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FDA approval for tisotumab vedotin in advanced cervical cancer
There is currently no standard option for these patients. The mainstay of therapy in this setting is monotherapy with chemotherapy, but the benefit-risk profiles are poor, and overall response rates (ORRs) are less than 15%.
In the clinical trial that led to the accelerated approval, tisotumab vedotin-tftv yielded an ORR of 24%, which an expert not connected with the trial said was “impressive.”
“Tivdak’s approval as a monotherapy in the U.S. is an important milestone for women with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, as they are in need of a new treatment option and we look forward to making it available to them,” Jan van de Winkel, PhD, chief executive officer of Genmab, said in a statement.
Tisotumab vedotin is an antibody–drug conjugate: A human monoclonal antibody directed against tissue factor, which is highly expressed on many solid tumors, is attached to the microtubule-disrupting agent monomethyl auristatin E.
Details of clinical trial data
The accelerated approval was based on the results of the innovaTV 204, an open-label, multicenter, single-arm clinical trial, which was published online on April 9 in The Lancet Oncology, as reported at the time.
The trial included 101 women with recurrent or metastatic squamous cell, adenocarcinoma, or adenosquamous cervical cancer whose disease had progressed with or after doublet chemotherapy with bevacizumab (if eligible by local standards) and who had received two or fewer previous systemic regimens for recurrent or metastatic disease.
All patients received tisotumab vendotin intravenously at a dose of 2.0 mg/kg (up to a maximum of 200 mg) once every 3 weeks until disease progression or unacceptable toxicity.
The confirmed ORR was 24% and included seven (7%) complete responses and 17 (17%) partial responses.
The disease control rate was 72%, and the median duration of response was 8.3 months. The median progression-free survival was 4.2 months; the 6-month progression-free survival rate was 30%.
Median overall survival (OS) was 12.1 months. OS rates were 79% at 6 months and 51% at 12 months.
Overall, the safety profile with tisotumab vedotin was manageable, the trialists reported. The most common treatment-related adverse events were alopecia (38%), epistaxis (30%), nausea (27%), conjunctivitis (26%), fatigue (26%), and dry eye (23%). Adverse events of grade 3 or higher were reported by 28% of patients and included neutropenia (3%), fatigue (2%), ulcerative keratitis (2%), and peripheral neuropathies (2%). One patient died as a result of septic shock that was considered by the investigators to be related to therapy.
The new product labeling includes a boxed warning for ocular toxicity. It notes that tisotumab vedotin “caused changes in the corneal epithelium and conjunctiva resulting in changes in vision, including severe vision loss, and corneal ulceration.” It recommends that clinicians conduct an ophthalmic exam at baseline, prior to each dose, and as clinically indicated and that patients adhere to premedication and required eye care before, during, and after infusion.
Confirmatory trial underway
Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.
The confirmatory trial for tisotumab vedotin is already underway: The global phase 3 innovaTV 301 trial began in January 2021. It will compare tisotumab vendotin to chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed) for patients with recurrent or metastatic cervical cancer who have received one or two prior lines of systemic therapy.
A version of this article first appeared on Medscape.com.
There is currently no standard option for these patients. The mainstay of therapy in this setting is monotherapy with chemotherapy, but the benefit-risk profiles are poor, and overall response rates (ORRs) are less than 15%.
In the clinical trial that led to the accelerated approval, tisotumab vedotin-tftv yielded an ORR of 24%, which an expert not connected with the trial said was “impressive.”
“Tivdak’s approval as a monotherapy in the U.S. is an important milestone for women with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, as they are in need of a new treatment option and we look forward to making it available to them,” Jan van de Winkel, PhD, chief executive officer of Genmab, said in a statement.
Tisotumab vedotin is an antibody–drug conjugate: A human monoclonal antibody directed against tissue factor, which is highly expressed on many solid tumors, is attached to the microtubule-disrupting agent monomethyl auristatin E.
Details of clinical trial data
The accelerated approval was based on the results of the innovaTV 204, an open-label, multicenter, single-arm clinical trial, which was published online on April 9 in The Lancet Oncology, as reported at the time.
The trial included 101 women with recurrent or metastatic squamous cell, adenocarcinoma, or adenosquamous cervical cancer whose disease had progressed with or after doublet chemotherapy with bevacizumab (if eligible by local standards) and who had received two or fewer previous systemic regimens for recurrent or metastatic disease.
All patients received tisotumab vendotin intravenously at a dose of 2.0 mg/kg (up to a maximum of 200 mg) once every 3 weeks until disease progression or unacceptable toxicity.
The confirmed ORR was 24% and included seven (7%) complete responses and 17 (17%) partial responses.
The disease control rate was 72%, and the median duration of response was 8.3 months. The median progression-free survival was 4.2 months; the 6-month progression-free survival rate was 30%.
Median overall survival (OS) was 12.1 months. OS rates were 79% at 6 months and 51% at 12 months.
Overall, the safety profile with tisotumab vedotin was manageable, the trialists reported. The most common treatment-related adverse events were alopecia (38%), epistaxis (30%), nausea (27%), conjunctivitis (26%), fatigue (26%), and dry eye (23%). Adverse events of grade 3 or higher were reported by 28% of patients and included neutropenia (3%), fatigue (2%), ulcerative keratitis (2%), and peripheral neuropathies (2%). One patient died as a result of septic shock that was considered by the investigators to be related to therapy.
The new product labeling includes a boxed warning for ocular toxicity. It notes that tisotumab vedotin “caused changes in the corneal epithelium and conjunctiva resulting in changes in vision, including severe vision loss, and corneal ulceration.” It recommends that clinicians conduct an ophthalmic exam at baseline, prior to each dose, and as clinically indicated and that patients adhere to premedication and required eye care before, during, and after infusion.
Confirmatory trial underway
Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.
The confirmatory trial for tisotumab vedotin is already underway: The global phase 3 innovaTV 301 trial began in January 2021. It will compare tisotumab vendotin to chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed) for patients with recurrent or metastatic cervical cancer who have received one or two prior lines of systemic therapy.
A version of this article first appeared on Medscape.com.
There is currently no standard option for these patients. The mainstay of therapy in this setting is monotherapy with chemotherapy, but the benefit-risk profiles are poor, and overall response rates (ORRs) are less than 15%.
In the clinical trial that led to the accelerated approval, tisotumab vedotin-tftv yielded an ORR of 24%, which an expert not connected with the trial said was “impressive.”
“Tivdak’s approval as a monotherapy in the U.S. is an important milestone for women with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, as they are in need of a new treatment option and we look forward to making it available to them,” Jan van de Winkel, PhD, chief executive officer of Genmab, said in a statement.
Tisotumab vedotin is an antibody–drug conjugate: A human monoclonal antibody directed against tissue factor, which is highly expressed on many solid tumors, is attached to the microtubule-disrupting agent monomethyl auristatin E.
Details of clinical trial data
The accelerated approval was based on the results of the innovaTV 204, an open-label, multicenter, single-arm clinical trial, which was published online on April 9 in The Lancet Oncology, as reported at the time.
The trial included 101 women with recurrent or metastatic squamous cell, adenocarcinoma, or adenosquamous cervical cancer whose disease had progressed with or after doublet chemotherapy with bevacizumab (if eligible by local standards) and who had received two or fewer previous systemic regimens for recurrent or metastatic disease.
All patients received tisotumab vendotin intravenously at a dose of 2.0 mg/kg (up to a maximum of 200 mg) once every 3 weeks until disease progression or unacceptable toxicity.
The confirmed ORR was 24% and included seven (7%) complete responses and 17 (17%) partial responses.
The disease control rate was 72%, and the median duration of response was 8.3 months. The median progression-free survival was 4.2 months; the 6-month progression-free survival rate was 30%.
Median overall survival (OS) was 12.1 months. OS rates were 79% at 6 months and 51% at 12 months.
Overall, the safety profile with tisotumab vedotin was manageable, the trialists reported. The most common treatment-related adverse events were alopecia (38%), epistaxis (30%), nausea (27%), conjunctivitis (26%), fatigue (26%), and dry eye (23%). Adverse events of grade 3 or higher were reported by 28% of patients and included neutropenia (3%), fatigue (2%), ulcerative keratitis (2%), and peripheral neuropathies (2%). One patient died as a result of septic shock that was considered by the investigators to be related to therapy.
The new product labeling includes a boxed warning for ocular toxicity. It notes that tisotumab vedotin “caused changes in the corneal epithelium and conjunctiva resulting in changes in vision, including severe vision loss, and corneal ulceration.” It recommends that clinicians conduct an ophthalmic exam at baseline, prior to each dose, and as clinically indicated and that patients adhere to premedication and required eye care before, during, and after infusion.
Confirmatory trial underway
Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.
The confirmatory trial for tisotumab vedotin is already underway: The global phase 3 innovaTV 301 trial began in January 2021. It will compare tisotumab vendotin to chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed) for patients with recurrent or metastatic cervical cancer who have received one or two prior lines of systemic therapy.
A version of this article first appeared on Medscape.com.
Relapse risk increased with antidepressant discontinuation
a new study shows.
The results of the Antidepressants to Prevent Relapse in Depression (ANTLER) trial also suggest that “many patients can discontinue their antidepressants safely in primary care without relapsing, when there is a tapering regime,” said lead investigator Gemma Lewis, PhD, from University College London, in an interview.
The multicenter, randomized, double-blind trial, which was published in the New England Journal of Medicine (2021;385:1257-67), included 478 patients, from 150 primary care practices in the United Kingdom.
The participants (73% female, average age 54 years) had a history of at least two depressive episodes or had been taking antidepressants (citalopram, fluoxetine, sertraline, or mirtazapine) for at least 2 years. The vast majority of patients – 70% – had been using the drugs for more than 3 years, the researchers wrote.
Study participants were randomized to either maintain their antidepressant regimen or to taper off for up to 2 months before switching to a placebo.
Over a follow-up of 52 weeks, relapse occurred in 56% of those who discontinued, compared with 39% of those who maintained their regimen (hazard ratio, 2.06; P < .001). Relapse also occurred sooner in the discontinuation group (13 weeks vs. 19 weeks).
The definition of relapse was answering yes to either of the following two questions:
- Have you had a spell of feeling sad, miserable, or depressed?
- Have you been unable to enjoy or take an interest in things as much as you usually do?
Patients also had to report that one of these experiences had lasted for 2 weeks or more, and having had at least one of the following symptoms: depressive thoughts, fatigue, loss of concentration, or sleep disturbance.
By the end of the trial, 39% of patients in the group who discontinued taking an antidepressant had returned to taking that type of drug.
“We found that remaining on antidepressants long-term does effectively reduce the risk of relapse. However, we also found that 44% of those who discontinued their antidepressants did not relapse after a full year,” Dr. Lewis said.
Who can stop medications without relapsing is unknown
“Many people can stop their medication without relapsing, though at present we cannot identify who those people are,” noted Dr. Lewis.
“Our study did not investigate who is at higher risk of relapse … but this is something we will focus on in the future,” she said.
For primary care clinicians whose patients are considering discontinuation of antidepressant medication, “current best practice is to engage with patients’ priorities and collaborate in coming to a decision,” she noted.
“For the individual patient, it is only possible to know about the average likelihood of relapse – and the severity of potential relapses will also be unpredictable. Our findings will give patients and clinicians an estimate of the likely benefits and harms of stopping long-term maintenance antidepressants to inform shared decision-making in primary care.”
Findings are ‘important’ but ‘disappointing’
In an editorial published alongside the study (N Engl J Med. 2021;385:1327-8), Jeffrey L. Jackson, MD, MPH, from the Zablocki VA Medical Center and the Medical College of Wisconsin in Milwaukee characterized the findings as “important but disappointing.”
