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Novel drug approvals of 2020
In 2020, the Food and Drug Administration approved 53 new drugs for humans. One of these agents, Annovera (segesterone and ethinyl estradiol), is a vaginal ring to prevent pregnancy and is not relevant in this article. A second drug, Asparlas (calaspargase pegol), indicated to treat acute lymphoblastic leukemia, has not yet been released by its manufacturer. Orgovyx (relugolix) is used for prostate cancer and Lampit (nifurtimox) is drug used in children – neither of these two agents will be covered. The remaining 49 are covered below. The agents with molecular weights less than 1,000 probably cross the placenta in the first half of pregnancy, but nearly all, regardless of MW, will cross in the second half of pregnancy.
No human pregnancy data for these agents has been found, but there are five drugs included in pregnancy registries. It will take some time before the outcomes of these drugs are published. The routine absence of pregnancy data for most drugs was pointed out in an article that I coauthored, “Should pregnant women be included in phase 4 clinical drug trials?”. The article makes a strong argument for including some pregnant women in these trials.
Anti-infectives
Artesunate (384)
The drug appears low risk when used in the second and third trimesters. There is inadequate information regarding its use in the first trimester, so the safest course for the embryo appears to be avoiding its use during this period. A single intravenous dose given to rats early in gestation resulted in embryolethality.
Ebanga (ansuvimab) (147,000)
Studies on its use in pregnant animals have not been conducted.
Inmazeb (atoltivimab, maftivimab, odesivimab) (144,000-146,000)
Inmazeb is a combination of the three agents. Studies on its use in pregnant animals have not been conducted.
Veklury (remdesivir) (603)
Veklury is indicated for the treatment of pregnant women hospitalized with COVID-19 who are at risk for serious morbidity and mortality. The drug should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus.
Antineoplastics
Ayvakit (avapritinib) (499)
The drug may cause fetal harm. The drug was teratogenic in animals.
Blenrep (belantamab mafodotin-blmf) (152,000)
A B-cell maturation antigen, it is indicated for the treatment of multiple myeloma. No human or animal pregnancy data have been located.
Danyelza (naxitamab-gqgk) (144,000)
This agent is used for the treatment of neuroblastoma. Based on its mechanism of action it may cause fetal harm if used in pregnancy.
Gavreto (pralsetinib) (534)
Gavreto is indicated for the treatment of small cell lung cancer. It may cause embryo-fetal harm if used in pregnancy.
Inqovi (cedazuridine + decitabine) (268,228)
The drug combination can cause fetal harm in human pregnancy. It is toxic in pregnant animals.
Margenza (margetuximab-cmkb) (149,000)
Although there are no data on the use of this drug in human pregnancy, the findings in animals and mechanism of action suggest that it will cause fetal harm.
Monjuvi (tafasitamab-cxix) (150,000)
This drug is a cytolytic antibody that is indicated in combination with lenalidomide. The combination may cause fetal harm.
Pemazyre (pemigatinib) (488)
It is indicated for the treatment of cholangiocarcinoma. In an animal study, the drug caused fetal defects, fetal growth retardation, and embryo-fetal death at maternal exposures lower than the human exposure.
Qinlock (ripretinib) (510)
This drug is used for the treatment of patients with advanced gastrointestinal stromal tumor. The drug was teratogenic in pregnant animals.
Retevmo (selpercatinib) (526)
This is a kinase inhibitor used for the treatment of small cell lung cancer. The drug is teratogenic in animals.
Sarclisa (isatuximab-irfc) (148,000)This drug is used in combination with pomalidomide and dexamethasone. The combination would probably cause major toxicity in an embryo or fetus.
Tabrecta (capmatinib) (412 – free base)Capmatinib is a kinase inhibitor used for the treatment of metastatic non–small cell lung cancer. It is teratogenic in animals.
Tazverik (tazemetostat) (654)Tazemetostat is indicated for the treatment of epithelioid sarcoma and follicular lymphoma, The drug is teratogenic in animals.
