Effectiveness of Methotrexate Versus Prednisolone as First-line Therapy for Pulmonary Sarcoidosis

Sarcoidosis, Pulmonary Clinical Trial

— PREDMETH  

Official title:

The PREDMETH Trial: Effectiveness of Methotrexate Versus Prednisolone as First-line Therapy for Pulmonary Sarcoidosis - A Randomized Controlled Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04314193
• Other study ID #: NL71782.078.19
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: June 1, 2020
• Est. completion date: July 2026

Study information

• Verified date: March 2024
• Source: Erasmus Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a prospective, randomized, non-blinded, multi-center, non-inferiority trial designed to compare effectiveness and side-effects of methotrexate versus prednisolone as first-line therapy for pulmonary sarcoidosis..

Description:

Sarcoidosis is a multisystem, granulomatous disorder, most commonly affecting the lungs. Symptom burden is high, and quality of life (QoL) and social participation are negatively affected. In patients with pulmonary sarcoidosis, treatment is recommended in case of significant symptoms and/or impaired or deteriorating lung function. Evidence-based treatment recommendations are limited, outdated and largely based on expert opinion.

Prednisone is currently the first-choice therapy in pulmonary sarcoidosis and leads to short-term improvement of lung function. Unfortunately, prednisone has major side-effects and is associated with impaired QoL. Methotrexate is presently considered second-line therapy, and appears to have fewer side-effects. The investigators hypothesize that first-line treatment with methotrexate is as effective as prednisone, with fewer side-effects and better QoL.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 138
• Est. completion date: July 2026
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of sarcoidosis according to the ATS/ERS/WASOG criteria, in case of absent histology a diagnosis of sarcoidosis can also be established in a multidisciplinary team meeting in a sarcoidosis expert center based on a highly suggestive clinical and radiological picture.

• Age =18 years.

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

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

Exclusion Criteria:

• Any condition or circumstance that, in the opinion of the investigator, may make a subject 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 for another disease than sarcoidosis

• Pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study 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 last dose of the randomized study phase.

• Primary systemic treatment indication being an extra pulmonary location of sarcoidosis (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, parasitic infections or other immunodeficiency syndromes

• mouth, stomach or duodenal ulcers

Related Conditions & MeSH terms

• Sarcoidosis
• Sarcoidosis, Pulmonary

Intervention

Drug:
• Methotrexate
Oral methotrexate (15 mg weekly to be increased to 25 mg weekly) for 24 weeks.
• Prednisolone
Oral prednisolone (start 40 mg daily, to be tapered to 10 mg daily) for 24 weeks.

Locations

Country	Name	City	State
Netherlands	Jeroen Bosch Ziekenhuis	's-Hertogenbosch
Netherlands	Academisch Medisch Centrum	Amsterdam
Netherlands	Onze Lieve Vrouwe Gasthuis	Amsterdam
Netherlands	Vrije Universiteit Medisch Centrum	Amsterdam
Netherlands	Rijnstate Ziekenhuis	Arnhem
Netherlands	Amphia hospital	Breda
Netherlands	Catharina Ziekenhuis	Eindhoven
Netherlands	Medisch Spectrum Twente	Enschede
Netherlands	Martini Ziekenhuis	Groningen
Netherlands	Zuyderland Medisch Centrum	Heerlen
Netherlands	Medical Center Leeuwarden	Leeuwarden
Netherlands	Leids Universitair Medisch Centrum	Leiden
Netherlands	Haaglanden Medisch Centrum	Leidschendam
Netherlands	Sint Antonius Ziekenhuis	Nieuwegein
Netherlands	Canisius Wilhelmina Ziekenhuis	Nijmegen
Netherlands	Erasmus MC	Rotterdam
Netherlands	VieCuri Medical Center	Venlo
Netherlands	Isala Klinieken	Zwolle

Sponsors (3)

Lead Sponsor	Collaborator
Erasmus Medical Center	Longfonds, St. Antonius Hospital