“They confirm what most primary care physicians already knew or intuited. The frequency of relapse after the discontinuation of treatment is high, particularly among patients with several previous depressive episodes,” he explained.
Dr. Jackson also pointed out some unknowns about the trial, including the length trial participants had been in remission for depression.
“It is unclear whether the trial results are generalizable to primary care patients with a first episode of depression,” he said, and noted that participants with three or more previous depressive episodes were more than twice as likely to relapse, compared with participants with fewer episodes.
“I encourage patients with a single bout of depression, especially episodes that are triggered by a life event, such as loss of a loved one, to consider weaning antidepressant treatment after at least 6 months of remission,” he wrote. “For those with three or more previous bouts of depression, my practice has been to recommend that they anticipate medical treatment for life or, if they wish to stop taking medication, explore nonpharmacologic approaches, such as cognitive-behavior therapy.”
Protective effect of antidepressants was clear
“This is an important paper providing an evidence base to the often-cited recommendation that after two or more episodes of depression, antidepressant medication should be continued indefinitely,” said Neil Skolnik, MD, professor of family and community medicine at the Sidney Kimmel Medical College, Thomas Jefferson University in Philadelphia, who was not involved in the study.
“The protective effect of antidepressant medication here was clear – those who discontinued antidepressant medication had a clinically and significantly higher rate of relapse at the end of a year.”
Side effects can be significant
“It is important to note, though, that in the discontinuation group, 44% of patients did not experience a relapse,” Dr. Skolnik said. “While antidepressants work without significant side effects for many patients, for others there are significant side effects that include adverse sexual side effects, effects on appetite and weight, nighttime sweats, and other side effects.”
“So, this study should not be confused to mean that all patients who have had recurrent depression should remain on antidepressants long term. The decision about whether to continue an antidepressant is influenced by many things and should be a shared decision-making process between clinician and patient, informed by the important results of this study, the current situation of the patient, and most importantly, the patient’s informed decision of what they would like to do,” he said.
The study was funded by the U.K. National Institute for Health Research
Dr. Lewis, Dr. Jackson, and Dr. Skolnik reported no conflicts of interest.
a new study shows.
The results of the Antidepressants to Prevent Relapse in Depression (ANTLER) trial also suggest that “many patients can discontinue their antidepressants safely in primary care without relapsing, when there is a tapering regime,” said lead investigator Gemma Lewis, PhD, from University College London, in an interview.
The multicenter, randomized, double-blind trial, which was published in the New England Journal of Medicine (2021;385:1257-67), included 478 patients, from 150 primary care practices in the United Kingdom.
The participants (73% female, average age 54 years) had a history of at least two depressive episodes or had been taking antidepressants (citalopram, fluoxetine, sertraline, or mirtazapine) for at least 2 years. The vast majority of patients – 70% – had been using the drugs for more than 3 years, the researchers wrote.
Study participants were randomized to either maintain their antidepressant regimen or to taper off for up to 2 months before switching to a placebo.
Over a follow-up of 52 weeks, relapse occurred in 56% of those who discontinued, compared with 39% of those who maintained their regimen (hazard ratio, 2.06; P < .001). Relapse also occurred sooner in the discontinuation group (13 weeks vs. 19 weeks).
The definition of relapse was answering yes to either of the following two questions:
- Have you had a spell of feeling sad, miserable, or depressed?
- Have you been unable to enjoy or take an interest in things as much as you usually do?
Patients also had to report that one of these experiences had lasted for 2 weeks or more, and having had at least one of the following symptoms: depressive thoughts, fatigue, loss of concentration, or sleep disturbance.
By the end of the trial, 39% of patients in the group who discontinued taking an antidepressant had returned to taking that type of drug.
“We found that remaining on antidepressants long-term does effectively reduce the risk of relapse. However, we also found that 44% of those who discontinued their antidepressants did not relapse after a full year,” Dr. Lewis said.
Who can stop medications without relapsing is unknown
“Many people can stop their medication without relapsing, though at present we cannot identify who those people are,” noted Dr. Lewis.
“Our study did not investigate who is at higher risk of relapse … but this is something we will focus on in the future,” she said.
For primary care clinicians whose patients are considering discontinuation of antidepressant medication, “current best practice is to engage with patients’ priorities and collaborate in coming to a decision,” she noted.
“For the individual patient, it is only possible to know about the average likelihood of relapse – and the severity of potential relapses will also be unpredictable. Our findings will give patients and clinicians an estimate of the likely benefits and harms of stopping long-term maintenance antidepressants to inform shared decision-making in primary care.”
Findings are ‘important’ but ‘disappointing’
In an editorial published alongside the study (N Engl J Med. 2021;385:1327-8), Jeffrey L. Jackson, MD, MPH, from the Zablocki VA Medical Center and the Medical College of Wisconsin in Milwaukee characterized the findings as “important but disappointing.”
“They confirm what most primary care physicians already knew or intuited. The frequency of relapse after the discontinuation of treatment is high, particularly among patients with several previous depressive episodes,” he explained.
Dr. Jackson also pointed out some unknowns about the trial, including the length trial participants had been in remission for depression.
“It is unclear whether the trial results are generalizable to primary care patients with a first episode of depression,” he said, and noted that participants with three or more previous depressive episodes were more than twice as likely to relapse, compared with participants with fewer episodes.
“I encourage patients with a single bout of depression, especially episodes that are triggered by a life event, such as loss of a loved one, to consider weaning antidepressant treatment after at least 6 months of remission,” he wrote. “For those with three or more previous bouts of depression, my practice has been to recommend that they anticipate medical treatment for life or, if they wish to stop taking medication, explore nonpharmacologic approaches, such as cognitive-behavior therapy.”
Protective effect of antidepressants was clear
“This is an important paper providing an evidence base to the often-cited recommendation that after two or more episodes of depression, antidepressant medication should be continued indefinitely,” said Neil Skolnik, MD, professor of family and community medicine at the Sidney Kimmel Medical College, Thomas Jefferson University in Philadelphia, who was not involved in the study.
“The protective effect of antidepressant medication here was clear – those who discontinued antidepressant medication had a clinically and significantly higher rate of relapse at the end of a year.”
Side effects can be significant
“It is important to note, though, that in the discontinuation group, 44% of patients did not experience a relapse,” Dr. Skolnik said. “While antidepressants work without significant side effects for many patients, for others there are significant side effects that include adverse sexual side effects, effects on appetite and weight, nighttime sweats, and other side effects.”
“So, this study should not be confused to mean that all patients who have had recurrent depression should remain on antidepressants long term. The decision about whether to continue an antidepressant is influenced by many things and should be a shared decision-making process between clinician and patient, informed by the important results of this study, the current situation of the patient, and most importantly, the patient’s informed decision of what they would like to do,” he said.
The study was funded by the U.K. National Institute for Health Research
Dr. Lewis, Dr. Jackson, and Dr. Skolnik reported no conflicts of interest.
a new study shows.
The results of the Antidepressants to Prevent Relapse in Depression (ANTLER) trial also suggest that “many patients can discontinue their antidepressants safely in primary care without relapsing, when there is a tapering regime,” said lead investigator Gemma Lewis, PhD, from University College London, in an interview.
The multicenter, randomized, double-blind trial, which was published in the New England Journal of Medicine (2021;385:1257-67), included 478 patients, from 150 primary care practices in the United Kingdom.
The participants (73% female, average age 54 years) had a history of at least two depressive episodes or had been taking antidepressants (citalopram, fluoxetine, sertraline, or mirtazapine) for at least 2 years. The vast majority of patients – 70% – had been using the drugs for more than 3 years, the researchers wrote.
Study participants were randomized to either maintain their antidepressant regimen or to taper off for up to 2 months before switching to a placebo.
Over a follow-up of 52 weeks, relapse occurred in 56% of those who discontinued, compared with 39% of those who maintained their regimen (hazard ratio, 2.06; P < .001). Relapse also occurred sooner in the discontinuation group (13 weeks vs. 19 weeks).
The definition of relapse was answering yes to either of the following two questions:
- Have you had a spell of feeling sad, miserable, or depressed?
- Have you been unable to enjoy or take an interest in things as much as you usually do?
Patients also had to report that one of these experiences had lasted for 2 weeks or more, and having had at least one of the following symptoms: depressive thoughts, fatigue, loss of concentration, or sleep disturbance.
By the end of the trial, 39% of patients in the group who discontinued taking an antidepressant had returned to taking that type of drug.
“We found that remaining on antidepressants long-term does effectively reduce the risk of relapse. However, we also found that 44% of those who discontinued their antidepressants did not relapse after a full year,” Dr. Lewis said.
Who can stop medications without relapsing is unknown
“Many people can stop their medication without relapsing, though at present we cannot identify who those people are,” noted Dr. Lewis.
“Our study did not investigate who is at higher risk of relapse … but this is something we will focus on in the future,” she said.
For primary care clinicians whose patients are considering discontinuation of antidepressant medication, “current best practice is to engage with patients’ priorities and collaborate in coming to a decision,” she noted.
“For the individual patient, it is only possible to know about the average likelihood of relapse – and the severity of potential relapses will also be unpredictable. Our findings will give patients and clinicians an estimate of the likely benefits and harms of stopping long-term maintenance antidepressants to inform shared decision-making in primary care.”
Findings are ‘important’ but ‘disappointing’
In an editorial published alongside the study (N Engl J Med. 2021;385:1327-8), Jeffrey L. Jackson, MD, MPH, from the Zablocki VA Medical Center and the Medical College of Wisconsin in Milwaukee characterized the findings as “important but disappointing.”
“They confirm what most primary care physicians already knew or intuited. The frequency of relapse after the discontinuation of treatment is high, particularly among patients with several previous depressive episodes,” he explained.
Dr. Jackson also pointed out some unknowns about the trial, including the length trial participants had been in remission for depression.
“It is unclear whether the trial results are generalizable to primary care patients with a first episode of depression,” he said, and noted that participants with three or more previous depressive episodes were more than twice as likely to relapse, compared with participants with fewer episodes.
“I encourage patients with a single bout of depression, especially episodes that are triggered by a life event, such as loss of a loved one, to consider weaning antidepressant treatment after at least 6 months of remission,” he wrote. “For those with three or more previous bouts of depression, my practice has been to recommend that they anticipate medical treatment for life or, if they wish to stop taking medication, explore nonpharmacologic approaches, such as cognitive-behavior therapy.”
Protective effect of antidepressants was clear
“This is an important paper providing an evidence base to the often-cited recommendation that after two or more episodes of depression, antidepressant medication should be continued indefinitely,” said Neil Skolnik, MD, professor of family and community medicine at the Sidney Kimmel Medical College, Thomas Jefferson University in Philadelphia, who was not involved in the study.
“The protective effect of antidepressant medication here was clear – those who discontinued antidepressant medication had a clinically and significantly higher rate of relapse at the end of a year.”
Side effects can be significant
“It is important to note, though, that in the discontinuation group, 44% of patients did not experience a relapse,” Dr. Skolnik said. “While antidepressants work without significant side effects for many patients, for others there are significant side effects that include adverse sexual side effects, effects on appetite and weight, nighttime sweats, and other side effects.”
“So, this study should not be confused to mean that all patients who have had recurrent depression should remain on antidepressants long term. The decision about whether to continue an antidepressant is influenced by many things and should be a shared decision-making process between clinician and patient, informed by the important results of this study, the current situation of the patient, and most importantly, the patient’s informed decision of what they would like to do,” he said.
