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The following is a summary of “Development of rheumatoid arthritis after methotrexate in anticitrullinated protein antibody-negative people with clinically suspect arthralgia at risk of rheumatoid arthritis: 4-year data from the TREAT EARLIER trial,” published in the December 2024 issue of Rheumatology by Dumoulin et al. 

Prevention of rheumatoid arthritis has become a definitive target. However, whether prevention of anti-citrullinated protein antibody (ACPA)-negative rheumatoid arthritis is possible is still unknown. 

Researchers conducted a retrospective study to assess the efficacy of a 1-year course of methotrexate in preventing rheumatoid arthritis in ACPA-negative individuals with clinically suspected arthralgia. 

They analyzed 4-year data from the TREAT EARLIER trial, a randomized, double-blind, placebo-controlled study in the southwest Netherlands (2015–2023). Adults with arthralgia and subclinical joint inflammation at risk for rheumatoid arthritis were randomly assigned (1:1) to 120 mg methylprednisolone and 1 year of methotrexate or placebo. Follow-up visits occurred every 4 months for 2 years. Participants were stratified into risk groups using a prediction model. The primary outcome was the development of rheumatoid arthritis. 

The results showed that 901 people with clinically suspected arthralgia were assessed, and 236 enrolled in TREAT EARLIER. Of these, 217 (92%) completed a 4-year follow-up. Among the participants, 154 (65%) were women, 82 (35%) were men, 182 (77%) were ACPA-negative, and 54 (23%) were ACPA-positive. After 4 years, 52 (22%) developed rheumatoid arthritis, with 25 (21%) in the treatment group and 27 (23%) in the placebo group. Among ACPA-negative participants at increased risk, 3 (9%) of 35 in the treatment group developed rheumatoid arthritis compared to 9 (29%) in the placebo group (hazard ratio (HR) 0.27, P=0.034). Among the 116 ACPA-negative participants at low risk, 4 (8%) of 53 in the treatment group developed rheumatoid arthritis vs 6 (10%) of 63 in the placebo group (0.79, 95% CI 0.22–2.80; P=0.71). Methotrexate reduced the rate of ACPA-negative rheumatoid arthritis in those at increased risk and improved subclinical inflammation, physical functioning, and grip strength in this group. 

They concluded that risk stratification helped identify ACPA-negative individuals who could benefit from methotrexate. 

Source: thelancet.com/journals/lanrhe/article/PIIS2665-9913(24)00196-6/abstract