Methotrexate Usage Comparable Between Patients With PsA, RA

Data from a Swedish clinical practice showed methotrexate use is similar in patients with psoriatic arthritis (PsA) and rheumatoid arthritis (RA), regarding methotrexate retention as well as initiation of other disease-modifying antirheumatic drugs (DMARDs), according to a study published in Rheumatic and Musculoskeletal Diseases.¹ Disease activity improved during methotrexate monotherapy in both conditions on a group level; however, it improved more in the RA cohort.

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Ten years ago, a large, randomized controlled trial (RCT) failed to prove any statistically significant benefit over placebo regarding the use of methotrexate in PsA. Additionally, a RCT published in 2019 (SEAM-PsA) suggested that etanercept was superior to methotrexate, and combining medications demonstrated no additional benefits over etanercept monotherapy. Therefore, the American College of Rheumatology (ACR) guidelines suggest tumor necrosis factor inhibitors (TNF), instead of methotrexate, as first-line DMARDs in treating patients with PsA.²

However, methotrexate is recommended as the first-line DMARD for patients with PsA with peripheral arthritis by the European alliance of associations for rheumatology (EULAR).³

“Since there are no further ongoing placebo-controlled trials of methotrexate in PsA, and in light of the diverging opinions regarding its effectiveness, in the current work, we aimed to revisit the questions of retention (a commonly used surrogate measure of treatment efficacy in observational studies) and response to methotrexate monotherapy in PsA, when used in clinical practice,” wrote Ulf Lindström, MD, PhD, Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Sweden, and a group of Swedish investigators.

Investigators compared proportions of patients with newly diagnosed PsA and RA remaining on methotrexate, regardless of other DMARD-changes, and the proportions of patients not having started another DMARD, within 2 years of initiating methotrexate. Patients with PsA who were DMARD-naïve and initiating methotrexate between 2011 and 2019 were identified from high-quality national Swedish registers and matched 1:1 to comparable patients with RA.

Proportions of patients remaining on methotrexate who did not start another DMARD were calculated. The response to methotrexate monotherapy was compared through logistic regression for patients with disease activity data at baseline and 6 months, applying non-responder imputation.

In total, 3641 patients with PsA and 3642 patients with RA were included in the study. Although baseline patient-reported pain and global health were comparable, patients with RA had higher 28-joint scores and evaluator-assessed disease activity. At the 2-year mark after methotrexate initiation, 71% of patients with PsA and 76% of patients with RA remained on methotrexate. Further, 66% vs 60% had not started any other DMARD and 77 vs 74% had not started a biologic or targeted synthetic DMARD (PsA vs RA, respectively).

At the 6-month mark, the proportions of patients with PsA compared with RA who achieved pain-scores ≤15 mm were 26% vs 36, global health ≤20 mm were 32% vs 42%, and evaluator-assessed “remission” was 20% vs 27%, respectively.

Investigators noted that the large, nationwide study using prospectively collected, contemporary, real-world data strengthened the study. Additionally, the matched study design was able to compare PsA with RA, a condition in which methotrexate efficacy is well documented.

However, the registers contained limited data on PsA-features excluding joint disease, making comparisons to other studies more difficult. Additionally, the lack of control group hindered comparisons. The prescription data available did not allow for a reliable evaluation of the effect of different methotrexate doses and investigators were not able to ascertain whether methotrexate was prescribed primarily for PsA instead of cutaneous psoriasis, which may have introduced a bias.

“The current observational results support that methotrexate can be an effective treatment in PsA, although not as effective as in RA, and as such should continue to have a place in the treatment algorithm of PsA,” investigators concluded.

References

1. ^{Lindström U, di Giuseppe D, Exarchou S, et al. Methotrexate treatment in early psoriatic arthritis in comparison to rheumatoid arthritis: an observational nationwide study. RMD Open. 2023;9(2):e002883. doi:10.1136/rmdopen-2022-002883}
2. ^{Singh JA , Guyatt G , Ogdie A , et al . 2018 American College of rheumatology/national psoriasis Foundation guideline for the treatment of psoriatic arthritis. Arthritis Rheumatol 2019;71:5–32. doi:10.1002/art.40726 Available: https://onlinelibrary.wiley.com/toc/23265205/71/1}
3. ^{Gossec L , Baraliakos X , Kerschbaumer A , et al . EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2019 update. Ann Rheum Dis 2020;79:700. doi:10.1136/annrheumdis-2020-217159}