Cut-off value to identify a flare using the Flare Assessment in Rheumatoid Arthritis (FLARE-RA) questionnaire: analysis of the TOSCA study

Abstract

Objective The Flare Assessment in Rheumatoid Arthritis (FLARE-RA) self-administered questionnaire aims to identify patients who had flare in the interval between 2 consultations. This study aimed to establish a threshold for FLARE-RA score to identify RA flare. Methods The Tocilizumab SubCutAneous (TOSCA) study evaluated the efficacy and safety of subcutaneous Tocilizumab (TCZ) to patients with active RA. Disease activity was assessed with the DAS28ESR at baseline and at week 2 (W2), W4, W12, and W24. The FLARE-RA questionnaire was administered at W12 and W24. Patient satisfaction, assessed at baseline and W24 with the Patient Acceptable Symptom State (PASS), was used as a surrogate marker of no flare. A correlation was sought between the FLARE-RA score at W12 and W24 and the area under the receiver operating characteristic (ROC) curve (AUC) for monthly DAS28ESR. The optimal FLARE-RA cut-off below which patient satisfaction reached the PASS was explored with an ROC curve. Results 139 patients were included (mean age 57.3 ± 13.8 years, 74.1% women, mean RA duration 10.8 ± 9.2 years, mean DAS28ESR 5.8 ± 1.1). The correlation between the FLARE-RA score and DAS28ESR AUC was moderate at all times: rho = 0.41 at W12 (p<0.0001) and 0.51 at W24 (p<0.0001). The optimal cut-off for the FLARE-RA score to identify absence of flare (i.e. an acceptable situation based on the PASS) was 2.3 with an AUC of 0.81. Conclusion FLARE-RA and DAS28ESR assessment differ; we propose a FLARE-RA cut-off of 2.3, below which the situation (i.e. without flare) is acceptable for patients.

Insights Into the Concept of Rheumatoid Arthritis Flare

“…Myasoedova et al ( 24 ) identified a lower (for clinical detection) and upper (for therapeutic change) cutoff varying depending on the duration of disease. More recently, Aouad et al ( 25 ) identified a clearer cutoff of 2.3 for the FLARE-RA general score, able to detect a patient “in flare” (above) vs. “not in flare” (below) over the past 3 months or since the last visit.…”

Defining and managing flares in axial spondyloarthritis

“…Thus, flares are associated with symptoms but also with mental disease burden and consequences on social life, as has been shown in other inflammatory rheumatic diseases [6,35 ▪ ,36].…”

“…Patient-perceived flares do not only reflect inflammation. For example, in rheumatoid arthritis, flares reported by patients are linked not only to inflammation, but also to functional impairment, structural damage and higher cardiovascular risk [6]. Probably for this reason, both in axSpA and rheumatoid arthritis, physicians and patients may have different perceptions of flares [32].…”

“…In recent years, many attempts have been made to define flares in different chronic rheumatic diseases like rheumatoid arthritis [6]. However, in a very heterogeneous disease such as axSpA, defining the concept of flare or remission is very challenging [7].…”