Effects of Concomitant Immunomodulator Therapy on Efficacy and Safety of Anti-Tumor Necrosis Factor Therapy for Crohn's Disease: A Meta-analysis of Placebo-controlled Trials.

Abstract

BACKGROUND & AIMS:

There is debate over whether patients with Crohn's disease who start anti-tumor necrosis factor (TNF) therapy after failed immunomodulator therapy should continue to receive concomitant immunomodulators. We conducted a meta-analysis of subgroups from randomized controlled trials (RCTs) of anti-TNF agents to compare the efficacy and safety of concomitant immunomodulator therapy vs anti-TNF monotherapy.

METHODS:

We performed a systematic review of literature published from 1980 through 2008 and identified 11 RCTs of anti-TNF agents in patients with luminal or fistulizing Crohn's disease. We excluded RCTs of patients who were naive to anti-TNF and immunomodulator therapy. The primary end points were clinical response at weeks 4-14 and 24-30 and remission at weeks 24-30. Secondary end points included infusion site or injection site reactions and selected adverse events. A priori subgroup analyses were performed to evaluate fistula closure and the efficacy and safety of combination therapy with different anti-TNF agents.

RESULTS:

Overall, combination therapy was no more effective than monotherapy in inducing 6-month remission (odds ratio [OR], 1.02; 95% confidence interval [CI], 0.80-1.31), inducing a response (OR, 1.08; 95% CI, 0.79-1.48), maintaining a response (OR, 1.53; 95% CI, 0.67-3.49), or inducing partial (OR, 1.25; 95% CI, 0.84-1.88) or complete fistula closure (OR, 1.10; 95% CI, 0.68-1.78). In subgroup analyses of individual anti-TNF agents, combination therapy was not more effective than monotherapy in inducing 6-month remission in those treated with infliximab (OR, 1.73; 95% CI, 0.97-3.07), adalimumab (OR, 0.88; 95% CI, 0.58-1.35), or certolizumab (OR, 0.93; 95% CI, 0.65-1.34). Overall, combination therapy was not associated with an increase in adverse events, but inclusion of infliximab was associated with fewer injection site reactions (OR, 0.46; 95% CI, 0.26-0.79.)

CONCLUSIONS:

On the basis of a meta-analysis, continued use of immunomodulator therapy after starting anti-TNF therapy is no more effective than anti-TNF monotherapy in inducing or maintaining response or remission. RCTs are needed to adequately assess the efficacy of continued immunomodulator therapy after anti-TNF therapy is initiated.

• Authors: Jennifer L Jones, Gilaad G Kaplan, Laurent Peyrin-Biroulet, Leonard Baidoo, Shane Devlin, Gil Y Melmed, Divine Tanyingoh, Laura Raffals, Peter Irving, Patricia Kozuch, Miles Sparrow, Fernando Velayos, Brian Bressler, Adam Cheifetz, Jean-Frederic Colombel, Corey A Siegel
• Journal: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (Clin Gastroenterol Hepatol) Vol. 13 Issue 13 Pg. 2233-40.e1-2; quiz e177-8 (Dec 2015) ISSN: 1542-7714 [Electronic] United States
• PMID: 26142167 (Publication Type: Journal Article, Meta-Analysis, Review, Systematic Review)
• Copyright: Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Chemical References

• Immunologic Factors
• Placebos
• Tumor Necrosis Factor-alpha

Topics

• Crohn Disease (drug therapy)
• Drug Therapy, Combination (adverse effects, methods)
• Drug-Related Side Effects and Adverse Reactions (epidemiology, pathology)
• Humans
• Immunologic Factors (administration & dosage, adverse effects)
• Placebos (administration & dosage)
• Randomized Controlled Trials as Topic
• Treatment Outcome
• Tumor Necrosis Factor-alpha (antagonists & inhibitors)