Background/Purpose: The Ankylosing Spondylitis Disease Activity Score (ASDAS) is a composite measure of disease activity in axial spondyloarthritis. It  was  suggested  that  when  the  conventional  CRP  (cCRP)  is  below  the  limit  of  detection,  and  high sensitivity  CRP  (hsCRP)  is  not  available,  50%  of  the  threshold  value  should  be  used  to  calculate ASDAS-CRP.  However,  this  recommendation  was  not  data  driven  and  requires  further  testing. Our aims were to investigate the most appropriate ASDAS-C-reactive protein (ASDAS-CRP) calculation method when the cCRP is below the limit of detection, to study the arithmetic influence of low CRP values in ASDAS-CRP results and to test agreement between different ASDAS formulae.

Methods: Baseline data from the Devenir des Spondylarthropathies Indifférenciées Récentes (DESIR) cohort was used. Patients with axial spondyloarthritis and cCRP below the limit of detection (5mg/L, n=257) were selected. ASDAS-cCRP was calculated using eleven imputation strategies for the cCRP (range 0-5, at 0.5 intervals). ASDAS-high sensitivity CRP (hsCRP) and ASDAS-ESR were also calculated. Agreement between ASDAS formulae was tested. The effect of low CRP values in ASDAS-CRP results was studied.

Results: ASDAS-CRP(1.5), ASDAS-CRP(2) and ASDAS-erythrocyte sedimentation rate (ESR) had better agreement with ASDAS-hsCRP than other imputed formulae (table). Disagreement was mainly in lower disease activity states (inactive/moderate disease activity). When the CRP value is <2mg/L, the CRP component of the ASDAS-CRP formula can take very low values that may result in inappropriately low ASDAS-CRP values.

 

Table: Agreement between ASDAS-hsCRP and other ASDAS formulae (ASDAS-cCRP with multiple imputation strategies and ASDAS-ESR)
ASDAS formulae	ASDAS-hsCRP
	ASDAS values		ASDAS disease activity states
	ICC (95% CI)	Mean difference (95%CI)	Weighted kappa (95%CI)	Disagreement (%)
ASDAS-CRP(0)	0.78 (-0.06 to 0.94)	-0.52 (-1.02 to -0.03)	0.51 (0.44 to 0.57)	46.7%
ASDAS-CRP(0.5)	0.89 (0.33 to 0.96)	-0.29 (-0.79 to 0.21)	0.73 (0.67 to 0.79)	25.0%
ASDAS-CRP(1)	0.94 (0.89 to 0.96)	-0.12 (-0.62 to 0.38)	0.73 (0.67 to 0.79)	24.4%
ASDAS-CRP(1.5)	0.95 (0.93 to 0.96)	0.01 (-0.49 to 0.51)	0.75 (0.69 to 0.81)	21.9%
ASDAS-CRP(2)	0.94 (0.90 to 0.96)	0.11 (-0.38 to 0.61)	0.76 (0.70 to 0.81)	21.8%
ASDAS-CRP(2.5)	0.92 (0.70 to 0.96)	0.20 (-0.29 to 0.70)	0.71 (0.65 to 0.77)	25.3%
ASDAS-CRP(3)	0.89 (0.37 to 0.96)	0.28 (-0.22 to 0.78)	0.66 (0.60 to 0.73)	29.1%
ASDAS-CRP(3.5)	0.86 (0.11 to 0.96)	0.35 (-0.15 to 0.85)	0.64 (0.58 to 0.70)	31.6%
ASDAS-CRP(4)	0.83 (0.00 to 0.95)	0.41 (-0.09 to 0.91)	0.61 (0.54 to 0.67)	4.3%
ASDAS-CRP(4.5)	0.81 (-0.04 to 0.94)	0.47 (-0.03 to 0.96)	0.59 (0.53 to 0.65)	35.8%
ASDAS-CRP(5)	0.78 (-0.06 to 0.94)	0.52 (0.02 to 1.01)	0.50 (0.44 to 0.57)	43.6%
ASDAS-ESR	0.91 (0.85 to 0.94)	0.13 (-0.52 to 0.79)	0.69 (0.63 to 0.76)	8.1%

 

Conclusion: When the cCRP is below the limit of detection or when the hsCRP is <2mg/L, the constant value of 2mg/L should be used to calculate ASDAS-CRP. There is good agreement between ASDAS-hsCRP and ASDAS-ESR; however, formulae are not interchangeable. ASDAS is increasingly being used as a measure of disease activity in clinical practice, clinical trials and observational studies. This study contributes to further standardisation of the ASDAS and to a more homogeneous and reproducible application of this new index.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/how-should-we-calculate-the-asdas-if-the-conventional-c-reactive-protein-is-below-the-limit-of-detection-an-analysis-in-the-desir-cohort/