The role of DMARDs in reducing the immunogenicity of TNF inhibitors in chronic inflammatory diseases

Rheumatology (Oxford). 2014 Feb;53(2):213-22. doi: 10.1093/rheumatology/ket260. Epub 2013 Aug 14.


The management of RA, SpA, psoriasis and inflammatory bowel disease has significantly improved over the last decade with the addition of tumour necrosis factor inhibitors (anti-TNFs) to the therapeutic armamentarium. Immunogenicity in response to monoclonal antibody therapies (anti-drug antibodies) may give rise to low serum drug levels, loss of therapeutic response, poor drug survival and/or adverse events such as infusion reactions. To combat these, the use of concomitant MTX may attenuate the frequency of anti-drug antibodies in RA, SpA and Crohn's disease. Although a similar effect to methotrexate has been observed with AZA usage in the management of Crohn's disease, there is insufficient evidence to suggest that other DMARDs impact immunogenicity. In this article we review the evidence to date on the effect of immunomodulatory therapy when co-administered with anti-TNFs. We also discuss whether such a strategy should be employed in SpA and psoriasis, and if optimization of the MTX dose could improve biologic drug survival and thereby benefit disease management.

Keywords: anti-TNFs; anti-drug antibodies; azathioprine; biologics; disease-modifying anti-rheumatic drugs; immunogenicity; methotrexate.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / immunology
  • Biological Products / therapeutic use*
  • Humans
  • Immunomodulation
  • Inflammation / drug therapy*
  • Inflammation / genetics
  • Inflammation / immunology
  • Inflammatory Bowel Diseases / drug therapy
  • Inflammatory Bowel Diseases / genetics
  • Inflammatory Bowel Diseases / immunology
  • Methotrexate / therapeutic use
  • Spondylitis, Ankylosing / drug therapy
  • Spondylitis, Ankylosing / genetics
  • Spondylitis, Ankylosing / immunology
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Antirheumatic Agents
  • Biological Products
  • Tumor Necrosis Factor-alpha
  • Methotrexate