Early methotrexate course may prevent rheumatoid arthritis in some high-risk patients
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WASHINGTON — An early, 1-year course of methotrexate may prevent anti-citrullinated protein autoantibody-negative rheumatoid arthritis in high-risk patients with clinically suspect arthralgia, noted a presenter at ACR Convergence 2024.
“Patients with clinically suspect arthralgia (CSA) are at risk for rheumatoid arthritis,” Quirine Dumoulin, MD, of Leiden University Medical Centre, in the Netherlands, told attendees.
She added that patients with CSA and RA are similar because both experience arthralgia of the small joints and morning stiffness, among other symptoms. Consequently, patients with CSA may be optimal targets for RA prevention strategies.
“It is important to study high-risk patients separately from low-risk patients,” Dumoulin said, adding that part of the risk profile of a patient with CSA may include the presence of anti-citrullinated protein antibodies (ACPAs).
To assess the ability of methotrexate — administered in a 1-year course — to reduce RA development in patients with CSA who are ACPA-negative, following risk stratification, Dumoulin and colleagues analyzed data from the TREAT EARLIER study. The randomized, double-blind, controlled trial included 182 patients who were ACPA-negative and 54 who were ACPA-positive, all with CSA and subclinical joint inflammation. These participants were assigned in a 1:1 ratio to receive either a 1-year course of up to 25 mg per week of oral methotrexate or placebo. All patients additionally received a single, intramuscular glucocorticoid injection of 120 mg.
Included patients were stratified based on risk for RA, with low risk defined as a less than 25% predicted risk for disease development, increased risk set at 25% to 70%, and high risk defined as 70% or more. The researchers assessed the primary endpoint — RA development — after 4-years, with methotrexate efficacy determined per risk-group.
Among the ACPA-negative group, 36% were considered higher risk and 64% low risk.
Four-year follow-up results in the ACPA-negative, increased-risk group showed that 8.6% of patients on active therapy developed RA, compared with 29% in the placebo arm (HR = 0.27; 95% CI, 0.07-0.99).
“In ACPA-negative patients, we see a clear treatment effect,” Dumoulin said. “There may be some prevention in this group.”
In the ACPA-negative low-risk group, RA developed in 7.5% of patients on active therapy, compared with 9.5% of those who received placebo (HR = 0.79; 95% CI, 0.22-2.8). Similarly, no difference was observed in the ACPA-positive group, with 58.1% of patients treated with active therapy developing RA, vs. 52.2% of those in the placebo group (HR = 0.93; 95% CI, 0.45-1.93).
“The 4-year update of the TREAT EARLIER trial gives us an indication that a 1-year course of methotrexate in ACPA-negative patients with CSA, with an increased risk for RA, leads to prevention of ACPA-negative RA and reduction of disease burden,” Dumoulin said.
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Dumoulin Q. Abstract #2672. Presented at: ACR Convergence 2024; Nov. 14-19, 2024; Washington, D.C.
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