Background/Purpose: To assess long-term sustainability of responses to upadacitinib (UPA), a JAK inhibitor, with or without background csDMARD(s) in patients (pts) with rheumatoid arthritis (RA).

Methods: Data are from two phase 3 trials of UPA in RA pts with roughly similar baseline disease characteristics: SELECT-NEXT enrolled pts with inadequate response (IR) to csDMARD(s) on background stable csDMARD(s) receiving UPA 15 or 30 mg once daily or placebo for 12 wks; SELECT-MONOTHERAPY enrolled methotrexate (MTX)-IR pts receiving UPA 15 or 30 mg monotherapy or blinded MTX for 14 wks. After 12/14 wks, pts could receive UPA 15 or 30 mg up to 5 years in a blinded long-term extension.  This post hoc analysis evaluated clinical remission (REM:CDAI ≤2.8; SDAI ≤3.3), low disease activity (LDA:CDAI≤10; SDAI≤11), and DAS28(CRP) < 2.6/≤3.2 at first occurrence before Wk 84; these were also evaluated at 3, 6, and 12 months after the first occurrence for total number of pts randomized to UPA 15 mg. Sustainability was evaluated by Kaplan-Meier for pts who achieved REM/LDA and was defined as time to the earliest date of losing response at two consecutive visits or discontinuation of study drug. Predictive ability of time to clinical REM/LDA was assessed using Harrell’s concordance (c)-index (~ 0.5, no ability to predict; closer to1 or -1, perfect prediction). Last follow up dates were 22 March 2018 (SELECT-NEXT) and 25 May, 2019 (SELECT-MONOTHERAPY), when all pts reached the Week 84 visit.

Results: Through Wk 84, CDAI REM/LDA was achieved in 43%/79% of pts receiving UPA 15 mg with background csDMARD(s) (SELECT-NEXT) and 37%/76% without background csDMARD(s) (SELECT-MONOTHERAPY). 35%/25% of pts randomized to UPA 15 mg with background csDMARD(s) and 27%/23% without background csDMARD(s) achieved sustained CDAI REM through 6/12 months after first occurrence. 64%/56% of pts randomized to UPA 15 mg with background csDMARD(s) and 61%/56% without background csDMARD(s) achieved sustained CDAI LDA through 6/12 months after first occurrence (Figure 1). Time to initial clinical REM/LDA did not appear to be associated with sustained disease control. The c-indices (95%CI) for CDAI REM in the UPA 15 mg with background csDMARD(s) and without background csDMARD(s) groups were 0.541 (0.47, 0.62) and 0.568 (0.49, 0.65) and LDA were 0.521 (0.46, 0.58) and 0.498 (0.43, 0.56), respectively. Through last follow-up visit, 55% of pts receiving UPA 15 mg with background csDMARD(s) and 62% without background csDMARD(s) remained in CDAI REM while 72% and 70% of pts remained in CDAI LDA, respectively (Figure 2). Similar results were observed across other disease activity measures (SDAI REM/LDA and DAS28(CRP)
< 2.6/≤3.2).

Conclusion: More than a quarter and more than a half of pts with RA and prior IR to csDMARD(s) receiving UPA with or without background csDMARD therapy achieved sustained clinical REM and LDA, respectively, across disease activity measures. Sustainability of responses appeared comparable among pts receiving UPA with or without background csDMARDs through up to 84 wks.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/sustainability-of-response-to-upadacitinib-as-monotherapy-or-in-combination-among-patients-with-rheumatoid-arthritis-and-prior-inadequate-response-to-conventional-synthetic-dmards/