Background The natural course of axial spondyloarthritis (SpA) includes periods of flares and remission. Flares are important to measure particularly in the context of trials and drug tapering in clinical practice. However, to date a consensual definition of flare in axial SpA is lacking.
Objectives To develop a consensual definition for flare (or worsening) in axial SpA, based on validated composite indices, and to be used in the context of clinical trial design.
Methods (1) Systematic literature review to collect the definitions of flare used in published randomized controlled trials (RCTs) of NSAIDs or anti TNF in axial SpA patients. (2) Vignette exercise among ASAS members from July to December 2014. Based on a single scenario of a typical axial SpA patient at 2 consecutive visits, 223 scenarios were constructed based on change between the 2 visits of either pain (0-10), BASDAI (0-10), [BASDAI and CRP], or ASDAS-CRP. All the ASAS experts were asked to vote in a random sample of 46 scenarios, if in their opinion the patient was flaring, yes or no. ROC curves were applied to derive optimal cutoff values to define a flare from the physician's perspective. Change in each variable was analysed and coupled if necessary to the value of the variable observed at the time of flare (e.g., change in pain of at least 2 points and pain value of at least 4). (3) Results were presented to the ASAS experts during a workshop in January 2015, coupled with real patient data if available (ref), and consensus on a preliminary set of draft definitions was reached.
Results (1)The literature review yielded 37 studies using some definition of flare, with 26 different definitions. The two most frequently used definitions were: absolute BASDAI ≥4/10 with absolute physician assessment ≥4/10 used in 6 studies, and increase in pain ≥30% with absolute pain ≥4/10 used in 6 studies. (2) 121 ASAS experts contributed to the vignette exercise; 4999 flare votes could be analysed. The areas under the ROC curves were high (range, 0.88-0.89). Preliminary cutoffs for pain (N=2), BASDAI (N=4), and ASDAS-CRP (N=6) were defined, with good sensitivities (0.60 to 0.99) but lower specificities (0.40 to 0.94) in the vignette exercise. (3) During the ASAS consensus process, 2 additional cutoffs were proposed and the decision was taken to further cross-validate these 14 preliminary definitions (Table) in different “real patients” databases.
Conclusions This data-based consensus process, instigated by the ASAS group, has led to 14 preliminary draft definitions of flare in axial SpA, based on widely used indices. Further steps will allow the assessment of these preliminary definitions on real patient data in order to select the most relevant definition(s). This work is important in the context of clinical trial design e.g. in tapering trials, to better define flares in future clinical studies.
Godfrin-Valnet M, Wendling D. Flare in spondyloarthritis: Thresholds of disease activity variations. Joint Bone Spine 2015 in press.
Acknowledgements The ASAS experts.
Disclosure of Interest None declared