TABLE 2

Summary of data from included studies

First author [ref.]Study designPatients (n) and characteristicsInterventionOther systemic therapyPrimary outcomesSecondary outcomes
Anti-TNF-α and anti-IL-12 and -23 therapy
 Utz [11]Open labelPulmonary sarcoidosis with progressive infiltrates or worsening pulmonary function (n=17)Etanercept 25 mg s.c.; twice weekly for 12 monthsNo immunosuppressive therapy in the past 3 monthsPulmonary function, chest radiograph, dyspnoeaHRoQL (SF-36)
 Baughman [12, 13]RCTChronic pulmonary sarcoidosis with FVC ≥50% and ≤85% (n=138)
Subset analysis: chronic cutaneous sarcoidosis (n=17)
Infliximab 3/5 mg·kg−1 i.v.; at weeks 0, 2, 6, 12, 18, 24.
Placebo
≥10 mg prednisone or one or more immunosuppressants for ≥3 months prior to screening, stable dosed ≥1 month prior to screening
Background medication stable during study
Pulmonary function (FVC)HRQoL (SGRQ, SF-36)
 Erckens [14]Open labelSarcoidosis with refractory chronic uveitis, non-responsive to prednisone and methotrexate (n=26)Adalimumab 40 mg s.c.; weekly for a minimum of 6 monthsPrior to study 100% of patients treated with oral prednisone 20–60 mg with methotrexate added if required
Background medication was tapered during study
Uveitis manifestationsChest radiograph, pulmonary function, fatigue (FAS)
 Milman [15]Open labelIntrathoracic (90%) and extrathoracic (40%) sarcoidosis non-responsive to systemic immunosuppressants; FDG-PET uptake (n=10)Adalimumab 40 mg s.c.; bi-weekly for 24 weeksPrednisolone 5–10 mg daily and/or methotrexate 10–15 mg weekly
Stable dosed during study
FDG-PET uptake, HRQoL (SF-36)Pulmonary function
 Pariser [16]RCT/Open label phaseChronic cutaneous sarcoidosis (n=16)RCT phase: adalimumab 40 mg s.c.; weekly for 12 weeks.
Placebo.
Open label phase: adalimumab 40 mg s.c.; weekly for 12 weeks
Systemic treatment stopped ≥4 weeks prior to study or continued at a maximum of 20% of study baseline doseAssessment cutaneous lesionsHRQoL (SHQ), pulmonary function, chest radiograph
 Judson [17]RCTChronic pulmonary and/or cutaneous sarcoidosis, FVC 45–80%, dyspnoea (n=173)Ustekinumab 180 mg s.c. at week 0 followed by 90 mg s.c. at weeks 8, 16, 24.
Golimumab 200 mg s.c. at week 0 followed by 100 mg every 4 weeks to week 24 Placebo
Systemic treatment with 10–25 mg prednisone equivalent and/or ≥1 immunomodulator for ≥3 months with a stable dose for ≥4 weeks prior to screening. Baseline medication tapered in second half of the studyPulmonary function (FVC)HRQoL (SGRQ, SF-36, SAT), fatigue (FAS)
 Vorselaars [18]Open labelActive, chronic and severe sarcoidosis, refractory to first- and second-line treatment (n=56)Infliximab 5 mg·kg−1 i.v. at weeks 0 and 2, subsequently every 4 weeks totalling 6 months>90% of patients had used corticosteroids and methotrexate prior to the study; 34% of patients used prednisone during the study
Prednisone dose was tapered during the study
Functional response including pulmonary functionHRQoL (SF-36, PGA)
Corticosteroids and corticotropin
 Aggarwal [19]Open labelNewly diagnosed, symptomatic pulmonary sarcoidosis (n=51)Prednisolone 0.75 mg·kg−1 orally daily for 1 month; subsequently tapered and stopped for a total of 6 monthsNo previous treatmentFatigue (FAS)HRQoL (SHQ)
 Baughman [20]RCTChronic pulmonary sarcoidosis, pulmonary deterioration in the past year (n=16)RCI 80 units s.c. daily during 10 days; followed by 40 or 80 units RCI s.c. twice weekly during 22 weeks.
RCI used as steroid-sparing agent
≥3 months stable dose of ≥5 mg prednisone equivalent, subsequently tapered during studyPrednisone sparingPulmonary function, chest radiograph, HRQoL (KSQ, SGRQ), fatigue (FAS)
Other immunosuppressive and/or immunomodulating therapies
 Judson [21]Open labelSteroid dependent, chronic pulmonary sarcoidosis with deterioration upon reduction or discontinuation of corticosteroids in the past 2 years (n=10)Thalidomide 200 mg orally daily during 24 weeks.
Thalidomide used as steroid-sparing agent
≥6 months stable dose of 5–20 mg prednisone daily, subsequently tapered during studyPulmonary function, HRQoL (SF-36)
 Heij [22]RCTSarcoidosis with small fibre neuropathy; 86% pulmonary involvement (n=22)ARA 290 2 mg i.v.; three times weekly during 4 weeks. PlaceboOral corticosteroids in 6 out of 22 patients, other systemic anti-inflammatory drugs in 3 out of 22 patients
Stable dosed during study
Pain (SF-36), neuropathic symptoms, HRQoL (SF-36), fatigue (FAS)
 Drake [23]Open labelChronic pulmonary sarcoidosis, FVC 45–80% (n=15)Broad-spectrum antimycobacterial therapy (CLEAR regimen) for 8 weeks47% of patients received concomitant corticosteroids (range 3.75–30 mg daily) and/or immunomodulators
All therapies were stable dosed for ≥6 months
Pulmonary function (FVC)HRQoL (SGRQ)
Stimulants
 Lower [24]RCT; crossoverPulmonary sarcoidosis for >2 years; with chronic fatigue (n=10)d-MPH 5 mg orally; twice daily during 2×8 weeks.
Placebo
100% of patients received ≥1 immunosuppressive and/or immunomodulatory agents.
Stable dosed during study
Fatigue (FACIT-F, FAS)HRQoL (SGRQ)
 Lower [25]RCT; crossoverPulmonary sarcoidosis with persistent fatigue despite stable systemic treatment (n=15)Armodafinil 150 to 250 mg orally; daily during 2×8 weeks. Placebo100% of patients received ≥1 immunosuppressive and/or immunomodulatory agents
Stable dosed for ≥3 months prior to study and stable dosed during study
Fatigue (FACIT-F, FAS)HRQoL (SF-36, SHQ)

TNF: tumour necrosis factor; IL: interleukin; HRQoL: health-related quality of life; RCT: randomised controlled trial; FVC: forced vital capacity; SGRQ: St George's Respiratory Questionnaire; SF-36: Short Form-36 Health Survey Questionnaire; FAS: Fatigue Assessment Scale; FDG: fluorodeoxyglucose; PET: positron emission tomography; SHQ: Sarcoidosis Health Questionnaire; SAT: Sarcoidosis Assessment Tool; PGA: Patient Global Assessment; RCI: repository corticotropin; KSQ: Kings Sarcoidosis Questionnaire; CLEAR: concomitant levofloxacin, ethambutol, azithromycin, and rifampin: levofloxacin, 500 mg orally, daily+ethambutol 15 mg·kg−1 orally, daily+azithromycin 250 mg orally, daily+rifampin 10 mg·kg−1 orally, daily or rifabutin, 300 mg orally, daily; d-MPH: dexmethylphenidate; FACIT-F: Functional Assessment of Chronic Illness Therapy Fatigue.