Preliminary definitions of ‘flare’ in axial spondyloarthritis, based on pain, BASDAI and ASDAS-CRP: an ASAS initiative

Abstract

International audienceIntroduction Flares may be used as outcomes in axial spondyloarthritis (axSpA) trials or observational studies. The objective was to develop a definition for ‘flare’ (or worsening) in axSpA, based on validated composite indices, to be used in the context of clinical trial design.Methods (1) Systematic literature review of definitions of ‘flare’ in published randomised controlled trials in axSpA. (2) Vignette exercise: 140 scenarios were constructed for a typical patient with axSpA seen at two consecutive visits. Each scenario included a change in one of the following outcomes: pain, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BASDAI plus C-reactive protein (CRP) or Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP. Each Assessment of Spondyloarthritis (ASAS) expert determined if every scenario from a random sample of 46 scenarios was considered a flare (yes/no). Receiver-operating characteristic (ROC) analyses were applied to derive optimal cut-off values. (3) ASAS consensus was reached.Results (1) The literature review yielded 38 studies using some definition of ‘flare’, with 27 different definitions indicating important heterogeneity. The most frequent definitions were based on BASDAI changes or pain changes. (2) 121 ASAS experts completed 4999 flare assessments. The areas under the ROC curves were high (range: 0.88–0.89). Preliminary cut-offs for pain (N=3), BASDAI (N=5) and ASDAS-CRP (N=4) were chosen, with a range of sensitivity 0.60–0.99 and range of specificity 0.40–0.94 against the expert's opinions.Conclusions This data-driven ASAS consensus process has led to 12 preliminary draft definitions of ‘flare’ in axSpA, based on widely used indices. These preliminary definitions will need validation in real patient data

Challenges and Advances in Targeting Remission in Axial Spondyloarthritis

“…Future studies are required to investigate this issue further, as well as the role of any residual inflammation in flares. Various definitions of flare have been proposed, yet none have been universally accepted and validated 30 . Further, both patients and physicians may have difficulty distinguishing mechanical overload from an inflammatory flare, so providing education on the key differences may be essential to ensure consistency in disease activity measurement.…”

An Assessment in SpondyloArthritis International Society (ASAS)-endorsed definition of clinically important worsening in axial spondyloarthritis based on ASDAS

“…Thus, 127 (10.8%) patients fulfilled the external standard definition of clinical worsening according to the patient’s perception. Table 2 summarises these performances, along with those from the physician case-vignette exercise in which the external standard was the physician’s perception 3. The three cut-offs of ASDAS change (ie, increase of 0.6, 0.9 and 1.1 points) yielded a sensitivity of 0.55, 0.38 and 0.33, respectively, and a specificity of 0.91, 0.96 and 0.98, respectively.…”

“…The final definition is the result of a comprehensive process involving a systematic literature review, a case-vignette exercise using the physician’s perspective as external standard,3 a real life study on worsening with the patient’s perspective as external standard and a consensus and voting procedure among SpA experts.…”

“…Four ASDAS-based cut-offs were proposed based on the previous exercise, with only three absolute changes:3 an increase in ASDAS of at least 0.6; an increase in ASDAS of at least 0.6 points and a final ASDAS≥1.3; an increase in ASDAS of at least 0.9 points; and an increase in ASDAS of at least 1.1 points.…”

“…ASAS has decided to also define a cut-off for clinically important worsening in axSpA. The first two steps of this process have already been reported:3 first, a systematic literature review of definitions of ‘disease worsening’ in published randomised controlled trials in axSpA was performed, yielding 38 studies using some definition of ‘disease worsening’ and 27 different definitions, most frequently based on Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)4 or pain. Second, a vignette exercise was performed involving 121 ASAS experts and 140 scenarios of disease worsening: each scenario included a change in one of the outcomes (pain, BASDAI, BASDAI plus C reactive protein (CRP) or ASDAS)1.…”