Background/Purpose: Patients with sarcoidosis refractory to standard treatment are a therapeutic challenge and are often managed by a variety of specialists due to the heterogeneity of disease manifestations. Treatment options for symptomatic sarcoidosis have improved in recent years and we are now using tumor necrosis factor (TNF) inhibitors for moderate or severe disease. Currently treatment response in pulmonary sarcoidosis is assessed via pulmonary function, chest imaging, and quality of life measures. Our objective was to evaluate the safety and efficacy of TNF inhibitors in multi-system sarcoidosis.

Methods: A systematic English literature review and meta-analysis using PubMed was performed on published studies and case series. Search strategy involved screening for articles between 1996 and 2017 which reported use of TNF inhibitors (etanercept (ETN), adalimumab (ADA), infliximab (INF), golimumab or certolizumab) for the treatment of biopsy proven sarcoidosis. We selected studies that directly assessed the effects of TNF inhibitors on treatment outcomes in systemic sarcoidosis. We excluded case reports, sarcoidosis that developed while on a TNFi, and disease limited to cutaneous involvement. Data regarding disease phenotype, past therapies, treatment outcomes, and adverse events were extracted by two reviewers and is undergoing assessment to be pooled in a meta-analysis.

Results: There were 470 abstracts identified. Selection was made of 102 original articles using TNF inhibitors in sarcoidosis. Fourteen studies were evaluated: five comparative trials and nine observational. The most robust studies were comparative trials in patients with pulmonary sarcoidosis. 450 cases of biopsy proven sarcoidosis underwent treatment with TNF inhibitors. Variation in objective results (including pulmonary function tests) was seen. Adverse events leading to discontinuation were infrequent. Observational studies assessed patients with more wide ranging phenotypes including cutaneous, ocular, central nervous system (CNS), cardiac, pulmonary, liver, and musculoskeletal manifestations. Clear benefit with INF in neurosarcoidosis (when used with mycophenolate) and in multi-system sarcoidosis was seen. Both INF and ADA led to improved outcomes in uveitis. In one open label study, INF led to improvement in FDG PET in a majority of patients and improvement in FVC by 6.6%. ADA improved or stabilized FVC in all patients with severe, symptomatic pulmonary sarcoid and led to improved 6MWT, Borg dyspnea score, and both patient and physician global assessment. An open label study with ETN for stage II and III pulmonary sarcoid was terminated early due to frequency of treatment failure. Case series support use in a wide range of extra-pulmonary organ systems, most notably neurosarcoidosis.

Conclusion: Current results from randomized and open label studies appear to support use of monoclonal antibody TNF inhibitors, for use in extra-pulmonary sarcoid disease, with particularly compelling evidence for use in uveitis and neurosarcoidosis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/tumor-necrosis-factor-inhibitors-for-sarcoidosis/