There are multiple benefits and few harms from sharing clinical notes in patients with mental illness, results of a poll of international experts show.

As of April 5, 2021, new federal rules in the United States mandate that all patients are offered online access to their electronic health record. 

“Given that sharing notes in psychiatry is likely to be more complicated than in some other specialties, we were unsure whether experts would consider the practice more harmful than beneficial,” Charlotte Blease, PhD, of Beth Israel Deaconess Medical Center in Boston, told this news organization.

“However, the results of our poll suggest clinicians’ anxieties about sharing mental health notes with patients may be misplaced. We found clear consensus among experts that the benefits of online access to clinical notes could outweigh the risks,” Dr. Blease said in a news release.

The study was published online in PLOS ONE.

Empowering patients

Investigators used an online Delphi poll, an established methodology used to investigate emerging health care policy – including in psychiatry – to solicit the views of an international panel of experts on the mental health effects of sharing clinical notes.

The panel included clinicians, chief medical information officers, patient advocates, and informatics experts with extensive experience and research knowledge about patient access to mental health notes.

There was consensus among the panel that offering online access to mental health notes could enhance patients’ understanding about their diagnosis, care plan, and rationale for treatments.

There was also consensus that access to clinical notes could enhance patient recall about what was communicated and improve mental health patients’ sense of control over their health care.

The panel also agreed that blocking mental health notes could lead to greater harms including increased feelings of stigmatization.

Confirmatory findings

The poll results support an earlier study by Dr. Blease and colleagues that evaluated the experiences of patients in accessing their online clinical notes. 

Among these patients with major depressive disorder, schizophrenia, schizoaffective disorder, or bipolar-related disorder, “access helped to clarify why medications had been prescribed, improved understanding about side effects, and 20% of patients reported doing a better job taking their meds as prescribed,” said Dr. Blease.

However, the expert panel in the Delphi poll predicted that with “open notes” some patients might demand changes to their clinical notes, and that mental health clinicians might be less detailed/accurate in documenting negative aspects of the patient relationship, details about patients’ personalities, or symptoms of paranoia in patients.

“If some patients feel more judged or offended by what they read, this may undermine the therapeutic relationship. We also need more research into the experiences of patients hospitalized for their care,” she added.

“In some clinical cases where there is more focus on emergency care than in forming a therapeutic relationship, for example emergency department visits, we know almost nothing about the risks and benefits associated with OpenNotes,” senior author John Torous, MD, with Beth Israel Deaconess Medical Center and Harvard Medical School, said in an interview.

“One thing is clear,” Dr. Blease said. “Patient access to their online medical records is now mainstream, and we need more clinician education on how to write notes that patients will read, and more guidance among patients on the benefits and risks of accessing their notes.”

Support for this research was provided by a J. F. Keane Scholar Award and a Swedish Research Council on Health, Working Life, and Welfare grant. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

There are multiple benefits and few harms from sharing clinical notes in patients with mental illness, results of a poll of international experts show.

As of April 5, 2021, new federal rules in the United States mandate that all patients are offered online access to their electronic health record. 

“Given that sharing notes in psychiatry is likely to be more complicated than in some other specialties, we were unsure whether experts would consider the practice more harmful than beneficial,” Charlotte Blease, PhD, of Beth Israel Deaconess Medical Center in Boston, told this news organization.

“However, the results of our poll suggest clinicians’ anxieties about sharing mental health notes with patients may be misplaced. We found clear consensus among experts that the benefits of online access to clinical notes could outweigh the risks,” Dr. Blease said in a news release.

The study was published online in PLOS ONE.

Empowering patients

Investigators used an online Delphi poll, an established methodology used to investigate emerging health care policy – including in psychiatry – to solicit the views of an international panel of experts on the mental health effects of sharing clinical notes.

The panel included clinicians, chief medical information officers, patient advocates, and informatics experts with extensive experience and research knowledge about patient access to mental health notes.

There was consensus among the panel that offering online access to mental health notes could enhance patients’ understanding about their diagnosis, care plan, and rationale for treatments.

There was also consensus that access to clinical notes could enhance patient recall about what was communicated and improve mental health patients’ sense of control over their health care.

The panel also agreed that blocking mental health notes could lead to greater harms including increased feelings of stigmatization.

Confirmatory findings

The poll results support an earlier study by Dr. Blease and colleagues that evaluated the experiences of patients in accessing their online clinical notes. 

Among these patients with major depressive disorder, schizophrenia, schizoaffective disorder, or bipolar-related disorder, “access helped to clarify why medications had been prescribed, improved understanding about side effects, and 20% of patients reported doing a better job taking their meds as prescribed,” said Dr. Blease.

However, the expert panel in the Delphi poll predicted that with “open notes” some patients might demand changes to their clinical notes, and that mental health clinicians might be less detailed/accurate in documenting negative aspects of the patient relationship, details about patients’ personalities, or symptoms of paranoia in patients.

“If some patients feel more judged or offended by what they read, this may undermine the therapeutic relationship. We also need more research into the experiences of patients hospitalized for their care,” she added.

“In some clinical cases where there is more focus on emergency care than in forming a therapeutic relationship, for example emergency department visits, we know almost nothing about the risks and benefits associated with OpenNotes,” senior author John Torous, MD, with Beth Israel Deaconess Medical Center and Harvard Medical School, said in an interview.

“One thing is clear,” Dr. Blease said. “Patient access to their online medical records is now mainstream, and we need more clinician education on how to write notes that patients will read, and more guidance among patients on the benefits and risks of accessing their notes.”

Support for this research was provided by a J. F. Keane Scholar Award and a Swedish Research Council on Health, Working Life, and Welfare grant. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

There are multiple benefits and few harms from sharing clinical notes in patients with mental illness, results of a poll of international experts show.

As of April 5, 2021, new federal rules in the United States mandate that all patients are offered online access to their electronic health record. 

“Given that sharing notes in psychiatry is likely to be more complicated than in some other specialties, we were unsure whether experts would consider the practice more harmful than beneficial,” Charlotte Blease, PhD, of Beth Israel Deaconess Medical Center in Boston, told this news organization.

“However, the results of our poll suggest clinicians’ anxieties about sharing mental health notes with patients may be misplaced. We found clear consensus among experts that the benefits of online access to clinical notes could outweigh the risks,” Dr. Blease said in a news release.

The study was published online in PLOS ONE.

Empowering patients

Investigators used an online Delphi poll, an established methodology used to investigate emerging health care policy – including in psychiatry – to solicit the views of an international panel of experts on the mental health effects of sharing clinical notes.

The panel included clinicians, chief medical information officers, patient advocates, and informatics experts with extensive experience and research knowledge about patient access to mental health notes.

There was consensus among the panel that offering online access to mental health notes could enhance patients’ understanding about their diagnosis, care plan, and rationale for treatments.

There was also consensus that access to clinical notes could enhance patient recall about what was communicated and improve mental health patients’ sense of control over their health care.

The panel also agreed that blocking mental health notes could lead to greater harms including increased feelings of stigmatization.

Confirmatory findings

The poll results support an earlier study by Dr. Blease and colleagues that evaluated the experiences of patients in accessing their online clinical notes. 

Among these patients with major depressive disorder, schizophrenia, schizoaffective disorder, or bipolar-related disorder, “access helped to clarify why medications had been prescribed, improved understanding about side effects, and 20% of patients reported doing a better job taking their meds as prescribed,” said Dr. Blease.

However, the expert panel in the Delphi poll predicted that with “open notes” some patients might demand changes to their clinical notes, and that mental health clinicians might be less detailed/accurate in documenting negative aspects of the patient relationship, details about patients’ personalities, or symptoms of paranoia in patients.

“If some patients feel more judged or offended by what they read, this may undermine the therapeutic relationship. We also need more research into the experiences of patients hospitalized for their care,” she added.

“In some clinical cases where there is more focus on emergency care than in forming a therapeutic relationship, for example emergency department visits, we know almost nothing about the risks and benefits associated with OpenNotes,” senior author John Torous, MD, with Beth Israel Deaconess Medical Center and Harvard Medical School, said in an interview.

“One thing is clear,” Dr. Blease said. “Patient access to their online medical records is now mainstream, and we need more clinician education on how to write notes that patients will read, and more guidance among patients on the benefits and risks of accessing their notes.”

Support for this research was provided by a J. F. Keane Scholar Award and a Swedish Research Council on Health, Working Life, and Welfare grant. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Medical transition in transgender patients

I just read the article “Writing letters for transgender patients undergoing medical transition” by Dr. Amy Riese (Pearls, Current Psychiatry, August 2021, p. 51-52). I very much appreciate this topic being brought into the light and her excellent guidelines for patients who suffer from gender dysphoria and require medical transition.

I would like to use her piece as an opportunity to highlight what has become a chasm in psychiatric care. Dr. Riese’s article was on the letter itself and not the assessment of a patient with possible gender dysphoria, but assessment is barely mentioned, and is the single most important part of a gender transition process. Assessment has become the huge chasm in treatment. In my community, both personally and professionally, I have witnessed very little assessment taking place, yet a lot of transitioning is happening.

Concerned and caring family members take their child (or self-present if the patient is an adult) to gender specialists for their expertise. What is happening during these evaluations are brief conversations during which the gender specialist accepts a patient’s (sometimes a minor’s) self-diagnosis of gender dysphoria. There is discussion of the importance of being gender-affirming, and the beginning of a discussion of hormone therapy. During these discussions of hormone therapy, there is very little disclosure of some of the untoward effects. I understand this is a generalization, and there are some gender specialists who are doing excellent, thorough assessments. But this is what I am seeing in my community, to the point that I have no local specialists to whom I feel comfortable sending my patients who may have gender dysphoria.

During discussions, some of the significant medical outcomes of hormone therapy (immunosuppression, loss of bone density, sterility, increased risk of certain types of cancer, etc.) are not mentioned, or are mentioned in passing. Clinicians have begun using euphemisms such as “top surgery” or “upper body surgery,” as used in Dr. Riese’s article, rather than the medically accurate term, which is “bilateral mastectomy.” These behaviors are being manifested by mostly well-meaning clinicians, and start the process of ushering a patient down a one-way street toward a medical transition.

In April of this year, a prestigious institution in my state did a training on aspects of treating transgender and nonbinary youth. The training advocated giving less information to transgender youth regarding the effects of treatment on fertility, arguing that giving adequate information would disrupt the normal course of development. However, we are allowing these same youth to consent for treatment.

This is a very destructive phenomenon, and only time will tell what the psychiatric outcomes will be for patients who medically transition who did not have an adequate assessment. After so much loss under the auspices of treatment, one would hope that at the very least, these children and young adults would be in a better place psychologically, that they would finally be happy and fulfilled in their new reality, that their mental anguish would evaporate, and with it, their risk of suicide. And this may be true if the patient had gender dysphoria.

But what about the patients who did not have an adequate assessment, whose self-diagnosis was accepted without question, the gender-affirming model immediately implemented, and referrals quickly made for medical treatment? For those patients, once everything has been done, every hormone taken, every surgery performed, but still not male enough, not convincingly male in every aspect, now what? Where does one go from there?

Only time will tell what the psychiatric outcomes will be for these patients, who are primarily youth and young adults at this point. What about the psychological pain that brought them to identify as transgender in the first place? Since the patient was colluded with in the diagnosis of gender dysphoria, that pain was never identified and addressed. What will the suicide rate be of these fully transitioned patients who never had gender dysphoria?

And what shall become of the clinicians who treated them without pause or careful consideration, who bypassed informed consent, treating teens as if they had the judgment and psychological maturity of an adult? What will be their defense when the malpractice lawsuits begin to mount against them, when patients and their families emerge on the other side of the medical transition to find that life, identity, intimacy, and the most basic biological functions have been altered forever based on the capricious and suggestible whims of children?

According to the DSM-5, the prevalence of gender dysphoria is very low. Even if we were to double the DSM-5 estimate, it is still very low. As psychiatrists, we are leaders in the mental health field, and need to set the tone and guide nonphysician clinicians toward extremely careful assessment of these patients.

While Dr. Riese gives excellent information about how to write a letter for a patient who needs transition, far fewer of these letters should be written. The upward trend in the numbers of patients receiving a diagnosis, and subsequently letters, is largely imposed by clinicians who disregard the DSM-5 and fail to apply critical thought to this assessments.

Medical transition in transgender patients

I just read the article “Writing letters for transgender patients undergoing medical transition” by Dr. Amy Riese (Pearls, Current Psychiatry, August 2021, p. 51-52). I very much appreciate this topic being brought into the light and her excellent guidelines for patients who suffer from gender dysphoria and require medical transition.

I would like to use her piece as an opportunity to highlight what has become a chasm in psychiatric care. Dr. Riese’s article was on the letter itself and not the assessment of a patient with possible gender dysphoria, but assessment is barely mentioned, and is the single most important part of a gender transition process. Assessment has become the huge chasm in treatment. In my community, both personally and professionally, I have witnessed very little assessment taking place, yet a lot of transitioning is happening.

Concerned and caring family members take their child (or self-present if the patient is an adult) to gender specialists for their expertise. What is happening during these evaluations are brief conversations during which the gender specialist accepts a patient’s (sometimes a minor’s) self-diagnosis of gender dysphoria. There is discussion of the importance of being gender-affirming, and the beginning of a discussion of hormone therapy. During these discussions of hormone therapy, there is very little disclosure of some of the untoward effects. I understand this is a generalization, and there are some gender specialists who are doing excellent, thorough assessments. But this is what I am seeing in my community, to the point that I have no local specialists to whom I feel comfortable sending my patients who may have gender dysphoria.

During discussions, some of the significant medical outcomes of hormone therapy (immunosuppression, loss of bone density, sterility, increased risk of certain types of cancer, etc.) are not mentioned, or are mentioned in passing. Clinicians have begun using euphemisms such as “top surgery” or “upper body surgery,” as used in Dr. Riese’s article, rather than the medically accurate term, which is “bilateral mastectomy.” These behaviors are being manifested by mostly well-meaning clinicians, and start the process of ushering a patient down a one-way street toward a medical transition.

In April of this year, a prestigious institution in my state did a training on aspects of treating transgender and nonbinary youth. The training advocated giving less information to transgender youth regarding the effects of treatment on fertility, arguing that giving adequate information would disrupt the normal course of development. However, we are allowing these same youth to consent for treatment.

This is a very destructive phenomenon, and only time will tell what the psychiatric outcomes will be for patients who medically transition who did not have an adequate assessment. After so much loss under the auspices of treatment, one would hope that at the very least, these children and young adults would be in a better place psychologically, that they would finally be happy and fulfilled in their new reality, that their mental anguish would evaporate, and with it, their risk of suicide. And this may be true if the patient had gender dysphoria.

But what about the patients who did not have an adequate assessment, whose self-diagnosis was accepted without question, the gender-affirming model immediately implemented, and referrals quickly made for medical treatment? For those patients, once everything has been done, every hormone taken, every surgery performed, but still not male enough, not convincingly male in every aspect, now what? Where does one go from there?

Only time will tell what the psychiatric outcomes will be for these patients, who are primarily youth and young adults at this point. What about the psychological pain that brought them to identify as transgender in the first place? Since the patient was colluded with in the diagnosis of gender dysphoria, that pain was never identified and addressed. What will the suicide rate be of these fully transitioned patients who never had gender dysphoria?

And what shall become of the clinicians who treated them without pause or careful consideration, who bypassed informed consent, treating teens as if they had the judgment and psychological maturity of an adult? What will be their defense when the malpractice lawsuits begin to mount against them, when patients and their families emerge on the other side of the medical transition to find that life, identity, intimacy, and the most basic biological functions have been altered forever based on the capricious and suggestible whims of children?

According to the DSM-5, the prevalence of gender dysphoria is very low. Even if we were to double the DSM-5 estimate, it is still very low. As psychiatrists, we are leaders in the mental health field, and need to set the tone and guide nonphysician clinicians toward extremely careful assessment of these patients.

While Dr. Riese gives excellent information about how to write a letter for a patient who needs transition, far fewer of these letters should be written. The upward trend in the numbers of patients receiving a diagnosis, and subsequently letters, is largely imposed by clinicians who disregard the DSM-5 and fail to apply critical thought to this assessments.

Medical transition in transgender patients

I just read the article “Writing letters for transgender patients undergoing medical transition” by Dr. Amy Riese (Pearls, Current Psychiatry, August 2021, p. 51-52). I very much appreciate this topic being brought into the light and her excellent guidelines for patients who suffer from gender dysphoria and require medical transition.

I would like to use her piece as an opportunity to highlight what has become a chasm in psychiatric care. Dr. Riese’s article was on the letter itself and not the assessment of a patient with possible gender dysphoria, but assessment is barely mentioned, and is the single most important part of a gender transition process. Assessment has become the huge chasm in treatment. In my community, both personally and professionally, I have witnessed very little assessment taking place, yet a lot of transitioning is happening.

Concerned and caring family members take their child (or self-present if the patient is an adult) to gender specialists for their expertise. What is happening during these evaluations are brief conversations during which the gender specialist accepts a patient’s (sometimes a minor’s) self-diagnosis of gender dysphoria. There is discussion of the importance of being gender-affirming, and the beginning of a discussion of hormone therapy. During these discussions of hormone therapy, there is very little disclosure of some of the untoward effects. I understand this is a generalization, and there are some gender specialists who are doing excellent, thorough assessments. But this is what I am seeing in my community, to the point that I have no local specialists to whom I feel comfortable sending my patients who may have gender dysphoria.

