Patient- and physician-reported outcomes from two phase 3 randomized studies (RAJ3 and RAJ4) of peficitinib (ASP015K) in Asian patients with rheumatoid arthritis

Yoshiya Tanaka,Mitsuhiro Rokuda,Tsutomu Takeuchi,Yuichiro Kaneko,Musashi Fukuda,Hiroyuki Izutsu,Neil M Schultz,Daisuke Kato

doi:10.1186/s13075-021-02590-z

Abstract

BackgroundPeficitinib (ASP015K), a novel oral Janus kinase inhibitor, has demonstrated efficacy and safety in the treatment of patients with rheumatoid arthritis (RA). This study evaluated the effect of peficitinib on patient- and physician-reported outcomes in Asian patients with RA and an inadequate response to prior disease-modifying antirheumatic drugs (DMARDs).MethodsPatients from two randomized, placebo-controlled, double-blind, phase 3 trials (RAJ3 and RAJ4) received once-daily peficitinib 100 mg, peficitinib 150 mg, or placebo, alone or in combination with DMARDs (RAJ3), or in combination with methotrexate (RAJ4). Mean changes in Work Productivity and Activity Impairment (WPAI) questionnaire domain scores from baseline, and percentages of patients achieving minimal clinically important differences (MCIDs) for patient- and physician-reported outcomes (WPAI, Health Assessment Questionnaire – Disability Index [HAQ-DI], and Subject’s Global Assessment of Pain [SGAP]), and Physician’s Global Assessment of disease activity (PGA) were evaluated at weeks 4, 8, 12, and 12/early termination (ET).ResultsData from 1025 patients were analyzed. At week 12/ET in both studies, patients who received peficitinib 100 mg or 150 mg reported significantly improved WPAI domain scores from baseline (except for absenteeism in RAJ4) compared with placebo (both doses, p<0.05). A higher proportion of peficitinib- versus placebo-treated patients achieved MCID in WPAI, HAQ-DI, SGAP, and PGA in studies RAJ3 and RAJ4. Significant differences with peficitinib versus placebo were evident in both studies as early as week 4 in HAQ-DI (peficitinib 150 mg only), SGAP, and PGA, and week 8 in WPAI loss of work productivity and daily activity impairment. At week 12/ET, significantly higher proportions of patients receiving peficitinib versus placebo achieved MCID in HAQ-DI, SGAP, PGA, and WPAI domains of presenteeism (RAJ3 only), loss of work productivity (RAJ3 only), and daily activity impairment (p<0.05 for all comparisons).ConclusionsPeficitinib 100 mg or 150 mg administered daily over 12 weeks resulted in clinically meaningful improvements in outcomes that are important to RA patients, including pain, physical function, and work productivity and activity. These observations were reinforced through similar improvements in physicians’ rating of disease activity.Trial registrationRAJ3: ClinicalTrials.gov, NCT02308163, registered 4 December 2014.RAJ4: ClinicalTrials.gov, NCT02305849, registered 3 December 2014.

Highlights

Peficitinib (ASP015K), a novel oral Janus kinase inhibitor, has demonstrated efficacy and safety in the treatment of patients with rheumatoid arthritis (RA)
Patient populations Overall, 1025 patients were included in the analysis set (507 in RAJ3 and 518 in RAJ4) [14, 15]
Demographic characteristics, baseline disease activity, and RA history were generally similar across the treatment groups in the RAJ3 and RAJ4 studies [14, 15]

Summary

Introduction

Peficitinib (ASP015K), a novel oral Janus kinase inhibitor, has demonstrated efficacy and safety in the treatment of patients with rheumatoid arthritis (RA). This study evaluated the effect of peficitinib on patient- and physician-reported outcomes in Asian patients with RA and an inadequate response to prior disease-modifying antirheumatic drugs (DMARDs). A range of PROs and physician-reported outcomes have been validated to evaluate health, quality of life, and treatment response in studies of patients with RA [4, 5]. These include a core set of PROs and physician-reported outcomes established by the American College of Rheumatology (ACR) [5, 6]. Statistically significant changes in these outcome scores do not necessarily mean that the changes are clinically relevant [7, 8]. Interpretation of PRO and physician-reported data is improved by considering minimal clinically important differences (MCIDs), which help to determine the clinical relevance of observed changes, without relying solely on the presence or absence of statistical significance [7]

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Results

Discussion

Conclusion