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Open Access Research

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

Vibeke Strand1, Mark Kosinski2*, Ari Gnanasakthy3, Usha Mallya3 and Shephard Mpofu4

Author Affiliations

1 Stanford University Division of Immunology/Rheumatology, Palo Alto, CA, USA

2 QualityMetric Incorporated, 24 Albion Road, Lincoln, RI, USA

3 Novartis Pharmaceuticals Corporation, New Jersey, East Hanover, USA

4 Novartis Pharma AG, Basel, Switzerland

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Health and Quality of Life Outcomes 2014, 12:31  doi:10.1186/1477-7525-12-31

Published: 5 March 2014

Abstract

Background

The 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).

Method

Adult RA patients (nā€‰=ā€‰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 (nā€‰=ā€‰187).

Results

Mean 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.

Conclusion

Results 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.