title: Efficacy and Safety of Baricitinib in Japanese Patients with Active Rheumatoid Arthritis Receiving Background Methotrexate Therapy: A 12-week, Double-blind, Randomized Placebo-controlled Study.
abstract: OBJECTIVE
  To evaluate efficacy and safety, baricitinib [Janus kinase (JAK) 1/JAK2 inhibitor] was compared with placebo in Japanese patients with active rheumatoid arthritis (RA) despite background treatment with methotrexate (MTX).
  
  
  METHODS
  This was a phase IIB, double-blind, randomized, placebo-controlled study (clinicaltrials.gov: NCT01469013). Patients had moderate to severe active adult-onset RA despite stable treatment with MTX. Patients (n = 145) were randomized in a 2:1:1:1:1 ratio to placebo or 1 mg, 2 mg, 4 mg, or 8 mg oral baricitinib daily for 12 weeks. The primary analysis compared the combined 4/8-mg dose groups with placebo for the American College of Rheumatology (ACR) 20 response rate at 12 weeks. Other outcomes included additional measures of disease activity, physical function, laboratory abnormalities, and adverse events.
  
  
  RESULTS
  A significantly higher proportion of patients in the combined 4/8-mg baricitinib group (37/48, 77%) compared with the placebo group (15/49, 31%) had at least an ACR20 response after 12 weeks of treatment (p < 0.001). Significant improvements in disease activity, remission, and physical function were observed as early as Week 2 of treatment with baricitinib, particularly with daily doses of ≥ 4 mg. Only 1 patient receiving baricitinib discontinued because of an adverse event. Adverse event rates with baricitinib doses ≤ 4 mg daily were similar to placebo, but there was a higher incidence of adverse events and laboratory abnormalities in the 8-mg group.
  
  
  CONCLUSIONS
  In this phase II study, baricitinib was well tolerated and rapidly improved the signs, symptoms, and physical function of Japanese patients with active RA, supporting continued development of baricitinib (clinicaltrials.gov NCT01469013).
authors.affiliation: From the First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu; Eli Lilly and Co., Tokyo; Eli Lilly Japan K.K., Kobe, Japan; Eli Lilly and Co., Indianapolis, Indiana, USA.Sponsored by Eli Lilly Japan K.K. and Eli Lilly and Co., manufacturer/licensee of baricitinib. Eli Lilly Japan K.K. and Eli Lilly and Co. were involved in the study design, data collection, data analysis, and preparation of the manuscript. Medical writing assistance was provided by Janelle Keys, PhD, CMPP, and Rebecca Lew, PhD, CMPP, of ProScribe, part of the Envision Pharma Group, and was funded by Eli Lilly Japan K.K. ProScribe's services complied with international guidelines for Good Publication Practice (GPP2). ZC and TA are employees of Eli Lilly Japan K.K. KE, DS, TR, and WM are employees of Eli Lilly and Co. and KE owns stock in the company.Y. Tanaka, MD, PhD, Professor, First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health; K. Emoto, MD, PhD, Medical Advisor, Eli Lilly and Co.; Z. Cai, PhD, Senior Associate, Eli Lilly Japan K.K.; T. Aoki, PhD, Senior Associate, Eli Lilly Japan K.K.; D. Schlichting, RN, MS, Principal Research Scientist, Eli Lilly and Co.; T. Rooney, MD, Medical Director, Eli Lilly and Co.; W. Macias, MD, PhD, Distinguished Medical Fellow, Eli Lilly and Co.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: From the First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu; Eli Lilly and Co., Tokyo; Eli Lilly Japan K.K., Kobe, Japan; Eli Lilly and Co., Indianapolis, Indiana, USA.Sponsored by Eli Lilly Japan K.K. and Eli Lilly and Co., manufacturer/licensee of baricitinib. Eli Lilly Japan K.K. and Eli Lilly and Co. were involved in the study design, data collection, data analysis, and preparation of the manuscript. Medical writing assistance was provided by Janelle Keys, PhD, CMPP, and Rebecca Lew, PhD, CMPP, of ProScribe, part of the Envision Pharma Group, and was funded by Eli Lilly Japan K.K. ProScribe's services complied with international guidelines for Good Publication Practice (GPP2). ZC and TA are employees of Eli Lilly Japan K.K. KE, DS, TR, and WM are employees of Eli Lilly and Co. and KE owns stock in the company.Y. Tanaka, MD, PhD, Professor, First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health; K. Emoto, MD, PhD, Medical Advisor, Eli Lilly and Co.; Z. Cai, PhD, Senior Associate, Eli Lilly Japan K.K.; T. Aoki, PhD, Senior Associate, Eli Lilly Japan K.K.; D. Schlichting, RN, MS, Principal Research Scientist, Eli Lilly and Co.; T. Rooney, MD, Medical Director, Eli Lilly and Co.; W. Macias, MD, PhD, Distinguished Medical Fellow, Eli Lilly and Co. emoto_kahaku@lilly.com.
