Background/Purpose: We evaluated long-term achievement of treatment targets, sustained clinical response, and safety of upadacitinib (UPA) over 2 years in patients with moderate-to-severe rheumatoid arthritis (RA).

Methods: UPHOLD (NCT04497597) is an observational cohort study of UPA-naïve adults with RA (data collected: 16 October 2020-15 May 2024). Co-primary endpoints were achievement of DAS28(CRP) remission < 2.6 (6 months) and maintenance of DAS28(CRP) remission (or ≤0.6-point increase) at 12 months (analyzed by modified non-responder imputation (NRI) or as observed [AO]). mFAS1 included patients in FAS (receiving ≥1 UPA dose) who completed 6 months and those who discontinued before 6 months; mFAS2 included patients achieving DAS28(CRP) remission within mFAS1 who completed 12 months and those discontinuing between 6 and 12 months. Key endpoints were proportion achieving/maintaining DAS28(CRP) low disease activity (LDA≤3.2); maintaining DAS28(CRP) remission/LDA by treatment strategy (UPA monotherapy or csDMARD combined) and prior therapy exposure (ts/bDMARD-naïve, ts/bDMARD-experienced, tsDMARD-experienced or TNF inhibitor only-experienced); mean DAS28(CRP) values; proportion in each DAS28(CRP)/CDAI/SDAI disease category; PROs change from baseline.

Results: 1699 of 1715 total participants received ≥1 UPA dose (FAS; UPA monotherapy [48.3%], +/- csDMARDs [51.7%]). 1029 (60.0%) completed 24 months and 686 (40.0%) prematurely discontinued (lack of efficacy [15.2%], adverse events [9.5%] and loss to follow-up [5.5%]). 1524 participants received prior therapy (≥1 bDMARD [64.3%] and ≥1 tsDMARD [18.3%]). In mFAS1 (n=1073, 6 months), 46.3% (mNRI) and 55.3% (AO) achieved DAS28(CRP) remission. In mFAS2 (n=341, 12 months), 79.2% (mNRI) and 84.9% (AO) maintained DAS28(CRP) remission. Similar trends for 6 and 12 months were observed with higher rates for DAS28(CRP) LDA (Figure 1A). Of 6-month responders, most maintained response until the end of the study at 24 months (DAS28(CRP) remission: 62.9% [mNRI]; 83.9% [AO]; DAS28(CRP) LDA: 65.7% [mNRI]; 90.1% [AO]) (Figure 1A). DAS28(CRP), CDAI(≤2.8) and SDAI(≤3.3) remission was achieved at 24 months in 66.8%, 36.1% and 36.7% participants, respectively (FAS; AO). Mean DAS28(CRP) decreased from 4.6 at baseline to 2.9 (3 months) and 2.3 (24 months) (Figure 1B). Improvements were observed regardless of UPA monotherapy/csDMARD combined treatment or prior therapy exposure in all assessed PROs at 3 months and maintained or improved through 24 months. 2922 TEAEs and 265 serious TEAEs were reported. Rates of herpes zoster, serious infection, hepatic disorder, malignancy excluding non-melanoma skin cancer (NMSC), NMSC, VTE and MACE were consistent with previous UPA safety data (Figure 2).2

Conclusion: UPA was effective in treating RA in RW practice. About half of patients treated with UPA achieved DAS28(CRP) remission at 6 months; almost 80% maintained remission at 12 months and >60% at 2 years (mNRI). The benefit–risk profile remains consistent with phase 3 clinical trials.1,2References1. Conaghan, PG et al. Rheumatol Adv Pract 2023;7(1):rkad017.2. Burmester, GR et al. RMD Open 2023;9:e002735.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/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-s/