TNF Inhibitors + Immunosuppressants Reduce Anti-Drug Antibody Formation

SAN DIEGO, CA—According to data from a meta-analysis, concomitant immunosuppressants given with the studied TNF-inhibitors reduced the effect of anti-drug antibodies, as presented at the 2013 ACR/ARHP Annual Meeting.

Tumor necrosis factor (TNF) inhibitors are a mainstay in the treatment of rheumatoid arthritis (RA), as well as in the management of spondyloarthritis (SpA) and inflammatory bowel disease (IBD). However, “a significant portion of patients taking these drugs require escalating doses to achieve response, while others lose response altogether,” explained Sarah Thomas, MD, from the Division of Rheumatology at David Geffen School of Medicine at UCLA, Los Angeles, CA. This response may be due to the development of antibodies against TNF inhibitors.

Dr. Thomas and her team set out to examine the immunogenicity of 5 TNF inhibitors: adalimumab, infliximab, etanercept, golimumab, and certolizumab pegol in RA, SpA, and IBD. The team also examined the potential effect of anti-drug antibodies on the loss of clinical rezones through a systematic literature review and meta-analysis.

PubMed, Web of Science, and the Cochrane Library were utilized for the comprehensive literature search to identify studies examining the immunogenicity of TNF inhibitors in autoimmune diseases between January 1966 and December 1, 2012.

A total of 10,227 patients across 51 studies were examined. In general, anti-drug antibodies were detected in 17% of the patients (95% CI [0.13–0.22]). Anti-drug antibodies development was seen for all 5 TNF inhibitors: 30% of patients taking infliximab (95% CI [0.23–0.37]); 23% of patients taking adalimumab (95% CI [0.17–0.28]); 4% of patients taking golimumab (95% CI [0.01–0.07]); 2% of patients taking etanercept (95% CI [0.06–0.09]); and 6% of patients taking certolizumab pegol (95% CI [0.02–0.11]).

The use of concomitant immunosuppressants (eg, methotrexate, 6-mercaptopurine, azathioprine, others) reduced anti-drug antibodies formation in all patients by 30% [RR 0.70, 95% CI [0.62–0.79]). Anti-drug antibodies reduced overall clinical response by 50%, researchers added.

“Concomitant immunosuppressants reduced anti-drug antibodies, which are associated with a reduced clinical response,” noted Dr. Thomas.