Background Baricitinib (BARI) is an oral Janus Kinase (JAK)1/JAK2 inhibitor in development for patients (pts) with active rheumatoid arthritis (RA). Compared to the general population, RA pts have an increased rate of serious infection events (SIE) due to disease state and concomitant therapies.1
Objectives To evaluate the incidence rate (IR) of SIE and associated risk factors in BARI-treated pts with active RA across 8 completed studies (4 Ph3, 3 Ph2, 1 Ph1) and 1 ongoing long-term extension (LTE) study.
Methods The ALL BARI RA analysis set included pts exposed to any BARI dose, with exposure up to 5 years (yrs) (Phase [Ph] 1–3 and LTE studies); the comparison with placebo (PBO) was based on 6 studies (Ph 2–3) with BARI 4 mg once daily (QD) and PBO arms up to Week (Wk) 24; dose response assessment was based on 4 studies (Ph 2–3) with both BARI 2 and 4 mg QD arms up to Wk 24. An extensive list of potential risk factors for SIE was investigated in the ALL BARI RA set using Cox models; SIE risk factors among BARI-treated pts are reported (Table).
Results The most frequent SIE observed in the ALL BARI RA set (N=3492; 5133 pt-yrs (PY) of exposure [PYE] were pneumonia, herpes zoster, urinary tract infection, and cellulitis (all <1%), and 2 patients with SIE died (IR=0.04/100 PY). In the ALL BARI RA set, SIE were reported in 150 pts (IR=2.9/100 PY). During 0–24 Wks, similar SIE rates were observed in BARI 4 mg (N=997; 417 PYE) and PBO (N=1070; 403 PYE) groups in the 6-study set, and between BARI 2 mg (N=479; 192 PYE) and 4 mg (N=479; 194 PYE) dose groups in the 4-study set (Figure). Prior biologic use, advancing age, region of Asia (excluding Japan), non-normal body mass index (BMI), and corticosteroid use were identified as independent factors for SIE in the ALL BARI RA set (Table). Among these SIE risk factors, none significantly differed between BARI 4 mg and PBO in the 6-study dataset (data not shown).
Conclusions SIE incidence was similar between BARI- and PBO-treated RA pts. SIE risk factors include concomitant corticosteroids, prior biologics, non-normal BMI, Asian region of enrollment, and advancing age.
Listing J et al. Rheumatology. 2013;52:53–61.
Disclosure of Interest K. Winthrop Grant/research support from: Pfizer, BMS, Consultant for: Pfizer, UCB, Abbvie, Eli Lilly and Company, Amgen, BMS, M. Genovese Grant/research support from: Eli Lilly and Company, Abbvie, Astellas, Galapagos, Pfizer, Vertex, Crescendo Bioscience, Consultant for: Eli Lilly and Company, Abbvie, Astellas, Galapagos, Pfizer, Vertex, Crescendo Bioscience, M. Harigai Grant/research support from: Bristol-Myers Squibb KK, Eisai Co Ltd, Ono Pharma, Takeda Pharma Ltd, Consultant for: Eli Lilly and Company, L. Chen Employee of: Eli Lilly and Company, C. Dickson Employee of: Eli Lilly and Company, D. Hyslop Employee of: Eli Lilly and Company, A. Nishikawa Employee of: Eli Lilly Japan K.K., J. Bradley Employee of: Eli Lilly and Company, M. Dougados Grant/research support from: Abbvie, Pfizer, Eli Lilly and Company, Novartis, UCB, Merck, Roche, BMS, Consultant for: Abbvie, Pfizer, Eli Lilly and Company, Novartis, UCB, Merck, Roche, BMS