authors.forename: Kahaku
authors.initials: K
authors.lastname: Emoto
authors.affiliation: From the First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu; Eli Lilly and Co., Tokyo; Eli Lilly Japan K.K., Kobe, Japan; Eli Lilly and Co., Indianapolis, Indiana, USA.Sponsored by Eli Lilly Japan K.K. and Eli Lilly and Co., manufacturer/licensee of baricitinib. Eli Lilly Japan K.K. and Eli Lilly and Co. were involved in the study design, data collection, data analysis, and preparation of the manuscript. Medical writing assistance was provided by Janelle Keys, PhD, CMPP, and Rebecca Lew, PhD, CMPP, of ProScribe, part of the Envision Pharma Group, and was funded by Eli Lilly Japan K.K. ProScribe's services complied with international guidelines for Good Publication Practice (GPP2). ZC and TA are employees of Eli Lilly Japan K.K. KE, DS, TR, and WM are employees of Eli Lilly and Co. and KE owns stock in the company.Y. Tanaka, MD, PhD, Professor, First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health; K. Emoto, MD, PhD, Medical Advisor, Eli Lilly and Co.; Z. Cai, PhD, Senior Associate, Eli Lilly Japan K.K.; T. Aoki, PhD, Senior Associate, Eli Lilly Japan K.K.; D. Schlichting, RN, MS, Principal Research Scientist, Eli Lilly and Co.; T. Rooney, MD, Medical Director, Eli Lilly and Co.; W. Macias, MD, PhD, Distinguished Medical Fellow, Eli Lilly and Co.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Cai
authors.affiliation: From the First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu; Eli Lilly and Co., Tokyo; Eli Lilly Japan K.K., Kobe, Japan; Eli Lilly and Co., Indianapolis, Indiana, USA.Sponsored by Eli Lilly Japan K.K. and Eli Lilly and Co., manufacturer/licensee of baricitinib. Eli Lilly Japan K.K. and Eli Lilly and Co. were involved in the study design, data collection, data analysis, and preparation of the manuscript. Medical writing assistance was provided by Janelle Keys, PhD, CMPP, and Rebecca Lew, PhD, CMPP, of ProScribe, part of the Envision Pharma Group, and was funded by Eli Lilly Japan K.K. ProScribe's services complied with international guidelines for Good Publication Practice (GPP2). ZC and TA are employees of Eli Lilly Japan K.K. KE, DS, TR, and WM are employees of Eli Lilly and Co. and KE owns stock in the company.Y. Tanaka, MD, PhD, Professor, First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health; K. Emoto, MD, PhD, Medical Advisor, Eli Lilly and Co.; Z. Cai, PhD, Senior Associate, Eli Lilly Japan K.K.; T. Aoki, PhD, Senior Associate, Eli Lilly Japan K.K.; D. Schlichting, RN, MS, Principal Research Scientist, Eli Lilly and Co.; T. Rooney, MD, Medical Director, Eli Lilly and Co.; W. Macias, MD, PhD, Distinguished Medical Fellow, Eli Lilly and Co.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Aoki
authors.affiliation: From the First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu; Eli Lilly and Co., Tokyo; Eli Lilly Japan K.K., Kobe, Japan; Eli Lilly and Co., Indianapolis, Indiana, USA.Sponsored by Eli Lilly Japan K.K. and Eli Lilly and Co., manufacturer/licensee of baricitinib. Eli Lilly Japan K.K. and Eli Lilly and Co. were involved in the study design, data collection, data analysis, and preparation of the manuscript. Medical writing assistance was provided by Janelle Keys, PhD, CMPP, and Rebecca Lew, PhD, CMPP, of ProScribe, part of the Envision Pharma Group, and was funded by Eli Lilly Japan K.K. ProScribe's services complied with international guidelines for Good Publication Practice (GPP2). ZC and TA are employees of Eli Lilly Japan K.K. KE, DS, TR, and WM are employees of Eli Lilly and Co. and KE owns stock in the company.Y. Tanaka, MD, PhD, Professor, First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health; K. Emoto, MD, PhD, Medical Advisor, Eli Lilly and Co.; Z. Cai, PhD, Senior Associate, Eli Lilly Japan K.K.; T. Aoki, PhD, Senior Associate, Eli Lilly Japan K.K.; D. Schlichting, RN, MS, Principal Research Scientist, Eli Lilly and Co.; T. Rooney, MD, Medical Director, Eli Lilly and Co.; W. Macias, MD, PhD, Distinguished Medical Fellow, Eli Lilly and Co.
