Patient-reported outcomes from a phase 3 study of baricitinib versus placebo or adalimumab in rheumatoid arthritis: secondary analyses from the RA-BEAM study

Abstract

Background: To assess the effect of baricitinib on patient-reported outcomes (PROs) in patients with active rheumatoid arthritis and an inadequate response to methotrexate (MTX).

Methods: In this double-blind phase 3 study, patients were randomised 3:3:2 to placebo (n=488), baricitinib 4 mg once daily (n=487), or adalimumab 40 mg biweekly (n=330) with background MTX. PROs included the SF-36, EuroQol 5-D (EQ-5D) index scores and visual analogue scale, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient's Global Assessment of Disease Activity (PtGA), patient's assessment of pain and Work Productivity and Activity Impairment Questionnaire-Rheumatoid Arthritis (WPAI-RA), and measures collected in electronic patient daily diaries: duration and severity of morning joint stiffness (MJS), Worst Ttiredness and Worst Joint Pain. The primary study endpoint was at week 12. Treatment comparisons were assessed with logistic regression for categorical measures or analysis of covariance for continuous variables.

Results: Compared with placebo and adalimumab, baricitinib showed statistically significant improvements (p≤0.05) in HAQ-DI, PtGA, pain, FACIT-F, SF-36 physical component score, EQ-5D index scores and WPAI-RA daily activity at week 12. Improvements were maintained for measures assessed to week 52. Statistically significant improvement in patient diary measures (MJS duration and severity), worst tiredness and worst joint pain were observed for baricitinib versus placebo and adalimumab at week 12 (p≤0.05).

Conclusions: Baricitinib provided significantly greater improvement in most PROs compared with placebo and adalimumab, including physical function MJS, pain, fatigue and quality of life. Improvement was maintained to the end of the study (week 52).

Trial registration: NCT01710358.

Keywords: outcomes research; patient perspective; rheumatoid arthritis.

Conflict of interest statement

Competing interests: ECK has received grant/research support, consulting support or speaker bureau fees from Abbott, Amgen, AstraZeneca, Biotest, Bristol Myers Squibb, F. Hoffmann-La Roche Inc., Janssen, Eli Lilly and Company, Genentech, Janssen, Merck, Novartis, Pfizer, Sanofi-Aventis and UCB. PCT has received grant/research support or consulting support from AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Galapagos, GlaxoSmithKline, Merck, Pfizer, Takeda and UCB. YT has received grant/research support or speaker bureau fees from AbbVie, Astellas, Asahi Kasei, Bristol Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly and Company, GlaxoSmithKline, Janssen, Kyowa-Kirin, Mitsubishi-Tanabe, MSD, Pfizer, Santen, Takeda, Taisho-Toyama, Teijin and UCB. CG, AMD, TR, SdB, VA and BL are employees of Eli Lilly and Company, and all except AMD are shareholders of Eli Lilly and Company. AD is a consultant for Eli Lilly and Company. JVZ is a consultant for Eli Lilly and Company. JACC is a consultant for Eli Lilly and Company. MEW has received grant/research support or consulting support from AbbVie, Amgen, Bristol-Myers Squibb, Canfite, Corrona, Crescendo Bioscience, Genzyme, Idera, Infinity, Lycera, Eli Lilly and Company, Medimmune, Merck, Merck/serona, Momenta, Novartis, Pfizer, Roche, Samsung, Sanofi and UCB.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1

Change from baseline over time for the patient-reported ouctomes collected by the daily patient electronic diaries (data and either SD or 95% CIs are presented in online supplementary file 5). (A) Duration of Morning Joint Stiffness: data are mean duration of morning joint stiffness in minutes, based on daily diary entries. Daily question: ‘Please indicate how long your morning joint stiffness lasted today’. Indications of statistical significance based on analysis of median difference. (B) Severity of Morning Joint Stiffness: data are LS mean scores for severity of morning joint stiffness, based on daily diary entries. Higher values indicate greater severity with numeric rating scale anchors (0–10). Daily question: ‘Please rate the overall level of morning joint stiffness you had from the time you woke up today’. (C) Worst Tiredness: data are LS mean scores for Worst Tiredness, based on daily diary entries. Higher values indicate greater tiredness with numeric rating scale anchors (0–10). Daily question: ‘Please rate your tiredness by selecting the one number that describes your tiredness at its worst in the last 24 hours’. (D) Worst Joint Pain: data are LS mean scores for Worst Joint Pain, based on daily diary entries. Higher values indicate greater pain with numeric rating scale anchors (0–10). Daily question: ‘Please rate your joint pain by selecting the one number that describes your joint pain at its worst in the last 24 hours’. LS, least squares; NRS, numeric rating scale.p Value versus placebo: *p≤0.05; **p≤0.01; ***p≤0.001.p Value versus adalimumab: + p≤0.05; ++ p≤0.01; +++ p≤0.001.

Figure 2

Change from baseline over time for the FACIT-F. Higher scores indicate less fatigue. Range=0–52. FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; MCID, minimum clinically important differences.p Value versus placebo: *p≤0.05; **p≤0.01; ***p≤0.001.p Value versus adalimumab: +p≤0.05; ++p≤0.01; +++p≤0.001.

Figure 3

Change from baseline for the physical and mental component score for the SF-36. (A) Physical component score: data in table are % patients who met or exceeded the minimum clinically important difference in SF-36 PCS (≥5 points). Higher scores indicate improvement. (B) Mental component score: data in table are % patients who met or exceeded the minimum clinically important difference in SF-36 MCS (≥5 points). Higher scores indicate improvement. p Value versus placebo: *p≤0.05; **p≤0.01; ***p≤0.001.p Value versus adalimumab: +p≤0.05; ++p≤0.01; +++p≤0.001.