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No more ‘escape hatch’: Post Roe, new worries about meds linked to birth defects
As states ban or limit abortion in the wake of the demise of Roe v. Wade, physicians are turning their attention to widely-used drugs that can cause birth defects. At issue: Should these drugs still be prescribed to women of childbearing age if they don’t have the option of terminating their pregnancies?
“Doctors are going to understandably be terrified that a patient may become pregnant using a teratogen that they have prescribed,” said University of Pittsburgh rheumatologist Mehret Birru Talabi, MD, PhD, who works in a state where the future of abortion rights is uncertain. “While this was a feared outcome before Roe v. Wade was overturned, abortion provided an escape hatch by which women could avoid having to continue a pregnancy and potentially raise a child with congenital anomalies. I believe that prescribing is going to become much more defensive and conservative. Some clinicians may choose not to prescribe these medications to patients who have childbearing potential, even if they don’t have much risk for pregnancy.”
Other physicians expressed similar concerns in interviews. Duke University, Durham, N.C., rheumatologist Megan E. B. Clowse, MD, MPH, fears that physicians will be wary of prescribing a variety of medications – including new ones for which there are few pregnancy data – if abortion is unavailable. “Women who receive these new or teratogenic medications will likely lose their reproductive autonomy and be forced to choose between having sexual relationships with men, obtaining procedures that make them permanently sterile, or using contraception that may cause intolerable side effects,” she said. “I am very concerned that young women with rheumatic disease will now be left with active disease resulting in joint damage and renal failure.”
Abortion is now banned in at least six states, according to The New York Times. That number may rise to 16 as more restrictions become law. Another five states aren’t expected to ban abortion soon but have implemented gestational age limits on abortion or are expected to adopt them. In another nine states, courts or lawmakers will decide whether abortion remains legal.
Only 20 states and the District of Columbia have firm abortion protections in place.
Numerous drugs are considered teratogens, which means they may cause birth defects. Thalidomide is the most infamous, but there are many more, including several used in rheumatology, dermatology, and gastroenterology. Among the most widely used teratogenic medications are the acne drugs isotretinoin and methotrexate, which are used to treat a variety of conditions, such as cancer, rheumatoid arthritis, and psoriasis.
Dr. Clowse, who helps manage an industry-supported website devoted to reproductive care for women with lupus (www.LupusPregnancy.org), noted that several drugs linked to birth defects and pregnancy loss are commonly prescribed in rheumatology.
“Methotrexate is the most common medication and has been the cornerstone of rheumatoid arthritis [treatment] for at least two decades,” she said. “Mycophenolate is our best medication to treat lupus nephritis, which is inflammation in the kidneys caused by lupus. This is a common complication for young women with lupus, and all of our guideline-recommended treatment regimens include a medication that causes pregnancy loss and birth defects, either mycophenolate or cyclophosphamide.”
Rheumatologists also prescribe a large number of new drugs for which there are few data about pregnancy risks. “It typically takes about two decades to have sufficient data about the safety of our medications,” she said.
Reflecting the sensitivity of the topic, Dr. Clowse made clear that her opinions don’t represent the views of her institution. She works in North Carolina, where the fate of abortion rights is uncertain, according to The New York Times.
What about alternatives? “The short answer is that some of these medications work really well and sometimes much better than the nonteratogenic alternatives,” said Dr. Birru Talabi. “I’m worried about methotrexate. It has been used to induce abortions but is primarily used in the United States as a highly effective treatment for cancer as well as a myriad of rheumatic diseases. If legislators try to restrict access to methotrexate, we may see increasing disability and even death among people who need this medication but cannot access it.”
Rheumatologists aren’t the only physicians who are worrying about the fates of their patients in a new era of abortion restrictions. Gastroenterologist Sunanda Kane, MD, MSPH, of the Mayo Clinic, Rochester, Minn., said several teratogenic medications are used in her field to treat constipation, viral hepatitis, and inflammatory bowel disease.
“When treating women of childbearing age, there are usually alternatives. If we do prescribe a medication with a high teratogenic potential, we counsel and document that we have discussed two forms of birth control to avoid pregnancy. We usually do not prescribe a drug with teratogenic potential with the ‘out’ being an abortion if a pregnancy does occur,” she said. However, “if abortion is not even on the table as an option, we may be much less likely to prescribe these medications. This will be particularly true in patients who clearly do not have the means to travel to have an abortion in any situation.”
Abortion is expected to remain legal in Minnesota, where Dr. Kane practices, but it may be restricted or banned in nearby Wisconsin, depending on the state legislature. None of her patients have had abortions after becoming pregnant while taking the medications, she said, although she “did have a patient who because of her religious faith did not have an abortion after exposure and ended up with a stillbirth.”
The crackdown on abortion won’t just pose risks to patients who take potentially dangerous medications, physicians said. Dr. Kane said pregnancy itself is a significant risk for patients with “very active, uncontrolled gastrointestinal conditions where a pregnancy could be harmful to the mother’s health or result in offspring that are very unhealthy.” These include decompensated cirrhosis, uncontrolled Crohn’s disease or ulcerative colitis, refractory gastroparesis, uncontrolled celiac sprue, and chronic pancreatitis, she said.
“There have been times when after shared decisionmaking, a patient with very active inflammatory bowel disease has decided to terminate the pregnancy because of her own ongoing health issues,” she said. “Not having this option will potentially lead to disastrous results.”
Dr. Clowse, the Duke University rheumatologist, echoed Dr. Kane’s concerns about women who are too sick to bear children. “The removal of abortion rights puts the lives and quality of life for women with rheumatic disease at risk. For patients with lupus and other systemic rheumatic disease, pregnancy can be medically catastrophic, leading to permanent harm and even death to the woman and her offspring. I am worried that women in these conditions will die without lifesaving pregnancy terminations, due to worries about the legal consequences for their physicians.”
The U.S. Supreme Court’s ruling that overturned Roe v. Wade has also raised the prospect that the court could ultimately allow birth control to be restricted or outlawed.
While the ruling states that “nothing in this opinion should be understood to cast doubt on precedents that do not concern abortion,” Justice Clarence Thomas wrote a concurrence in which he said that the court should reconsider a 1960s ruling that forbids the banning of contraceptives. Republicans have dismissed concerns about bans being allowed, although Democrats, including the president and vice president, starkly warn that they could happen.
“If we as providers have to be concerned that there will be an unplanned pregnancy because of the lack of access to contraception,” Dr. Kane said, “this will have significant downstream consequences to the kind of care we can provide and might just drive some providers to not give care to female patients at all given this concern.”
The physicians quoted in this article report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
As states ban or limit abortion in the wake of the demise of Roe v. Wade, physicians are turning their attention to widely-used drugs that can cause birth defects. At issue: Should these drugs still be prescribed to women of childbearing age if they don’t have the option of terminating their pregnancies?
“Doctors are going to understandably be terrified that a patient may become pregnant using a teratogen that they have prescribed,” said University of Pittsburgh rheumatologist Mehret Birru Talabi, MD, PhD, who works in a state where the future of abortion rights is uncertain. “While this was a feared outcome before Roe v. Wade was overturned, abortion provided an escape hatch by which women could avoid having to continue a pregnancy and potentially raise a child with congenital anomalies. I believe that prescribing is going to become much more defensive and conservative. Some clinicians may choose not to prescribe these medications to patients who have childbearing potential, even if they don’t have much risk for pregnancy.”
Other physicians expressed similar concerns in interviews. Duke University, Durham, N.C., rheumatologist Megan E. B. Clowse, MD, MPH, fears that physicians will be wary of prescribing a variety of medications – including new ones for which there are few pregnancy data – if abortion is unavailable. “Women who receive these new or teratogenic medications will likely lose their reproductive autonomy and be forced to choose between having sexual relationships with men, obtaining procedures that make them permanently sterile, or using contraception that may cause intolerable side effects,” she said. “I am very concerned that young women with rheumatic disease will now be left with active disease resulting in joint damage and renal failure.”
Abortion is now banned in at least six states, according to The New York Times. That number may rise to 16 as more restrictions become law. Another five states aren’t expected to ban abortion soon but have implemented gestational age limits on abortion or are expected to adopt them. In another nine states, courts or lawmakers will decide whether abortion remains legal.
Only 20 states and the District of Columbia have firm abortion protections in place.
Numerous drugs are considered teratogens, which means they may cause birth defects. Thalidomide is the most infamous, but there are many more, including several used in rheumatology, dermatology, and gastroenterology. Among the most widely used teratogenic medications are the acne drugs isotretinoin and methotrexate, which are used to treat a variety of conditions, such as cancer, rheumatoid arthritis, and psoriasis.
Dr. Clowse, who helps manage an industry-supported website devoted to reproductive care for women with lupus (www.LupusPregnancy.org), noted that several drugs linked to birth defects and pregnancy loss are commonly prescribed in rheumatology.
“Methotrexate is the most common medication and has been the cornerstone of rheumatoid arthritis [treatment] for at least two decades,” she said. “Mycophenolate is our best medication to treat lupus nephritis, which is inflammation in the kidneys caused by lupus. This is a common complication for young women with lupus, and all of our guideline-recommended treatment regimens include a medication that causes pregnancy loss and birth defects, either mycophenolate or cyclophosphamide.”
Rheumatologists also prescribe a large number of new drugs for which there are few data about pregnancy risks. “It typically takes about two decades to have sufficient data about the safety of our medications,” she said.
Reflecting the sensitivity of the topic, Dr. Clowse made clear that her opinions don’t represent the views of her institution. She works in North Carolina, where the fate of abortion rights is uncertain, according to The New York Times.
What about alternatives? “The short answer is that some of these medications work really well and sometimes much better than the nonteratogenic alternatives,” said Dr. Birru Talabi. “I’m worried about methotrexate. It has been used to induce abortions but is primarily used in the United States as a highly effective treatment for cancer as well as a myriad of rheumatic diseases. If legislators try to restrict access to methotrexate, we may see increasing disability and even death among people who need this medication but cannot access it.”
Rheumatologists aren’t the only physicians who are worrying about the fates of their patients in a new era of abortion restrictions. Gastroenterologist Sunanda Kane, MD, MSPH, of the Mayo Clinic, Rochester, Minn., said several teratogenic medications are used in her field to treat constipation, viral hepatitis, and inflammatory bowel disease.
“When treating women of childbearing age, there are usually alternatives. If we do prescribe a medication with a high teratogenic potential, we counsel and document that we have discussed two forms of birth control to avoid pregnancy. We usually do not prescribe a drug with teratogenic potential with the ‘out’ being an abortion if a pregnancy does occur,” she said. However, “if abortion is not even on the table as an option, we may be much less likely to prescribe these medications. This will be particularly true in patients who clearly do not have the means to travel to have an abortion in any situation.”
Abortion is expected to remain legal in Minnesota, where Dr. Kane practices, but it may be restricted or banned in nearby Wisconsin, depending on the state legislature. None of her patients have had abortions after becoming pregnant while taking the medications, she said, although she “did have a patient who because of her religious faith did not have an abortion after exposure and ended up with a stillbirth.”
The crackdown on abortion won’t just pose risks to patients who take potentially dangerous medications, physicians said. Dr. Kane said pregnancy itself is a significant risk for patients with “very active, uncontrolled gastrointestinal conditions where a pregnancy could be harmful to the mother’s health or result in offspring that are very unhealthy.” These include decompensated cirrhosis, uncontrolled Crohn’s disease or ulcerative colitis, refractory gastroparesis, uncontrolled celiac sprue, and chronic pancreatitis, she said.
“There have been times when after shared decisionmaking, a patient with very active inflammatory bowel disease has decided to terminate the pregnancy because of her own ongoing health issues,” she said. “Not having this option will potentially lead to disastrous results.”
Dr. Clowse, the Duke University rheumatologist, echoed Dr. Kane’s concerns about women who are too sick to bear children. “The removal of abortion rights puts the lives and quality of life for women with rheumatic disease at risk. For patients with lupus and other systemic rheumatic disease, pregnancy can be medically catastrophic, leading to permanent harm and even death to the woman and her offspring. I am worried that women in these conditions will die without lifesaving pregnancy terminations, due to worries about the legal consequences for their physicians.”
The U.S. Supreme Court’s ruling that overturned Roe v. Wade has also raised the prospect that the court could ultimately allow birth control to be restricted or outlawed.
While the ruling states that “nothing in this opinion should be understood to cast doubt on precedents that do not concern abortion,” Justice Clarence Thomas wrote a concurrence in which he said that the court should reconsider a 1960s ruling that forbids the banning of contraceptives. Republicans have dismissed concerns about bans being allowed, although Democrats, including the president and vice president, starkly warn that they could happen.
“If we as providers have to be concerned that there will be an unplanned pregnancy because of the lack of access to contraception,” Dr. Kane said, “this will have significant downstream consequences to the kind of care we can provide and might just drive some providers to not give care to female patients at all given this concern.”
The physicians quoted in this article report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
As states ban or limit abortion in the wake of the demise of Roe v. Wade, physicians are turning their attention to widely-used drugs that can cause birth defects. At issue: Should these drugs still be prescribed to women of childbearing age if they don’t have the option of terminating their pregnancies?
“Doctors are going to understandably be terrified that a patient may become pregnant using a teratogen that they have prescribed,” said University of Pittsburgh rheumatologist Mehret Birru Talabi, MD, PhD, who works in a state where the future of abortion rights is uncertain. “While this was a feared outcome before Roe v. Wade was overturned, abortion provided an escape hatch by which women could avoid having to continue a pregnancy and potentially raise a child with congenital anomalies. I believe that prescribing is going to become much more defensive and conservative. Some clinicians may choose not to prescribe these medications to patients who have childbearing potential, even if they don’t have much risk for pregnancy.”
Other physicians expressed similar concerns in interviews. Duke University, Durham, N.C., rheumatologist Megan E. B. Clowse, MD, MPH, fears that physicians will be wary of prescribing a variety of medications – including new ones for which there are few pregnancy data – if abortion is unavailable. “Women who receive these new or teratogenic medications will likely lose their reproductive autonomy and be forced to choose between having sexual relationships with men, obtaining procedures that make them permanently sterile, or using contraception that may cause intolerable side effects,” she said. “I am very concerned that young women with rheumatic disease will now be left with active disease resulting in joint damage and renal failure.”
