Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: results from the RA-BUILD study.

Abstract

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.

TRIAL REGISTRATION NUMBER:

NCT01721057; Results.

• Authors: Maxime Dougados, Désirée van der Heijde, Ying-Chou Chen, Maria Greenwald, Edit Drescher, Jiajun Liu, Scott Beattie, Sarah Witt, Inmaculada de la Torre, Carol Gaich, Terence Rooney, Douglas Schlichting, Stephanie de Bono, Paul Emery
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 76 Issue 1 Pg. 88-95 (Jan 2017) ISSN: 1468-2060 [Electronic] England
• PMID: 27689735 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Chemical References

• Antirheumatic Agents
• Azetidines
• Protein Kinase Inhibitors
• Purines
• Pyrazoles
• Sulfonamides
• Janus Kinase 1
• Janus Kinase 2
• baricitinib

Topics

• Adult
• Antirheumatic Agents (therapeutic use)
• Arthritis, Rheumatoid (diagnostic imaging, drug therapy)
• Azetidines (administration & dosage, adverse effects, therapeutic use)
• Double-Blind Method
• Female
• Humans
• Janus Kinase 1 (antagonists & inhibitors)
• Janus Kinase 2 (antagonists & inhibitors)
• Male
• Middle Aged
• Protein Kinase Inhibitors (administration & dosage, adverse effects, therapeutic use)
• Purines
• Pyrazoles
• Radiography
• Retreatment
• Severity of Illness Index
• Sulfonamides (administration & dosage, adverse effects, therapeutic use)