Limited success of first-line methotrexate in real-world psoriatic arthritis study
medwireNews: Less than a fifth of patients with newly diagnosed psoriatic arthritis (PsA) who start treatment with methotrexate monotherapy in routine clinical practice have minimal disease activity (MDA) after 1 year, researchers report.
“Our results indicate the need for more treat-to-target and personalised therapy strategies in PsA,” say Marc Kok (Maasstad Hospital, Rotterdam, the Netherlands) and study co-authors.
The team used the DEPAR registry to evaluate the outcomes of PsA patients with oligoarthritis or polyarthritis who had data recorded between 2013 and 2018. Of a total of 219 patients, 84% commenced methotrexate monotherapy within 6 months of PsA diagnosis.
Among these 183 methotrexate-treated patients, 90 (49%) continued on methotrexate monotherapy until 12 months after diagnosis, while 25% had another DMARD added, 13% used methotrexate intermittently, and 14% switched to another DMARD.
At the 12-month follow-up, just 33 patients treated with methotrexate monotherapy had MDA, defined as meeting at least five out of seven remission criteria (swollen joint count ≤1, tender joint count ≤1, Leeds Enthesitis Index ≤1, PASI ≤1, patient global VAS ≤20 mm, patient pain VAS ≤15 mm, and HAQ ≤0.5). This represented 18% of the total number of patients initiating methotrexate.
Kok and colleagues categorized patients into methotrexate nonresponders (those who switched or added another DMARD after 3 months or had high disease activity at 6 months) and responders (those with low disease activity at 6 and 12 months) to evaluate potential predictors of methotrexate success. They found that nonresponders had significantly higher baseline serum levels ofinterleukin (IL)-23, tumor necrosis factor-α, interferon-γ, granulocyte–macrophage colony-stimulating factor, and IL-10 than responders.
Moreover, in a marginal model analysis, IL-23 and IL-10 concentrations over 6 months remained significant predictors of methotrexate response, and the researchers say that IL-23 was found to be “the best cytokine to differentiate between responders and nonresponders to [methotrexate].”
Patients who did not respond to methotrexate also had significantly higher tender joint count, pain VAS, global VAS, and HAQ scores, but lower enthesitis scores, compared with responders.
Together, these results suggest “that IL-23 serum levels can both objectively reflect patient-reported measures and [methotrexate] response, making it an interesting therapy-response biomarker,” write the study authors in RMD Open.
They say that their findings highlight “the potential value of use of new tools, such as measuring cytokine profiles, to stratify patients for underlying driving pathogenic mechanisms of their disease,” which “rheumatologists can use […] to personalise therapy choices.”
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