What Is Corticotrophin (ACTH)?

Corticotrophin, also called adrenocorticotropic hormone (ACTH), is an FDA-approved treatment for numerous conditions, including ankylosing spondylitis (AS), gout, psoriatic arthritis (PsA), and rheumatoid arthritis (RA). What's more, it's been on the market since the 1950s. So why haven't you heard of it?

The answer is complicated, but it largely boils down to cost and access. ACTH is more expensive than a simple steroid treatment, and it's obtained from a specialty pharmacy — a trustworthy resource that can help patients navigate health insurance, side effects, dosing and administration, and home delivery of the drug.

ACTH is used in lieu of corticosteroids (like prednisone or prednisolone) to control rheumatic and autoimmune disease flares; and like corticosteroids, it doesn't slow the progression of the disease. This is the job of the biologic or biosimilar.

ACTH is typically reserved to treat severe disease that isn't responding to numerous other therapies, or for patients who are intolerant to steroids. One key benefit: It's effective at a much lower dose than steroids, reducing the risk of possible side effects.

What Is ACTH (corticotrophin)?

ACTH is a hormone that's naturally produced by the pituitary gland. It travels to the adrenal glands where it prompts the secretion of cortisol, a stress hormone.

ACTH is sold under two brand names; no generic version is available. One is Acthar Gel, which is made by Mallinckrodt Pharmaceuticals and has been on the market since the 1950s. The other is Cortrophin Gel which was first approved by the FDA in 1954 but stopped being produced in the 1980s. Cortrophin was reintroduced to the market in 2021, about five years after ANI Pharmaceuticals acquired it from the previous manufacturer (Merck).

ANI Pharmaceutical's list price for Cortrophin Gel is about half that of Mallincrtodt's — $3,500 vs. $7,000 — yet most patients don't pay the list price for a drug. Instead, the patient pays a fraction of the cost of the drug through their employer-provided insurance, Medicare, Medicaid, or Tricare/Veteran's Administration. This can include copays, copay cards, deductibles, and the insurance premium itself. The fact that Cortrophin Gel has a 50 percent lower list price may induce some insurers to add it to the list of drugs they offer.

How taking ACTH helps people with autoimmune conditions isn't fully understood, but it is believed to stimulate the body to secrete more steroids, including cortisol. It also binds to melanocortin receptors, says Frederick T. Murphy, DO, a board-certified rheumatologist who is affiliated with several Pennsylvania-area hospitals. (These receptors are part of an ancient modeling system that is involved in dampening inflammation.) ACTH also decreases levels of interleukin-1 (IL-1), an inflammatory protein that plays a major role in gout, Dr. Murphy adds.

How Well Does It Work?

As with corticosteroids like prednisone, ACTH isn't designed to be a routine treatment for a chronic condition. But when used to combat rheumatic disease flares, especially gout, "it's a very effective therapy," says Dr. Murphy. The problem: "A lot of drug formularies won't approve it."  (A formulary is a list of drugs insurers prefer because they are more profitable.)

Research suggests that ACTH typically works just as well as steroids like prednisone, at least for certain conditions. A 2019 research review of this drug's use in gout found that it was "fast-acting, typically relieving the painful symptoms of acute gout within 24 [hours] of treatment. Furthermore, the average number of days needed to achieve 100 percent resolution of gout symptoms in patients treated with [ACTH] was similar to those of the corticosteroid triamcinolone."

Corticosteroids and ACTH have the potential to cause the same side effects, including stomach upset, mood swings, high blood sugar, high cholesterol, and osteoporosis. The risk of severe side effects increases along with the dose, which is why doctors aim to keep patients on the lowest effective dose for the shortest period of time necessary.

Anecdotally speaking, however, Dr. Murphy says that ACTH tends to cause fewer side effects, mostly because patients who are having a flare (perhaps related to lupus or gout), can usually get off the drug very quickly.

Additionally, he adds that patients who are flaring and given prednisone often require 20 mg to 40 mg of prednisone (or the equivalent) per day — and the risk of serious side effects goes up when you exceed 10mg.

With ACTH, flares can often be successfully treated with a dose that raises cortisol levels in the body in a way that's equivalent to taking 10 mg or less per day of prednisone.

Who Might Benefit from It?

ACTH may be used treat a variety of conditions, including AS, gout, lupus, multiple sclerosis, PsA, and RA.

As with steroids, it's not usually a routine medication but rather one that might be used to dampen a flare. ACTH is not a disease-modifying drug, which means it won't actually slow the progression of a disease such as RA.

Roy Fleischmann, MD, Clinical Professor of Medicine at the University of Texas Southwestern Medical Center, who has been involved in several studies regarding the use of ACTH in RA, told us he wouldn't necessarily use this drug for inflammatory arthritis flares. However, it might be appropriate for inflammatory arthritis patients whose disease activity remains high despite taking multiple medications, including prednisone, he said.

Dr. Murphy sometimes uses ACTH in patients who have lupus, sarcoidosis, or gout — "in people who have refractory, tophaceous gout," notes Dr. Murphy. Refractory gout means that it hasn't been controlled by other medications, including colchicine and pegloticase (Krystexxa). Tophaceous gout is the most severe form of the disease; it's characterized by the presence of numerous urate crystals (tophi) that look like bumps or nodules under the skin. "I'd love to use it for gout flare ups as well," not just the most severe, refractory cases, he adds. "But prednisone is so much less expensive."

How Much Does ACTH Cost?

Pricing varies, but Dr. Murphy estimates that Acthar costs about $7,000 per treatment and that Cortrophin costs about half ($3,500). The corticosteroid prednisone, in contract, costs around $10 for 7 tablets, according to drugs.com. But, as noted above, patients do not ordinarily pay the list price for a drug. It can cost very little or, in some case, nothing, depending on insurance coverage

Despite the low cost, not everyone who's flaring responds to corticosteroids. "Patients who are refractory or intolerant to corticosteroids have an especially urgent need for effective alternatives and are at risk of going organ damage with long-term disease," Mary Pao Seideman, MD, PhD, Chief Medical Officer of ANI Pharmaceuticals, said in a release.

Both Mallinckrodt (makers of Acthar) and ANI (makers of Cortrophin) offer patient assistance programs to make corticotrophin more accessible to patients. Some patients may even be able to access one of these drugs at low or no cost, despite the high sticker price.

The bottom line: The more you know about the available treatments, the more equipped you'll be to participate in shared decision making with your provider. Talk to your doctor about choosing the best medication for you — including what will work best with your medical history, symptoms, treatment goals, overall health, and budget.

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This article was made possible with support from ANI Pharmaceuticals.

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