Adalimumab Monotherapy Versus Combination Therapy with Immunomodulators in Patients with Crohn's Disease: A Systematic Review and Meta-Analysis

Background and aimsCombination therapy with infliximab and azathioprine has been shown to be superior to either treatment alone in Crohn's disease (CD). However, the benefit of combining adalimumab with an immunomodulator remains controversial.The aim of this study was to compare the efficacy of adalimumab monotherapy with combination therapy for induction and maintenance of response and remission in CD using a meta-analysis of the current literature.MethodsWe performed a systematic literature search using Medline, Embase, Cochrane and several other databases. Prospective randomized controlled trials, retrospective cohort and case-controlled studies were included. The primary outcomes included induction of response and remission (up to week 12), maintenance of clinical response and remission (1year) and the need for dose escalation. Several subgroup and sensitivity analyses were performed.ResultsEighteen out of 2743 retrieved studies were included. A meta-analysis of 7 studies assessing induction of remission (n=1984) showed that ADA monotherapy was inferior to combination therapy [OR=0.78 (0.64–0.96), p=0.02]. A meta-analysis of 4 studies revealed that combination therapy was not statistically different from ADA for maintenance of remission [OR=1.08 (0.79–1.48), p=0.48]. Combination therapy was also not different from ADA monotherapy in terms of requirement for dose escalation [OR=1.13 (0.69–1.85), p=0.62].ConclusionsCombination therapy with ADA and immunomodulator was mildly superior to ADA monotherapy for induction of remission in CD. The rate of remission at 1year and the need for dose escalation were similar in both groups. These findings should be interpreted with caution in view of possible confounders and should be further validated by randomized controlled trials.