Background/Purpose:  An increasing number of RA and PsA patients achieve low levels of disease activity under biological therapy. Thus, new biomarkers are needed to stratify disease activity, guiding therapeutic decisions. Calprotectin is a major S100 leucocyte protein, is associated with disease activity in this group of patients. Calprotectin is a potentially biomarker more sensitive of disease activity than conventional acute-phase proteins

Methods:  Prospective 1-year follow-up, single center study (INMUNOREMAR cohort). RA (ACR 1987) and PsA (CASPAR) patients in clinical remission (CR) (DAS28-ESR <2.6) or low disease activity (LDA) (DAS28-ESR <3.2) in ≥2 consecutive visits treated with adalimumab (ADA), etanercept (ETN) or infliximab (IFX) for ≥3 months were included. Demographic data, disease duration, time to initiate csDMARD and bDMARD, time to achieve remission, remission duration, autoantibody status, radiological data, concomitant csDMARD therapy, dose and duration of biological therapy were collected. Clinical and laboratory assessment was made every 4 months and at the time of flare. Calprotectin serum levels (ELISA Kit Calpro AS®) and TNFa trough serum levels (ELISA Kit Promonitor®, Progenika) were determined. Disease flare was defined as DAS28-ESR>3.2 and increase in ΔDAS28-ESR >0.6. Univariate and multivariate regression models were used to identify predictors of disease flare.

Results:  103 patients (47RA, 56PsA) were included. Mean Age 57 (30–81) years. 78 (75.8%) had CR and 25 (24.2%) LDA. Mean CR/LDA duration was 58 (4–163) months. 36 patients had received treatment with ADA, 50ETN, and 17IFX. Mean biologic treatment duration 61 (7–166) months. 47.4% patients were on monotherapy, 47% on reduced dose, and 17.9% received steroids. 84 patients (91%) remained in CR/LDA for 12 months, and 12 patients (13%; 8 RA, 4 PsA) experienced flares. Patients with flares had a longer time to achieve CR/LDA [CR/LDA (n=81) 3.1 (1–6) months vs. Flare (n=12) 20 (5–31) months, p<0.001], a shorter CR/LDA duration [CR/LDA (n=81) 59 (5–163) months vs. Flare (n=12) 25 (3–134) months, p=0.031], higher calprotectin levels [CR/LDA (n=81) 1.4 (0.6–3.7) μg/mL vs. Flare (n=12) 6 (4.5–7.9) μg/mL, p<0.001], and lower drug trough serum levels at baseline [CR/LDA (n=83) 2.6 (0.6–12) μg/mL vs. Flare (n=12) 0.6 (1–1.2) μg/mL; p<0.001], even when analyzed by biologic [ADA CR/LDA (n=30) 7 (0.2–12) μg/mL vs. Flare (n=4) 0.5 (0.4–1) μg/mL; p=0.003; ETN CR/LDA (n=44) 1.5 (0.7–4.7) μg/mL vs. Flare (n=5) 0.8 (0.9–1.2)μg/mL; p=0.039; IFX CR/LDA (n=14) 3.1 (0.5–7.7) μg/mL vs. Flare (n=3) 0.1 (0–1) μg/mL; p=0.021]. Baseline TNFi trough serum levels [hazard ratio (HR) = 0.47], steroid treatment (HR=3.21), time to CR/LDA (HR=1.17), and baseline calprotectin levels (HR=2.38) significantly predicted flare in the univariate analysis. However, only baseline calprotectin levels significantly predicted flare in the multivariate analysis [HR=2.74 (1.74–4.31); p<0.0001].

Conclusion:  Calprotectin was a strong independent predictor of flare in RA and PsA patients treated with TNF inhibitors with low levels of disease activity.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/calprotectin-serum-levels-strongly-predict-disease-flare-in-ra-and-psa-patients-with-low-disease-activity-treated-with-tnf-inhibitors-a-one-year-prospective-cohort-study/