Date: Monday, November 8, 2021
Session Type: Poster Session C
Session Time: 8:30AM-10:30AM
Background/Purpose: IL6 inhibitors (IL6i) have a dramatic effect on acute phase reactants (AFR) such as C reactive protein (CRP) in rheumatoid arthritis (RA). However, CRP serum levels do not correlate with inflammatory activity in RA patients under IL6i therapy. JAK inhibitors (JAKi) also partly inhibit IL6 signaling. Calprotectin is a protein that correlates closely with inflammatory activity and may be a biomarker that accurately reflects the disease status in IL6i and JAKi treated RA patients.
Methods: Cross-sectional study in RA patients (ACR/EULAR 2010) treated with IL6i (tocilizumab, sarilumab) or JAKi (tofacitinib, baricitinib). Demographic, serological data (autoantibodies, ESR, ultrasensitive CRP (usCRP), composite activity indices (DAS28, SDAI, CDAI, RAPID3), disability (HAQ) and therapy were evaluated. Plasma calprotectin levels were measured by ELISA (CALPROLAB ALP Menarini). Hand ultrasound was studied to calculate synovial hypertrophy (SH), power Doppler signal (PD) score and total ultrasound activity score (SH+PD) graded according to Szudlarek’s(1) . We compared plasma calprotectin and clinical and ultrasound variables in patients receiving IL6i and JAKi using Spearman’s correlation test.
Results: We included 78 patients (91% female, median age 58.9 years, median RA duration 14.5 years, 88.5% seropositive (RF and/or ACPA). Fifty two patients were treated with IL6i and 26 with JAKi [Table 1]. Ultrasound studies were made in 63 patients (42 receiving IL6i and 21 JAKi).
No significant between-group differences were observed in the TJC28, SJC28, CDAI, SDAI, and HAQ. DAS28 was higher in JAKi patients. There were no differences in ultrasound scores. The median (range) of plasma calprotectin was 0.36 μg/ml (0.12-2.39) in IL6i patients and 0.65 μg/ml (0.19-5.51) in JAKi patients (p=0.083) [Table 1].
In IL6i patients, plasma calprotectin weakly correlated with SJC28 but not with composite activity indices or with AFR (usCRP or ESR), although there was a significant correlation with all ultrasound scores (SH, PD and SH+PD) that was not found with usCRP or ESR. In JAKi patients, calprotectin showed a non-significant trend to correlation with TJC28, and a high correlation with all ultrasound scores (SH, PD and SH +PD) and usCRP levels, but not with activity indices [Table2].
Classification according to CDAI ≤10 vs. CDAI >10 showed no significant differences in calprotectin values: median (range) 0.33μg/ml (0.14-5.51) vs 0.59 μg/ml (0.12-5.50) p= 0.121). Classification according to ultrasound activity (ultrasound synovitis (SH ≥ 2 + PD≥1) in ≥ 1 joint showed -higher calprotectin levels in patients with ultrasound synovitis: median 0.70 μg/ml (0.18-5.03) vs 0.29 μg/ml (0.19-0.69) p< 0.001).
Conclusion: Plasma calprotectin in patients with low-moderate disease activity treated with IL6i or JAKi did not identify patients according to the degree of inflammation measured by the composite activity indices. However, in both groups and specially in patients treated with JAKi, calprotectin was related to ultrasound synovitis scores. Plasma calprotectin might be a biomarker of active synovitis in these patients.
TJC: tender joint count; SJC: swollen joint count; PGA: patient global assessment PhGA: physician global assessment; VAS visual analogue scale SH: synovial hypertrophy on ultrasound: PD power Doppler signal on ultrasound. Data expressed as median and (ranges)
To cite this abstract in AMA style:Frade-Sosa B, Ponce A, Gumucio R, inciarte-Mundo J, Torradeflot M, Ruiz-Esquide V, Morlà R, Azuaga A, Sapena N, Bassas M, Ramirez J, Cañete J, Gomez-Puerta J, Sanmarti R. Plasma Calprotectin as a Biomarker of Active Synovitis in Rheumatoid Arthritis: A Clinical and Ultrasound Study in Patients Treated with Il6 and JAK Inhibitors [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/plasma-calprotectin-as-a-biomarker-of-active-synovitis-in-rheumatoid-arthritis-a-clinical-and-ultrasound-study-in-patients-treated-with-il6-and-jak-inhibitors/. Accessed January 30, 2023.
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