Abstract

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.

Highlights

  • TNF-a inhibitors have transformed the treatment paradigm of autoimmune diseases such as RA, psoriasis, PsA, AS and IBD, where standard systemic agents have failed

  • A recent meta-analysis revealed that the use of immunosuppressants, primarily MTX, reduced the proportion of patients on infliximab and adalimumab with detectable anti-drug antibodies (ADAbs) by about 41% (RR = 0.59, 95% CI 0.50, 0.70) [60]

  • The mechanism whereby MTX acts on the immune response has not been fully demonstrated, suppression of early T and B cell expansion may be responsible for modulation of the immune response [61]

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Summary

Introduction

TNF-a inhibitors (anti-TNFs) have transformed the treatment paradigm of autoimmune diseases such as RA, psoriasis, PsA, AS and IBD, where standard systemic agents have failed. The development of antibodies was inversely associated with infliximab dose (53%, 21% and 7% in patients receiving 1, 3 and 10 mg/kg monotherapy, respectively), and the use of concomitant MTX at a dose of 7.5 mg/week greatly diminished the appearance of ADAbs, with incidence rates of 15%, 7% and 0% at the three dose levels.

Results
Conclusion
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