Defining Clinically Important Worsening Based on ASDAS-CRP for Axial Spondyloarthritis: A Data-Based Consensus By the Assessment in Spondyloarthritis International Society (ASAS)

Anna Molto¹, Laure Gossec², Robert B.M. Landewé³, Désirée van der Heijde⁴ and Maxime Dougados⁵, ¹Hôpital Cochin, Department of Rheumatology, Paris Descartes University, Paris, France, ²UPMC University Paris 06, Pitié-Salpétrière Hospital, Paris, France, ³Amsterdam Rheumatology & Immunology Center, Netherlands, Amsterdam, Netherlands, ⁴Rheumatology, Leiden University Medical Center, Leiden, Netherlands, ⁵Department of Rheumatology, Paris Descartes University, Hôpital Cochin, Paris, France

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: outcome measures and spondylarthritis

Session Information

Date: Tuesday, November 7, 2017

Title: Spondyloarthropathies and Psoriatic Arthritis – Clinical Aspects and Treatment Poster III: Outcomes, Outcome Measures, and Comorbidities

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Disease flares are increasingly used as outcomes in axial spondyloarthritis (axSpA) trials or observational studies. 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. after an SLR and a vignette-exercise among ASAS members: a theoretical ‘paper’ patient-vignette. After presentation of the results at the ASAS 2015 meeting it was decided that the proposed cut-off needed to be validated with real-life data. A 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): the 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. Different changes in the outcomes against both external standards for worsening (phy-worsening (vignettes) and pt-worsening) were tested 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 (ref)). (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.

Table. Sensitivity and specificity of different ASDAS cutoffs to define worsening, against phy-worsening and pt-worsening considered as external standards.

Cutoff values for change in ASDAS	Vignette exercise study (N=1150 physician judgments) against the external standard ‘phy-worsening’ (worsening in N=591)		Prospective real-life study (N=1169 patients), against the external standard ‘pt-worsening’ (worsening in N=127)
	Sensitivity (%)	Specificity (%)	Sensitivity (%)	Specificity (%)
>=0.6	97	65	55	91
>=0.9	85	87	38	96
>=1.1	60	94	33	98

Conclusion:

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.

Disclosure: A. Molto, None; L. Gossec, None; R. B. M. Landewé, Abbott/Abb Vie, Ablynx, Amgen, Astra-Zeneca, Bristol Myers Squibb, Celgene, Janssen, Galapagos, Glaxo-Smith-Kline, Novartis, Novo-Nordisk, Merck, Pfizer, Roche, Schering-Plough, TiGenix, UCB, Wyeth, 5,Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB, Wyeth, 2,Director of Rheumatology Consultancy BV, 4,Board Member Merit Foundation, 3; D. van der Heijde, None; M. Dougados, Abbvie, Pfizer, Eli Lilly and Company, Novartis, UCB, Merck, Roche, BMS UCB, 2,Abbvie, Pfizer, Eli Lilly and Company, Novartis, UCB, Merck, Roche, BMS, UCB, 5.

To cite this abstract in AMA style:

Molto A, Gossec L, Landewé RBM, van der Heijde D, Dougados M. Defining Clinically Important Worsening Based on ASDAS-CRP for Axial Spondyloarthritis: A Data-Based Consensus By the Assessment in Spondyloarthritis International Society (ASAS) [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/defining-clinically-important-worsening-based-on-asdas-crp-for-axial-spondyloarthritis-a-data-based-consensus-by-the-assessment-in-spondyloarthritis-international-society-asas/. Accessed .

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