Evaluation of the Disease Activity Score in Twenty‐Eight Joints–Based Flare Definitions in Rheumatoid Arthritis: Data From a Three‐Year Clinical Trial

Abstract

ObjectiveTo assess the flare rate using published criteria (Disease Activity Score in 28 joints [DAS28‐2] increase between visits of >1.2 or >0.6 if current DAS28 ≥3.2) in patients receiving constant treatment, and to compare published flare criteria to criteria used by study investigators after biologic treatment discontinuation in the ACT‐RAY study.MethodsPatients with rheumatoid arthritis (n = 553) were randomized to add tocilizumab to ongoing methotrexate, or switch to tocilizumab plus placebo. If DAS28 ≤3.2 occurred at week 24, treatment remained constant until week 52; here we assessed the DAS28‐2 flare rate. Between weeks 52 and 104, patients in sustained remission (DAS28 <2.6 at 2 consecutive visits 12 weeks apart) discontinued tocilizumab and were assessed every 4 weeks. Per protocol, flare was defined as a worsening of disease activity that required treatment beyond the permitted therapy based on investigator opinions (investigator flare) and was compared with the DAS28‐2 definition.ResultsAfter tocilizumab discontinuation, DAS28‐2 was sensitive (88–100%), but not specific (57–65%), for detecting investigator flare. Under constant treatment, DAS28‐2 criteria were met in 136 cases per 100 patient‐years despite stable disease activity. Sustained flares were infrequent. Other DAS28‐based criteria led to similar conclusions.ConclusionDAS28‐based flare occurred more often than investigator‐defined flares after biologic agent discontinuation. More stringent criteria may be more appropriate for clinical practice.

Insights Into the Concept of Rheumatoid Arthritis Flare

“…In some of these studies, to overcome the possibility of DAS28-based flare driven by subjective domains in the absence of objective synovitis, the additional or alternative presence of swollen joints was required ( 5 , 21 , 22 , 61 , 62 ). Indeed, it was observed that DAS28-based flare occurs more often than investigator-defined flare (1.7–7.3 times higher) ( 33 ) and, on the other hand, may miss patient-reported flare (PRF) ( 6 ). For this reason frequently the absolute threshold or minimal change in composite disease activity scores required to define flare were associated with or could be overcome by the investigator's judgment of flare ( 40 , 41 , 43 ).…”

“…The physician judgment or the necessity of treatment modification has been applied in various works as the solely possible definition of flare ( 33 , 34 , 39 ). The rheumatologist's view can be actually considered as the only comprehensive tool to integrate information derived from the objective and laboratory parameters with the patient's perspective through the filter of an expert interpretation.…”

Severity of the Rheumatoid Arthritis in Sub-Saharan Africa: Study of 403 Senegalese Observations

“…Dougados, et al, in a recent clinic test including the patients coming from 19 countries of Europe, America and Asia observed a base score of DAS 28 with an average of 6.4 ± 1 [28]. Besides the active illness, the severity of the RA in our patients was marked by an important structural damage constituted of characteristic articular deformations in 53.3% of cases with erosions and or articular pinches in all patients.…”

Disease activity flares and pain flares in an early rheumatoid arthritis inception cohort; characteristics, antecedents and sequelae

“…These DAS28-based flare criteria exceed 70% specificity and sensitivity, compared with the judgement of the patient [3]. They also showed sensitivity of 88–100%, and specificity of 57–65% for detecting investigator-defined flares and after biologic discontinuation in 1 clinical trial [5]. There is evidence that flares contribute to worsening cardiovascular morbidity, joint damage and other long-term outcomes [6].…”