CNS Sarcoidosis and Acthar Gel

Sarcoidosis is a chronic and frequently progressive systemic disease that affects the central
nervous system (CNS) in approximately 5% of patients. The hallmark of the disease is the
development of chronic inflammation with formation of non-caseating granulomas that can
involve the brain parenchyma and meninges and appear as contrast-enhancing mass lesions on
magnetic resonance imaging. The granulomas are primarily comprised of proinflammatory T cells
(Th1 cells and Th17 cells) and macrophages which accumulate during the early stages of
granuloma formation. The inflammation that is generated by these cells is modulated by
anti-inflammatory responses mediated by Th2 cells and regulatory T (Treg) cells that later
appear and populate the outer regions of the granuloma. The presence of Treg cells are of
particular interest since these cell are also detected in high numbers in peripheral blood
and the immune suppression that results may underlie the occurrence of anergy in patients
with the disease. The treatment of CNS sarcoidosis involves the use of either corticosteroids
or potent immunosuppressive agents, both which can induce severe long-term side effects. The
adverse effects of steroids may be avoided by treatment with adrenocorticotropic hormone
(ACTH), which is available for patient use as H.P. Acthar® Gel. The efficacy of H.P. Acthar®
Gel in the treatment of CNS sarcoidosis and the impact on quality of life have not been
previously examined. In addition, little is known regarding the expression of immune markers
in CNS sarcoidosis and the association of such markers with disease activity and response to
treatment. These issues, therefore, will be explored in the context of this proposal.

Inclusion Criteria:

- A highly probable diagnosis of sarcoidosis, as determined using the World Association
for Sarcoidosis and Other Granulomatous Disorders (WASOG) Sarcoidosis Organ Assessment
Instrument (Judson et al., 2014), with involvement not limited to the central nervous
system.

- At the time of enrollment, a history of clinical deterioration based on the
development of new symptoms or worsening previously present symptoms with confirmation
by clinical examination and objective clinical testing.

- If on steroids, on a stable dose of the medication for at least 3 months.

Exclusion Criteria: