THU0078 SAFETY PROFILE OF BARICITINIB FOR THE TREATMENT OF RHEUMATOID ARTHRITIS UP TO 7 YEARS: AN UPDATED INTEGRATED SAFETY ANALYSIS
Authors: Mark C. Genovese, Josef S. Smolen, Tsutomu Takeuchi, Gerd Rüdiger Burmester, Dennis Brinker, Terence Rooney, Jinglin Zhong, Daojun Mo, Chadi Saifan, Anabela Cardoso, Maher Issa, Wen-Shuo Wu, Kevin Winthrop
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Baricitinib (bari), is an oral, selective inhibitor of Janus kinase (JAK) 1/JAK 2, to treat moderately to severely active RA in adults. <h3>Objectives:</h3> To update bari's safety profile with data from an additional Phase (Ph) 3 trial and on-going long-term extension (LTE) study. <h3>Methods:</h3> Long-term safety of once-daily bari was evaluated in the All-Bari-RA dataset: all patients (pts) exposed to any bari dose from 9 randomized trials (5 Ph3, 3 Ph2, 1 Ph 1b) and 1 LTE (data to 13-Feb-2018). Placebo (PBO) comparisons were evaluated to Week 24 from 7 Ph2/3 trials: pts randomized to PBO, bari 2-mg or 4-mg, with censoring at rescue/treatment switch. Dose responses were evaluated in the 2-mg/4-mg extended dataset from 4 Ph2/3 trials: pts randomized to 2- or 4-mg, LTE data included; data censored at rescue/dose change (as-treated analysis) and, due to latent period for malignancy, analyzed without censoring (as-randomized analysis). Incidence rates (IR) per 100 patient-years (PY) were calculated. <h3>Results:</h3> 3770 pts received bari (10127 PYs); maximum exposure was 7 yrs (Table). No significant differences were seen for bari 4-mg vs PBO in adverse events leading to permanent drug discontinuation, death, malignancy, serious infection, or major adverse cardiovascular events. Herpes zoster IR was significantly higher for bari 4-mg vs PBO (3.8 vs 0.9) and numerically higher for bari 2-mg (3.1). IRs for deep vein thrombosis/pulmonary embolism were numerically higher in bari 4-mg vs PBO; IRs were similar by dose in 2-mg/4-mg-extended dataset. Malignancy (excluding non-melanoma skin cancer) IRs were 0.8 (2-mg) and 1.0 (4-mg; as-randomized analysis). Fewer than 1% of pts discontinued due to abnormal laboratory results. <h3>Conclusion:</h3> In this updated integrated analysis of pts with active RA exposed to bari for up to 7 yrs, across safety topics, bari maintained a safety profile similar to that previously reported<sup>1</sup> and acceptable in the context of demonstrated efficacy. <h3>Reference:</h3> [1] Smolen JS, et al. J Rheumatol. 2019;46:7-18. <h3>Disclosure of Interests:</h3> Mark C. Genovese Grant/research support from: Sanofi/Genzyme, Genentech/Roche, RPharm, Consultant for: Sanofi/Genzyme, Genentech/Roche, RPharm, Josef S. Smolen Grant/research support from: AbbVie, Eli Lilly, Janssen, MSD, Pfizer Inc, Roche, Consultant for: AbbVie, Amgen, AstraZeneca, Astro, Celgene, Celtrion, Eli Lilly, GlaxoSmithKline, ILTOO, Janssen, Medimmune, MSD, Novartis-Sandoz, Pfizer Inc, Roche, Samsung, Sanofi, UCB, Speakers bureau: AbbVie, Amgen, AstraZeneca, Astro, Celgene, Celtrion, Eli Lilly, GlaxoSmithKline, ILTOO, Janssen, Medimmune, MSD, Novartis-Sandoz, Pfizer Inc, Roche, Samsung, Sanofi, UCB, Tsutomu Takeuchi Grant/research support from: Astellas Pharma Inc, Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Takeda Pharmaceutical Co., Ltd., AbbVie GK, Asahikasei Pharma Corp., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Eisai Co., Ltd., AYUMI Pharmaceutical Corporation, Nipponkayaku Co. Ltd., Novartis Pharma K.K., Grant/research support from: AbbVie, Asahi Kasei, Astellas, AstraZeneca, AYUMI, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Janssen, Mitsubishi Tanabe, Nippon Kayaku, Novartis, Pfizer Japan Inc, Taiho, Taisho Toyama, Takeda, Teijin, Grant/research support from: Astellas Pharma Inc., Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., AbbVie GK, Asahi Kasei Pharma Corp., Taisho Toyama Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Ltd., Janssen Pharmaceutical K.K., Celltrion Inc., Nipponkayaku Co. Ltd., and UCB Japan, Consultant for: Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., Abbivie GK, Nipponkayaku Co.Ltd, Janssen Pharmaceutical K.K., Astellas Pharma Inc., Taiho Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., Taisho Toyama Pharmaceutical Co. Ltd., GlaxoSmithKline K.K., UCB Japan Co. Ltd., Consultant for: AbbVie, Asahi Kasei, Astellas, AstraZeneca, AYUMI, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Janssen, Mitsubishi Tanabe, Nippon Kayaku, Novartis, Pfizer Japan Inc, Taiho, Taisho Toyama, Takeda, Teijin, Consultant for: Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., Asahi Kasei Medical K.K., AbbVie GK, Daiichi Sankyo Co., Ltd., Bristol Myers Squibb, and Nipponkayaku Co. Ltd., Speakers bureau: Astellas Pharma Inc., Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., AbbVie GK, Asahi Kasei Pharma Corp., Taisho Toyama Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Ltd., Janssen Pharmaceutical K.K., Celltrion Inc., Nipponkayaku Co. Ltd., and UCB Japan, Speakers bureau: AbbVie, Asahi Kasei, Astellas, AstraZeneca, AYUMI, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Janssen, Mitsubishi Tanabe, Nippon Kayaku, Novartis, Pfizer Japan Inc, Taiho, Taisho Toyama, Takeda, Teijin, Speakers bureau: AbbVie GK., Bristol–Myers K.K., Chugai Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Astellas Pharma Inc, Diaichi Sankyo Co. Ltd., Eisai Co. Ltd., Sanofi K.K., Teijin Pharma Ltd., Takeda Pharmaceutical Co. Ltd., Novartis Pharma K.K., Gerd Rüdiger Burmester Consultant for: Roche, Sanofi-Genzyme, Speakers bureau: Roche, Sanofi-Genzyme, Dennis Brinker Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Terence Rooney Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Jinglin Zhong Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Daojun Mo Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Chadi Saifan Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Anabela Cardoso Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Maher Issa Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Wen-Shuo Wu Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Kevin Winthrop Consultant for: Gilead, Galapagos, Eli Lilly and Company, Abbvie, Pfizer, GSK