The study was funded by the U.K. National Institute for Health Research
Dr. Lewis, Dr. Jackson, and Dr. Skolnik reported no conflicts of interest.
FROM NEW ENGLAND JOURNAL OF MEDICINE
Polyethylene glycol linked to rare allergic reactions seen with mRNA COVID-19 vaccines
A common inert ingredient may be the culprit behind the rare allergic reactions reported among individuals who have received mRNA COVID-19 vaccines, according to investigators at a large regional health center that was among the first to administer the shots.
Blood samples from 10 of 11 individuals with suspected allergic reactions reacted to polyethylene glycol (PEG), a component of both the Pfizer and Moderna mRNA vaccines, according to a report in JAMA Network Open.
In total, only 22 individuals had suspected allergic reactions out of nearly 39,000 mRNA COVID-19 vaccine doses administered, the investigators reported, noting that the reactions were generally mild and all fully resolved.
Those findings should be reassuring to individuals who are reticent to sign up for a COVID-19 vaccine because of fear of an allergic reaction, said study senior author Kari Nadeau, MD, PhD, director of the Parker Center for Allergy and Asthma Research at Stanford (Calif.) University.
“We’re hoping that this word will get out and then that the companies could also think about making vaccines that have other products in them that don’t include polyethylene glycol,” Dr. Nadeau said in an interview.
PEG is a compound used in many products, including pharmaceuticals, cosmetics, and food. In the mRNA COVID-19 vaccines, PEG serves to stabilize the lipid nanoparticles that help protect and transport mRNA. However, its use in this setting has been linked to allergic reactions in this and previous studies.
No immunoglobulin E (IgE) antibodies to PEG were detected among the 22 individuals with suspected allergic reactions to mRNA COVID-19 vaccine, but PEG immunoglobulin G (IgG) was present. That suggests non-IgE mediated allergic reactions to PEG may be implicated for the majority of cases, Dr. Nadeau said.
This case series provides interesting new evidence to confirm previous reports that a mechanism other than the classic IgE-mediated allergic response is behind the suspected allergic reactions that are occurring after mRNA COVID-19 vaccine, said Aleena Banerji, MD, associate professor at Harvard Medical School, Boston, and clinical director of the Drug Allergy Program at Massachusetts General Hospital.
“We need to further understand the mechanism of these reactions, but what we know is that IGE mediated allergy to excipients like PEG is probably not the main cause,” Dr. Banerji, who was not involved in the study, said in an interview.
In a recent research letter published in JAMA Internal Medicine, Dr. Banerji and coauthors reported that all individuals with immediate suspected allergic reactions to mRNA COVID-19 vaccine went on to tolerate the second dose, with mild symptoms reported in the minority of patients (32 out of 159, or about 20%).
“Again, that is very consistent with not having an IgE-mediated allergy, so it seems to all be fitting with that picture,” Dr. Banerji said.
The case series by Dr. Nadeau and coauthors was based on review of nearly 39,000 mRNA COVID-19 vaccine doses administered between December 18, 2020 and January 26, 2021. Most mRNA vaccine recipients were Stanford-affiliated health care workers, according to the report.
Among recipients of those doses, they identified 148 individuals who had anaphylaxis-related ICD-10 codes recorded over the same time period. In a review of medical records, investigators pinpointed 22 individuals as having suspected allergy and invited them to participate in follow-up allergy testing.
A total of 11 individuals underwent skin prick testing, but none of them tested positive to PEG or to polysorbate 80, another excipient that has been linked to vaccine-related allergic reactions. One of the patients tested positive to the same mRNA vaccine they had previously received, according to the report.
Those same 11 individuals also underwent basophil activation testing (BAT). In contrast to the skin testing results, BAT results were positive for PEG in 10 of 11 cases (or 91%) and positive for their administered vaccine in all 11 cases, the report shows.
High levels of IgG to PEG were identified in blood samples of individuals with an allergy to the vaccine. Investigators said it’s possible that the BAT results were activated due to IgG via complement activation–related pseudoallergy, or CARPA, as has been hypothesized by some other investigators.
The negative skin prick testing results for PEG, which contrast with the positive BAT results to PEG, suggest that the former may not be appropriate for use as a predictive marker of potential vaccine allergy, according to Dr. Nadeau.
“The take-home message for doctors is to be careful,” she said. “Don’t assume that just because the person skin-tests negative to PEG or to the vaccine itself that you’re out of the woods, because the skin test would be often negative in those scenarios.”
The study was supported by a grants from the Asthma and Allergic Diseases Cooperative Research Centers, a grant from the National Institutes of Health, the National Institute of Allergy and Infectious Disease SARS Vaccine study, the Parker Foundation, the Crown Foundation, and the Sunshine Foundation. Dr. Nadeau reports numerous conflicts with various sources in the industry. Dr. Banerji has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A common inert ingredient may be the culprit behind the rare allergic reactions reported among individuals who have received mRNA COVID-19 vaccines, according to investigators at a large regional health center that was among the first to administer the shots.
Blood samples from 10 of 11 individuals with suspected allergic reactions reacted to polyethylene glycol (PEG), a component of both the Pfizer and Moderna mRNA vaccines, according to a report in JAMA Network Open.
In total, only 22 individuals had suspected allergic reactions out of nearly 39,000 mRNA COVID-19 vaccine doses administered, the investigators reported, noting that the reactions were generally mild and all fully resolved.
Those findings should be reassuring to individuals who are reticent to sign up for a COVID-19 vaccine because of fear of an allergic reaction, said study senior author Kari Nadeau, MD, PhD, director of the Parker Center for Allergy and Asthma Research at Stanford (Calif.) University.
“We’re hoping that this word will get out and then that the companies could also think about making vaccines that have other products in them that don’t include polyethylene glycol,” Dr. Nadeau said in an interview.
PEG is a compound used in many products, including pharmaceuticals, cosmetics, and food. In the mRNA COVID-19 vaccines, PEG serves to stabilize the lipid nanoparticles that help protect and transport mRNA. However, its use in this setting has been linked to allergic reactions in this and previous studies.
No immunoglobulin E (IgE) antibodies to PEG were detected among the 22 individuals with suspected allergic reactions to mRNA COVID-19 vaccine, but PEG immunoglobulin G (IgG) was present. That suggests non-IgE mediated allergic reactions to PEG may be implicated for the majority of cases, Dr. Nadeau said.
This case series provides interesting new evidence to confirm previous reports that a mechanism other than the classic IgE-mediated allergic response is behind the suspected allergic reactions that are occurring after mRNA COVID-19 vaccine, said Aleena Banerji, MD, associate professor at Harvard Medical School, Boston, and clinical director of the Drug Allergy Program at Massachusetts General Hospital.
“We need to further understand the mechanism of these reactions, but what we know is that IGE mediated allergy to excipients like PEG is probably not the main cause,” Dr. Banerji, who was not involved in the study, said in an interview.
In a recent research letter published in JAMA Internal Medicine, Dr. Banerji and coauthors reported that all individuals with immediate suspected allergic reactions to mRNA COVID-19 vaccine went on to tolerate the second dose, with mild symptoms reported in the minority of patients (32 out of 159, or about 20%).
“Again, that is very consistent with not having an IgE-mediated allergy, so it seems to all be fitting with that picture,” Dr. Banerji said.
The case series by Dr. Nadeau and coauthors was based on review of nearly 39,000 mRNA COVID-19 vaccine doses administered between December 18, 2020 and January 26, 2021. Most mRNA vaccine recipients were Stanford-affiliated health care workers, according to the report.
Among recipients of those doses, they identified 148 individuals who had anaphylaxis-related ICD-10 codes recorded over the same time period. In a review of medical records, investigators pinpointed 22 individuals as having suspected allergy and invited them to participate in follow-up allergy testing.
A total of 11 individuals underwent skin prick testing, but none of them tested positive to PEG or to polysorbate 80, another excipient that has been linked to vaccine-related allergic reactions. One of the patients tested positive to the same mRNA vaccine they had previously received, according to the report.
Those same 11 individuals also underwent basophil activation testing (BAT). In contrast to the skin testing results, BAT results were positive for PEG in 10 of 11 cases (or 91%) and positive for their administered vaccine in all 11 cases, the report shows.
High levels of IgG to PEG were identified in blood samples of individuals with an allergy to the vaccine. Investigators said it’s possible that the BAT results were activated due to IgG via complement activation–related pseudoallergy, or CARPA, as has been hypothesized by some other investigators.
The negative skin prick testing results for PEG, which contrast with the positive BAT results to PEG, suggest that the former may not be appropriate for use as a predictive marker of potential vaccine allergy, according to Dr. Nadeau.
“The take-home message for doctors is to be careful,” she said. “Don’t assume that just because the person skin-tests negative to PEG or to the vaccine itself that you’re out of the woods, because the skin test would be often negative in those scenarios.”
The study was supported by a grants from the Asthma and Allergic Diseases Cooperative Research Centers, a grant from the National Institutes of Health, the National Institute of Allergy and Infectious Disease SARS Vaccine study, the Parker Foundation, the Crown Foundation, and the Sunshine Foundation. Dr. Nadeau reports numerous conflicts with various sources in the industry. Dr. Banerji has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A common inert ingredient may be the culprit behind the rare allergic reactions reported among individuals who have received mRNA COVID-19 vaccines, according to investigators at a large regional health center that was among the first to administer the shots.
Blood samples from 10 of 11 individuals with suspected allergic reactions reacted to polyethylene glycol (PEG), a component of both the Pfizer and Moderna mRNA vaccines, according to a report in JAMA Network Open.
In total, only 22 individuals had suspected allergic reactions out of nearly 39,000 mRNA COVID-19 vaccine doses administered, the investigators reported, noting that the reactions were generally mild and all fully resolved.
Those findings should be reassuring to individuals who are reticent to sign up for a COVID-19 vaccine because of fear of an allergic reaction, said study senior author Kari Nadeau, MD, PhD, director of the Parker Center for Allergy and Asthma Research at Stanford (Calif.) University.
“We’re hoping that this word will get out and then that the companies could also think about making vaccines that have other products in them that don’t include polyethylene glycol,” Dr. Nadeau said in an interview.
PEG is a compound used in many products, including pharmaceuticals, cosmetics, and food. In the mRNA COVID-19 vaccines, PEG serves to stabilize the lipid nanoparticles that help protect and transport mRNA. However, its use in this setting has been linked to allergic reactions in this and previous studies.
No immunoglobulin E (IgE) antibodies to PEG were detected among the 22 individuals with suspected allergic reactions to mRNA COVID-19 vaccine, but PEG immunoglobulin G (IgG) was present. That suggests non-IgE mediated allergic reactions to PEG may be implicated for the majority of cases, Dr. Nadeau said.
This case series provides interesting new evidence to confirm previous reports that a mechanism other than the classic IgE-mediated allergic response is behind the suspected allergic reactions that are occurring after mRNA COVID-19 vaccine, said Aleena Banerji, MD, associate professor at Harvard Medical School, Boston, and clinical director of the Drug Allergy Program at Massachusetts General Hospital.
“We need to further understand the mechanism of these reactions, but what we know is that IGE mediated allergy to excipients like PEG is probably not the main cause,” Dr. Banerji, who was not involved in the study, said in an interview.
In a recent research letter published in JAMA Internal Medicine, Dr. Banerji and coauthors reported that all individuals with immediate suspected allergic reactions to mRNA COVID-19 vaccine went on to tolerate the second dose, with mild symptoms reported in the minority of patients (32 out of 159, or about 20%).
“Again, that is very consistent with not having an IgE-mediated allergy, so it seems to all be fitting with that picture,” Dr. Banerji said.