Abortion is now banned in at least six states, according to The New York Times. That number may rise to 16 as more restrictions become law. Another five states aren’t expected to ban abortion soon but have implemented gestational age limits on abortion or are expected to adopt them. In another nine states, courts or lawmakers will decide whether abortion remains legal.
Only 20 states and the District of Columbia have firm abortion protections in place.
Numerous drugs are considered teratogens, which means they may cause birth defects. Thalidomide is the most infamous, but there are many more, including several used in rheumatology, dermatology, and gastroenterology. Among the most widely used teratogenic medications are the acne drugs isotretinoin and methotrexate, which are used to treat a variety of conditions, such as cancer, rheumatoid arthritis, and psoriasis.
Dr. Clowse, who helps manage an industry-supported website devoted to reproductive care for women with lupus (www.LupusPregnancy.org), noted that several drugs linked to birth defects and pregnancy loss are commonly prescribed in rheumatology.
“Methotrexate is the most common medication and has been the cornerstone of rheumatoid arthritis [treatment] for at least two decades,” she said. “Mycophenolate is our best medication to treat lupus nephritis, which is inflammation in the kidneys caused by lupus. This is a common complication for young women with lupus, and all of our guideline-recommended treatment regimens include a medication that causes pregnancy loss and birth defects, either mycophenolate or cyclophosphamide.”
Rheumatologists also prescribe a large number of new drugs for which there are few data about pregnancy risks. “It typically takes about two decades to have sufficient data about the safety of our medications,” she said.
Reflecting the sensitivity of the topic, Dr. Clowse made clear that her opinions don’t represent the views of her institution. She works in North Carolina, where the fate of abortion rights is uncertain, according to The New York Times.
What about alternatives? “The short answer is that some of these medications work really well and sometimes much better than the nonteratogenic alternatives,” said Dr. Birru Talabi. “I’m worried about methotrexate. It has been used to induce abortions but is primarily used in the United States as a highly effective treatment for cancer as well as a myriad of rheumatic diseases. If legislators try to restrict access to methotrexate, we may see increasing disability and even death among people who need this medication but cannot access it.”
Rheumatologists aren’t the only physicians who are worrying about the fates of their patients in a new era of abortion restrictions. Gastroenterologist Sunanda Kane, MD, MSPH, of the Mayo Clinic, Rochester, Minn., said several teratogenic medications are used in her field to treat constipation, viral hepatitis, and inflammatory bowel disease.
“When treating women of childbearing age, there are usually alternatives. If we do prescribe a medication with a high teratogenic potential, we counsel and document that we have discussed two forms of birth control to avoid pregnancy. We usually do not prescribe a drug with teratogenic potential with the ‘out’ being an abortion if a pregnancy does occur,” she said. However, “if abortion is not even on the table as an option, we may be much less likely to prescribe these medications. This will be particularly true in patients who clearly do not have the means to travel to have an abortion in any situation.”
Abortion is expected to remain legal in Minnesota, where Dr. Kane practices, but it may be restricted or banned in nearby Wisconsin, depending on the state legislature. None of her patients have had abortions after becoming pregnant while taking the medications, she said, although she “did have a patient who because of her religious faith did not have an abortion after exposure and ended up with a stillbirth.”
The crackdown on abortion won’t just pose risks to patients who take potentially dangerous medications, physicians said. Dr. Kane said pregnancy itself is a significant risk for patients with “very active, uncontrolled gastrointestinal conditions where a pregnancy could be harmful to the mother’s health or result in offspring that are very unhealthy.” These include decompensated cirrhosis, uncontrolled Crohn’s disease or ulcerative colitis, refractory gastroparesis, uncontrolled celiac sprue, and chronic pancreatitis, she said.
“There have been times when after shared decisionmaking, a patient with very active inflammatory bowel disease has decided to terminate the pregnancy because of her own ongoing health issues,” she said. “Not having this option will potentially lead to disastrous results.”
Dr. Clowse, the Duke University rheumatologist, echoed Dr. Kane’s concerns about women who are too sick to bear children. “The removal of abortion rights puts the lives and quality of life for women with rheumatic disease at risk. For patients with lupus and other systemic rheumatic disease, pregnancy can be medically catastrophic, leading to permanent harm and even death to the woman and her offspring. I am worried that women in these conditions will die without lifesaving pregnancy terminations, due to worries about the legal consequences for their physicians.”
The U.S. Supreme Court’s ruling that overturned Roe v. Wade has also raised the prospect that the court could ultimately allow birth control to be restricted or outlawed.
While the ruling states that “nothing in this opinion should be understood to cast doubt on precedents that do not concern abortion,” Justice Clarence Thomas wrote a concurrence in which he said that the court should reconsider a 1960s ruling that forbids the banning of contraceptives. Republicans have dismissed concerns about bans being allowed, although Democrats, including the president and vice president, starkly warn that they could happen.
“If we as providers have to be concerned that there will be an unplanned pregnancy because of the lack of access to contraception,” Dr. Kane said, “this will have significant downstream consequences to the kind of care we can provide and might just drive some providers to not give care to female patients at all given this concern.”
The physicians quoted in this article report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Good chemo vs. bad chemo: When too much is a bad thing
A new study finds that mortality is significantly higher among patients with advanced solid tumors who are admitted to the hospital for chemotherapy treatment.
The findings – released in a poster session at the annual meeting of the American Society of Clinical Oncology – found that patients with solid tumors were more likely to be treated for nonurgent indications, not be referred to palliative care, and die within 60 days, compared with patients with hematologic malignancies.
Decisions about inpatient chemotherapy should not be uniform and instead should be based on a case-by-case basis, said Natalie Berger, MD, a hematologist-oncologist at Mount Sinai Hospital,, New York, and the study’s lead author.
Inpatient chemotherapy can be appropriate in certain situations, such as when chemotherapy must be given in the hospital and when it must be administered quickly after a patient presents with cancer symptoms and needs relief, she said.
However, “sometimes patients are admitted due to infection, side effects of chemotherapy or cancer, or for reasons unrelated to their cancer, and chemotherapy may be administered when it is not appropriate. It is also overutilized at the end of life which can lead to more aggressive end-of-life care rather than focusing on quality of life and supportive care,” Dr. Berger said.
The study is based on a retrospective chart review of 880 patients admitted to Mount Sinai Hospital between January 2016 and December 2017 to receive chemotherapy.
They found that the type of tumor was used to determine the urgency of an in-hospital stay for chemotherapy (odds ratio, 0.42; 95% CI, 0.25-0.72; P = .001). Patients with solid tumors or older patients or patients with a functional impairment score (Karnofsky Performance Scale) of 50% were less likely to respond to chemotherapy. There was also a decrease in quality of life among these patients, but only 46% of patients with solid tumors and 15% of patients with hematologic malignancies met with a palliative care professional.
One-third (34%) of patients with solid tumors didn’t have urgent indications, 43% of patients had no response to inpatient chemotherapy, and 20% died within 60 days, compared with patients with hematologic malignancies (19%, 19%, and 9%, respectively).
“There are many reasons why this [high mortality rate in patients with solid tumors] may be happening. Solid tumor patients are more often admitted at a later stage of their cancer when they are sicker, and they were also less likely to have a response to inpatient chemotherapy. Older patients and patients with a poor performance status were also less likely to respond to chemotherapy. This indicates that these patients were sicker, and chemotherapy use may not have been appropriate and palliative care may be underutilized,” she said.
Dr. Berger and colleagues have created a standardized protocol to assess “the appropriateness” of inpatient chemotherapy, improve quality of life, and reduce chemotherapy and health care utilization at the end of life. The protocol has been implemented as a pilot program at Mount Sinai Hospital, Dr. Berger said.
“Any inpatient chemotherapy case that meets standard accepted criteria for required inpatient administration are auto-approved through the electronic survey. For cases outside of standard criteria, further information must be inputted to determine appropriateness of inpatient treatment and are then scored electronically and reviewed by committee physicians and pharmacists,” she said.
Gabriel A. Brooks, MD, MPH, an oncologist with Dartmouth Hitchcock Medical Center, Lebanon, N.H., who was not affiliated with the study, said that inpatient chemotherapy treatment is under scrutiny elsewhere as well.
“There has been recognition that patients who are otherwise sick enough to require hospital admission are often too sick to benefit from chemotherapy,” although there are exceptions. “There is certainly a movement to limit inpatient chemotherapy to situations where it is most likely to be beneficial. Some of this is driven by cost pressures. For instance, Medicare pays for inpatient hospitalizations using the DRG [diagnosis-related group] system. Hospitals cannot charge a la carte for treatments given in the hospital. Instead, they are reimbursed at a fixed rate based on the hospital diagnoses. This will often lead to poor reimbursement of high-cost cancer treatments.”
Dr. Brooks said the study offers insight into who’s getting inpatient chemotherapy. However, “what I can’t tell from this poster is how often the solid tumor patients are getting first-line chemotherapy [as] these patients may be presenting late or may have a potentially treatable cancer with a narrow closing window for treatment versus later-line chemotherapy.”
He also noted that patient and family wishes are missing from the research. “This is critical. Patients and families should be informed that inpatient chemotherapy may not provide the benefit they are hoping for, especially for patients with solid tumors starting later lines of therapy. Patients should be informed that there are alternatives to inpatient chemotherapy, such as hospice referral or waiting for possible outpatient treatment – if their condition improves. But when a patient wants to try inpatient chemotherapy and their doctor wants to offer it, then it is likely a reasonable thing to try.”
Going forward, he said, “qualitative study is needed to better understand when and why inpatient chemotherapy is used. There are likely some clear good uses and some clear bad uses of inpatient chemotherapy. Can outpatient regimens be substituted for the regimens where patients are directly admitted? Or, can outpatient protocols be devised for these regimens? Are there specific situations where inpatient chemotherapy is the right thing (leukemia, esophageal cancer with worsening dysphagia, etc.)?”
No study funding was received.
A new study finds that mortality is significantly higher among patients with advanced solid tumors who are admitted to the hospital for chemotherapy treatment.
The findings – released in a poster session at the annual meeting of the American Society of Clinical Oncology – found that patients with solid tumors were more likely to be treated for nonurgent indications, not be referred to palliative care, and die within 60 days, compared with patients with hematologic malignancies.
Decisions about inpatient chemotherapy should not be uniform and instead should be based on a case-by-case basis, said Natalie Berger, MD, a hematologist-oncologist at Mount Sinai Hospital,, New York, and the study’s lead author.
Inpatient chemotherapy can be appropriate in certain situations, such as when chemotherapy must be given in the hospital and when it must be administered quickly after a patient presents with cancer symptoms and needs relief, she said.
However, “sometimes patients are admitted due to infection, side effects of chemotherapy or cancer, or for reasons unrelated to their cancer, and chemotherapy may be administered when it is not appropriate. It is also overutilized at the end of life which can lead to more aggressive end-of-life care rather than focusing on quality of life and supportive care,” Dr. Berger said.
The study is based on a retrospective chart review of 880 patients admitted to Mount Sinai Hospital between January 2016 and December 2017 to receive chemotherapy.
They found that the type of tumor was used to determine the urgency of an in-hospital stay for chemotherapy (odds ratio, 0.42; 95% CI, 0.25-0.72; P = .001). Patients with solid tumors or older patients or patients with a functional impairment score (Karnofsky Performance Scale) of 50% were less likely to respond to chemotherapy. There was also a decrease in quality of life among these patients, but only 46% of patients with solid tumors and 15% of patients with hematologic malignancies met with a palliative care professional.
One-third (34%) of patients with solid tumors didn’t have urgent indications, 43% of patients had no response to inpatient chemotherapy, and 20% died within 60 days, compared with patients with hematologic malignancies (19%, 19%, and 9%, respectively).
“There are many reasons why this [high mortality rate in patients with solid tumors] may be happening. Solid tumor patients are more often admitted at a later stage of their cancer when they are sicker, and they were also less likely to have a response to inpatient chemotherapy. Older patients and patients with a poor performance status were also less likely to respond to chemotherapy. This indicates that these patients were sicker, and chemotherapy use may not have been appropriate and palliative care may be underutilized,” she said.
Dr. Berger and colleagues have created a standardized protocol to assess “the appropriateness” of inpatient chemotherapy, improve quality of life, and reduce chemotherapy and health care utilization at the end of life. The protocol has been implemented as a pilot program at Mount Sinai Hospital, Dr. Berger said.
“Any inpatient chemotherapy case that meets standard accepted criteria for required inpatient administration are auto-approved through the electronic survey. For cases outside of standard criteria, further information must be inputted to determine appropriateness of inpatient treatment and are then scored electronically and reviewed by committee physicians and pharmacists,” she said.
Gabriel A. Brooks, MD, MPH, an oncologist with Dartmouth Hitchcock Medical Center, Lebanon, N.H., who was not affiliated with the study, said that inpatient chemotherapy treatment is under scrutiny elsewhere as well.
“There has been recognition that patients who are otherwise sick enough to require hospital admission are often too sick to benefit from chemotherapy,” although there are exceptions. “There is certainly a movement to limit inpatient chemotherapy to situations where it is most likely to be beneficial. Some of this is driven by cost pressures. For instance, Medicare pays for inpatient hospitalizations using the DRG [diagnosis-related group] system. Hospitals cannot charge a la carte for treatments given in the hospital. Instead, they are reimbursed at a fixed rate based on the hospital diagnoses. This will often lead to poor reimbursement of high-cost cancer treatments.”
Dr. Brooks said the study offers insight into who’s getting inpatient chemotherapy. However, “what I can’t tell from this poster is how often the solid tumor patients are getting first-line chemotherapy [as] these patients may be presenting late or may have a potentially treatable cancer with a narrow closing window for treatment versus later-line chemotherapy.”
He also noted that patient and family wishes are missing from the research. “This is critical. Patients and families should be informed that inpatient chemotherapy may not provide the benefit they are hoping for, especially for patients with solid tumors starting later lines of therapy. Patients should be informed that there are alternatives to inpatient chemotherapy, such as hospice referral or waiting for possible outpatient treatment – if their condition improves. But when a patient wants to try inpatient chemotherapy and their doctor wants to offer it, then it is likely a reasonable thing to try.”
Going forward, he said, “qualitative study is needed to better understand when and why inpatient chemotherapy is used. There are likely some clear good uses and some clear bad uses of inpatient chemotherapy. Can outpatient regimens be substituted for the regimens where patients are directly admitted? Or, can outpatient protocols be devised for these regimens? Are there specific situations where inpatient chemotherapy is the right thing (leukemia, esophageal cancer with worsening dysphagia, etc.)?”
