TABLE 2.
Summary of data from included studies
| First author [ref.] | Study design | Patients (n) and characteristics | Intervention | Other systemic therapy | Primary outcomes | Secondary outcomes |
| Anti-TNF-α and anti-IL-12 and -23 therapy | ||||||
| Utz [11] | Open label | Pulmonary sarcoidosis with progressive infiltrates or worsening pulmonary function (n=17) | Etanercept 25 mg s.c.; twice weekly for 12 months | No immunosuppressive therapy in the past 3 months | Pulmonary function, chest radiograph, dyspnoea | HRoQL (SF-36) |
| Baughman [12, 13] | RCT | Chronic 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 label | Sarcoidosis with refractory chronic uveitis, non-responsive to prednisone and methotrexate (n=26) | Adalimumab 40 mg s.c.; weekly for a minimum of 6 months | Prior to study 100% of patients treated with oral prednisone 20–60 mg with methotrexate added if required Background medication was tapered during study |
Uveitis manifestations | Chest radiograph, pulmonary function, fatigue (FAS) |
| Milman [15] | Open label | Intrathoracic (90%) and extrathoracic (40%) sarcoidosis non-responsive to systemic immunosuppressants; FDG-PET uptake (n=10) | Adalimumab 40 mg s.c.; bi-weekly for 24 weeks | Prednisolone 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 phase | Chronic 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 dose | Assessment cutaneous lesions | HRQoL (SHQ), pulmonary function, chest radiograph |
| Judson [17] | RCT | Chronic 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 study | Pulmonary function (FVC) | HRQoL (SGRQ, SF-36, SAT), fatigue (FAS) |
| Vorselaars [18] | Open label | Active, 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 function | HRQoL (SF-36, PGA) |
| Corticosteroids and corticotropin | ||||||
| Aggarwal [19] | Open label | Newly 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 months | No previous treatment | Fatigue (FAS) | HRQoL (SHQ) |
| Baughman [20] | RCT | Chronic 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 study | Prednisone sparing | Pulmonary function, chest radiograph, HRQoL (KSQ, SGRQ), fatigue (FAS) |
| Other immunosuppressive and/or immunomodulating therapies | ||||||
| Judson [21] | Open label | Steroid 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 study | Pulmonary function, HRQoL (SF-36) | – |
| Heij [22] | RCT | Sarcoidosis with small fibre neuropathy; 86% pulmonary involvement (n=22) | ARA 290 2 mg i.v.; three times weekly during 4 weeks. Placebo | Oral 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 label | Chronic pulmonary sarcoidosis, FVC 45–80% (n=15) | Broad-spectrum antimycobacterial therapy (CLEAR regimen) for 8 weeks | 47% 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; crossover | Pulmonary 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; crossover | Pulmonary sarcoidosis with persistent fatigue despite stable systemic treatment (n=15) | Armodafinil 150 to 250 mg orally; daily during 2×8 weeks. Placebo | 100% 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.