Systematic Review and Meta-analysis: Adalimumab Monotherapy Versus Combination Therapy with Immunomodulators for Induction and Maintenance of Remission and Response in Patients with Crohn's Disease.

Abstract

It is unclear whether the combination of adalimumab (ADA) and immunomodulators is superior to ADA monotherapy in patients with Crohn's disease. PubMed, Medline, Embase, Web of Science, and other databases were searched. Randomized controlled trials, open-label, prospective cohort, and retrospective studies, and pooled analyses were included. Primary outcomes were induction (≤12 wk) and maintenance (up to 56 wk) of remission and response. Secondary outcomes were severe adverse events, opportunistic infections, and development of antibodies to adalimumab. Twenty-four of 1194 articles were eligible for inclusion. No significant difference was noted between regimens for induction of remission (odds ratio [OR] 0.86; 95% confidence interval [CI]: 0.70-1.06; P = 0.19) and response (OR 1.01; 95% CI: 0.62-1.65; P = 0.96). Similarly, no difference was noted for maintenance of remission (OR 0.97; 95% CI: 0.79-1.14; P = 0.75) or response (OR 0.91; 95% CI: 0.54-1.54; P = 0.74). Severe adverse events and opportunistic infections were not different between arms. Patients on combination therapy had lower odds of developing antibodies to adalimumab (OR 0.24; 95% CI: 0.07-0.82; P = 0.02). Subgroup and sensitivity analyses showed significantly higher odds of successful induction (OR 1.26; 95% CI: 1.06-1.49, P = 0.008) and opportunistic infections (OR 2.44; 95% CI: 1.07-5.54, P = 0.03) in anti-TNF-experienced patients. The combination of ADA and immunomodulators does not seem superior to ADA monotherapy for induction and maintenance of remission and response in Crohn's disease. Combination therapy is associated with lower immunogenicity. Analyses associating combination therapy with better induction of remission in anti-TNF-experienced patients and a higher rate of opportunistic infections deserve further evaluation.