Few randomized clinical trials support corticotropin injection for most indications
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Few randomized clinical trials support using repository corticotropin injection for most FDA-approved indications, including rheumatoid arthritis, ankylosing spondylitis, lupus, optic neuritis and nephrotic syndrome, according to researchers.
Data published in JAMA Internal Medicine also found that most randomized clinical trials reported that corticotropin (H. P. Acthar Gel, Mallinckrodt Pharmaceuticals) was non-superior to lower-cost corticosteroids for multiple sclerosis and infantile spasms.
“The basic issue here is that repository corticotropin is a very old and very expensive medication that public payers — Medicare and Medicaid — spend hundreds of millions of dollars annually on,” Daniel M. Hartung, PharmD, MPH, of Oregon Health & Science University, in Portland, told Healio Rheumatology. “It was approved for a wide variety of inflammatory conditions prior to modernization of U.S. FDA approval standards.”
According to Hartung and colleagues, Questcor Pharmaceuticals acquired the rights to corticotropin in 2001 and subsequently “pursued an aggressive commercial expansion of the product.”
“A centerpiece of this strategy was an unprecedented price increase, from $36 per vial in 2001 to $23,269 per vial in 2007,” they wrote.
Questcor Pharmaceuticals later acquired an orphan drug indication for infantile spasms in 2010, and greatly expanded the use of corticotropin across its neurological, rheumatologic, and nephrological indications, according to the researchers. The company was acquired by Mallinckrodt Pharmaceuticals in 2014.
“Between 2011 and 2019, annual spending on corticotropin in the U.S. 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,” they added. “Because of the substantial increase in the price of corticotropin, there has been growing interest in evaluating the comparative evidence related to corticotropin relative to lower-cost corticosteroids. The few attempts to systematically catalog the evidence supporting corticotropin are either outdated, funded by the manufacturer, or of questionable quality.”
To assess the clinical evidence supporting corticotropin use for its various FDA-approved indications, Hartung and colleagues conducting a scoping review of studies published through May 12. The researchers used Ovid MEDLINE, the Cumulative Index of Nursing and Allied Health Literature (CINAHL), and the Cochrane Central Register of Controlled Trials to identify randomized clinical trials, nonrandomized and single-arm clinical trials, and prospective cohort studies that compared corticotropin with an active comparator, placebo, or no treatment. They also reviewed the bibliographies of retrieved studies through ClinicalTrials.gov, FDA documents and the manufacturer’s website.
Among the 1,059 records screened by the researchers, 203 full-text articles were reviewed for eligibility. In all, 41 studies including 2,235 participants met the inclusion criteria. Of these studies, 11 examined infantile spasms, 10 involved multiple sclerosis, 11 assessed rheumatological conditions, seven involved nephrotic syndrome, one studied ocular conditions, and one examined sarcoidosis. A total of 19 studies either included a single arm or exclusively compared varying corticotropin dosing regimens.
According to the researchers, the evidence was most robust for infantile spasms and multiple sclerosis. The largest number of studies comparing corticotropin with an active agent or placebo pertained to multiple sclerosis — four and five records, respectively — with nearly all demonstrating that corticotropin was superior to placebo but no different than corticosteroids.
For infantile spasms, the researchers identified eight controlled studies, among which six were randomized. Just one small randomized clinical trial demonstrated that corticotropin was significantly superior to corticosteroids. Among the 20 studies of patients with other conditions, 12 lacked a control group, five were placebo-controlled, and two exclusively examined different corticotropin dosing strategies.
Placebo-controlled randomized controlled trial of patients with rheumatoid arthritis, ankylosing spondylitis, optic neuritis, systemic lupus erythematosus and nephrotic syndrome were generally small and failed to consistently demonstrate superiority to placebo, the researchers wrote. In addition, blinded randomized clinical trials showed a similar or greater number of adverse effects with corticotropin compared with corticosteroids.
“We found that for most of its indications, the clinical evidence was very weak, comprised mostly of uncontrolled or small placebo-controlled studies,” Hartung said. “For two indications — infantile spasm and treatment of relapse of MS — the evidence base was more credible. However, for these indications, most trials indicated that repository corticotropin was no better than corticosteroids, which are substantially less expensive. The lack of compelling data that supports its use over lower cost corticosteroids calls into question the continued coverage of this medication by public payers such as Medicare.”
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