Safety Profile of Baricitinib for the Treatment of Rheumatoid Arthritis up to 7 Years: An Updated Integrated Safety Analysis

Mark Genovese¹, Josef Smolen ², Tsutomu Takeuchi ³, Gerd Burmester ⁴, Dennis Brinker ⁵, Terence Rooney ⁵, Jinglin Zhong ⁶, Daojun Mo ⁵, Chadi Saifan ⁵, Anabela Cardoso ⁵, Maher Issa ⁵, Wen-Shuo Wu ⁵ and Kevin Winthrop ⁷, ¹Stanford University, Stanford, CA, ²Medical University of Vienna, Vienna, Austria, ³Keio University School of Medicine, Tokyo, Japan, ⁴Charité—University Medicine Berlin, Berlin, Germany, ⁵Eli Lilly and Company, Indianapolis, IN, ⁶IQVIA, Morrisville, NC, ⁷Oregon Health and Science University, Portland, OR

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: Janus kinase (JAK) and safety, Rheumatoid arthritis (RA)

Session Information

Date: Sunday, November 10, 2019

Session Title: 3S080: RA – Treatments I: Safety and Outcomes (845–850)

Session Type: ACR Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: Baricitinib (bari), an oral, selective inhibitor of Janus kinase (JAK) 1 and 2, is used to treat moderately to severely active RA in adults. The objective of the study was to update bari’s safety profile with data from an additional Phase 3 trial and ongoing long-term extension (LTE) study.

Methods: Long-term safety of once-daily bari was evaluated in the All-Bari-RA dataset: all patients exposed to any bari dose from 9 randomized trials (5 Phase 3, 3 Phase 2, 1 Phase 1b) and 1 LTE (data to 13-Feb-2018). Placebo comparisons were evaluated to Week 24 from 7 Phase 2/3 trials: patients randomized to placebo, bari 2-mg, or 4-mg, with censoring at rescue/treatment switch. Dose responses were evaluated in the 2/4-mg extended dataset from 4 Phase 2/3 trials: patients 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 (IRs) per 100 patient-years were calculated.

Results: A total of 3770 patients received bari (10,127 patient-years); maximum exposure was 7 years (Table). No significant differences were seen for bari 4-mg versus placebo in adverse events leading to permanent drug discontinuation, death, malignancy, serious infection, or major adverse cardiovascular events. Herpes zoster incidence rate (IR) was significantly higher for bari 4-mg versus placebo (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 versus placebo; IRs were similar in 2/4-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 patients discontinued due to abnormal laboratory results.

Conclusion: In this updated integrated analysis of patients with active RA exposed to bari for up to 7 years, across safety topics, bari maintained a safety profile similar to that previously reported¹ and acceptable in the context of demonstrated efficacy.

Reference: 1. Smolen JS et al. J Rheumatol. 2019;46:7-18.

