Session Type: Poster Session (Sunday)
Session Time: 9:00AM-11:00AM
Background/Purpose: Upadacitinib (UPA), an oral JAK1-selective inhibitor, was evaluated in a comprehensive clinical program of 5 pivotal Phase 3 randomized-controlled trials (RCTs) across the full spectrum of RA patient (pt) populations1-5.
Assess the overall safety of UPA as monotherapy (mono) and as combination therapy with background csDMARDs in pts with moderately to severely active RA from the safety database of the Phase 3 clinical program.
Methods: Treatment-emergent adverse events (TEAEs) from 5 pivotal, randomized, double-blind, placebo- or active-controlled Phase 3 trials of UPA 15 mg (included in all 5 trials) or 30 mg QD (included in 4 trials) in RA pts were analyzed and summarized for the integrated placebo (PBO) (3 trials; 12/14 weeks), the integrated methotrexate (MTX) (2 trials; mean exposure: 36 weeks), the originator adalimumab (ADA) (mean exposure: 42 weeks), the UPA 15 mg (mean exposure: 53 weeks) and the UPA 30 mg (mean exposure: 59 weeks) groups as exposure adjusted event rates (EAERs; events/100 patient‑years [E/100PY]).
Results: Across the Phase 3 trials, 3834 pts received ≥1 dose of UPA 15 mg (n=2630) or 30 mg QD (n=1204), with no option to switch doses, for a total of 4020.1 PY of UPA exposure. The EAERs of overall SAEs and AEs leading to discontinuation on UPA 15 mg were comparable to ADA; while the rates of both were higher on UPA 30 vs UPA 15 mg and MTX. Across the studies, upper respiratory tract infection, nasopharyngitis and urinary tract infections were the most commonly reported AEs and occurred more frequently in the UPA compared with PBO. Rates of deaths were comparable across the treatment groups. Serious infection (SIEs) rates were comparable between UPA 15 mg and ADA while higher on UPA compared with MTX. Rates of herpes zoster (HZ) were higher in both UPA groups vs MTX and ADA. The rates of SIE and HZ were higher on UPA 30 vs 15 mg. Rates of malignancies (excluding non-melanoma skin cancer [NMSC]) and adjudicated MACE and VTE were comparable across the treatment groups. The rate of NMSC in UPA 15 mg, MTX and ADA groups were similar with higher rates in the UPA 30 mg group, however the rates for both UPA groups were in the range reported for RA patients treated with DMARDs3. The age-gender adjusted standardized incidence ratio (SIR, 95% CI) for malignancies other than NMSC (15 mg: 0.98 [0.61, 1.49], 30 mg: 1.49 [0.85, 2.42]) was within the range expected for the general population (SEER 18 Registry 2000-2015).
Conclusion: The rate of SIE on UPA 15 mg was similar to ADA. The rate of HZ was higher on both UPA doses compared to MTX and ADA. The rates of VTE, MACE, and malignancy were comparable with that observed in the MTX and ADA groups while also being consistent with reported rates in the RA population.
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- van Vollenhoven R, et al. Arthritis Rheumatol. 2018;70 (S 10) [Abs].
To cite this abstract in AMA style:Cohen S, van Vollenhoven R, Winthrop K, Zerbini C, Tanaka Y, Bessette L, Zhang Y, Khan N, Hendrickson B, Enejosa J, Burmester G. Safety Profile of Upadacitinib in Rheumatoid Arthritis: Integrated Analysis from the SELECT Phase 3 Clinical Program [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/safety-profile-of-upadacitinib-in-rheumatoid-arthritis-integrated-analysis-from-the-select-phase-3-clinical-program/. Accessed November 18, 2019.
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