Role of methotrexate in biologics use with psoriasis and psoriatic arthritis

Biologic agents have significantly improved treatment outcomes for psoriasis and psoriatic arthritis (PsA). However, their long-term effectiveness can decline due to the formation of anti-drug antibodies. The off-label addition of methotrexate (MTX) to biologics offers benefits through synergistic antipsoriatic effects and reduced immunogenicity, primarily by increasing extracellular adenosine levels and inducing the anergy state of T and B cells. In patients with psoriasis, the addition of MTX has been shown to improve the efficacy of tumor necrosis factor-α inhibitors, although controlled data on its combination with interleukin (IL)-17 or IL-23 inhibitors are limited. In PsA, however, combination therapy with MTX provides little to no additional efficacy compared to biologic monotherapy.