Patient-reported outcomes from a randomized, double-blind, placebo controlled, phase III study of baricitinib versus placebo in patients with moderately to severely active rheumatoid arthritis and an inadequate response to methotrexate therapy: results from the RA-BALANCE study

Abstract

Introduction: To assess the effect of baricitinib on patient-reported outcomes (PROs) in patients with moderately to severely active rheumatoid arthritis (RA) who had an inadequate response to methotrexate (MTX).

Methods: This was a 52-week, randomized, double-blind, placebo controlled, phase III study in patients with RA who had an inadequate response to MTX. Patients (n = 290) receiving stable background MTX were randomly assigned (1:1) to receive placebo or baricitinib 4 mg once daily with a primary endpoint at week 12. PROs assessed included Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient's Global Assessment of Disease Activity, patient's assessment of pain, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), European Quality of Life-5 Dimensions-5 Level index scores and visual analogue scale, and measures collected in electronic patient daily diaries: duration of morning joint stiffness, Worst Tiredness, and Worst Joint Pain. Treatment comparisons were made with logistic regression and analysis of covariance models for categorical and continuous variables, respectively.

Results: Statistically significant (p ⩽ 0.05) improvements in all PROs were observed in the baricitinib 4 mg group compared to placebo as early as week 1 to week 4; and were sustained to week 24. These improvements were maintained until week 52 for the baricitinib group. A significantly larger proportion of patients met or exceeded the minimum clinically important difference for HAQ-DI (⩾0.22) and FACIT-F (3.56) profiles in the baricitinib group.

Conclusion: Baricitinib provided significant improvements in PROs compared to placebo to 52 weeks of treatment in patients with RA who had an inadequate response to MTX.Clinicaltrials.gov identifier: https://clinicaltrials.gov/ct2/show/NCT02265705; NCT02265705; RA-BALANCE. Registered 13 October 2014.

Keywords: China; baricitinib; inadequate response; methotrexate; patient-reported outcomes; rheumatoid arthritis.

Figure 1.

(a) Change from baseline in HAQ-DI. Data presented are LSM change from baseline using mLOCF in the mITT population. **p⩽0.01, ***p⩽0.001 versus placebo; p-values are based on ANCOVA model. ANCOVA, analysis of covariance; HAQ-DI, Health Assessment Questionnaire-Disability Index; LSM, least squares mean; mITT, modified intent-to-treat; mLOCF, modified last observation carried forward. (b) Proportion of patients meeting or exceeding the HAQ-DI MCID of ⩾0.22. Data presented are with non-responder imputation in the mITT population. ***p⩽0.001 versus placebo; p-values are based on logistic regression model. HAQ-DI, Health Assessment Questionnaire-Disability Index; MCID, minimum clinically important difference; mITT, modified intent-to-treat; NRI, non-responder imputation.

Figure 2.

Change from baseline in patient’s global assessment of disease activity. Data presented are LSM change from baseline using mLOCF in the mITT population. *p⩽0.05, **p⩽0.01, ***p⩽0.001 versus placebo; p-values are based on the ANCOVA model. ANCOVA, analysis of covariance; LSM, least squares mean; mITT, modified intent-to-treat; mLOCF, modified last observation carried forward.

Figure 3.

(a) Change from baseline in patient’s assessment of pain. Data presented are LSM change from baseline using mLOCF in the mITT population. *p ⩽ 0.05, **p ⩽ 0.01, ***p ⩽ 0.001 versus placebo; p-values are based on ANCOVA model. ANCOVA, analysis of covariance; LSM, least squares mean; mITT, modified intent-to-treat; mLOCF, modified last observation carried forward. (b) Change from baseline in Worst Joint Pain over time. Data presented are LSM change from baseline using mLOCF in the mITT population. *p ⩽ 0.05, **p ⩽ 0.01, ***p ⩽ 0.001 versus placebo; p-values are based on ANCOVA model. ANCOVA, analysis of covariance; LSM, least squares mean; mITT, modified intent-to-treat; mLOCF, modified last observation carried forward. (c) Proportion of patients with change in pain VAS scores of ⩾10 mm. **p ⩽ 0.01 versusplacebo; p-values are based on the Fisher exact test. VAS, visual analogue scale.

Figure 4.

(a) Change from baseline in FACIT-F. Data presented are LSM using mLOCF and NRI in the mITT population. *p⩽0.05, **p⩽0.01, ***p⩽0.001 versus placebo; p-values in figure are based on ANCOVA model and p-values reported in table of MCID improvement are based on logistic regression model. ANCOVA, analysis of covariance; FACIT-F, functional assessment of chronic illness therapy-fatigue; LSM, least squares mean; MCID, minimum clinically important difference; mITT, modified intent-to-treat; mLOCF, modified last observation carried forward; NRI, non-responder imputation. (b) Change from baseline in Worst Tiredness over time. Data presented are LSM change from baseline using mLOCF in the mITT population. *p⩽0.05, **p⩽0.01, ***p⩽0.001 versus placebo; p-values are based on ANCOVA model. ANCOVA, analysis of covariance; LSM, least squares mean; mITT, modified intent-to-treat; mLOCF, modified last observation carried forward.

Figure 5.

Change from baseline in duration of morning joint stiffness. Data presented are in minutes. *p⩽0.05, **p⩽0.01, ***p⩽0.001 versus placebo; p-values are based on Wilcoxon rank sum test.