Study design and characterization of study subjects
Participants were identified amongst patients referred to Department of Respiratory Medicine, Karolinska University Hospital, Stockholm, Sweden, with deteriorating sarcoidosis despite previous treatment with corticosteroids and/ or methotrexate. None of the included patients had a history of serious infections (including tuberculosis and hepatitis), congestive heart failure or malignancy. All patients were diagnosed with sarcoidosis (non-Löfgren´s syndrome) according to criteria established by the World Association of Sarcoidosis and Other Granulomatous Disorders33. Informed consent was obtained from all subjects and ethical approval obtained from the Stockholm County Regional Ethical Committee (approval number: 2012/2083-31/3). Upon enrollment, information of the study was given both orally and written. All participants signed an informed consent according to the declaration of Helsinki. For clinical characteristics, see Table 1.
Before starting therapy with infliximab, patients were characterized with chest x-ray (classified according to Scadding´s staging system), CT scan and lung function including spirometry and measurement of diffusion capacity of the lung for carbon monoxide (DLCO). Bronchoscopy with BAL was performed on average 6 weeks before (range 3-9 weeks) start of therapy. All investigations were repeated at follow-up after the first half year on treatment.
To prevent antibody formation, TNF-α inhibitor treatment should be combined with a low dose of methotrexate and/ or glucocorticosteroids20. In order to make our study population as homogenous as possible, the intention was to use 5 mg prednisone as concomitant treatment during the whole study period. Patients that were on a higher dose before start of treatment were told to reduce the dose to 5 mg. However, patient number 2, 5 and 6 were not able to reduce the dose before infliximab therapy due to worsening symptoms and in those patients the dose was tapered down during the infliximab therapy. Patient number 13 did not take any concomitant immunosuppressant at all due to misunderstanding. All patients except number 2 had a previous history of methotrexate treatment. Patients that had an ongoing methotrexate treatment at inclusion were told to stop before the first bronchoscopy (patient number 3, 4, 6, 7, 9, 10). Patient number 8 suffered from a psychiatric disease, which had deteriorated during prednisone treatment, and therefore, this patient was put on a low dose of methotrexate as concomitant treatment. For detailed information on individual treatment, see Supplement 1.