Background Disease flares are increasingly used as outcomes in axial spondyloarthritis (axSpA) trials or observational studies.
Objectives The objective of this initiative was to define a cutoff for the ASDAS score that best defines the concept of “worsening in axSpA”, to be used in the context of clinical trials and longitudinal observational studies.
Methods Various steps were followed between 2014 and 2017. (a) Initial expert opinion within the steering group to define the scope of the project; (b) systematic literature review to collect cutoffs used for worsening in published studies; (c) vignette-exercise among ASAS members: a theoretical 'paper' patient-vignette, in whom an initial and a final value of an outcome was provided, was judged by the physicians on whether or not the patient had worsened (defining phy-worsening) (ref); (d) real-life multicenter international study: data necessary to calculate different outcomes were collected from real patients at 2 consecutive visits (spaced 7 days to 6 months): external standard was defined as a patient's report that he/she had worsened and he/she felt there was a need for treatment intensification. (e) Testing of different changes in the outcomes against both external standards for worsening (phy-worsening and pt-worsening) followed by a consensus and voting procedure among ASAS members in January 2017.
Results (a) There was consensus about worsening being an absolute change between 2 time-points (without defining time between the 2 time-points) and about exploring cutoffs for 3 outcomes: ASDAS-CRP, BASDAI and pain. (b) The literature review had yielded 27 different cutoffs in 38 studies indicating important heterogeneity (c) The vignette-exercise yielded 12 preliminary definitions for worsening to be tested (as previously reported). (d) In the prospective study the sensitivity and specificity of each cutoff was tested against pt-worsening and judged by the ASAS-community. (e) No consensus was reached for a BASDAI-based definition due to limited performance of all cut-offs, and it was decided to not define a value for a pain-based definition for worsening. Based on aggregated data (Table), a consensus was reached among the ASAS-members to define worsening as a deterioration in ASDAS of at least 0.9 points. While this cutoff led to only moderate sensitivity when tested against pt-worsening, the overall balance of sensitivity and specificity as well as the overall face validity of this cut-off value for ASDAS was deemed most acceptable.
Conclusions This data-driven ASAS consensus process has allowed to propose an ASDAS-based cutoff value defining worsening in axSpA. As has been observed in other settings, the change defining worsening (at least 0.9) is smaller than the change defining improvement which is 1.2 for ASDAS. This definition should now be applied in trials.
Gossec L, et al. Preliminary definitions of 'flare' in axial spondyloarthritis, based on pain, BASDAI and ASDAS-CRP: an ASAS initiative. Ann Rheum Dis. 2016;75:991–6.
Acknowledgements This study was supported by ASAS.
Disclosure of Interest None declared