Development and Validation of Minimal Disease Activity, Disease Flare, and Minimal Clinically Important Difference for Children with Chronic Nonbacterial Osteomyelitis Using a Consensus and Data-Driven Approach

ObjectivesTo create definitions for minimal disease activity (MDA), flare, and minimal clinically important difference (MCID) for chronic nonbacterial osteomyelitis (CNO). It is necessary to establish these criteria prior to starting clinical effectiveness trials for therapies in CNO. MethodsThree separate cohorts samples from an international observational CNO registry were presented to a panel of twenty experts in CNO, including 7 patients/caregivers via online and in-person voting using nominal group technique to define MDA, flare, and MCID, respectively. Experts classified the cases in each cohort as meeting the state for that specific cohort, ie. MDA or not, or flare or not, or meeting MCID or not. A consensus of [>=]80% was required. ResultsGeneral surveys identified the most important variables to include to define MDA, flare, and MCID. Clinical improvement of 30% or more in these critical parameters and improvement of CNO Clinical Disease Activity Score (CDAS) by at least 3 were considered meaningful by providers and consensus data. Conclusions This study provides the preliminary definitions of MDA, disease flare, and MCID in CNO which can serve as targets and potential outcomes from treatments. These definitions must now be validated in other cohorts and tested in clinical trials. Key MessagesO_ST_ABSWHAT IS ALREADY KNOWN ON THIS TOPICC_ST_ABSO_LIMeasurements of minimal disease activity (MDA), worsening disease activity ( flare), and minimally clinically important differences (MCID) in CNO are not well-established. For successful execution of clinical trials to identify effective treatment strategies in patients with CNO, standardized definitions of these terms are necessary. C_LI WHAT THIS STUDY ADDSO_LIUsing data from an international real-world registry of CNO patients, we developed and validated quantitative definitions for MDA, flare, and MCID. C_LI HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICYO_LIDefinitions of MDA, flare, and MCID will serve as potential outcomes in future clinical trials to study effectiveness of therapies in CNO. C_LI