During discussions, some of the significant medical outcomes of hormone therapy (immunosuppression, loss of bone density, sterility, increased risk of certain types of cancer, etc.) are not mentioned, or are mentioned in passing. Clinicians have begun using euphemisms such as “top surgery” or “upper body surgery,” as used in Dr. Riese’s article, rather than the medically accurate term, which is “bilateral mastectomy.” These behaviors are being manifested by mostly well-meaning clinicians, and start the process of ushering a patient down a one-way street toward a medical transition.

In April of this year, a prestigious institution in my state did a training on aspects of treating transgender and nonbinary youth. The training advocated giving less information to transgender youth regarding the effects of treatment on fertility, arguing that giving adequate information would disrupt the normal course of development. However, we are allowing these same youth to consent for treatment.

This is a very destructive phenomenon, and only time will tell what the psychiatric outcomes will be for patients who medically transition who did not have an adequate assessment. After so much loss under the auspices of treatment, one would hope that at the very least, these children and young adults would be in a better place psychologically, that they would finally be happy and fulfilled in their new reality, that their mental anguish would evaporate, and with it, their risk of suicide. And this may be true if the patient had gender dysphoria.

But what about the patients who did not have an adequate assessment, whose self-diagnosis was accepted without question, the gender-affirming model immediately implemented, and referrals quickly made for medical treatment? For those patients, once everything has been done, every hormone taken, every surgery performed, but still not male enough, not convincingly male in every aspect, now what? Where does one go from there?

Only time will tell what the psychiatric outcomes will be for these patients, who are primarily youth and young adults at this point. What about the psychological pain that brought them to identify as transgender in the first place? Since the patient was colluded with in the diagnosis of gender dysphoria, that pain was never identified and addressed. What will the suicide rate be of these fully transitioned patients who never had gender dysphoria?

And what shall become of the clinicians who treated them without pause or careful consideration, who bypassed informed consent, treating teens as if they had the judgment and psychological maturity of an adult? What will be their defense when the malpractice lawsuits begin to mount against them, when patients and their families emerge on the other side of the medical transition to find that life, identity, intimacy, and the most basic biological functions have been altered forever based on the capricious and suggestible whims of children?

According to the DSM-5, the prevalence of gender dysphoria is very low. Even if we were to double the DSM-5 estimate, it is still very low. As psychiatrists, we are leaders in the mental health field, and need to set the tone and guide nonphysician clinicians toward extremely careful assessment of these patients.

While Dr. Riese gives excellent information about how to write a letter for a patient who needs transition, far fewer of these letters should be written. The upward trend in the numbers of patients receiving a diagnosis, and subsequently letters, is largely imposed by clinicians who disregard the DSM-5 and fail to apply critical thought to this assessments.

A novel investigational allogeneic stem cell–derived treatment resulted in near reversal of type 1 diabetes in a patient who had lived with the condition for about 40 years.

CIPhotos/Getty Images

The patient was the first in Vertex Pharmaceuticals’ phase 1/2 multicenter, single-arm, open-label clinical trial of the insulin-producing islet cell therapy VX-880 for patients with type 1 diabetes who have impaired hypoglycemic awareness and severe hypoglycemia.

The cells are delivered by infusion into the hepatic portal vein. As of now, chronic immunosuppression is required to prevent rejection, but several approaches are being studied to overcome the limitation.

“There’s hope that this is a real advance. It’s been long awaited, and it looks really encouraging,” James Markmann, MD, PhD, the surgeon who performed the procedure, told this news organization.

The use of insulin-producing pancreatic beta cells derived from human pluripotent stem cells, first reported in 2014 by a team at the Harvard Stem Cell Institute, Boston, is seen as a major advance over use of cadaveric donor islet cells because stem cell–derived islets are available in unlimited and uncontaminated supplies.

Cadaveric donor islets are being used in products such as donislecel (CellTrans), which was endorsed by a Food and Drug Administration advisory committee in the summer for the treatment of type 1 diabetes that can’t be managed with current therapies.

The patient in the Vertex trial isn’t the first reported stem cell–derived islet recipient with type 1 diabetes, but these cells are the first to be transplanted into the liver.

“This Vertex patient stood out because the reduction in insulin requirement ... was so striking,” noted Dr. Markmann, chief of the division of transplant surgery at Massachusetts General Hospital, Boston, who has been transplanting islet cells from cadaveric donors into humans via the hepatic portal vein for over 20 years.

“Nobody knew what to expect, as it hadn’t been done before, but certainly the results in this patient are better than what I would have expected from a deceased donor islet transplant,” he added.

Asked to comment, A.M. James Shapiro, MD, agreed. “I think the most important finding is that a stem cell–derived islet is now transplanted into the liver of a patient safely, so far,” he said in an interview.

Dr. Shapiro is clinical director of the living donor and islet cell transplantation programs at the University of Alberta, Edmonton. He pioneered cadaveric donor islet cell transplantation more than 20 years ago with the watershed Edmonton Protocol.

‘Impressive finding ... bodes well for ongoing efforts’

Vertex announced the result by press release. The company plans to transplant another 16 patients, staggering them over time at multiple centers.

The first patient was treated with a single infusion of VX-880 at half the target dose (per protocol for the first two study subjects), along with standard immunosuppressive therapy. At 90 days, the patient’s C-peptide, a measure of endogenous insulin secretion, rose from undetectable to 280 pmol/L fasting and 560 pmol/L post mixed-meal tolerance testing.

Over the same period, the patient’s hemoglobin A1c dropped from 8.6% at baseline to 7.2%. And within 7 days, the individual’s daily exogenous insulin requirement dropped from an average of 34 units to just 2.9 units, a 91% decrease.

The patient had experienced five severe hypoglycemic episodes in the year prior to transplant. They experienced some mild hypoglycemia soon after the procedure while insulin doses were being adjusted, but none thereafter. 

Dr. Shapiro said in an interview: “I was absolutely thrilled to see the first patient results with high C-peptide and a 91% reduction in insulin. That’s a pretty impressive finding for half dosing in the very first patient in a trial. I think it bodes really well for ongoing efforts in this area by Vertex and by others that have similar kinds of cells. It’s very exciting.”

However, he cautioned, “we do need some longer-term data to be sure there’s no off-target growth or other concerns. But based on the purity of this product, that risk is likely to be low.”

And he noted, “I think we still have to address the challenges of setting this process up. A huge amount of work has gone into manufacturing the cell product for a single patient. I think it remains to be seen whether the same technology can be delivered at a larger scale ... i.e., being able to treat hundreds or thousands of patients.”

A blog post on the website of diabetes charity JDRF called the result “outstanding.” “It’s a big deal,” they added. However, they also cautioned: “There are a few things to keep in mind while assessing the data. One is that these are only results from a single person. Data are needed from many more to fully evaluate the potential of this therapy. The second is that this person only received half the target dose of cells.”

Dr. Shapiro is working with another company, ViaCyte, which has also developed stem cell–derived islets. In contrast to the Vertex product, which is fully differentiated and delivered to the liver, ViaCyte’s PEC-Direct product is comprised of stem cell-derived pancreatic islet progenitor cells that are implanted subcutaneously in a pouch, allowing for vascularization.

In a late-breaking poster at the annual scientific sessions of the American Diabetes Association in June 2021, ViaCyte reported on a patient given PEC-Direct. In that patient, stimulated C-peptide increased from 0.1 ng/mL at baseline to 0.8 ng/mL at week 39, and there was a drop in A1c from 7.4% to 6.6%, with no adverse events.

Immunosuppression: Which approach will come closer to cure?

Thus far, the requirement for lifelong immunosuppression has meant that any islet cell replacement approach, including with stem cell–derived islets, has been limited to use in people with type 1 diabetes who have hypoglycemic unawareness or severely unpredictable blood glucose levels.

Two broad approaches are simultaneously being explored to overcome the rejection problem: Encapsulation of the cells to protect them from the immune system, and genetic modification of the cells so that they don’t provoke the immune system in the first place.

In 2022, Vertex plans to file an investigational new drug application for an encapsulated islet cell program with the FDA.

Dr. Markmann believes the genetic modification approach is more promising. “I’m not a believer in encapsulation. I think the foreign body response is hard to overcome. I think the answer will ultimately be genetically modifying the [cell] lines. ... The cell could express something that would potentially turn off the lymphocytes or interfere with the lymphocytes trying to attack them.”

Moreover, he said, “you don’t have to get rid of immunosuppression completely. It’s all [a] risk-benefit [equation]. Even if you could get it down to a single less-toxic [immunosuppressive] agent that would be a huge step.”

Dr. Shapiro commented: “All efforts and eyes are laser-focused on developing cells or approaches that will allow transplantation of this kind of stem cell without any immunosuppression or with low-dose immunosuppression that could be regarded as being exceedingly low risk.”

“Then, and only then, I think we could offer this kind of treatment to children who are just diagnosed with diabetes or to [a bigger proportion of] patients with type 1 or type 2 diabetes. ... The science has to be done in a step-wise fashion,” he added.

Microencapsulation, Dr. Shapiro noted, “is a big challenge because the process of capturing the cells and putting them into a device is really injurious to their survival. ... That may or may not work.”

Dr. Shapiro and his Edmonton team are now embarking on a new trial with ViaCyte and CRISPR Therapeutics using gene-edited cells that contain two knock-in genes and two knock-out genes shown to be less immunogenic and anti-inflammatory in rodent models.

“They look to be promising. We’re going to start a first-in-human trial in the next few months with those cells to see if they really are able to withstand a transplant without the need for immunosuppression. That will be a very exciting trial in itself,” Dr. Shapiro said, noting that they expect to enroll the first patients in the next few months.

However, he cautioned, “first we have to make sure that the gene-edited product continues to function in patients in the way that the original product did, that the cells survive, and that the gene modifications are actually effective. ... Maybe other iterations will be needed.”

“I think, as we move forward, we will ultimately have a gene-edited stem cell–derived product that is immune evasive and will survive. So, I’m ... optimistic that this is not as long term as you might think, and it’s ... happening much more rapidly – at least in first-in-human trials to test safety and preliminary efficacy.”

Dr. Shapiro is a consultant for ViaCyte.

A version of this article first appeared on Medscape.com.

A novel investigational allogeneic stem cell–derived treatment resulted in near reversal of type 1 diabetes in a patient who had lived with the condition for about 40 years.

CIPhotos/Getty Images

The patient was the first in Vertex Pharmaceuticals’ phase 1/2 multicenter, single-arm, open-label clinical trial of the insulin-producing islet cell therapy VX-880 for patients with type 1 diabetes who have impaired hypoglycemic awareness and severe hypoglycemia.

The cells are delivered by infusion into the hepatic portal vein. As of now, chronic immunosuppression is required to prevent rejection, but several approaches are being studied to overcome the limitation.

“There’s hope that this is a real advance. It’s been long awaited, and it looks really encouraging,” James Markmann, MD, PhD, the surgeon who performed the procedure, told this news organization.

The use of insulin-producing pancreatic beta cells derived from human pluripotent stem cells, first reported in 2014 by a team at the Harvard Stem Cell Institute, Boston, is seen as a major advance over use of cadaveric donor islet cells because stem cell–derived islets are available in unlimited and uncontaminated supplies.

Cadaveric donor islets are being used in products such as donislecel (CellTrans), which was endorsed by a Food and Drug Administration advisory committee in the summer for the treatment of type 1 diabetes that can’t be managed with current therapies.

The patient in the Vertex trial isn’t the first reported stem cell–derived islet recipient with type 1 diabetes, but these cells are the first to be transplanted into the liver.

“This Vertex patient stood out because the reduction in insulin requirement ... was so striking,” noted Dr. Markmann, chief of the division of transplant surgery at Massachusetts General Hospital, Boston, who has been transplanting islet cells from cadaveric donors into humans via the hepatic portal vein for over 20 years.

“Nobody knew what to expect, as it hadn’t been done before, but certainly the results in this patient are better than what I would have expected from a deceased donor islet transplant,” he added.

Asked to comment, A.M. James Shapiro, MD, agreed. “I think the most important finding is that a stem cell–derived islet is now transplanted into the liver of a patient safely, so far,” he said in an interview.

Dr. Shapiro is clinical director of the living donor and islet cell transplantation programs at the University of Alberta, Edmonton. He pioneered cadaveric donor islet cell transplantation more than 20 years ago with the watershed Edmonton Protocol.

‘Impressive finding ... bodes well for ongoing efforts’

Vertex announced the result by press release. The company plans to transplant another 16 patients, staggering them over time at multiple centers.

The first patient was treated with a single infusion of VX-880 at half the target dose (per protocol for the first two study subjects), along with standard immunosuppressive therapy. At 90 days, the patient’s C-peptide, a measure of endogenous insulin secretion, rose from undetectable to 280 pmol/L fasting and 560 pmol/L post mixed-meal tolerance testing.

Over the same period, the patient’s hemoglobin A1c dropped from 8.6% at baseline to 7.2%. And within 7 days, the individual’s daily exogenous insulin requirement dropped from an average of 34 units to just 2.9 units, a 91% decrease.

The patient had experienced five severe hypoglycemic episodes in the year prior to transplant. They experienced some mild hypoglycemia soon after the procedure while insulin doses were being adjusted, but none thereafter. 

Dr. Shapiro said in an interview: “I was absolutely thrilled to see the first patient results with high C-peptide and a 91% reduction in insulin. That’s a pretty impressive finding for half dosing in the very first patient in a trial. I think it bodes really well for ongoing efforts in this area by Vertex and by others that have similar kinds of cells. It’s very exciting.”

However, he cautioned, “we do need some longer-term data to be sure there’s no off-target growth or other concerns. But based on the purity of this product, that risk is likely to be low.”

And he noted, “I think we still have to address the challenges of setting this process up. A huge amount of work has gone into manufacturing the cell product for a single patient. I think it remains to be seen whether the same technology can be delivered at a larger scale ... i.e., being able to treat hundreds or thousands of patients.”

A blog post on the website of diabetes charity JDRF called the result “outstanding.” “It’s a big deal,” they added. However, they also cautioned: “There are a few things to keep in mind while assessing the data. One is that these are only results from a single person. Data are needed from many more to fully evaluate the potential of this therapy. The second is that this person only received half the target dose of cells.”

Dr. Shapiro is working with another company, ViaCyte, which has also developed stem cell–derived islets. In contrast to the Vertex product, which is fully differentiated and delivered to the liver, ViaCyte’s PEC-Direct product is comprised of stem cell-derived pancreatic islet progenitor cells that are implanted subcutaneously in a pouch, allowing for vascularization.

In a late-breaking poster at the annual scientific sessions of the American Diabetes Association in June 2021, ViaCyte reported on a patient given PEC-Direct. In that patient, stimulated C-peptide increased from 0.1 ng/mL at baseline to 0.8 ng/mL at week 39, and there was a drop in A1c from 7.4% to 6.6%, with no adverse events.

Immunosuppression: Which approach will come closer to cure?

Thus far, the requirement for lifelong immunosuppression has meant that any islet cell replacement approach, including with stem cell–derived islets, has been limited to use in people with type 1 diabetes who have hypoglycemic unawareness or severely unpredictable blood glucose levels.

Two broad approaches are simultaneously being explored to overcome the rejection problem: Encapsulation of the cells to protect them from the immune system, and genetic modification of the cells so that they don’t provoke the immune system in the first place.

In 2022, Vertex plans to file an investigational new drug application for an encapsulated islet cell program with the FDA.

Dr. Markmann believes the genetic modification approach is more promising. “I’m not a believer in encapsulation. I think the foreign body response is hard to overcome. I think the answer will ultimately be genetically modifying the [cell] lines. ... The cell could express something that would potentially turn off the lymphocytes or interfere with the lymphocytes trying to attack them.”

Moreover, he said, “you don’t have to get rid of immunosuppression completely. It’s all [a] risk-benefit [equation]. Even if you could get it down to a single less-toxic [immunosuppressive] agent that would be a huge step.”

Dr. Shapiro commented: “All efforts and eyes are laser-focused on developing cells or approaches that will allow transplantation of this kind of stem cell without any immunosuppression or with low-dose immunosuppression that could be regarded as being exceedingly low risk.”

“Then, and only then, I think we could offer this kind of treatment to children who are just diagnosed with diabetes or to [a bigger proportion of] patients with type 1 or type 2 diabetes. ... The science has to be done in a step-wise fashion,” he added.

Microencapsulation, Dr. Shapiro noted, “is a big challenge because the process of capturing the cells and putting them into a device is really injurious to their survival. ... That may or may not work.”

Dr. Shapiro and his Edmonton team are now embarking on a new trial with ViaCyte and CRISPR Therapeutics using gene-edited cells that contain two knock-in genes and two knock-out genes shown to be less immunogenic and anti-inflammatory in rodent models.

“They look to be promising. We’re going to start a first-in-human trial in the next few months with those cells to see if they really are able to withstand a transplant without the need for immunosuppression. That will be a very exciting trial in itself,” Dr. Shapiro said, noting that they expect to enroll the first patients in the next few months.

However, he cautioned, “first we have to make sure that the gene-edited product continues to function in patients in the way that the original product did, that the cells survive, and that the gene modifications are actually effective. ... Maybe other iterations will be needed.”

“I think, as we move forward, we will ultimately have a gene-edited stem cell–derived product that is immune evasive and will survive. So, I’m ... optimistic that this is not as long term as you might think, and it’s ... happening much more rapidly – at least in first-in-human trials to test safety and preliminary efficacy.”

Dr. Shapiro is a consultant for ViaCyte.

A version of this article first appeared on Medscape.com.

