Retention rate of upadacitinib therapy in rheumatoid arthritis. results of a large italian multicenter real-world study

Abstract. Background. Upadacitinib (UPA) is an oral Janus kinase inhibitor (JAKi) recently approved for the rheumatoid arthritis (RA) treatment. Although registrational studies have demonstrated the efficacy of UPA in RA, data on the long-term retention rate of this drug are still lacking. Objective: The objective of the study was to evaluate the real-world retention rate of UPA in patients with RA, analyze possible reasons for treatment discontinuation, and attempt to identify independent factors possibly associated with persistence of UPA treatment. Methods: We conducted a multicenter retrospective observational study of patients with RA referred to tertiary rheumatology hospitals in Italy. One-hundred-eleven consecutive patients who received UPA in different lines of treatment were enrolled. Clinical history, previous treatments, and RA disease activity at baseline were recorded. The retention rate of UPA was assessed by Kaplan-Meier curve study. Cox proportional regression analysis was also performed to study the effect of independent factors on UPA therapy retention rate including age, sex, smoking habit, presence of anti-citrullinated protein antibody (ACPA)/ rheumatoid factor (RF), disease duration, disease activity, line of treatment and concomitant treatments. Results: Analysis of demographic data revealed an M:F ratio of 28:83, a median age of 58 years with an interquartile Range (IQR) of 50-65 years, and a median disease duration 78 months (IQR: 40-167). The median observation period was 6.0 months (IQR 3.2-10.0). Most patients were on monotherapy or receiving concomitant steroids (55.0% and 58.6%, respectively). The UPA retention rate at 6 and 12 months was 90.4% and 74.7%, respectively. Reasons for treatment discontinuation included lack of efficacy (8/19), lost efficacy (6/19), infections (3/19) and cancer onset (2/19). Other factors affecting the rate of UPA maintenance were duration of illness and RA seropositivity. Conclusion: The high retention rate of UPA indirectly suggests the good efficacy and acceptable safety profile of this drug in RA therapy. From our study data, we conclude that UPA could be an appropriate choice in most patients with RA, even after failure of previous lines of treatment. We also found that the drug had a higher retention rate in patients with seropositive RA than in their seronegative counterparts.