219 Safety summary results of baricitinib focusing on serious infections events and preselected comorbidities

Abstract

Background: Baricitinib (BARI) is an oral selective JAK1/JAK2 inhibitor for the treatment of patients with rheumatoid arthritis (RA) with an acceptable safety profile. Objective is to evaluate the incidence rate (IR) of serious infection events (SIE), associated risk factors, and the effect of selected comorbidities on safety in BARI-treated patients with active RA. Methods: Exposure adjusted IR of SIE were summarised in 6-studyand 4-study- PBO-controlled sets, 0-24 weeks, plus in ALL-BARI-RA set (any BARI dose for ≤5 years (Ph 1-3/LTE studies)). Potential risk factors for SIE were investigated in ALL-BARI-RA set using Cox models. Sensitivity analysis for preselected historical or current comorbidities included conventional DMARD-Inadequate Responder patients (N=1683) from five studies (BARI 4mg/PBO) up to 16 weeks. Four analysis sets defined in table footnote. Results: The most frequent SIE observed in the ALL-BARI-RA set (N=3492; 5133 patient-years (PY) of exposure [PYE]) were pneumonia, herpes zoster, urinary tract infection, and cellulitis (all <1%), 150 patients reported SIE (IR=2.9/100PY), and two patients with SIE died (IR=0.04/100PY). During weeks 0-24, similar SIE rates were observed in BARI 4mg (N=997; 417PYE) and PBO (N=1070; 403PYE) groups in the 6-study set, and between BARI 2/4mg (N=479; 192PYE/N=479; 194PYE) dose groups in the 4-study set. Prior biologic use, advancing age, region of Asia (excluding Japan), abnormal body mass index (BMI), and corticosteroid use were identified as independent factors for SIE in the ALL-BARI-RA set, and none differed significantly between BARI 4mg and PBO in the 6-study dataset (data not shown). The presence of selected comorbidities did not affect the incidence of treatment emergent adverse events (TEAEs), serious adverse events (SAEs), discontinuations, or deaths caused by SAEs for BARI 4mg vs PBO (Table). The most common TEAEs were nasopharyngitis and upper respiratory tract infection. Conclusion: SIE incidence was similar between BARI- and PBO- and BARI 2mg and 4mg treated RA patients up to week 24. No trends were noted for patients in each preselected comorbidity subgroup for increased risk of events after treatment with BARI 4mg compared with PBO up to week 16. (Table Presented).