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.