No study funding was received.
A new study finds that mortality is significantly higher among patients with advanced solid tumors who are admitted to the hospital for chemotherapy treatment.
The findings – released in a poster session at the annual meeting of the American Society of Clinical Oncology – found that patients with solid tumors were more likely to be treated for nonurgent indications, not be referred to palliative care, and die within 60 days, compared with patients with hematologic malignancies.
Decisions about inpatient chemotherapy should not be uniform and instead should be based on a case-by-case basis, said Natalie Berger, MD, a hematologist-oncologist at Mount Sinai Hospital,, New York, and the study’s lead author.
Inpatient chemotherapy can be appropriate in certain situations, such as when chemotherapy must be given in the hospital and when it must be administered quickly after a patient presents with cancer symptoms and needs relief, she said.
However, “sometimes patients are admitted due to infection, side effects of chemotherapy or cancer, or for reasons unrelated to their cancer, and chemotherapy may be administered when it is not appropriate. It is also overutilized at the end of life which can lead to more aggressive end-of-life care rather than focusing on quality of life and supportive care,” Dr. Berger said.
The study is based on a retrospective chart review of 880 patients admitted to Mount Sinai Hospital between January 2016 and December 2017 to receive chemotherapy.
They found that the type of tumor was used to determine the urgency of an in-hospital stay for chemotherapy (odds ratio, 0.42; 95% CI, 0.25-0.72; P = .001). Patients with solid tumors or older patients or patients with a functional impairment score (Karnofsky Performance Scale) of 50% were less likely to respond to chemotherapy. There was also a decrease in quality of life among these patients, but only 46% of patients with solid tumors and 15% of patients with hematologic malignancies met with a palliative care professional.
One-third (34%) of patients with solid tumors didn’t have urgent indications, 43% of patients had no response to inpatient chemotherapy, and 20% died within 60 days, compared with patients with hematologic malignancies (19%, 19%, and 9%, respectively).
“There are many reasons why this [high mortality rate in patients with solid tumors] may be happening. Solid tumor patients are more often admitted at a later stage of their cancer when they are sicker, and they were also less likely to have a response to inpatient chemotherapy. Older patients and patients with a poor performance status were also less likely to respond to chemotherapy. This indicates that these patients were sicker, and chemotherapy use may not have been appropriate and palliative care may be underutilized,” she said.
Dr. Berger and colleagues have created a standardized protocol to assess “the appropriateness” of inpatient chemotherapy, improve quality of life, and reduce chemotherapy and health care utilization at the end of life. The protocol has been implemented as a pilot program at Mount Sinai Hospital, Dr. Berger said.
“Any inpatient chemotherapy case that meets standard accepted criteria for required inpatient administration are auto-approved through the electronic survey. For cases outside of standard criteria, further information must be inputted to determine appropriateness of inpatient treatment and are then scored electronically and reviewed by committee physicians and pharmacists,” she said.
Gabriel A. Brooks, MD, MPH, an oncologist with Dartmouth Hitchcock Medical Center, Lebanon, N.H., who was not affiliated with the study, said that inpatient chemotherapy treatment is under scrutiny elsewhere as well.
“There has been recognition that patients who are otherwise sick enough to require hospital admission are often too sick to benefit from chemotherapy,” although there are exceptions. “There is certainly a movement to limit inpatient chemotherapy to situations where it is most likely to be beneficial. Some of this is driven by cost pressures. For instance, Medicare pays for inpatient hospitalizations using the DRG [diagnosis-related group] system. Hospitals cannot charge a la carte for treatments given in the hospital. Instead, they are reimbursed at a fixed rate based on the hospital diagnoses. This will often lead to poor reimbursement of high-cost cancer treatments.”
Dr. Brooks said the study offers insight into who’s getting inpatient chemotherapy. However, “what I can’t tell from this poster is how often the solid tumor patients are getting first-line chemotherapy [as] these patients may be presenting late or may have a potentially treatable cancer with a narrow closing window for treatment versus later-line chemotherapy.”
He also noted that patient and family wishes are missing from the research. “This is critical. Patients and families should be informed that inpatient chemotherapy may not provide the benefit they are hoping for, especially for patients with solid tumors starting later lines of therapy. Patients should be informed that there are alternatives to inpatient chemotherapy, such as hospice referral or waiting for possible outpatient treatment – if their condition improves. But when a patient wants to try inpatient chemotherapy and their doctor wants to offer it, then it is likely a reasonable thing to try.”
Going forward, he said, “qualitative study is needed to better understand when and why inpatient chemotherapy is used. There are likely some clear good uses and some clear bad uses of inpatient chemotherapy. Can outpatient regimens be substituted for the regimens where patients are directly admitted? Or, can outpatient protocols be devised for these regimens? Are there specific situations where inpatient chemotherapy is the right thing (leukemia, esophageal cancer with worsening dysphagia, etc.)?”
No study funding was received.
FROM ASCO 2022
Twin study offers new insight into genetics of migraine
DENVER – , even though testosterone is thought to be protective. The findings, presented at the annual meeting of the American Headache Society, also hint at a possible role played by the prenatal environment.
The study marks the first time a large-scale twin dataset has been used to assess sex differences in underlying genetic factors of migraine, lead author Morgan Fitzgerald, a senior research associate at the University of California at San Diego, said in a presentation at the conference. The findings were previously published in Frontiers in Pain Research.
More than genetics
The researchers analyzed data regarding 51,872 participants in the Swedish Twin Registry. According to Dr. Fitzgerald, the database is ideal because it is large and includes both genders.
Per the database, female twins were more likely to have migraines without aura than were male twins (17.6% vs. 5.5%, respectively), reflecting global numbers that suggest 18% of females and 6% of males have migraines each year.
To better understand heritability, the researchers compared identical twins with fraternal twins, and looked for gender-related correlations, Dr. Fitzgerald said.
One analysis suggests that migraine is equally heritable in men and women with a broad sense heritability of 0.45 (95% confidence interval [CI], 0.40-0.50). However, another analysis model provides evidence “that there are differences in the underlying genetic factors contributing to migraine across males and females,” she said.
Unexpectedly, the researchers also found that females with male twins were more likely to have migraines than were those with female twins (odds ratio, 1.51, 95% CI, 1.26-1.81) even though males are less affected by the headaches.
“These results suggest that the prominent sex difference in migraine prevalence is not entirely accounted for by genetic factors, while demonstrating that masculinization of the prenatal environment may increase migraine risk for females,” the authors wrote in the published study. “This effect points to a potential prenatal neuroendocrine factor in the development of migraine.”
Probing the migraine gender gap
Commenting on the research, University of Texas at Dallas neuroscientist and headache researcher Gregory Dussor, PhD, said the new study is “a very unique approach to address the question of nature versus nurture in migraine. It was well designed and used robust statistical modeling.”
As for the findings, “the conclusion that genetics do not explain sex differences in migraine risk by themselves is not surprising given how big of a role hormones in later life are likely to play in the disease and how many factors there are that can influence hormone levels,” he said.
“On the other hand, the surprising part of the findings was that the presence of a male co-twin increases risk of migraine in females. I would have expected to see the opposite, given the lower prevalence of migraine in males and the seemingly protective role that male hormones can play in migraine.”
Overall, the study adds to data implicating environment and hormones in the migraine gender gap, he said. “One thing I wonder from this study is what influence a female co-twin growing up with a male co-twin can have on migraine susceptibility. That female co-twin may end up with a very different set of childhood experiences than if she was with another female co-twin. Twins generally spend an enormous amount of time together and the same sex versus opposite sex experiences are likely to be quite different. This may have an influence on migraine later in life.”
As for the value of the study in terms of diagnosis, treatment, or prevention of migraine, Dr. Dussor said, “it’s possible it could help to identify risk factors for higher migraine susceptibility but it’s far too early to know how this could be used.”
The authors have no disclosures. Dr. Dussor disclosed an NIH-funded grant to study the role of the hormone prolactin in preclinical migraine models.
DENVER – , even though testosterone is thought to be protective. The findings, presented at the annual meeting of the American Headache Society, also hint at a possible role played by the prenatal environment.
The study marks the first time a large-scale twin dataset has been used to assess sex differences in underlying genetic factors of migraine, lead author Morgan Fitzgerald, a senior research associate at the University of California at San Diego, said in a presentation at the conference. The findings were previously published in Frontiers in Pain Research.
More than genetics
The researchers analyzed data regarding 51,872 participants in the Swedish Twin Registry. According to Dr. Fitzgerald, the database is ideal because it is large and includes both genders.
Per the database, female twins were more likely to have migraines without aura than were male twins (17.6% vs. 5.5%, respectively), reflecting global numbers that suggest 18% of females and 6% of males have migraines each year.
To better understand heritability, the researchers compared identical twins with fraternal twins, and looked for gender-related correlations, Dr. Fitzgerald said.
One analysis suggests that migraine is equally heritable in men and women with a broad sense heritability of 0.45 (95% confidence interval [CI], 0.40-0.50). However, another analysis model provides evidence “that there are differences in the underlying genetic factors contributing to migraine across males and females,” she said.
Unexpectedly, the researchers also found that females with male twins were more likely to have migraines than were those with female twins (odds ratio, 1.51, 95% CI, 1.26-1.81) even though males are less affected by the headaches.
“These results suggest that the prominent sex difference in migraine prevalence is not entirely accounted for by genetic factors, while demonstrating that masculinization of the prenatal environment may increase migraine risk for females,” the authors wrote in the published study. “This effect points to a potential prenatal neuroendocrine factor in the development of migraine.”
Probing the migraine gender gap
Commenting on the research, University of Texas at Dallas neuroscientist and headache researcher Gregory Dussor, PhD, said the new study is “a very unique approach to address the question of nature versus nurture in migraine. It was well designed and used robust statistical modeling.”
As for the findings, “the conclusion that genetics do not explain sex differences in migraine risk by themselves is not surprising given how big of a role hormones in later life are likely to play in the disease and how many factors there are that can influence hormone levels,” he said.
“On the other hand, the surprising part of the findings was that the presence of a male co-twin increases risk of migraine in females. I would have expected to see the opposite, given the lower prevalence of migraine in males and the seemingly protective role that male hormones can play in migraine.”
Overall, the study adds to data implicating environment and hormones in the migraine gender gap, he said. “One thing I wonder from this study is what influence a female co-twin growing up with a male co-twin can have on migraine susceptibility. That female co-twin may end up with a very different set of childhood experiences than if she was with another female co-twin. Twins generally spend an enormous amount of time together and the same sex versus opposite sex experiences are likely to be quite different. This may have an influence on migraine later in life.”
As for the value of the study in terms of diagnosis, treatment, or prevention of migraine, Dr. Dussor said, “it’s possible it could help to identify risk factors for higher migraine susceptibility but it’s far too early to know how this could be used.”
The authors have no disclosures. Dr. Dussor disclosed an NIH-funded grant to study the role of the hormone prolactin in preclinical migraine models.
DENVER – , even though testosterone is thought to be protective. The findings, presented at the annual meeting of the American Headache Society, also hint at a possible role played by the prenatal environment.
The study marks the first time a large-scale twin dataset has been used to assess sex differences in underlying genetic factors of migraine, lead author Morgan Fitzgerald, a senior research associate at the University of California at San Diego, said in a presentation at the conference. The findings were previously published in Frontiers in Pain Research.
More than genetics
The researchers analyzed data regarding 51,872 participants in the Swedish Twin Registry. According to Dr. Fitzgerald, the database is ideal because it is large and includes both genders.
Per the database, female twins were more likely to have migraines without aura than were male twins (17.6% vs. 5.5%, respectively), reflecting global numbers that suggest 18% of females and 6% of males have migraines each year.
To better understand heritability, the researchers compared identical twins with fraternal twins, and looked for gender-related correlations, Dr. Fitzgerald said.
One analysis suggests that migraine is equally heritable in men and women with a broad sense heritability of 0.45 (95% confidence interval [CI], 0.40-0.50). However, another analysis model provides evidence “that there are differences in the underlying genetic factors contributing to migraine across males and females,” she said.
Unexpectedly, the researchers also found that females with male twins were more likely to have migraines than were those with female twins (odds ratio, 1.51, 95% CI, 1.26-1.81) even though males are less affected by the headaches.
“These results suggest that the prominent sex difference in migraine prevalence is not entirely accounted for by genetic factors, while demonstrating that masculinization of the prenatal environment may increase migraine risk for females,” the authors wrote in the published study. “This effect points to a potential prenatal neuroendocrine factor in the development of migraine.”
Probing the migraine gender gap
Commenting on the research, University of Texas at Dallas neuroscientist and headache researcher Gregory Dussor, PhD, said the new study is “a very unique approach to address the question of nature versus nurture in migraine. It was well designed and used robust statistical modeling.”
As for the findings, “the conclusion that genetics do not explain sex differences in migraine risk by themselves is not surprising given how big of a role hormones in later life are likely to play in the disease and how many factors there are that can influence hormone levels,” he said.
“On the other hand, the surprising part of the findings was that the presence of a male co-twin increases risk of migraine in females. I would have expected to see the opposite, given the lower prevalence of migraine in males and the seemingly protective role that male hormones can play in migraine.”
Overall, the study adds to data implicating environment and hormones in the migraine gender gap, he said. “One thing I wonder from this study is what influence a female co-twin growing up with a male co-twin can have on migraine susceptibility. That female co-twin may end up with a very different set of childhood experiences than if she was with another female co-twin. Twins generally spend an enormous amount of time together and the same sex versus opposite sex experiences are likely to be quite different. This may have an influence on migraine later in life.”
As for the value of the study in terms of diagnosis, treatment, or prevention of migraine, Dr. Dussor said, “it’s possible it could help to identify risk factors for higher migraine susceptibility but it’s far too early to know how this could be used.”
The authors have no disclosures. Dr. Dussor disclosed an NIH-funded grant to study the role of the hormone prolactin in preclinical migraine models.
AT AHS 2022
Autoimmune disorder drugs top list of meds linked to headache
DENVER – in a federal side effect database that anyone can contribute to, according to a new study presented at the annual meeting of the American Headache Society.