Disclosure: M. Genovese, AbbVie, 2, 5, Abbvie, 2, 5, AbbVie, Inc., 9, Astellas, 2, 5, Eli Lilly, 2, 5, Eli Lilly and Company, 2, 5, EMD Merck Serono, 2, 5, Galapagos, 2, 5, Galapagos NV, 2, 5, 9, Genentech/Roche, 2, 5, Gilead, 2, 5, Gilead Science, 9, Gilead Sciences, Inc., 2, 5, 9, GSK, 5, Lilly, 2, 5, 9, Novartis, 2, 5, Pfizer, 2, 5, 9, Pfizer Inc, 2, 5, Pfizer, Inc., 9, Pzier, 9, RPharm, 5, Sanofi Genzyme, 2, 5, Vertex, 2, 5; J. Smolen, AbbVie, 2, 5, 8, Abbvie, 2, 5, Amgen, 5, 8, AstraZeneca, 2, 5, 8, Astra-Zeneca, 5, Astro, 5, 8, BMS, 5, Celgene, 5, 8, Celltrion, 5, Celtrion, 5, 8, Chugai, 5, Eli Lilly and Company, 2, 5, Gilead, 5, GlaxoSmithKline, 5, 8, ILTOO, 5, 8, ILTOO Janssen, 5, Janssen, 2, 5, 8, Lilly, 2, 5, 8, Medimmune, 5, 8, MSD, 2, 5, 8, Novartis, 2, 5, Novartis- Sandoz, 5, Novartis-Sandoz, 2, 5, 8, Pfizer, 2, 5, 8, Pfizer Inc, 5, Roche, 2, 5, Roche;, 2, 5, 8, Samsung, 5, 8, Sanofi, 5, 8, Sanofi-Aventis, 5, UCB, 5, 8; T. Takeuchi, AbbVie, 2, 5, 8, AbbVie GK, 2, 9, Asahi Kasei, 2, Asahikasei, 2, Asahikasei Pharma Corp., 2, Astellas, 2, 8, 9, Astellas Pharma Inc, 2, Astellas Pharma, Inc., 2, 5, 8, 9, Astra Zeneca, 2, AstraZeneca, 8, AYUMI, 2, 9, AYUMI Pharmaceutical Corporation, 2, BMS, 2, 8, Boehringer-ingelheim, 9, Bristol–Myers K.K., 9, Bristol-Myers, 2, Bristol-Myers Squibb, 8, Chugai, 2, 8, 9, Chugai Pharmaceutical Co, Ltd., 2, Daiichi Sankyo, 2, 8, 9, Daiichi Sankyo Co., Ltd., 2, Eisai, 2, 5, 8, 9, Eisai Co., Ltd., 2, Eli Lilly, 2, 8, Eli Lilly Japan, 9, Gilead Sciences, Inc., 9, GlaxoSmithKline K.K, 9, GSK, 8, Janssen, 2, 8, Janssen Pharmaceutical K.K, 9, Mitsubishi Tanabe, 2, 9, Mitsubishi Tanabe Pharma Co., 2, Mitsubishi-Tanabe Pharma Corp, 2, 8, 9, Nippon Kayaku, 2, Nipponkayaku, 2, 9, Nipponkayaku Co.Ltd., 2, Novartis, 2, 8, Novartis Pharma K.K, 2, 9, Novartis Pharma K.K., 2, Pfizer, 2, 8, Pfizer Japan, 2, 9, Pfizer Japan Inc., 2, Sanofi, 8, Sanofi K.K, 9, Shionogi & Co., 2, Shionogi & Co., LTD., 2, Taiho, 2, 8, 9, Taisho, 9, Taisho Toyama, 2, 8, Takahashi Industrial and Economic Research Foundation, 2, Takeda, 2, 8, Takeda Pharmaceutical Co., Ltd., 2, Teijin, 2, 8, UCB, 8, 9, UCB Japan, 9; G. Burmester, AbbVie, 5, 8, Abbvie, 5, 8, AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma., 5, 8, AbbVie Inc., 5, 8, BMS, 5, 8, Eli Lilly, 5, 8, Eli Lilly and Company, 5, Gilead, 5, 8, Gilead Sciences, Inc., 5, 8, Janssen, 5, 8, Lilly, 5, 8, Merck, 5, 8, Merck Shar & Dohme, 5, 8, MSD, 5, 8, Pfizer, 2, 5, 8, Roche, 2, 5, 8, Roche, Sanofi-Genzyme, 5, 8, Sanofi, 5, 8, UCB, 5, 8, Union Chimique Belge, 2, 5, 8; D. Brinker, Eli Lilly and Company, 1, 3; T. Rooney, Eli Lilly and Company, 1, 3; J. Zhong, None; D. Mo, Eli Lilly and Company, 1, 3; C. Saifan, Eli Lilly and Company, 1, 3; A. Cardoso, Eli Lilly and Company, 1, 3; M. Issa, Eli Lilly and Company, 1, 3; W. Wu, Eli Lilly and Company, 1, 3; K. Winthrop, AbbVie, 5, Abbvie, 5, Bristol-Myers Squibb, 2, 5, Eli Lilly, 5, Galapagos, 5, Galapagos NV, 5, Gilead, 5, Gilead Sciences, Inc., 5, GSK, 5, Lilly, 5, Pfizer, 2, 5, Roche, 5, UCB, 5, UCB Pharma, 5, UCB Pharma, Pfizer, Bristol-Myers Squibb, Eli Lilly, AbbVie, and Roche., 2, 5.

To cite this abstract in AMA style:

Genovese M, Smolen J, Takeuchi T, Burmester G, Brinker D, Rooney T, Zhong J, Mo D, Saifan C, Cardoso A, Issa M, Wu W, Winthrop K. Safety Profile of Baricitinib for the Treatment of Rheumatoid Arthritis up to 7 Years: An Updated Integrated Safety Analysis [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/safety-profile-of-baricitinib-for-the-treatment-of-rheumatoid-arthritis-up-to-7-years-an-updated-integrated-safety-analysis/. Accessed January 30, 2023.

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