Session Title: 3S109: RA – Treatments II: Novel Treatments for RA (927–932)
Session Type: ACR Abstract Session
Session Time: 4:30PM-6:00PM
Background/Purpose: Upadacitinib (UPA), a JAK1-selective inhibitor, was efficacious as monotherapy upto 24 weeks (wks) in MTX-naive patients (pts) with active RA.1
To assess safety and efficacy of UPA through 48 wks in an ongoing extension of the ph 3 SELECT-EARLY RCT.
Methods: SELECT-EARLY had a 48-wk double-blind active comparator-controlled period. Pts were initially randomized to monotherapy (mono) with UPA 15 or 30 mg or MTX (titrated up to Wk8). Rescue therapy was offered if pts met the following: (1) From Wk 12-24, pts without ≥20% improvement from BL (Δ) in both TJC and SJC at 2 consecutive visits continued blinded study drug with optimized background RA medications. (2) At Wk26, pts with CDAI ≤2.8 continued their original study drug; in pts with CDAI >2.8 and < 20% Δ in TJC and SJC, for those on MTX, UPA15/30mg was added; for those on UPA15/30mg, MTX was added. For pts with CDAI >2.8 but ≥20%Δ in TJC and SJC, background medications were optimized. Background csDMARDs could be initiated after Wk26. After Wk48, pts could continue in a long-term extension. Efficacy data up to the Wk48 visit are reported based on initial randomized treatment. For binary non-radiographic endpoints, NRI was used for missing data and rescue handling; for continuous non- radiographic endpoints, LOCF was used for rescue handling. Radiographic analyses are based on linear extrapolation for missing data imputation and rescue handling. Adverse events (AE) per 100 pt yrs (PY) are summarized up to a cut-off date of Aug 16 2018.
Results: Of 945 pts randomized and treated, 747(79%) completed Wk48 treatment, 163 (17.2%) discontinued (D/C) study drug prior to Wk48, 35 pts (4%) had not completed the Wk48 treatment as of this analysis. Primary reasons for D/C were AEs for 62 pts (6.5%), and lack of efficacy in 20 pts (2.1%). At Wk26, UPA15/30 was added for 37 (12%) of pts on MTX; MTX was added for 19 (6%) and 9 (3%) of pts on UPA15 and UPA30, respectively. Cumulative exposures to MTX mono, UPA15 mono and UPA30 mono were 314.4, 343.1 and 336.7 PYs, respectively. Through Wk48, pts on UPA15 and 30 vs MTX continued to have significantly greater improvements in clinical, functional and pt-reported outcomes (except FACIT-F for UPA15, p=.058 vs MTX) (Table 1). At Wk 48, CDAI Remission (REM) was achieved by 33% and 40% of pts on UPA15 and 30 respectively vs 17% on MTX; 28% and 33% vs 13% achieved Boolean REM. At Wk48, ΔmTSS were significantly less on UPA15 and UPA30 vs MTX. The safety profile of UPA15 and UPA30 mono was generally similar to MTX, except for total AEs and herpes zoster, which were higher with UPA15 and 30 vs MTX (Table 2). There were 11 deaths (including 3 non-treatment emergent deaths) due to varied causes.
Conclusion: UPA15 and 30 monotherapy continued to show significant improvements in RA signs and symptoms and inhibition of structural damage vs MTX through 48 wks. Only a small proportion of pts required MTX addition to UPA mono at Wk26 to achieve and maintain response. The safety profile based on all exposure remained consistent with ph 2 and 3 RCTs in RA, although an integrated safety analysis of UPA across the full ph 3 RA program will provide a more comprehensive understanding of the benefit:risk profile of UPA in RA.
To cite this abstract in AMA style:van Vollenhoven R, Takeuchi T, Pangan A, Friedman A, Chen S, Rischmueller M, Blanco R, Xavier R, Strand V. Monotherapy with Upadacitinib in MTX-naïve Patients with Rheumatoid Arthritis: Results at 48 Weeks [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/monotherapy-with-upadacitinib-in-mtx-naive-patients-with-rheumatoid-arthritis-results-at-48-weeks/. Accessed January 27, 2023.
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