Systemic treatment strategies in severe sarcoidosis

Abstract

The main goal of this thesis was to investigate various second and third-line systemic therapeutic options in severe sarcoidosis, that is refractory to first-line therapy, and to evaluate which patients benefit most from the different treatment options in order to find predictive markers for clinical decision making. We describe that azathioprine and methotrexate are equally effective in second-line treatment of sarcoidosis, except for a higher infection rate in the azathioprine group. Furthermore we found that patients with high levels of biomarkers ACE and sIL-2R responded best to methotrexate treatment. Third line therapy with the biological drug infliximab was very effective and well-tolerated. Significant changes were seen in lung function, inflammation and quality of life. The most benefit in lung function was seen in patients with high activity on FDG-PET scan. These were also the patients with the highest relapse rate after discontinuation of the drug. During infliximab treatment molecular markers on monocytes change significantly, whether this correlates with response has yet to be determined.