Secukinumab treatment in rheumatoid arthritis is associated with incremental benefit in the clinical outcomes and HRQoL improvements that exceed minimally important thresholds

Vibeke Strand,Mark Kosinski,Ari Gnanasakthy,Usha Mallya,Shephard Mpofu

doi:10.1186/1477-7525-12-31

Abstract

BackgroundThe primary aim of rheumatoid arthritis (RA) treatment is to induce remission, the absence of disease activity. The objective of this study was to explore the association between clinical endpoints used to gauge RA treatment efficacy and patient-reported outcomes of health-related quality of life, fatigue, and physical function in RA patients treated with secukinumab in a phase 2 randomized controlled trial (RCT).MethodAdult RA patients (n = 237) with incomplete responses to methotrexate were randomized equally to receive monthly s.c. injections of secukinumab 25 mg, 75 mg, 150 mg, 300 mg or placebo. Clinical endpoints used in this study included the ACR response criteria and its components and simplified disease activity score. Patient-reported outcomes (PRO) included Health Assessment Questionnaire-Disability Index (HAQ-DI), Medical Outcomes Study Short Form-36 [SF-36] Survey, and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue). Patients were categorized into mutually exclusive groups according to the magnitude and direction of change from baseline to week 16 in each clinical endpoint. Definitions of minimal important differences [MID] in each clinical endpoint were used to categorize patients, as well as thresholds beyond MID. Mean changes from baseline to week 16 were computed for each PRO and analyses of variance to test the differences in PRO changes observed across groups of patients that differed in each clinical endpoint. Analyses were limited to patients randomized to secukinumab treatment. All dose groups were combined (n = 187).ResultsMean changes from baseline in each PRO differed significantly across groups of patients in the expected direction. With few exceptions, there was considerable agreement between clinical endpoints and PROs concerning the magnitude of change defined as clinically meaningful. More importantly, results demonstrated that greater improvements in clinical endpoints were associated with incrementally better improvements in HRQoL, fatigue, and physical function.ConclusionResults of this study show considerable agreement between minimal thresholds of improvement established for PROs and clinical outcome measures used in RA treatment studies and provide thresholds to be considered in gauging the importance of a treatment effect that goes beyond what is considered as minimally important for PRO measures.

Highlights

The primary aim of rheumatoid arthritis (RA) treatment is to induce remission, the absence of disease activity
There was considerable agreement between clinical endpoints and Patient-reported outcomes (PRO) concerning the magnitude of change defined as clinically meaningful
Results demonstrated that greater improvements in clinical endpoints were associated with incrementally better improvements in health-related quality of life (HRQoL), fatigue, and physical function

Summary

Introduction

The primary aim of rheumatoid arthritis (RA) treatment is to induce remission, the absence of disease activity. Rheumatoid arthritis (RA) is a systemic, chronic inflammatory disease characterized by joint inflammation and structural damage symmetrically in the hands and feet and large joints. It affects approximately 0.5-1% of the population in developed countries [1,2,3]. The annual direct costs of care attributable to RA from the societal perspective was estimated to be $3.6 billion [4] and as the disease progresses, patients often experience an increase in functional impairment that often leads to work disability [5,6,7,8]. It is estimated that RA reduces the lifespan of patients by anywhere from 3 to 12 years [10]

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