“Surprising findings included the significant number of immunosuppressants and immunomodulators present in the data,” study lead author Brett Musialowicz, a medical student at Robert Wood Johnson Medical School, New Brunswich, N.J., said in an interview. “Additionally, our data provides evidence that suggests that several medications belonging to these drug classes were less likely to be associated with medication-induced headaches,” raising questions about the mechanism.
Drugs most frequently linked to headaches
The researchers launched their study to better understand headache as a side effect of medication use, Mr. Musialowicz said. They analyzed entries from the Food and Drug Administration’s Adverse Event Reporting System for the period from July 2018 to March 2020 and listed the top 30 most commonly reported medications linked to headaches and their reported odds ratio. According to a website devoted to pharmacovigilance training, ROR refers to “the odds of a certain event occurring with your medicinal product, compared with the odds of the same event occurring with all other medicinal products in the database.”
After generic and brand name data was consolidated, the drug most frequently linked to headaches was apremilast with 8,672 reports, followed by adalimumab (5,357), tofacitinib (4,276), fingolimod (4,123), and etanercept (4,111). These drugs treat autoimmune disorders such as psoriasis, multiple sclerosis, and Crohn’s disease.
The other drugs in the top 15 ranked by frequency are treatments for hepatitis C (4 drugs), pulmonary arterial hypertension (4 drugs), arthritis (1 drug), and asthma (1 drug).
Of the top 30 drugs most frequently linked to headaches, the pulmonary hypertension drug epoprostenol – ranked 23rd – had the highest ROR at 12.8. The next highest were the hepatitis C drugs glecaprevir and pibrentasvir, tied at 10th in the frequency analysis and both with an ROR of 9.4.
“Pulmonary arterial dilators and vasodilators are believed to cause headaches by sensitizing extracranial arteries. Clinical evidence suggests there a vascular component to some types of headache,” Mr. Musialowicz said. “Monoclonal antibodies are suggested to cause headache by means of an immune response. Several monoclonal antibodies are in trials targeting [the calcitonin gene-related peptide] receptor, which is believed to be involved in migraine headache. These trials will help further elucidate the mechanisms of headache and potential drugs to treat these conditions.”
Is the data useful?
Stewart Tepper, MD, a neurologist at Geisel School of Medicine at Dartmouth, Hanover, N.H., who’s familiar with the study findings, discounted the new research in an interview. He noted that any member of the public can contribute to the federal database of adverse effects (drug manufacturers are required to contribute to it), and the data says nothing about denominators.
“It’s not a reasonable way to evaluate adverse effects, to just have everyone and their uncle saying ‘This particular drug did this to me.’ It’s not in any way useful,” he said. However, he added that the database sometimes “gives you a bit of a signal so you can go back and try to get scientifically collected data.”
When asked to respond, study coauthor and neurologist Pengfei (Phil) Zhang, MD, of Robert Wood Johnson Medical School, noted that the FDA created the database “for a reason.” He also noted that the researchers used a statistical analysis technique – ROR – that was invented to adjust for weaknesses in databases.
No study funding is reported. Mr. Musialowicz reported no disclosures. Dr. Zhang has received honorarium from Alder Biopharmaceuticals, Board Vitals, and Fieve Clinical Research. He collaborates with Headache Science Incorporated without receiving financial support, and he has ownership interest in Cymbeline. Another author reports research grant support from the American Epilepsy Society and the New Jersey Health Foundation. Dr. Tepper reported multiple disclosures.
DENVER – in a federal side effect database that anyone can contribute to, according to a new study presented at the annual meeting of the American Headache Society.
“Surprising findings included the significant number of immunosuppressants and immunomodulators present in the data,” study lead author Brett Musialowicz, a medical student at Robert Wood Johnson Medical School, New Brunswich, N.J., said in an interview. “Additionally, our data provides evidence that suggests that several medications belonging to these drug classes were less likely to be associated with medication-induced headaches,” raising questions about the mechanism.
Drugs most frequently linked to headaches
The researchers launched their study to better understand headache as a side effect of medication use, Mr. Musialowicz said. They analyzed entries from the Food and Drug Administration’s Adverse Event Reporting System for the period from July 2018 to March 2020 and listed the top 30 most commonly reported medications linked to headaches and their reported odds ratio. According to a website devoted to pharmacovigilance training, ROR refers to “the odds of a certain event occurring with your medicinal product, compared with the odds of the same event occurring with all other medicinal products in the database.”
After generic and brand name data was consolidated, the drug most frequently linked to headaches was apremilast with 8,672 reports, followed by adalimumab (5,357), tofacitinib (4,276), fingolimod (4,123), and etanercept (4,111). These drugs treat autoimmune disorders such as psoriasis, multiple sclerosis, and Crohn’s disease.
The other drugs in the top 15 ranked by frequency are treatments for hepatitis C (4 drugs), pulmonary arterial hypertension (4 drugs), arthritis (1 drug), and asthma (1 drug).
Of the top 30 drugs most frequently linked to headaches, the pulmonary hypertension drug epoprostenol – ranked 23rd – had the highest ROR at 12.8. The next highest were the hepatitis C drugs glecaprevir and pibrentasvir, tied at 10th in the frequency analysis and both with an ROR of 9.4.
“Pulmonary arterial dilators and vasodilators are believed to cause headaches by sensitizing extracranial arteries. Clinical evidence suggests there a vascular component to some types of headache,” Mr. Musialowicz said. “Monoclonal antibodies are suggested to cause headache by means of an immune response. Several monoclonal antibodies are in trials targeting [the calcitonin gene-related peptide] receptor, which is believed to be involved in migraine headache. These trials will help further elucidate the mechanisms of headache and potential drugs to treat these conditions.”
Is the data useful?
Stewart Tepper, MD, a neurologist at Geisel School of Medicine at Dartmouth, Hanover, N.H., who’s familiar with the study findings, discounted the new research in an interview. He noted that any member of the public can contribute to the federal database of adverse effects (drug manufacturers are required to contribute to it), and the data says nothing about denominators.
“It’s not a reasonable way to evaluate adverse effects, to just have everyone and their uncle saying ‘This particular drug did this to me.’ It’s not in any way useful,” he said. However, he added that the database sometimes “gives you a bit of a signal so you can go back and try to get scientifically collected data.”
When asked to respond, study coauthor and neurologist Pengfei (Phil) Zhang, MD, of Robert Wood Johnson Medical School, noted that the FDA created the database “for a reason.” He also noted that the researchers used a statistical analysis technique – ROR – that was invented to adjust for weaknesses in databases.
No study funding is reported. Mr. Musialowicz reported no disclosures. Dr. Zhang has received honorarium from Alder Biopharmaceuticals, Board Vitals, and Fieve Clinical Research. He collaborates with Headache Science Incorporated without receiving financial support, and he has ownership interest in Cymbeline. Another author reports research grant support from the American Epilepsy Society and the New Jersey Health Foundation. Dr. Tepper reported multiple disclosures.
DENVER – in a federal side effect database that anyone can contribute to, according to a new study presented at the annual meeting of the American Headache Society.
“Surprising findings included the significant number of immunosuppressants and immunomodulators present in the data,” study lead author Brett Musialowicz, a medical student at Robert Wood Johnson Medical School, New Brunswich, N.J., said in an interview. “Additionally, our data provides evidence that suggests that several medications belonging to these drug classes were less likely to be associated with medication-induced headaches,” raising questions about the mechanism.
Drugs most frequently linked to headaches
The researchers launched their study to better understand headache as a side effect of medication use, Mr. Musialowicz said. They analyzed entries from the Food and Drug Administration’s Adverse Event Reporting System for the period from July 2018 to March 2020 and listed the top 30 most commonly reported medications linked to headaches and their reported odds ratio. According to a website devoted to pharmacovigilance training, ROR refers to “the odds of a certain event occurring with your medicinal product, compared with the odds of the same event occurring with all other medicinal products in the database.”
After generic and brand name data was consolidated, the drug most frequently linked to headaches was apremilast with 8,672 reports, followed by adalimumab (5,357), tofacitinib (4,276), fingolimod (4,123), and etanercept (4,111). These drugs treat autoimmune disorders such as psoriasis, multiple sclerosis, and Crohn’s disease.
The other drugs in the top 15 ranked by frequency are treatments for hepatitis C (4 drugs), pulmonary arterial hypertension (4 drugs), arthritis (1 drug), and asthma (1 drug).
Of the top 30 drugs most frequently linked to headaches, the pulmonary hypertension drug epoprostenol – ranked 23rd – had the highest ROR at 12.8. The next highest were the hepatitis C drugs glecaprevir and pibrentasvir, tied at 10th in the frequency analysis and both with an ROR of 9.4.
“Pulmonary arterial dilators and vasodilators are believed to cause headaches by sensitizing extracranial arteries. Clinical evidence suggests there a vascular component to some types of headache,” Mr. Musialowicz said. “Monoclonal antibodies are suggested to cause headache by means of an immune response. Several monoclonal antibodies are in trials targeting [the calcitonin gene-related peptide] receptor, which is believed to be involved in migraine headache. These trials will help further elucidate the mechanisms of headache and potential drugs to treat these conditions.”
Is the data useful?
Stewart Tepper, MD, a neurologist at Geisel School of Medicine at Dartmouth, Hanover, N.H., who’s familiar with the study findings, discounted the new research in an interview. He noted that any member of the public can contribute to the federal database of adverse effects (drug manufacturers are required to contribute to it), and the data says nothing about denominators.
“It’s not a reasonable way to evaluate adverse effects, to just have everyone and their uncle saying ‘This particular drug did this to me.’ It’s not in any way useful,” he said. However, he added that the database sometimes “gives you a bit of a signal so you can go back and try to get scientifically collected data.”
When asked to respond, study coauthor and neurologist Pengfei (Phil) Zhang, MD, of Robert Wood Johnson Medical School, noted that the FDA created the database “for a reason.” He also noted that the researchers used a statistical analysis technique – ROR – that was invented to adjust for weaknesses in databases.
No study funding is reported. Mr. Musialowicz reported no disclosures. Dr. Zhang has received honorarium from Alder Biopharmaceuticals, Board Vitals, and Fieve Clinical Research. He collaborates with Headache Science Incorporated without receiving financial support, and he has ownership interest in Cymbeline. Another author reports research grant support from the American Epilepsy Society and the New Jersey Health Foundation. Dr. Tepper reported multiple disclosures.
AT AHS 2022
Recommended headache treatments get mixed reception in EDs
DENVER – a new study finds. But the use of diphenhydramine (Benadryl) more than doubled even though guidelines caution against it, while recommended drugs such triptans and corticosteroids were rarely prescribed.
From 2007-2010 to 2015-2018, researchers reported at the annual meeting of the American Headache Society, a database reveals that opioid use in headache cases at EDs fell from 54% to 28%. Diphenhydramine use grew from 17% to 36% (both (P < .001). The percentage of cases in which EDs sought neuroimaging stayed stable at about 36%, a number that the study authors described as too high.
“Future studies are warranted to identify strategies to promote evidence-based treatments for headaches and appropriate outpatient referrals for follow-up and to reduce unnecessary neuroimaging orders in EDs,” lead author Seonkyeong Yang, MS, of the University of Florida, Gainesville, said in an interview.
Ms. Yang said researchers launched the study to update previous data in light of changes in opioid prescribing and the 2016 release of American Headache Society guidelines for the treatment of acute migraines in the ED setting. The research was published in the Journal of Clinical Medicine.
Headache treatment in the ED
For the study, researchers analyzed data from the U.S. National Hospital Ambulatory Medical Care survey and focused on adults who had a primary discharge diagnosis of headache.
For the 2015-2018 period, per weighted numbers, the survey encompassed 10.2 million headaches mostly among people younger than 50 (71%), female (73%), and White (73%). Migraines made up 33% of the total, with nonspecified headache accounting for almost all of the remainder (63%).
In 68% of cases, two or more medications were administered in the ED. This number rose to 83% among patients with migraine. But most of the time (54%), no medications were prescribed at discharge.
Among recommended medications, antiemetics – the most commonly used class of drugs in these patients – were prescribed 59% of the time in both 2007-2010 and 2015-2018 (P = .88). Usage of acetaminophens and NSAIDs grew from 37% to 52% over that time period.
Despite recommendations, the use of ergot alkaloids/triptans and corticosteroids remained low (less than 6% of the time).
“Several factors may contribute to the underuse of triptans in EDs, including their cardiovascular contraindications, ED physicians’ unfamiliarity with injectable triptans, higher costs, and treatment failures with triptans before ED visits,” Ms. Yang said. “We observed an upward trend in dexamethasone use over time. However, it was still underutilized. [The corticosteroid was only used 3.5% of the time from 2015-2018.] The 2016 AHS guideline strongly recommends dexamethasone use to prevent migraine recurrence after ED discharge. Identifying patients at high risk of headache recurrence for dexamethasone use may further improve patient outcomes of acute headache management in ED settings.”
Ms. Yang also reported that the use of diphenhydramine grew even though it’s not recommended. “Diphenhydramine is more likely to be used to prevent akathisia, a side effect of some antiemetics [that is, dopamine receptor antagonists] in headache-related ED visits,” she said. “However, the 2016 AHS guideline recommends against diphenhydramine use due to its limited efficacy in relieving headache pain. In addition, there is also conflicting evidence on diphenhydramine’s efficacy in preventing akathisia when coadministered with antiemetics. Diphenhydramine use requires caution due to its sedative effect and abuse potential.”
As for medication combinations, Ms. Yang said “the most broadly used therapy among headache-related ED visits in 2007-2010 was an opioid with an antiemetic (21.0%), which decreased to 6.6% in 2015-2018. Meanwhile, the combined use of acetaminophen/NSAIDs with antiemetic and diphenhydramine increased substantially from 3.9% to 15.7% and became the most prevalent therapy in 2015-2018. Opioid monotherapy use gradually decreased during the study period [from 8.8% to 1.9%].”
Evidence-based treatments underutilized
Commenting on the findings, New York University Langone neurologist and headache researcher Mia Tova Minen, MD, MPH, noted in an interview that AHS guidelines do not indicate acetaminophen/NSAIDs, diphenhydramine, and corticosteroids for the acute treatment of migraine. “The recommended treatments are sumatriptan subcutaneous, IV metoclopramide, and IV prochlorperazine. Steroids can be helpful in the prevention of migraine recurrence but not for the acute treatment of the migraine itself,” she said. “We need to ensure that patients with migraine get the top evidence-based treatments for migraine.”
