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Eculizumab frequently used for off-label indications, researchers suggest
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Eculizumab, which is only approved by the FDA for the treatment of three rare conditions, may be used frequently for off-label indications that lack strong scientific evidence, according to a study published in JAMA Internal Medicine.
“It isn’t just that the use is off-label,” Vinay Prasad, MD, MPH, hematologist-oncologist and associate professor of medicine at Oregon Health and Science University, told Healio Primary Care. “It is off-label and the evidence base is weak. The combination means costly, toxic drugs are used and we don’t know if people are better off.”
Eculizumab (Soliris, Alexion) is currently approved by the FDA for paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome and refractory generalized myasthenia gravis.
According to the Securities and Exchange Commission, revenue from the drug skyrocketed from $66 million in 2007 to more than $3.5 billion in 2018. The researchers said they were concerned that the increase in revenue was related to its off-label use for non-FDA approved indications that may not have strong supporting evidence.
To evaluate the level of evidence for FDA approved on-label and off-label indications for eculizumab, Prasad and Myung S. Kim, MD, also of Oregon Health and Science University, searched ClinicalTrials.gov for registered trials using eculizumab and searched Google Scholar and PubMed for published trials.
A total of 372 publications were identified, including 22 clinical trials and 39 observational studies. Case series and reports comprised 84% of the published studies, and most published clinical trials included less than 50 patients (77%).
The publications included studies for 39 distinct indications for eculizumab. Indications included nonmalignant and malignant hematologic disorders, autoimmune disorders, transplant-related indications and renal disorders.
Of the three FDA approved indications, only two — paroxysmal nocturnal hemoglobinuria and myasthenia gravis — had confirmatory trials available.
Randomized clinical trials were not reported for 27 of the indications, meaning published literature consisted solely of observational studies, case series and case reports for those indications.
Previous research showed that that off-label drug use, particularly without strong scientific evidence, was associated with adverse drug events.
“When a new drug comes to market, don’t be surprised to soon read case reports for it to be used for other purposes,” Prasad said. “You have to be very cautious reading these reports and hold these drugs to the standards of evidence-based medicine.”– by Erin Michael
Disclosures: Prasad reported receiving research funding and that his work is funded by the Laura and John Arnold Foundation; royalties from his book Ending Medical Reversal; receiving honoraria for Grand Rounds/lectures from several universities, medical centers, and professional societies and payments for contributions to Medscape. Prasad also hosts the podcast Plenary Session, which has Patreon backers.