The case series by Dr. Nadeau and coauthors was based on review of nearly 39,000 mRNA COVID-19 vaccine doses administered between December 18, 2020 and January 26, 2021. Most mRNA vaccine recipients were Stanford-affiliated health care workers, according to the report.
Among recipients of those doses, they identified 148 individuals who had anaphylaxis-related ICD-10 codes recorded over the same time period. In a review of medical records, investigators pinpointed 22 individuals as having suspected allergy and invited them to participate in follow-up allergy testing.
A total of 11 individuals underwent skin prick testing, but none of them tested positive to PEG or to polysorbate 80, another excipient that has been linked to vaccine-related allergic reactions. One of the patients tested positive to the same mRNA vaccine they had previously received, according to the report.
Those same 11 individuals also underwent basophil activation testing (BAT). In contrast to the skin testing results, BAT results were positive for PEG in 10 of 11 cases (or 91%) and positive for their administered vaccine in all 11 cases, the report shows.
High levels of IgG to PEG were identified in blood samples of individuals with an allergy to the vaccine. Investigators said it’s possible that the BAT results were activated due to IgG via complement activation–related pseudoallergy, or CARPA, as has been hypothesized by some other investigators.
The negative skin prick testing results for PEG, which contrast with the positive BAT results to PEG, suggest that the former may not be appropriate for use as a predictive marker of potential vaccine allergy, according to Dr. Nadeau.
“The take-home message for doctors is to be careful,” she said. “Don’t assume that just because the person skin-tests negative to PEG or to the vaccine itself that you’re out of the woods, because the skin test would be often negative in those scenarios.”
The study was supported by a grants from the Asthma and Allergic Diseases Cooperative Research Centers, a grant from the National Institutes of Health, the National Institute of Allergy and Infectious Disease SARS Vaccine study, the Parker Foundation, the Crown Foundation, and the Sunshine Foundation. Dr. Nadeau reports numerous conflicts with various sources in the industry. Dr. Banerji has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Study supports chemotherapy with immunotherapy for some never-smokers with lung cancer
Median overall survival was similar at 21.0 months and 22.1 months in 169 patients who received cancer immunotherapy plus chemotherapy and 351 who received cancer immunotherapy monotherapy, respectively (adjusted hazard ratio, 1.03). Median real-world progression-free survival (PFS) was also similar in the two groups (10.8 vs. 11.5 months; aHR, 1.04), Solange Peters, MD, reported at the 2021 European Society for Medical Oncology Congress on Sept. 17 (abstract VP2_2021).
However, in a small subgroup of 50 never-smokers, CIT plus chemotherapy showed significant and meaningful improvement in both overall survival and real-world progression-free survival, compared with CIT monotherapy, said Dr. Peters, ESMO president and professor and chair of medical oncology at the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
The hazard ratios for overall survival and progression-free survival, after adjusting for baseline characteristics, were 0.50 and 0.40 in this subgroup, Dr. Peters said.
She and her colleagues reviewed data from the nationwide Flatiron Health Electronic Health Record–derived deidentified database for patients with metastatic nonsquamous NSCLC with a PD-L1 tumor proportion score at least 50% expression who initiated first-line CIT monotherapy or CIT plus chemotherapy between Oct. 24, 2016, and Feb. 28, 2019.
Median follow-up was 23.5 and 19.9 months in the monotherapy and combination therapy groups, respectively.
The findings are notable because “this is a very important scientific question, which by the way, is a daily question we have,” Dr. Peters said during a plenary debate session at the conference.
“One in four patients [with metastatic nonsquamous NSCLC has] this high PDL expression,” she explained, noting that both treatment approaches are commonly used in the first-line setting in this patient population.
The findings highlight the value of “well-conducted real-world evidence trials” in the absence of randomized trial results, she said.
Invited discussant Marina Chiara Garassino, MBBS, professor of medicine at the University of Chicago, also acknowledged the importance of the findings, noting the “multiple possibilities” for treatment selection in the metastatic nonsquamous NSCLC patient population.
Although patients with PD-L1 expression below 50% derive clear benefit from combination versus single-agent therapy, treatment selection for those with high PD-L1 expression is “very tricky and debatable,” she said.
For those with high PD-L1 expression, the choice is less clear and wrought with uncertainties – particularly for certain subgroups like never-smokers and those with PD-L1 expression over 90%, she said.
The findings reinforce those seen in prior meta-analyses and other clinical trials, particularly with respect to the role of smoking history when making treatment decisions.
“After these results and previous subgroup analyses, in my opinion, in [patients with] PD-L1 expression over 50%, we should consider the combination of chemotherapy and immunotherapy,” she said.
Conversely, findings from this study showing no difference in outcomes between the treatment approaches in patients with brain or liver metastases are based on small numbers and lack power for drawing any conclusions, she said. It also remains unclear whether there is a differential effect for women and those with PD-L1 expression over 90%, high tumor mutation burden, performance score greater than 2, and age over 75 years.
Both Dr. Garassino and Dr. Peters said they are looking to the INSIGNA trial, which is currently recruiting patients in the United States to evaluate the timing of pembrolizumab alone or with chemotherapy as first-line treatment and maintenance in NSCLC, to provide more clarification regarding the best treatment approaches.
This study was funded by F. Hoffmann–La Roche. Dr. Peters and Dr. Garassino each disclosed personal and/or institutional financial relationships with numerous pharmaceutical companies.
Median overall survival was similar at 21.0 months and 22.1 months in 169 patients who received cancer immunotherapy plus chemotherapy and 351 who received cancer immunotherapy monotherapy, respectively (adjusted hazard ratio, 1.03). Median real-world progression-free survival (PFS) was also similar in the two groups (10.8 vs. 11.5 months; aHR, 1.04), Solange Peters, MD, reported at the 2021 European Society for Medical Oncology Congress on Sept. 17 (abstract VP2_2021).
However, in a small subgroup of 50 never-smokers, CIT plus chemotherapy showed significant and meaningful improvement in both overall survival and real-world progression-free survival, compared with CIT monotherapy, said Dr. Peters, ESMO president and professor and chair of medical oncology at the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
The hazard ratios for overall survival and progression-free survival, after adjusting for baseline characteristics, were 0.50 and 0.40 in this subgroup, Dr. Peters said.
She and her colleagues reviewed data from the nationwide Flatiron Health Electronic Health Record–derived deidentified database for patients with metastatic nonsquamous NSCLC with a PD-L1 tumor proportion score at least 50% expression who initiated first-line CIT monotherapy or CIT plus chemotherapy between Oct. 24, 2016, and Feb. 28, 2019.
Median follow-up was 23.5 and 19.9 months in the monotherapy and combination therapy groups, respectively.
The findings are notable because “this is a very important scientific question, which by the way, is a daily question we have,” Dr. Peters said during a plenary debate session at the conference.
“One in four patients [with metastatic nonsquamous NSCLC has] this high PDL expression,” she explained, noting that both treatment approaches are commonly used in the first-line setting in this patient population.
The findings highlight the value of “well-conducted real-world evidence trials” in the absence of randomized trial results, she said.
Invited discussant Marina Chiara Garassino, MBBS, professor of medicine at the University of Chicago, also acknowledged the importance of the findings, noting the “multiple possibilities” for treatment selection in the metastatic nonsquamous NSCLC patient population.
Although patients with PD-L1 expression below 50% derive clear benefit from combination versus single-agent therapy, treatment selection for those with high PD-L1 expression is “very tricky and debatable,” she said.
For those with high PD-L1 expression, the choice is less clear and wrought with uncertainties – particularly for certain subgroups like never-smokers and those with PD-L1 expression over 90%, she said.
The findings reinforce those seen in prior meta-analyses and other clinical trials, particularly with respect to the role of smoking history when making treatment decisions.
“After these results and previous subgroup analyses, in my opinion, in [patients with] PD-L1 expression over 50%, we should consider the combination of chemotherapy and immunotherapy,” she said.
Conversely, findings from this study showing no difference in outcomes between the treatment approaches in patients with brain or liver metastases are based on small numbers and lack power for drawing any conclusions, she said. It also remains unclear whether there is a differential effect for women and those with PD-L1 expression over 90%, high tumor mutation burden, performance score greater than 2, and age over 75 years.
Both Dr. Garassino and Dr. Peters said they are looking to the INSIGNA trial, which is currently recruiting patients in the United States to evaluate the timing of pembrolizumab alone or with chemotherapy as first-line treatment and maintenance in NSCLC, to provide more clarification regarding the best treatment approaches.
This study was funded by F. Hoffmann–La Roche. Dr. Peters and Dr. Garassino each disclosed personal and/or institutional financial relationships with numerous pharmaceutical companies.
Median overall survival was similar at 21.0 months and 22.1 months in 169 patients who received cancer immunotherapy plus chemotherapy and 351 who received cancer immunotherapy monotherapy, respectively (adjusted hazard ratio, 1.03). Median real-world progression-free survival (PFS) was also similar in the two groups (10.8 vs. 11.5 months; aHR, 1.04), Solange Peters, MD, reported at the 2021 European Society for Medical Oncology Congress on Sept. 17 (abstract VP2_2021).
However, in a small subgroup of 50 never-smokers, CIT plus chemotherapy showed significant and meaningful improvement in both overall survival and real-world progression-free survival, compared with CIT monotherapy, said Dr. Peters, ESMO president and professor and chair of medical oncology at the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
The hazard ratios for overall survival and progression-free survival, after adjusting for baseline characteristics, were 0.50 and 0.40 in this subgroup, Dr. Peters said.
She and her colleagues reviewed data from the nationwide Flatiron Health Electronic Health Record–derived deidentified database for patients with metastatic nonsquamous NSCLC with a PD-L1 tumor proportion score at least 50% expression who initiated first-line CIT monotherapy or CIT plus chemotherapy between Oct. 24, 2016, and Feb. 28, 2019.
Median follow-up was 23.5 and 19.9 months in the monotherapy and combination therapy groups, respectively.
The findings are notable because “this is a very important scientific question, which by the way, is a daily question we have,” Dr. Peters said during a plenary debate session at the conference.
“One in four patients [with metastatic nonsquamous NSCLC has] this high PDL expression,” she explained, noting that both treatment approaches are commonly used in the first-line setting in this patient population.
The findings highlight the value of “well-conducted real-world evidence trials” in the absence of randomized trial results, she said.
Invited discussant Marina Chiara Garassino, MBBS, professor of medicine at the University of Chicago, also acknowledged the importance of the findings, noting the “multiple possibilities” for treatment selection in the metastatic nonsquamous NSCLC patient population.
Although patients with PD-L1 expression below 50% derive clear benefit from combination versus single-agent therapy, treatment selection for those with high PD-L1 expression is “very tricky and debatable,” she said.
For those with high PD-L1 expression, the choice is less clear and wrought with uncertainties – particularly for certain subgroups like never-smokers and those with PD-L1 expression over 90%, she said.
The findings reinforce those seen in prior meta-analyses and other clinical trials, particularly with respect to the role of smoking history when making treatment decisions.
“After these results and previous subgroup analyses, in my opinion, in [patients with] PD-L1 expression over 50%, we should consider the combination of chemotherapy and immunotherapy,” she said.
Conversely, findings from this study showing no difference in outcomes between the treatment approaches in patients with brain or liver metastases are based on small numbers and lack power for drawing any conclusions, she said. It also remains unclear whether there is a differential effect for women and those with PD-L1 expression over 90%, high tumor mutation burden, performance score greater than 2, and age over 75 years.
