Objective <p>This study investigates the predictive capacity of LACC1 regarding the response to upadacitinib (UPA) in individuals with rheumatoid arthritis (RA).</p> Methods <p>The study involved sixty adult patients with active RA who either did not respond well to or could not tolerate methotrexate. The regimen involved UPA monotherapy at 15&#xa0;mg/day, while maintaining a fixed dose of glucocorticoids was acceptable. Follow-up was planned for 24&#xa0;weeks. Treatment response was assessed using Clinical Disease Activity Index, Simplified Disease Activity Index, tender joint count (TJC), swollen joint count, and Health Assessment Questionnaire. Moreover, parameters associated with treatment response to UPA were measured.</p> Results <p>Serum LACC1 levels may be protective in predicting response to UPA therapy. Age, prolonged disease duration, increased use of csDMARDs, low neutrophil counts, and higher inflammatory markers were strongly associated with non-good response. Prolonged disease duration, increased TJC/68, low neutrophil count, and high GM-CSF levels were all independent unfavorable predictors of good response to UPA treatment, while higher serum LACC1 levels were more helpful in predicting good response. Patients with an extended disease course, high TJC/68, and significantly increased inflammatory cytokines should be advised of the potential for poor early outcomes.</p> Conclusion <p>Higher serum LACC1 levels are associated with better efficacy of UPA, with implications for optimizing clinical individualized dosing strategies.</p>