A novel investigational allogeneic stem cell–derived treatment resulted in near reversal of type 1 diabetes in a patient who had lived with the condition for about 40 years.

CIPhotos/Getty Images

The patient was the first in Vertex Pharmaceuticals’ phase 1/2 multicenter, single-arm, open-label clinical trial of the insulin-producing islet cell therapy VX-880 for patients with type 1 diabetes who have impaired hypoglycemic awareness and severe hypoglycemia.

The cells are delivered by infusion into the hepatic portal vein. As of now, chronic immunosuppression is required to prevent rejection, but several approaches are being studied to overcome the limitation.

“There’s hope that this is a real advance. It’s been long awaited, and it looks really encouraging,” James Markmann, MD, PhD, the surgeon who performed the procedure, told this news organization.

The use of insulin-producing pancreatic beta cells derived from human pluripotent stem cells, first reported in 2014 by a team at the Harvard Stem Cell Institute, Boston, is seen as a major advance over use of cadaveric donor islet cells because stem cell–derived islets are available in unlimited and uncontaminated supplies.

Cadaveric donor islets are being used in products such as donislecel (CellTrans), which was endorsed by a Food and Drug Administration advisory committee in the summer for the treatment of type 1 diabetes that can’t be managed with current therapies.

The patient in the Vertex trial isn’t the first reported stem cell–derived islet recipient with type 1 diabetes, but these cells are the first to be transplanted into the liver.

“This Vertex patient stood out because the reduction in insulin requirement ... was so striking,” noted Dr. Markmann, chief of the division of transplant surgery at Massachusetts General Hospital, Boston, who has been transplanting islet cells from cadaveric donors into humans via the hepatic portal vein for over 20 years.

“Nobody knew what to expect, as it hadn’t been done before, but certainly the results in this patient are better than what I would have expected from a deceased donor islet transplant,” he added.

Asked to comment, A.M. James Shapiro, MD, agreed. “I think the most important finding is that a stem cell–derived islet is now transplanted into the liver of a patient safely, so far,” he said in an interview.

Dr. Shapiro is clinical director of the living donor and islet cell transplantation programs at the University of Alberta, Edmonton. He pioneered cadaveric donor islet cell transplantation more than 20 years ago with the watershed Edmonton Protocol.

‘Impressive finding ... bodes well for ongoing efforts’

Vertex announced the result by press release. The company plans to transplant another 16 patients, staggering them over time at multiple centers.

The first patient was treated with a single infusion of VX-880 at half the target dose (per protocol for the first two study subjects), along with standard immunosuppressive therapy. At 90 days, the patient’s C-peptide, a measure of endogenous insulin secretion, rose from undetectable to 280 pmol/L fasting and 560 pmol/L post mixed-meal tolerance testing.

Over the same period, the patient’s hemoglobin A1c dropped from 8.6% at baseline to 7.2%. And within 7 days, the individual’s daily exogenous insulin requirement dropped from an average of 34 units to just 2.9 units, a 91% decrease.

The patient had experienced five severe hypoglycemic episodes in the year prior to transplant. They experienced some mild hypoglycemia soon after the procedure while insulin doses were being adjusted, but none thereafter. 

Dr. Shapiro said in an interview: “I was absolutely thrilled to see the first patient results with high C-peptide and a 91% reduction in insulin. That’s a pretty impressive finding for half dosing in the very first patient in a trial. I think it bodes really well for ongoing efforts in this area by Vertex and by others that have similar kinds of cells. It’s very exciting.”

However, he cautioned, “we do need some longer-term data to be sure there’s no off-target growth or other concerns. But based on the purity of this product, that risk is likely to be low.”

And he noted, “I think we still have to address the challenges of setting this process up. A huge amount of work has gone into manufacturing the cell product for a single patient. I think it remains to be seen whether the same technology can be delivered at a larger scale ... i.e., being able to treat hundreds or thousands of patients.”

A blog post on the website of diabetes charity JDRF called the result “outstanding.” “It’s a big deal,” they added. However, they also cautioned: “There are a few things to keep in mind while assessing the data. One is that these are only results from a single person. Data are needed from many more to fully evaluate the potential of this therapy. The second is that this person only received half the target dose of cells.”

Dr. Shapiro is working with another company, ViaCyte, which has also developed stem cell–derived islets. In contrast to the Vertex product, which is fully differentiated and delivered to the liver, ViaCyte’s PEC-Direct product is comprised of stem cell-derived pancreatic islet progenitor cells that are implanted subcutaneously in a pouch, allowing for vascularization.

In a late-breaking poster at the annual scientific sessions of the American Diabetes Association in June 2021, ViaCyte reported on a patient given PEC-Direct. In that patient, stimulated C-peptide increased from 0.1 ng/mL at baseline to 0.8 ng/mL at week 39, and there was a drop in A1c from 7.4% to 6.6%, with no adverse events.

Immunosuppression: Which approach will come closer to cure?

Thus far, the requirement for lifelong immunosuppression has meant that any islet cell replacement approach, including with stem cell–derived islets, has been limited to use in people with type 1 diabetes who have hypoglycemic unawareness or severely unpredictable blood glucose levels.

Two broad approaches are simultaneously being explored to overcome the rejection problem: Encapsulation of the cells to protect them from the immune system, and genetic modification of the cells so that they don’t provoke the immune system in the first place.

In 2022, Vertex plans to file an investigational new drug application for an encapsulated islet cell program with the FDA.

Dr. Markmann believes the genetic modification approach is more promising. “I’m not a believer in encapsulation. I think the foreign body response is hard to overcome. I think the answer will ultimately be genetically modifying the [cell] lines. ... The cell could express something that would potentially turn off the lymphocytes or interfere with the lymphocytes trying to attack them.”

Moreover, he said, “you don’t have to get rid of immunosuppression completely. It’s all [a] risk-benefit [equation]. Even if you could get it down to a single less-toxic [immunosuppressive] agent that would be a huge step.”

Dr. Shapiro commented: “All efforts and eyes are laser-focused on developing cells or approaches that will allow transplantation of this kind of stem cell without any immunosuppression or with low-dose immunosuppression that could be regarded as being exceedingly low risk.”

“Then, and only then, I think we could offer this kind of treatment to children who are just diagnosed with diabetes or to [a bigger proportion of] patients with type 1 or type 2 diabetes. ... The science has to be done in a step-wise fashion,” he added.

Microencapsulation, Dr. Shapiro noted, “is a big challenge because the process of capturing the cells and putting them into a device is really injurious to their survival. ... That may or may not work.”

Dr. Shapiro and his Edmonton team are now embarking on a new trial with ViaCyte and CRISPR Therapeutics using gene-edited cells that contain two knock-in genes and two knock-out genes shown to be less immunogenic and anti-inflammatory in rodent models.

“They look to be promising. We’re going to start a first-in-human trial in the next few months with those cells to see if they really are able to withstand a transplant without the need for immunosuppression. That will be a very exciting trial in itself,” Dr. Shapiro said, noting that they expect to enroll the first patients in the next few months.

However, he cautioned, “first we have to make sure that the gene-edited product continues to function in patients in the way that the original product did, that the cells survive, and that the gene modifications are actually effective. ... Maybe other iterations will be needed.”

“I think, as we move forward, we will ultimately have a gene-edited stem cell–derived product that is immune evasive and will survive. So, I’m ... optimistic that this is not as long term as you might think, and it’s ... happening much more rapidly – at least in first-in-human trials to test safety and preliminary efficacy.”

Dr. Shapiro is a consultant for ViaCyte.

A version of this article first appeared on Medscape.com.

Nearly two-thirds of Americans are not confident that they understood their doctor’s recommendations and the health information they discussed with their doctor after a visit, according to a new survey.

Confusion over health information and doctor advice is even higher among people who care for patients than among those who don’t provide care to their loved ones, the nationally representative survey from the AHIMA Foundation found.

The survey also shows that 80% of Americans – and an even higher portion of caregivers – are likely to research medical recommendations online after a doctor’s visit. But 1 in 4 people don’t know how to access their own medical records or find it difficult to do so.

The findings reflect the same low level of health literacy in the U.S. population that earlier surveys did. The results also indicate that little has changed since the Department of Health and Human Services released a National Action Plan to Improve Health Literacy in 2010.

That plan emphasized the need to develop and share accurate health information that helps people make decisions; to promote changes in the health care system that improve health information, communication, informed decision-making, and access to health services; and to increase the sharing and use of evidence-based health literacy practices.

According to the AHIMA Foundation report, 62% of Americans are not sure they understand their doctor’s advice and the health information discussed during a visit. Twenty-four percent say they don’t comprehend any of it, and 31% can’t remember what was said during the visit. Fifteen percent of those surveyed said they were more confused about their health than they were before the encounter with their doctor.
 

Caregivers have special issues

Forty-three percent of Americans are caregivers, the report notes, and 91% of those play an active role in managing someone else’s health. Millennials (65%) and Gen Xers (50%) are significantly more likely than Gen Zers (39%) and Boomers (20%) to be a caregiver.

Most caregivers have concerns about their loved ones’ ability to manage their own health. Most of them believe that doctors provide enough information, but 38% don’t believe a doctor can communicate effectively with the patient if the caregiver is not present.

Forty-three percent of caretakers don’t think their loved ones can understand medical information on their own. On the other hand, caregivers are more likely than people who don’t provide care to say the doctor confused them and to research the doctor’s advice after an appointment.

For many patients and caregivers, communications break down when they are with their health care provider. Twenty-two percent of Americans say they do not feel comfortable asking their doctor certain health questions. This inability to have a satisfactory dialogue with their doctor means that many patients leave their appointments without getting clear answers to their questions (24%) or without having an opportunity to ask any questions at all (17%).

This is not surprising, considering that a 2018 study found that doctors spend only 11 seconds, on average, listening to patients before interrupting them.
 

Depending on the internet

Overall, the AHIMA survey found, 42% of Americans research their doctor’s recommendations after an appointment. A higher percentage of caregivers than noncaregiver peers do so (47% vs. 38%). Eighty percent of respondents say they are “likely” to research their doctor’s advice online after a visit.

When they have a medical problem or a question about their condition, just as many Americans (59%) turn to the internet for an answer as contact their doctor directly, the survey found. Twenty-nine percent of the respondents consult friends, family, or colleagues; 23% look up medical records if they’re easily accessible; 19% ask pharmacists for advice; and 6% call an unspecified 800 number.

Americans feel secure in the health information they find on the internet. Among those who go online to look up information, 86% are confident that it is credible. And 42% report feeling relieved that they can find a lot of information about their health concerns. Respondents also say that the information they gather allows them to feel more confident in their doctor’s recommendations (35%) and that they feel better after having learned more on the internet than their doctor had told them (39%). Men are more likely than women to say that their confidence in their doctor’s recommendations increased after doing online research (40% vs. 30%).
 

Access to health records

Access to medical records would help people better understand their condition or diagnosis. But nearly half of Americans (48%) admit they don’t usually review their medical records until long after an appointment, and 52% say they rarely access their records at all.

One in four Americans say that they don’t know where to go to access their health information or that they didn’t find the process easy. More than half of those who have never had to find their records think the process would be difficult if they had to try.

Eighty-one percent of Americans use an online platform or portal to access their medical records or health information. Two-thirds of Americans who use an online portal trust that their medical information is kept safe and not shared with other people or organizations.

Four in five respondents agree that if they had access to all of their health information, including medical records, recommendations, conditions, and test results, they’d see an improvement in their health management. Fifty-nine percent of them believe they’d also be more confident about understanding their health, and 47% say they’d have greater trust in their doctor’s recommendations. Higher percentages of caregivers than noncaregivers say the same.

Younger people, those with a high school degree or less, and those who earn less than $50,000 are less likely than older, better educated, and more affluent people to understand their doctor’s health information and to ask questions of their providers.

People of color struggle with their relationships with doctors, are less satisfied than white people with the information they receive during visits, and are more likely than white peers to feel that if they had access to all their health information, they’d manage their health better and be more confident in their doctors’ recommendations, the survey found.

A version of this article first appeared on WebMD.com.

Nearly two-thirds of Americans are not confident that they understood their doctor’s recommendations and the health information they discussed with their doctor after a visit, according to a new survey.

Confusion over health information and doctor advice is even higher among people who care for patients than among those who don’t provide care to their loved ones, the nationally representative survey from the AHIMA Foundation found.

The survey also shows that 80% of Americans – and an even higher portion of caregivers – are likely to research medical recommendations online after a doctor’s visit. But 1 in 4 people don’t know how to access their own medical records or find it difficult to do so.

The findings reflect the same low level of health literacy in the U.S. population that earlier surveys did. The results also indicate that little has changed since the Department of Health and Human Services released a National Action Plan to Improve Health Literacy in 2010.

That plan emphasized the need to develop and share accurate health information that helps people make decisions; to promote changes in the health care system that improve health information, communication, informed decision-making, and access to health services; and to increase the sharing and use of evidence-based health literacy practices.

According to the AHIMA Foundation report, 62% of Americans are not sure they understand their doctor’s advice and the health information discussed during a visit. Twenty-four percent say they don’t comprehend any of it, and 31% can’t remember what was said during the visit. Fifteen percent of those surveyed said they were more confused about their health than they were before the encounter with their doctor.
 

Caregivers have special issues

Forty-three percent of Americans are caregivers, the report notes, and 91% of those play an active role in managing someone else’s health. Millennials (65%) and Gen Xers (50%) are significantly more likely than Gen Zers (39%) and Boomers (20%) to be a caregiver.

Most caregivers have concerns about their loved ones’ ability to manage their own health. Most of them believe that doctors provide enough information, but 38% don’t believe a doctor can communicate effectively with the patient if the caregiver is not present.

Forty-three percent of caretakers don’t think their loved ones can understand medical information on their own. On the other hand, caregivers are more likely than people who don’t provide care to say the doctor confused them and to research the doctor’s advice after an appointment.

For many patients and caregivers, communications break down when they are with their health care provider. Twenty-two percent of Americans say they do not feel comfortable asking their doctor certain health questions. This inability to have a satisfactory dialogue with their doctor means that many patients leave their appointments without getting clear answers to their questions (24%) or without having an opportunity to ask any questions at all (17%).

This is not surprising, considering that a 2018 study found that doctors spend only 11 seconds, on average, listening to patients before interrupting them.
 

Depending on the internet

Overall, the AHIMA survey found, 42% of Americans research their doctor’s recommendations after an appointment. A higher percentage of caregivers than noncaregiver peers do so (47% vs. 38%). Eighty percent of respondents say they are “likely” to research their doctor’s advice online after a visit.

When they have a medical problem or a question about their condition, just as many Americans (59%) turn to the internet for an answer as contact their doctor directly, the survey found. Twenty-nine percent of the respondents consult friends, family, or colleagues; 23% look up medical records if they’re easily accessible; 19% ask pharmacists for advice; and 6% call an unspecified 800 number.

Americans feel secure in the health information they find on the internet. Among those who go online to look up information, 86% are confident that it is credible. And 42% report feeling relieved that they can find a lot of information about their health concerns. Respondents also say that the information they gather allows them to feel more confident in their doctor’s recommendations (35%) and that they feel better after having learned more on the internet than their doctor had told them (39%). Men are more likely than women to say that their confidence in their doctor’s recommendations increased after doing online research (40% vs. 30%).
 

Access to health records

Access to medical records would help people better understand their condition or diagnosis. But nearly half of Americans (48%) admit they don’t usually review their medical records until long after an appointment, and 52% say they rarely access their records at all.

One in four Americans say that they don’t know where to go to access their health information or that they didn’t find the process easy. More than half of those who have never had to find their records think the process would be difficult if they had to try.

Eighty-one percent of Americans use an online platform or portal to access their medical records or health information. Two-thirds of Americans who use an online portal trust that their medical information is kept safe and not shared with other people or organizations.

Four in five respondents agree that if they had access to all of their health information, including medical records, recommendations, conditions, and test results, they’d see an improvement in their health management. Fifty-nine percent of them believe they’d also be more confident about understanding their health, and 47% say they’d have greater trust in their doctor’s recommendations. Higher percentages of caregivers than noncaregivers say the same.

Younger people, those with a high school degree or less, and those who earn less than $50,000 are less likely than older, better educated, and more affluent people to understand their doctor’s health information and to ask questions of their providers.

People of color struggle with their relationships with doctors, are less satisfied than white people with the information they receive during visits, and are more likely than white peers to feel that if they had access to all their health information, they’d manage their health better and be more confident in their doctors’ recommendations, the survey found.

A version of this article first appeared on WebMD.com.

Nearly two-thirds of Americans are not confident that they understood their doctor’s recommendations and the health information they discussed with their doctor after a visit, according to a new survey.

Confusion over health information and doctor advice is even higher among people who care for patients than among those who don’t provide care to their loved ones, the nationally representative survey from the AHIMA Foundation found.

The survey also shows that 80% of Americans – and an even higher portion of caregivers – are likely to research medical recommendations online after a doctor’s visit. But 1 in 4 people don’t know how to access their own medical records or find it difficult to do so.

The findings reflect the same low level of health literacy in the U.S. population that earlier surveys did. The results also indicate that little has changed since the Department of Health and Human Services released a National Action Plan to Improve Health Literacy in 2010.

That plan emphasized the need to develop and share accurate health information that helps people make decisions; to promote changes in the health care system that improve health information, communication, informed decision-making, and access to health services; and to increase the sharing and use of evidence-based health literacy practices.

