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DOP074. Adalimumab monotherapy versus combination therapy with adalimumab and immunomodulators for Crohn's disease: A meta-analysis

U. Kopylov1, T. Al-Taweel1, M. Yaghoobi2, W. Afif3, A. Bitton1, P.L. Lakatos4, S. Ben-Horin5, E.G. Seidman1, 1McGill University Health Center, Gastroenterology, Montreal, Canada, 2Medical University of South Carolina, Gastroenterology, Charleston, SC, United States, 3McGill University, Division of Gastroenterology, Montreal Quebec, Canada, 4Summelweis University, Gastroenterology, Budapest, Hungary, 5Sheba Medical Center, Gastroenterology, Ramat Gan, Israel

Background

Combination therapy with infliximab and azathioprine was shown to be superior to either treatment alone in Crohn's disease (CD) by the SONIC trial. However, the benefit of combining adalimumab with an immunomodulator in CD remains controversial, as no clinical trial has been performed to directly assess these two strategies. In this study we performed a meta-analysis comparing the efficacy of adalimumab monotherapy with an immunomodulator for induction and maintenance of response and remission in CD.

Methods

An extensive search of the PubMed and Embase was performed by two independent reviewers. All published prospective controlled, retrospective cohort, case–controlled studies, as well as abstracts presented at major gastroenterology conferences were included. The search was not restricted by language. Bibliographies of the included publications were also manually searched for relevant publications. Authors were contacted to obtain missing data. The primary outcomes included induction of response and remission (up to week 12), maintenance of clinical response and remission (week 52) and the need for dose escalation during follow-up. Random model Mantel–Haenszel meta-analysis was used. Q test and I2 were reported to assess heterogeneity. Funnel plot was used to assess publication bias. Several subgroup and sensitivity analyses were done to confirm the accuracy of the results.

Results

Twenty out of 2743 retrieved studies were included (6 of which were RCT). Meta-analysis of 7 studies assessing induction of remission (n = 1984) showed that ADA monotherapy was significantly inferior to combination therapy [OR = 0.78 (0.64–0.95), p = 0.01]. There was no significant heterogeneity (I2=0%, p = 0.59). Meta-analysis of 6 studies revealed that the combination therapy was not statistically different from ADA alone for clinical response rate [OR = 0.68 (0.37–1.25), p = 0.22]. Meta-analysis of 6 studies revealed that combination therapy was not statistically different from ADA for maintenance of remission [OR = 1.08 (0.87–1.33), p = 0.48] or for maintenance of response [3 studies, OR = 1.21 (0.74–1.99), p = 0.44]. Combination therapy was also not different from ADA therapy in terms of requirement for dose escalation [OR = 1.24 (0.70–2.20), p = 0.46].

Conclusion

Combination therapy with ADA and immunomodulators was slightly superior to monotherapy with ADA alone for induction of remission in CD. Response rate or maintenance of response was not significantly better with combination therapy. The need for dose escalation was not different in the two groups. These findings should be interpreted with caution in view of significant confounders (such as disease phenotype and severity) and merit further verification in a randomized controlled trial.