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Forced Vital Capacity (FVC)	Change in hospital-measured FVC between baseline and 24 weeks	24 weeks after inclusion
Secondary	Forced Vital Capacity (FVC)	Change in hospital-measured FVC between baseline and 4 weeks.	4 weeks
Secondary	Forced Vital Capacity (FVC)	Change in hospital-measured FVC between baseline and 16 weeks.	16 weeks
Secondary	Time to major pulmonary improvement measured by FVC	Time to major pulmonary improvement measured by home-measured FVC, whereby major pulmonary improvement is defined as 80% of the maximum percent predicted FVC reached anywhere during the first 24 weeks of treatment.	24 weeks
Secondary	Change in FVC	The percentage of patients with a 5 and 10% improvement or decline in FVC at 4 weeks.	4 weeks
Secondary	Change in FVC	The percentage of patients with a 5 and 10% improvement or decline in FVC at 16 weeks.	16 weeks
Secondary	Change in FVC	The percentage of patients with a 5 and 10% improvement or decline in FVC at 24 weeks.	24 weeks
Secondary	Change in DLCO	The percentage of patients with a 10% or > 10% improvement or decline in DLCO at 4 weeks.	4 weeks
Secondary	Change in DLCO	The percentage of patients with a 10% or > 10% improvement or decline in DLCO at 16 weeks.	16 weeks
Secondary	Change in DLCO	The percentage of patients with a 10% or > 10% improvement or decline in DLCO at 24 weeks.	24 weeks
Secondary	Changes in Angiotensin-Converting Enzyme (ACE)	Differences in serum levels of sACE (U/ml) in serum of sarcoidosis patients before, during and after treatment	2 years
Secondary	Between group changes in sACE levels during treatment	Differences in serum levels of sACE (U/ml) in serum of sarcoidosis patients on prednisolone versus methotrexate	2 years
Secondary	Changes in soluble interleukin-2 receptor (sIL-2R)	Differences in serum levels of sIL-2R (U/ml) in serum of sarcoidosis patients before, during and after treatment	2 years
Secondary	Between group changes in sIL-2R levels during treatment	Differences in serum levels of sIL-2R (U/ml) in serum of sarcoidosis patients on prednisolone versus methotrexate	2 years
Secondary	Changes in extracellular vesicles during treatment	Differences in absolute numbers of extracellular vesicles in serum of sarcoidosis patients before, during and after treatment	2 years
Secondary	Between group changes in extracellular vesicles absolute numbers	Differences in absolute numbers of extracellular vesicles in serum of sarcoidosis patients on prednisolone versus methotrexate	2 years
Secondary	Changes in protein expression levels in extracellular vesicles during treatment	Differences in protein expression in extracellular vesicles in serum of sarcoidosis patients before, during and after treatment	2 years
Secondary	Between group changes in protein expression levels in extracellular vesicles	Differences in protein expression in extracellular vesicles in serum of sarcoidosis patients on prednisolone versus methotrexate	2 years
Secondary	Changes in T lymphocyte phenotypes during Treatment	Flow cytometry analysis will be used to determine how the frequencies and distribution of different cell subtypes change during treatment. Different phenotypes can be identified through expression of a number of cell surface markers, expression is measured in MFI (mean fluorescence intensity).; Differences in phenotype of T-cells (MFI) in peripheral blood of sarcoidosis patients before, during and after treatment.	2 years
Secondary	Between group changes in T lymphocyte phenotypes	Flow cytometry analysis will be used to determine how the frequencies and distribution of different cell subtypes change during treatment. Different phenotypes can be identified through expression of a number of cell surface markers, expression is measured in MFI (mean fluorescence intensity).; Differences in phenotype of T-cells (MFI) in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate	2 years
Secondary	Changes in T lymphocyte absolute cell numbers	Differences in the absolute numbers of T-cells (cells/ml) in peripheral blood of sarcoidosis patients before, during and after treatment	2 years
Secondary	Between group changes in T lymphocyte absolute cell numbers	Differences in the absolute numbers of T-cells (cells/ml) in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate	2 years
Secondary	Changes in the distribution of T lymphocytes during treatment	Differences in the frequencies of T-cells (%) in peripheral blood of sarcoidosis patients before, during and after treatment	2 years
Secondary	Between group changes in the distribution of T lymphocytes	Differences in the frequencies of T-cells (%) in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate	2 years
Secondary	Changes in dendritic cell phenotypes during Treatment	Flow cytometry analysis will be used to determine how the frequencies and distribution of different cell subtypes change during treatment. Different phenotypes can be identified through expression of a number of cell surface markers, expression is measured in MFI (mean fluorescence intensity).; Differences in phenotype of dendritic cells (MFI) in peripheral blood of sarcoidosis patients before, during and after treatment	2 years