According to the AHIMA Foundation report, 62% of Americans are not sure they understand their doctor’s advice and the health information discussed during a visit. Twenty-four percent say they don’t comprehend any of it, and 31% can’t remember what was said during the visit. Fifteen percent of those surveyed said they were more confused about their health than they were before the encounter with their doctor.
 

Caregivers have special issues

Forty-three percent of Americans are caregivers, the report notes, and 91% of those play an active role in managing someone else’s health. Millennials (65%) and Gen Xers (50%) are significantly more likely than Gen Zers (39%) and Boomers (20%) to be a caregiver.

Most caregivers have concerns about their loved ones’ ability to manage their own health. Most of them believe that doctors provide enough information, but 38% don’t believe a doctor can communicate effectively with the patient if the caregiver is not present.

Forty-three percent of caretakers don’t think their loved ones can understand medical information on their own. On the other hand, caregivers are more likely than people who don’t provide care to say the doctor confused them and to research the doctor’s advice after an appointment.

For many patients and caregivers, communications break down when they are with their health care provider. Twenty-two percent of Americans say they do not feel comfortable asking their doctor certain health questions. This inability to have a satisfactory dialogue with their doctor means that many patients leave their appointments without getting clear answers to their questions (24%) or without having an opportunity to ask any questions at all (17%).

This is not surprising, considering that a 2018 study found that doctors spend only 11 seconds, on average, listening to patients before interrupting them.
 

Depending on the internet

Overall, the AHIMA survey found, 42% of Americans research their doctor’s recommendations after an appointment. A higher percentage of caregivers than noncaregiver peers do so (47% vs. 38%). Eighty percent of respondents say they are “likely” to research their doctor’s advice online after a visit.

When they have a medical problem or a question about their condition, just as many Americans (59%) turn to the internet for an answer as contact their doctor directly, the survey found. Twenty-nine percent of the respondents consult friends, family, or colleagues; 23% look up medical records if they’re easily accessible; 19% ask pharmacists for advice; and 6% call an unspecified 800 number.

Americans feel secure in the health information they find on the internet. Among those who go online to look up information, 86% are confident that it is credible. And 42% report feeling relieved that they can find a lot of information about their health concerns. Respondents also say that the information they gather allows them to feel more confident in their doctor’s recommendations (35%) and that they feel better after having learned more on the internet than their doctor had told them (39%). Men are more likely than women to say that their confidence in their doctor’s recommendations increased after doing online research (40% vs. 30%).
 

Access to health records

Access to medical records would help people better understand their condition or diagnosis. But nearly half of Americans (48%) admit they don’t usually review their medical records until long after an appointment, and 52% say they rarely access their records at all.

One in four Americans say that they don’t know where to go to access their health information or that they didn’t find the process easy. More than half of those who have never had to find their records think the process would be difficult if they had to try.

Eighty-one percent of Americans use an online platform or portal to access their medical records or health information. Two-thirds of Americans who use an online portal trust that their medical information is kept safe and not shared with other people or organizations.

Four in five respondents agree that if they had access to all of their health information, including medical records, recommendations, conditions, and test results, they’d see an improvement in their health management. Fifty-nine percent of them believe they’d also be more confident about understanding their health, and 47% say they’d have greater trust in their doctor’s recommendations. Higher percentages of caregivers than noncaregivers say the same.

Younger people, those with a high school degree or less, and those who earn less than $50,000 are less likely than older, better educated, and more affluent people to understand their doctor’s health information and to ask questions of their providers.

People of color struggle with their relationships with doctors, are less satisfied than white people with the information they receive during visits, and are more likely than white peers to feel that if they had access to all their health information, they’d manage their health better and be more confident in their doctors’ recommendations, the survey found.

A version of this article first appeared on WebMD.com.

The Food and Drug Administration has authorized Pfizer’s COVID-19 vaccine for children ages 5 to 11, which means vaccines could be available to school-aged children starting next week.

The move brings families with young children a step closer to resuming their normal activities, and it should help further slow transmission of the coronavirus virus in the United States.

States have already placed their orders for initial doses of the vaccines. The Oct. 29 FDA authorization triggers the shipment of millions of doses to pediatricians, family practice doctors, children’s hospitals, community health centers, and pharmacies.

Next, a panel of experts known as the Advisory Committee on Immunization Practices, or ACIP, will meet Nov. 2 to vote on recommendations for use of the vaccine.

As soon as the Centers for Disease Control and Prevention’s director signs off on those recommendations, children can get the shots, perhaps as early as Nov. 3.

Pfizer’s vaccine for children is 10 micrograms, or one-third of the dose given to teens and adults. Kids get two doses of the vaccine 3 weeks apart. In clinical trials, the most common side effects were pain at the injection site, fatigue, and headache. These side effects were mild and disappeared quickly. There were no serious adverse events detected in the studies, which included about 3,100 children. In one study, the vaccine was 90% effective at preventing COVID-19 infections with symptoms in younger children.

There are about 28 million children in the United States between the ages of 5 and 12.

“As a mother and a physician, I know that parents, caregivers, school staff, and children have been waiting for today’s authorization. Vaccinating younger children against COVID-19 will bring us closer to returning to a sense of normalcy,” Acting FDA Commissioner Janet Woodcock, MD, said in an FDA news release.

“Our comprehensive and rigorous evaluation of the data pertaining to the vaccine’s safety and effectiveness should help assure parents and guardians that this vaccine meets our high standards,” she said.

A version of this article first appeared on WebMD.com.

The Food and Drug Administration has authorized Pfizer’s COVID-19 vaccine for children ages 5 to 11, which means vaccines could be available to school-aged children starting next week.

The move brings families with young children a step closer to resuming their normal activities, and it should help further slow transmission of the coronavirus virus in the United States.

States have already placed their orders for initial doses of the vaccines. The Oct. 29 FDA authorization triggers the shipment of millions of doses to pediatricians, family practice doctors, children’s hospitals, community health centers, and pharmacies.

Next, a panel of experts known as the Advisory Committee on Immunization Practices, or ACIP, will meet Nov. 2 to vote on recommendations for use of the vaccine.

As soon as the Centers for Disease Control and Prevention’s director signs off on those recommendations, children can get the shots, perhaps as early as Nov. 3.

Pfizer’s vaccine for children is 10 micrograms, or one-third of the dose given to teens and adults. Kids get two doses of the vaccine 3 weeks apart. In clinical trials, the most common side effects were pain at the injection site, fatigue, and headache. These side effects were mild and disappeared quickly. There were no serious adverse events detected in the studies, which included about 3,100 children. In one study, the vaccine was 90% effective at preventing COVID-19 infections with symptoms in younger children.

There are about 28 million children in the United States between the ages of 5 and 12.

“As a mother and a physician, I know that parents, caregivers, school staff, and children have been waiting for today’s authorization. Vaccinating younger children against COVID-19 will bring us closer to returning to a sense of normalcy,” Acting FDA Commissioner Janet Woodcock, MD, said in an FDA news release.

“Our comprehensive and rigorous evaluation of the data pertaining to the vaccine’s safety and effectiveness should help assure parents and guardians that this vaccine meets our high standards,” she said.

A version of this article first appeared on WebMD.com.

The Food and Drug Administration has authorized Pfizer’s COVID-19 vaccine for children ages 5 to 11, which means vaccines could be available to school-aged children starting next week.

The move brings families with young children a step closer to resuming their normal activities, and it should help further slow transmission of the coronavirus virus in the United States.

States have already placed their orders for initial doses of the vaccines. The Oct. 29 FDA authorization triggers the shipment of millions of doses to pediatricians, family practice doctors, children’s hospitals, community health centers, and pharmacies.

Next, a panel of experts known as the Advisory Committee on Immunization Practices, or ACIP, will meet Nov. 2 to vote on recommendations for use of the vaccine.

As soon as the Centers for Disease Control and Prevention’s director signs off on those recommendations, children can get the shots, perhaps as early as Nov. 3.

Pfizer’s vaccine for children is 10 micrograms, or one-third of the dose given to teens and adults. Kids get two doses of the vaccine 3 weeks apart. In clinical trials, the most common side effects were pain at the injection site, fatigue, and headache. These side effects were mild and disappeared quickly. There were no serious adverse events detected in the studies, which included about 3,100 children. In one study, the vaccine was 90% effective at preventing COVID-19 infections with symptoms in younger children.

There are about 28 million children in the United States between the ages of 5 and 12.

“As a mother and a physician, I know that parents, caregivers, school staff, and children have been waiting for today’s authorization. Vaccinating younger children against COVID-19 will bring us closer to returning to a sense of normalcy,” Acting FDA Commissioner Janet Woodcock, MD, said in an FDA news release.

“Our comprehensive and rigorous evaluation of the data pertaining to the vaccine’s safety and effectiveness should help assure parents and guardians that this vaccine meets our high standards,” she said.

A version of this article first appeared on WebMD.com.

U.S. regulators have made it easier for physicians, patients, and researchers to determine the status of cancer medicines cleared for sale based on limited evidence, including a public list detailing cases where accelerated approvals have been rescinded for lack of evidence.

On Oct. 29, the Food and Drug Administration posted new websites detailing the status of oncology medicines given these special clearances:

• Ongoing | Cancer Accelerated Approvals 
• Verified Clinical Benefit | Cancer Accelerated Approvals
• Withdrawn | Cancer Accelerated Approvals

The FDA’s cancer center also has created a web page called Project Confirm to provide more information on the way it uses accelerated approvals.

There has been increased concern about medicines cleared by accelerated approvals in recent years, culminating in an uproar over the controversial June approval of aducanumab (Aduhelm) for Alzheimer’s disease. This drew more attention to a debate already underway about how much data supports some of the indications for some cancer drugs.

Federal and state officials and advisers are putting more pressure on pharmaceutical companies to prove that medicines that are put on the market through accelerated approval do deliver meaningful benefits for patients.

In addition, earlier this month two of the top health advisers in Barack Obama’s administration proposed a new model through which Medicare could reduce payments for certain cancer drugs cleared through accelerated approvals – and even cut off reimbursements in cases where companies fail to deliver confirmatory evidence for expected benefits.

This “Pay for Drugs That Work Model” was proposed by Richard Frank, PhD, and Ezekiel Emanuel, MD, PhD, in a recent JAMA article. In their view, the FDA’s accelerated drug approval process allows for too many delays in obtaining answers as to whether medicines cleared this way provide expected benefits.

“The proposed Pay for Drugs That Work model could test a modified approach for incentivizing rapid completion of confirmatory trials to inform clinicians and patients about the true risks and benefits of new drugs and improve the value for money of cancer drugs that receive accelerated approval,” they wrote.
 

Excel files, regular updates

For the FDA, accelerated approvals require balancing an estimated potential benefit for people facing serious diseases (for example, cancer) against serious risks, including potentially exposing patients to costly, toxic drugs that will later be shown not to work for their conditions.

For many years, there has been significant pressure on the FDA to lean toward speedier approvals, with members of Congress, advocacy groups, and drugmakers advocating for broad use of surrogate data in deciding on clearances. The FDA posts biannual reports on its website that highlight how quickly approvals have been granted. But these biannual reports don’t provide much information on the status of accelerated-approval drugs, other than to say if they have been given full approval or withdrawn.

The newly created websites from the FDA’s oncology division appear to reflect growing public interest in knowing what standards the agency sets for confirmatory trials and what deadlines companies face to deliver evidence of significant benefit for their drugs.

The new sortable websites also include details on trials and have links to Excel files which will help researchers and others seeking to track patterns with accelerated approvals. The FDA said in an interview that it intends to update these sites when there are developments with accelerated approvals for cancer drugs, such as new clearances of this type, conversions to regular approvals, and withdrawn approvals.

Julia Beaver, MD, chief of medical oncology at the FDA’s Oncology Center of Excellence, and acting deputy director of the Office of Oncologic Diseases of the FDA’s Center for Drug Evaluation and Research, described the new websites as part of a “commitment to preserve the integrity” of the accelerated approval program.

“These new web pages will make information on our accelerated approvals more transparent,” Dr. Beaver said in an email to this news organization.

The FDA has been able to speed many medicines to market and clear additional uses for drugs already sold through the program, giving people earlier access in many cases to critical medicines, Dr. Beaver said.

More than 165 oncology indications have received accelerated approval, with almost half converted to regular approval in a median of 3 years. Less than 10% of these indications were withdrawn, Dr. Beaver said.

“Of those accelerated approvals that were converted to regular approval, many demonstrated survival advantages to patients with several types of cancer or provided meaningful therapeutic options where none previously existed,” she said.

However, Dr. Beaver also has made public the FDA’s concerns with what she and Richard Pazdur, MD, director of the Oncology Center of Excellence, have described as “dangling” accelerated approvals. 

These are cases where the required trials did not end up confirming benefit for a medicine, yet the manufacturer did not move to withdraw an accelerated approval. The FDA’s cancer center has already announced that it is doing an “industry-wide evaluation of accelerated approvals in oncology in which confirmatory trials did not confirm clinical benefit.”

This stems in part from what can be called the FDA’s “growing pains” in its efforts to manage the rapidly changing landscape for these immunotherapy checkpoint inhibitors. This field of medicine has experienced an “unprecedented level of drug development” in recent years, FDA officials said in briefing materials for an Oncologic Drugs Advisory Committee (ODAC) meeting last April on dangling accelerated approvals.

A newly posted chart on withdrawn oncology accelerated approvals, posted by the FDA’s cancer division, makes it clear that the pace of these rescinded clearances has picked up. The chart lists a total 14 withdrawn indications of oncology accelerated approvals.

Six of these withdrawals happened this year.

There were two withdrawals in 2020, including the December withdrawal of nivolumab, (Opdivo) for a form of metastatic lung cancer.

Then there was a significant gap, with no withdrawals going back to 2013 (when there was one). There were two withdrawals in 2012 and three in 2011.

A version of this article first appeared on Medscape.com.

U.S. regulators have made it easier for physicians, patients, and researchers to determine the status of cancer medicines cleared for sale based on limited evidence, including a public list detailing cases where accelerated approvals have been rescinded for lack of evidence.

On Oct. 29, the Food and Drug Administration posted new websites detailing the status of oncology medicines given these special clearances:

• Ongoing | Cancer Accelerated Approvals 
• Verified Clinical Benefit | Cancer Accelerated Approvals
• Withdrawn | Cancer Accelerated Approvals

The FDA’s cancer center also has created a web page called Project Confirm to provide more information on the way it uses accelerated approvals.

There has been increased concern about medicines cleared by accelerated approvals in recent years, culminating in an uproar over the controversial June approval of aducanumab (Aduhelm) for Alzheimer’s disease. This drew more attention to a debate already underway about how much data supports some of the indications for some cancer drugs.

Federal and state officials and advisers are putting more pressure on pharmaceutical companies to prove that medicines that are put on the market through accelerated approval do deliver meaningful benefits for patients.

In addition, earlier this month two of the top health advisers in Barack Obama’s administration proposed a new model through which Medicare could reduce payments for certain cancer drugs cleared through accelerated approvals – and even cut off reimbursements in cases where companies fail to deliver confirmatory evidence for expected benefits.

This “Pay for Drugs That Work Model” was proposed by Richard Frank, PhD, and Ezekiel Emanuel, MD, PhD, in a recent JAMA article. In their view, the FDA’s accelerated drug approval process allows for too many delays in obtaining answers as to whether medicines cleared this way provide expected benefits.

“The proposed Pay for Drugs That Work model could test a modified approach for incentivizing rapid completion of confirmatory trials to inform clinicians and patients about the true risks and benefits of new drugs and improve the value for money of cancer drugs that receive accelerated approval,” they wrote.
 

Excel files, regular updates

For the FDA, accelerated approvals require balancing an estimated potential benefit for people facing serious diseases (for example, cancer) against serious risks, including potentially exposing patients to costly, toxic drugs that will later be shown not to work for their conditions.

For many years, there has been significant pressure on the FDA to lean toward speedier approvals, with members of Congress, advocacy groups, and drugmakers advocating for broad use of surrogate data in deciding on clearances. The FDA posts biannual reports on its website that highlight how quickly approvals have been granted. But these biannual reports don’t provide much information on the status of accelerated-approval drugs, other than to say if they have been given full approval or withdrawn.

The newly created websites from the FDA’s oncology division appear to reflect growing public interest in knowing what standards the agency sets for confirmatory trials and what deadlines companies face to deliver evidence of significant benefit for their drugs.

The new sortable websites also include details on trials and have links to Excel files which will help researchers and others seeking to track patterns with accelerated approvals. The FDA said in an interview that it intends to update these sites when there are developments with accelerated approvals for cancer drugs, such as new clearances of this type, conversions to regular approvals, and withdrawn approvals.

Julia Beaver, MD, chief of medical oncology at the FDA’s Oncology Center of Excellence, and acting deputy director of the Office of Oncologic Diseases of the FDA’s Center for Drug Evaluation and Research, described the new websites as part of a “commitment to preserve the integrity” of the accelerated approval program.

“These new web pages will make information on our accelerated approvals more transparent,” Dr. Beaver said in an email to this news organization.

The FDA has been able to speed many medicines to market and clear additional uses for drugs already sold through the program, giving people earlier access in many cases to critical medicines, Dr. Beaver said.

More than 165 oncology indications have received accelerated approval, with almost half converted to regular approval in a median of 3 years. Less than 10% of these indications were withdrawn, Dr. Beaver said.

“Of those accelerated approvals that were converted to regular approval, many demonstrated survival advantages to patients with several types of cancer or provided meaningful therapeutic options where none previously existed,” she said.

