A new analysis of the use of methotrexate in people with psoriatic disease indicates that although men were more likely than women to continue the drug for psoriatic arthritis (PsA), they were less likely to keep taking it for psoriasis.

“Sex-specific medicine is often about females, which is of course very important given the current knowledge gaps there are, but actually it’s not about choosing sides; it’s about improving care for everyone, and in some cases, this means that we should not forget the [men],” said author Liana Barenbrug, MSc, PhD candidate in dermatology at Radboud University Medical Center in Nijmegen, Netherlands. She presented the research at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2026 Annual Meeting and Trainee Symposium in Lisbon, Portugal.

Sex Differences Between PsA and Psoriasis

PsA and psoriasis reportedly affect men and women more or less equally, although there are known differences in terms of disease presentation, severity of disease, and response to treatment. With regard to the latter, the duration that women remain on treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) is lower than that for men, and it is unclear whether this could also be true for methotrexate.

“Given that methotrexate is still being widely used as a first-line treatment option in these diseases, it is important to gain more insights into the potential sex differences,” Barenbrug said.

Gaining Real-World Insights

To gain real-world insight into methotrexate response between the sexes, Barenbrug and associates obtained clinical data from patients with psoriasis or PsA treated with methotrexate monotherapy who had been enrolled into two prospective registries.

They analyzed data from 525 patients with PsA (50% women) in the Dutch southwest Early Psoriatic Arthritis Registry and 217 patients with psoriasis (41% women) in the Continuous Assessment of Psoriasis Treatment Use Registry with Methotrexate.

There were a couple of notable points regarding baseline characteristics. The first was that patients with PsA tended to start methotrexate treatment much sooner than those with psoriasis, at 0.04 vs 13.9 years, respectively.

The team had assessed only whether bDMARDs had been used previously and had not assessed the use of other medications. Prior bDMARD use was not reported in the PsA cohort, and because very few patients in the psoriasis cohort had previously used bDMARDs, the researchers did not adjust for this in the confounder-adjusted analyses.

The second was that disease activity — measured using the Psoriasis Area and Severity Index (PASI) for psoriasis and the Psoriatic Arthritis Disease Activity Score (PASDAS) for PsA — was similar among men and women. The respective PASI scores were 6.9 and 7.8, and PASDAS scores were 4.3 and 4.4.

Main Findings

“[For] our main outcome, which was the drug survival analysis, we found for the PsA cohort that the [women] had a worse drug survival, which was comparable with the previous studies for the biological DMARDs,” Barenbrug said in reporting the study’s findings. “However, in the psoriasis cohort, we found that this pattern was reversed and that the [men] had worse outcomes.”

Using male sex as the reference, the adjusted hazard ratio for drug survival in women in the PsA cohort was 2.5 (95% CI, 1.6-4.1; P < .001) and 0.6 (95% CI, 0.4-0.9; P = .008) in the psoriasis cohort.

Reasons for methotrexate discontinuation were adverse events, ineffectiveness, remission, death, family planning or pregnancy, or “other,” Barenbrug later told Medscape Medical News.

The same pattern was seen when looking specifically at discontinuation due to ineffectiveness, with women stopping treatment earlier than men in the PsA cohort but not in the psoriasis cohort.

Methotrexate discontinuation due to adverse events occurred at a similar rate in men and women in the psoriasis cohort, but women in the PsA cohort discontinued the drug for this reason earlier than men.

Barenbrug said that the study was not set up to look for predictors of methotrexate discontinuation, and because the research is currently undergoing review for publication, no data could be given on the number of people who discontinued treatment.

No data on the actual doses of methotrexate used could be shared. The methotrexate dose used was comparable between the sexes, although it was higher in those with PsA than in those with psoriasis overall while being actively treated. The dose at the moment of discontinuation was comparable between the PsA cohort and the psoriasis cohort and comparable between the sexes in both cohorts.

At the time of methotrexate discontinuation, disease activity according to the PASDAS was higher in women than in men in the PsA cohort, but men in the psoriasis cohort had higher disease activity than women as measured by the PASI.

Lively Discussion

Rheumatologist and professor of medicine at the University of California, San Diego, Arthur Kavanaugh, MD, who was in the audience, commented: “One difference between methotrexate and other agents is the potential effect on reproductive health.” Had the researchers been able “to capture that as a possible contributor to the discontinuation among the female patients?” he questioned.

Barenbrug noted that only three women had discontinued methotrexate for reasons related to family planning or pregnancy. “We also thought that that would be an effect on discontinuation, but apparently not that much,” she said.

Epidemiologist Susanne Gulliver, MPH, Newlab Clinical Research, St. John’s, Newfoundland and Labrador, Canada, interjected that “the reason a lot of the women may not have discontinued due to reproductive reasons is because they weren’t put on [methotrexate] in the first place.”

In the US, “if you are of childbearing potential, you get to skip methotrexate with a lot of payors, so that may not have been captured at all because they were just never exposed.”

Gulliver also suggested that the reason why women with psoriasis may have done better than men in terms of remaining on the drug could have been because of poor adherence in men, who may decide to stop methotrexate when their psoriasis clears but then go on to have a disease flare.

Rheumatologist Walter P. Maksymowych, MD, professor of medicine at the University of Alberta in Edmonton, Alberta, Canada, added his thoughts: “Could the difference in [methotrexate discontinuation and disease activity among men and women with] PsA reflect nociplastic pain in women?”

Maksymowych added: “So, when you say that they have comparable disease activity, was that reflecting tender joints, or were you also seeing comparable measures for swollen joints, CRP [C-reactive protein], etc? I always wonder about nociplastic pain in women when I see this kind of data.”

Barenbrug later responded to Medscape Medical News that disease activity had been measured using the PASDAS or PASI. These were outcome measures that were calculated on the basis of different subscores assessed either by a physician or by the patient.

“At methotrexate initiation, the objective measures were comparable between males and females, but the patient-reported outcomes were worse for females. At methotrexate discontinuation, some objective measures were also worse in females,” she explained. “We do not have any data on nociplastic pain specifically.”

The analysis had no commercial funding. No relevant conflicts of interest were declared by Barenbrug or any of the commentators. 

Sara Freeman, BSc, MSc, is a freelance medical journalist based in London, England. She has been reporting for specialist healthcare news organizations for more than 20 years.