As for diphenhydramine, she said it “is not a treatment for headache disorders. It does not have proven efficacy. It is sometimes given to reduce side effects of more acute treatments of headache, but it can make patients fatigued and keep them in the ED longer.”
Overuse of neuroimaging
Ms. Yang also highlighted study data about the frequency of neuroimaging. “Understandably, ED physicians do not want to miss any life-threatening secondary headaches like stroke,” she said. “However, other factors also contribute to the overuse of neuroimaging in headache-related ED visits: patient demands, financial incentives, a busy ED practice where clinical evaluation is replaced by tests, and ED physicians’ unfamiliarity with ICHD-3 diagnostic criteria for primary headache disorders. There is still much room for improvement in neuroimaging use for headaches in ED settings.”
For her part, Dr. Minen said scans are often performed reflexively and can be overused. “A CT scan is really only good in the case of acute trauma to rule out a fracture or a bleed or if there are signs of an emergent neurologic emergency like herniation or if a MRI is contraindicated. An MRI of the brain is typically the best test to examine brain tissue, though sometimes vessel imaging is also warranted. In the case of no red flags and a normal neurologic exam, the use of neuroimaging is low yield.”
The research has no funding. Ms. Yang and two other authors disclosed research funding from Merck. Dr. Minen reports no disclosures.
DENVER – a new study finds. But the use of diphenhydramine (Benadryl) more than doubled even though guidelines caution against it, while recommended drugs such triptans and corticosteroids were rarely prescribed.
From 2007-2010 to 2015-2018, researchers reported at the annual meeting of the American Headache Society, a database reveals that opioid use in headache cases at EDs fell from 54% to 28%. Diphenhydramine use grew from 17% to 36% (both (P < .001). The percentage of cases in which EDs sought neuroimaging stayed stable at about 36%, a number that the study authors described as too high.
“Future studies are warranted to identify strategies to promote evidence-based treatments for headaches and appropriate outpatient referrals for follow-up and to reduce unnecessary neuroimaging orders in EDs,” lead author Seonkyeong Yang, MS, of the University of Florida, Gainesville, said in an interview.
Ms. Yang said researchers launched the study to update previous data in light of changes in opioid prescribing and the 2016 release of American Headache Society guidelines for the treatment of acute migraines in the ED setting. The research was published in the Journal of Clinical Medicine.
Headache treatment in the ED
For the study, researchers analyzed data from the U.S. National Hospital Ambulatory Medical Care survey and focused on adults who had a primary discharge diagnosis of headache.
For the 2015-2018 period, per weighted numbers, the survey encompassed 10.2 million headaches mostly among people younger than 50 (71%), female (73%), and White (73%). Migraines made up 33% of the total, with nonspecified headache accounting for almost all of the remainder (63%).
In 68% of cases, two or more medications were administered in the ED. This number rose to 83% among patients with migraine. But most of the time (54%), no medications were prescribed at discharge.
Among recommended medications, antiemetics – the most commonly used class of drugs in these patients – were prescribed 59% of the time in both 2007-2010 and 2015-2018 (P = .88). Usage of acetaminophens and NSAIDs grew from 37% to 52% over that time period.
Despite recommendations, the use of ergot alkaloids/triptans and corticosteroids remained low (less than 6% of the time).
“Several factors may contribute to the underuse of triptans in EDs, including their cardiovascular contraindications, ED physicians’ unfamiliarity with injectable triptans, higher costs, and treatment failures with triptans before ED visits,” Ms. Yang said. “We observed an upward trend in dexamethasone use over time. However, it was still underutilized. [The corticosteroid was only used 3.5% of the time from 2015-2018.] The 2016 AHS guideline strongly recommends dexamethasone use to prevent migraine recurrence after ED discharge. Identifying patients at high risk of headache recurrence for dexamethasone use may further improve patient outcomes of acute headache management in ED settings.”
Ms. Yang also reported that the use of diphenhydramine grew even though it’s not recommended. “Diphenhydramine is more likely to be used to prevent akathisia, a side effect of some antiemetics [that is, dopamine receptor antagonists] in headache-related ED visits,” she said. “However, the 2016 AHS guideline recommends against diphenhydramine use due to its limited efficacy in relieving headache pain. In addition, there is also conflicting evidence on diphenhydramine’s efficacy in preventing akathisia when coadministered with antiemetics. Diphenhydramine use requires caution due to its sedative effect and abuse potential.”
As for medication combinations, Ms. Yang said “the most broadly used therapy among headache-related ED visits in 2007-2010 was an opioid with an antiemetic (21.0%), which decreased to 6.6% in 2015-2018. Meanwhile, the combined use of acetaminophen/NSAIDs with antiemetic and diphenhydramine increased substantially from 3.9% to 15.7% and became the most prevalent therapy in 2015-2018. Opioid monotherapy use gradually decreased during the study period [from 8.8% to 1.9%].”
Evidence-based treatments underutilized
Commenting on the findings, New York University Langone neurologist and headache researcher Mia Tova Minen, MD, MPH, noted in an interview that AHS guidelines do not indicate acetaminophen/NSAIDs, diphenhydramine, and corticosteroids for the acute treatment of migraine. “The recommended treatments are sumatriptan subcutaneous, IV metoclopramide, and IV prochlorperazine. Steroids can be helpful in the prevention of migraine recurrence but not for the acute treatment of the migraine itself,” she said. “We need to ensure that patients with migraine get the top evidence-based treatments for migraine.”
As for diphenhydramine, she said it “is not a treatment for headache disorders. It does not have proven efficacy. It is sometimes given to reduce side effects of more acute treatments of headache, but it can make patients fatigued and keep them in the ED longer.”
Overuse of neuroimaging
Ms. Yang also highlighted study data about the frequency of neuroimaging. “Understandably, ED physicians do not want to miss any life-threatening secondary headaches like stroke,” she said. “However, other factors also contribute to the overuse of neuroimaging in headache-related ED visits: patient demands, financial incentives, a busy ED practice where clinical evaluation is replaced by tests, and ED physicians’ unfamiliarity with ICHD-3 diagnostic criteria for primary headache disorders. There is still much room for improvement in neuroimaging use for headaches in ED settings.”
For her part, Dr. Minen said scans are often performed reflexively and can be overused. “A CT scan is really only good in the case of acute trauma to rule out a fracture or a bleed or if there are signs of an emergent neurologic emergency like herniation or if a MRI is contraindicated. An MRI of the brain is typically the best test to examine brain tissue, though sometimes vessel imaging is also warranted. In the case of no red flags and a normal neurologic exam, the use of neuroimaging is low yield.”
The research has no funding. Ms. Yang and two other authors disclosed research funding from Merck. Dr. Minen reports no disclosures.
DENVER – a new study finds. But the use of diphenhydramine (Benadryl) more than doubled even though guidelines caution against it, while recommended drugs such triptans and corticosteroids were rarely prescribed.
From 2007-2010 to 2015-2018, researchers reported at the annual meeting of the American Headache Society, a database reveals that opioid use in headache cases at EDs fell from 54% to 28%. Diphenhydramine use grew from 17% to 36% (both (P < .001). The percentage of cases in which EDs sought neuroimaging stayed stable at about 36%, a number that the study authors described as too high.
“Future studies are warranted to identify strategies to promote evidence-based treatments for headaches and appropriate outpatient referrals for follow-up and to reduce unnecessary neuroimaging orders in EDs,” lead author Seonkyeong Yang, MS, of the University of Florida, Gainesville, said in an interview.
Ms. Yang said researchers launched the study to update previous data in light of changes in opioid prescribing and the 2016 release of American Headache Society guidelines for the treatment of acute migraines in the ED setting. The research was published in the Journal of Clinical Medicine.
Headache treatment in the ED
For the study, researchers analyzed data from the U.S. National Hospital Ambulatory Medical Care survey and focused on adults who had a primary discharge diagnosis of headache.
For the 2015-2018 period, per weighted numbers, the survey encompassed 10.2 million headaches mostly among people younger than 50 (71%), female (73%), and White (73%). Migraines made up 33% of the total, with nonspecified headache accounting for almost all of the remainder (63%).
In 68% of cases, two or more medications were administered in the ED. This number rose to 83% among patients with migraine. But most of the time (54%), no medications were prescribed at discharge.
Among recommended medications, antiemetics – the most commonly used class of drugs in these patients – were prescribed 59% of the time in both 2007-2010 and 2015-2018 (P = .88). Usage of acetaminophens and NSAIDs grew from 37% to 52% over that time period.
Despite recommendations, the use of ergot alkaloids/triptans and corticosteroids remained low (less than 6% of the time).
“Several factors may contribute to the underuse of triptans in EDs, including their cardiovascular contraindications, ED physicians’ unfamiliarity with injectable triptans, higher costs, and treatment failures with triptans before ED visits,” Ms. Yang said. “We observed an upward trend in dexamethasone use over time. However, it was still underutilized. [The corticosteroid was only used 3.5% of the time from 2015-2018.] The 2016 AHS guideline strongly recommends dexamethasone use to prevent migraine recurrence after ED discharge. Identifying patients at high risk of headache recurrence for dexamethasone use may further improve patient outcomes of acute headache management in ED settings.”
Ms. Yang also reported that the use of diphenhydramine grew even though it’s not recommended. “Diphenhydramine is more likely to be used to prevent akathisia, a side effect of some antiemetics [that is, dopamine receptor antagonists] in headache-related ED visits,” she said. “However, the 2016 AHS guideline recommends against diphenhydramine use due to its limited efficacy in relieving headache pain. In addition, there is also conflicting evidence on diphenhydramine’s efficacy in preventing akathisia when coadministered with antiemetics. Diphenhydramine use requires caution due to its sedative effect and abuse potential.”
As for medication combinations, Ms. Yang said “the most broadly used therapy among headache-related ED visits in 2007-2010 was an opioid with an antiemetic (21.0%), which decreased to 6.6% in 2015-2018. Meanwhile, the combined use of acetaminophen/NSAIDs with antiemetic and diphenhydramine increased substantially from 3.9% to 15.7% and became the most prevalent therapy in 2015-2018. Opioid monotherapy use gradually decreased during the study period [from 8.8% to 1.9%].”
Evidence-based treatments underutilized
Commenting on the findings, New York University Langone neurologist and headache researcher Mia Tova Minen, MD, MPH, noted in an interview that AHS guidelines do not indicate acetaminophen/NSAIDs, diphenhydramine, and corticosteroids for the acute treatment of migraine. “The recommended treatments are sumatriptan subcutaneous, IV metoclopramide, and IV prochlorperazine. Steroids can be helpful in the prevention of migraine recurrence but not for the acute treatment of the migraine itself,” she said. “We need to ensure that patients with migraine get the top evidence-based treatments for migraine.”
As for diphenhydramine, she said it “is not a treatment for headache disorders. It does not have proven efficacy. It is sometimes given to reduce side effects of more acute treatments of headache, but it can make patients fatigued and keep them in the ED longer.”
Overuse of neuroimaging
Ms. Yang also highlighted study data about the frequency of neuroimaging. “Understandably, ED physicians do not want to miss any life-threatening secondary headaches like stroke,” she said. “However, other factors also contribute to the overuse of neuroimaging in headache-related ED visits: patient demands, financial incentives, a busy ED practice where clinical evaluation is replaced by tests, and ED physicians’ unfamiliarity with ICHD-3 diagnostic criteria for primary headache disorders. There is still much room for improvement in neuroimaging use for headaches in ED settings.”
For her part, Dr. Minen said scans are often performed reflexively and can be overused. “A CT scan is really only good in the case of acute trauma to rule out a fracture or a bleed or if there are signs of an emergent neurologic emergency like herniation or if a MRI is contraindicated. An MRI of the brain is typically the best test to examine brain tissue, though sometimes vessel imaging is also warranted. In the case of no red flags and a normal neurologic exam, the use of neuroimaging is low yield.”
The research has no funding. Ms. Yang and two other authors disclosed research funding from Merck. Dr. Minen reports no disclosures.
AT AHS 2022
Bariatric surgery can be a tool to relieve migraine
DENVER – , a neurologist told colleagues at the annual meeting of the American Headache Society. “There’s evidence-based medicine to support bariatric surgery, a lot of it, and the outcomes are actually pretty good,” said Jennifer McVige, MD, MA, of Dent Neurologic Institute in Buffalo, N.Y.
As Dr. McVige noted, research has linked obesity to migraine even after adjustment for comorbidities. A 2007 analysis of a survey of 30,215 participants, for example, found that “the proportion of subjects with severe headache pain increased with BMI, doubling in the morbidly obese relative to the normally weighted (odds ratio [OR] = 1.9).” And a 2011 study of 3,733 pregnant women found that risk of migraine increased in line with level of obesity: “obese women had a 1.48-fold increased odds of migraine (OR = 1.48; 95% confidence interval [CI], 1.12-1.96). Severely obese (OR = 2.07; 95% CI, 1.27-3.39) and morbidly obese (OR = 2.75; 95% CI, 1.60-4.70) had the highest odds of migraines.”
The link between obesity and headaches is unclear, she said, but there are hints at possible factors. For one, calcitonin gene-related peptide (CGRP) is increased in people with obesity and is an important factor in migraines. Additionally, nausea is quite common in people with migraine, suggesting a possible gut-brain interaction – or not.
“Nausea is associated with a lot of the medicines that we give patients with migraine. Is it the nausea that’s associated with the migraine medicine, or is nausea occurring at the end of the migraine?” she asked. “That’s always been kind of a conundrum for us.”
Whatever the case, she said, bariatric surgery appears to be helpful for patients with headache. Some studies have been small, but a 2021 analysis of 1,680 patients with migraine found that 55% experienced remission with no need for medication at 180 days post surgery. Women, older patients, and those taking more migraine medications were less likely to reach remission.
Research also suggests that bariatric surgery can relieve headache symptoms in patients with idiopathic intracranial hypertension.
Dr. McVige cautioned, however, that medical professionals must take special care when they talk to patients about their weight. “I’ve learned from conversations with my patients that they don’t like hearing ‘obese,’ or ‘fat,’ or ‘diet,’ or ‘losing weight.’ What they do like is ‘maybe we could try to find ways to be more healthy, to help your body to look the way that you would like it to look in the future. Let me help you. Maybe we can talk about nutrition. Maybe we can talk about exercise. Let’s talk about energy. Let’s talk about those types of things.’”
