Common genetic variants do not impact clinical prediction of methotrexate treatment outcomes in early rheumatoid arthritis

• DOI: 10.1111/joim.20087
• Publication Date: 2025-04-07T06:54:30Z
• Authors: Anton Öberg Sysojev; Bénédicte Delcoigne; Thomas Frisell; Lars Alfredsson; Lars Klareskog; ; Saedis Saevarsdottir; Magnus Boman; Leonid Padyukov; Johan Askling; Helga Westerlind
• Keywords: Discontinuation; Linkage (software)

Abstract Background Methotrexate (MTX) is the mainstay initial treatment of rheumatoid arthritis (RA), but individual response varies and remains difficult to predict. The role genetics unclear, studies suggest its importance. Methods Incident RA patients starting MTX‐monotherapy were identified through a large‐scale Swedish register linkage. Demographic, clinical, medical, drug history features combined with fully imputed genotype data used train evaluate multiple learning models predict key MTX outcomes. Results Among 2432 patients, we consistently observed an estimated area under curve (AUC) ∼0.62, outperforming trained on sex age. best performance was for EULAR primary (AUC = 0.67), whereas struggled most predicting discontinuation. Genetics provided negligible improvements prediction quality. Conclusions Despite extensive study population broad multi‐modal data, outcomes challenge. Common genetic variants added minimal predictive power over clinical features.