Both Dr. Garassino and Dr. Peters said they are looking to the INSIGNA trial, which is currently recruiting patients in the United States to evaluate the timing of pembrolizumab alone or with chemotherapy as first-line treatment and maintenance in NSCLC, to provide more clarification regarding the best treatment approaches.
This study was funded by F. Hoffmann–La Roche. Dr. Peters and Dr. Garassino each disclosed personal and/or institutional financial relationships with numerous pharmaceutical companies.
FROM ESMO 2021
‘Alarming’ increase in fake pills laced with fentanyl, methamphetamine, DEA warns
The U.S. Drug Enforcement Administration has issued a public safety alert over an “alarming” increase in fake prescription pills laced with the synthetic opioid fentanyl or the stimulant methamphetamine.
“The United States is facing an unprecedented crisis of overdose deaths fueled by illegally manufactured fentanyl and methamphetamine,” DEA Administrator Anne Milgram said in the alert.
“Counterfeit pills that contain these dangerous and extremely addictive drugs are more lethal and more accessible than ever before. DEA is focusing resources on taking down the violent drug traffickers causing the greatest harm and posing the greatest threat to the safety and health of Americans,” Ms. Milgram said.
Criminal drug networks are mass-producing fake fentanyl- and methamphetamine-laced pills and deceptively marketing them as legitimate prescription pills, the DEA warns.
such as oxycodone (Oxycontin, Percocet), hydrocodone (Vicodin), and alprazolam (Xanax); or stimulants like amphetamines (Adderall).
The agency has seized fake pills in every U.S. state. More than 9.5 million fake pills have been seized so far this year – more than the last 2 years combined.
The number of seized counterfeit pills with fentanyl has jumped nearly 430% since 2019. DEA lab tests reveal that two out of every five pills with fentanyl contain a potentially lethal dose.
These deadly pills are widely accessible and often sold on social media and e-commerce platforms – making them available to anyone with a smartphone, including minors, the DEA warns.
More than 93,000 people died of a drug overdose in the United States last year, according to federal statistics, and fentanyl is the primary driver of this alarming increase in overdose deaths, the DEA says.
The agency has launched a “One Pill Can Kill” public awareness campaign to educate the public of the dangers of counterfeit pills purchased outside of a licensed pharmacy. These pills are “illegal, dangerous, and potentially lethal,” the DEA warns.
This alert does not apply to legitimate pharmaceutical medications prescribed by doctors and dispensed by licensed pharmacists, the DEA says.
“The legitimate prescription supply chain is not impacted. Anyone filling a prescription at a licensed pharmacy can be confident that the medications they receive are safe when taken as directed by a medical professional,” the agency says.
A version of this article first appeared on Medscape.com.
The U.S. Drug Enforcement Administration has issued a public safety alert over an “alarming” increase in fake prescription pills laced with the synthetic opioid fentanyl or the stimulant methamphetamine.
“The United States is facing an unprecedented crisis of overdose deaths fueled by illegally manufactured fentanyl and methamphetamine,” DEA Administrator Anne Milgram said in the alert.
“Counterfeit pills that contain these dangerous and extremely addictive drugs are more lethal and more accessible than ever before. DEA is focusing resources on taking down the violent drug traffickers causing the greatest harm and posing the greatest threat to the safety and health of Americans,” Ms. Milgram said.
Criminal drug networks are mass-producing fake fentanyl- and methamphetamine-laced pills and deceptively marketing them as legitimate prescription pills, the DEA warns.
such as oxycodone (Oxycontin, Percocet), hydrocodone (Vicodin), and alprazolam (Xanax); or stimulants like amphetamines (Adderall).
The agency has seized fake pills in every U.S. state. More than 9.5 million fake pills have been seized so far this year – more than the last 2 years combined.
The number of seized counterfeit pills with fentanyl has jumped nearly 430% since 2019. DEA lab tests reveal that two out of every five pills with fentanyl contain a potentially lethal dose.
These deadly pills are widely accessible and often sold on social media and e-commerce platforms – making them available to anyone with a smartphone, including minors, the DEA warns.
More than 93,000 people died of a drug overdose in the United States last year, according to federal statistics, and fentanyl is the primary driver of this alarming increase in overdose deaths, the DEA says.
The agency has launched a “One Pill Can Kill” public awareness campaign to educate the public of the dangers of counterfeit pills purchased outside of a licensed pharmacy. These pills are “illegal, dangerous, and potentially lethal,” the DEA warns.
This alert does not apply to legitimate pharmaceutical medications prescribed by doctors and dispensed by licensed pharmacists, the DEA says.
“The legitimate prescription supply chain is not impacted. Anyone filling a prescription at a licensed pharmacy can be confident that the medications they receive are safe when taken as directed by a medical professional,” the agency says.
A version of this article first appeared on Medscape.com.
The U.S. Drug Enforcement Administration has issued a public safety alert over an “alarming” increase in fake prescription pills laced with the synthetic opioid fentanyl or the stimulant methamphetamine.
“The United States is facing an unprecedented crisis of overdose deaths fueled by illegally manufactured fentanyl and methamphetamine,” DEA Administrator Anne Milgram said in the alert.
“Counterfeit pills that contain these dangerous and extremely addictive drugs are more lethal and more accessible than ever before. DEA is focusing resources on taking down the violent drug traffickers causing the greatest harm and posing the greatest threat to the safety and health of Americans,” Ms. Milgram said.
Criminal drug networks are mass-producing fake fentanyl- and methamphetamine-laced pills and deceptively marketing them as legitimate prescription pills, the DEA warns.
such as oxycodone (Oxycontin, Percocet), hydrocodone (Vicodin), and alprazolam (Xanax); or stimulants like amphetamines (Adderall).
The agency has seized fake pills in every U.S. state. More than 9.5 million fake pills have been seized so far this year – more than the last 2 years combined.
The number of seized counterfeit pills with fentanyl has jumped nearly 430% since 2019. DEA lab tests reveal that two out of every five pills with fentanyl contain a potentially lethal dose.
These deadly pills are widely accessible and often sold on social media and e-commerce platforms – making them available to anyone with a smartphone, including minors, the DEA warns.
More than 93,000 people died of a drug overdose in the United States last year, according to federal statistics, and fentanyl is the primary driver of this alarming increase in overdose deaths, the DEA says.
The agency has launched a “One Pill Can Kill” public awareness campaign to educate the public of the dangers of counterfeit pills purchased outside of a licensed pharmacy. These pills are “illegal, dangerous, and potentially lethal,” the DEA warns.
This alert does not apply to legitimate pharmaceutical medications prescribed by doctors and dispensed by licensed pharmacists, the DEA says.
“The legitimate prescription supply chain is not impacted. Anyone filling a prescription at a licensed pharmacy can be confident that the medications they receive are safe when taken as directed by a medical professional,” the agency says.
A version of this article first appeared on Medscape.com.
Should Geriatric Veterans Get Immunotherapy?
Patients in their 90s with cancer tolerated immunotherapy well with few serious adverse effects, and they lived for an average of 1.6 years after treatment, a small new study within the US Department of Veterans Affairs (VA) health system reports.
Only 6.3% of 48 patients who were treated with immune checkpoint inhibitors experienced the most severe types of side effects – grade III/IV events – and a total of 27% had any adverse effects, according to the report, which was presented at the 2021 annual meeting of the Association of VA Hematology/Oncology (AVAHO) being held virtually and inperson in Denver Colorado, September 24 to September 26, 2021.
“Our project should help give confidence to oncologists treating the elderly,” said Andrew Joseph Benefield, MD, a hematology/oncology fellow at Wake Forest Baptist Medical Center, in an interview. “Immunotherapy can be given safely and likely effectively in select individuals over the age of 90 with good performance status.”
Benefield and colleagues launched their study to gain insight into a little-studied area: How does cancer treatment affects nonagenarians? “I think many oncologists have been in a situation where they encounter an individual over the age of 90 years who has a good performance status, and they've wondered if immunotherapy would be helpful and safe, particularly given our knowledge of waning immune strength as people age,” he said.
The researchers retrospectively tracked patients with cancer who were at least 90 years old from 2016 to 2017 and were treated with immune checkpoint inhibitors. Most were fit or fairly fit with Eastern Cooperative Oncology Group (ECOG) physical performance scales of 0 or 1 (n = 26), and nearly all had cancer in stage IV (n = 42). Melanoma was the most common type of cancer (n = 19), followed by non-small-cell lung cancer (n = 15). Patients were treated with an average of 12.2 cycles.
“In general, we saw that treatment was well-tolerated,” Dr. Benefield said. “We also noted that a trend toward better long-term survival outcomes in individuals with very good performance status at the start of treatment. We hope to parse this out more as we add more data to our data-set, as the numbers are still too small for confident direct comparison.”
Dr. Benefield said he has treated a limited number of patients in their 90s who were highly physical fit for their age and “very eager” to be treated. “They wanted to do anything they could to maintain their lifestyle,” he said. “In my experience, aggressive supportive care and close monitoring for developing toxicities has been most helpful.”
The researchers don’t know the causes of death of many of the patients, and it’s not clear how they fared in their final days. Still, Dr. Benefield said, “extending someone's life by more than 1 year with relatively low risk of adverse effects is reasonable.”
Oncologist Melisa Wong, MD, MAS, of the University of California, San Francisco, reviewed the study and said in an interview that it “a valuable description of outcomes for nonagenarians receiving immunotherapy in the VA healthcare system.” As she noted, “many other studies of immunotherapy among older adults focus on patients aged 65 or 70 and older while very few focus on octogenarians or nonagenarians.”
The findings suggest that “it is important to move beyond chronological age and assess patients’ physiologic age through a geriatric assessment,” she said. “Geriatric assessment-derived risk scores have been shown to predict chemotherapy toxicity for older adults and research to develop similar tools for immunotherapy are ongoing.”
However, she cautioned that older patients may become suffer so much from the most common side effect of immunotherapy -- fatigue – that “their independence is at stake.”
“Some of these patient choose to stop immunotherapy because the side effects aren’t worth it anymore,” she said. “The challenge for oncologists is not knowing in advance which patients will fall into each of these categories.”
She added that her geriatric oncology research focuses on improving risk stratification for older adults, such as those who are at least 70 with lung adenocarcinoma.
Oncologist Grant R. Williams, MD, MSPH, director of the Cancer & Aging Program at the University of Alabama at Birmingham, agreed in an interview that comprehensive geriatric assessments are important to guide treatment in the oldest adults. “In addition, it is important to elicit the goals of treatment as well,” he said. “For older adults that are fit or at least pre-frail and desire aggressive treatment, immunotherapy is a very reasonable approach, particularly when patients are closely monitored for side effects.”
No study funding is reported. The authors report no disclosures. Dr. Wong discloses an immediate family member is an employee and stock holder of Genentech. Dr. Williams has no disclosures.
Patients in their 90s with cancer tolerated immunotherapy well with few serious adverse effects, and they lived for an average of 1.6 years after treatment, a small new study within the US Department of Veterans Affairs (VA) health system reports.
Only 6.3% of 48 patients who were treated with immune checkpoint inhibitors experienced the most severe types of side effects – grade III/IV events – and a total of 27% had any adverse effects, according to the report, which was presented at the 2021 annual meeting of the Association of VA Hematology/Oncology (AVAHO) being held virtually and inperson in Denver Colorado, September 24 to September 26, 2021.
“Our project should help give confidence to oncologists treating the elderly,” said Andrew Joseph Benefield, MD, a hematology/oncology fellow at Wake Forest Baptist Medical Center, in an interview. “Immunotherapy can be given safely and likely effectively in select individuals over the age of 90 with good performance status.”