Unfortunately, there’s little research into how to have these conversations, Dr. McVige said. Still, “we need to be the first people to come forward and say, ‘This is a tough topic for me to talk about too. It makes me uncomfortable as well. I know you’re uncomfortable, but I have to talk to you because I care about you as a patient.’”
She also advised colleagues to not bring up weight right out of the gate. “It’s easier to say some of those things after you develop a relationship,” she said, “when they know you care about them.”
Dr. McVige reported multiple disclosures related to research funding and speaker fees.
DENVER – , a neurologist told colleagues at the annual meeting of the American Headache Society. “There’s evidence-based medicine to support bariatric surgery, a lot of it, and the outcomes are actually pretty good,” said Jennifer McVige, MD, MA, of Dent Neurologic Institute in Buffalo, N.Y.
As Dr. McVige noted, research has linked obesity to migraine even after adjustment for comorbidities. A 2007 analysis of a survey of 30,215 participants, for example, found that “the proportion of subjects with severe headache pain increased with BMI, doubling in the morbidly obese relative to the normally weighted (odds ratio [OR] = 1.9).” And a 2011 study of 3,733 pregnant women found that risk of migraine increased in line with level of obesity: “obese women had a 1.48-fold increased odds of migraine (OR = 1.48; 95% confidence interval [CI], 1.12-1.96). Severely obese (OR = 2.07; 95% CI, 1.27-3.39) and morbidly obese (OR = 2.75; 95% CI, 1.60-4.70) had the highest odds of migraines.”
The link between obesity and headaches is unclear, she said, but there are hints at possible factors. For one, calcitonin gene-related peptide (CGRP) is increased in people with obesity and is an important factor in migraines. Additionally, nausea is quite common in people with migraine, suggesting a possible gut-brain interaction – or not.
“Nausea is associated with a lot of the medicines that we give patients with migraine. Is it the nausea that’s associated with the migraine medicine, or is nausea occurring at the end of the migraine?” she asked. “That’s always been kind of a conundrum for us.”
Whatever the case, she said, bariatric surgery appears to be helpful for patients with headache. Some studies have been small, but a 2021 analysis of 1,680 patients with migraine found that 55% experienced remission with no need for medication at 180 days post surgery. Women, older patients, and those taking more migraine medications were less likely to reach remission.
Research also suggests that bariatric surgery can relieve headache symptoms in patients with idiopathic intracranial hypertension.
Dr. McVige cautioned, however, that medical professionals must take special care when they talk to patients about their weight. “I’ve learned from conversations with my patients that they don’t like hearing ‘obese,’ or ‘fat,’ or ‘diet,’ or ‘losing weight.’ What they do like is ‘maybe we could try to find ways to be more healthy, to help your body to look the way that you would like it to look in the future. Let me help you. Maybe we can talk about nutrition. Maybe we can talk about exercise. Let’s talk about energy. Let’s talk about those types of things.’”
Unfortunately, there’s little research into how to have these conversations, Dr. McVige said. Still, “we need to be the first people to come forward and say, ‘This is a tough topic for me to talk about too. It makes me uncomfortable as well. I know you’re uncomfortable, but I have to talk to you because I care about you as a patient.’”
She also advised colleagues to not bring up weight right out of the gate. “It’s easier to say some of those things after you develop a relationship,” she said, “when they know you care about them.”
Dr. McVige reported multiple disclosures related to research funding and speaker fees.
DENVER – , a neurologist told colleagues at the annual meeting of the American Headache Society. “There’s evidence-based medicine to support bariatric surgery, a lot of it, and the outcomes are actually pretty good,” said Jennifer McVige, MD, MA, of Dent Neurologic Institute in Buffalo, N.Y.
As Dr. McVige noted, research has linked obesity to migraine even after adjustment for comorbidities. A 2007 analysis of a survey of 30,215 participants, for example, found that “the proportion of subjects with severe headache pain increased with BMI, doubling in the morbidly obese relative to the normally weighted (odds ratio [OR] = 1.9).” And a 2011 study of 3,733 pregnant women found that risk of migraine increased in line with level of obesity: “obese women had a 1.48-fold increased odds of migraine (OR = 1.48; 95% confidence interval [CI], 1.12-1.96). Severely obese (OR = 2.07; 95% CI, 1.27-3.39) and morbidly obese (OR = 2.75; 95% CI, 1.60-4.70) had the highest odds of migraines.”
The link between obesity and headaches is unclear, she said, but there are hints at possible factors. For one, calcitonin gene-related peptide (CGRP) is increased in people with obesity and is an important factor in migraines. Additionally, nausea is quite common in people with migraine, suggesting a possible gut-brain interaction – or not.
“Nausea is associated with a lot of the medicines that we give patients with migraine. Is it the nausea that’s associated with the migraine medicine, or is nausea occurring at the end of the migraine?” she asked. “That’s always been kind of a conundrum for us.”
Whatever the case, she said, bariatric surgery appears to be helpful for patients with headache. Some studies have been small, but a 2021 analysis of 1,680 patients with migraine found that 55% experienced remission with no need for medication at 180 days post surgery. Women, older patients, and those taking more migraine medications were less likely to reach remission.
Research also suggests that bariatric surgery can relieve headache symptoms in patients with idiopathic intracranial hypertension.
Dr. McVige cautioned, however, that medical professionals must take special care when they talk to patients about their weight. “I’ve learned from conversations with my patients that they don’t like hearing ‘obese,’ or ‘fat,’ or ‘diet,’ or ‘losing weight.’ What they do like is ‘maybe we could try to find ways to be more healthy, to help your body to look the way that you would like it to look in the future. Let me help you. Maybe we can talk about nutrition. Maybe we can talk about exercise. Let’s talk about energy. Let’s talk about those types of things.’”
Unfortunately, there’s little research into how to have these conversations, Dr. McVige said. Still, “we need to be the first people to come forward and say, ‘This is a tough topic for me to talk about too. It makes me uncomfortable as well. I know you’re uncomfortable, but I have to talk to you because I care about you as a patient.’”
She also advised colleagues to not bring up weight right out of the gate. “It’s easier to say some of those things after you develop a relationship,” she said, “when they know you care about them.”
Dr. McVige reported multiple disclosures related to research funding and speaker fees.
AT AHS 2022
Psychedelic drugs ‘truly have potential’ in headache care
DENVER – Psychedelics such as psilocybin “truly have the potential to transform how we treat a number of neuropsychiatric diseases, including headaches,” a neuropharmacologist told colleagues at the annual meeting of the American Headache Society.
However, Bryan Roth, MD, PhD, professor of pharmacology at the University of North Carolina at Chapel Hill, also offered a major cautionary note: There have been no randomized, phase 3 trials of psychedelics, and he bluntly said that “I do not recommend the use of psychedelics for any medical condition.”
The potential disease-altering powers of psychedelics have received a tremendous amount of research and media attention over the past several years. A landmark randomized, double-blind study released in 2016 triggered much of the interest, Dr. Roth said, when it suggested that high-dose psilocybin significantly lowered levels of depressed mood/anxiety in patients with life-threatening cancer. At 6 months, 80% of patients who took the dose reported moderate or greater improvement in well-being/life satisfaction.
“You have the potential – unprecedented in psychiatry – that a single dose of a therapeutic agent may induce a rapid, robust, and sustained antidepressant action,” he said. Also of note: The “vast majority” of subjects say their encounter with a psychedelic was “one of the most meaningful experiences of their lives.”
Dr. Roth said his own research suggests that psychedelics cause a “huge increase” in the asynchronous firing of neurons. “Noise is being injected into the system and is interpreted by the brain or the mind, which always likes to make a story about what’s going on. The story it makes up is idiosyncratic to every person and memorable for reasons that are not understood.”
Now, Dr. Roth said, he and colleagues are working to “create drugs that have this potential remarkable therapeutic efficacy in psychiatric and neurologic disorders without the psychedelic effects.” A $27 million grant from the Defense Advanced Research Projects Agency is providing support for their efforts, he said.
For the moment, he said, there’s no way to know if “the psychedelic experience is essential to the therapeutic action of these drugs. But it’s a testable hypothesis.”
As he noted, a tiny 2010 study of 2-bromo-lysergic acid diethylamide (LSD), which doesn’t cause hallucinations, showed promise as a treatment for cluster headaches.
For now, Dr. Roth said, his lab is synthesizing and testing new compounds that interact with the crucial 5-HT2A receptor.
Additional research
In another presentation at the AHS annual meeting, neurologist Emmanuelle A. D. Schindler, MD, PhD, of Yale School of Medicine, highlighted her 2021 study of an exploratory double-blind, placebo-controlled, cross-over study of psilocybin versus placebo for migraine headache. A single oral dose of the drug, the researchers found, reduced headache frequency and pain over 2 weeks. The study is small, with just 10 subjects, and multiple exclusion criteria.
She also revealed preliminary findings from an ongoing randomized, double-blind, placebo-controlled study of psilocybin versus placebo in cluster headaches. In 14 subjects, a psilocybin pulse was linked to fewer cluster attacks over 3 weeks, although the effect wasn’t statistically significant. However, there was a statistically significant reduction over 8 weeks in patients with chronic headache.
Dr. Schindler noted that “with these early studies, we only looked out to 2 weeks for migraine, and we only looked out to 2 months for cluster.” There are multiple other limitations, she acknowledged. “We have to do a lot more research and consider safety as well.”
However, “there is a really unique capacity for lasting effects after limited dosing,” she added, and the studies do show reductions in headache burden “that do not correlate with acute psychedelic effects.”
Moving forward, Dr. Roth cautioned that while U.S. states are allowing the use of psychedelics for medical purposes, “we don’t know if they ultimately are therapeutic. And we have strong reason to believe that microdosing or chronic dosing of these compounds is ultimately going to be deleterious to the health of our patients.”
Dr. Roth did not provide disclosure information. Dr. Schindler discloses research funding (Ceruvia Lifesciences, Wallace Research Foundation, Clusterbusters, Department of Veterans Affairs), serves on advisory boards (Ceruvia Lifesciences, Clusterbusters), and has a patent.
DENVER – Psychedelics such as psilocybin “truly have the potential to transform how we treat a number of neuropsychiatric diseases, including headaches,” a neuropharmacologist told colleagues at the annual meeting of the American Headache Society.
However, Bryan Roth, MD, PhD, professor of pharmacology at the University of North Carolina at Chapel Hill, also offered a major cautionary note: There have been no randomized, phase 3 trials of psychedelics, and he bluntly said that “I do not recommend the use of psychedelics for any medical condition.”
The potential disease-altering powers of psychedelics have received a tremendous amount of research and media attention over the past several years. A landmark randomized, double-blind study released in 2016 triggered much of the interest, Dr. Roth said, when it suggested that high-dose psilocybin significantly lowered levels of depressed mood/anxiety in patients with life-threatening cancer. At 6 months, 80% of patients who took the dose reported moderate or greater improvement in well-being/life satisfaction.
“You have the potential – unprecedented in psychiatry – that a single dose of a therapeutic agent may induce a rapid, robust, and sustained antidepressant action,” he said. Also of note: The “vast majority” of subjects say their encounter with a psychedelic was “one of the most meaningful experiences of their lives.”
Dr. Roth said his own research suggests that psychedelics cause a “huge increase” in the asynchronous firing of neurons. “Noise is being injected into the system and is interpreted by the brain or the mind, which always likes to make a story about what’s going on. The story it makes up is idiosyncratic to every person and memorable for reasons that are not understood.”
Now, Dr. Roth said, he and colleagues are working to “create drugs that have this potential remarkable therapeutic efficacy in psychiatric and neurologic disorders without the psychedelic effects.” A $27 million grant from the Defense Advanced Research Projects Agency is providing support for their efforts, he said.
For the moment, he said, there’s no way to know if “the psychedelic experience is essential to the therapeutic action of these drugs. But it’s a testable hypothesis.”
As he noted, a tiny 2010 study of 2-bromo-lysergic acid diethylamide (LSD), which doesn’t cause hallucinations, showed promise as a treatment for cluster headaches.
For now, Dr. Roth said, his lab is synthesizing and testing new compounds that interact with the crucial 5-HT2A receptor.
Additional research
In another presentation at the AHS annual meeting, neurologist Emmanuelle A. D. Schindler, MD, PhD, of Yale School of Medicine, highlighted her 2021 study of an exploratory double-blind, placebo-controlled, cross-over study of psilocybin versus placebo for migraine headache. A single oral dose of the drug, the researchers found, reduced headache frequency and pain over 2 weeks. The study is small, with just 10 subjects, and multiple exclusion criteria.
She also revealed preliminary findings from an ongoing randomized, double-blind, placebo-controlled study of psilocybin versus placebo in cluster headaches. In 14 subjects, a psilocybin pulse was linked to fewer cluster attacks over 3 weeks, although the effect wasn’t statistically significant. However, there was a statistically significant reduction over 8 weeks in patients with chronic headache.
Dr. Schindler noted that “with these early studies, we only looked out to 2 weeks for migraine, and we only looked out to 2 months for cluster.” There are multiple other limitations, she acknowledged. “We have to do a lot more research and consider safety as well.”
However, “there is a really unique capacity for lasting effects after limited dosing,” she added, and the studies do show reductions in headache burden “that do not correlate with acute psychedelic effects.”
Moving forward, Dr. Roth cautioned that while U.S. states are allowing the use of psychedelics for medical purposes, “we don’t know if they ultimately are therapeutic. And we have strong reason to believe that microdosing or chronic dosing of these compounds is ultimately going to be deleterious to the health of our patients.”
Dr. Roth did not provide disclosure information. Dr. Schindler discloses research funding (Ceruvia Lifesciences, Wallace Research Foundation, Clusterbusters, Department of Veterans Affairs), serves on advisory boards (Ceruvia Lifesciences, Clusterbusters), and has a patent.
DENVER – Psychedelics such as psilocybin “truly have the potential to transform how we treat a number of neuropsychiatric diseases, including headaches,” a neuropharmacologist told colleagues at the annual meeting of the American Headache Society.
However, Bryan Roth, MD, PhD, professor of pharmacology at the University of North Carolina at Chapel Hill, also offered a major cautionary note: There have been no randomized, phase 3 trials of psychedelics, and he bluntly said that “I do not recommend the use of psychedelics for any medical condition.”
