Acthar Gel (repository corticotropin injection) is approved by the U.S. Food and Drug Administration for the treatment of multiple conditions, including pulmonary sarcoidosis.

Although the medicine’s approval dates back to 1952, clinical experience with Acthar Gel is very limited because of high costs and an inconvenient delivery method; the therapy is administered by injection under the skin or into the muscle tissue.

Acthar Gel recently re-emerged as an alternative to prednisone, a corticosteroid hormone, as a first-line treatment for sarcoidosis because many patients either do not tolerate or do not respond to prednisone treatment.

How Acthar Gel works

Acthar Gel’s exact mechanism of action is unknown. The active ingredient of Acthar Gel is adrenocorticotropic hormone (ACTH), a peptide, or small protein, that binds to melanocortin receptors (MCRs). There are five different MCRs, found in many different cell types throughout the body, and ACTH can bind to all of them. MCRs are also present on immune cells. When ACTH binds to an MCR on an immune cell, this initiates a signaling cascade that leads to NF-ĸB inhibition. NF-ĸB is a protein that plays an essential role in inflammatory processes. Inhibiting this protein has an anti-inflammatory effect and suppresses the proliferation of inflammatory cells.

ACTH can also bind to MCRs on adrenal cortical cells found in the adrenal glands above the kidneys. The binding of ACTH to MCRs on adrenal cells stimulates the production of the cortisol hormone. Because cortisol is a corticosteroid, which are used to treat sarcoidosis, ACTH’s benefit in sarcoidosis patients might be partly explained by its ability to increase the production of corticosteroids.

Acthar in clinical trials

The FDA approval of Acthar Gel for pulmonary sarcoidosis is based on a limited number of case reports. Therefore, information regarding the dosage, toxicity, and effectiveness of the treatment is very limited.

A randomized, double-blind Phase 4 clinical trial (NCT02188017) in chronic pulmonary sarcoidosis patients who had previously received prednisone treatment assessed whether Acthar Gel allowed for a lower prednisone dose. The study compared two different doses of Acthar Gel, 40 and 80 units, twice a week. A total of 16 patients completed the 24-week study.

The dose of prednisone was decreased by half if the patient’s condition was stable or improved. Acthar Gel led to a significant reduction in the prednisone dose required within seven weeks of treatment and persisted until the end of the study. Diffusing capacity of the lungs for carbon monoxide (DLCO), which is part of a lung function test, and general health status of the patients improved significantly during the study despite the withdrawal of prednisone. There was no significant difference in therapy response between the two treatment groups.

A retrospective study (NCT02356445) included 47 sarcoidosis patients who were taking corticosteroids or had taken them in the past. Each patient received at least one dose of Acthar, and 29 of the 47 patients received it for at least three months.

In 11 patients, the condition of the affected organ improved. Eight of these 11 patients were able to lower their corticosteroid dose by at least 50 percent. Sixteen patients were stable, and the condition of the affected organ remained unchanged. Two patients had a relapse, and the affected organ became worse.

A multicenter, randomized, double-blind Phase 4 clinical trial (NCT03320070) recently started recruiting pulmonary sarcoidosis patients who are receiving prednisone treatment to assess the effectiveness and safety of Acthar Gel. Patients will receive either 80 units of Acthar Gel or a placebo twice a week for 24 weeks. The study is recruiting participants in 10 U.S. states.

Two other clinical trials aim to assess the effect of Acthar Gel in patients with sarcoidosis affecting the central nervous system. One trial (NCT02298491) is currently recruiting participants in Maryland, and results are expected in December 2018. The second trial (NCT02920710) will start in June 2018 and is not yet recruiting. It is expected to end in December 2019.

Additional information

Acthar Gel’s side effects are similar to corticosteroids, the most common being high blood sugar, high blood pressure, behavior and mood changes, and changes in appetite and weight.

Because Acthar Gel suppresses the immune system, its use increases the risk of infections.


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