Benefield and colleagues launched their study to gain insight into a little-studied area: How does cancer treatment affects nonagenarians? “I think many oncologists have been in a situation where they encounter an individual over the age of 90 years who has a good performance status, and they've wondered if immunotherapy would be helpful and safe, particularly given our knowledge of waning immune strength as people age,” he said.
The researchers retrospectively tracked patients with cancer who were at least 90 years old from 2016 to 2017 and were treated with immune checkpoint inhibitors. Most were fit or fairly fit with Eastern Cooperative Oncology Group (ECOG) physical performance scales of 0 or 1 (n = 26), and nearly all had cancer in stage IV (n = 42). Melanoma was the most common type of cancer (n = 19), followed by non-small-cell lung cancer (n = 15). Patients were treated with an average of 12.2 cycles.
“In general, we saw that treatment was well-tolerated,” Dr. Benefield said. “We also noted that a trend toward better long-term survival outcomes in individuals with very good performance status at the start of treatment. We hope to parse this out more as we add more data to our data-set, as the numbers are still too small for confident direct comparison.”
Dr. Benefield said he has treated a limited number of patients in their 90s who were highly physical fit for their age and “very eager” to be treated. “They wanted to do anything they could to maintain their lifestyle,” he said. “In my experience, aggressive supportive care and close monitoring for developing toxicities has been most helpful.”
The researchers don’t know the causes of death of many of the patients, and it’s not clear how they fared in their final days. Still, Dr. Benefield said, “extending someone's life by more than 1 year with relatively low risk of adverse effects is reasonable.”
Oncologist Melisa Wong, MD, MAS, of the University of California, San Francisco, reviewed the study and said in an interview that it “a valuable description of outcomes for nonagenarians receiving immunotherapy in the VA healthcare system.” As she noted, “many other studies of immunotherapy among older adults focus on patients aged 65 or 70 and older while very few focus on octogenarians or nonagenarians.”
The findings suggest that “it is important to move beyond chronological age and assess patients’ physiologic age through a geriatric assessment,” she said. “Geriatric assessment-derived risk scores have been shown to predict chemotherapy toxicity for older adults and research to develop similar tools for immunotherapy are ongoing.”
However, she cautioned that older patients may become suffer so much from the most common side effect of immunotherapy -- fatigue – that “their independence is at stake.”
“Some of these patient choose to stop immunotherapy because the side effects aren’t worth it anymore,” she said. “The challenge for oncologists is not knowing in advance which patients will fall into each of these categories.”
She added that her geriatric oncology research focuses on improving risk stratification for older adults, such as those who are at least 70 with lung adenocarcinoma.
Oncologist Grant R. Williams, MD, MSPH, director of the Cancer & Aging Program at the University of Alabama at Birmingham, agreed in an interview that comprehensive geriatric assessments are important to guide treatment in the oldest adults. “In addition, it is important to elicit the goals of treatment as well,” he said. “For older adults that are fit or at least pre-frail and desire aggressive treatment, immunotherapy is a very reasonable approach, particularly when patients are closely monitored for side effects.”
No study funding is reported. The authors report no disclosures. Dr. Wong discloses an immediate family member is an employee and stock holder of Genentech. Dr. Williams has no disclosures.
Patients in their 90s with cancer tolerated immunotherapy well with few serious adverse effects, and they lived for an average of 1.6 years after treatment, a small new study within the US Department of Veterans Affairs (VA) health system reports.
Only 6.3% of 48 patients who were treated with immune checkpoint inhibitors experienced the most severe types of side effects – grade III/IV events – and a total of 27% had any adverse effects, according to the report, which was presented at the 2021 annual meeting of the Association of VA Hematology/Oncology (AVAHO) being held virtually and inperson in Denver Colorado, September 24 to September 26, 2021.
“Our project should help give confidence to oncologists treating the elderly,” said Andrew Joseph Benefield, MD, a hematology/oncology fellow at Wake Forest Baptist Medical Center, in an interview. “Immunotherapy can be given safely and likely effectively in select individuals over the age of 90 with good performance status.”
Benefield and colleagues launched their study to gain insight into a little-studied area: How does cancer treatment affects nonagenarians? “I think many oncologists have been in a situation where they encounter an individual over the age of 90 years who has a good performance status, and they've wondered if immunotherapy would be helpful and safe, particularly given our knowledge of waning immune strength as people age,” he said.
The researchers retrospectively tracked patients with cancer who were at least 90 years old from 2016 to 2017 and were treated with immune checkpoint inhibitors. Most were fit or fairly fit with Eastern Cooperative Oncology Group (ECOG) physical performance scales of 0 or 1 (n = 26), and nearly all had cancer in stage IV (n = 42). Melanoma was the most common type of cancer (n = 19), followed by non-small-cell lung cancer (n = 15). Patients were treated with an average of 12.2 cycles.
“In general, we saw that treatment was well-tolerated,” Dr. Benefield said. “We also noted that a trend toward better long-term survival outcomes in individuals with very good performance status at the start of treatment. We hope to parse this out more as we add more data to our data-set, as the numbers are still too small for confident direct comparison.”
Dr. Benefield said he has treated a limited number of patients in their 90s who were highly physical fit for their age and “very eager” to be treated. “They wanted to do anything they could to maintain their lifestyle,” he said. “In my experience, aggressive supportive care and close monitoring for developing toxicities has been most helpful.”
The researchers don’t know the causes of death of many of the patients, and it’s not clear how they fared in their final days. Still, Dr. Benefield said, “extending someone's life by more than 1 year with relatively low risk of adverse effects is reasonable.”
Oncologist Melisa Wong, MD, MAS, of the University of California, San Francisco, reviewed the study and said in an interview that it “a valuable description of outcomes for nonagenarians receiving immunotherapy in the VA healthcare system.” As she noted, “many other studies of immunotherapy among older adults focus on patients aged 65 or 70 and older while very few focus on octogenarians or nonagenarians.”
The findings suggest that “it is important to move beyond chronological age and assess patients’ physiologic age through a geriatric assessment,” she said. “Geriatric assessment-derived risk scores have been shown to predict chemotherapy toxicity for older adults and research to develop similar tools for immunotherapy are ongoing.”
However, she cautioned that older patients may become suffer so much from the most common side effect of immunotherapy -- fatigue – that “their independence is at stake.”
“Some of these patient choose to stop immunotherapy because the side effects aren’t worth it anymore,” she said. “The challenge for oncologists is not knowing in advance which patients will fall into each of these categories.”
She added that her geriatric oncology research focuses on improving risk stratification for older adults, such as those who are at least 70 with lung adenocarcinoma.
Oncologist Grant R. Williams, MD, MSPH, director of the Cancer & Aging Program at the University of Alabama at Birmingham, agreed in an interview that comprehensive geriatric assessments are important to guide treatment in the oldest adults. “In addition, it is important to elicit the goals of treatment as well,” he said. “For older adults that are fit or at least pre-frail and desire aggressive treatment, immunotherapy is a very reasonable approach, particularly when patients are closely monitored for side effects.”
No study funding is reported. The authors report no disclosures. Dr. Wong discloses an immediate family member is an employee and stock holder of Genentech. Dr. Williams has no disclosures.
FDA approves first oral drug for NSCLC with EGFR Exon 20 insertion
The drug is limited to use in patients whose disease has progressed on or after platinum-based chemotherapy and who have had the EGFR Exon 20 insertion mutation detected on an FDA-approved test.
Mobocertinib is the first oral tyrosine kinase inhibitor (TKI) specifically designed to target these mutations, which are less common than the more predominant EGFR mutations in this lung cancer.
“EGFR Exon 20 insertion+ NSCLC is an underserved cancer that we have been unable to target effectively with traditional EGFR TKIs,” said Pasi Jänne, MD, PhD, of the Dana Farber Cancer Institute, Boston, in a press statement from the maker, Takeda.
“The approval of [mobocertinib] marks another important step forward that provides physicians and their patients with a new targeted oral therapy specifically designed for this patient population that has shown clinically meaningful and sustained responses,” Dr. Jänne added.
According to the company, EGFR Exon 20 insertion+ NSCLC makes up approximately 1%-2% of patients with NSCLC and is more common in Asian populations compared with Western populations.
The new approval is based on overall response rate (ORR) and duration of response (DoR) results from a phase 1/2 trial consisting of 114 patients with EGFR Exon 20 insertion+ NSCLC who received prior platinum-based therapy and were treated with the 160-mg dose.
Per an independent review committee, mobocertinib demonstrated a confirmed ORR of 28% and a median DoR of 17.5 months.
Median overall survival was 24 months and median progression-free survival was 7.3 months.
The FDA-approved next-generation sequencing (NGS) companion diagnostic for mobocertinib is Thermo Fisher Scientific’s Oncomine Dx Target Test, which identifies NSCLC patients with EGFR Exon 20 insertions.
“NGS testing is critical for these patients, as it can enable more accurate diagnoses compared to polymerase chain reaction (PCR) testing, which detects less than 50% of EGFR Exon 20 insertions,” according to the company.
Results from the phase 1/2 trial used in the FDA approval were presented at the 2021 American Society of Clinical Oncology Annual Meeting.
The most common adverse reactions (greater than 20%) were diarrhea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin, and musculoskeletal pain, according to the company.
The prescribing information includes a boxed warning for QTc prolongation and Torsades de Pointes, and warnings and precautions for interstitial lung disease/pneumonitis, cardiac toxicity, and diarrhea.
“Patients with EGFR Exon 20 insertion+ NSCLC have historically faced a unique set of challenges living with a very rare lung cancer that is not only underdiagnosed but also lacking targeted treatment options that can improve response rates,” said Marcia Horn, executive director, Exon 20 Group at the International Cancer Advocacy Network, in the press statement.
The FDA review was conducted under Project Orbis, an FDA initiative that enables concurrent submission and review of oncology products among international partners.
The new drug was also granted priority review and received breakthrough therapy, fast track, and orphan drug designations from the FDA.
A version of this article first appeared on Medscape.com.
The drug is limited to use in patients whose disease has progressed on or after platinum-based chemotherapy and who have had the EGFR Exon 20 insertion mutation detected on an FDA-approved test.
Mobocertinib is the first oral tyrosine kinase inhibitor (TKI) specifically designed to target these mutations, which are less common than the more predominant EGFR mutations in this lung cancer.
“EGFR Exon 20 insertion+ NSCLC is an underserved cancer that we have been unable to target effectively with traditional EGFR TKIs,” said Pasi Jänne, MD, PhD, of the Dana Farber Cancer Institute, Boston, in a press statement from the maker, Takeda.
“The approval of [mobocertinib] marks another important step forward that provides physicians and their patients with a new targeted oral therapy specifically designed for this patient population that has shown clinically meaningful and sustained responses,” Dr. Jänne added.
According to the company, EGFR Exon 20 insertion+ NSCLC makes up approximately 1%-2% of patients with NSCLC and is more common in Asian populations compared with Western populations.
The new approval is based on overall response rate (ORR) and duration of response (DoR) results from a phase 1/2 trial consisting of 114 patients with EGFR Exon 20 insertion+ NSCLC who received prior platinum-based therapy and were treated with the 160-mg dose.
Per an independent review committee, mobocertinib demonstrated a confirmed ORR of 28% and a median DoR of 17.5 months.
Median overall survival was 24 months and median progression-free survival was 7.3 months.
The FDA-approved next-generation sequencing (NGS) companion diagnostic for mobocertinib is Thermo Fisher Scientific’s Oncomine Dx Target Test, which identifies NSCLC patients with EGFR Exon 20 insertions.
“NGS testing is critical for these patients, as it can enable more accurate diagnoses compared to polymerase chain reaction (PCR) testing, which detects less than 50% of EGFR Exon 20 insertions,” according to the company.