However, Dr. Beaver also has made public the FDA’s concerns with what she and Richard Pazdur, MD, director of the Oncology Center of Excellence, have described as “dangling” accelerated approvals. 

These are cases where the required trials did not end up confirming benefit for a medicine, yet the manufacturer did not move to withdraw an accelerated approval. The FDA’s cancer center has already announced that it is doing an “industry-wide evaluation of accelerated approvals in oncology in which confirmatory trials did not confirm clinical benefit.”

This stems in part from what can be called the FDA’s “growing pains” in its efforts to manage the rapidly changing landscape for these immunotherapy checkpoint inhibitors. This field of medicine has experienced an “unprecedented level of drug development” in recent years, FDA officials said in briefing materials for an Oncologic Drugs Advisory Committee (ODAC) meeting last April on dangling accelerated approvals.

A newly posted chart on withdrawn oncology accelerated approvals, posted by the FDA’s cancer division, makes it clear that the pace of these rescinded clearances has picked up. The chart lists a total 14 withdrawn indications of oncology accelerated approvals.

Six of these withdrawals happened this year.

There were two withdrawals in 2020, including the December withdrawal of nivolumab, (Opdivo) for a form of metastatic lung cancer.

Then there was a significant gap, with no withdrawals going back to 2013 (when there was one). There were two withdrawals in 2012 and three in 2011.

A version of this article first appeared on Medscape.com.

U.S. regulators have made it easier for physicians, patients, and researchers to determine the status of cancer medicines cleared for sale based on limited evidence, including a public list detailing cases where accelerated approvals have been rescinded for lack of evidence.

On Oct. 29, the Food and Drug Administration posted new websites detailing the status of oncology medicines given these special clearances:

• Ongoing | Cancer Accelerated Approvals 
• Verified Clinical Benefit | Cancer Accelerated Approvals
• Withdrawn | Cancer Accelerated Approvals

The FDA’s cancer center also has created a web page called Project Confirm to provide more information on the way it uses accelerated approvals.

There has been increased concern about medicines cleared by accelerated approvals in recent years, culminating in an uproar over the controversial June approval of aducanumab (Aduhelm) for Alzheimer’s disease. This drew more attention to a debate already underway about how much data supports some of the indications for some cancer drugs.

Federal and state officials and advisers are putting more pressure on pharmaceutical companies to prove that medicines that are put on the market through accelerated approval do deliver meaningful benefits for patients.

In addition, earlier this month two of the top health advisers in Barack Obama’s administration proposed a new model through which Medicare could reduce payments for certain cancer drugs cleared through accelerated approvals – and even cut off reimbursements in cases where companies fail to deliver confirmatory evidence for expected benefits.

This “Pay for Drugs That Work Model” was proposed by Richard Frank, PhD, and Ezekiel Emanuel, MD, PhD, in a recent JAMA article. In their view, the FDA’s accelerated drug approval process allows for too many delays in obtaining answers as to whether medicines cleared this way provide expected benefits.

“The proposed Pay for Drugs That Work model could test a modified approach for incentivizing rapid completion of confirmatory trials to inform clinicians and patients about the true risks and benefits of new drugs and improve the value for money of cancer drugs that receive accelerated approval,” they wrote.
 

Excel files, regular updates

For the FDA, accelerated approvals require balancing an estimated potential benefit for people facing serious diseases (for example, cancer) against serious risks, including potentially exposing patients to costly, toxic drugs that will later be shown not to work for their conditions.

For many years, there has been significant pressure on the FDA to lean toward speedier approvals, with members of Congress, advocacy groups, and drugmakers advocating for broad use of surrogate data in deciding on clearances. The FDA posts biannual reports on its website that highlight how quickly approvals have been granted. But these biannual reports don’t provide much information on the status of accelerated-approval drugs, other than to say if they have been given full approval or withdrawn.

The newly created websites from the FDA’s oncology division appear to reflect growing public interest in knowing what standards the agency sets for confirmatory trials and what deadlines companies face to deliver evidence of significant benefit for their drugs.

The new sortable websites also include details on trials and have links to Excel files which will help researchers and others seeking to track patterns with accelerated approvals. The FDA said in an interview that it intends to update these sites when there are developments with accelerated approvals for cancer drugs, such as new clearances of this type, conversions to regular approvals, and withdrawn approvals.

Julia Beaver, MD, chief of medical oncology at the FDA’s Oncology Center of Excellence, and acting deputy director of the Office of Oncologic Diseases of the FDA’s Center for Drug Evaluation and Research, described the new websites as part of a “commitment to preserve the integrity” of the accelerated approval program.

“These new web pages will make information on our accelerated approvals more transparent,” Dr. Beaver said in an email to this news organization.

The FDA has been able to speed many medicines to market and clear additional uses for drugs already sold through the program, giving people earlier access in many cases to critical medicines, Dr. Beaver said.

More than 165 oncology indications have received accelerated approval, with almost half converted to regular approval in a median of 3 years. Less than 10% of these indications were withdrawn, Dr. Beaver said.

“Of those accelerated approvals that were converted to regular approval, many demonstrated survival advantages to patients with several types of cancer or provided meaningful therapeutic options where none previously existed,” she said.

However, Dr. Beaver also has made public the FDA’s concerns with what she and Richard Pazdur, MD, director of the Oncology Center of Excellence, have described as “dangling” accelerated approvals. 

These are cases where the required trials did not end up confirming benefit for a medicine, yet the manufacturer did not move to withdraw an accelerated approval. The FDA’s cancer center has already announced that it is doing an “industry-wide evaluation of accelerated approvals in oncology in which confirmatory trials did not confirm clinical benefit.”

This stems in part from what can be called the FDA’s “growing pains” in its efforts to manage the rapidly changing landscape for these immunotherapy checkpoint inhibitors. This field of medicine has experienced an “unprecedented level of drug development” in recent years, FDA officials said in briefing materials for an Oncologic Drugs Advisory Committee (ODAC) meeting last April on dangling accelerated approvals.

A newly posted chart on withdrawn oncology accelerated approvals, posted by the FDA’s cancer division, makes it clear that the pace of these rescinded clearances has picked up. The chart lists a total 14 withdrawn indications of oncology accelerated approvals.

Six of these withdrawals happened this year.

There were two withdrawals in 2020, including the December withdrawal of nivolumab, (Opdivo) for a form of metastatic lung cancer.

Then there was a significant gap, with no withdrawals going back to 2013 (when there was one). There were two withdrawals in 2012 and three in 2011.

A version of this article first appeared on Medscape.com.

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry . All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style. For more information, contact [email protected].

Bipolar disorder is a chronic mental disorder, often with onset at a young age. An estimated 4.4% of US adults experience bipolar disorder at some time in their lives.¹ According to the National Comorbidity Survey Replication, the past-year prevalence of bipolar disorder in adults age ≥60 is 0.7%.¹ An estimated 83% of people with bipolar disorder have serious impairment, which is the highest percentage of serious impairment among mood disorders.¹ Bipolar I disorder affects men and women equally, whereas bipolar II disorder seems to occur more frequently in women.² Symptoms of bipolar disorder include episodes of mania, depression, and mixed states.²

A variety of medications—including mood stabilizers, lithium, and antipsychotics (Table 1,^3,4 and Table 2,⁴)—and somatic treatments such as electro­convulsive therapy and transcranial magnetic stimulation are used to manage the depressive and manic/mixed episodes of bipolar disorder. Treatment should be individualized based on the patient’s symptom severity, sensitivity, response to treatment, and preferences.

Continue to: CASE REPORT...

CASE REPORT

Mrs. G, age 65, lives with her husband. She has a history of bipolar disorder, chronic kidney disease, diabetes mellitus type 2, obstructive sleep apnea, hypertension associated with hyperaldosteronism, and obesity, for which she has undergone bariatric surgery. Symptoms of bipolar disorder started when she was in her 30s, following the death of her father. Her initial symptoms included depressed mood, anger, irritability, difficulty sleeping, racing thoughts, and impulsive spending. She did not have any suicidal ideation or homicidal ideation. She did not have anxiety, posttraumatic stress disorder, or obsessive-compulsive disorder symptoms. She was diagnosed with bipolar disorder. For some time, she took perphenazine, 16 mg/d, divalproex sodium, 1,500 mg/d, and temazepam, 30 mg/d at bedtime. These doses were reduced as her mood stabilized. Over time, divalproex sodium was tapered and discontinued, and perphenazine was reduced to 4 mg/d at bedtime. Lithium was tried briefly but discontinued because Mrs. G did not tolerate it well. She has never been hospitalized for mental health issues, but did have one emergency department visit a very long time ago. She has no history of suicide attempts, and there is no family history of completed suicide. There is a family history of bipolar disorder in her mother.

Mrs. G was born and raised outside the United States in a stable, two-parent home. She had no maltreatment during childhood. She has a bachelor’s degree and was employed. She is a social drinker, with no history of treatment for alcohol use disorder.

Mrs. G was stable on perphenazine, 4 mg/d, and temazepam, 30 mg/d, until 5 years ago. In 2016, she became concerned about her weight and overall health, and underwent bariatric surgery (gastric sleeve). After this surgery, Mrs. G experienced changes in mood and thought. She felt paranoid and had ideas of reference, social sensitivity, increased irritability, and poor self-esteem. Perphenazine was discontinued, divalproex was reintroduced, and lurasidone was started. Lurasidone was titrated up to 120 mg/d, and divalproex up to 1,500 mg/d. Temazepam, 30 mg/d at bedtime, was continued for her insomnia. She also occasionally took over-the-counter melatonin, 5 to 10 mg, as needed for insomnia.

Mrs. G improved on this combination, and became stable and euthymic in September 2017. Other than a brief hypomanic episode in Spring 2018 that resolved quickly, she remained euthymic. During routine follow-up visits, Mrs. G’s nephrologist noticed that her sodium levels had been fluctuating. Mrs. G said her nephrologist was not sure exactly what was causing these fluctuations, and she continued to take the same medications.

In June 2018, Mrs. G developed tremors, slowing, and lethargy. Lurasidone was gradually reduced to 60 mg/d and divalproex to 750 mg/d. Temazepam, 30 mg/d at bedtime, was continued. In July 2018, divalproex was further reduced to 500 mg/d because Mrs. G’s free valproic acid levels were elevated. In February 2019, lurasidone was further reduced to 40 mg/d due to blunted affect, and in April 2019, escitalopram, 10 mg/d, was added for symptoms of depression (off-label), and anxiety. In June 2019, Mrs. G’s sodium level was 127 mEq/L (reference range: 135 to 145 mEq/L). Because escitalopram can cause hyponatremia, it was discontinued in August 2019, but Mrs. G continued to take lurasidone, 40 mg/d, divalproex, 500 mg/d, and temazepam, 30 mg/d.

In October and November 2020, Mrs. G’s sodium level remained low at 123 and 127 mEq/L. Our treatment team wondered if lurasidone could be causing Mrs. G’s sodium levels to fall. Lurasidone was tapered over 3 days and discontinued. Repeat blood work showed that Mrs. G’s sodium levels soon returned to normal range. In January through March 2021, her sodium levels were 138, 139, and 136 mEq/L, all of which were within normal range. This confirmed our suspicion that lurasidone had caused the hyponatremia, though briefly it may have been made worse by escitalopram. Currently, Mrs. G is stable on perphenazine, 4 mg twice a day, divalproex, 500 mg/d, temazepam, 30 mg/d at bedtime, and melatonin, 5 mg at bedtime.

Continue to: Syndrome of inappropriate antidiuretic hormone secretion...

Syndrome of inappropriate antidiuretic hormone (SIADH) secretion can result in hyponatremia. Classes of medications that can cause SIADH include antidepressants, antipsychotics, anticonvulsants, cytotoxic agents, and pain medications.⁵ The class of drugs most commonly associated with SIADH is selective serotonin reuptake inhibitors, particularly citalopram.⁵ Among the antipsychotics, risperidone is most associated with hyponatremia. The proposed mechanism of medication-induced SIADH is an increase in the release of ADH.⁶ Treatment options include discontinuing the offending medication(s) or switching to a different medication.

Hyponatremia is a rare adverse effect of lurasidone, with a reported incidence <1%.⁷ Although hyponatremia is potentially life-threatening, there is no recommendation to routinely monitor sodium levels in patients treated with lurasidone or other psychotropics, and patients who are prescribed lurasidone are not routinely monitored for sodium deficiency. Table 3^8,9 outlines risk factors for developing hyponatremia among patients taking psychotropic medications.

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry . All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style. For more information, contact [email protected].

Bipolar disorder is a chronic mental disorder, often with onset at a young age. An estimated 4.4% of US adults experience bipolar disorder at some time in their lives.¹ According to the National Comorbidity Survey Replication, the past-year prevalence of bipolar disorder in adults age ≥60 is 0.7%.¹ An estimated 83% of people with bipolar disorder have serious impairment, which is the highest percentage of serious impairment among mood disorders.¹ Bipolar I disorder affects men and women equally, whereas bipolar II disorder seems to occur more frequently in women.² Symptoms of bipolar disorder include episodes of mania, depression, and mixed states.²

A variety of medications—including mood stabilizers, lithium, and antipsychotics (Table 1,^3,4 and Table 2,⁴)—and somatic treatments such as electro­convulsive therapy and transcranial magnetic stimulation are used to manage the depressive and manic/mixed episodes of bipolar disorder. Treatment should be individualized based on the patient’s symptom severity, sensitivity, response to treatment, and preferences.

Continue to: CASE REPORT...

CASE REPORT

Mrs. G, age 65, lives with her husband. She has a history of bipolar disorder, chronic kidney disease, diabetes mellitus type 2, obstructive sleep apnea, hypertension associated with hyperaldosteronism, and obesity, for which she has undergone bariatric surgery. Symptoms of bipolar disorder started when she was in her 30s, following the death of her father. Her initial symptoms included depressed mood, anger, irritability, difficulty sleeping, racing thoughts, and impulsive spending. She did not have any suicidal ideation or homicidal ideation. She did not have anxiety, posttraumatic stress disorder, or obsessive-compulsive disorder symptoms. She was diagnosed with bipolar disorder. For some time, she took perphenazine, 16 mg/d, divalproex sodium, 1,500 mg/d, and temazepam, 30 mg/d at bedtime. These doses were reduced as her mood stabilized. Over time, divalproex sodium was tapered and discontinued, and perphenazine was reduced to 4 mg/d at bedtime. Lithium was tried briefly but discontinued because Mrs. G did not tolerate it well. She has never been hospitalized for mental health issues, but did have one emergency department visit a very long time ago. She has no history of suicide attempts, and there is no family history of completed suicide. There is a family history of bipolar disorder in her mother.

Mrs. G was born and raised outside the United States in a stable, two-parent home. She had no maltreatment during childhood. She has a bachelor’s degree and was employed. She is a social drinker, with no history of treatment for alcohol use disorder.

Mrs. G was stable on perphenazine, 4 mg/d, and temazepam, 30 mg/d, until 5 years ago. In 2016, she became concerned about her weight and overall health, and underwent bariatric surgery (gastric sleeve). After this surgery, Mrs. G experienced changes in mood and thought. She felt paranoid and had ideas of reference, social sensitivity, increased irritability, and poor self-esteem. Perphenazine was discontinued, divalproex was reintroduced, and lurasidone was started. Lurasidone was titrated up to 120 mg/d, and divalproex up to 1,500 mg/d. Temazepam, 30 mg/d at bedtime, was continued for her insomnia. She also occasionally took over-the-counter melatonin, 5 to 10 mg, as needed for insomnia.

Mrs. G improved on this combination, and became stable and euthymic in September 2017. Other than a brief hypomanic episode in Spring 2018 that resolved quickly, she remained euthymic. During routine follow-up visits, Mrs. G’s nephrologist noticed that her sodium levels had been fluctuating. Mrs. G said her nephrologist was not sure exactly what was causing these fluctuations, and she continued to take the same medications.

In June 2018, Mrs. G developed tremors, slowing, and lethargy. Lurasidone was gradually reduced to 60 mg/d and divalproex to 750 mg/d. Temazepam, 30 mg/d at bedtime, was continued. In July 2018, divalproex was further reduced to 500 mg/d because Mrs. G’s free valproic acid levels were elevated. In February 2019, lurasidone was further reduced to 40 mg/d due to blunted affect, and in April 2019, escitalopram, 10 mg/d, was added for symptoms of depression (off-label), and anxiety. In June 2019, Mrs. G’s sodium level was 127 mEq/L (reference range: 135 to 145 mEq/L). Because escitalopram can cause hyponatremia, it was discontinued in August 2019, but Mrs. G continued to take lurasidone, 40 mg/d, divalproex, 500 mg/d, and temazepam, 30 mg/d.

In October and November 2020, Mrs. G’s sodium level remained low at 123 and 127 mEq/L. Our treatment team wondered if lurasidone could be causing Mrs. G’s sodium levels to fall. Lurasidone was tapered over 3 days and discontinued. Repeat blood work showed that Mrs. G’s sodium levels soon returned to normal range. In January through March 2021, her sodium levels were 138, 139, and 136 mEq/L, all of which were within normal range. This confirmed our suspicion that lurasidone had caused the hyponatremia, though briefly it may have been made worse by escitalopram. Currently, Mrs. G is stable on perphenazine, 4 mg twice a day, divalproex, 500 mg/d, temazepam, 30 mg/d at bedtime, and melatonin, 5 mg at bedtime.

Continue to: Syndrome of inappropriate antidiuretic hormone secretion...

