Corticotropin

ACTH stimulates the adrenal cortex to release cortisol, corticosterone, aldosterone and weak androgens, so much of its effect resembles a surge of the body's own steroid hormones¹. Long, high exposure enlarges the adrenal cortex and keeps cortisol output high. Normally the hypothalamus and pituitary regulate ACTH release, and rising cortisol switches it off¹. The labels warn that after prolonged treatment the body's own adrenal axis can stay suppressed for a time once the drug is stopped^1,2. The Acthar label adds that the product is also reported to bind melanocortin receptors, and states that how it works in infantile spasms is unknown¹.

In people, the clearest data are in infantile spasms. A small randomized, single-blinded trial in 29 infants found that a short high-dose ACTH course stopped spasms and cleared the characteristic EEG pattern in 13 of 15 infants, versus 4 of 14 given prednisone³.

A 2022 scoping review of 41 human studies (2,235 participants) behind the FDA-listed uses found the strongest evidence for infantile spasms and multiple sclerosis relapses, yet most randomized trials showed ACTH was no better than ordinary corticosteroids for either; in infantile spasms, only one small randomized trial found it superior⁴. Trials in rheumatoid arthritis, lupus, nephrotic syndrome and other conditions were generally small and did not consistently beat placebo⁴. The reviewers note that its 1952 approval predated modern FDA evidence standards⁴.

FDA-approved since 1952 as Acthar Gel, for infantile spasms in children under two, multiple sclerosis relapses in adults, and a list of rheumatic, collagen, skin, allergic, eye, respiratory and edematous conditions¹. Purified Cortrophin Gel, a separate product first approved in 1954, is labeled for a similar list of inflammatory conditions, including MS relapses, but not infantile spasms².

The labels warn of steroid-type effects: higher infection risk, raised blood pressure, salt and water retention, low potassium, raised blood sugar, stomach ulcers and bleeding, mood changes up to depression or psychosis, cataracts, glaucoma and Cushing-like changes. Stopping after long use can leave the adrenal axis suppressed. Allergic reactions, including anaphylaxis, have been reported. It must never be given into a vein. In infants treated for spasms, infections, convulsions, high blood pressure, irritability and fever were most common^1,2.

1. FDA label: Acthar GelFDA
2. FDA label: Purified Cortrophin GelFDA
3. Baram et al., Pediatrics 1996PubMed
4. Tran et al., JAMA Intern Med 2022PubMed