2273: Impact of Upadacitinib on Glucocorticoid Reduction in Patients with Moderate-to-Severe RA Who Achieved and Maintained Clinical Remission in the 2-Year UPHOLD Study

Background/Purpose: Glucocorticoids (GCs) are fast-acting drugs used to support csDMARD therapy for RA, but should be used sparingly and for short periods.¹ Upadacitinib, an oral Janus kinase inhibitor, is approved for the treatment of adults with moderate-to-severe RA.² This post hoc analysis assessed the real-world impact of upadacitinib on GC discontinuation, and the effect of GC discontinuation on efficacy and safety, in patients with RA taking GCs at study onset, who achieved and maintained remission through 2 years in the UPHOLD study.

Methods: UPHOLD (NCT04497597), a 2-year, non-interventional, multi-country, observational, cohort study, assessed the real-world effectiveness and safety of upadacitinib (15 mg QD) in upadacitinib-naïve adults with moderate-to-severe RA. This post hoc analysis assessed the impact of upadacitinib in achieving and maintaining GC-free clinical remission (defined as 28-joint DAS with CRP [DAS28-CRP] < 2.6, Clinical Disease Activity Index [CDAI] ≤2.8, and Simplified Disease Activity Index [SDAI] ≤3.3) at 6, 12, and 24 months (mo) among patients taking GCs at baseline. Safety was assessed by DAS28-CRP remission status subgroup (yes/no) and reported as exposure-adjusted events/100 patient-years. Data are presented as observed.

Results: At baseline, 455 patients had concomitant GC use; mean (standard deviation [SD]) GC dose: 8.1 (7.6) mg/day; patient number (%) by GC dose (mg/day): 65 (14.3), < 5; 207 (45.5), 5; 120 (26.4), >5–10; and 63 (13.8), >10; mean (SD) disease duration: 9.8 (8.8) years; and mean (SD) disease activity scores: DAS28-CRP, 4.76 (1.2); CDAI, 27.9 (12.4); SDAI, 30.2 (13.7). At 6 mo, DAS28-CRP remission was achieved by 58.5% (n/N: 158/270), CDAI remission by 22.4% (64/286), and SDAI remission by 24.6% (61/248) of patients. Of patients achieving DAS28-CRP, CDAI, and SDAI remission at 6 mo, 28.5% (45/158), 39.1% (25/64), and 41.0% (25/61), respectively, were GC-free. Of patients with GC-free remission at 6 mo, who maintained remission and had data available at 12 mo (DAS28-CRP, 90.9% [30/33]; CDAI, 72.2% [13/18]; SDAI, 81.3% [13/16]), most were GC-free (DAS28-CRP, 93.3% [28/30]; CDAI, 100.0% [13/13]; SDAI, 84.6% [11/13]) (Figure 1). At 12 mo, 64.6% (144/223) patients had DAS28-CRP, 27.3% (65/238) had CDAI, and 28.8% (62/215) had SDAI remission, and almost half were GC-free (DAS28-CRP, 41.0% [59/144]; CDAI, 49.2% [32/65]; SDAI, 48.4% [30/62]). Of patients with GC-free remission at 12 mo, who maintained remission and had data available at 24 mo (DAS28-CRP, 80.4% [37/46]; CDAI, 83.3% [20/24]; SDAI, 77.3% [17/22]), 100% were GC-free (DAS28-CRP, 37/37; CDAI, 20/20; SDAI, 17/17) (Figure 2). Treatment-emergent adverse events were similar regardless of DAS28-CRP remission status at 6, 12, and 24 mo, and consistent with previously published UPHOLD dat

Conclusion: Upadacitinib reduced GC use in patients with moderate-to-severe RA and enabled persistent GC-free clinical remission through 2 years in a real-world setting.


References
1. Buttgereit F. Nat Rev Rheumatol. 2020;16:239–46.
2. Rinvoq prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/211675s015lbl.pdf. Accessed April 2025.