INTRODUCTION:
The presence of anti-drug antibodies (ADA) to tumor necrosis factor (TNF) inhibitors (infliximab or adalimumab) is one of the reasons for the diminished clinical response in patients with inflammatory bowel disease (IBD). To overcome the loss of response, dose escalation of TNF inhibitors or addition of immunomodulators (methotrexate or thiopurines) is considered before switching to other drugs due to limited therapeutic options. We conducted a systematic review and meta-analysis to assess the overall efficacy of immunomodulators (methotrexate or thiopurines) to reverse the loss of clinical response in IBD patients with TNF inhibitors antibodies.
METHODS:
We conducted a comprehensive search of multiple electronic databases and conference proceedings including PubMed, EMBASE, Web of Science databases, Google Scholar and manual search of references (from inception through October 2018) to identify studies that reported the clinical response in patients with IBD on TNF inhibitors after the addition of immunomodulators (methotrexate or thiopurines). Clinical response was defined as improvement of symptoms, with either decrease or complete elimination of ADA against TNF inhibitors. The meta-analysis was performed using Der Simonian and Laird random effect model.
RESULTS:
A total of 4 studies reporting on 72 patients receiving either infliximab (27) or adalimumab (45) were included in our final meta-analysis. 49/72 (68%) patients received either thiopurines (30) or methotrexate (19). Total no of males: females were 32: 40. The mean age and follow up were 37.1 years and 13.5 months respectively. The overall pooled clinical response (Table 1) was 73.86% (95% CI = 47.36-94.38, I2 = 60.77%). Significant heterogeneity was noted in the studies included in our meta-analysis.
CONCLUSION:
In our limited meta-analysis, addition of immunomodulators to TNF inhibitors were 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 further validate these findings
