Elevated Serum Amyloid a Levels Are not Specific for Sarcoidosis but Associate with a Fibrotic Pulmonary Phenotype.

Elevated Serum Amyloid A (SAA) levels have been found in several inflammatory diseases, including sarcoidosis. SAA is suggested to be involved in sarcoidosis pathogenesis by involvement in granuloma formation and maintenance. We hypothesized that SAA serum levels would be higher in sarcoidosis compared to other non-infectious granulomatous and non-granulomatous diseases. SAA levels were measured in serum from sarcoidosis, Hypersensitivity pneumonitis (HP), and (eosinophilic) granulomatosis with polyangiitis ((E)GPA) patients. Idiopathic pulmonary fibrosis (IPF) patients were included as non-granulomatous disease group. SAA levels of patients with sarcoidosis (31.0 µg/mL), HP (23.4 µg/mL), (E)GPA (36.9 µg/mL), and IPF (22.1 µg/mL) were all higher than SAA levels of healthy controls (10.1 µg/mL). SAA levels did not differ between the diagnostic groups. When SAA serum levels were analyzed in sarcoidosis subgroups, fibrotic sarcoidosis patients showed higher SAA levels than sarcoidosis patients without fibrosis (47.8 µg/mL vs. 29.4 µg/mL, p = 0.005). To conclude, the observation that fibrotic sarcoidosis patients have higher SAA levels, together with our finding that SAA levels were also increased in IPF patients, suggests that SAA may next to granulomatous processes also reflect the process of fibrogenesis. Further studies should clarify the exact role of SAA in fibrosis and the underlying mechanisms involved.

Quantification of pulmonary disease activity in sarcoidosis measured with 18F-FDG PET/CT: SUVmax versus total lung glycolysis.

BACKGROUND: 18F-FDG PET/CT has proven to be a reliable tool for therapy monitoring in sarcoidosis. Previous PET studies investigated the SUVmax as a marker for disease activity. Total lung glycolysis (TLuG) is a new tool, quantifying the glycolysis of the entire lung. Since SUVmax represents the maximum activity in only one pixel, we hypothesize that TLuG is a more accurate marker for active pulmonary disease and predictor of response than SUVmax. METHODS: In this retrospective cohort study, 27 patients started on infliximab for refractory pulmonary sarcoidosis. Patients received infliximab intravenously monthly at a dose of 5 mg/kg. We performed a lung function test and an 18F-FDG PET/CT before initiation of infliximab and after 6 months of treatment. SUVmax and TLuG were determined in the pre- and post-scan. Change in lung function was correlated with the change in SUVmax and TLuG and was correlated to the initial SUVmax and TLuG to evaluate the predictive value of the initial metabolic activity. RESULTS: ΔSUVmax significantly correlated with ΔFVC (r = - 0.497, p = 0.008) and with ΔFEV1 (r = - 0.467, p = 0.014). Furthermore, ΔTLuG significantly correlated with ΔFVC (r = - 0.430, p = 0.025), ΔFEV1 (r = - 0.532, p = 0.004) and ΔDLCOc (r = - 0.423, p = 0.039). Change in SUVmax and TLuG significantly correlated (r = 0.735, p < 0.001). Initial SUVmax significantly correlated with the change in FVC and DLCOc. In addition, initial TLuG significantly correlated with the change in FEV1 and DLCOc. A SUVmax > 7.5 at initiation of infliximab was predictive for 5% response in FVC, whereas SUVmax > 9.2 was predictive for 5% response in DLCOc. In addition, high TLuG > 4100 at initiation of infliximab was predictive for 5% response in FVC and FEV1 and TLuG > 4500 was predictive for response in DLCOc. CONCLUSION: SUVmax and TLuG are equal in determining the response to infliximab in pulmonary sarcoidosis patients. Furthermore, SUVmax and TLuG at initiation of infliximab can predict change in lung function after treatment. Since TLuG is a more time-consuming tool, we recommend to use SUVmax of the lung parenchyma for response monitoring in pulmonary sarcoidosis.

Efficacy and safety of infliximab biosimilar Inflectra® in severe sarcoidosis.

BACKGROUND: Infliximab, a monoclonal antibody against tumor necrosis factor alpha (TNF-α) is effective third-line therapy in severe sarcoidosis. The originator product of Infliximab, Remicade®, is expensive, limiting universal access. Recently, a less expensive biosimilar of infliximab, Inflectra®, has become available, but the efficacy and tolerability has not been studied in sarcoidosis. METHODS: In this retrospective cohort study, 29 patients treated with the infliximab biosimilar Inflectra®, were analysed. Patients received Inflectra® intravenously monthly at a dose of 5 mg/kg. We measured trough levels before every infusion. Before and after 6 months of induction therapy pulmonary function and disease activity were evaluated using Standardised Uptake Value (SUV) of the 18F-fluorodeoxyglucose by positron emission tomography (18F-FDG PET), soluble interleukin-2 receptor (sIL-2R), angiotensin converting enzyme (ACE) and health-related quality of life (HRQOL). RESULTS: In patients with pulmonary sarcoidosis as main treatment indication (n = 15) the predicted FVC improved with 8.1%, p < 0.05. Furthermore, in the whole group HRQoL improved significantly (p < 0.001), whereas SUVmax and sIL-2R significantly reduced (p < 0.001 and p = 0.001 respectively). Hospitalisation due to infections occurred in four patients. None of the patients discontinued Inflectra® due to side-effects. Furthermore, all patients had detectable trough levels indicating development of neutralizing antibodies. CONCLUSION: Infliximab biosimilar Inflectra® seems effective in the treatment of refractory sarcoidosis with a comparable safety profile to the reference product Remicade®. Inflectra® can be considered as an alternative and less expensive option for patients with refractory sarcoidosis.