Syndrome of inappropriate antidiuretic hormone (SIADH) secretion can result in hyponatremia. Classes of medications that can cause SIADH include antidepressants, antipsychotics, anticonvulsants, cytotoxic agents, and pain medications.⁵ The class of drugs most commonly associated with SIADH is selective serotonin reuptake inhibitors, particularly citalopram.⁵ Among the antipsychotics, risperidone is most associated with hyponatremia. The proposed mechanism of medication-induced SIADH is an increase in the release of ADH.⁶ Treatment options include discontinuing the offending medication(s) or switching to a different medication.

Hyponatremia is a rare adverse effect of lurasidone, with a reported incidence <1%.⁷ Although hyponatremia is potentially life-threatening, there is no recommendation to routinely monitor sodium levels in patients treated with lurasidone or other psychotropics, and patients who are prescribed lurasidone are not routinely monitored for sodium deficiency. Table 3^8,9 outlines risk factors for developing hyponatremia among patients taking psychotropic medications.

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry . All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style. For more information, contact [email protected].

Bipolar disorder is a chronic mental disorder, often with onset at a young age. An estimated 4.4% of US adults experience bipolar disorder at some time in their lives.¹ According to the National Comorbidity Survey Replication, the past-year prevalence of bipolar disorder in adults age ≥60 is 0.7%.¹ An estimated 83% of people with bipolar disorder have serious impairment, which is the highest percentage of serious impairment among mood disorders.¹ Bipolar I disorder affects men and women equally, whereas bipolar II disorder seems to occur more frequently in women.² Symptoms of bipolar disorder include episodes of mania, depression, and mixed states.²

A variety of medications—including mood stabilizers, lithium, and antipsychotics (Table 1,^3,4 and Table 2,⁴)—and somatic treatments such as electro­convulsive therapy and transcranial magnetic stimulation are used to manage the depressive and manic/mixed episodes of bipolar disorder. Treatment should be individualized based on the patient’s symptom severity, sensitivity, response to treatment, and preferences.

Continue to: CASE REPORT...

CASE REPORT

Mrs. G, age 65, lives with her husband. She has a history of bipolar disorder, chronic kidney disease, diabetes mellitus type 2, obstructive sleep apnea, hypertension associated with hyperaldosteronism, and obesity, for which she has undergone bariatric surgery. Symptoms of bipolar disorder started when she was in her 30s, following the death of her father. Her initial symptoms included depressed mood, anger, irritability, difficulty sleeping, racing thoughts, and impulsive spending. She did not have any suicidal ideation or homicidal ideation. She did not have anxiety, posttraumatic stress disorder, or obsessive-compulsive disorder symptoms. She was diagnosed with bipolar disorder. For some time, she took perphenazine, 16 mg/d, divalproex sodium, 1,500 mg/d, and temazepam, 30 mg/d at bedtime. These doses were reduced as her mood stabilized. Over time, divalproex sodium was tapered and discontinued, and perphenazine was reduced to 4 mg/d at bedtime. Lithium was tried briefly but discontinued because Mrs. G did not tolerate it well. She has never been hospitalized for mental health issues, but did have one emergency department visit a very long time ago. She has no history of suicide attempts, and there is no family history of completed suicide. There is a family history of bipolar disorder in her mother.

Mrs. G was born and raised outside the United States in a stable, two-parent home. She had no maltreatment during childhood. She has a bachelor’s degree and was employed. She is a social drinker, with no history of treatment for alcohol use disorder.

Mrs. G was stable on perphenazine, 4 mg/d, and temazepam, 30 mg/d, until 5 years ago. In 2016, she became concerned about her weight and overall health, and underwent bariatric surgery (gastric sleeve). After this surgery, Mrs. G experienced changes in mood and thought. She felt paranoid and had ideas of reference, social sensitivity, increased irritability, and poor self-esteem. Perphenazine was discontinued, divalproex was reintroduced, and lurasidone was started. Lurasidone was titrated up to 120 mg/d, and divalproex up to 1,500 mg/d. Temazepam, 30 mg/d at bedtime, was continued for her insomnia. She also occasionally took over-the-counter melatonin, 5 to 10 mg, as needed for insomnia.

Mrs. G improved on this combination, and became stable and euthymic in September 2017. Other than a brief hypomanic episode in Spring 2018 that resolved quickly, she remained euthymic. During routine follow-up visits, Mrs. G’s nephrologist noticed that her sodium levels had been fluctuating. Mrs. G said her nephrologist was not sure exactly what was causing these fluctuations, and she continued to take the same medications.

In June 2018, Mrs. G developed tremors, slowing, and lethargy. Lurasidone was gradually reduced to 60 mg/d and divalproex to 750 mg/d. Temazepam, 30 mg/d at bedtime, was continued. In July 2018, divalproex was further reduced to 500 mg/d because Mrs. G’s free valproic acid levels were elevated. In February 2019, lurasidone was further reduced to 40 mg/d due to blunted affect, and in April 2019, escitalopram, 10 mg/d, was added for symptoms of depression (off-label), and anxiety. In June 2019, Mrs. G’s sodium level was 127 mEq/L (reference range: 135 to 145 mEq/L). Because escitalopram can cause hyponatremia, it was discontinued in August 2019, but Mrs. G continued to take lurasidone, 40 mg/d, divalproex, 500 mg/d, and temazepam, 30 mg/d.

In October and November 2020, Mrs. G’s sodium level remained low at 123 and 127 mEq/L. Our treatment team wondered if lurasidone could be causing Mrs. G’s sodium levels to fall. Lurasidone was tapered over 3 days and discontinued. Repeat blood work showed that Mrs. G’s sodium levels soon returned to normal range. In January through March 2021, her sodium levels were 138, 139, and 136 mEq/L, all of which were within normal range. This confirmed our suspicion that lurasidone had caused the hyponatremia, though briefly it may have been made worse by escitalopram. Currently, Mrs. G is stable on perphenazine, 4 mg twice a day, divalproex, 500 mg/d, temazepam, 30 mg/d at bedtime, and melatonin, 5 mg at bedtime.

Continue to: Syndrome of inappropriate antidiuretic hormone secretion...

Syndrome of inappropriate antidiuretic hormone (SIADH) secretion can result in hyponatremia. Classes of medications that can cause SIADH include antidepressants, antipsychotics, anticonvulsants, cytotoxic agents, and pain medications.⁵ The class of drugs most commonly associated with SIADH is selective serotonin reuptake inhibitors, particularly citalopram.⁵ Among the antipsychotics, risperidone is most associated with hyponatremia. The proposed mechanism of medication-induced SIADH is an increase in the release of ADH.⁶ Treatment options include discontinuing the offending medication(s) or switching to a different medication.

Hyponatremia is a rare adverse effect of lurasidone, with a reported incidence <1%.⁷ Although hyponatremia is potentially life-threatening, there is no recommendation to routinely monitor sodium levels in patients treated with lurasidone or other psychotropics, and patients who are prescribed lurasidone are not routinely monitored for sodium deficiency. Table 3^8,9 outlines risk factors for developing hyponatremia among patients taking psychotropic medications.

The antidepressant fluvoxamine (Luvox) may prevent hospitalization and death in outpatients with COVID-19, new research suggests.

HconQ/ThinkStock

Results from the placebo-controlled, multisite, phase 3 TOGETHER trial showed that in COVID-19 outpatients at high risk for complications, hospitalizations were cut by 66% and deaths were reduced by 91% in those who tolerated fluvoxamine.

“Our trial has found that fluvoxamine, an inexpensive existing drug, reduces the need for advanced disease care in this high-risk population,” wrote the investigators, led by Gilmar Reis, MD, PhD, research division, Cardresearch, Belo Horizonte, Brazil.

The findings were published online Oct. 27 in The Lancet Global Health.
 

Alternative mechanisms

Fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), is an antidepressant commonly prescribed for obsessive-compulsive disorder.

Besides its known effects on serotonin, the drug acts in other molecular pathways to dampen the production of inflammatory cytokines. Those alternative mechanisms are the ones believed to help patients with COVID-19, said coinvestigator Angela Reiersen, MD, child psychiatrist at Washington University, St. Louis.

Based on cell culture and mouse studies showing effects of the molecule’s binding to the sigma-1 receptor in the endoplasmic reticulum, Dr. Reiersen came up with the idea of testing if fluvoxamine could keep COVID-19 from progressing in newly infected patients.

Dr. Reiersen and psychiatrist Eric Lenze, MD, also from Washington University, led the phase 2 trial that initially suggested fluvoxamine’s promise as an outpatient medication. They are coinvestigators on the new phase 3 adaptive platform trial called TOGETHER, which was conducted by an international team of investigators in Brazil, Canada, and the United States.

For this latest study, researchers at McMaster University, Hamilton, Ont., partnered with the research clinic Cardresearch in Brazil to recruit unvaccinated, high-risk adults within 7 days of developing flu-like symptoms from COVID-19. They analyzed 1,497 newly symptomatic COVID-19 patients at 11 clinical sites in Brazil.

Patients entered the trial between January and August 2021 and were assigned to receive 100 mg fluvoxamine or placebo pills twice a day for 10 days. Investigators monitored participants through 28 days post treatment, noting whether complications developed requiring hospitalization or more than 6 hours of emergency care.

In the placebo group, 119 of 756 patients (15.7%) worsened to this extent. In comparison, 79 of 741 (10.7%) fluvoxamine-treated patients met these primary criteria. This represented a 32% reduction in hospitalizations and emergency visits.
 

Additional analysis requested

As Lancet Global Health reviewed these findings from the submitted manuscript, journal reviewers requested an additional “pre-protocol analysis” that was not specified in the trial’s original protocol. The request was to examine the subgroup of patients with good adherence (74% of treated group, 82% of placebo group).

Among these three quarters of patients who took at least 80% of their doses, benefits were better.

Fluvoxamine cut serious complications in this group by 66% and reduced mortality by 91%. In the placebo group, 12 people died compared with one who received the study drug.

Based on accumulating data, Dr. Reiersen said, some experts are recommending fluvoxamine for COVID-19 patients at high risk for morbidity and mortality from complications of the infection.

However, clinicians should note that the drug can cause side effects such as nausea, dizziness, and insomnia, she added. In addition, because it prevents the body from metabolizing caffeine, patients should limit their daily intake to half of a small cup of coffee or one can of soda or one tea while taking the drug.

Previous research has shown that fluvoxamine affects the metabolism of some drugs, such as theophylline, clozapine, olanzapine, and tizanidine.

Despite huge challenges with studying generic drugs as early COVID-19 treatment, the TOGETHER trial shows it is possible to produce quality evidence during a pandemic on a shoestring budget, noted co-principal investigator Edward Mills, PhD, professor in the department of health research methods, evidence, and impact at McMaster University.

To screen more than 12,000 patients and enroll 4,000 to test nine interventions, “our total budget was less than $8 million,” Dr. Mills said. The trial was funded by Fast Grants and the Rainwater Charitable Foundation.
 

‘A $10 medicine’

Commenting on the findings, David Boulware, MD, MPH, an infectious disease physician-researcher at the University of Minnesota in Minneapolis, noted fluvoxamine is “a $10 medicine that’s available and has a very good safety record.”

By comparison, a 5-day course of Merck’s antiviral molnupiravir, another oral drug that the company says can cut hospitalizations in COVID-19 outpatients, costs $700. However, the data have not been peer reviewed – and molnupiravir is not currently available and has unknown long-term safety implications, Dr. Boulware said.

Pharmaceutical companies typically spend tens of thousands of dollars on a trial evaluating a single drug, he noted.

In addition, the National Institutes of Health’s ACTIV-6 study, a nationwide trial on the effect of fluvoxamine and other repurposed generic drugs on thousands of COVID-19 outpatients, is a $110 million effort, according to Dr. Boulware, who cochairs its steering committee.

ACTIV-6 is currently enrolling outpatients with COVID-19 to test a lower dose of fluvoxamine, at 50 mg twice daily instead of the 100-mg dose used in the TOGETHER trial, as well as ivermectin and inhaled fluticasone. The COVID-OUT trial is also recruiting newly diagnosed COVID-19 patients to test various combinations of fluvoxamine, ivermectin, and the diabetes drug metformin.

Unanswered safety, efficacy questions

In an accompanying editorial in The Lancet Global Health, Otavio Berwanger, MD, cardiologist and clinical trialist, Academic Research Organization, Hospital Israelita Albert Einstein, São Paulo, Brazil, commends the investigators for rapidly generating evidence during the COVID-19 pandemic.

However, despite the important findings, “some questions related to efficacy and safety of fluvoxamine for patients with COVID-19 remain open,” Dr. Berwanger wrote.

The effects of the drug on reducing both mortality and hospitalizations also “still need addressing,” he noted.

“In addition, it remains to be established whether fluvoxamine has an additive effect to other therapies such as monoclonal antibodies and budesonide, and what is the optimal fluvoxamine therapeutic scheme,” wrote Dr. Berwanger.

In an interview, he noted that 74% of the Brazil population have currently received at least one dose of a COVID-19 vaccine and 52% have received two doses. In addition, deaths have gone down from 4,000 per day during the March-April second wave to about 400 per day. “That is still unfortunate and far from ideal,” he said. In total, they have had about 600,000 deaths because of COVID-19.

Asked whether public health authorities are now recommending fluvoxamine as an early treatment for COVID-19 based on the TOGETHER trial data, Dr. Berwanger answered, “Not yet.

“I believe medical and scientific societies will need to critically appraise the manuscript in order to inform their decisions and recommendations. This interesting trial adds another important piece of information in this regard,” he said.

Dr. Reiersen and Dr. Lenze are inventors on a patent application related to methods for treating COVID-19, which was filed by Washington University. Dr. Mills reports no relevant financial relationships, as does Dr. Boulware – except that the TOGETHER trial funders are also funding the University of Minnesota COVID-OUT trial. Dr. Berwanger reports having received research grants outside of the submitted work that were paid to his institution by AstraZeneca, Bayer, Amgen, Servier, Novartis, Pfizer, and Boehringer Ingelheim.

A version of this article first appeared on Medscape.com.

The antidepressant fluvoxamine (Luvox) may prevent hospitalization and death in outpatients with COVID-19, new research suggests.

HconQ/ThinkStock

Results from the placebo-controlled, multisite, phase 3 TOGETHER trial showed that in COVID-19 outpatients at high risk for complications, hospitalizations were cut by 66% and deaths were reduced by 91% in those who tolerated fluvoxamine.

“Our trial has found that fluvoxamine, an inexpensive existing drug, reduces the need for advanced disease care in this high-risk population,” wrote the investigators, led by Gilmar Reis, MD, PhD, research division, Cardresearch, Belo Horizonte, Brazil.

The findings were published online Oct. 27 in The Lancet Global Health.
 

Alternative mechanisms

Fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), is an antidepressant commonly prescribed for obsessive-compulsive disorder.

Besides its known effects on serotonin, the drug acts in other molecular pathways to dampen the production of inflammatory cytokines. Those alternative mechanisms are the ones believed to help patients with COVID-19, said coinvestigator Angela Reiersen, MD, child psychiatrist at Washington University, St. Louis.

Based on cell culture and mouse studies showing effects of the molecule’s binding to the sigma-1 receptor in the endoplasmic reticulum, Dr. Reiersen came up with the idea of testing if fluvoxamine could keep COVID-19 from progressing in newly infected patients.

Dr. Reiersen and psychiatrist Eric Lenze, MD, also from Washington University, led the phase 2 trial that initially suggested fluvoxamine’s promise as an outpatient medication. They are coinvestigators on the new phase 3 adaptive platform trial called TOGETHER, which was conducted by an international team of investigators in Brazil, Canada, and the United States.

For this latest study, researchers at McMaster University, Hamilton, Ont., partnered with the research clinic Cardresearch in Brazil to recruit unvaccinated, high-risk adults within 7 days of developing flu-like symptoms from COVID-19. They analyzed 1,497 newly symptomatic COVID-19 patients at 11 clinical sites in Brazil.

Patients entered the trial between January and August 2021 and were assigned to receive 100 mg fluvoxamine or placebo pills twice a day for 10 days. Investigators monitored participants through 28 days post treatment, noting whether complications developed requiring hospitalization or more than 6 hours of emergency care.

In the placebo group, 119 of 756 patients (15.7%) worsened to this extent. In comparison, 79 of 741 (10.7%) fluvoxamine-treated patients met these primary criteria. This represented a 32% reduction in hospitalizations and emergency visits.
 

Additional analysis requested

As Lancet Global Health reviewed these findings from the submitted manuscript, journal reviewers requested an additional “pre-protocol analysis” that was not specified in the trial’s original protocol. The request was to examine the subgroup of patients with good adherence (74% of treated group, 82% of placebo group).

Among these three quarters of patients who took at least 80% of their doses, benefits were better.

Fluvoxamine cut serious complications in this group by 66% and reduced mortality by 91%. In the placebo group, 12 people died compared with one who received the study drug.

Based on accumulating data, Dr. Reiersen said, some experts are recommending fluvoxamine for COVID-19 patients at high risk for morbidity and mortality from complications of the infection.

However, clinicians should note that the drug can cause side effects such as nausea, dizziness, and insomnia, she added. In addition, because it prevents the body from metabolizing caffeine, patients should limit their daily intake to half of a small cup of coffee or one can of soda or one tea while taking the drug.

Previous research has shown that fluvoxamine affects the metabolism of some drugs, such as theophylline, clozapine, olanzapine, and tizanidine.

