SAT0236 Long-term safety and efficacy of upadacitinib (ABT-494), an oral jak-1 inhibitor in patients with rheumatoid arthritis in an open label extension study

Background: Upadacitinib (UPA, ABT-494) is a selective, oral JAK-1 inhibitor studied in two phase 2 randomized controlled trials (RCTs) in patients (pts) with rheumatoid arthritis (RA). Objectives: We assessed UPA safety and efficacy in BALANCE-EXTEND, an ongoing, combined open-label extension (OLE) of the phase 2 RCTs. Methods: Pts completing the two 12-week RCTs (in TNF-IR and (MTX-IR pts) 1,2 could enter the OLE. Pts switched to 6 mg UPA from their RCT dose of UPA 3, 6, 12, 18 mg twice daily (BID), 24 mg once daily (QD) or Placebo. A dose increase to 12 mg BID was required for pts with Results: Out of 516 pts who completed the 2 RCTs, 494 entered the OLE, 493 were dosed, 328 (66.5 %) were never-titrated, 150 (30.4%) were titrated-up, and 15 (3%) were titrated-up and back down; 150 pts (30.4%) were discontinued [42 (8.5%) withdrew consent, 37 (7.5%) due to AE and 24 (4.9%) due to lack of efficacy]. Mean exposure to UPA was 525.4±221.4 days (range 1–961 days), and cumulative exposure was 725.1 PY (Table ). The E/100PY for any AE in the OLE (170.5) were lower than for the RCTs in the TNF-IR (697.9, 48 PY) and MTX-IR (408.4, 54.6 PY) study populations. The E/100PY were 2.3 for serious infection, 3.7 for herpes zoster, 0.8 for malignancies excluding non-melanoma skin cancer, and 0.7 for adjudicated cardiovascular events. There were 2 deaths: one sudden death (adjudicated as undetermined or unknown cause of death) and one death due to Hodgkin’s lymphoma. Changes from baseline in laboratory parameters were consistent with observations from phase 2 RCTs. For those pts completing Wk 72, efficacy was maintained in pts on 6 mg BID UPA from day 1 of OLE (never-titrated); 55% pts met ACR70 and 83% were in LDA by DAS28-CRP and CDAI based on as observed data (Table) . Conclusions: The safety profile of UPA remained consistent with that expected for an RA population treated with JAKi. Efficacy responses were maintained up to 72 wks in pts on 6 mg BID UPA in the OLE. References [1]Kremer, et al. Arth u0026 Rheum2016;68:2867 [2]Genovese, et al. Arth u0026 Rheum2016;68:2857. Acknowledgements: AbbVie and the authors thank the patients, study sites and investigators who participated in this clinical trial. AbbVie Inc was the study sponsor, contributed to study design, data collection, analysis u0026 interpretation, and to writing, reviewing, and approval of final version. Medical writing support was provided by Naina Barretto, PhD, of AbbVie, Inc. Disclosure of Interest: M. Genovese Grant/research support from: AbbVie, Lilly, Astellas, Pfizer, Galapagos, Gilead, Consultant for: AbbVie, Lilly, Astellas, Pfizer, Galapagos, Gilead, J. Kremer Shareholder of: Corona, Grant/research support from: AbbVie, Lilly, Novartis, Pfizer, MedImmune, Sanofi, and Regeneron, Consultant for: AbbVie, Lilly, Novartis, Pfizer, MedImmune, Sanofi, and Regeneron, Employee of: Corona, S. Zhong Shareholder of: AbbVie, Employee of: AbbVie, A. Friedman Shareholder of: AbbVie, Employee of: AbbVie