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FRI0132 LONG-TERM SAFETY AND EFFICACY OF UPADACITINIB IN PATIENTS WITH RHEUMATOID ARTHRITIS AND AN INADEQUATE RESPONSE TO CSDMARDS: RESULTS AT 60 WEEKS FROM THE SELECT-NEXT STUDY

2019; BMJ; Linguagem: Inglês

10.1136/annrheumdis-2019-eular.3082

1468-2060

Gerd R Burmester, Filip Van den Bosch, Louis Bessette, Alan Kivitz, Yihan Li, Alan Friedman, Aileen L. Pangan, Heidi S. Camp, Joel M. Kremer,

Biosimilars and Bioanalytical Methods

Background Upadacitinib (UPA), an oral, JAK1-selective inhibitor showed efficacy over 12 weeks (wks) in patients (pts) with moderately to severely active rheumatoid arthritis (RA) and inadequate response to csDMARDs (SELECT-NEXT). 1 Objectives We assessed safety and efficacy of UPA through Wk60 in an ongoing extension of the phase 3 SELECT-NEXT study. Methods Pts received once-daily (QD) UPA at 15 mg (UPA15), 30 mg (UPA30) or placebo (PBO) for 12 wks on stable background csDMARDs. From Wk12, the start of a long-term blinded extension, pts initially randomized to PBO at BL were switched to UPA15mg or 30mg per pre-specified assignment at BL. Pts randomized to UPA continued their assigned dose. No dose adjustments of UPA were allowed; however, starting at Wk24, adjustments to background RA medications were permitted. Sites/subjects remain blinded to UPA dose throughout the extension period. Efficacy data up to Wk60 are reported “As Observed”. Adverse events (AE) per 100 pt yrs (PY) are summarized based on a cut-off date of Mar 22 2018. Results 611/661 (92%) pts completed Wk12 and continued on to the extension. By the safety data cut-off date, 125/611 (20%) had discontinued study drug, 50 (8.2%) discontinued due to an AE, and 10 (1.6%) due to lack of efficacy. Cumulative exposure was 393.3 PYs and 372.4 PYs for UPA15 and UPA30 respectively. Based on As Observed analysis, for pts who continued on UPA15 (262/310 [85%]) and UPA30 (243/301 [81%]), clinical and functional outcomes continued to improve or were maintained through Wk60, with 59% and 56% of pts achieving DAS28-CRP <2.6 and 35% and 32% achieving CDAI remission (≤2.8) with UPA 15 and 30 mg, respectively. Pts who switched from PBO to UPA15 or UPA30 showed comparable efficacy to those initially randomized to UPA (Table 1). The most frequently reported AEs were nasopharyngitis, urinary tract infection, upper respiratory tract infection, bronchitis, blood creatine phosphokinase increased, alanine aminotransferase increased, herpes zoster (HZ) and nausea. Most frequent AEs (≥0.8/100PYs) leading to premature study drug discontinuation were pneumonia, transaminase elevations, HZ and pyrexia. Event rates (E/100PYs) were numerically higher in UPA30 vs UPA15 for serious AE, AE leading to discontinuation, serious infections, HZ and malignancies, and were similar in UPA15 and UPA30 for adjudicated major adverse cardiovascular events and venous thromboembolic events (Table 2). Conclusion UPA15mg and 30mg on background csDMARD therapy demonstrated consistent efficacy and safety over 60 weeks in RA patients with inadequate response to csDMARDs. Both doses of UPA showed a similar efficacy profile at Wk 60, with numerically higher rates for certain safety events noted in the UPA30 group. An integrated safety analysis of upadacitinib across the phase 3 program is required to fully characterize the benefit:risk of UPA in RA. Reference [1] Burmester, et al. Lancet. 2018 Jun 23;391(10139):2503-2512 Acknowledgement 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, of AbbVie, Inc. Disclosure of Interests Gerd Rüdiger Burmester Consultant for: Roche, Sanofi-Genzyme, Speakers bureau: Roche, Sanofi-Genzyme, Filip van den Bosch Consultant for: AbbVie, BMS, Galapagos, Janssen, Lilly, Merck, Novartis, Pfizer and UCB, Speakers bureau: AbbVie, BMS, Janssen, Lilly, Merck, Novartis, Pfizer and UCB., Louis Bessette Grant/research support from: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Consultant for: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Speakers bureau: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Alan Kivitz Shareholder of: Novartis, Consultant for: Abbvie, Janssen, Pfizer, UCB, Genzyme, Sanofi, Regeneron, Boehringer Ingelheim, Sun Pharma Advanced Research, Flexion., Paid instructor for: Celgene, Horizon, Merck, Novartis, Pfizer, Genzyme, Sanofi, Regeneron, Speakers bureau: Celgene, Horizon, Merck and Genetech, Flexion, Yihan Li Shareholder of: AbbVie, Employee of: AbbVie, Alan Friedman Shareholder of: AbbVie, Employee of: AbbVie, Aileen Pangan Shareholder of: AbbVie, Employee of: AbbVie, Heidi Camp Shareholder of: AbbVie, Employee of: AbbVie, Joel Kremer Grant/research support from: AbbVie, Genentech, Lilly, Novartis, Pfizer, Consultant for: AbbVie, Amgen, BMS, Genentech, Lilly, Regeneron, Sanofi, Pfizer