Despite huge challenges with studying generic drugs as early COVID-19 treatment, the TOGETHER trial shows it is possible to produce quality evidence during a pandemic on a shoestring budget, noted co-principal investigator Edward Mills, PhD, professor in the department of health research methods, evidence, and impact at McMaster University.

To screen more than 12,000 patients and enroll 4,000 to test nine interventions, “our total budget was less than $8 million,” Dr. Mills said. The trial was funded by Fast Grants and the Rainwater Charitable Foundation.
 

‘A $10 medicine’

Commenting on the findings, David Boulware, MD, MPH, an infectious disease physician-researcher at the University of Minnesota in Minneapolis, noted fluvoxamine is “a $10 medicine that’s available and has a very good safety record.”

By comparison, a 5-day course of Merck’s antiviral molnupiravir, another oral drug that the company says can cut hospitalizations in COVID-19 outpatients, costs $700. However, the data have not been peer reviewed – and molnupiravir is not currently available and has unknown long-term safety implications, Dr. Boulware said.

Pharmaceutical companies typically spend tens of thousands of dollars on a trial evaluating a single drug, he noted.

In addition, the National Institutes of Health’s ACTIV-6 study, a nationwide trial on the effect of fluvoxamine and other repurposed generic drugs on thousands of COVID-19 outpatients, is a $110 million effort, according to Dr. Boulware, who cochairs its steering committee.

ACTIV-6 is currently enrolling outpatients with COVID-19 to test a lower dose of fluvoxamine, at 50 mg twice daily instead of the 100-mg dose used in the TOGETHER trial, as well as ivermectin and inhaled fluticasone. The COVID-OUT trial is also recruiting newly diagnosed COVID-19 patients to test various combinations of fluvoxamine, ivermectin, and the diabetes drug metformin.

Unanswered safety, efficacy questions

In an accompanying editorial in The Lancet Global Health, Otavio Berwanger, MD, cardiologist and clinical trialist, Academic Research Organization, Hospital Israelita Albert Einstein, São Paulo, Brazil, commends the investigators for rapidly generating evidence during the COVID-19 pandemic.

However, despite the important findings, “some questions related to efficacy and safety of fluvoxamine for patients with COVID-19 remain open,” Dr. Berwanger wrote.

The effects of the drug on reducing both mortality and hospitalizations also “still need addressing,” he noted.

“In addition, it remains to be established whether fluvoxamine has an additive effect to other therapies such as monoclonal antibodies and budesonide, and what is the optimal fluvoxamine therapeutic scheme,” wrote Dr. Berwanger.

In an interview, he noted that 74% of the Brazil population have currently received at least one dose of a COVID-19 vaccine and 52% have received two doses. In addition, deaths have gone down from 4,000 per day during the March-April second wave to about 400 per day. “That is still unfortunate and far from ideal,” he said. In total, they have had about 600,000 deaths because of COVID-19.

Asked whether public health authorities are now recommending fluvoxamine as an early treatment for COVID-19 based on the TOGETHER trial data, Dr. Berwanger answered, “Not yet.

“I believe medical and scientific societies will need to critically appraise the manuscript in order to inform their decisions and recommendations. This interesting trial adds another important piece of information in this regard,” he said.

Dr. Reiersen and Dr. Lenze are inventors on a patent application related to methods for treating COVID-19, which was filed by Washington University. Dr. Mills reports no relevant financial relationships, as does Dr. Boulware – except that the TOGETHER trial funders are also funding the University of Minnesota COVID-OUT trial. Dr. Berwanger reports having received research grants outside of the submitted work that were paid to his institution by AstraZeneca, Bayer, Amgen, Servier, Novartis, Pfizer, and Boehringer Ingelheim.

A version of this article first appeared on Medscape.com.

The antidepressant fluvoxamine (Luvox) may prevent hospitalization and death in outpatients with COVID-19, new research suggests.

HconQ/ThinkStock

Results from the placebo-controlled, multisite, phase 3 TOGETHER trial showed that in COVID-19 outpatients at high risk for complications, hospitalizations were cut by 66% and deaths were reduced by 91% in those who tolerated fluvoxamine.

“Our trial has found that fluvoxamine, an inexpensive existing drug, reduces the need for advanced disease care in this high-risk population,” wrote the investigators, led by Gilmar Reis, MD, PhD, research division, Cardresearch, Belo Horizonte, Brazil.

The findings were published online Oct. 27 in The Lancet Global Health.
 

Alternative mechanisms

Fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), is an antidepressant commonly prescribed for obsessive-compulsive disorder.

Besides its known effects on serotonin, the drug acts in other molecular pathways to dampen the production of inflammatory cytokines. Those alternative mechanisms are the ones believed to help patients with COVID-19, said coinvestigator Angela Reiersen, MD, child psychiatrist at Washington University, St. Louis.

Based on cell culture and mouse studies showing effects of the molecule’s binding to the sigma-1 receptor in the endoplasmic reticulum, Dr. Reiersen came up with the idea of testing if fluvoxamine could keep COVID-19 from progressing in newly infected patients.

Dr. Reiersen and psychiatrist Eric Lenze, MD, also from Washington University, led the phase 2 trial that initially suggested fluvoxamine’s promise as an outpatient medication. They are coinvestigators on the new phase 3 adaptive platform trial called TOGETHER, which was conducted by an international team of investigators in Brazil, Canada, and the United States.

For this latest study, researchers at McMaster University, Hamilton, Ont., partnered with the research clinic Cardresearch in Brazil to recruit unvaccinated, high-risk adults within 7 days of developing flu-like symptoms from COVID-19. They analyzed 1,497 newly symptomatic COVID-19 patients at 11 clinical sites in Brazil.

Patients entered the trial between January and August 2021 and were assigned to receive 100 mg fluvoxamine or placebo pills twice a day for 10 days. Investigators monitored participants through 28 days post treatment, noting whether complications developed requiring hospitalization or more than 6 hours of emergency care.

In the placebo group, 119 of 756 patients (15.7%) worsened to this extent. In comparison, 79 of 741 (10.7%) fluvoxamine-treated patients met these primary criteria. This represented a 32% reduction in hospitalizations and emergency visits.
 

Additional analysis requested

As Lancet Global Health reviewed these findings from the submitted manuscript, journal reviewers requested an additional “pre-protocol analysis” that was not specified in the trial’s original protocol. The request was to examine the subgroup of patients with good adherence (74% of treated group, 82% of placebo group).

Among these three quarters of patients who took at least 80% of their doses, benefits were better.

Fluvoxamine cut serious complications in this group by 66% and reduced mortality by 91%. In the placebo group, 12 people died compared with one who received the study drug.

Based on accumulating data, Dr. Reiersen said, some experts are recommending fluvoxamine for COVID-19 patients at high risk for morbidity and mortality from complications of the infection.

However, clinicians should note that the drug can cause side effects such as nausea, dizziness, and insomnia, she added. In addition, because it prevents the body from metabolizing caffeine, patients should limit their daily intake to half of a small cup of coffee or one can of soda or one tea while taking the drug.

Previous research has shown that fluvoxamine affects the metabolism of some drugs, such as theophylline, clozapine, olanzapine, and tizanidine.

Despite huge challenges with studying generic drugs as early COVID-19 treatment, the TOGETHER trial shows it is possible to produce quality evidence during a pandemic on a shoestring budget, noted co-principal investigator Edward Mills, PhD, professor in the department of health research methods, evidence, and impact at McMaster University.

To screen more than 12,000 patients and enroll 4,000 to test nine interventions, “our total budget was less than $8 million,” Dr. Mills said. The trial was funded by Fast Grants and the Rainwater Charitable Foundation.
 

‘A $10 medicine’

Commenting on the findings, David Boulware, MD, MPH, an infectious disease physician-researcher at the University of Minnesota in Minneapolis, noted fluvoxamine is “a $10 medicine that’s available and has a very good safety record.”

By comparison, a 5-day course of Merck’s antiviral molnupiravir, another oral drug that the company says can cut hospitalizations in COVID-19 outpatients, costs $700. However, the data have not been peer reviewed – and molnupiravir is not currently available and has unknown long-term safety implications, Dr. Boulware said.

Pharmaceutical companies typically spend tens of thousands of dollars on a trial evaluating a single drug, he noted.

In addition, the National Institutes of Health’s ACTIV-6 study, a nationwide trial on the effect of fluvoxamine and other repurposed generic drugs on thousands of COVID-19 outpatients, is a $110 million effort, according to Dr. Boulware, who cochairs its steering committee.

ACTIV-6 is currently enrolling outpatients with COVID-19 to test a lower dose of fluvoxamine, at 50 mg twice daily instead of the 100-mg dose used in the TOGETHER trial, as well as ivermectin and inhaled fluticasone. The COVID-OUT trial is also recruiting newly diagnosed COVID-19 patients to test various combinations of fluvoxamine, ivermectin, and the diabetes drug metformin.

Unanswered safety, efficacy questions

In an accompanying editorial in The Lancet Global Health, Otavio Berwanger, MD, cardiologist and clinical trialist, Academic Research Organization, Hospital Israelita Albert Einstein, São Paulo, Brazil, commends the investigators for rapidly generating evidence during the COVID-19 pandemic.

However, despite the important findings, “some questions related to efficacy and safety of fluvoxamine for patients with COVID-19 remain open,” Dr. Berwanger wrote.

The effects of the drug on reducing both mortality and hospitalizations also “still need addressing,” he noted.

“In addition, it remains to be established whether fluvoxamine has an additive effect to other therapies such as monoclonal antibodies and budesonide, and what is the optimal fluvoxamine therapeutic scheme,” wrote Dr. Berwanger.

In an interview, he noted that 74% of the Brazil population have currently received at least one dose of a COVID-19 vaccine and 52% have received two doses. In addition, deaths have gone down from 4,000 per day during the March-April second wave to about 400 per day. “That is still unfortunate and far from ideal,” he said. In total, they have had about 600,000 deaths because of COVID-19.

Asked whether public health authorities are now recommending fluvoxamine as an early treatment for COVID-19 based on the TOGETHER trial data, Dr. Berwanger answered, “Not yet.

“I believe medical and scientific societies will need to critically appraise the manuscript in order to inform their decisions and recommendations. This interesting trial adds another important piece of information in this regard,” he said.

Dr. Reiersen and Dr. Lenze are inventors on a patent application related to methods for treating COVID-19, which was filed by Washington University. Dr. Mills reports no relevant financial relationships, as does Dr. Boulware – except that the TOGETHER trial funders are also funding the University of Minnesota COVID-OUT trial. Dr. Berwanger reports having received research grants outside of the submitted work that were paid to his institution by AstraZeneca, Bayer, Amgen, Servier, Novartis, Pfizer, and Boehringer Ingelheim.

A version of this article first appeared on Medscape.com.

LAS VEGAS – An oral Janus kinase 1 inhibitor upadacitinib (Rinvoq, AbbVie) showed high efficacy and good safety as a treatment for ulcerative colitis in a phase 3 trial.

The finding could provide some reassurance after the Food and Drug Administration recently warned of an increased risk of cancer and heart disease associated with medications in the same class as upadacitinib.

“Serious adverse events were numerically lower in patients on upadacitinib, and discontinuations from the study due to adverse events were also lower” than in patients taking a placebo, said Edward Loftus, MD, a gastroenterologist at the Mayo Clinic in Rochester, Minn.

Dr. Loftus presented the findings from the U-ACCOMPLISH study at the annual meeting of the American College of Gastroenterology.

Although other medications are approved for the treatment of ulcerative colitis, including biologics, many patients do not respond. In 2019, tofacitinib (Xeljanz) became the first JAK inhibitor approved for this condition. It works by blocking the JAK1 and JAK3 inflammation pathways, and at high concentrations, it also blocks the tyrosine kinase 2 and JAK2 pathways.

However, adverse events seen in clinical trials of tofacitinib include pneumonia, herpes zoster, anal abscess, and Clostridioides difficile infections. And, as reported by this news organization in September, the FDA required its manufacturer, Pfizer, to add a boxed warning that includes information about the risks of stroke, cancer, blood clots, and death.

Upadacitinib may be more selective and reversible because it preferentially blocks JAK1 or JAK1/3. In August 2019, it received FDA approval at a dose of 15 mg for adult patients with moderately to severely active RA who have had an inadequate response or intolerance to methotrexate.

But the FDA applied the same warnings to upadacitinib – and to a third related drug, baricitinib (Olumiant) – that it required for tofacitinib, even though they are not as well studied.

The FDA also limited approved uses of these three medications to patients who have not responded well to tumor necrosis factor blockers to ensure their benefits outweigh their risks.
 

A well-tolerated treatment

U-ACCOMPLISH is one of two phase 3 trials induction trials completed on upadacitinib.

Investigators randomized 522 people with moderately to severely active ulcerative colitis, defined as Adapted Mayo Score 5-9 with a centrally read endoscopic score of 2-3. Of those patients, the intent to treat population included 341 in the upadacitinib group (45 mg once daily) and 174 in the placebo group.

The baseline demographics and disease characteristics were similar between groups. More than two-thirds of patients in both groups were White, and more than two-thirds were men. In the upadacitinib group, 50.7% had responded inadequately to biologic treatments, compared with 51.1% in the placebo group.

After 8 weeks, a significantly higher proportion of patients receiving upadacitinib achieved clinical remission as defined by the adapted Mayo Score (stool frequency subscore ≤1 and not greater than baseline, rectal bleeding subscore of 0, and Mayo endoscopic subscore ≤1).

“In terms of the efficacy, I think it’s very, very promising,” said Derrick Eichele, MD, an assistant professor of gastroenterology-hepatology at the University of Nebraska Medical Center in Omaha, who was not involved in the trial.

The efficacy data were similar to those reported for tofacitinib in clinical trials, he said in an interview. “But I think again, what we’re waiting to see is how is this going to be positioned in relation to tofacitinib in terms of safety profile.”

More patients in the upadacitinib group reported adverse events, including those deemed related to the drug. However, the proportion that were severe, serious, or led to discontinuation was higher in the placebo group. No one in the study died, and no one in the upadacitinib group had an adjudicated major adverse cardiovascular event, tuberculosis, or malignancy.

The most common adverse events were acne, blood creatine phosphokinase elevation, and anemia, which were all more common in the upadacitinib group, and headache and worsening of ulcerative colitis, which were more common in the placebo group.

Among adverse events of special interest, anemia, neutropenia, hepatic disorder, lymphopenia, serious infection, and opportunistic infection were more common in the upadacitinib group than in the placebo group. The four opportunistic infections in the upadacitinib group included two cases of herpes zoster.

In reviewing the poster presented at this meeting, the cases of neutropenia and hepatic disorder in the upadacitinib group stood out for Dr. Eichele. But he said it’s hard to pass judgment based on this amount of data. He is looking forward to a peer-reviewed publication. “I’ll be interested to see what it shows in terms of the details.”

Phase 3 trials of upadacitinib are underway in atopic dermatitis, RA, psoriatic arthritis, axial spondyloarthritis, Crohn’s disease, giant cell arteritis, and Takayasu arteritis as well as ulcerative colitis.

In a 52-week maintenance trial, according to a press release, malignancies (excluding nonmelanoma skin cancer) included one event among 148 people taking a 15-mg dose of upadacitinib 15, two events among 154 people taking a 30-mg dose of upadacitinib, and one event among 149 people in the placebo group.

Two cases of pulmonary embolism were reported in the 15-mg group and two cases of deep vein thrombosis were reported in the 30-mg group, compared with one event of ovarian vein thrombosis in the placebo group. One adjudicated major cardiovascular event each were reported in the upadacitinib 30-mg group and the placebo group. No one died.

The study was funded by AbbVie. Dr. Loftus reported that he is a consultant for AbbVie as well as multiple other gastroenterology drug companies. Dr. Eichele disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

LAS VEGAS – An oral Janus kinase 1 inhibitor upadacitinib (Rinvoq, AbbVie) showed high efficacy and good safety as a treatment for ulcerative colitis in a phase 3 trial.

The finding could provide some reassurance after the Food and Drug Administration recently warned of an increased risk of cancer and heart disease associated with medications in the same class as upadacitinib.

“Serious adverse events were numerically lower in patients on upadacitinib, and discontinuations from the study due to adverse events were also lower” than in patients taking a placebo, said Edward Loftus, MD, a gastroenterologist at the Mayo Clinic in Rochester, Minn.

Dr. Loftus presented the findings from the U-ACCOMPLISH study at the annual meeting of the American College of Gastroenterology.

Although other medications are approved for the treatment of ulcerative colitis, including biologics, many patients do not respond. In 2019, tofacitinib (Xeljanz) became the first JAK inhibitor approved for this condition. It works by blocking the JAK1 and JAK3 inflammation pathways, and at high concentrations, it also blocks the tyrosine kinase 2 and JAK2 pathways.

However, adverse events seen in clinical trials of tofacitinib include pneumonia, herpes zoster, anal abscess, and Clostridioides difficile infections. And, as reported by this news organization in September, the FDA required its manufacturer, Pfizer, to add a boxed warning that includes information about the risks of stroke, cancer, blood clots, and death.

Upadacitinib may be more selective and reversible because it preferentially blocks JAK1 or JAK1/3. In August 2019, it received FDA approval at a dose of 15 mg for adult patients with moderately to severely active RA who have had an inadequate response or intolerance to methotrexate.

But the FDA applied the same warnings to upadacitinib – and to a third related drug, baricitinib (Olumiant) – that it required for tofacitinib, even though they are not as well studied.

The FDA also limited approved uses of these three medications to patients who have not responded well to tumor necrosis factor blockers to ensure their benefits outweigh their risks.
 

