Evaluating Methotrexate Monotherapy for Minimal Disease Activity Achievement in Early PsA

Researchers assessed the response to methotrexate monotherapy in newly diagnosed patients with psoriatic arthritis.

Methotrexate (MTX) monotherapy may be insufficient for achieving sustained minimal disease activity in patients with psoriatic arthritis (PsA), according to study data published in RMD Open. In a cohort of patients with PsA who were initiated with MTX, only 18% maintained minimal disease activity over 1 year of treatment. Methotrexate nonresponders vs responders were more likely to have interleukin (IL)-23-driven disease.

Investigators abstracted data from the Dutch Southwest Early Psoriatic Arthritis Cohort (DEPAR) study collected between 2013 and 2018. The DEPAR enrollees with oligoarthritis or polyarthritis who had ≥1 year of follow-up data were eligible for inclusion in the study. According to the DEPAR protocol, patients provided clinical data and blood samples before treatment initiation and every 3 months thereafter. Minimal disease activity was defined according to the following parameters: swollen and tender joint counts ≤1; Leeds Enthesitis Index ≤1; Psoriasis Area Severity Index ≤1; patient’s global assessment by visual analog scale (VAS) ≤20 mm; patient’s pain assessment by VAS ≤15 mm; and Health Assessment Questionnaire ≤0.5. Serum cytokine concentrations were determined at baseline, 3 months, and 6 months using a bead-based immunoassay.

The study cohort included 219 patients (50% men), with mean age at enrollment of 53±14 years. Overall, 183 patients (84%) were initiated with MTX monotherapy within 6 months of PsA diagnosis, of whom 49% remained on MTX monotherapy for 1 year. A total of 44 patients (24%) reached minimal disease activity at 6 months. At 1 year, 33 patients (18%) remained in minimal disease activity.

Compared with patients who had minimal disease activity at 1 year, patients who did not respond to treatment with MTX had higher mean baseline concentrations of IL-23 (17.44±4.78 vs 62.94±25.02), tumor necrosis factor (2.63±0.66 vs 7.83±2.79), granulocyte-macrophage colony-stimulating factor (2.78±0.64 vs 6.5±2.07), interferon gamma (6.67±1.29 vs 19.74±6.85), and IL-10 (1.03±0.13 vs 2.08±0.6; all P <.05). Concentrations of IL-10 and IL-23 remained significantly higher among nonresponders at 6 months.

In this observational care cohort of patients with PsA, only 18% who were initiated on MTX remained in minimal disease activity at 1 year. Higher baseline and follow-up concentrations of IL-23 and IL-10 were observed in nonresponders. Further study is necessary to confirm the validity of these biomarkers for MTX response.

Study limitations included potential confounding factors and the need to validate the use of serum IL-23 as a therapy-response biomarker. Overall, conclusions about the effect of MTX therapy must be drawn with caution.

“This study highlights the potential value of use of new tools, such as measuring cytokine profiles, to stratify patients for underlying driving pathogenic mechanisms of their disease,” the investigators concluded.


den Braanker H, Wervers K, Mus AMC, et al. Achieving sustained minimal disease activity with methotrexate in early interleukin 23-driven early psoriatic arthritis. RMD Open. 2020;6(2):e001175.