The potential disease-altering powers of psychedelics have received a tremendous amount of research and media attention over the past several years. A landmark randomized, double-blind study released in 2016 triggered much of the interest, Dr. Roth said, when it suggested that high-dose psilocybin significantly lowered levels of depressed mood/anxiety in patients with life-threatening cancer. At 6 months, 80% of patients who took the dose reported moderate or greater improvement in well-being/life satisfaction.
“You have the potential – unprecedented in psychiatry – that a single dose of a therapeutic agent may induce a rapid, robust, and sustained antidepressant action,” he said. Also of note: The “vast majority” of subjects say their encounter with a psychedelic was “one of the most meaningful experiences of their lives.”
Dr. Roth said his own research suggests that psychedelics cause a “huge increase” in the asynchronous firing of neurons. “Noise is being injected into the system and is interpreted by the brain or the mind, which always likes to make a story about what’s going on. The story it makes up is idiosyncratic to every person and memorable for reasons that are not understood.”
Now, Dr. Roth said, he and colleagues are working to “create drugs that have this potential remarkable therapeutic efficacy in psychiatric and neurologic disorders without the psychedelic effects.” A $27 million grant from the Defense Advanced Research Projects Agency is providing support for their efforts, he said.
For the moment, he said, there’s no way to know if “the psychedelic experience is essential to the therapeutic action of these drugs. But it’s a testable hypothesis.”
As he noted, a tiny 2010 study of 2-bromo-lysergic acid diethylamide (LSD), which doesn’t cause hallucinations, showed promise as a treatment for cluster headaches.
For now, Dr. Roth said, his lab is synthesizing and testing new compounds that interact with the crucial 5-HT2A receptor.
Additional research
In another presentation at the AHS annual meeting, neurologist Emmanuelle A. D. Schindler, MD, PhD, of Yale School of Medicine, highlighted her 2021 study of an exploratory double-blind, placebo-controlled, cross-over study of psilocybin versus placebo for migraine headache. A single oral dose of the drug, the researchers found, reduced headache frequency and pain over 2 weeks. The study is small, with just 10 subjects, and multiple exclusion criteria.
She also revealed preliminary findings from an ongoing randomized, double-blind, placebo-controlled study of psilocybin versus placebo in cluster headaches. In 14 subjects, a psilocybin pulse was linked to fewer cluster attacks over 3 weeks, although the effect wasn’t statistically significant. However, there was a statistically significant reduction over 8 weeks in patients with chronic headache.
Dr. Schindler noted that “with these early studies, we only looked out to 2 weeks for migraine, and we only looked out to 2 months for cluster.” There are multiple other limitations, she acknowledged. “We have to do a lot more research and consider safety as well.”
However, “there is a really unique capacity for lasting effects after limited dosing,” she added, and the studies do show reductions in headache burden “that do not correlate with acute psychedelic effects.”
Moving forward, Dr. Roth cautioned that while U.S. states are allowing the use of psychedelics for medical purposes, “we don’t know if they ultimately are therapeutic. And we have strong reason to believe that microdosing or chronic dosing of these compounds is ultimately going to be deleterious to the health of our patients.”
Dr. Roth did not provide disclosure information. Dr. Schindler discloses research funding (Ceruvia Lifesciences, Wallace Research Foundation, Clusterbusters, Department of Veterans Affairs), serves on advisory boards (Ceruvia Lifesciences, Clusterbusters), and has a patent.
FROM AHS 2022
Risk of drug interactions is on the rise as MS drugs evolve
NATIONAL HARBOR, MD – How often do patients with multiple sclerosis (MS) end up taking drugs that could dangerously interact with other medications they’re taking? A new German study provides a disturbing hint, a pharmacist who spoke at the annual meeting of the Consortium of Multiple Sclerosis Centers told colleagues: Out of 627 patients who took an average of 5.3 drugs each, about 1 in 25 faced a potentially severe interaction, and nearly two-thirds had at least one potentially risky interaction.
It’s crucial to “work on identifying those interactions,” said Jenelle H. Montgomery, PharmD, of Duke University Hospital, Durham, N.C., and to understand the risks. As she noted, interactions don’t just put patients at risk of adverse effects and hospitalization. They can also lead to secondary comorbidities and therapeutic failures.
Newer versus older drugs
Drug interactions in MS have become more common as disease-modifying therapies have evolved, she said. Some older drugs – such as glatiramer acetate, beta-interferons, and fumarates – have low interaction profiles. But newer drugs have more drug interactions caused in part by their side-effect profiles, oral routes of administration, and immunosuppressive instead of immunomodulatory effects, she said. Teriflunomide, for example, interacts with rosuvastatin and warfarin.
S1P modulators are especially complex on the interaction front, Dr. Montgomery said. Cardiology consults are recommended for patients taking siponimod, ozanimod, and ponesimod, and there are a number of potential interactions between these drugs and other medications.
In regard to other MS drugs, other medications can disrupt the metabolism of cladribine, she said, and the manufacturer recommends separating any other oral drug doses by 3 hours. Even MS-related drugs can interact: carbamazepine, used to treat MS-related neuropathic pain, interacts with drugs such as siponimod.
Who is most at risk?
One strategy could be to focus on patients who may be more susceptible. Dr. Montgomery highlighted the kinds of patients who were most at risk of polypharmacy, per the 2022 German study: older people, those with lower education levels, and those with more disability. And she pointed out that 77% of all drug interactions were between prescription drugs. Another 19% were between prescription drugs and over-the-counter medications, and 4% were between OTC drugs.
She also emphasized the importance of asking about everything that a patient is taking, including herbal supplements, as nearly 60% of people aged 20 and over take them, and about 75% of those over 60. A quarter of people over age 60 take at least four supplements.
Information about interactions with supplements isn’t always available, she said, but she did mention concerns about St. John’s wort interactions with siponimod and cladribine.
Dr. Montgomery also offered several tips: Periodically ask patients to bring in medication bottles or pillboxes; encourage annual checkups with primary physicians; and use drug resources such as Facts and Comparisons, Lexicomp, Clinical Pharmacology, Micromedex, and Natural Medicines.
Disclosures for Dr. Montgomery were not available.
NATIONAL HARBOR, MD – How often do patients with multiple sclerosis (MS) end up taking drugs that could dangerously interact with other medications they’re taking? A new German study provides a disturbing hint, a pharmacist who spoke at the annual meeting of the Consortium of Multiple Sclerosis Centers told colleagues: Out of 627 patients who took an average of 5.3 drugs each, about 1 in 25 faced a potentially severe interaction, and nearly two-thirds had at least one potentially risky interaction.
It’s crucial to “work on identifying those interactions,” said Jenelle H. Montgomery, PharmD, of Duke University Hospital, Durham, N.C., and to understand the risks. As she noted, interactions don’t just put patients at risk of adverse effects and hospitalization. They can also lead to secondary comorbidities and therapeutic failures.
Newer versus older drugs
Drug interactions in MS have become more common as disease-modifying therapies have evolved, she said. Some older drugs – such as glatiramer acetate, beta-interferons, and fumarates – have low interaction profiles. But newer drugs have more drug interactions caused in part by their side-effect profiles, oral routes of administration, and immunosuppressive instead of immunomodulatory effects, she said. Teriflunomide, for example, interacts with rosuvastatin and warfarin.
S1P modulators are especially complex on the interaction front, Dr. Montgomery said. Cardiology consults are recommended for patients taking siponimod, ozanimod, and ponesimod, and there are a number of potential interactions between these drugs and other medications.
In regard to other MS drugs, other medications can disrupt the metabolism of cladribine, she said, and the manufacturer recommends separating any other oral drug doses by 3 hours. Even MS-related drugs can interact: carbamazepine, used to treat MS-related neuropathic pain, interacts with drugs such as siponimod.
Who is most at risk?
One strategy could be to focus on patients who may be more susceptible. Dr. Montgomery highlighted the kinds of patients who were most at risk of polypharmacy, per the 2022 German study: older people, those with lower education levels, and those with more disability. And she pointed out that 77% of all drug interactions were between prescription drugs. Another 19% were between prescription drugs and over-the-counter medications, and 4% were between OTC drugs.
She also emphasized the importance of asking about everything that a patient is taking, including herbal supplements, as nearly 60% of people aged 20 and over take them, and about 75% of those over 60. A quarter of people over age 60 take at least four supplements.
Information about interactions with supplements isn’t always available, she said, but she did mention concerns about St. John’s wort interactions with siponimod and cladribine.
Dr. Montgomery also offered several tips: Periodically ask patients to bring in medication bottles or pillboxes; encourage annual checkups with primary physicians; and use drug resources such as Facts and Comparisons, Lexicomp, Clinical Pharmacology, Micromedex, and Natural Medicines.
Disclosures for Dr. Montgomery were not available.
NATIONAL HARBOR, MD – How often do patients with multiple sclerosis (MS) end up taking drugs that could dangerously interact with other medications they’re taking? A new German study provides a disturbing hint, a pharmacist who spoke at the annual meeting of the Consortium of Multiple Sclerosis Centers told colleagues: Out of 627 patients who took an average of 5.3 drugs each, about 1 in 25 faced a potentially severe interaction, and nearly two-thirds had at least one potentially risky interaction.
It’s crucial to “work on identifying those interactions,” said Jenelle H. Montgomery, PharmD, of Duke University Hospital, Durham, N.C., and to understand the risks. As she noted, interactions don’t just put patients at risk of adverse effects and hospitalization. They can also lead to secondary comorbidities and therapeutic failures.
Newer versus older drugs
Drug interactions in MS have become more common as disease-modifying therapies have evolved, she said. Some older drugs – such as glatiramer acetate, beta-interferons, and fumarates – have low interaction profiles. But newer drugs have more drug interactions caused in part by their side-effect profiles, oral routes of administration, and immunosuppressive instead of immunomodulatory effects, she said. Teriflunomide, for example, interacts with rosuvastatin and warfarin.
S1P modulators are especially complex on the interaction front, Dr. Montgomery said. Cardiology consults are recommended for patients taking siponimod, ozanimod, and ponesimod, and there are a number of potential interactions between these drugs and other medications.
In regard to other MS drugs, other medications can disrupt the metabolism of cladribine, she said, and the manufacturer recommends separating any other oral drug doses by 3 hours. Even MS-related drugs can interact: carbamazepine, used to treat MS-related neuropathic pain, interacts with drugs such as siponimod.
Who is most at risk?
One strategy could be to focus on patients who may be more susceptible. Dr. Montgomery highlighted the kinds of patients who were most at risk of polypharmacy, per the 2022 German study: older people, those with lower education levels, and those with more disability. And she pointed out that 77% of all drug interactions were between prescription drugs. Another 19% were between prescription drugs and over-the-counter medications, and 4% were between OTC drugs.
She also emphasized the importance of asking about everything that a patient is taking, including herbal supplements, as nearly 60% of people aged 20 and over take them, and about 75% of those over 60. A quarter of people over age 60 take at least four supplements.
Information about interactions with supplements isn’t always available, she said, but she did mention concerns about St. John’s wort interactions with siponimod and cladribine.
Dr. Montgomery also offered several tips: Periodically ask patients to bring in medication bottles or pillboxes; encourage annual checkups with primary physicians; and use drug resources such as Facts and Comparisons, Lexicomp, Clinical Pharmacology, Micromedex, and Natural Medicines.
Disclosures for Dr. Montgomery were not available.
AT CMSC 2022
Consider the wider picture in relapsing remitting MS
NATIONAL HARBOR, MD. – Consider his 40-year-old female patient who’s averse to vaccines, often misses appointments, and seems to be unable to take blood pressure drugs as prescribed. In this case, the best strategy may not be the drug with the highest efficacy.
“There’s no pharmaceutical insert that’s going to tell you what to do with all of this information,” John R. Rinker II, MD, of the University of Alabama at Birmingham, said in a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers. “It’s important to not only know about the disease and the specifics of the pharmaceuticals, but also about the patient’s personal circumstances, their comorbidities, their social situation, and how it all ties together.”
Fortunately, he said, there are about two dozen medication options now available for RRMS. Noting that his scale is at best “a crude approximation of reality,” he said their efficacy runs the gamut from low (glatiramer acetate and beta-interferons) to high (cladribine, alemtuzumab). He places sphingosine-1 phosphate (SIP1) modulators in the mid-range in terms of efficacy and B cell-depleting agents and natalizumab toward the high side.
Why go low?
Why put someone on a low-efficacy drug? One reason is because they’re the safest options, he said, while the two highest-efficacy drugs – cladribine and alemtuzumab – are the least safe. But even the older, safer drugs can cause problems: Beta interferons can cause flu-like symptoms early on along with depression and miscarriage, and glatiramer acetate can spur injection site reactions and acute post injection syndrome “that can feel like a panic attack or even a heart attack.”
Dimethyl fumarate “is probably the easiest of the oral agents to initiate because there’s no extra doctor’s appointments. And there’s no concerns really about hair loss, liver failure, or birth defects,” he said. “But it’s one of the oral agents that has the most side effects associated with it.” Flushing is almost universal but “rarely a cause of discontinuation,” while gastrointestinal symptoms can lead to discontinuation.
Alemtuzumab, a high-efficacy drug that’s administered in two annual cycles, he said, is especially convenient but monthly labs are required for years to check for problems due to its dampening of the immune system. Patients on ocrelizumab must be closely monitored for the same reason.
There are other factors to consider. Lower-efficacy drugs tend to be better options in younger patients – “they’re more resilient, and they tend to recover a little bit better after their early relapses,” Dr. Rinker said.
The drugs are especially helpful in patients who recover well after their initial episodes and who have sensory instead of motor symptoms, he said.
The case for high efficacy
Higher-efficacy drugs are best for older patients and those with heavy disease burden.
What about the 40-year-old patient? She’s female (women get less sick from MS) and has low disease burden, suggesting that a lower-efficacy drug may be appropriate, he said. “On the other hand, she has an incomplete recovery, and she’s got spinal cord disease and motor symptoms, so the tendency is going to be more towards the higher-efficacy end of the [drug] spectrum.”
But which drug? S1P modulators aren’t a good option since they require redosing or titration if doses are missed: “It’s important that you don’t prescribe them to patients where you have concerns about compliance.”
Also, he said, “we don’t think we’re to the point that we’re willing to put her at risk of severe medical complications by putting her on medicines with a high monitoring burden like cladribine or alemtuzumab.”
