Open Label Study of Acthar SQ Gel Injection in Patients With Active Anterior Uveitis
Status:
Terminated
Trial end date:
2017-01-06
Target enrollment:
Participant gender:
Summary
Uveitis is an acute or chronic inflammatory condition of unknown etiology. Although uveitis
often responds adequately to topical corticosteroids, there are many patients for which this
treatment is either inadequate or not tolerated. A patient with inadequate response to
treatment would manifest uveitis activity by slit lamp examination determination of anterior
chamber cellularity. Lack of tolerance of therapy commonly manifests as ocular hypertension
(greater than 21 mmHg measured by tonometry)complicating chronic topical corticosteroid
administration, leading to glaucoma and permanent visual loss. Moreover, systemic
corticosteroids may be required at a dose unsafe for chronic administration. In these
situations, an immunosuppressive medication is often added as a "steroid-sparing" agent. If
and when there is clinical response to the added immunosuppressive, the oral and/or topical
corticosteroid dose can be reduced or eliminated to avoid toxicity.
There are several reasons for believing that Acthar might be beneficial in the treatment of
uveitis patients. In addition to increasing adrenal production or cortisol, Acthar has
another important mechanisms of action mediated by its binding of melanocortin receptors.
Melanocortin down-regulates activity of B and T lymphocytes, monocytes and macrophages. In
animal studies, melanocortin peptides down-regulate T helper cells, up-regulate T Regulatory
cells, and decrease B lymphocyte production of B Lymphocyte Stimulator. In macrophages, there
is down-regulation of IL-1, IL-2, INF gamma, TNF alpha, nitric oxide and adhesion molecules.
In other cells, in addition to IL-10 upregulation (monocytes), there is down-regulation of
VACM and ECAM (endothelial cells), prostaglandins (fibroblasts) and MCP-1 and RANTES (renal
tubules).CNS mediation of systemic inflammation may also be down-regulated by melanocortin
receptor binding by Acthar.