P128 Long-term safety and efficacy of upadacitinib in patients with rheumatoid arthritis: final results from the BALANCE-EXTEND open-label extension study
Authors: Kivitz Alan , Wells Alvin F , Vargas Juan I , Baraf Herbert S B , Rischmueller Maureen , Klaff Justin , Khan Nasser , Li Yihan , Carter Kyle , Friedman Alan , Durez Patrick 
Published: April 2023

Abstract

Background/Aims
Upadacitinib (UPA) was previously evaluated in two Phase 2, randomized, controlled trials (RCTs) in patients (pts) with rheumatoid arthritis (RA) and inadequate response to tumor necrosis factor inhibitors (BALANCE-1) or methotrexate (BALANCE-2). Objectives: To assess the final safety and efficacy of UPA in BALANCE-EXTEND, a 312-week open-label extension (OLE) enrolling pts who completed either BALANCE1 or BALANCE-2.

Methods
All pts initially received UPA 6 mg twice daily (BID). Increase to 12 mg BID was required for pts with &lt;20% improvement in swollen or tender joint counts (S/TJC) at Week 6 or 12, and permitted for those not achieving Clinical Disease Activity Index (CDAI) low disease activity (LDA). Pts with &lt;20% improvement in SJC or TJC 6 weeks after escalation, or at any two consecutive visits, discontinued. Return to 6 mg BID was permitted for safety or tolerability reasons. After January 2017, the 6 and 12 mg BID doses were replaced by 15 and 30 mg once-daily (QD) extended-release equivalents. As-observed efficacy data are shown at Week 312 for three subgroups: pts who received 6 mg BID/15 mg QD throughout (“Never titrated”), those titrated up to 12 mg BID/30 mg QD for efficacy (“Titrated up”), and those titrated up to 12 BID/30 mg QD and then back to 6 mg BID/15 mg QD due to safety concerns (“Titrated up and down”). Exposure-adjusted adverse events (EAERs) per 100 patient-years (PY) of exposure were summarized from OLE Day 1 in all pts who received UPA (Any UPA).

Results
Overall, 493 pts entered the OLE, receiving UPA for ≤6.2 years (Never titrated, n = 306; Titrated up, n = 149; Titrated up and down, n = 38), and 270 pts (54.8%) discontinued, mostly due to withdrawal of consent (16.8%; n = 83) or AEs (14.6%; n = 72). Mean (standard deviation) duration of UPA exposure was 3.8 (2.4) years (range &lt;1-6.2 years); cumulative exposure was 1863 PY. The AE profile in pts receiving UPA 15 mg was generally similar to the Any UPA population, and to that observed in the Phase 3 UPA 15 mg clinical trial population. Efficacy was maintained to Week 312, with 84.5% and 86.6% of pts in the Never titrated group achieving DAS28-CRP ≤3.2 and CDAI LDA, respectively.

Conclusion
In this OLE, UPA treatment over ∼312 weeks showed sustained long-term efficacy in pts with RA who had completed Phase 2 RCTs. Overall safety results showed that UPA was well tolerated over time; the types and frequencies of AEs were consistent with those in pts with similar populations of moderately to severely active RA receiving Janus kinase inhibitors.
Disclosure
A. Kivitz: Consultancies; A Kivitz has received consulting fees and/or honoraria from AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly and Company, Flexion, Genzyme, Gilead, Horizon, Janssen, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sanofi Aventis, SUN Pharma Advanced Research, and UCB. Shareholder/stock ownership; A Kivitz owns stocks or options in Amgen, Gilead, GlaxoSmithKline, Novartis, Pfizer, and Sanofi. Honoraria; A Kivitz has received honoraria from AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly and Company, Flexion, Genzyme, Gilead, Horizon, Janssen, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sanofi Aventis, SUN Pharma Advanced Research, and UCB. Grants/research support; A Kivitz's institution received fees from AbbVie for his role as a Principal Investigator in the study. A.F. Wells: Consultancies; AF Wells has received consulting fees from AbbVie. J.I. Vargas: Honoraria; JI Vargas has received honoraria from AbbVie. Grants/research support; JI Vargas has received fees from AbbVie as Principal Investigator in the study. H.S.B. Baraf: Consultancies; HSB Baraf has acted as a consultant for Gilead and Janssen. Grants/research support; HSB Baraf has received grant/research support from AbbVie, Eli Lilly, Genentech, Gilead, and Janssen. M. Rischmueller: Consultancies; M Rischmueller has acted as a consultant for AbbVie, Bristol-Myers Squibb, CSL Behring, Eli Lilly, Gilead Sciences, Janssen Global Services, Pfizer, Sanofi US Services, and UCB Biosciences. Grants/research support; M Rischmueller has received grant/research support from AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Janssen Global Services, Novartis, Pfizer, Sanofi Pasteur Biologics, and UCB Biosciences. J. Klaff: Shareholder/stock ownership; J Klaff is employee of AbbVie and may own stocks or options. N. Khan: Shareholder/stock ownership; N Khan is an employee of AbbVie and may own stocks or options. Y. Li: Shareholder/stock ownership; Yihan Li is an employee of AbbVie and may own stocks and options. K. Carter: Shareholder/stock ownership; K Carter is an employee of AbbVie and may own stocks and options. A. Friedman: Shareholder/stock ownership; A Friedman is an employee of AbbVie and may own stocks and options. P. Durez: Corporate appointments; P Durez has received speaker fees from Eli Lilly and Galapagos.