Secondary	Between group changes in dendritic cell phenotypes	Flow cytometry analysis will be used to determine how the frequencies and distribution of different cell subtypes change during treatment. Different phenotypes can be identified through expression of a number of cell surface markers, expression is measured in MFI (mean fluorescence intensity).; Differences in phenotype of dendritic cells (MFI) in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate	2 years
Secondary	Changes in dendritic cell absolute cell numbers	Differences in the absolute numbers of dendritic cells (cells/ml) in peripheral blood of sarcoidosis patients before, during and after treatment	2 years
Secondary	Between group changes in dendritic cell absolute cell numbers	Differences in the absolute numbers of dendritic cells (cells/ml) in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate	2 years
Secondary	Changes in the distribution of dendritic cells during treatment	Differences in the frequencies of dendritic cells (%) in peripheral blood of sarcoidosis patients before, during and after treatment	2 years
Secondary	Between group changes in the distribution of dendritic cells	Differences in the frequencies of dendritic cells (%) in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate	2 years
Secondary	Changes in monocyte subset phenotypes during Treatment	Flow cytometry analysis will be used to determine how the frequencies and distribution of different cell subtypes change during treatment. Different phenotypes can be identified through expression of a number of cell surface markers, expression is measured in MFI (mean fluorescence intensity).; Differences in expression of monocyte specific cell surface markers on monocytes (MFI) in peripheral blood of sarcoidosis patients before, during and after treatment	2 years
Secondary	Between group changes in monocyte subset phenotypes	Flow cytometry analysis will be used to determine how the frequencies and distribution of different cell subtypes change during treatment. Different phenotypes can be identified through expression of a number of cell surface markers, expression is measured in MFI (mean fluorescence intensity).; Differences expression of monocyte specific cell surface markers on monocytes (MFI) in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate	2 years
Secondary	Changes in monocyte absolute cell numbers	Differences in the absolute numbers of monocytes (cells/ml) in peripheral blood of sarcoidosis patients before, during and after treatment	2 years
Secondary	Between group changes in monocyte absolute cell numbers	Differences in the absolute numbers of monocytes (cells/ml) in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate	2 years
Secondary	Changes in the distribution of monocytes during treatment	Differences in the frequencies of monocytes in peripheral blood of sarcoidosis patients before, during and after treatment	2 years
Secondary	Between group changes in the distribution of monocytes	Differences in the frequencies of monocytes in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate	2 years
Secondary	Correlation between biomarkers and clinical parameters	The differences in percentage of biomarkers is compared with the differences in change of FVC and DLCOc.; Biomarkers are measured in peripheral blood and include: monocytes, measured by flow cytometry (MFI); Th-cells, measured by flow cytometry (MFI); dendritic cells, measured by flow cytometry (MFI); Proteins, measured by ELISA (ng/ml); Serum biomarkers (U/l)	2 years
Secondary	The King's Sarcoidosis Questionnaire (KSQ)	The King's Sarcoidosis Questionnaire (KSQ) assesses health status in patients with sarcoidosis. It comprises 29 items in 5 subdomains: general health status, lung, medication, skin and eyes. All scores range from 0 to 100, higher scores signifying beter health status. It takes about 3-5 minutes to complete.	baseline
Secondary	The King's Sarcoidosis Questionnaire (KSQ)	The King's Sarcoidosis Questionnaire (KSQ) assesses health status in patients with sarcoidosis. It comprises 29 items in 5 subdomains: general health status, lung, medication, skin and eyes. All scores range from 0 to 100, higher scores signifying beter health status. It takes about 3-5 minutes to complete.	baseline and 4 weeks after inclusion
Secondary	The King's Sarcoidosis Questionnaire (KSQ)	The King's Sarcoidosis Questionnaire (KSQ) assesses health status in patients with sarcoidosis. It comprises 29 items in 5 subdomains: general health status, lung, medication, skin and eyes. All scores range from 0 to 100, higher scores signifying beter health status. It takes about 3-5 minutes to complete.	baseline and 16 weeks after inclusion
Secondary	The King's Sarcoidosis Questionnaire (KSQ)	The King's Sarcoidosis Questionnaire (KSQ) assesses health status in patients with sarcoidosis. It comprises 29 items in 5 subdomains: general health status, lung, medication, skin and eyes. All scores range from 0 to 100, higher scores signifying beter health status. It takes about 3-5 minutes to complete.	baseline and 24 weeks after inclusion
