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

Abstract

BackgroundBaricitinib is an oral, reversible, selective Janus kinase 1 and 2 inhibitor.MethodsIn 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.ResultsMore 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.ConclusionsIn 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 numberNCT01721057; Results.

Baricitinib in Patients with Rheumatoid Arthritis and an Inadequate Response to Conventional Disease-Modifying Antirheumatic Drugs in United States and Rest of World: A Subset Analysis

“…This is a post hoc pooled analysis from RA-BUILD (NCT01721057) [8] and RA-BEAM (NCT01710358) [9]. In both trials, key inclusion criteria included C 6 out of 68 tender joints, C 6 out of 66 swollen joints, and IR to at least one csDMARD (stable background csDMARD permitted).…”

“…In two global, double-blind phase 3 studies in patients with active RA and either inadequate response (IR) to csDMARDs (RA-BUILD) [8] or IR to methotrexate (RA-BEAM) [9], once daily (QD) baricitinib was associated with clinical improvements through 24 weeks, with an acceptable safety profile. Geographic differences in RA presentation and its management may affect patient outcomes.…”

“…Understanding these characteristics can provide additional information for the clinician that is relevant to their patient population and assessment of response. The dose of baricitinib 4 mg was chosen because it was common to both RA-BEAM and RA-BUILD [8,9].…”

Baricitinib: a new oral treatment for rheumatoid arthritis

“…Treatment should not be initiated in patients with an absolute lymphocyte count of <0.5 x 10 9 cells/L, an absolute neutrophil count <1 x 10 9 cells/L or haemoglobin <8g/dL. 5 RA BUILD 6 and RA BEAM. 7 The primary endpoint was the American College of Rheumatology 20% response (ACR20, a 20% reduction in scores for joints, pain, patient and investigator assessments, and disability).…”

“…10 A total of 684 patients with an insufficient response or intolerance to a conventional DMARD but no prior treatment with a biological DMARD were randomised to treatment with baricitinib 2 or 4mg daily or placebo in RA BUILD. 6 Most patients were taking methotrexate, alone or with a second DMARD.…”