No abstract

Inconclusive evidence for the efficacy of infliximab in sarcoidosis hinders the global use of this potentially beneficial drug. To study infliximab efficacy in a clinical setting, we performed a prospective open-label trial in patients refractory to conventional treatment.Patients (n=56) received eight infusions of 5 mg·kg -1 infliximab. Pulmonary function, disease activity measured by 18 F-fluorodeoxyglucose (FDG) by positron emission tomography (PET) and quality of life were part of the clinical work-up. Infliximab levels were measured before every infusion.After 26 weeks of infliximab treatment, mean improvement in forced vital capacity (FVC) was 6.6% predicted ( p=0.0007), whereas in the 6 months before start of treatment, lung function decreased. Maximum standardised uptake value (SUVmax) of pulmonary parenchyma on 18 F-FDG PET decreased by 3.93 ( p<0.0001). High SUVmax of pulmonary parenchyma at baseline predicted FVC improvement (R=0.62, p=0.0004). An overall beneficial response was seen in 79% of patients and a partial response was seen in 17% of patients. No correlation between infliximab trough level (mean 18.0 µg·mL -1 ) and initial response was found.In conclusion, infliximab causes significant improvement in FVC in refractory

No abstract

Sarcoidosis is a heterogeneous disease in terms of presentation, duration, and severity. Due to this heterogeneity, it is difficult to align treatment decisions. Biomarkers have proved to be useful for the diagnosis and prognosis of many diseases, and over the years, many biomarkers have been proposed to facilitate diagnosis, prognosis, and treatment decisions. Unfortunately, the ideal biomarker for sarcoidosis has not yet been discovered. The most commonly used biomarkers are serum and bronchoalveolar lavage biomarkers, but these lack the necessary specificity and sensitivity. In sarcoidosis, therefore, a combination of these biomarkers is often used to establish a proper diagnosis or detect possible progression. Other potential biomarkers include imaging tools and cell signaling pathways. Fluor-18-deoxyglucose positron emission tomography and high-resolution computed tomography have been proven to be more sensitive for the diagnosis and prognosis of both pulmonary and cardiac sarcoidosis than the serum biomarkers ACE and sIL-2R. There is an upcoming role for exploration of signaling pathways in sarcoidosis pathogenesis. The JAK/STAT and mTOR pathways in particular have been investigated because of their role in granuloma formation. The activation of these signaling pathways also proved to be a specific biomarker for the prognosis of sarcoidosis. Furthermore, both imaging and cell signaling biomarkers also enable patients who might benefit from a particular type of treatment to be distinguished from those who will not. In conclusion, the diagnostic and prognostic path of sarcoidosis involves many different types of existing and new biomarker. Research addressing biomarkers and disease pathology is ongoing in order to find the ideal sensitive and specific biomarker for this disease.

Infliximab is effective as a third-line therapeutic for severe sarcoidosis; however, long-term efficacy is unknown. The aim of this study was to assess the relapse rate after discontinuation of infliximab in sarcoidosis patients and predict relapse by analysis of the activity marker soluble interleukin (IL)-2 receptor (sIL-2R) and maximum standardised uptake value (SUVmax) of 18 F-fluorodeoxyglucose positron emission tomography (FDG PET).In this retrospective cohort study, the proportion of relapse was analysed using the Kaplan-Meier method and predicting factors were studied using Cox regression.47 sarcoidosis patients who started infliximab therapy were included in the risk analysis. Kaplan-Meier analysis revealed a median time to relapse of 11.1 months and showed that 25% of the cohort relapsed within 4 months. Both mediastinal SUVmax o6.0 on FDG PET (hazard ratio 3.77, p,0.001) and serum sIL-2R o4000 pg?mL -1 (hazard ratio 2.24, p50.033) at start of therapy predicted relapse. In multivariate analysis, a mediastinal SUVmax o6.0 at initiation of therapy was an independent predictor of relapse (hazard ratio 4.33, p,0.001).The majority of patients that discontinued infliximab therapy relapsed. High serum sIL-2R and high SUVmax on FDG PET at initiation of therapy were significant predictors of relapse. These results suggest close monitoring of patients in this category when they discontinue infliximab treatment. @ERSpublications Two significant predictors of relapse after discontinuation of infliximab therapy for severe sarcoidosis