Trodelvy (sacituzumab govitecan-hziy) (1,602)This agent is used for the treatment of breast cancer. The drug has not been tested in pregnant animals. However, according to the manufacturer, there is a high possibility of human teratogenicity if it is given to a pregnant woman.
Tukysa (tucatinib) (481)
Tukysa is a tyrosine kinase inhibitor that is used in combination with trastuzumab and capecitabine for the treatment of breast cancer. The drug is teratogenic in animals.
Zeposia (ozanimod) (441)
Zeposia is indicated for the treatment of multiple sclerosis. The drug takes about 3 months to eliminate from the body. The drug is teratogenic in animals.
Zepzelca (lurbinectedin) (785)
This agent is used for the treatment of metastatic small cell lung cancer. The drug is teratogenic in animals.
Antiemetics
Barhemsys (amisulpride) (369)
This agent is Indicated to prevent nausea and vomiting. Animal data suggest low risk of embryo/fetal birth defects.
Antimigraine
Nurtec (rimegepant) (611)
Nurtec is indicated for acute treatment of migraine. Development toxicity was not observed in animals given doses similar to those used in humans.
Vyepti (eptinezumab-jjmr) (143,000)
A humanized monoclonal antibody that is given every 3 months to prevent migraine. There was no embryo-fetal harm in animals given the drug.
CNS
Byfavo (remimazolam) (493 – free base)
This drug is indicated for procedural sedation in adults undergoing procedures lasting 30 minutes or less. No defects were observed in animals.
Diagnostics
Cerianna (fluoroestradiol F 18) (289)
It is indicated for use with PET for characterization of estrogen receptor status in patients with ER-positive breast cancer. It has the potential to cause fetal harm depending on the fetal stage of development and the magnitude of radiation dose. There are no data on its use in pregnant women or animals.
Detectnet (copper CU-64 dotatate) (1,497)
All radiopharmaceuticals have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of the radiation dose. There are no pregnancy data in humans or animals
Miscellaneous
Dojolvi (triheptanoin) (429)
This agent is indicated as a source of calories and fatty acids for the treatment of pediatric and adult patients with molecularly confirmed long-chain fatty acid oxidation disorders. Advise patients that there is a pregnancy safety study that collects pregnancy outcome data in women taking Dojolvi during pregnancy. Pregnant patients can enroll in the study by calling 1-888-756-8657.
Enspryng (satralizumab-mwge) (143,000)
It is indicated for the treatment of neuromyelitis optica spectrum disorder in adult patients who are anti–aquaporin-4 (AQP4) antibody positive. No information is available on the risks, if any, in pregnancy. No adverse effects on maternal or fetal development were observed in pregnant monkeys and their offspring.
Evrysdi (risdiplam) (401)
This is a prescription medicine used to treat spinal muscular atrophy in adults and children aged 2 months and older. In pregnant animals the drug caused adverse effects on fetal development.
Gemtesa (vibegron) (445)
Gemtesa is used in adults to treat the symptoms of overactive bladder. The drug had no adverse effects on pregnant animals.
Imcivree (setmelanotide) (1,117)
This drug is indicated for chronic weight management in adult and pediatric patients aged 6 years and older with obesity because of proopiomelanocortin, proprotein convertase subtilisin/kexin type 1, or leptin receptor deficiency. The drug was not embryo toxic in animals.
Isturisa (osilodrostat) (325)
Isturisa is a cortisol synthesis inhibitor indicated for the treatment of adult patients with Cushing’s disease. No adverse fetal effects were observed in pregnant animals.
Klisyri (tirbanibulin) (431)
Tirbanibulin ointment is a microtubule inhibitor that is used to treat actinic keratosis. Information on its effects in pregnancy is not available.
Koselugo (selumetinib) (556)
This is a kinase inhibitor indicated for the treatment of pediatric patients aged 2 years and older. The drug is toxic in pregnant animals but its effects in human pregnancy are not known.
Nexletol (bempedoic acid) (344)
Nexletol is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of LDL cholesterol. The drug was not teratogenic in animals. Discontinue Nexletol when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus.
