American college of rheumatology preliminary definition of improvement in rheumatoid arthritis

TLDR

Rheumatoid arthritis trials typically report average responses, but individual patient improvement is more clinically relevant, and multiple definitions of improvement are currently used. This study aimed to establish and validate a single, universally applicable definition of improvement for RA trials. The authors employed a three‑step process: surveying rheumatologists to align definitions with clinical impressions, testing remaining definitions for treatment discrimination and placebo minimization, and selecting the most user‑friendly definition. The chosen definition requires ≥20% improvement in tender and swollen joint counts plus ≥20% improvement in at least three of the five ACR core set measures, and validation demonstrated strong statistical power with minimal placebo misclassification.

Abstract

Trials of rheumatoid arthritis (RA) treatments report the average response in multiple outcome measures for treated patients. It is more clinically relevant to test whether individual patients improve with treatment, and this identifies a single primary efficacy measure. Multiple definitions of improvement are currently in use in different trials. The goal of this study was to promulgate a single definition for use in RA trials.Using the American College of Rheumatology (ACR) core set of outcome measures for RA trials, we tested 40 different definitions of improvement, using a 3-step process. First, we performed a survey of rheumatologists, using actual patient cases from trials, to evaluate which definitions corresponded best to rheumatologists' impressions of improvement, eliminating most candidate definitions of improvement. Second, we tested 20 remaining definitions to determine which maximally discriminated effective treatment from placebo treatment and also minimized placebo response rates. With 8 candidate definitions of improvement remaining, we tested to see which were easiest to use and were best in accord with rheumatologists' impressions of improvement.The following definition of improvement was selected: 20% improvement in tender and swollen joint counts and 20% improvement in 3 of the 5 remaining ACR core set measures: patient and physician global assessments, pain, disability, and an acute-phase reactant. Additional validation of this definition was carried out in a comparative trial, and the results suggest that the definition is statistically powerful and does not identify a large percentage of placebo-treated patients as being improved.We present a definition of improvement which we hope will be used widely in RA trials.