Etanercept and methotrexate as first-line treatment in PsA

There is conclusive evidence from the phase 3 SEAM-PsA trial that both etanercept and combined treatment of etanercept and methotrexate are more efficacious than methotrexate monotherapy in patients with psoriatic arthritis (PsA) naïve to biologic drugs. Combining etanercept and methotrexate offers little benefit over etanercept monotherapy. Compared with the joint-focused DAPSA, PASDAS captured a wider range of PsA manifestations and performed better in this trial [1].

The benefits of methotrexate alone and in combination with tumour necrosis factor inhibitor (TNFi) therapy have been demonstrated in RA, but the same cannot be said for PsA. Studies of methotrexate monotherapy in PsA have been largely mixed [2]. “How do we optimally use methotrexate in combination with TNFi therapy in PsA patients naïve to biologics,” asked Prof. Philip Mease (University of Washington, USA). “There has been very little trial data looking at methotrexate in PsA, and we thought of it as a relatively ineffective agent in PsA,” he said.

Therefore, Prof. Mease and his team aimed to examine the efficacy of methotrexate monotherapy relative to etanercept monotherapy, and the value of combining methotrexate and etanercept in patients with PsA. In addition, the relative performance of PsA-specific composite measures was assessed by using trial efficacy data. The 24-week randomised, double-blind, placebo-controlled SEAM-PsA trial included 851 biologic-naïve patients with active PsA. In addition, they had not received prior methotrexate treatment. Patients were randomised (1:1:1) to weekly treatment comprising oral methotrexate 20 mg plus placebo, etanercept 50 mg plus placebo, or etanercept 50 mg plus oral methotrexate 20 mg (combination therapy). Baseline data were balanced in the 3 arms. The mean age was about 48 years and mean PsA duration 3.2 years.

While acceptable results were obtained with methotrexate monotherapy, etanercept monotherapy showed superiority in terms of ACR20 response and minimal disease activity response at week 24, with rates of 60.9 vs 50.7% (P=0.029) and 35.9 vs 22.9% (P=0.005), respectively. The corresponding rates for combination therapy compared with methotrexate monotherapy were 65.0 vs 50.7% (P=0.005) and 35.7 vs 22.9% (P=0.005). PASDAS also showed differences between each etanercept containing arm vs methotrexate alone and no difference for etanercept mono- vs combination therapy, whereas study arm differences were not seen with DAPSA. PASDAS had a greater effect size and standardised response than DAPSA. “In terms of safety, the main difference was nausea in the methotrexate-treated patients as compared with the etanercept-treated patients,” added Prof. Mease.

1. Mease P, et al. Abstract OP0111. EULAR 2019
2. Merola JF, Ogdie A. Arthritis Rheumatol. 2019 Jul;71(7):1027-1029.

Posted on 4 September 201916 February 2024