Olinvyk (oliceridine) (503)
Olinvyk injection is indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic. Prolonged use of Olinvyk during pregnancy can result in neonatal opioid withdrawal syndrome. The drug was not teratogenic in animals.
Ongentys (opicapone) (413)
Ongentys is indicated as adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease experiencing “off” episodes. The drug was teratogenic in rabbits but not in rats.
Orladeyo (berotralstat) (635)
This drug is a plasma kallikrein inhibitor indicated for prophylaxis to prevent attacks of hereditary angioedema. It was not teratogenic in animals.
Oxlumo (lumasiran) (17,286)
Oxlumo is a HAO1-directed small interfering ribonucleic acid indicated for the treatment of primary hyperoxaluria type 1 to lower urinary oxalate levels. No adverse effects on pregnancy or embryo-fetal development related to the drug were observed in animals.
Pizensy (lactitol) (344)
Lactitol is minimally absorbed systemically following oral administration. It is unknown whether maternal use will result in fetal exposure to the drug. No effects on embryo-fetal development were observed in animals at doses much higher than the maximum recommended human dosage.
Rukobia (fostemsavir) (705; 584 for free acid)
This drug is an HIV-1–directed attachment inhibitor, in combination with other antiretrovirals. There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to the drug during pregnancy. Health care providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry at 1-800-258-4263.
Sogroya (somapacitan-beco) (23,305)
This is a human growth hormone analog indicated for replacement of endogenous growth hormone in adults with growth hormone deficiency. The drug was not teratogenic in animals.
Tepezza (teprotumumab-trbw) (148,000)
Drug is indicated for the treatment of thyroid eye disease. The drug was teratogenic in cynomolgus monkeys. The manufacturer states that because of the risk, the drug should not be used in pregnancy.
Tauvid (flortaucipir F-18) (262)
This drug is indicated for use with PET imaging of the brain to evaluate for Alzheimer’s disease. It is a radioactive drug and should not be used in pregnant women.
Uplizna (inebilizumab-cdon) (149,000)
Uplizna is indicated for the treatment of neuromyelitis optica spectrum disorder in adult patients who are anti-AQP4 antibody positive. It is a humanized IgG1 monoclonal antibody and immunoglobulins are known to cross the placental barrier. Based on animal data, the drug can cause fetal harm because of B-cell lymphopenia and reduce antibody response in offspring exposed to the drug. Women of childbearing potential should use contraception while receiving Uplizna and for 6 months after the last dose.
Winlevi (clascoterone) (403)
This cream is an androgen receptor inhibitor that is indicated for the topical treatment of acne vulgaris in patients aged 12 years and older. Subcutaneous use in animals was associated with fetal defects.
Xeglyze (abametapir) (1,840)
Xeglyze is indicated for the topical treatment of head lice infestation in patients aged 6 months and older. The drug was not teratogenic in animals.
Zokinvy (lonafarnib) (639)
Zokinvy is indicated in patients 12 months or older to reduce the risk of mortality in several conditions. Animal studies have found embryo-fetal harm.
Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at obnews@mdedge.com.
In 2020, the Food and Drug Administration approved 53 new drugs for humans. One of these agents, Annovera (segesterone and ethinyl estradiol), is a vaginal ring to prevent pregnancy and is not relevant in this article. A second drug, Asparlas (calaspargase pegol), indicated to treat acute lymphoblastic leukemia, has not yet been released by its manufacturer. Orgovyx (relugolix) is used for prostate cancer and Lampit (nifurtimox) is drug used in children – neither of these two agents will be covered. The remaining 49 are covered below. The agents with molecular weights less than 1,000 probably cross the placenta in the first half of pregnancy, but nearly all, regardless of MW, will cross in the second half of pregnancy.
No human pregnancy data for these agents has been found, but there are five drugs included in pregnancy registries. It will take some time before the outcomes of these drugs are published. The routine absence of pregnancy data for most drugs was pointed out in an article that I coauthored, “Should pregnant women be included in phase 4 clinical drug trials?”. The article makes a strong argument for including some pregnant women in these trials.
