereby inhibits interleukin (IL)-2-mediated proliferation of lymphocytes. IL-2 might contribute to the resistance of T cells to corticosteroids. We investigated the efficacy and safety of basiliximab as a corticosteroid-sensitizing agent in patients with corticosteroid-refractory ulcerative colitis (UC).

METHODS:

We studied 149 patients with moderate to severe UC (Mayo score ≥6 and endoscopic subscore ≥2) despite treatment for at least 14 days with oral prednisone (40-50 mg/day). Subjects were randomly assigned to groups that were given 20 mg (n = 46) or 40 mg (n = 52) basiliximab or placebo (n = 51) at weeks 0, 2, and 4. All subjects received 30 mg/day prednisone through week 2; the dose was reduced by 5 mg each week to 20 mg/day, which was maintained until week 8. At week 8, we compared the rates of clinical remission (Mayo score ≤2, no subscore >1) for patients given basiliximab with the rate for patients given placebo.

RESULTS:

Twenty-eight percent of patients given placebo, 29% of those given the 40-mg dose of basiliximab, and 26% of those given the 20-mg dose of basiliximab achieved clinical remission (P = 1.00 vs placebo for each dose). Basiliximab was generally well tolerated. Six subjects who received basiliximab had serious adverse events (6.1%) compared with 2 who received placebo (3.9%; P = .72). In subjects given basiliximab, incomplete saturation of CD25 (<50%) on peripheral T cells was associated with the presence of anti-basiliximab antibodies (odds ratio, 21; 95% confidence interval, 2.4-184).

CONCLUSIONS:

Basiliximab does not increase the effect of corticosteroids in the induction of remission in outpatients with corticosteroid-resistant moderate to severe UC.

• Authors: Bruce E Sands, William J Sandborn, Tom J Creed, Colin M Dayan, Ashwin D Dhanda, Gert A Van Assche, Miloš Greguš, Ajit Sood, Gourdas Choudhuri, Mary Jean Stempien, Daniel Levitt, Christopher S Probert
• Journal: Gastroenterology (Gastroenterology) Vol. 143 Issue 2 Pg. 356-64.e1 (Aug 2012) ISSN: 1528-0012 [Electronic] United States
• PMID: 22549092 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Glucocorticoids
• Immunosuppressive Agents
• Recombinant Fusion Proteins
• Basiliximab
• Prednisone

Topics

• Adolescent
• Adult
• Aged
• Antibodies, Monoclonal (pharmacokinetics, therapeutic use)
• Basiliximab
• Colitis, Ulcerative (drug therapy)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Administration Schedule
• Drug Therapy, Combination
• Female
• Glucocorticoids (therapeutic use)
• Humans
• Immunosuppressive Agents (pharmacokinetics, therapeutic use)
• Induction Chemotherapy
• Male
• Middle Aged
• Prednisone (therapeutic use)
• Recombinant Fusion Proteins (pharmacokinetics, therapeutic use)
• Severity of Illness Index
• Treatment Outcome
• Young Adult