Methotrexate Use Linked to Lower Infection Risk in Early RA

TOPLINE:

In patients with early rheumatoid arthritis (RA), methotrexate-based strategies were associated with a lower risk for serious infections compared with strategies using other conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Increasing age, smoking, and comorbidities were identified as important predictors of an increased risk for serious infections.

METHODOLOGY:

• Researchers conducted an observational cohort study to assess the risk for serious infections among patients with early RA on the basis of prescribed treatment strategies.
• They used audit data of 17,472 adults with newly diagnosed RA (mean age, 59 years; 63% women) in England and Wales between May 2018 and April 2023.
• At 3 months, 63% of patients had initiated methotrexate-based therapy (either as monotherapy or in combination with another csDMARD), 26% had initiated other csDMARDs, and 11% had delayed initiating csDMARDs. Additionally, 79% were on concomitant corticosteroids as part of the initial treatment regimen.
• The primary outcome was a serious infection event, defined as an infection requiring hospitalization or resulting in death, assessed over a mean follow-up duration of 2.62 years.

TAKEAWAY:

• The overall incidence rate of serious infections was 3.02 per 100 person-years; 41% of these infections were respiratory infections, followed by COVID (15%) and sepsis/bacteraemia (12%).
• Patients on methotrexate regimens had a 24% lower risk for serious infections than those on other csDMARDs (adjusted hazard ratio, 0.76; P < .001).
• Factors associated with an increased risk for serious infections included increasing age, current or past smoking, comorbidities (diabetes, lung disease, and hypertension), seropositivity for rheumatoid factor, and higher baseline disease severity (P < .01 for all).
• Patients who did not initiate csDMARDs at diagnosis had a higher incidence rate of serious infections than those who initiated csDMARDs.

IN PRACTICE:

“Channelling bias due to residual confounding is likely part of this explanation, but our data still suggest that avoidance of methotrexate because of concerns surrounding serious infection risk are not strongly supported by evidence,” the authors wrote.

SOURCE:

This study was led by Maryam A. Adas, Centre for Rheumatic Disease, King’s College London, London, England. It was published online on June 5, 2025, in Rheumatology.

LIMITATIONS:

Data on treatment with csDMARDs were available only at diagnosis and up to 3 months, preventing assessment of subsequent drug transitions or continuations. Certain confounding factors, such as the type or severity of lung disease, were not captured. Data on treatment adherence, steroid dosing, and the route of treatment administration were unavailable.

DISCLOSURES:

This study received no specific funding. One author reported receiving consulting fees and research grant income from pharmaceutical companies, including UCB and BMS. Several other authors reported receiving honoraria or speaker fees, holding positions, or having other financial ties with multiple companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.