Anti-infectives
Artesunate (384)
The drug appears low risk when used in the second and third trimesters. There is inadequate information regarding its use in the first trimester, so the safest course for the embryo appears to be avoiding its use during this period. A single intravenous dose given to rats early in gestation resulted in embryolethality.
Ebanga (ansuvimab) (147,000)
Studies on its use in pregnant animals have not been conducted.
Inmazeb (atoltivimab, maftivimab, odesivimab) (144,000-146,000)
Inmazeb is a combination of the three agents. Studies on its use in pregnant animals have not been conducted.
Veklury (remdesivir) (603)
Veklury is indicated for the treatment of pregnant women hospitalized with COVID-19 who are at risk for serious morbidity and mortality. The drug should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus.
Antineoplastics
Ayvakit (avapritinib) (499)
The drug may cause fetal harm. The drug was teratogenic in animals.
Blenrep (belantamab mafodotin-blmf) (152,000)
A B-cell maturation antigen, it is indicated for the treatment of multiple myeloma. No human or animal pregnancy data have been located.
Danyelza (naxitamab-gqgk) (144,000)
This agent is used for the treatment of neuroblastoma. Based on its mechanism of action it may cause fetal harm if used in pregnancy.
Gavreto (pralsetinib) (534)
Gavreto is indicated for the treatment of small cell lung cancer. It may cause embryo-fetal harm if used in pregnancy.
Inqovi (cedazuridine + decitabine) (268,228)
The drug combination can cause fetal harm in human pregnancy. It is toxic in pregnant animals.
Margenza (margetuximab-cmkb) (149,000)
Although there are no data on the use of this drug in human pregnancy, the findings in animals and mechanism of action suggest that it will cause fetal harm.
Monjuvi (tafasitamab-cxix) (150,000)
This drug is a cytolytic antibody that is indicated in combination with lenalidomide. The combination may cause fetal harm.
Pemazyre (pemigatinib) (488)
It is indicated for the treatment of cholangiocarcinoma. In an animal study, the drug caused fetal defects, fetal growth retardation, and embryo-fetal death at maternal exposures lower than the human exposure.
Qinlock (ripretinib) (510)
This drug is used for the treatment of patients with advanced gastrointestinal stromal tumor. The drug was teratogenic in pregnant animals.
Retevmo (selpercatinib) (526)
This is a kinase inhibitor used for the treatment of small cell lung cancer. The drug is teratogenic in animals.
Sarclisa (isatuximab-irfc) (148,000)This drug is used in combination with pomalidomide and dexamethasone. The combination would probably cause major toxicity in an embryo or fetus.
Tabrecta (capmatinib) (412 – free base)Capmatinib is a kinase inhibitor used for the treatment of metastatic non–small cell lung cancer. It is teratogenic in animals.
Tazverik (tazemetostat) (654)Tazemetostat is indicated for the treatment of epithelioid sarcoma and follicular lymphoma, The drug is teratogenic in animals.
Trodelvy (sacituzumab govitecan-hziy) (1,602)This agent is used for the treatment of breast cancer. The drug has not been tested in pregnant animals. However, according to the manufacturer, there is a high possibility of human teratogenicity if it is given to a pregnant woman.
Tukysa (tucatinib) (481)
Tukysa is a tyrosine kinase inhibitor that is used in combination with trastuzumab and capecitabine for the treatment of breast cancer. The drug is teratogenic in animals.
Zeposia (ozanimod) (441)
Zeposia is indicated for the treatment of multiple sclerosis. The drug takes about 3 months to eliminate from the body. The drug is teratogenic in animals.
Zepzelca (lurbinectedin) (785)
This agent is used for the treatment of metastatic small cell lung cancer. The drug is teratogenic in animals.
Antiemetics
Barhemsys (amisulpride) (369)
This agent is Indicated to prevent nausea and vomiting. Animal data suggest low risk of embryo/fetal birth defects.
Antimigraine
Nurtec (rimegepant) (611)
Nurtec is indicated for acute treatment of migraine. Development toxicity was not observed in animals given doses similar to those used in humans.
