POS0714 POOLED SAFETY ANALYSIS OF BARICITINIB IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS: RESULTS FROM THREE RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED, CLINICAL TRIALS

Abstract

BackgroundBaricitinib (BARI), an oral selective inhibitor of Janus kinase 1 and 2 approved for the treatment of rheumatoid arthritis and atopic dermatitis, has been evaluated in clinical studies in patients with systemic lupus erythematosus (SLE).ObjectivesTo assess the safety profile of BARI in patients with SLE.MethodsPatients with SLE receiving stable background therapy were randomised 1:1:1 to BARI 2-mg, 4-mg, or placebo (PBO) once daily in one 24-week, phase 2 (NCT02708095) and two 52-week, phase 3, PBO controlled studies (NCT03616912 and NCT03616964).ResultsA total of 1,849 patients were included in this pooled analysis, representing 1,463.5 patient years of exposure (PYE). The incidence rates per 100 PYR at risk (IR/100 PYR) for serious adverse events (SAEs) were 9.5, 14.7, and 14.1 respectively for PBO, BARI 2-mg, and BARI 4-mg. There were no clinically meaningful differences between treatment groups for discontinuations due to AEs or death (Table 1).Table 1.Overview of safety measures of baricitinib in patients with SLESafety measurePBOBARI 2-mgBARI 4-mgPooled-BARIN=614N=621N=614N=1235PYE=488.1PYE=494.0PYE=481.4PYE=975.4n(%)n(%)n(%)n(%)PYRPYRPYRPYR[IR; 95%CI][IR; 95%CI][IR; 95%CI][IR; 95%CI]SAEs45 (7.3)70 (11.3)*65 (10.6)*135 (10.9)*473.2476.6461.9938.5[9.5; 6.9, 12.7][14.7; 11.5, 18.6][14.1; 10.9, 17.9][14.4; 12.1, 17.0]Discontinuation of study drug due to AE48 (7.8)58 (9.3)57 (9.3)115 (9.3)485.3492.3480.6973.0[9.9; 7.3, 13.1][11.8; 8.9, 15.2][11.9; 9.0, 15.4][11.8; 9.8, 14.2]Death4 (0.7)1 (0.2)4 (0.7)5 (0.4)488.2494.0481.5975.5[0.8; 0.2, 2.1][0.2; 0.0, 1.1][0.8; 0.2, 2.1][0.5; 0.2, 1.2]Serious infections12 (2.0)22 (3.5)28 (4.6)*50 (4.0)*484.3487.2472.5959.7[2.5; 1.3, 4.3][4.5; 2.8, 6.8][5.9; 3.9, 8.6][5.2; 3.9, 6.9]Herpes Zoster18 (2.9)17 (2.7)29 (4.7)46 (3.7)481.1486.5468.6955.1[3.7; 2.2, 5.9][3.5; 2.0, 5.6][6.2; 4.1, 8.9][4.8; 3.5, 6.4]VTEs#6 (1.2)3 (0.6)1 (0.2)4 (0.4)444.0450.2438.1888.3[1.4; 0.5, 2.9][0.7; 0.1, 1.9][0.2; 0.0, 1.3][0.5; 0.1, 1.2]MACE#01 (0.2)3 (0.6)4 (0.4)443.9450.1438.1888.3[0.0; NA, 0.8][0.2; 0.0, 1.2][0.7; 0.1, 2.0][0.5; 0.1, 1.2]Malignancy excluding NMSC2 (0.3)3 (0.5)2 (0.3)5 (0.4)488.0494.1481.4975.5[0.4; 0.0, 1.5][0.6; 0.1, 1.8][0.4; 0.1, 1.5][0.5; 0.2, 1.2]NMSC2 (0.3)000*486.7494.0481.4975.4[0.4; 0.0, 1.5][0.0; NA, 0.7][0.0; NA, 0.8][0.0; NA, 0.4]Data are n (%) patients PYR [IR; 95% CI]. #Phase 2 study data not included. AE=adverse event; CI=confidence interval; MACE=major adverse cardiac event; NMSC=non-melanoma skin cancers; VTE=venous thrombotic event (includes deep vein thrombosis and pulmonary embolism); IR=incidence rate (100 times the number of patients reporting an adverse event divided by the event-specific exposure to treatment); N=number of patients in the analysis population; n=number of patients in the specified category; PYE=patient-year of exposure; PYR=patient years at risk; SAE=serious adverse event. *p≤0.05 vs placebo.The IR/100 PYR for serious infections were 2.5, 4.5, and 5.9 respectively for PBO, BARI 2-mg, and BARI 4-mg. The risk of Herpes Zoster was higher in BARI 4-mg (4.7%) vs PBO (2.9%) (Table 1).The IR/100 PYR for positively adjudicated venous thrombotic events (VTEs) were 1.4, 0.7, and 0.2 respectively for PBO, BARI 2-mg, and BARI 4-mg. The IR/100 PYR for positively adjudicated major adverse cardiac event (MACE) was numerically higher in BARI 2-mg (0.2) and BARI 4-mg (0.7) vs PBO (0.0), however the pooled-BARI IR/PYR (0.5) was within the range of background disease (1). No increased risk for malignancies was observed.ConclusionThe safety profile of BARI in SLE patients was consistent with the known BARI safety profile. There was no increased risk of VTE in BARI treatment groups.