The best option may be teriflunomide, a once-daily pill, he said. It’s forgiving if a patient misses a dose since the medication stays in the body for a long time.
“There’s no single right answer,” Dr. Rinker said. “But there are ways to eliminate a lot of the choices based upon what we know about the medications and what we know about the patient. Then we can tailor a specific range of medications for a specific patient.”
Dr. Rinker disclosed research support from GW Pharmaceuticals.
NATIONAL HARBOR, MD. – Consider his 40-year-old female patient who’s averse to vaccines, often misses appointments, and seems to be unable to take blood pressure drugs as prescribed. In this case, the best strategy may not be the drug with the highest efficacy.
“There’s no pharmaceutical insert that’s going to tell you what to do with all of this information,” John R. Rinker II, MD, of the University of Alabama at Birmingham, said in a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers. “It’s important to not only know about the disease and the specifics of the pharmaceuticals, but also about the patient’s personal circumstances, their comorbidities, their social situation, and how it all ties together.”
Fortunately, he said, there are about two dozen medication options now available for RRMS. Noting that his scale is at best “a crude approximation of reality,” he said their efficacy runs the gamut from low (glatiramer acetate and beta-interferons) to high (cladribine, alemtuzumab). He places sphingosine-1 phosphate (SIP1) modulators in the mid-range in terms of efficacy and B cell-depleting agents and natalizumab toward the high side.
Why go low?
Why put someone on a low-efficacy drug? One reason is because they’re the safest options, he said, while the two highest-efficacy drugs – cladribine and alemtuzumab – are the least safe. But even the older, safer drugs can cause problems: Beta interferons can cause flu-like symptoms early on along with depression and miscarriage, and glatiramer acetate can spur injection site reactions and acute post injection syndrome “that can feel like a panic attack or even a heart attack.”
Dimethyl fumarate “is probably the easiest of the oral agents to initiate because there’s no extra doctor’s appointments. And there’s no concerns really about hair loss, liver failure, or birth defects,” he said. “But it’s one of the oral agents that has the most side effects associated with it.” Flushing is almost universal but “rarely a cause of discontinuation,” while gastrointestinal symptoms can lead to discontinuation.
Alemtuzumab, a high-efficacy drug that’s administered in two annual cycles, he said, is especially convenient but monthly labs are required for years to check for problems due to its dampening of the immune system. Patients on ocrelizumab must be closely monitored for the same reason.
There are other factors to consider. Lower-efficacy drugs tend to be better options in younger patients – “they’re more resilient, and they tend to recover a little bit better after their early relapses,” Dr. Rinker said.
The drugs are especially helpful in patients who recover well after their initial episodes and who have sensory instead of motor symptoms, he said.
The case for high efficacy
Higher-efficacy drugs are best for older patients and those with heavy disease burden.
What about the 40-year-old patient? She’s female (women get less sick from MS) and has low disease burden, suggesting that a lower-efficacy drug may be appropriate, he said. “On the other hand, she has an incomplete recovery, and she’s got spinal cord disease and motor symptoms, so the tendency is going to be more towards the higher-efficacy end of the [drug] spectrum.”
But which drug? S1P modulators aren’t a good option since they require redosing or titration if doses are missed: “It’s important that you don’t prescribe them to patients where you have concerns about compliance.”
Also, he said, “we don’t think we’re to the point that we’re willing to put her at risk of severe medical complications by putting her on medicines with a high monitoring burden like cladribine or alemtuzumab.”
The best option may be teriflunomide, a once-daily pill, he said. It’s forgiving if a patient misses a dose since the medication stays in the body for a long time.
“There’s no single right answer,” Dr. Rinker said. “But there are ways to eliminate a lot of the choices based upon what we know about the medications and what we know about the patient. Then we can tailor a specific range of medications for a specific patient.”
Dr. Rinker disclosed research support from GW Pharmaceuticals.
NATIONAL HARBOR, MD. – Consider his 40-year-old female patient who’s averse to vaccines, often misses appointments, and seems to be unable to take blood pressure drugs as prescribed. In this case, the best strategy may not be the drug with the highest efficacy.
“There’s no pharmaceutical insert that’s going to tell you what to do with all of this information,” John R. Rinker II, MD, of the University of Alabama at Birmingham, said in a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers. “It’s important to not only know about the disease and the specifics of the pharmaceuticals, but also about the patient’s personal circumstances, their comorbidities, their social situation, and how it all ties together.”
Fortunately, he said, there are about two dozen medication options now available for RRMS. Noting that his scale is at best “a crude approximation of reality,” he said their efficacy runs the gamut from low (glatiramer acetate and beta-interferons) to high (cladribine, alemtuzumab). He places sphingosine-1 phosphate (SIP1) modulators in the mid-range in terms of efficacy and B cell-depleting agents and natalizumab toward the high side.
Why go low?
Why put someone on a low-efficacy drug? One reason is because they’re the safest options, he said, while the two highest-efficacy drugs – cladribine and alemtuzumab – are the least safe. But even the older, safer drugs can cause problems: Beta interferons can cause flu-like symptoms early on along with depression and miscarriage, and glatiramer acetate can spur injection site reactions and acute post injection syndrome “that can feel like a panic attack or even a heart attack.”
Dimethyl fumarate “is probably the easiest of the oral agents to initiate because there’s no extra doctor’s appointments. And there’s no concerns really about hair loss, liver failure, or birth defects,” he said. “But it’s one of the oral agents that has the most side effects associated with it.” Flushing is almost universal but “rarely a cause of discontinuation,” while gastrointestinal symptoms can lead to discontinuation.
Alemtuzumab, a high-efficacy drug that’s administered in two annual cycles, he said, is especially convenient but monthly labs are required for years to check for problems due to its dampening of the immune system. Patients on ocrelizumab must be closely monitored for the same reason.
There are other factors to consider. Lower-efficacy drugs tend to be better options in younger patients – “they’re more resilient, and they tend to recover a little bit better after their early relapses,” Dr. Rinker said.
The drugs are especially helpful in patients who recover well after their initial episodes and who have sensory instead of motor symptoms, he said.
The case for high efficacy
Higher-efficacy drugs are best for older patients and those with heavy disease burden.
What about the 40-year-old patient? She’s female (women get less sick from MS) and has low disease burden, suggesting that a lower-efficacy drug may be appropriate, he said. “On the other hand, she has an incomplete recovery, and she’s got spinal cord disease and motor symptoms, so the tendency is going to be more towards the higher-efficacy end of the [drug] spectrum.”
But which drug? S1P modulators aren’t a good option since they require redosing or titration if doses are missed: “It’s important that you don’t prescribe them to patients where you have concerns about compliance.”
Also, he said, “we don’t think we’re to the point that we’re willing to put her at risk of severe medical complications by putting her on medicines with a high monitoring burden like cladribine or alemtuzumab.”
The best option may be teriflunomide, a once-daily pill, he said. It’s forgiving if a patient misses a dose since the medication stays in the body for a long time.
“There’s no single right answer,” Dr. Rinker said. “But there are ways to eliminate a lot of the choices based upon what we know about the medications and what we know about the patient. Then we can tailor a specific range of medications for a specific patient.”
Dr. Rinker disclosed research support from GW Pharmaceuticals.
AT CMSC 2022
MS and family planning: Bring it up at every office visit
NATIONAL HARBOR, MD – Just 2 days before she spoke in a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers, University of Colorado neurologist Anna Shah, MD, asked a 26-year-old patient with MS about whether she planned to have children. Absolutely not, the young woman replied. “I read online that I can give birth to a baby with MS, which is crazy.”
The patient didn’t understand the risk of having a child with MS – it’s thought to be 2%-5% if one parent has the condition – but she wouldn’t have learned the facts if Dr. Shah hadn’t asked the right questions. “It’s really important for us as a community to know how to be proactive with discussions [about pregnancy],” she said.
As she noted, an estimated 75% of patients with MS are women, most are diagnosed during prime child-bearing years, and many pregnancies in general – an estimated half – are not planned. And while a higher percentage of women with MS are having children than in the past, she said, misinformation remains common. In fact, physicians can be part of the problem.
Dr. Shaw highlighted a 2019 Italian survey that found that 16% of 395 people with MS reported that they were discouraged from having children, mainly by medical professionals, after their diagnosis. Seven percent said they never wanted to become parents because of their MS. A 2021 survey of 332 patients with MS in the United States, United Kingdom, France, Germany, Italy, and Spain, found that 56% reported that MS played a role in their decisions about family planning, and 14% of those decided not to have children.
In regard to women of child-bearing age, Dr. Shah recommends that Open-ended, individualized questions are key. “We don’t know what patients don’t share with us,” she said.
Make sure to consider the timing of any plans to have children, she said. If the patient wants to have children within a year, talk about matters such as whether disease activity is well-controlled (6-12 months of good control is ideal) and whether current disease-modifying therapies are safe. Make sure to get a baseline prepartum MRI scan, she said.
If the patients don’t want to have children, make sure they are using a reliable strategy to avoid conception. Be aware that modafinil – “not one that immediately comes to mind” – may decrease the efficacy of oral contraceptives, she said, as can anticonvulsants (phenytoin, carbamazepine, oxcarbazepine, topiramate, and primidone). Oral contraceptives, meanwhile, may decrease levels of lamotrigine.
What if a patient has trouble conceiving? There are some hints in research that MS may boost the risk of infertility in women, Dr. Shah said. That’s why she recommends that colleagues consider referring a patient to an infertility specialist after attempting conception for 6 months as opposed to the general recommendation for 12 months.
Dr. Shah disclosed advisory board service (Genentech) and development of nonbranded educational programming through Novartis and the National Committee for Quality Assurance.
NATIONAL HARBOR, MD – Just 2 days before she spoke in a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers, University of Colorado neurologist Anna Shah, MD, asked a 26-year-old patient with MS about whether she planned to have children. Absolutely not, the young woman replied. “I read online that I can give birth to a baby with MS, which is crazy.”
The patient didn’t understand the risk of having a child with MS – it’s thought to be 2%-5% if one parent has the condition – but she wouldn’t have learned the facts if Dr. Shah hadn’t asked the right questions. “It’s really important for us as a community to know how to be proactive with discussions [about pregnancy],” she said.
As she noted, an estimated 75% of patients with MS are women, most are diagnosed during prime child-bearing years, and many pregnancies in general – an estimated half – are not planned. And while a higher percentage of women with MS are having children than in the past, she said, misinformation remains common. In fact, physicians can be part of the problem.
Dr. Shaw highlighted a 2019 Italian survey that found that 16% of 395 people with MS reported that they were discouraged from having children, mainly by medical professionals, after their diagnosis. Seven percent said they never wanted to become parents because of their MS. A 2021 survey of 332 patients with MS in the United States, United Kingdom, France, Germany, Italy, and Spain, found that 56% reported that MS played a role in their decisions about family planning, and 14% of those decided not to have children.
In regard to women of child-bearing age, Dr. Shah recommends that Open-ended, individualized questions are key. “We don’t know what patients don’t share with us,” she said.
Make sure to consider the timing of any plans to have children, she said. If the patient wants to have children within a year, talk about matters such as whether disease activity is well-controlled (6-12 months of good control is ideal) and whether current disease-modifying therapies are safe. Make sure to get a baseline prepartum MRI scan, she said.
If the patients don’t want to have children, make sure they are using a reliable strategy to avoid conception. Be aware that modafinil – “not one that immediately comes to mind” – may decrease the efficacy of oral contraceptives, she said, as can anticonvulsants (phenytoin, carbamazepine, oxcarbazepine, topiramate, and primidone). Oral contraceptives, meanwhile, may decrease levels of lamotrigine.
What if a patient has trouble conceiving? There are some hints in research that MS may boost the risk of infertility in women, Dr. Shah said. That’s why she recommends that colleagues consider referring a patient to an infertility specialist after attempting conception for 6 months as opposed to the general recommendation for 12 months.
Dr. Shah disclosed advisory board service (Genentech) and development of nonbranded educational programming through Novartis and the National Committee for Quality Assurance.
NATIONAL HARBOR, MD – Just 2 days before she spoke in a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers, University of Colorado neurologist Anna Shah, MD, asked a 26-year-old patient with MS about whether she planned to have children. Absolutely not, the young woman replied. “I read online that I can give birth to a baby with MS, which is crazy.”
The patient didn’t understand the risk of having a child with MS – it’s thought to be 2%-5% if one parent has the condition – but she wouldn’t have learned the facts if Dr. Shah hadn’t asked the right questions. “It’s really important for us as a community to know how to be proactive with discussions [about pregnancy],” she said.
As she noted, an estimated 75% of patients with MS are women, most are diagnosed during prime child-bearing years, and many pregnancies in general – an estimated half – are not planned. And while a higher percentage of women with MS are having children than in the past, she said, misinformation remains common. In fact, physicians can be part of the problem.
Dr. Shaw highlighted a 2019 Italian survey that found that 16% of 395 people with MS reported that they were discouraged from having children, mainly by medical professionals, after their diagnosis. Seven percent said they never wanted to become parents because of their MS. A 2021 survey of 332 patients with MS in the United States, United Kingdom, France, Germany, Italy, and Spain, found that 56% reported that MS played a role in their decisions about family planning, and 14% of those decided not to have children.
In regard to women of child-bearing age, Dr. Shah recommends that Open-ended, individualized questions are key. “We don’t know what patients don’t share with us,” she said.
Make sure to consider the timing of any plans to have children, she said. If the patient wants to have children within a year, talk about matters such as whether disease activity is well-controlled (6-12 months of good control is ideal) and whether current disease-modifying therapies are safe. Make sure to get a baseline prepartum MRI scan, she said.
If the patients don’t want to have children, make sure they are using a reliable strategy to avoid conception. Be aware that modafinil – “not one that immediately comes to mind” – may decrease the efficacy of oral contraceptives, she said, as can anticonvulsants (phenytoin, carbamazepine, oxcarbazepine, topiramate, and primidone). Oral contraceptives, meanwhile, may decrease levels of lamotrigine.
What if a patient has trouble conceiving? There are some hints in research that MS may boost the risk of infertility in women, Dr. Shah said. That’s why she recommends that colleagues consider referring a patient to an infertility specialist after attempting conception for 6 months as opposed to the general recommendation for 12 months.
Dr. Shah disclosed advisory board service (Genentech) and development of nonbranded educational programming through Novartis and the National Committee for Quality Assurance.
At CMSC 2022