The FDA’s Joint Advisory Committee on Tuesday announced a review of the Risk Evaluation and Mitigation Strategies (REMS) program designed around the risk of severe neutropenia associated with clozapine, a drug used to treat schizophrenia and schizoaffective disorder. The abolition was approved by an overwhelming majority.
All but one of the 15 voting committee members agreed that the current requirements for documentation of absolute neutrophil count (ANC) results for prescribers and verification of results by pharmacies are insufficient to ensure that atypical antipsychotics are safe. He said it was not necessary to ensure its use.
Similarly, in a 14-1 vote, Pharmaceutical Safety and Risk Management Advisory Committee and Psychiatric Drugs Advisory Committee It stated that there is no need for education requirements for health care professionals regarding the neutropenic risks of clozapine.
“I very passionately voted against it because I have dreamed of eliminating clozapine REMS for years,” said panelist Jacob Barron, MD, MPH, of Stanford University in California.
“We do not believe that the documented and enforced REMS approach is serving patient health, community needs, and provider well-being,” said Sasha Dublin, M.D., of Kaiser Permanente Washington Health. he added. Institute in Seattle. “I hope we can find a better way to support proper oversight that doesn’t have the kind of punitive, technocratic approach that becomes a burden.”
A small percentage of patients taking clozapine develop severe neutropenia, which is associated with an increased risk of serious and fatal infections.
The current REMS program requires patients to have weekly blood draws during the first 6 months of treatment, biweekly blood draws through the 12th month, and monthly blood draws thereafter. Prescribers must document the patient’s ANC via fax or web-based REMS system, which authorizes REMS-registered pharmacies to dispense clozapine.
But the program has been plagued by technical problems and human error, creating barriers to accessing the only approved drug for treatment-resistant schizophrenia.
As the only panelist to vote in favor of REMS, Walter Dunn, MD, of the University of California, Los Angeles, called for a “more streamlined” option that would eliminate the ANC’s documentation requirements, but with a role for formal organizations. said. Blood tests should be performed within 18 weeks of treatment when the risk of neutropenia is highest.
Some panel members noted that REMS places an undue burden on health care providers and discourages prescribing clozapine. Panelists also noted that REMS places a significant burden on patients, likely disproportionately impacting the most vulnerable populations who do not have easy access to weekly testing.
Dr. Gopal Vyas of the University of Maryland School of Medicine in Baltimore changes his vote after an emotional hearing in which advocates described how patients struggled to fill prescriptions for REMS. He said he did. Speakers recounted difficult stories of treatment interruptions that led some patients to suicide attempts, institutionalization, and incarceration.
Dr. Vyas said he “would have said yes” to ANC monitoring at 18 weeks, but added that it was more important to reduce “any barriers” to clozapine. “The only way to do it is to… eliminate [the REMS]. ”
The panelists also said that healthcare providers are well-equipped and have a personal responsibility as clinicians to educate them about important medications, and that this education does not need to be part of a regulated program. . Some proposed providers may have avoided participating in REMS for fear of liability.
“I trust physicians to take care of their patients, and they have the ability to do that outside of the REMS program,” said John Hartig, Ph.D., Pharm.D., of Butler University’s College of Pharmacy and Health Sciences in Indianapolis. He has the skills,” he said. .
Megan Ehret, Pharm.D., Ph.D., of the University of Maryland School of Pharmacy in Baltimore, said in a study presented during the conference that no studies were convincing that knowledge learned through REMS can prevent severe neutropenia. “Health care providers are not learning about the risks and benefits of clozapine from the REMS themselves. They know this before undergoing the evaluation,” she said.
The general consensus among the panelists was that prescribing clinicians have everything they need to know. clozapine label.
FDA does not have to follow the advisory committee’s recommendations, but it usually does.
