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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 <20% improvement in both SJC and TJC on 6 mg BID (at wk 6 or 12), and permitted for pts not meeting CDAI LDA. Pts without 20% improvement in SJC and TJC 6 wks after escalation, or at any 2 consecutive visits, were discontinued. The dose was decreased to 6 mg BID only in pts with a safety concern or intolerability. Pts are grouped as: Never-titrated (on 6 mg BID throughout); Titrated-up (from 6 to 12 mg BID); Titrated-up and back down (to 6 mg BID). After Jan 2017, the 6 and 12 mg BID doses were replaced by 15 and 30 mg QD extended-release equivalents currently being studied in phase 3. Data up to Jan 13 2017 are reported. Adverse events (AE) per 100 yrs of pt exposure (PY) are summarized starting from day 1 of OLE. Efficacy is assessed by ACR20/50/70 and LDA (by DAS28-CRP and CDAI), and observed data are presented up to Wk 72 of OLE due to sample size consideration. 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 & Rheum2016;68:2867 [2]Genovese, et al. Arth & 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 & 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