Safety Profile of Baricitinib in Patients with Active Rheumatoid Arthritis: An Integrated Analysis
Erica Tierney (non-author presenter)1, Josef S. Smolen2, Mark C. Genovese3, Tsutomu Takeuchi4, David Hyslop5, William L. Macias5, Terence P. Rooney5, Lei Chen5, Christina Dickson5, Jennifer Riddle5, Tracy E. Cardillo5, Kevin Winthrop6
1Eli Lilly and Company Limited, Lilly Ireland, Dublin, Ireland; 2Medical University of Vienna, Vienna, Austria; 3Stanford University Medical Center, Palo Alto, CA, USA; 4Keio University, Tokyo, Japan; 5Eli Lilly and Company, Indianapolis, IN, USA; 6Oregon Health Sciences University, Portland, OR, USA
Baricitinib (bari) (an oral janus kinase [JAK]1/JAK2 inhibitor) is in development for patients (pts) with active rheumatoid arthritis (RA).
To assess the safety of bari in pts with active RA across 8 completed studies (4 phase 3, 3 phase 2, 1 phase 1b) and 1 ongoing long-term extension study).
Primary safety analysis was based on 6 studies (all with bari 4-mg once daily [QD] and placebo [PBO] arms) and dose response assessments on 4 studies (all with bari 2- and 4-mg QD and PBO arms). In addition, the “all-bari” RA set included all pts exposed to any bari dose. Two studies contained active comparators.
In total, 3464 pts were exposed to bari (4214 patient-years [PY]; 2166 pts [62.5%] >1 year; 467 [13.5%] >2 years). In controlled periods of the program, no increases in deaths, adverse events leading to study drug discontinuation, malignancies, major adverse cardiac events, or serious infections were seen for bari versus PBO/active treatment. Herpes zoster was reported more frequently for bari vs PBO. In randomized, controlled periods of the program, tuberculosis (TB) was reported in 2 pts: 1 bari 4 mg, 1 adalimumab; in uncontrolled periods, 6 TB events were reported (bari 4 mg: 2 with incomplete TB screening, 3 without organism confirmed). All TB occurred in endemic areas. Two gastrointestinal perforations were reported (0.05/100 PY). Bari treatment has been associated with changes in selected hematology/clinical chemistry analytes; few pts (<1%) discontinued due to abnormal laboratory results. There was no observed increased risk over time for the above outcome measures with longer exposure.
In the context of reported efficacy, bari had an acceptable safety profile in pts with moderately to severely active RA.
This abstract was previously presented at EULAR 2016 London, UK 8-11 June and published in the Annals of the Rheumatic Diseases, June 2016, Volume 75 (Supplement 2), pages 243-244.