Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: results from the RA-BUILD study.
BACKGROUND
Baricitinib is an oral, reversible, selective Janus kinase 1 and 2 inhibitor.


METHODS
In this phase III, double-blind 24-week study, 684 biologic disease-modifying antirheumatic drug (DMARD)-naïve patients with rheumatoid arthritis and inadequate response or intolerance to ≥1 conventional synthetic DMARDs were randomly assigned 1:1:1 to placebo or baricitinib (2 or 4 mg) once daily, stratified by region and the presence of joint erosions. Endpoint measures included American College of Rheumatology 20% response (ACR20, primary endpoint), Disease Activity Score (DAS28) and Simplified Disease Activity Index (SDAI) score ≤3.3.


RESULTS
More patients achieved ACR20 response at week 12 with baricitinib 4 mg than with placebo (62% vs 39%, p≤0.001). Compared with placebo, statistically significant improvements in DAS28, SDAI remission, Health Assessment Questionnaire-Disability Index, morning joint stiffness, worst joint pain and worst tiredness were observed. In a supportive analysis, radiographic progression of structural joint damage at week 24 was reduced with baricitinib versus placebo. Rates of adverse events during the treatment period and serious adverse events (SAEs), including serious infections, were similar among groups (SAEs: 5% for baricitinib 4 mg and placebo). One patient had an adverse event of tuberculosis (baricitinib 4 mg); one patient had an adverse event of non-melanoma skin cancer (baricitinib 4 mg). Two deaths and three major adverse cardiovascular events occurred (placebo). Baricitinib was associated with a decrease in neutrophils and increases in low-density and high-density lipoprotein.


CONCLUSIONS
In patients with rheumatoid arthritis and an inadequate response or intolerance to conventional synthetic DMARDs, baricitinib was associated with clinical improvement and inhibition of progression of radiographic joint damage.


BACKGROUND
NCT01721057; Results.
Department of Rheumatology, Paris Descartes University, Hôpital Cochin, Assistance Publique, Hôpitaux de Paris, INSERM (U1151), Clinical Epidemiology and Biostatistics, PRES Sorbonne Paris-Cité, Paris, France.
Maxime
M
Dougados
Leiden University Medical Center, Leiden, The Netherlands.
Désirée
http://orcid.org/0000-0002-5781-158X
D
van der Heijde
Division of Rheumatology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan; Chang Gung Memorial Hospital - Kaohsiung Medical Center, Chang Gung University College of Medicine, Taiwan.
Ying-Chou
YC
Chen
Desert Medical Advances, Palm Desert, California, USA.
Maria
M
Greenwald
Veszprém Csolnoky Ferenc County Hospital, Veszprém, Hungary.
Edit
E
Drescher
Eli Lilly and Company, Indianapolis, Indiana, USA.
Jiajun
J
Liu
Eli Lilly and Company, Indianapolis, Indiana, USA.
Scott
S
Beattie
Eli Lilly and Company, Indianapolis, Indiana, USA.
Sarah
S
Witt
Eli Lilly and Company, Indianapolis, Indiana, USA.
Inmaculada
I
de la Torre
Eli Lilly and Company, Indianapolis, Indiana, USA.
Carol
C
Gaich
Eli Lilly and Company, Indianapolis, Indiana, USA.
Terence
T
Rooney
Eli Lilly and Company, Indianapolis, Indiana, USA.
Douglas
D
Schlichting
Eli Lilly and Company, Indianapolis, Indiana, USA.
Stephanie
S
de Bono
Leeds Institute of Rheumatic and Musculoskeletal Medicine, NIHR Leeds Musculoskeletal Biomedical Research Unit, LTHT, University of Leeds, Leeds, UK.
Paul
P
Emery
D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy*; D001384:Azetidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D053613:Janus Kinase 1 / Q000037:antagonists & inhibitors; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011687:Purines; D011720:Pyrazoles; D011859:Radiography; D019233:Retreatment; D012720:Severity of Illness Index; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D018501:Antirheumatic Agents; D001384:Azetidines; D047428:Protein Kinase Inhibitors; D011687:Purines; D011720:Pyrazoles; D013449:Sulfonamides; D053613:Janus Kinase 1; D053614:Janus Kinase 2; C000596027:baricitinib
DMARDs (synthetic); Rheumatoid Arthritis; Treatment
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