Ab0481 upadicitinib Effectiveness in Rheumatoid Arthritis: Observation From an Italian Multi-Centric Cohort

Abstract

BackgroundJanus kinase (JAK) inhibitors have been approved for the treatment of Rheumatoid Arthitis (RA) and other systemic or organ-specific autoimmune diseases. Sustained remission or low disease activity are target treatments recomended by European League Against Rheumatism (EULAR) in RA patients [1]. Upadacitinib (UPA), a reversible, oral JAK inhibitor, has been engineered to have a greater selectivity for JAK1 vs JAK2, JAK3, and tyrosine kinase. In the Phase 3 SELECT clinical trial program, UPA has been shown to be effective and well tollerate in patients with RA [2]. However, data on the use of UPA in real-world clinical practice are limited.ObjectivesTo evaluate UPA effectiveness in RA patients and to report the main reasons of suspension and the most relevant factor related to treatment persistence.MethodsIn 25 Italian rheumatological referral centers, all RA consecutive patients who received UPA were enrolled. Anamnestic data, treatment history and RA disease activity at baseline were recorded.The 6 and 12 months UPA retention rate was assessed with the Kaplan-Meier curve methods. The Cox analysis investigated the effect of age, sex, smoke habit, ACPA/RF presence, disease duration, DAS28-CRP, line of treatment, concomitant csDMARD treatment on UPA retention rate. A p-value < 0.05 was considered statistically significant.ResultsThe one-hundred-eleven enrolled patients median age 57 (IQR 50-65 yrs); M:F 28:83; disease duration 78 (IQR 40-170 months). The median observation period was 6.1 (IQR 3.2-10.2) months. The observation lasted 812 patients-months. The majority of patients (54.0%) were in mono-therapy and received steroids (respectively 54.0% and 58.6%) (Table 1).The UPA retention rate at 6, 12 months was, respectively 90.4% and 74.7% (Figure 1). The main discontinuation reason was lack of efficacy (42% of interruptions), cancer onset and infections (both 11%). No thromboembolic events were reported.According to the Cox analysis, no one of the above mentioned parameters were associated to high risk of treatment interruption.Table 1.Baseline characteristics UPACharacteristicsValueM:F28:83Age, median [IQR] yrs58 [50-65]Smokers, n (%) (**)YesFormerNo16 (16,5)17 (17,5)64 (66,0)Body Mass Index, median [IQR] kg/m^2 (*)24,7 [22,4-27,7]Disease Duration, median [IQR], months78 [40-170]RF positivity, n (%)72 (64,9)ACPA positivity, n (%)68 (61,3)SJC, median [IQR]4 [3-8]TJC, median [IQR]8 [5-11]ESR, median [IQR], mm/h32 [20-53]CRP, median [IQR], mg/dl1,2 [0,5-3,3]VAS Patient (0-100), median [IQR]70 [50-80]DAS28, median [IQR]5,5 [4,9-5,9]Line of treatment, [IQR]3 [2-4]Concomitant csDMARDs use, n (%)MTXLFNSSZHCQ41 (36,9)3 (2,7)1 (0,9)5 (4,5)Concomitant steroids use, n (%)65 (58,6)Steroids dose (PDN-Eq), median, mg/die5 [5-6]Prior bDMARDs use, n (%)TNFiIL6iIL1iCD20iCD80i53 (47,7)13 (11,7)02 (1,8)11 (9,9)Prior tsDMARDs use, n (%)BaricitinibTofacitinib9 (8,1)2 (1,8)Concomitant relevant disease, n (%)DiabetesHypercholesterolemiaMACEArterial HypertensionCancer12 (10,8)23 (20,7)5 (4,5)34 (30,6)4 (3,6)Figure 1.ConclusionUPA effectiveness appears to be confirmed. The safety profile of UPA 15 mg in real-world practice is consistent with data from Phase 3 SELECT trials, with no new safety signals.References[1]Smolen JS, et al. Ann Rheum Diseases 2023;82:3-18.[2]Burmester GR et al.Lancet 2018; 23;391(10139):2503-2512Acknowledgements:NIL.Disclosure of InterestsNone Declared.