Disease flares in rheumatoid arthritis are associated with joint damage progression and disability: 10-year results from the BeSt study

Abstract

Introduction: Flares in patients with rheumatoid arthritis are suggested to sometimes spontaneously resolve. Targeted therapy could then entail possible overtreatment. We aimed to determine the flare prevalence in patients who are treated-to-target and to evaluate associations between flares and patient-reported outcomes and radiographic progression.

Methods: In the BeSt study, 508 patients were treated-to-target for 10 years. After initial treatment adjustments to achieve disease activity score ≤2.4, a flare was defined from the second year of follow-up onwards, according to three definitions. The first definition is a disease activity score >2.4 with an increase of ≥0.6 regardless of the previous disease activity score. The other definitions will be described in the manuscript.

Results: The flare prevalence was 4-11 % per visit; 67 % of the patients experienced ≥1 flare during 9 years of treatment (median 0 per patient per year). During a flare, functional ability decreased with a mean difference of 0.25 in health assessment questionnaire (p < 0.001), and the odds ratios (95 % confidence intervals) for an increase in patients' assessment of disease activity, pain and morning stiffness of ≥20 mm on a visual analogue scale were 8.5 (7.3-9.8), 8.4 (7.2-9.7) and 5.6 (4.8-6.6), respectively, compared to the absence of a flare. The odds ratio for radiographic progression was 1.7 (1.1-2.8) in a year with a flare compared to a year without a flare. The more flares a patient experienced, the higher the health assessment questionnaire at year 10 (p < 0.001) and the more radiographic progression from baseline to year 10 (p = 0.005).

Conclusion: Flares were associated with concurrent increase in patient's assessment of disease activity, pain and morning stiffness, functional deterioration and development of radiographic progression with a dose-response-effect, both during the flare and long term. This suggests that intensifying treatment during a flare outweighs the risk of possible overtreatment.

Trial registration: Dutch trial registry NTR262 (7 September 2005) and NTR265 (8 September 2005).

Fig. 1

Percentage of patients with a flare per performed visit over time. Flare A: from any DAS to DAS >2.4 with an increase in DAS of ≥0.6; minor flare B: from DAS ≤2.4 to DAS >2.4 with an increase in DAS of <0.6; major flare B: from DAS ≤2.4 to DAS >2.4 with an increase in DAS of ≥0.6. Note, flares are defined from year 2 to year 10

Fig. 2

Total number of flares during year 2 to year 10 in all patients (n = 480), according to the following definitions: Flare A (n = 882/11,458): from any DAS to DAS >2.4 with an increase in DAS ≥0.6; Minor flare B (n = 281/11,458): from DAS ≤2.4 to DAS >2.4 with an increase in DAS <0.6; Major flare B (n = 721/11,458): from DAS ≤2.4 to DAS >2.4 with an increase in DAS ≥0.6. It indicates the concordance and discordance between the definitions of flare. Note, more than one flare according to the same definition or according to another definition can occur in the same patient

Fig. 3

Cumulative probability plots of the mean functional ability (measured with the health assessment questionnaire (HAQ)) during year 2 to year 10 of follow-up, stratified for definition and number of flares. a According to the definition of flare A (DAS >2.4, with an increase in DAS of at least 0.6 from a previous DAS of any value). b According to the definition of minor flare B (DAS >2.4, from a previous DAS ≤2.4 with an increase of DAS <0.6). c According to the definition of major flare B (DAS >2.4 from a previous DAS ≤2.4 with an increase in DAS ≥0.6)

Fig. 4

Cumulative probability plots of radiographic progression (measured with the Sharp/ van der Heijde score (SHS)) during 10-year follow-up, stratified for definition and number of flares. a According to the definition of flare A (DAS >2.4, with an increase in DAS of at least 0.6 from a previous DAS of any value). b According to the definition of minor flare B (DAS >2.4, from a previous DAS ≤2.4 with an increase of DAS <0.6). c According to the definition of major flare B (DAS >2.4 from a previous DAS ≤2.4 with an increase in DAS ≥0.6)