Results From a Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Repository Corticotropin Injection for the Treatment of Pulmonary Sarcoidosis.

INTRODUCTION: Long-term treatment of pulmonary sarcoidosis with glucocorticoids has been associated with toxicity and other adverse events, highlighting the need for alternative therapies. The goal of this study was to evaluate the efficacy and safety of repository corticotropin injection (RCI, Acthar® Gel) in patients with pulmonary sarcoidosis and to validate endpoints for use in future clinical trials. METHODS: In this multicenter, randomized, placebo-controlled trial, subjects received subcutaneous RCI (80 U) twice weekly or matching placebo through 24 weeks in a double-blind treatment phase, followed by an optional 24-week open-label extension. Efficacy was measured by glucocorticoid tapering, pulmonary function tests, chest imaging, patient-reported outcomes, and a novel sarcoidosis treatment score (STS). Safety was assessed by adverse events, physical examinations, vital signs, clinical laboratory abnormalities, and imaging. The study was terminated early due to low enrollment caused by the COVID-19 pandemic, thereby precluding statistical analysis. RESULTS: Fifty-five subjects were randomized to receive either RCI (n = 27) or placebo (n = 28). Mean STS at week 24 showed greater improvement with RCI (1.4) compared with placebo (0.7). At week 48, those who remained on RCI had an STS of 1.8 compared with 0.9 in those who switched from placebo to RCI. More subjects in the RCI group discontinued glucocorticoids at week 24 compared to the placebo group. Glucocorticoid discontinuation was comparable at week 48 for those who switched from placebo to RCI and those who continued RCI. Similar trends in favor of RCI over placebo were observed with the other efficacy endpoints. No new or unexpected safety signals were identified. CONCLUSIONS: RCI was safe and well tolerated, with trends in efficacy data suggesting greater improvement with RCI compared to placebo in patients receiving standard-of-care therapy for pulmonary sarcoidosis. The study also provided validation of efficacy endpoints that may be used in larger trials for pulmonary sarcoidosis. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03320070.

Pulmonary sarcoidosis is a disease characterized by inflammation of the lungs. Standard treatments include glucocorticoids, which may have harmful side effects. This clinical trial investigated whether repository corticotropin injection (RCI, Acthar^® Gel) was safe and effective in patients who were already taking glucocorticoids to treat pulmonary sarcoidosis. Patients were randomly assigned to be in one of two treatment groups: RCI or placebo. In the first 24 weeks of the study, 27 patients were injected with RCI twice weekly, while 28 patients were injected with an inactive substance (placebo). Forty-seven patients continued into an optional phase of the study for an additional 24 weeks in which all patients received RCI twice weekly. A sarcoidosis treatment score and assessments of lung health, general health, and fatigue were used to determine whether RCI was effective. These assessments showed greater improvements with RCI compared to placebo. Patients who switched from placebo to RCI showed similar improvements to those who remained on RCI throughout the entire study. Patients receiving RCI were able to discontinue their use of glucocorticoids more quickly than those taking placebo, thus helping them to avoid the harmful side effects of the glucocorticoids. Side effects for RCI were mostly mild or moderate, and no new or unexpected safety concerns for RCI were seen throughout the study.

Management of Advanced Pulmonary Sarcoidosis.

The term "advanced sarcoidosis" is used for forms of sarcoidosis with a significant risk of loss of organ function or death. Advanced sarcoidosis often involves the lung and is described as "advanced pulmonary sarcoidosis" (APS), which includes advanced pulmonary fibrosis, associated complications such as bronchiectasis and infections, and pulmonary hypertension. Although APS affects a small proportion of patients with sarcoidosis, it is the leading cause of poor outcomes, including death. Here we review the major patterns of APS with a focus on the current management as well as potential approaches for improved outcomes for this most serious sarcoidosis phenotype.

COVID-19 and Sarcoidosis, Readiness for Vaccination: Challenges and Opportunities.

Sarcoidosis is an immune mediated chronic inflammatory disorder that is best characterized by non-caseating granulomas found in one or more affected organs. The COVID-19 pandemic poses a challenge for clinicians caring for sarcoidosis patients who may be at increased risk of infection compared to the general population. With the recent availability of COVID-19 vaccines, it is expected that clinicians raise questions regarding efficacy and safety in sarcoidosis. However, studies examining safety and efficacy of vaccines in sarcoidosis are lacking. In this review, we examine the current literature regarding vaccination in immunocompromised populations and apply them to sarcoidosis patients. The available literature suggests that vaccines are safe and effective in patients with autoimmune disorders and in those taking immunosuppressive medications. We strongly recommend the administration of COVID-19 vaccines in patients with sarcoidosis. We also present a clinical decision algorithm to provide guidance on vaccination of sarcoidosis patients against COVID-19.

Risk and outcome of COVID-19 infection in sarcoidosis patients: results of a self-reporting questionnaire.

BACKGROUND: It has been suggested that sarcoidosis patients, especially those on immunosuppressive medications, are at increased risk for COVID-19 infection and more severe disease. METHODS: A questionnaire was developed in four languages (English, Dutch, Italian, and Spanish). The questionnaire queried whether patients had been infected with COVID-19 and outcome of the infection. Risk factors for COVID-19 infection were collected. RESULTS: A total of 5200 sarcoidosis patients completed the questionnaire with 116 (2.23%) reporting infection and 18 (15.8%) required hospitalization. Increased hazard ratio (HR) for COVID-19 infection were seen for those with a COVID-19 infected roommate (HR=27.44, p<0.0001), health care provider (HR=2.4, p=0.0001), pulmonary sarcoidosis (HR=2.48, p=0.001), neurosarcoidosis (HR=2.02, p<0.01), or rituximab treatment (HR=5.40, p<0.0001). A higher rate of hospitalization was found for those with underlying heart disease (HR=3.19 (1.297-7.855), p<0.02). No other feature including race, other immunosuppressive agent, age, or underlying condition was associated with a significant increased risk for infection or more severe disease. CONCLUSION: The overall rate of COVID-19 was 2.23%, suggesting an increased rate of COVID-19 infection. However, when an analysis of the questionnaires of sarcoidosis and non-sarcoidosis patients was performed in one localized area over this time period, the rate of COVID-19 infection was similar in both groups. Sarcoidosis patients who cohabitated with COVID-19 infected individuals, worked in health care, had pulmonary or neurologic sarcoidosis, or were treated with rituximab had an increased risk for COVID-19 infection. No significant increased risk for hospitalization could be identified based on age, race, gender or any specific immunosuppressive treatment. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (4): e2020009).