Secondary	The King's Sarcoidosis Questionnaire (KSQ)	The King's Sarcoidosis Questionnaire (KSQ) assesses health status in patients with sarcoidosis. It comprises 29 items in 5 subdomains: general health status, lung, medication, skin and eyes. All scores range from 0 to 100, higher scores signifying beter health status. It takes about 3-5 minutes to complete.	baseline and 1 year after inclusion
Secondary	The King's Sarcoidosis Questionnaire (KSQ)	The King's Sarcoidosis Questionnaire (KSQ) assesses health status in patients with sarcoidosis. It comprises 29 items in 5 subdomains: general health status, lung, medication, skin and eyes. All scores range from 0 to 100, higher scores signifying beter health status. It takes about 3-5 minutes to complete.	baseline and 2 years after inclusion
Secondary	The Chronic Respiratory Questionnaire (CRQ)	The Chronic Respiratory Questionnaire (CRQ) is a 20-item self-reported validated questionnaire for HRQOL in patients with chronic respiratory disease. Scores range from 0 - 100 and higher scores signifying beter health quality.The minimal clinically important difference (MCID) is 0,5 points per item. It takes about 3-5 minutes to complete.	baseline
Secondary	The Chronic Respiratory Questionnaire (CRQ)	The Chronic Respiratory Questionnaire (CRQ) is a 20-item self-reported validated questionnaire for HRQOL in patients with chronic respiratory disease. Scores range from 0 - 100 and higher scores signifying beter health quality.The minimal clinically important difference (MCID) is 0,5 points per item. It takes about 3-5 minutes to complete.	baseline and 4 weeks after inclusion
Secondary	The Chronic Respiratory Questionnaire (CRQ)	The Chronic Respiratory Questionnaire (CRQ) is a 20-item self-reported validated questionnaire for HRQOL in patients with chronic respiratory disease. Scores range from 0 - 100 and higher scores signifying beter health quality.The minimal clinically important difference (MCID) is 0,5 points per item. It takes about 3-5 minutes to complete.	baseline and 16 weeks after inclusion
Secondary	The Chronic Respiratory Questionnaire (CRQ)	The Chronic Respiratory Questionnaire (CRQ) is a 20-item self-reported validated questionnaire for HRQOL in patients with chronic respiratory disease. Scores range from 0 - 100 and higher scores signifying beter health quality.The minimal clinically important difference (MCID) is 0,5 points per item. It takes about 3-5 minutes to complete.	baseline and 24 weeks after inclusion
Secondary	The Chronic Respiratory Questionnaire (CRQ)	The Chronic Respiratory Questionnaire (CRQ) is a 20-item self-reported validated questionnaire for HRQOL in patients with chronic respiratory disease. Scores range from 0 - 100 and higher scores signifying beter health quality.The minimal clinically important difference (MCID) is 0,5 points per item. It takes about 3-5 minutes to complete.	baseline and 1 year after inclusion
Secondary	The Chronic Respiratory Questionnaire (CRQ)	The Chronic Respiratory Questionnaire (CRQ) is a 20-item self-reported validated questionnaire for HRQOL in patients with chronic respiratory disease. Scores range from 0 - 100 and higher scores signifying beter health quality.The minimal clinically important difference (MCID) is 0,5 points per item. It takes about 3-5 minutes to complete.	baseline and 2 years after inclusion
Secondary	The global rating of change scale (GRC)	The global rating of change scale (GRC) is a measure in which patients are asked to rate if their QOL is improved or deteriorated over a certain period of time on a scale from -7 to +7. It consists of one questions and takes <1 minute to complete.	baseline
Secondary	The global rating of change scale (GRC)	The global rating of change scale (GRC) is a measure in which patients are asked to rate if their QOL is improved or deteriorated over a certain period of time on a scale from -7 to +7. It consists of one questions and takes <1 minute to complete.	baseline and 4 weeks after inclusion
Secondary	The global rating of change scale (GRC)	The global rating of change scale (GRC) is a measure in which patients are asked to rate if their QOL is improved or deteriorated over a certain period of time on a scale from -7 to +7. It consists of one questions and takes <1 minute to complete.	baseline and 16 weeks after inclusion
Secondary	The global rating of change scale (GRC)	The global rating of change scale (GRC) is a measure in which patients are asked to rate if their QOL is improved or deteriorated over a certain period of time on a scale from -7 to +7. It consists of one questions and takes <1 minute to complete.	baseline and 24 weeks after inclusion
Secondary	The global rating of change scale (GRC)	The global rating of change scale (GRC) is a measure in which patients are asked to rate if their QOL is improved or deteriorated over a certain period of time on a scale from -7 to +7. It consists of one questions and takes <1 minute to complete.	baseline and 1 year after inclusion
