OP0031 AN INCREASE IN SERUM CALPROTECTIN LEVEL IN ANCA-ASSOCIATED VASCULITIDES PATIENTS DURING MAINTENANCE THERAPY IS ASSOCIATED WITH MORE RELAPSE AND ACCELERATED RENAL FUNCTION DECLINE
Authors: X. Romand, A. Courtier, M. V. C. Nguyen, M. H. Paclet, P. Gaudin, L. Guillevin, B. Terrier, A. Baillet
Journal: Annals of the Rheumatic Diseases (2020)

Background: Calprotectin (S100A8/A9), a protein secreted by activated neutrophils and monocytes in inflammatory conditions, is upregulated in active ANCA-associated vasculitides. Serum calprotectin level variation during induction therapy is associated with disease relapse in PR3-ANCA-associated vasculitides (1). However, the place of this biomarker during maintenance therapy is unknown. Objectives: To demonstrate whether variation in serum calprotectin level during maintenance therapy could be used as a biomarker predicting subsequent relapse in ANCA-associated vasculitides. Methods: Patients with ANCA-associated vasculitides in complete remission (BVAS=0) after induction therapy with cyclophosphamide and included in the MAINRITSAN trial (2) were analyzed. Patients were randomized to receive rituximab or azathioprine as maintenance therapy. Relapse was defined as the re-occurrence or new onset of disease attributable to active vasculitis. Accelerated decline renal function (estimated Glomerular Filtration Rate (eGFR) assessed using the MDRD equation) was defined in concordance with NICE 2015 guideline (3) as “a decrease in eGFR of 25% or more and a change in GFR category or a sustained decrease in eGFR of 15 ml/min/1.73m 2 over 12 months”. Calprotectin was assessed in the serum at inclusion and 6 months by ELISA (IDK® Calprotectin ELISA kit, Immunodiagnostik). We defined an increase in serum levels of calprotectin as a positive variation of calprotectin level at M6 compared to baseline. Results: Of all, 96 patients (female 45.8%, mean age 55.3±13.5, 69.8% PR3+, 62.5% ANCA positive at inclusion) had at least a calprotectin dosage (86 at baseline, 86 at M6 and 76 patients at this 2 time-point). Calprotectin level at baseline or 6 months was not significantly different between relapsing patients and those without relapse after 18 months of follow-up, whereas the calprotectin variation at M6 compared to baseline was higher in relapsing patients (n=10) (mean (SD) 17991 (±28972) ng/ml) than in patients not experiencing any relapse (n=66) (9419 (±50002) ng/mL; p=0.03). An increase in serum calprotectin level at 6 months was significantly associated with an increased risk of relapse in PR3-ANCA patients (OR=5.6 (95%CI, 1.0-31.3; p=0,049) but not in the whole study group (OR=3.3 (95%CI, 0.8-14.1; p=0.1), and identified patients with accelerated renal function decline (all cohort: OR=10.6 (95%CI, 2.9-39.6; p=0.002; PR3+ patients: OR=5.909 (95%CI, 2.9-39.6; p=0.01)), whereas calprotectin level did not correlate with glomerular filtration rate (r = -0.07, p=0.35). Conclusion: An increase in serum calprotectin during the first 6 months of maintenance therapy in ANCA-associated vasculitides is a useful biomarker predicting vasculitis relapse and accelerated renal function deterioration in the following 12 months. Increase calprotectin serum at 6 months identify relapser and accelerated decline renal function at 1 year. Kaplan-Meier survival curves of ANCA-associated vasculitis patients with an increase in serum calprotectin at 6 months (solid line) or not (dotted line) remaining total relapse-free or accelerated decline renal function-free. Gehan-Beslow-Wilcoxon test. References: [1]Pepper RJ et al. Arthritis Rheumatol. 2017;69(1):185-93. [2]Guillevin L et al. N Engl J Med. 2014;371(19):1771-80. [3]NIH. Chronic kidney disease 2014. Acknowledgments: Supported by a grant from the Programme Hospitalier de Recherche Clinique, French Ministry of Health (2008-002846-51). Disclosure of Interests: Xavier Romand Consultant of: Xavier ROMAND has received honorarium fees from Abbvie, Anais Courtier: None declared, Minh Vu Chuong Nguyen: None declared, Marie-Hélène Paclet: None declared, Philippe Gaudin Speakers bureau: Lilly, Loïc Guillevin: None declared, Benjamin Terrier: None declared, Athan Baillet Consultant of: Athan BAILLET has received honorarium fees from Abbvie for his participation as the coordinator of the systematic literature review