Background/Purpose: To investigate the impact of disease duration on treatment response in patients with axial spondylarthritis (SPA) treated with etanercept (ETA) or adalimumab (ADA).

Methods: Data of 112 patients with axial SpA originally enrolled in two randomized controlled trials were pooled and analyzed. The following outcome parameters assessed after one year of treatment with ETA n=66 (1) or ADA n= 46 (2) were investigated: Bath AS disease activity index (BASDAI), functional index (BASFI), AS disease activity score (ASDAS), CRP, and active inflammation on MRI in the sacroiliac joints (SIJ) and spine. Comparisons were made between patients with a short (< 4 years) versus  those with a longer (>=4 years) duration of symptoms.  A  mixed model approach was applied to compare the changes in the outcome parameters between baseline and end of year one between the symptom duration groups after adjustment for baseline status and gender. Partial Spearman correlation coefficients were calculated to analyse the relationship between change scores after taking their dependence from the baseline scores into account.

Results:

Clinical parameters such as BASDAI, BASFI and ASDAS showed significantly better improvement in short vs longer diseased patients (Table 1). No significant differences were observed for MRI scores and for CRP. Furthermore, in short diseased patients the change in BASDAI correlated significantly with the change in SIJ score (rho=0.33, p=0.03) and the change in CRP (rho=0.40, p=0.003). In contrast, in patients with a long disease duration this correlations was poor (change in BASDAI vs change in SIJ score rho=-0.01, p=0.95, change in BASDAI vs change in CRP rho=0.22, p=0.13). We further stratified the patients into CRP positive and CRP negative patients according to their status at baseline and observed larger differences between short and longer diseased patients in the CRP negative subgroup (improvement: BASDAI: 3 [2.3, 3.7] vs. 1.31 [0.7, 1.9], BASFI: 2.42 [1.8, 3.1] vs. 0.93 [0.4, 1.5]) than in the CRP positive subgroup (improvement BASDAI: 3.34 [2.7, 4] vs. 2.41 [1.5, 3.3]), BASFI: 2.44 [1.8, 3] vs. 1.79 [0.9, 2.7]). 

 

Parameter	Baseline value (mean)	Adjusted mean changes (95% CI)		p-value
		<4 years n=58	>=4 years n=54
BASDAI	5.4	3.2 (2.7, 3.7)	1.7 (1.1, 2.2)	<.0001
BASFI	4.4	2.4 (2, 2.9)	1.2 (0.7, 1.6)	0.0003
BASMI	1.8	0.3 (0, 0.6)	-0.1 (-0.4, 0.2)	0.09
ASDAS	3.1	1.5 (1.3, 1.8)	1.1 (0.8, 1.4)	0.04
CRP	8.0	3.8 (1.7, 5.9)	1.2 (-0.9, 3.3)	0.09
MRI spine score	1.8	0.8 (0.4, 1.3)	1.5 (0.8, 2.1)	0.10
MRI SIJ score	6.0	3.9 (3.3, 4.6)	3.7 (2.8, 4.6)	0.71

Table 1:Mean changes in clinical outcome parameters adjusted for the status at baseline and gender

Conclusion:

1. Axial SpA patients with short symptom duration respond clearly better to TNF-blocker therapy. 2. A good correlation between improvement of patients’ reported outcome parameters and objective parameters of inflammation was found in short but not  in longer diseased patients. 3. CRP-negative axial SpA patients respond well in case of short symptom duration. These data indicate that patients with longer symptom duration, even in absence of significant structural damage and despite good suppression of inflammation, respond less well to TNF-blockade for reasons which have still to be defined.

1. Haibel H et al. Arthritis Rheum 2008;58:1981-1991
2. Song et al, Ann Rheum Dis 2011; 70:590-96

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/analysis-of-clinical-crp-and-mri-responses-to-tnf-blockade-in-axial-spondyloarthritis-patients-with-short-vs-long-symptom-duration/