A well-tolerated treatment

U-ACCOMPLISH is one of two phase 3 trials induction trials completed on upadacitinib.

Investigators randomized 522 people with moderately to severely active ulcerative colitis, defined as Adapted Mayo Score 5-9 with a centrally read endoscopic score of 2-3. Of those patients, the intent to treat population included 341 in the upadacitinib group (45 mg once daily) and 174 in the placebo group.

The baseline demographics and disease characteristics were similar between groups. More than two-thirds of patients in both groups were White, and more than two-thirds were men. In the upadacitinib group, 50.7% had responded inadequately to biologic treatments, compared with 51.1% in the placebo group.

After 8 weeks, a significantly higher proportion of patients receiving upadacitinib achieved clinical remission as defined by the adapted Mayo Score (stool frequency subscore ≤1 and not greater than baseline, rectal bleeding subscore of 0, and Mayo endoscopic subscore ≤1).

“In terms of the efficacy, I think it’s very, very promising,” said Derrick Eichele, MD, an assistant professor of gastroenterology-hepatology at the University of Nebraska Medical Center in Omaha, who was not involved in the trial.

The efficacy data were similar to those reported for tofacitinib in clinical trials, he said in an interview. “But I think again, what we’re waiting to see is how is this going to be positioned in relation to tofacitinib in terms of safety profile.”

More patients in the upadacitinib group reported adverse events, including those deemed related to the drug. However, the proportion that were severe, serious, or led to discontinuation was higher in the placebo group. No one in the study died, and no one in the upadacitinib group had an adjudicated major adverse cardiovascular event, tuberculosis, or malignancy.

The most common adverse events were acne, blood creatine phosphokinase elevation, and anemia, which were all more common in the upadacitinib group, and headache and worsening of ulcerative colitis, which were more common in the placebo group.

Among adverse events of special interest, anemia, neutropenia, hepatic disorder, lymphopenia, serious infection, and opportunistic infection were more common in the upadacitinib group than in the placebo group. The four opportunistic infections in the upadacitinib group included two cases of herpes zoster.

In reviewing the poster presented at this meeting, the cases of neutropenia and hepatic disorder in the upadacitinib group stood out for Dr. Eichele. But he said it’s hard to pass judgment based on this amount of data. He is looking forward to a peer-reviewed publication. “I’ll be interested to see what it shows in terms of the details.”

Phase 3 trials of upadacitinib are underway in atopic dermatitis, RA, psoriatic arthritis, axial spondyloarthritis, Crohn’s disease, giant cell arteritis, and Takayasu arteritis as well as ulcerative colitis.

In a 52-week maintenance trial, according to a press release, malignancies (excluding nonmelanoma skin cancer) included one event among 148 people taking a 15-mg dose of upadacitinib 15, two events among 154 people taking a 30-mg dose of upadacitinib, and one event among 149 people in the placebo group.

Two cases of pulmonary embolism were reported in the 15-mg group and two cases of deep vein thrombosis were reported in the 30-mg group, compared with one event of ovarian vein thrombosis in the placebo group. One adjudicated major cardiovascular event each were reported in the upadacitinib 30-mg group and the placebo group. No one died.

The study was funded by AbbVie. Dr. Loftus reported that he is a consultant for AbbVie as well as multiple other gastroenterology drug companies. Dr. Eichele disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

LAS VEGAS – An oral Janus kinase 1 inhibitor upadacitinib (Rinvoq, AbbVie) showed high efficacy and good safety as a treatment for ulcerative colitis in a phase 3 trial.

The finding could provide some reassurance after the Food and Drug Administration recently warned of an increased risk of cancer and heart disease associated with medications in the same class as upadacitinib.

“Serious adverse events were numerically lower in patients on upadacitinib, and discontinuations from the study due to adverse events were also lower” than in patients taking a placebo, said Edward Loftus, MD, a gastroenterologist at the Mayo Clinic in Rochester, Minn.

Dr. Loftus presented the findings from the U-ACCOMPLISH study at the annual meeting of the American College of Gastroenterology.

Although other medications are approved for the treatment of ulcerative colitis, including biologics, many patients do not respond. In 2019, tofacitinib (Xeljanz) became the first JAK inhibitor approved for this condition. It works by blocking the JAK1 and JAK3 inflammation pathways, and at high concentrations, it also blocks the tyrosine kinase 2 and JAK2 pathways.

However, adverse events seen in clinical trials of tofacitinib include pneumonia, herpes zoster, anal abscess, and Clostridioides difficile infections. And, as reported by this news organization in September, the FDA required its manufacturer, Pfizer, to add a boxed warning that includes information about the risks of stroke, cancer, blood clots, and death.

Upadacitinib may be more selective and reversible because it preferentially blocks JAK1 or JAK1/3. In August 2019, it received FDA approval at a dose of 15 mg for adult patients with moderately to severely active RA who have had an inadequate response or intolerance to methotrexate.

But the FDA applied the same warnings to upadacitinib – and to a third related drug, baricitinib (Olumiant) – that it required for tofacitinib, even though they are not as well studied.

The FDA also limited approved uses of these three medications to patients who have not responded well to tumor necrosis factor blockers to ensure their benefits outweigh their risks.
 

A well-tolerated treatment

U-ACCOMPLISH is one of two phase 3 trials induction trials completed on upadacitinib.

Investigators randomized 522 people with moderately to severely active ulcerative colitis, defined as Adapted Mayo Score 5-9 with a centrally read endoscopic score of 2-3. Of those patients, the intent to treat population included 341 in the upadacitinib group (45 mg once daily) and 174 in the placebo group.

The baseline demographics and disease characteristics were similar between groups. More than two-thirds of patients in both groups were White, and more than two-thirds were men. In the upadacitinib group, 50.7% had responded inadequately to biologic treatments, compared with 51.1% in the placebo group.

After 8 weeks, a significantly higher proportion of patients receiving upadacitinib achieved clinical remission as defined by the adapted Mayo Score (stool frequency subscore ≤1 and not greater than baseline, rectal bleeding subscore of 0, and Mayo endoscopic subscore ≤1).

“In terms of the efficacy, I think it’s very, very promising,” said Derrick Eichele, MD, an assistant professor of gastroenterology-hepatology at the University of Nebraska Medical Center in Omaha, who was not involved in the trial.

The efficacy data were similar to those reported for tofacitinib in clinical trials, he said in an interview. “But I think again, what we’re waiting to see is how is this going to be positioned in relation to tofacitinib in terms of safety profile.”

More patients in the upadacitinib group reported adverse events, including those deemed related to the drug. However, the proportion that were severe, serious, or led to discontinuation was higher in the placebo group. No one in the study died, and no one in the upadacitinib group had an adjudicated major adverse cardiovascular event, tuberculosis, or malignancy.

The most common adverse events were acne, blood creatine phosphokinase elevation, and anemia, which were all more common in the upadacitinib group, and headache and worsening of ulcerative colitis, which were more common in the placebo group.

Among adverse events of special interest, anemia, neutropenia, hepatic disorder, lymphopenia, serious infection, and opportunistic infection were more common in the upadacitinib group than in the placebo group. The four opportunistic infections in the upadacitinib group included two cases of herpes zoster.

In reviewing the poster presented at this meeting, the cases of neutropenia and hepatic disorder in the upadacitinib group stood out for Dr. Eichele. But he said it’s hard to pass judgment based on this amount of data. He is looking forward to a peer-reviewed publication. “I’ll be interested to see what it shows in terms of the details.”

Phase 3 trials of upadacitinib are underway in atopic dermatitis, RA, psoriatic arthritis, axial spondyloarthritis, Crohn’s disease, giant cell arteritis, and Takayasu arteritis as well as ulcerative colitis.

In a 52-week maintenance trial, according to a press release, malignancies (excluding nonmelanoma skin cancer) included one event among 148 people taking a 15-mg dose of upadacitinib 15, two events among 154 people taking a 30-mg dose of upadacitinib, and one event among 149 people in the placebo group.

Two cases of pulmonary embolism were reported in the 15-mg group and two cases of deep vein thrombosis were reported in the 30-mg group, compared with one event of ovarian vein thrombosis in the placebo group. One adjudicated major cardiovascular event each were reported in the upadacitinib 30-mg group and the placebo group. No one died.

The study was funded by AbbVie. Dr. Loftus reported that he is a consultant for AbbVie as well as multiple other gastroenterology drug companies. Dr. Eichele disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A number of fatal child poisonings have been linked to common cough and cold medications, according to a report.

The Pediatric Cough and Cold Safety Surveillance System, which tracks fatal child poisonings, has identified 40 such deaths in recent years and raised particular concern about medications containing diphenhydramine, a common antihistamine that can be sedating.

“There is little evidence that cough and cold medicines make children feel better or reduce their symptoms, but there is evidence they can suffer harm,” says Kevin Osterhoudt, MD, medical director of the Poison Control Center at the Children’s Hospital of Philadelphia.

In recent years, the FDA has advised labeling changes and recommended that cough and cold medications not be given to children younger than 2. Drugmakers also voluntarily relabeled these products to state “do not use in children under 4 years of age.”

Compared to older children or adults, young children have a different physiology when they breathe, so any product containing antihistamines can be a danger to little kids, Dr. Osterhoudt says.

But a recent survey shows about half of American parents gave their child cough and cold medication the last time they were ill, Dr. Osterhoudt says. And the findings suggest that cough and cold medications are in homes where children might find them.

Using the new evidence from the national surveillance system, investigators set up an expert panel to review the results. They found that most of the deaths were in children under the age of 2. The results were reported in the October issue of Pediatrics.

In seven instances, death followed the intentional use of medication to sedate the child, reports lead investigator Laurie Seidel Halmo, MD, from Children’s Hospital Colorado, Aurora.

“It’s not uncommon for parents to use sedatives like diphenhydramine to make their child sleepy for activities like air travel,” Dr. Osterhoudt says.

While antihistamines can be sedating, “an overdose of antihistamines like diphenhydramine can paradoxically become a stimulant,” having the opposite effect, he explains.

Adults and teens who take overdoses will sometimes become delirious, hallucinate, and have a racing heart.

But in young children, “if not careful with your dosing, you could actually give too much and create this stimulant activity,” Dr. Osterhoudt says.

In six other cases, the cough and cold medication was given to murder the child, the investigators reported.

The findings are “concerning,” especially with “more than one-half of nontherapeutic intent cases determined to be malicious in nature,” Michele Burns, MD, from Boston Children’s Hospital, and Madeline Renny, MD, from the Grossman School of Medicine in New York, wrote in a commentary with the report.

This important fatality review shows that despite safety efforts, young children remain at risk for death, they report.

The investigators point out that labeling changes do not seem to have protected vulnerable children, and they recommend that doctors educate parents and caregivers about the risk of cough and cold medications.

Dr. Halmo and her team also recommend that the medical community and child welfare advocates be on the lookout for medication use as a source of child abuse.

At home, preventing accidental ingestion could go along with other practices already ingrained in the minds of many, Dr. Osterhoudt says.

“We know to change the clocks in the spring and fall and make sure your smoke detector and carbon monoxide detector has fresh batteries, but maybe it’s also a good time to look at medicines in the house.”

In other words, after you change the clocks, it’s time to take inventory of medications around the house, and if they’re no longer in use, safely dispose of them.

The American Academy of Pediatrics offers guidelines on the safe home storage of medications to keep them out of reach of children and the use of protective caps on drugs.

A version of this article first appeared on WebMD.com.

A number of fatal child poisonings have been linked to common cough and cold medications, according to a report.

The Pediatric Cough and Cold Safety Surveillance System, which tracks fatal child poisonings, has identified 40 such deaths in recent years and raised particular concern about medications containing diphenhydramine, a common antihistamine that can be sedating.

“There is little evidence that cough and cold medicines make children feel better or reduce their symptoms, but there is evidence they can suffer harm,” says Kevin Osterhoudt, MD, medical director of the Poison Control Center at the Children’s Hospital of Philadelphia.

In recent years, the FDA has advised labeling changes and recommended that cough and cold medications not be given to children younger than 2. Drugmakers also voluntarily relabeled these products to state “do not use in children under 4 years of age.”

Compared to older children or adults, young children have a different physiology when they breathe, so any product containing antihistamines can be a danger to little kids, Dr. Osterhoudt says.

But a recent survey shows about half of American parents gave their child cough and cold medication the last time they were ill, Dr. Osterhoudt says. And the findings suggest that cough and cold medications are in homes where children might find them.

Using the new evidence from the national surveillance system, investigators set up an expert panel to review the results. They found that most of the deaths were in children under the age of 2. The results were reported in the October issue of Pediatrics.

In seven instances, death followed the intentional use of medication to sedate the child, reports lead investigator Laurie Seidel Halmo, MD, from Children’s Hospital Colorado, Aurora.

“It’s not uncommon for parents to use sedatives like diphenhydramine to make their child sleepy for activities like air travel,” Dr. Osterhoudt says.

While antihistamines can be sedating, “an overdose of antihistamines like diphenhydramine can paradoxically become a stimulant,” having the opposite effect, he explains.

Adults and teens who take overdoses will sometimes become delirious, hallucinate, and have a racing heart.

But in young children, “if not careful with your dosing, you could actually give too much and create this stimulant activity,” Dr. Osterhoudt says.

In six other cases, the cough and cold medication was given to murder the child, the investigators reported.

The findings are “concerning,” especially with “more than one-half of nontherapeutic intent cases determined to be malicious in nature,” Michele Burns, MD, from Boston Children’s Hospital, and Madeline Renny, MD, from the Grossman School of Medicine in New York, wrote in a commentary with the report.

This important fatality review shows that despite safety efforts, young children remain at risk for death, they report.

The investigators point out that labeling changes do not seem to have protected vulnerable children, and they recommend that doctors educate parents and caregivers about the risk of cough and cold medications.

Dr. Halmo and her team also recommend that the medical community and child welfare advocates be on the lookout for medication use as a source of child abuse.

At home, preventing accidental ingestion could go along with other practices already ingrained in the minds of many, Dr. Osterhoudt says.

“We know to change the clocks in the spring and fall and make sure your smoke detector and carbon monoxide detector has fresh batteries, but maybe it’s also a good time to look at medicines in the house.”

In other words, after you change the clocks, it’s time to take inventory of medications around the house, and if they’re no longer in use, safely dispose of them.

The American Academy of Pediatrics offers guidelines on the safe home storage of medications to keep them out of reach of children and the use of protective caps on drugs.

A version of this article first appeared on WebMD.com.

A number of fatal child poisonings have been linked to common cough and cold medications, according to a report.

The Pediatric Cough and Cold Safety Surveillance System, which tracks fatal child poisonings, has identified 40 such deaths in recent years and raised particular concern about medications containing diphenhydramine, a common antihistamine that can be sedating.

“There is little evidence that cough and cold medicines make children feel better or reduce their symptoms, but there is evidence they can suffer harm,” says Kevin Osterhoudt, MD, medical director of the Poison Control Center at the Children’s Hospital of Philadelphia.

In recent years, the FDA has advised labeling changes and recommended that cough and cold medications not be given to children younger than 2. Drugmakers also voluntarily relabeled these products to state “do not use in children under 4 years of age.”

Compared to older children or adults, young children have a different physiology when they breathe, so any product containing antihistamines can be a danger to little kids, Dr. Osterhoudt says.

But a recent survey shows about half of American parents gave their child cough and cold medication the last time they were ill, Dr. Osterhoudt says. And the findings suggest that cough and cold medications are in homes where children might find them.

Using the new evidence from the national surveillance system, investigators set up an expert panel to review the results. They found that most of the deaths were in children under the age of 2. The results were reported in the October issue of Pediatrics.

In seven instances, death followed the intentional use of medication to sedate the child, reports lead investigator Laurie Seidel Halmo, MD, from Children’s Hospital Colorado, Aurora.

“It’s not uncommon for parents to use sedatives like diphenhydramine to make their child sleepy for activities like air travel,” Dr. Osterhoudt says.

While antihistamines can be sedating, “an overdose of antihistamines like diphenhydramine can paradoxically become a stimulant,” having the opposite effect, he explains.

Adults and teens who take overdoses will sometimes become delirious, hallucinate, and have a racing heart.

But in young children, “if not careful with your dosing, you could actually give too much and create this stimulant activity,” Dr. Osterhoudt says.

In six other cases, the cough and cold medication was given to murder the child, the investigators reported.

The findings are “concerning,” especially with “more than one-half of nontherapeutic intent cases determined to be malicious in nature,” Michele Burns, MD, from Boston Children’s Hospital, and Madeline Renny, MD, from the Grossman School of Medicine in New York, wrote in a commentary with the report.

This important fatality review shows that despite safety efforts, young children remain at risk for death, they report.

The investigators point out that labeling changes do not seem to have protected vulnerable children, and they recommend that doctors educate parents and caregivers about the risk of cough and cold medications.

Dr. Halmo and her team also recommend that the medical community and child welfare advocates be on the lookout for medication use as a source of child abuse.

At home, preventing accidental ingestion could go along with other practices already ingrained in the minds of many, Dr. Osterhoudt says.

“We know to change the clocks in the spring and fall and make sure your smoke detector and carbon monoxide detector has fresh batteries, but maybe it’s also a good time to look at medicines in the house.”

In other words, after you change the clocks, it’s time to take inventory of medications around the house, and if they’re no longer in use, safely dispose of them.

The American Academy of Pediatrics offers guidelines on the safe home storage of medications to keep them out of reach of children and the use of protective caps on drugs.

A version of this article first appeared on WebMD.com.