Immunogenicity of biologic treatments for psoriasis: therapeutic consequences and the potential value of concomitant methotrexate

Abstract

The five biologic agents approved for the treatment of psoriasis-etanercept, infliximab, adalimumab, ustekinumab, and secukinumab-have been transformative in the clinical management of severe forms of the disease. However, a significant number of patients fail to respond to these agents or experience a loss of efficacy over time, which may be attributable to the development of antidrug antibodies (ADAs). Increasing evidence, primarily in the context of rheumatoid arthritis or other chronic inflammatory diseases, suggests that concomitant administration of methotrexate may prevent or diminish the development of ADAs, thereby improving response rates. However, methotrexate is infrequently coadministered with biologic agents in patients with psoriasis, and the potential benefits of this strategy in the context of psoriasis are largely unexplored. In this review, we discuss clinical studies regarding the development and consequences of antibodies targeting biologic agents used in the treatment of psoriasis and present key findings describing the potential role of methotrexate as an inhibitor of immunogenicity. We also discuss clinical considerations pertaining to the use of methotrexate as a tool to reduce immunogenicity, and encourage further investigation into potential techniques to optimize this treatment approach in patients with psoriasis.