Definition of rheumatoid arthritis flare based on SDAI and CDAI

Objective To develop and validate definitions for disease flares in rheumatoid arthritis (RA) based on the quantitative Simplified and Clinical Disease Activity Indices (SDAI, CDAI). Methods We analysed RA treatment courses from the Norwegian disease-modifying antirheumatic drug registry (NOR-DMARD) and the Vienna RA cohort. In a receiver operating curve analysis, we determined flare definitions for absolute changes in SDAI and CDAI based on a semiquantitative patient anchor. NOR-DMARD was sampled into an 80%-training cohort for cut point derivation and a 20%-test cohort for internal validation. The definitions were then externally validated in the independent Vienna RA cohort and tested regarding their performance on longitudinal, content, face, and construct validity. Results We analysed 4256 treatment courses from NOR-DMARD and 2557 from the Vienna RA cohort. The preliminary definitions for absolute changes in SDAI and CDAI for flare are an increase of 4.7 and 4.5, respectively. The definitions performed well in the test and external validation cohorts, and showed clinical face and construct validity, as flares significantly impact both functional ( Delta Health Assessment Questionnaire flare vs no-flare +0.43; p<0.001) and structural ( Delta modified Sharp Score 43% higher after flare; p<0.001) disease outcomes, and reflect consistent worsening across all disease core sets, both patient reported and objective. Conclusion We here provide novel definitions for flare in RA based on SDAI and CDAI, validated in two large independent real-world cohorts. In times of highly effective medications for RA, and consideration of their tapering, these definitions will be useful for guiding decision making in clinical practice and designing clinical trials.