Impact of NOD2/CARD15 polymorphisms on response to monoclonal antibody therapy in Crohn’s disease: a systematic review and meta-analysis

Abstract

Objective: Crohn’s disease (CD) is frequently treated with anti-tumor necrosis factor (TNF)α monoclonal antibodies, and NOD2/CARD15 polymorphisms have been reported to predict treatment response. The purpose of this study was to perform a meta-analysis to determine the effect of NOD2/CARD15 polymorphisms on treatment response in patients with CD.

Methods: Medline, Cochrane, EMBASE, and Google Scholar databases were searched until 19 December 2015 using the keywords: NOD2, CARD15, polymorphism, Crohn’s disease. Randomized controlled trials, prospective, retrospective, and cohort studies of patients with CD who received NOD2/CARD15 genetic analysis and were treated with monoclonal antibodies were included. The primary outcome was treatment response.

Results: Of 104 records identified, only four studies were relevant and included in the analysis. The four studies included 355 patients with CD, patient age ranged from 35 to 41 years, and the proportion of males ranged from 33% to 38%; however, only two studies reported age and sex data. Patients were treated with adalimumab and/or infliximab. Analysis revealed that NOD2/CARD15 mutations were not significantly associated with response to adalimumab or infliximab treatment (pooled odds ratio [OR] = 1.35, 95% confidence interval [CI]: 0.78 to 2.32, p = .278).

Conclusions: NOD2/CARD15 polymorphisms do not predict response to adalimumab and infliximab in patients with CD. However, the number of included studies was small and treatment protocols varied. Further studies are necessary to determine the role of NOD2/CARD15 polymorphisms in patients with CD.

Keywords:

• CARD14
• Crohn’s disease
• NOD2
• Monoclonal
• Polymorphism

Transparency

Declaration of funding

This study was supported by the National Natural Science Foundation of China [No. 81200260].

Declaration of financial relationship

X.W., L.Q., J.C., and J.Z. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article. CMRO peer reviewers on this study have no relevant financial or other relationships to disclose.