Patients with active psoriatic arthritis are better off with monotherapy with ustekinumab compared with the combination of methotrexate and ustekinumab. The combination causes more side effects and does not enhance efficacy or quality of life in these patients.


Research shows that biologics like TNF inhibitors or cytokine blockers are the most effective agents in treating active psoriatic arthritis (PsA). However, in most countries, biologics can only be prescribed in patients not responding to previous conventional therapy with DMARDs. Methotrexate is often used as a first-line agent in these patients. “The value of methotrexate together with biologic DMARDs is still unclear,” said Dr. Michaela Köhm (Goethe-University Frankfurt, Germany). Therefore, Dr. Köhm and her team designed an investigator-initiated, randomized, placebo-controlled trial in active PsA to examine if treatment outcomes with ustekinumab in combination with methotrexate (either newly initiated or ongoing) differ from ustekinumab monotherapy.1

In total, 173 patients with active PsA were randomized to ustekinumab with methotrexate or ustekinumab with placebo. Baseline data were well balanced between treatment groups. Differences were only seen in dactylitis (24.1% vs 19.0%), body surface area (BSA; 2.9% vs 1.0%), and quality of life, assessed in the Dermatology Life Quality Index (8.6 vs 6.9).

At week 24, the mean DAS28-ESR disease activity score decreased by 1.7 points for both the combination and for ustekinumab plus placebo groups. Changes in other outcomes at week 24 were also similar between groups. Effect of initiation or withdrawal of methotrexate on ustekinumab efficacy was also explored in subgroups of patients who were treatment-naïve or pre-treated with methotrexate, respectively. Again, methotrexate had no significant impact.

Patients who received methotrexate together with ustekinumab experienced 18% more adverse events and the only two serious infections documented in this study.

The authors concluded that ustekinumab is an effective treatment for active PsA, independent of methotrexate use. As the latter has no positive impact on efficacy for arthritis, enthesitis, dactylitis, skin, quality of life, and function, there is no evidence to either add methotrexate or maintain ongoing methotrexate when starting ustekinumab.


  1. Köhm M, et al. Neither add-on nor withdrawal of methotrexate impacts efficacy of IL12/23 inhibition in active PsA: data from a multicenter investigator-initiated randomized placebo-controlled clinical trial on arthritis, dactylitis, enthesitis, psoriasis, QoL and function. Abstract L12. ACR Convergence 2021, 3– November.

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