POS0686\u2005BARICITINIB DECREASES ANTI-DSDNA AND IGG ANTIBODIES IN ADULTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS FROM A PHASE 2 DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED TRIAL

Abstract

Baricitinib (BARI), an oral, selective Janus kinase (JAK)1 and JAK2 inhibitor, improved disease severity in adults with systemic lupus erythematosus (SLE) receiving standard background therapy in a phase 2 trial1. There were no meaningful reductions in least squares mean change from baseline (BL) in levels of serologic biomarkers for SLE with BARI treatment, including anti-double-stranded deoxyribonucleic acid (anti-dsDNA) antibodies and complement component (C)3 and C41.Evaluate the median change from BL in serologic biomarkers in subgroups and the overall population of BARI-treated SLE patients, in addition to the Systemic Lupus Erythematosus Responder Index-4 (SRI-4) response by normalization of anti-dsDNA.Data were assessed from the phase 2 trial JAHH (NCT02708095). The median change from BL in anti-dsDNA, IgG, C3, and C4 was evaluated over time among the following populations at BL: anti-dsDNA positive (≥30 IU/mL), low C3 (<90\u2009mg/dL), low C4 (<10\u2009mg/dL), and all patients for IgG. Statistical tests were conducted for BARI 2-mg and 4-mg compared with placebo (PBO). Among patients who were anti-dsDNA positive at BL, SRI-4 responder rate was compared for those who stayed positive or achieved normal levels by Week (Wk) 24.Among patients who were anti-dsDNA positive at BL, significant decreases of anti-dsDNA antibodies were observed for BARI 2-mg and 4-mg compared to PBO beginning at Wks 2 and 4, respectively, and continuing through Wk 24 (Figure 1 and Table 1). Moreover, reductions of IgG levels were found for BARI-treated patients including significant decreases for BARI 4-mg compared to PBO at Wks 12 and 24 (Table 1). Among patients who had low levels of C3 and C4 at BL, no significant differences in median change from BL were observed over time with BARI compared to PBO. For patients who were anti-dsDNA positive at BL, no relationship in SRI-4 responder rate was observed for those who stayed positive or achieved normal levels by Wk 24, possibly due to the limited sample size.BARI treatment resulted in a rapid and sustained significant decrease in anti-dsDNA antibodies compared to PBO among anti-dsDNA positive SLE patients at BL, as well as a significant decrease in IgG levels in the 4-mg group at Wks 12 and 24. These data suggest that BARI may have an effect on B cell activity in SLE.[1]Wallace D et al. Lancet. 2018;392:222-231.Table 1.PBOBARI 2-mgBARI 4-mgWeek412244122441224Anti-dsDNA (IU/mL)a0.2 (-17.2, 17.3)2.6 (-14.8, 18.4)3.0 (-14.9, 28.3)-15.4** (-31.4, 1.9)-18.1* (-42.0, 4.1)-29.6** (-55.1, 10.3)-17.9** (-42.7, 1.8)-23.3*** (-50.9, -5.9)-15.1** (-71.9, -4.6)IgG (g/L)b-0.31 (-1.1, 0.4)0.09 (-1.1, 0.7)-0.04 (-0.9, 0.9)-0.60 (-1.3, 0.6)-0.30 (-1.3, 0.4)-0.51 (-1.7, 0.6)-0.56 (-1.2, 0.2)-0.65** (-1.3, 0.2)-0.60** (-1.7, 0.2)Data are median change from baseline (25th, 75th percentiles). aData were assessed for patients that were anti-dsDNA positive (≥30 IU/mL) at baseline (PBO N=51, BARI 2-mg N=56, BARI 4-mg N=53). bData were assessed for all patients (PBO N=105, BARI 2-mg N=105, BARI 4-mg N=104). *p≤0.05, **p≤0.01, ***p≤0.001 for BARI vs. PBO.The authors would like to acknowledge Nicole L. Byers, of Eli Lilly and Company, for medical writing and process support.Thomas Dörner Speakers bureau: Eli Lilly and Company, Roche, and Samsung, Consultant of: AbbVie, Celgene, Eli Lilly and Company, Janssen, Novartis, Roche, Samsung, and UCB, Grant/research support from: Janssen, Novartis, Roche, Sanofi, and UCB, Ronald van Vollenhoven Consultant of: Abbvie, Biotest, BMS, Celgene, Crescendo, Eli Lilly and Company, GSK, Janssen, Merck, Novartis, Pfizer, Roche, UCB, and Vertex, Grant/research support from: Abbvie, Amgen, BMS, GSK, Pfizer, Roche, and UCB, Andrea Doria Speakers bureau: GSK, Janssen, Pfizer, and Roche, Consultant of: Celgene, Eli Lilly and Company, and GSK, Bochao Jia Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Damiano Fantini Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Jorge Ross Terres Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Maria Silk Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Stephanie de Bono Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Peter Fischer Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Daniel J. Wallace Consultant of: Amgen, Aurunia, Eli Lilly and Company, EMD Merck Serono, GSK, and Pfizer