Neither add-on nor withdrawal of methotrexate impacts efficacy of IL12/IL23 inhibition in active PsA: Data from a multicenter investigator-initiated randomized placebo-controlled clinical trial on arthritis, dactylitis, enthesitis, psoriasis, QoL and function
Authors: Michaela Koehm al.
Methotrexate is often used as first-line csDMARD therapy in patients with active psoriatic arthritis. Clinical trials that evaluate bDMARDs or tsDMARDs usually include patients with failure to previous csDMARD therapy and often require continuation of MTX or other csDMARDs. This investigator-initated trial was designed to examine whether or not ustekinumab (UST) therapy benefits from ongoing or newly started MTX. 186 patients with active disease (TJC > 4, SJC > 4 out of 68/66 joint count) were randomized to UST + MTX (new or ongoing) versus UST+ Placebo. The primary endpoint was non-inferiority of UST monotherapy with regard to DAS28-ESR at week 24 versus combination with MTX. At week 24, mean DAS28-ESR decreased to 3.1 (+ 1.42) for UST + MTX versus 2.9 (+ 1.31) for UST + Placebo fulfilling the criterion of non-inferiority. Changes in other outcomes (enthesitis, dactylitis, skin, QoL, function) were similar between the two groups. In conclusion, based on this trial, there is no evidence to support addition or continuation of MTX when starting UST.
These data are interesting and demonstrate that trials add to our understanding of treat-ment optimization. They also show that simple extrapolation from RA (where, according to EULAR recommendations, MTX should be maintained in patients who tolerate it) is not necessarily the best option for PsA patients. Most importantly, the results did not only address arthritis, but also extend to dactylitis, enthesitis and skin manifestation.