Background Baricitinib, a novel, oral inhibitor of JAK1/JAK2 in the JAK-STAT signaling pathway, was evaluated in a blinded Phase 2b study in Japanese patients (pts) with rheumatoid arthritis (RA) with an inadequate response to methotrexate (MTX).
Objectives The primary objective was to evaluate the efficacy of baricitinib as determined by the combined proportion of pts in the 4- and 8-mg dose groups who achieved an ACR20 response compared to placebo at Week 12.
Methods Pts were randomized 2:1:1:1:1 to receive placebo (PBO) or 1 of 4 once-daily baricitinib doses (1, 2, 4, or 8 mg, respectively) for 12 weeks.
Results Of the 145 pts randomized, 77% of the combined 4- and 8-mg (67% of the 4-mg and 88% of the 8-mg dose) groups achieved ACR20 responses compared with 31% of PBO-treated pts (p≤0.001) at Week 12. Significant differences versus PBO (p<0.05) were observed in the proportion of patients achieving ACR50 in a dose-dependent manner at Week 12 (Table). Greater benefit was also seen in the 4- and 8-mg groups compared to PBO using additional measures of efficacy including DAS28-CRP and HAQ-DI (Table). The rates of treatment-emergent adverse events (AEs) were similar in the PBO and combined baricitinib groups through 12 weeks (53% vs 55%, respectively). Most AEs were mild. Serious AEs were reported in 2 pts. There were no opportunistic infections and no deaths. Hemoglobin changes (median, in mmol/L) from baseline at 12 weeks were -0.13, 0.13, -0.10, 0.0, and -0.19 for PBO, 1-, 2-, 4-, and 8-mg groups, respectively. Neutrophil count changes (median, in109/L) from baseline at 12 weeks were -0.25, -0.32, -0.60, -1.12, and -0.48 for PBO, 1-, 2-, 4-, and 8-mg groups, respectively. Dose-related increases from baseline (median) in serum creatinine and both HDL- and LDL-cholesterol were observed at 12 weeks, with the largest changes observed for the 8-mg group. Dose-dependent changes in several bone metabolic markers were also observed.
Conclusions Clinical efficacy was demonstrated in this Phase 2b study of baricitinib in combination with background MTX in Japanese RA pts through 12 weeks. Safety signals observed through 12 weeks were consistent with a previous study of baricitinib in non-Japanese pts with RA.1
Keystone et al. Ann Rheum Dis 2012; 71(Suppl3):152
Acknowledgements Study sponsored by Eli Lilly Japan K.K.
Disclosure of Interest : Y. Tanaka Grant/research support: Bristol-Meyers Squibb, Mitsubishi Tanabe Pharma, AbbVie, MSD, Chugai Pharmaceutical, Astellas Pharma, Daiichi Sankyo, Consultant for: Mitsubishi Tanabe Pharma, Eisai, Chugai Pharmaceutical, Abbott Japan, Astellas Pharma, Daiichi Sankyo, AbbVie, Janssen Pharmaceuticals, Pfizer Japan, Takeda Pharmaceutical Company Limited, AstraZeneca, Eli Lilly Japan, GlaxoSmithKline, Quintiles, MSD, and Asahi Kasei Pharma, K. Emoto Shareholder of: Eli Lilly Japan K.K., Employee of: Eli Lilly Japan K.K., M. Tsujimoto Employee of: Eli Lilly Japan K.K., D. Schlichting Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, W. Macias Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company