Reversal of anti-drug antibodies against tumor necrosis factor inhibitors with addition of immunomodulators: A systematic review and meta-analysis.

Abstract

The development of anti-drug antibodies (ADA) to tumor necrosis factor (TNF-α) inhibitors is a significant result contributing to the loss of clinical response in inflammatory bowel disease (IBD). We performed a systematic review and meta-analysis to assess whether the addition of immunomodulators to TNF-α inhibitors lead to reversal of antibody formation in TNF-α inhibitor-treated IBD patients. We conducted a comprehensive search of electronic databases from inception through October 2018 in order to identify specific studies describing clinical response in IBD patients following the addition of immunomodulators (methotrexate or thiopurines) to TNF-α inhibitors. Clinical response was expressed as an improvement of symptoms, with a noted decrease or complete elimination of ADA against TNF-α inhibitors. The meta-analysis was performed using the DerSimonian and Laird random-effect model. Four studies were included in our final meta-analysis, which reported outcomes in 72 patients receiving TNF-α inhibitors. Forty-nine of the seventy-two (68%) patients received either methotrexate (19) or thiopurines (30). The average follow up period was 13.5months. The overall pooled clinical response was 73.86% (95% confidence interval [CI] = 47.36-94.38, I2= 60.77%). In our meta-analysis, addition of immunomodulators to TNF-α inhibitors was shown to restore the clinical response in 74% of the patients by either decreasing or completely eliminating anti-drug antibody levels. Further long-term multicenter studies are needed to validate these findings.