title: Secukinumab treatment in rheumatoid arthritis is associated with incremental benefit in the clinical outcomes and HRQoL improvements that exceed minimally important thresholds.
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).
  
  
  METHODS
  Adult 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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.forename: Vibeke
authors.initials: V
authors.lastname: Strand
authors.affiliation: QualityMetric Incorporated, 24 Albion Road, Lincoln, RI, USA. mkosinski@qualitymetric.com.
authors.forename: Mark
authors.initials: M
authors.lastname: Kosinski
authors.forename: Ari
authors.initials: A
authors.lastname: Gnanasakthy
authors.forename: Usha
authors.initials: U
authors.lastname: Mallya
authors.forename: Shephard
authors.initials: S
authors.lastname: Mpofu
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000503:physiopathology; D004185:Disability Evaluation; D004359:Drug Therapy, Combination; D005260:Female; D006304:Health Status; D006306:Health Surveys; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D010919:Placebos; D011788:Quality of Life; D020127:Recovery of Function; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D010919:Placebos; D008727:Methotrexate