Secondary	The global rating of change scale (GRC)	The global rating of change scale (GRC) is a measure in which patients are asked to rate if their QOL is improved or deteriorated over a certain period of time on a scale from -7 to +7. It consists of one questions and takes <1 minute to complete.	baseline and 2 years after inclusion
Secondary	The EuroQol five dimensions 5-level questionnaire (EQ-5D-5L)	Patients will complete the EQ-5D-5L questionnaire, a standardized instrument to measure health outcomes in two components: health description and valuation. It comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression on a 5-point scale. From these 5 answers an index value is derived between 0 and 1, with a higher value corresponding with a better QoL. In the valuation part the patients' general health status is evaluated using a VAS-score from 0 to 100, with a higher score representing a better QoL.	baseline
Secondary	The EuroQol five dimensions 5-level questionnaire (EQ-5D-5L)	Patients will complete the EQ-5D-5L questionnaire, a standardized instrument to measure health outcomes in two components: health description and valuation. It comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression on a 5-point scale. From these 5 answers an index value is derived between 0 and 1, with a higher value corresponding with a better QoL. In the valuation part the patients' general health status is evaluated using a VAS-score from 0 to 100, with a higher score representing a better QoL.	baseline and 4 weeks after inclusion
Secondary	The EuroQol five dimensions 5-level questionnaire (EQ-5D-5L)	Patients will complete the EQ-5D-5L questionnaire, a standardized instrument to measure health outcomes in two components: health description and valuation. It comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression on a 5-point scale. From these 5 answers an index value is derived between 0 and 1, with a higher value corresponding with a better QoL. In the valuation part the patients' general health status is evaluated using a VAS-score from 0 to 100, with a higher score representing a better QoL.	baseline and 16 weeks after inclusion
Secondary	The EuroQol five dimensions 5-level questionnaire (EQ-5D-5L)	Patients will complete the EQ-5D-5L questionnaire, a standardized instrument to measure health outcomes in two components: health description and valuation. It comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression on a 5-point scale. From these 5 answers an index value is derived between 0 and 1, with a higher value corresponding with a better QoL. In the valuation part the patients' general health status is evaluated using a VAS-score from 0 to 100, with a higher score representing a better QoL.	baseline and 24 weeks after inclusion
Secondary	The EuroQol five dimensions 5-level questionnaire (EQ-5D-5L)	Patients will complete the EQ-5D-5L questionnaire, a standardized instrument to measure health outcomes in two components: health description and valuation. It comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression on a 5-point scale. From these 5 answers an index value is derived between 0 and 1, with a higher value corresponding with a better QoL. In the valuation part the patients' general health status is evaluated using a VAS-score from 0 to 100, with a higher score representing a better QoL.	baseline and 1 year after inclusion
Secondary	The EuroQol five dimensions 5-level questionnaire (EQ-5D-5L)	Patients will complete the EQ-5D-5L questionnaire, a standardized instrument to measure health outcomes in two components: health description and valuation. It comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression on a 5-point scale. From these 5 answers an index value is derived between 0 and 1, with a higher value corresponding with a better QoL. In the valuation part the patients' general health status is evaluated using a VAS-score from 0 to 100, with a higher score representing a better QoL.	baseline and 2 years after inclusion
Secondary	The Medical Research Council Dyspnea scale	The Medical Research Council Dyspnea scale consists of one question measuring dyspnea on a scale from 0-5.	Baseline
Secondary	The Medical Research Council Dyspnea scale	The Medical Research Council Dyspnea scale consists of one question measuring dyspnea on a scale from 0-5.	Baseline and 4 weeks after inclusion
Secondary	The Medical Research Council Dyspnea scale	The Medical Research Council Dyspnea scale consists of one question measuring dyspnea on a scale from 0-5.	Baseline and 16 weeks after inclusion
Secondary	The Medical Research Council Dyspnea scale	The Medical Research Council Dyspnea scale consists of one question measuring dyspnea on a scale from 0-5.	Baseline and 24 weeks after inclusion
Secondary	The Medical Research Council Dyspnea scale	The Medical Research Council Dyspnea scale consists of one question measuring dyspnea on a scale from 0-5.	Baseline and 1 year after inclusion
Secondary	The Medical Research Council Dyspnea scale	The Medical Research Council Dyspnea scale consists of one question measuring dyspnea on a scale from 0-5.	Baseline and 2 years after inclusion
