Effectiveness of Methotrexate Versus Prednisone As First-line Therapy for Pulmonary Sarcoidosis

Inclusion Criteria:

• Diagnosis of sarcoidosis according to the ATS/ERS/WASOG criteria, in case of absenthistology a diagnosis of sarcoidosis can also be established in a multidisciplinaryteam meeting in a sarcoidosis expert center based on a highly suggestive clinicaland radiological picture.

• Age ≥18 years.

• A pulmonary indication for treatment and parenchymal involvement on X-ray or CT-scanconducted within three months before inclusion (determined by the treating physicianand conform current guidelines).

• A forced vital capacity (FVC) of ≤90% of predicted, or a diffusion capacity of thelung for carbon monoxide (DLCO) ≤70% of predicted, or ≥5% FVC absolute decline/≥10%DLCO absolute decline in the past year. For pulmonary functions tests GLI referencevalues are used.

Exclusion Criteria:

• Any condition or circumstance that, in the opinion of the investigator, may make asubject unlikely or unable to complete the study or comply with study procedures.

• Previous immunosuppressive treatment for sarcoidosis

• Use of systemic immunosuppressive therapy within the preceding three months foranother disease than sarcoidosis

• Pregnant, breastfeeding, or planning to become pregnant or breastfeed during thestudy treatment or within 90 days after the last dose in the randomized study phase.For males; planning to pro-create during the study or within 90 days after the lastdose of the randomized study phase.

• Primary systemic treatment indication being an extra pulmonary location ofsarcoidosis (e.g. cardiac of neurological)

• Contra-indication for methotrexate or corticosteroids:

• severely impaired renal function (creatinine clearance <30 ml/min)

• impaired hepatic function (serum bilirubin-value >5 mg/dl or 85,5 micromole/l)

• bone marrow insufficiency with severe leukopenia, thrombocytopenia, or anaemia

• severe acute or chronic infections, such as tuberculosis, HIV, parasiticinfections or other immunodeficiency syndromes

• mouth, stomach or duodenal ulcers