Predictive value of serum calprotectin (S100A8/A9) for clinical response after starting or tapering anti-TNF treatment in patients with rheumatoid arthritis

Lieke Tweehuysen; Nathan den Broeder; Noortje van Herwaarden; Leo A B Joosten; Peter L van Lent; Thomas Vogl; Frank H J van den Hoogen; Rogier M Thurlings; Alfons A den Broeder

doi:10.1136/rmdopen-2018-000654

Predictive value of serum calprotectin (S100A8/A9) for clinical response after starting or tapering anti-TNF treatment in patients with rheumatoid arthritis

RMD Open. 2018 Apr 9;4(1):e000654. doi: 10.1136/rmdopen-2018-000654. eCollection 2018.

Authors

Affiliations

¹ Department of Rheumatology, Sint Maartenskliniek, Nijmegen, The Netherlands.
² Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
³ Department of Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands.
⁴ Department of Immunology, University of Münster, Münster, Germany.
⁵ Department of Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands.

Abstract

Objectives: Calprotectin (S100A8/A9) has been correlated with disease activity in rheumatoid arthritis (RA). The aim of this study was to investigate the predictive value of serum calprotectin for clinical response after starting and tapering anti-tumour necrosis factor treatment in RA.

Methods: Serum samples and clinical outcomes were derived from two longitudinal RA studies.At baseline (starting or tapering of adalimumab or etanercept), calprotectin levels were determined by ELISA. In the Biologic Individual Optimised Treatment Outcome Prediction (BIO-TOP) study, treatment effect was assessed after 6 months using the European League Against Rheumatism (EULAR) response criteria. In the Dose Reduction Strategies of Subcutaneous TNF Inhibitors (DRESS) study, patients were classified at 18 months as being successfully dose reduced, discontinued or not able to reduce the dose. Area under the receiver operating characteristic curves (AUC) were generated to evaluate the predictive value of calprotectin and logistic prediction models were created to assess its added value.

Results: In the BIO-TOP study, calprotectin levels were higher in responders (n=50: 985 ng/mL (p25-p75: 558-1417)) compared with non-responders (n=75: 645 ng/mL (p25-p75: 415-973), p=0.04).AUC for predicting EULAR good response was 0.61 (95% CI 0.50 to 0.71). The prediction model with calprotectin (AUC 0.77, 95% CI 0.68 to 0.85) performed similarly to the baseline model (AUC 0.74, 95% CI 0.65 to 0.82, p=0.29). In the DRESS study, calprotectin levels were similar between the three groups (n=47; n=19; n=36) and calprotectin was not predictive for clinical response after tapering.

Conclusions: Serum calprotectin has some predictive value for clinical response after starting anti-TNF treatment, although it has no added value to other clinical factors. In patients with low disease activity, serum calprotectin is not predictive for clinical response after tapering anti-TNF treatment.

Trial registration number: NTR4647 (BIO-TOP study) and NTR3216 (DRESS study); Pre-results.

Keywords: biologic agents; biomarkers; calprotectin; prediction of response; rheumatoid arthritis; tapering.