Secondary	The fatigue assessment scale (FAS)	The fatigue assessment scale (FAS) is a 10-item self-administered questionnaire about fatigue in patients with sarcoidosis. The score ranges from 5-50 points, with a score of = 22 points as cut-off for fatigue. The MCID is 4 points or a 10% lower score.	Baseline
Secondary	The fatigue assessment scale (FAS)	The fatigue assessment scale (FAS) is a 10-item self-administered questionnaire about fatigue in patients with sarcoidosis. The score ranges from 5-50 points, with a score of = 22 points as cut-off for fatigue. The MCID is 4 points or a 10% lower score.	Baseline and 4 weeks after inclusion
Secondary	The fatigue assessment scale (FAS)	The fatigue assessment scale (FAS) is a 10-item self-administered questionnaire about fatigue in patients with sarcoidosis. The score ranges from 5-50 points, with a score of = 22 points as cut-off for fatigue. The MCID is 4 points or a 10% lower score.	Baseline and 16 weeks after inclusion
Secondary	The fatigue assessment scale (FAS)	The fatigue assessment scale (FAS) is a 10-item self-administered questionnaire about fatigue in patients with sarcoidosis. The score ranges from 5-50 points, with a score of = 22 points as cut-off for fatigue. The MCID is 4 points or a 10% lower score.	Baseline and 24 weeks after inclusion
Secondary	The fatigue assessment scale (FAS)	The fatigue assessment scale (FAS) is a 10-item self-administered questionnaire about fatigue in patients with sarcoidosis. The score ranges from 5-50 points, with a score of = 22 points as cut-off for fatigue. The MCID is 4 points or a 10% lower score.	Baseline and 1 year after inclusion
Secondary	The fatigue assessment scale (FAS)	The fatigue assessment scale (FAS) is a 10-item self-administered questionnaire about fatigue in patients with sarcoidosis. The score ranges from 5-50 points, with a score of = 22 points as cut-off for fatigue. The MCID is 4 points or a 10% lower score.	Baseline and 2 years after inclusion
Secondary	Number of patients who discontinue/switch medication	Every week patients register whether they missed pills (and the amount of pills wasted). Discontinuation or switch of medication is registered both by patients and researchers.	During 24 weeks
Secondary	Patient Experience and Satisfaction with Medication questionnaire	Correlation between patient expectations with medication and consecutive experiences measured with the PESaM questionnaire which assess patient expectations at baseline in an 11-item questionnaire and patient experiences and side-effects with medication after 12 weeks in a 26-item questionnaire on a 0-4 Likert scale. For each question it is different whether a higher score represents better or worse outcomes.	baseline
Secondary	Patient Experience and Satisfaction with Medication questionnaire	Correlation between patient expectations with medication and consecutive experiences measured with the PESaM questionnaire which assess patient expectations at baseline in an 11-item questionnaire and patient experiences and side-effects with medication after 12 weeks in a 26-item questionnaire on a 0-4 Likert scale. For each question it is different whether a higher score represents better or worse outcomes.	4 weeks
Secondary	Patient Experience and Satisfaction with Medication questionnaire	Correlation between patient expectations with medication and consecutive experiences measured with the PESaM questionnaire which assess patient expectations at baseline in an 11-item questionnaire and patient experiences and side-effects with medication after 12 weeks in a 26-item questionnaire on a 0-4 Likert scale. For each question it is different whether a higher score represents better or worse outcomes.	16 weeks
Secondary	Patient Experience and Satisfaction with Medication questionnaire	Correlation between patient expectations with medication and consecutive experiences measured with the PESaM questionnaire which assess patient expectations at baseline in an 11-item questionnaire and patient experiences and side-effects with medication after 12 weeks in a 26-item questionnaire on a 0-4 Likert scale. For each question it is different whether a higher score represents better or worse outcomes.	24 weeks
Secondary	Patient Experience and Satisfaction with Medication questionnaire	Correlation between patient expectations with medication and consecutive experiences measured with the PESaM questionnaire which assess patient expectations at baseline in an 11-item questionnaire and patient experiences and side-effects with medication after 12 weeks in a 26-item questionnaire on a 0-4 Likert scale. For each question it is different whether a higher score represents better or worse outcomes.	1 year
Secondary	Patient Experience and Satisfaction with Medication questionnaire	Correlation between patient expectations with medication and consecutive experiences measured with the PESaM questionnaire which assess patient expectations at baseline in an 11-item questionnaire and patient experiences and side-effects with medication after 12 weeks in a 26-item questionnaire on a 0-4 Likert scale. For each question it is different whether a higher score represents better or worse outcomes.	2 years