Is a One-Year Course of Methotrexate in Patients With Arthralgia At-Risk for Rheumatoid Arthritis Cost-Effective? A Cost-Effectiveness Analysis of the Randomized Placebo-Controlled Treat Earlier Trial

OBJECTIVES: Rheumatoid arthritis (RA) affects approximately 1% of the population and causes joint damage, disability, and increased morbidity. Early diagnosis and treatment are important for management of RA. Currently, RA is diagnosed after swollen joints are detected but patients at-risk of developing RA often already show symptoms in an earlier phase. The TREAT EARLIER trial targeted these patients at risk. While RA-development was not prevented in the total trial population, it did induce improvements in joint inflammation, functioning and productivity. This study provides a cost-utility analysis of the TREAT EARLIER trial.

METHODS: The trial involved 236 patients with clinically suspect arthralgia (CSA) and subclinical joint inflammation. Participants were randomized to either a single intramuscular glucocorticoid injection and a one-year methotrexate course, or placebo. They were followed for two years, unless they developed RA, causing missingness not at random. To address this, lower and upper limit scenario analysis were conducted from societal and healthcare perspectives. Bootstrapping with 10,000 replications was used to assess uncertainty.

RESULTS: From a societal perspective, the treatment arm resulted in €-4809(-12,382 to 2,726) costs per patient compared to placebo in the lower limit scenario, and €-7420(-15,484 to 771) in the upper limit. Health gains were 0.0408(-0.0499 to 0.0905) QALYs for the lower limit, and 0.0440(-0.0499 to 0.0906) for the upper limit. From the healthcare perspective, costs were €-405(-1130 to 248) for the lower limit, and €-517(-1,269 to103) for the upper limit. Using a threshold of €50,000, 88% (societal perspective) and 78% (healthcare perspective) of the iterations were cost-effective for the lower limit scenario, and 98% and 82% for the upper limit.

CONCLUSIONS: Treatment with glucocorticoids and methotrexate in CSA patients with subclinical inflammation improves work productivity, reduces healthcare costs, and improves quality of life over two years. This is the first evidence suggesting that secondary prevention of RA could be cost-effective.