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

Abstract

Introduction: This article evaluates the efficacy and safety of baricitinib 4 mg versus placebo in United States including Puerto Rico (US) and rest of the world (ROW) subpopulations using data pooled from RA-BEAM and RA-BUILD, which enrolled patients with moderate-to-severe adult-onset rheumatoid arthritis (RA).

Methods: In RA-BEAM, patients with an inadequate response (IR) to methotrexate, at least one X-ray erosion, and high sensitivity C-reactive protein (hsCRP) ≥ 6 mg/L were randomized to placebo or orally administered baricitinib 4 mg daily or subcutaneously administered adalimumab 40 mg every other week. In RA-BUILD, patients with an IR to at least one conventional synthetic disease-modifying antirheumatic drug (csDMARD) and with hsCRP ≥ 3.6 mg/L were randomized to placebo or baricitinib 2 or 4 mg daily. Patients in both trials were biologic naive. In this post hoc analysis, data from both studies were pooled (714 baricitinib 4 mg-treated, 716 placebo-treated patients).

Results: Overall, 188 US and 1242 ROW patients were included. Subgroups differed in baseline characteristics including race, weight, age, time since RA diagnosis, current corticosteroid use, and previous csDMARD use. At weeks 12 and 24, baricitinib-treated patients had larger responses compared to placebo-treated patients for multiple efficacy outcomes: American College of Rheumatology 20/50/70 response, low disease activity, remission, Disease Activity Score 28-C-reactive protein, and Health Assessment Questionnaire-Disability Index. Overall, similar efficacy was observed in US and ROW subgroups with no notable safety differences between subgroups at weeks 12 or 24.

Conclusion: Baricitinib 4 mg was efficacious compared to placebo in US and ROW subpopulations. Safety was similar between subgroups.

Funding: Eli Lilly & Company and Incyte Corporation.

Trial registration: ClinicalTrials.gov identifiers, NCT01721057; NCT01710358.

Keywords: Baricitinib; Clinical Trial; Rheumatoid Arthritis; United States.

Figures

Fig. 1

Efficacy at 12 and 24 weeks: baricitinib 4 mg versus placebo. Percentage (95% CI) of patients achieving ACR20, ACR50, and ACR70 at 12 weeks (a) and 24 weeks (c) using nonresponder imputation. The numbers within the bars are the actual percentages. Odds ratios (95% CI) for the baricitinib versus placebo comparisons at 12 weeks (b) and 24 weeks (d) for ACR20, ACR50, and ACR70. The values within the bars are the odds ratios. ACR20, 20% improvement using American College of Rheumatology criteria; ACR50, 50% improvement using American College of Rheumatology criteria; ACR70, 70% improvement using American College of Rheumatology criteria; BARI, baricitinib 4 mg; CI, confidence interval; N, population size; PBO, placebo; ROW, rest of the world; US, United States including Puerto Rico

Fig. 2

Change from baseline in DAS28-CRP and HAQ-DI at 12 and 24 weeks: baricitinib 4 mg versus placebo. Least squares mean (95% CI) using mLOCF are shown for DAS28-hsCRP at 12 (a) and 24 weeks (b) and for HAQ-DI at 12 (c) and 24 weeks (d). The numbers within the bars are the actual values. BARI, baricitinib 4 mg; CI, confidence interval; DAS28-CRP, Disease Activity Score 28 joints high sensitivity C-reactive protein; HAQ-DI, Health Assessment Questionnaire-Disability Index; mLOCF, modified last observation carried forward; LSM, least squares mean; N, population size; PBO, placebo; ROW, rest of the world; US, United States including Puerto Rico

Fig. 3

CDAI at 12 and 24 weeks: baricitinib 4 mg versus placebo. The percentage (95% CI) of patients achieving low disease activity defined as CDAI ≤ 10 at 12 weeks (a) and 24 weeks (b) and remission defined as CDAI ≤ 2.8 at 12 weeks (c) and 24 weeks (d) using NRI are shown. The numbers within the bars are the actual percentages. BARI, baricitinib 4 mg; CI, confidence interval; CDAI, Clinical Disease Activity Index; N, population size; NRI nonresponder imputation; PBO, placebo; ROW, rest of the world; US, United States including Puerto Rico

Fig. 4

SDAI at 12 and 24 weeks: baricitinib 4 mg versus placebo. The percentage (95% CI) of patients achieving low disease activity defined as SDAI ≤ 11 at 12 weeks (a) and 24 weeks (b) and remission defined as SDAI ≤ 3.3 at 12 weeks (c) and 24 weeks (d) using NRI are shown. The numbers within the bars are the actual percentages. BARI, baricitinib 4 mg; CI, confidence interval; N, population size; NRI, nonresponder imputation; PBO, placebo; ROW, rest of the world; SDAI, Simplified Disease Activity Index; US, United States including Puerto Rico