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

Abstract

Objective: To 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.

Methods: Patients 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.

Results: After 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.

Conclusion: DAS28-based flare occurred more often than investigator-defined flares after biologic agent discontinuation. More stringent criteria may be more appropriate for clinical practice.

Trial registration: ClinicalTrials.gov NCT00810199.

© 2015, American College of Rheumatology.

Figures

Figure 1

Overview of patient analysis set. ITT = intent‐to‐treat; MTX = methotrexate; TCZ = tocilizumab.

Figure 2

Flares corresponded mostly to isolated disease activity peaks followed by return to previous levels. For patients randomized to receive tocilizumab plus methotrexate (MTX) (A) or placebo (B), red dots indicate DAS28‐2 flares (Disease Activity Score in 28 joints between 2 visits >1.2, or >0.6 if the current DAS28 ≥3.2). The analysis is based on the constant treatment population (n = 313), i.e., patients with DAS28 <3.2 (horizontal broken line) at week 24.