Results from the phase 1/2 trial used in the FDA approval were presented at the 2021 American Society of Clinical Oncology Annual Meeting.
The most common adverse reactions (greater than 20%) were diarrhea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin, and musculoskeletal pain, according to the company.
The prescribing information includes a boxed warning for QTc prolongation and Torsades de Pointes, and warnings and precautions for interstitial lung disease/pneumonitis, cardiac toxicity, and diarrhea.
“Patients with EGFR Exon 20 insertion+ NSCLC have historically faced a unique set of challenges living with a very rare lung cancer that is not only underdiagnosed but also lacking targeted treatment options that can improve response rates,” said Marcia Horn, executive director, Exon 20 Group at the International Cancer Advocacy Network, in the press statement.
The FDA review was conducted under Project Orbis, an FDA initiative that enables concurrent submission and review of oncology products among international partners.
The new drug was also granted priority review and received breakthrough therapy, fast track, and orphan drug designations from the FDA.
A version of this article first appeared on Medscape.com.
The drug is limited to use in patients whose disease has progressed on or after platinum-based chemotherapy and who have had the EGFR Exon 20 insertion mutation detected on an FDA-approved test.
Mobocertinib is the first oral tyrosine kinase inhibitor (TKI) specifically designed to target these mutations, which are less common than the more predominant EGFR mutations in this lung cancer.
“EGFR Exon 20 insertion+ NSCLC is an underserved cancer that we have been unable to target effectively with traditional EGFR TKIs,” said Pasi Jänne, MD, PhD, of the Dana Farber Cancer Institute, Boston, in a press statement from the maker, Takeda.
“The approval of [mobocertinib] marks another important step forward that provides physicians and their patients with a new targeted oral therapy specifically designed for this patient population that has shown clinically meaningful and sustained responses,” Dr. Jänne added.
According to the company, EGFR Exon 20 insertion+ NSCLC makes up approximately 1%-2% of patients with NSCLC and is more common in Asian populations compared with Western populations.
The new approval is based on overall response rate (ORR) and duration of response (DoR) results from a phase 1/2 trial consisting of 114 patients with EGFR Exon 20 insertion+ NSCLC who received prior platinum-based therapy and were treated with the 160-mg dose.
Per an independent review committee, mobocertinib demonstrated a confirmed ORR of 28% and a median DoR of 17.5 months.
Median overall survival was 24 months and median progression-free survival was 7.3 months.
The FDA-approved next-generation sequencing (NGS) companion diagnostic for mobocertinib is Thermo Fisher Scientific’s Oncomine Dx Target Test, which identifies NSCLC patients with EGFR Exon 20 insertions.
“NGS testing is critical for these patients, as it can enable more accurate diagnoses compared to polymerase chain reaction (PCR) testing, which detects less than 50% of EGFR Exon 20 insertions,” according to the company.
Results from the phase 1/2 trial used in the FDA approval were presented at the 2021 American Society of Clinical Oncology Annual Meeting.
The most common adverse reactions (greater than 20%) were diarrhea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin, and musculoskeletal pain, according to the company.
The prescribing information includes a boxed warning for QTc prolongation and Torsades de Pointes, and warnings and precautions for interstitial lung disease/pneumonitis, cardiac toxicity, and diarrhea.
“Patients with EGFR Exon 20 insertion+ NSCLC have historically faced a unique set of challenges living with a very rare lung cancer that is not only underdiagnosed but also lacking targeted treatment options that can improve response rates,” said Marcia Horn, executive director, Exon 20 Group at the International Cancer Advocacy Network, in the press statement.
The FDA review was conducted under Project Orbis, an FDA initiative that enables concurrent submission and review of oncology products among international partners.
The new drug was also granted priority review and received breakthrough therapy, fast track, and orphan drug designations from the FDA.
A version of this article first appeared on Medscape.com.
Moderna vaccine more effective than Pfizer and J&J
the Centers for Disease Control and Protection has said.
“Among U.S. adults without immunocompromising conditions, vaccine effectiveness against COVID-19 hospitalization during March 11–Aug. 15, 2021, was higher for the Moderna vaccine (93%) than the Pfizer-BioNTech vaccine (88%) and the Janssen vaccine (71%),” the agency’s Morbidity and Mortality Weekly Report said. Janssen refers to the Johnson & Johnson vaccine.
The CDC said the data could help people make informed decisions.
“Understanding differences in VE [vaccine effectiveness] by vaccine product can guide individual choices and policy recommendations regarding vaccine boosters. All Food and Drug Administration–approved or authorized COVID-19 vaccines provide substantial protection against COVID-19 hospitalization,” the report said.
The study also broke down effectiveness for longer periods. Moderna came out on top again.
After 120 days, the Moderna vaccine provided 92% effectiveness against hospitalization, whereas the Pfizer vaccine’s effectiveness dropped to 77%, the CDC said. There was no similar calculation for the Johnson & Johnson vaccine.
The CDC studied 3,689 adults at 21 hospitals in 18 states who got the two-shot Pfizer or Moderna vaccine or the one-shot Johnson & Johnson vaccine between March and August.
The agency noted some factors that could have come into play.
“Differences in vaccine effectiveness between the Moderna and Pfizer-BioNTech vaccine might be due to higher mRNA content in the Moderna vaccine, differences in timing between doses (3 weeks for Pfizer-BioNTech vs. 4 weeks for Moderna), or possible differences between groups that received each vaccine that were not accounted for in the analysis,” the report said.
The CDC noted limitations in the findings. Children, immunocompromised adults, and vaccine effectiveness against COVID-19 that did not result in hospitalization were not studied.
Other studies have shown all three U.S. vaccines provide a high rate of protection against coronavirus.
A version of this article first appeared on WebMD.com.
the Centers for Disease Control and Protection has said.
“Among U.S. adults without immunocompromising conditions, vaccine effectiveness against COVID-19 hospitalization during March 11–Aug. 15, 2021, was higher for the Moderna vaccine (93%) than the Pfizer-BioNTech vaccine (88%) and the Janssen vaccine (71%),” the agency’s Morbidity and Mortality Weekly Report said. Janssen refers to the Johnson & Johnson vaccine.
The CDC said the data could help people make informed decisions.
“Understanding differences in VE [vaccine effectiveness] by vaccine product can guide individual choices and policy recommendations regarding vaccine boosters. All Food and Drug Administration–approved or authorized COVID-19 vaccines provide substantial protection against COVID-19 hospitalization,” the report said.
The study also broke down effectiveness for longer periods. Moderna came out on top again.
After 120 days, the Moderna vaccine provided 92% effectiveness against hospitalization, whereas the Pfizer vaccine’s effectiveness dropped to 77%, the CDC said. There was no similar calculation for the Johnson & Johnson vaccine.
The CDC studied 3,689 adults at 21 hospitals in 18 states who got the two-shot Pfizer or Moderna vaccine or the one-shot Johnson & Johnson vaccine between March and August.
The agency noted some factors that could have come into play.
“Differences in vaccine effectiveness between the Moderna and Pfizer-BioNTech vaccine might be due to higher mRNA content in the Moderna vaccine, differences in timing between doses (3 weeks for Pfizer-BioNTech vs. 4 weeks for Moderna), or possible differences between groups that received each vaccine that were not accounted for in the analysis,” the report said.
The CDC noted limitations in the findings. Children, immunocompromised adults, and vaccine effectiveness against COVID-19 that did not result in hospitalization were not studied.
Other studies have shown all three U.S. vaccines provide a high rate of protection against coronavirus.
A version of this article first appeared on WebMD.com.
the Centers for Disease Control and Protection has said.
“Among U.S. adults without immunocompromising conditions, vaccine effectiveness against COVID-19 hospitalization during March 11–Aug. 15, 2021, was higher for the Moderna vaccine (93%) than the Pfizer-BioNTech vaccine (88%) and the Janssen vaccine (71%),” the agency’s Morbidity and Mortality Weekly Report said. Janssen refers to the Johnson & Johnson vaccine.
The CDC said the data could help people make informed decisions.
“Understanding differences in VE [vaccine effectiveness] by vaccine product can guide individual choices and policy recommendations regarding vaccine boosters. All Food and Drug Administration–approved or authorized COVID-19 vaccines provide substantial protection against COVID-19 hospitalization,” the report said.
The study also broke down effectiveness for longer periods. Moderna came out on top again.
After 120 days, the Moderna vaccine provided 92% effectiveness against hospitalization, whereas the Pfizer vaccine’s effectiveness dropped to 77%, the CDC said. There was no similar calculation for the Johnson & Johnson vaccine.
The CDC studied 3,689 adults at 21 hospitals in 18 states who got the two-shot Pfizer or Moderna vaccine or the one-shot Johnson & Johnson vaccine between March and August.
The agency noted some factors that could have come into play.
“Differences in vaccine effectiveness between the Moderna and Pfizer-BioNTech vaccine might be due to higher mRNA content in the Moderna vaccine, differences in timing between doses (3 weeks for Pfizer-BioNTech vs. 4 weeks for Moderna), or possible differences between groups that received each vaccine that were not accounted for in the analysis,” the report said.
The CDC noted limitations in the findings. Children, immunocompromised adults, and vaccine effectiveness against COVID-19 that did not result in hospitalization were not studied.
Other studies have shown all three U.S. vaccines provide a high rate of protection against coronavirus.
A version of this article first appeared on WebMD.com.
Nonopioid med promising for neuropathic pain
Top-line results from a phase 2 study suggest vixotrigine (BIIB074, Biogen), a nonopioid investigational oral pain medication, reduces chronic neuropathic pain caused by small fiber neuropathy (SFN) and is generally well tolerated.
“We are encouraged by the overall results of the CONVEY study, especially given the significant unmet medical need for additional agents to treat chronic painful neuropathy,” Katherine Dawson, MD, senior vice president and head of the therapeutics development unit at Biogen, said in a news release.
Vixotrigine (BIIB074) is a peripherally and centrally acting, orally administered, voltage- and use-dependent voltage-gated sodium channel blocker.
CONVEY was a phase 2, placebo-controlled, double-blind, randomized withdrawal study of 265 patients experiencing pain from confirmed idiopathic or diabetes-associated SFN.
Following a 4-week open-label run-in period, 123 responders to vixotrigine were randomly allocated to 200 mg or 350 mg vixotrigine or placebo twice daily for 12 weeks in the double-blind portion of the study.
At week 12, vixotrigine 200 mg twice daily met the primary endpoint of a statistically significant reduction from baseline in the mean average daily pain (ADP) score versus placebo (P = .0501).
A subgroup analysis showed a treatment effect in patients with diabetes-associated SFN but not in the smaller subgroup of patients with idiopathic SFN.
The 200-mg dose also led to a significant improvement over placebo in mean worst daily pain score at 12 weeks (P = .0455).
A numeric advantage of 200 mg vixotrigine over placebo was observed in additional secondary endpoints, including the proportion of patients with at least a 2-point improvement in ADP score and the proportion with at least a 30% reduction in ADP at week 12, but these failed to reach statistical significance.
Vixotrigine 350 mg twice daily did not meet the primary endpoint of mean change in ADP at 12 weeks.
However, treatment at the higher dose led to a significant increase in the proportion of patients who reported being “very much improved” or “much improved” over baseline (P = .0580), Biogen reported.
In addition, a numeric advantage of 350 mg over placebo was observed in the proportion of patients with a 2-point or greater improvement in ADP score and the proportion with at least a 30% reduction in ADP at 12 weeks, but these also did not reach statistical significance.
