PO:07:108 | Achievement of Treatment Targets and Maintenance of Response with Upadacitinib in Patients with Moderate-to-Severe Rheumatoid Arthritis in a Real-world Setting: Final 2-year Outcomes from the UPHOLD Study

Enrico Marchetta¹, Andrew Östör^2|8, Eugen Feist³, Prodromos Sidiropoulos⁴, Jérôme Avouac⁵, Martin Rebella^6|7, Rajaie Namas⁹, Erin Mcdearmon Blondell¹⁰, Ivan Lagunes¹⁰, Tianming Gao¹⁰, Tim Shaw¹⁰, Suzan Attar¹¹ | ¹AbbVie Srl Roma, Italy; ²Monash University and Emeritus Research, Melbourne, Victoria, Melbourne, Australia; ³Helios Department of Rheumatology and Clinical Immunology, Vogelsang-Gommern, Vogelsang Gommern, Germany; ⁴Faculty of Medicine, University of Crete, Heraklion, Heraklion, Greece; ⁵Service de Rhumatologie, Hôpital Cochin, AP HP Centre Université Paris Cité, Parigi, France; ⁶Departamento de Medicina, Facultad de Medicina, Universidad de la República, Montevideo, Montevideo, Uruguay; ⁷Unidad de Enfermedades Autoinmunes Sistémicas, MUCAM, Montevideo, Montevideo, Uruguay; ⁸Australian National University, Camberra, Australia; ⁹Medical Subspecialties Institute, Division of Rheumatology, Cleveland Clinic Abu Dhabi, United Arab Emirates; ¹⁰AbbVie Inc., North Chicago, Illinois, United States of America Chicago, USA; ¹¹King Abdulaziz University, Jeddah, Saudi Arabia

Purpose. To evaluate the data from the UPHOLD study on long-term achievement of treatment targets, sustained clinical response and safety of UPA over 2-years in patients with RA.

Methods. UPHOLD (NCT04497597) is an international, observational cohort study of UPA-naïve adults with RA who initiated UPA 15mg once daily. Data are reported between 16-October-2020 to 15-May-2024. The co-primary endpoints were the proportion of patients who achieved DAS28(CRP) remission (< 2.6) at 6-months, and the proportion of those patients who maintained DAS28(CRP) remission (or had a <=0.6-point increase in DAS28[CRP]) at 12-months (analysed by modified non-responder imputation [mNRI] and as observed [AO] in modified full-analysis set [mFAS]1 and mFAS2). Key secondary endpoints included: proportion of patients achieving and maintaining DAS28(CRP) low disease activity (LDA;<=3.2); proportion of patients maintaining DAS28(CRP) remission/LDA by treatment strategy and prior therapy exposure; mean DAS28(CRP) values by visit; proportion of patients in each DAS28(CRP)/CDAI/SDAI disease category (remission, LDA, moderate, and high disease activity) by visit; and change from baseline in patient-reported outcomes (PROs). All treatment-emergent adverse events (TEAEs) and selected TEAEs of interest in the FAS are reported as exposure-adjusted event rates (events per 100 patient-years [E/100PY]).

Results. Of the 1715 participants, 1713 were enrolled and 1699 received >=1 UPA dose. Of 1715 participants, 1029 (60.0%) completed the 24-month follow-up and 686 (40.0%) prematurely discontinued the study. Of FAS patients, 48.3% initiated UPA as monotherapy and 51.7% in combination with csDMARDs. Of 1524 patients who reported prior RA therapy, 64.3% received >=1 bDMARD and 18.3% >=1 tsDMARD. Of the 1073 patients in the mFAS1, 46.3% (mNRI) and 55.3% (AO) achieved DAS28(CRP) remission at 6-months. Of the 341 patients in the mFAS2, 79.2% (mNRI) and 84.9% (AO) maintained DAS28(CRP) remission at 12-months (Fig.1A). Patients with a response at 6-months, 62.9% (mNRI) and 83.9% (AO) maintained DAS28(CRP) remission, and 65.7% (mNRI) and 90.1% (AO) maintained DAS28(CRP) LDA at 24-months (Fig.1A). The overall proportions of patients achieving DAS28(CRP), CDAI (<=2.8) and SDAI (<=3.3) remission at 24-months were 66.8%, 36.1% and 36.7%, respectively (FAS; AO). The mean DAS28(CRP) value decreased from 4.6 at baseline to 2.9 at 3-months and 2.3 at 24-months (Fig.1B). Responses were generally similar whether patients were treated with UPA as monotherapy or in combination with csDMARDs, and across subgroups of patients per prior therapy exposure. Improvements were observed in all assessed PROs at 3-months, which were maintained or improved through 24-months. A total of 2922 TEAEs, including 265 serious TEAEs, were reported. Rates of selected TEAEs of interest, as reported in Figure 2, were consistent with the UPA safety data from previous phase-3 clinical trials1,2.

Conclusions. The benefit–risk profile of UPA in a RW-setting appears consistent with that demonstrated in phase-3 clinical trials1,2. 1.Conaghan,PG RheumatolAdvPract2023;7(1):rkad017. 2.Burmester, GRRMDOpen2023;9:e002735.