Background Approximately 60% of RA patients do not achieve good clinical response after 6 months of treatment with a TNF inhibitor (TNFi).¹ To date, no clinically useful baseline biomarkers have been found to predict response.² Calprotectin (a heterodimer of S100A8/S100A9) was shown to be modestly predictive for treatment response to adalimumab (ADA) (area under the curve (AUC): 0.69) while no difference in calprotectin levels was found between responders and non-responders in RA patients treated with etanercept (ETN) and methotrexate.^3,4

Objectives To assess the added predictive value of serum calprotectin for clinical response after 6 months treatment with ADA or ETN in RA patients.

Methods RA patients starting treatment with ADA or ETN in the BIO-TOP study (a prospective cohort study) were included. Patients who discontinued TNFi treatment within 2 months were excluded from analysis. Serum calprotectin was measured at baseline using ELISA. EULAR response was measured at 6 months (good versus moderate/no response). Discontinuation of TNFi before 6 months was regarded as non-response (in case of lack of effect) and clinical response at 3 months was carried forward (when stopped for other reasons). First calprotectin levels were correlated cross-sectionally with several clinical baseline markers. Thereafter receiver-operator-characteristic (ROC) curves were created for ADA and ETN separately. Finally logistic prediction models (basic model and calprotectin added model) were created using backward selection, including baseline characteristics and calprotectin levels to examine the added predictive value of calprotectin.

Results Data on calprotectin levels and EULAR response were available for 125 patients (ADA (n=50), ETN (n=75)) with 40% of patients achieving EULAR good response. Responders showed significantly higher calprotectin levels at baseline: 985 ng/mL (p25-p75: 558–1417) versus 645 ng/mL (p25-p75: 415–973) (p=0.04). Calprotectin levels were significantly correlated to DAS28-CRP (Spearman ρ=0.32, p<0.01) and C-reactive protein (CRP) levels (Spearman ρ=0.57, p<0.01) and significantly higher in rheumatoid factor positive patients (p=0.03). No significant correlation was found between calprotectin and age, gender or ACPA positivity. The AUC for serum calprotectin in the ADA and ETN group were 0.68 (95% CI: 0.49–0.88) and 0.49 (95% CI: 0.35–0.63), respectively. The basic model (backward selected variables: baseline DAS28-CRP and medication used (ADA versus ETN)) showed an AUC of 0.73 (95% CI: 0.64–0.82). The calprotectin added model performed similarly with an AUC of 0.76 (95% CI: 0.67–0.84) (p=0.27).

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Conclusions Serum calprotectin is modestly predictive for EULAR good response to ADA but not ETN treatment after 6 months in RA patients. However, calprotectin does not provide additional predictive value over a basic clinical prediction model.

References

1. Hetland et al. Arthritis Rheum 2010;62(1):22–32.

2. Cuppen et al. Rheumatology (Oxford) 2016;55(5):826–39.

3. Choi IY et al. Ann Rheum Dis 2015;74(3):499–505.

4. Obry A et al. PLoS One 2014;9(12):e115800.

References

Disclosure of Interest L. Tweehuysen: None declared, N. den Broeder: None declared, L. Joosten: None declared, T. Vogl: None declared, F. van den Hoogen Consultant for: Biogen, Celltrion, Janssen, Mundipharma and Sandoz, R. Thurlings: None declared, A. den Broeder Consultant for: Amgen