Both doses of vixotrigine were “generally well tolerated and the safety profile was consistent with previous studies of vixotrigine with no evidence of abuse potential,” the company said.
In the open-label period, common adverse events seen in at least 2.5% of patients were dizziness, headache, vertigo, and nausea; adverse events led 5.3% of patients to discontinue the open-label portion of the study. Across the entire study, most adverse events were mild or moderate in severity.
“The totality of data from the vixotrigine program will inform potential doses for study in future phase 3 clinical trials,” the company said.
A version of this article first appeared on Medscape.com.
Top-line results from a phase 2 study suggest vixotrigine (BIIB074, Biogen), a nonopioid investigational oral pain medication, reduces chronic neuropathic pain caused by small fiber neuropathy (SFN) and is generally well tolerated.
“We are encouraged by the overall results of the CONVEY study, especially given the significant unmet medical need for additional agents to treat chronic painful neuropathy,” Katherine Dawson, MD, senior vice president and head of the therapeutics development unit at Biogen, said in a news release.
Vixotrigine (BIIB074) is a peripherally and centrally acting, orally administered, voltage- and use-dependent voltage-gated sodium channel blocker.
CONVEY was a phase 2, placebo-controlled, double-blind, randomized withdrawal study of 265 patients experiencing pain from confirmed idiopathic or diabetes-associated SFN.
Following a 4-week open-label run-in period, 123 responders to vixotrigine were randomly allocated to 200 mg or 350 mg vixotrigine or placebo twice daily for 12 weeks in the double-blind portion of the study.
At week 12, vixotrigine 200 mg twice daily met the primary endpoint of a statistically significant reduction from baseline in the mean average daily pain (ADP) score versus placebo (P = .0501).
A subgroup analysis showed a treatment effect in patients with diabetes-associated SFN but not in the smaller subgroup of patients with idiopathic SFN.
The 200-mg dose also led to a significant improvement over placebo in mean worst daily pain score at 12 weeks (P = .0455).
A numeric advantage of 200 mg vixotrigine over placebo was observed in additional secondary endpoints, including the proportion of patients with at least a 2-point improvement in ADP score and the proportion with at least a 30% reduction in ADP at week 12, but these failed to reach statistical significance.
Vixotrigine 350 mg twice daily did not meet the primary endpoint of mean change in ADP at 12 weeks.
However, treatment at the higher dose led to a significant increase in the proportion of patients who reported being “very much improved” or “much improved” over baseline (P = .0580), Biogen reported.
In addition, a numeric advantage of 350 mg over placebo was observed in the proportion of patients with a 2-point or greater improvement in ADP score and the proportion with at least a 30% reduction in ADP at 12 weeks, but these also did not reach statistical significance.
Both doses of vixotrigine were “generally well tolerated and the safety profile was consistent with previous studies of vixotrigine with no evidence of abuse potential,” the company said.
In the open-label period, common adverse events seen in at least 2.5% of patients were dizziness, headache, vertigo, and nausea; adverse events led 5.3% of patients to discontinue the open-label portion of the study. Across the entire study, most adverse events were mild or moderate in severity.
“The totality of data from the vixotrigine program will inform potential doses for study in future phase 3 clinical trials,” the company said.
A version of this article first appeared on Medscape.com.
Top-line results from a phase 2 study suggest vixotrigine (BIIB074, Biogen), a nonopioid investigational oral pain medication, reduces chronic neuropathic pain caused by small fiber neuropathy (SFN) and is generally well tolerated.
“We are encouraged by the overall results of the CONVEY study, especially given the significant unmet medical need for additional agents to treat chronic painful neuropathy,” Katherine Dawson, MD, senior vice president and head of the therapeutics development unit at Biogen, said in a news release.
Vixotrigine (BIIB074) is a peripherally and centrally acting, orally administered, voltage- and use-dependent voltage-gated sodium channel blocker.
CONVEY was a phase 2, placebo-controlled, double-blind, randomized withdrawal study of 265 patients experiencing pain from confirmed idiopathic or diabetes-associated SFN.
Following a 4-week open-label run-in period, 123 responders to vixotrigine were randomly allocated to 200 mg or 350 mg vixotrigine or placebo twice daily for 12 weeks in the double-blind portion of the study.
At week 12, vixotrigine 200 mg twice daily met the primary endpoint of a statistically significant reduction from baseline in the mean average daily pain (ADP) score versus placebo (P = .0501).
A subgroup analysis showed a treatment effect in patients with diabetes-associated SFN but not in the smaller subgroup of patients with idiopathic SFN.
The 200-mg dose also led to a significant improvement over placebo in mean worst daily pain score at 12 weeks (P = .0455).
A numeric advantage of 200 mg vixotrigine over placebo was observed in additional secondary endpoints, including the proportion of patients with at least a 2-point improvement in ADP score and the proportion with at least a 30% reduction in ADP at week 12, but these failed to reach statistical significance.
Vixotrigine 350 mg twice daily did not meet the primary endpoint of mean change in ADP at 12 weeks.
However, treatment at the higher dose led to a significant increase in the proportion of patients who reported being “very much improved” or “much improved” over baseline (P = .0580), Biogen reported.
In addition, a numeric advantage of 350 mg over placebo was observed in the proportion of patients with a 2-point or greater improvement in ADP score and the proportion with at least a 30% reduction in ADP at 12 weeks, but these also did not reach statistical significance.
Both doses of vixotrigine were “generally well tolerated and the safety profile was consistent with previous studies of vixotrigine with no evidence of abuse potential,” the company said.
In the open-label period, common adverse events seen in at least 2.5% of patients were dizziness, headache, vertigo, and nausea; adverse events led 5.3% of patients to discontinue the open-label portion of the study. Across the entire study, most adverse events were mild or moderate in severity.
“The totality of data from the vixotrigine program will inform potential doses for study in future phase 3 clinical trials,” the company said.
A version of this article first appeared on Medscape.com.
Low RA flare rate reported after Pfizer COVID vaccination
Patients with rheumatoid arthritis in remission had a rate of flare following vaccination with the Pfizer/BioNtech COVID-19 vaccine that appears to be on par with rates seen with other vaccines in patients with RA, according to results from a small Italian cohort study.
“Our data show a very low flare rate [7.8% (6 of 77)] after the BNT162b2 COVID-19 vaccine in patients with RA in remission and are consistent with previous findings about varicella-zoster virus (6.7%) and hepatitis B virus (2.2%) vaccinations,” Riccardo Bixio, MD, and colleagues from University of Verona (Italy) Hospital Trust wrote in ACR Open Rheumatology. “Because remission is not commonly obtained in the real world, we are aware that our findings may not be generalizable to all patients with RA receiving COVID-19 vaccination.”
Other studies of flare rate after COVID-19 vaccination in patients with a variety of rheumatic and musculoskeletal diseases have reported rates ranging from 5% to 17%, they said.
The 77 consecutive patients from the University of Verona center that conducted the study were all in clinical remission in the 3 months before vaccination based on a 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) of less than 2.6, and all had discontinued antirheumatic therapies according to American College of Rheumatology COVID-19 recommendations. The researchers defined flares as agreement between patient and rheumatologist assessments and a DAS28-CRP increase of more than 1.2.
Five of the six people with a flare had it occur after the second dose at a mean of 2.6 days later, and all flares were resolved within 2 weeks using glucocorticoids with or without anti-inflammatory drugs. One flare was called severe. The overall disease activity of the cohort after 3 months was not significantly changed after vaccination.
In noting that five out of the six patients with flares had withdrawn or delayed antirheumatic therapies around the time of vaccination according to ACR recommendations, the authors wrote that “Even if there is no direct evidence that holding therapies could occur in a higher proportion of disease flares, we suggest that clinicians consider this possibility when counseling patients about COVID-19 vaccination.”
The authors had no outside funding for the study and had no potential conflicts of interest to disclose.
Patients with rheumatoid arthritis in remission had a rate of flare following vaccination with the Pfizer/BioNtech COVID-19 vaccine that appears to be on par with rates seen with other vaccines in patients with RA, according to results from a small Italian cohort study.
“Our data show a very low flare rate [7.8% (6 of 77)] after the BNT162b2 COVID-19 vaccine in patients with RA in remission and are consistent with previous findings about varicella-zoster virus (6.7%) and hepatitis B virus (2.2%) vaccinations,” Riccardo Bixio, MD, and colleagues from University of Verona (Italy) Hospital Trust wrote in ACR Open Rheumatology. “Because remission is not commonly obtained in the real world, we are aware that our findings may not be generalizable to all patients with RA receiving COVID-19 vaccination.”
Other studies of flare rate after COVID-19 vaccination in patients with a variety of rheumatic and musculoskeletal diseases have reported rates ranging from 5% to 17%, they said.
The 77 consecutive patients from the University of Verona center that conducted the study were all in clinical remission in the 3 months before vaccination based on a 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) of less than 2.6, and all had discontinued antirheumatic therapies according to American College of Rheumatology COVID-19 recommendations. The researchers defined flares as agreement between patient and rheumatologist assessments and a DAS28-CRP increase of more than 1.2.
Five of the six people with a flare had it occur after the second dose at a mean of 2.6 days later, and all flares were resolved within 2 weeks using glucocorticoids with or without anti-inflammatory drugs. One flare was called severe. The overall disease activity of the cohort after 3 months was not significantly changed after vaccination.
In noting that five out of the six patients with flares had withdrawn or delayed antirheumatic therapies around the time of vaccination according to ACR recommendations, the authors wrote that “Even if there is no direct evidence that holding therapies could occur in a higher proportion of disease flares, we suggest that clinicians consider this possibility when counseling patients about COVID-19 vaccination.”
The authors had no outside funding for the study and had no potential conflicts of interest to disclose.
Patients with rheumatoid arthritis in remission had a rate of flare following vaccination with the Pfizer/BioNtech COVID-19 vaccine that appears to be on par with rates seen with other vaccines in patients with RA, according to results from a small Italian cohort study.
“Our data show a very low flare rate [7.8% (6 of 77)] after the BNT162b2 COVID-19 vaccine in patients with RA in remission and are consistent with previous findings about varicella-zoster virus (6.7%) and hepatitis B virus (2.2%) vaccinations,” Riccardo Bixio, MD, and colleagues from University of Verona (Italy) Hospital Trust wrote in ACR Open Rheumatology. “Because remission is not commonly obtained in the real world, we are aware that our findings may not be generalizable to all patients with RA receiving COVID-19 vaccination.”
Other studies of flare rate after COVID-19 vaccination in patients with a variety of rheumatic and musculoskeletal diseases have reported rates ranging from 5% to 17%, they said.
The 77 consecutive patients from the University of Verona center that conducted the study were all in clinical remission in the 3 months before vaccination based on a 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) of less than 2.6, and all had discontinued antirheumatic therapies according to American College of Rheumatology COVID-19 recommendations. The researchers defined flares as agreement between patient and rheumatologist assessments and a DAS28-CRP increase of more than 1.2.
Five of the six people with a flare had it occur after the second dose at a mean of 2.6 days later, and all flares were resolved within 2 weeks using glucocorticoids with or without anti-inflammatory drugs. One flare was called severe. The overall disease activity of the cohort after 3 months was not significantly changed after vaccination.
In noting that five out of the six patients with flares had withdrawn or delayed antirheumatic therapies around the time of vaccination according to ACR recommendations, the authors wrote that “Even if there is no direct evidence that holding therapies could occur in a higher proportion of disease flares, we suggest that clinicians consider this possibility when counseling patients about COVID-19 vaccination.”
The authors had no outside funding for the study and had no potential conflicts of interest to disclose.
FROM ACR OPEN RHEUMATOLOGY