Calprotectin and serum amyloid A for disease activity assessment in giant cell arteritis and polymyalgia rheumatica: results from a prospective single-centre cohort study

Monitoring disease activity in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) is commonly based on C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Both markers are unreliable during interleukin-6 receptor inhibitor (IL-6Ri) therapy. We evaluated calprotectin (CALPR) and serum amyloid A (SAA) as alternative biomarkers. In a prospective single-centre cohort, we obtained 576 serial measurements from 98 patients with GCA (n = 81) or PMR (n = 17) between 2019 and 2022. Disease activity was classified as “active” or “remission” according to current EULAR recommendations. CRP, ESR, CALPR, and SAA were analysed and compared between patients treated with and without tocilizumab (TCZ). Univariate mixed-effects logistic regression models were fitted for the marker and used for receiver operating characteristic (ROC) analyses; multivariable mixed-effects models were used to adjust for clinical covariates. Active disease was present at 131 of 576 visits (22.7%), and 140 visits (24.3%) occurred under tocilizumab (TCZ) treatment. In patients without TCZ, ROC analysis showed the best discrimination for CRP (AUC 0.76, 95% CI 0.69–0.83), followed by SAA (0.74, 0.67–0.81), ESR (0.70, 0.63–0.78), and calprotectin (CALPR; 0.66, 0.59–0.73). Under TCZ treatment, SAA achieved the highest AUC (0.72, 95% CI 0.51–0.90), outperforming CRP (0.58, 0.42–0.77), CALPR (0.56, 0.32–0.74), and ESR (0.48, 0.30–0.67). In multivariable mixed-effects models, CRP, ESR, and SAA remained significantly associated with active disease in patients without TCZ, whereas none of the markers distinguished active disease from remission under TCZ treatment. SAA outperformed conventional markers in detecting active disease during IL-6Ri therapy in univariate analysis, but no biomarker retained significance after adjustment. These findings underscore the limitations of current laboratory monitoring in GCA and PMR under IL-6 inhibition and highlight the need for further evaluation of IL-6–independent biomarkers.