Little Evidence Acthar Gel Better Than Cheaper Substitutes: Review

There is minimal evidence that the expensive anti-inflammatory medication Acthar Gel (repository corticotropin injection) is more effective than inexpensive corticosteroids for the treatment of multiple sclerosis (MS) and other diseases, according to a new review paper.

“We found no evidence where it was a conclusive slam dunk that this drug was superior to very cheap corticosteroids,” Daniel Hartung, a professor at Oregon Health and Science University and Oregon State University and co-author of the paper said in a press release.

Whereas a single course of Acthar Gel commonly costs $100,000 or more, a similar course of corticosteroids often costs less than $100.

Based on the finding, Hartung and colleagues are advising that publicly funded insurance programs like Medicare — the U.S. program that mainly insures Americans ages 65 and older — should not cover treatment with Acthar Gel unless more studies are done on its efficacy.

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“In the absence of evidence from head-to-head (randomized controlled trials) comparing [Acthar] to synthetic corticosteroids, continued use of [Acthar Gel] should be discouraged by professional societies and not covered by payers such as Medicare,” the team concluded.

They said that the widespread use of this expensive medication and its continual coverage by payers like Medicare “is emblematic of dysfunction in the pharmaceutical market.”

The paper, “Characterization of the Clinical Evidence Supporting Repository Corticotropin Injection for FDA-Approved Indications: A Scoping Review,” was published in JAMA Internal Medicine.

Acthar Gel is a decades-old medication initially developed in the 1940s and has been marketed by Mallinckrodt Pharmaceuticals since 2014.

In the U.S., Acthar Gel first received regulatory approval in 1952, which was years before modern standards for drug approval by the U.S. Food and Drug Administration (FDA) were implemented. Since then, that approval has been expanded several times, including an indication to treat MS in 1979.

In the last decade or two, public spending on Acthar Gel has ballooned: “Between 2011 and 2019, annual spending on [Acthar Gel] in the US Medicare program increased nearly 15-fold, from $49.5 million to $724.6 million, making it one of the most expensive medications in the program,” the researchers wrote. They added that nearly two-thirds of the total revenue made on Acthar Gel comes from Medicare.

“This is an excessively priced drug that has been aggressively marketed in recent years for a variety of indications,” Hartung said.

This increase in costs has led to renewed interest in the medicine’s effectiveness. Here, a team of scientists conducted a wide-sweeping review of the scientific literature to better understand Acthar Gel’s efficacy in different conditions. The review included 41 studies in total, including 10 studies where the medicine was used to manage MS relapses.

The team noted that many of the studies were small — most MS studies included only a few dozen participants — and often study design limited the ability to draw firm conclusions. For example, in nearly half of the studies, there was no placebo or other treatment arm against which to compare Acthar Gel.

“Despite corticotropin being available for nearly 70 years, the clinical evidence supporting the use of corticotropin for most FDA-approved indications was limited by low-quality study designs with modest enrollment,” the researchers wrote.

For the data that was available, several studies showed that treatment with Acthar Gel was generally superior to placebo at relieving symptoms of MS and other conditions. However, other studies found little or no difference in efficacy between Acthar Gel and synthetic corticosteroids, a type of anti-inflammatory medicine that is inexpensive and widely available.

Corticosteroids work by mimicking the activity of one of the body’s hormones, called cortisol. Notably, Acthar Gel is thought to work by increasing levels of cortisol in the body.

“Although several RCTs [randomized controlled trials] provided evidence that corticotropin was effective for treating exacerbations of MS and infantile spasms, the evidence did not consistently find that corticotropin performed substantially better than synthetic steroid medications,” the team concluded.

“We found that the evidence base is very weak at best and definitely doesn’t justify the hundreds of millions of dollars that are spent annually on it by public payers, specifically the Medicare program,” Hartung said.

Hartung added that Acthar Gel, as an example of an approved medicine with fairly small benefits and high costs, “embodies many of the worst parts of our health care system.”