authors.forename: Douglas
authors.initials: D
authors.lastname: Schlichting
authors.affiliation: From the First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu; Eli Lilly and Co., Tokyo; Eli Lilly Japan K.K., Kobe, Japan; Eli Lilly and Co., Indianapolis, Indiana, USA.Sponsored by Eli Lilly Japan K.K. and Eli Lilly and Co., manufacturer/licensee of baricitinib. Eli Lilly Japan K.K. and Eli Lilly and Co. were involved in the study design, data collection, data analysis, and preparation of the manuscript. Medical writing assistance was provided by Janelle Keys, PhD, CMPP, and Rebecca Lew, PhD, CMPP, of ProScribe, part of the Envision Pharma Group, and was funded by Eli Lilly Japan K.K. ProScribe's services complied with international guidelines for Good Publication Practice (GPP2). ZC and TA are employees of Eli Lilly Japan K.K. KE, DS, TR, and WM are employees of Eli Lilly and Co. and KE owns stock in the company.Y. Tanaka, MD, PhD, Professor, First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health; K. Emoto, MD, PhD, Medical Advisor, Eli Lilly and Co.; Z. Cai, PhD, Senior Associate, Eli Lilly Japan K.K.; T. Aoki, PhD, Senior Associate, Eli Lilly Japan K.K.; D. Schlichting, RN, MS, Principal Research Scientist, Eli Lilly and Co.; T. Rooney, MD, Medical Director, Eli Lilly and Co.; W. Macias, MD, PhD, Distinguished Medical Fellow, Eli Lilly and Co.
authors.forename: Terence
authors.initials: T
authors.lastname: Rooney
authors.affiliation: From the First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu; Eli Lilly and Co., Tokyo; Eli Lilly Japan K.K., Kobe, Japan; Eli Lilly and Co., Indianapolis, Indiana, USA.Sponsored by Eli Lilly Japan K.K. and Eli Lilly and Co., manufacturer/licensee of baricitinib. Eli Lilly Japan K.K. and Eli Lilly and Co. were involved in the study design, data collection, data analysis, and preparation of the manuscript. Medical writing assistance was provided by Janelle Keys, PhD, CMPP, and Rebecca Lew, PhD, CMPP, of ProScribe, part of the Envision Pharma Group, and was funded by Eli Lilly Japan K.K. ProScribe's services complied with international guidelines for Good Publication Practice (GPP2). ZC and TA are employees of Eli Lilly Japan K.K. KE, DS, TR, and WM are employees of Eli Lilly and Co. and KE owns stock in the company.Y. Tanaka, MD, PhD, Professor, First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health; K. Emoto, MD, PhD, Medical Advisor, Eli Lilly and Co.; Z. Cai, PhD, Senior Associate, Eli Lilly Japan K.K.; T. Aoki, PhD, Senior Associate, Eli Lilly Japan K.K.; D. Schlichting, RN, MS, Principal Research Scientist, Eli Lilly and Co.; T. Rooney, MD, Medical Director, Eli Lilly and Co.; W. Macias, MD, PhD, Distinguished Medical Fellow, Eli Lilly and Co.
authors.forename: William
authors.initials: W
authors.lastname: Macias
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy*; D001384:Azetidines / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D011687:Purines; D011720:Pyrazoles; D012074:Remission Induction; D012720:Severity of Illness Index; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D063189:Symptom Assessment; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D001384:Azetidines; D011687:Purines; D011720:Pyrazoles; D013449:Sulfonamides; C000596027:baricitinib; D008727:Methotrexate
keywords: BARICITINIB; JAPAN; RHEUMATOID ARTHRITIS