Vyepti (eptinezumab-jjmr) (143,000)
A humanized monoclonal antibody that is given every 3 months to prevent migraine. There was no embryo-fetal harm in animals given the drug.
CNS
Byfavo (remimazolam) (493 – free base)
This drug is indicated for procedural sedation in adults undergoing procedures lasting 30 minutes or less. No defects were observed in animals.
Diagnostics
Cerianna (fluoroestradiol F 18) (289)
It is indicated for use with PET for characterization of estrogen receptor status in patients with ER-positive breast cancer. It has the potential to cause fetal harm depending on the fetal stage of development and the magnitude of radiation dose. There are no data on its use in pregnant women or animals.
Detectnet (copper CU-64 dotatate) (1,497)
All radiopharmaceuticals have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of the radiation dose. There are no pregnancy data in humans or animals
Miscellaneous
Dojolvi (triheptanoin) (429)
This agent is indicated as a source of calories and fatty acids for the treatment of pediatric and adult patients with molecularly confirmed long-chain fatty acid oxidation disorders. Advise patients that there is a pregnancy safety study that collects pregnancy outcome data in women taking Dojolvi during pregnancy. Pregnant patients can enroll in the study by calling 1-888-756-8657.
Enspryng (satralizumab-mwge) (143,000)
It is indicated for the treatment of neuromyelitis optica spectrum disorder in adult patients who are anti–aquaporin-4 (AQP4) antibody positive. No information is available on the risks, if any, in pregnancy. No adverse effects on maternal or fetal development were observed in pregnant monkeys and their offspring.
Evrysdi (risdiplam) (401)
This is a prescription medicine used to treat spinal muscular atrophy in adults and children aged 2 months and older. In pregnant animals the drug caused adverse effects on fetal development.
Gemtesa (vibegron) (445)
Gemtesa is used in adults to treat the symptoms of overactive bladder. The drug had no adverse effects on pregnant animals.
Imcivree (setmelanotide) (1,117)
This drug is indicated for chronic weight management in adult and pediatric patients aged 6 years and older with obesity because of proopiomelanocortin, proprotein convertase subtilisin/kexin type 1, or leptin receptor deficiency. The drug was not embryo toxic in animals.
Isturisa (osilodrostat) (325)
Isturisa is a cortisol synthesis inhibitor indicated for the treatment of adult patients with Cushing’s disease. No adverse fetal effects were observed in pregnant animals.
Klisyri (tirbanibulin) (431)
Tirbanibulin ointment is a microtubule inhibitor that is used to treat actinic keratosis. Information on its effects in pregnancy is not available.
Koselugo (selumetinib) (556)
This is a kinase inhibitor indicated for the treatment of pediatric patients aged 2 years and older. The drug is toxic in pregnant animals but its effects in human pregnancy are not known.
Nexletol (bempedoic acid) (344)
Nexletol is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of LDL cholesterol. The drug was not teratogenic in animals. Discontinue Nexletol when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus.
Olinvyk (oliceridine) (503)
Olinvyk injection is indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic. Prolonged use of Olinvyk during pregnancy can result in neonatal opioid withdrawal syndrome. The drug was not teratogenic in animals.
Ongentys (opicapone) (413)
Ongentys is indicated as adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease experiencing “off” episodes. The drug was teratogenic in rabbits but not in rats.
Orladeyo (berotralstat) (635)
This drug is a plasma kallikrein inhibitor indicated for prophylaxis to prevent attacks of hereditary angioedema. It was not teratogenic in animals.
Oxlumo (lumasiran) (17,286)
Oxlumo is a HAO1-directed small interfering ribonucleic acid indicated for the treatment of primary hyperoxaluria type 1 to lower urinary oxalate levels. No adverse effects on pregnancy or embryo-fetal development related to the drug were observed in animals.
Pizensy (lactitol) (344)
Lactitol is minimally absorbed systemically following oral administration. It is unknown whether maternal use will result in fetal exposure to the drug. No effects on embryo-fetal development were observed in animals at doses much higher than the maximum recommended human dosage.
Rukobia (fostemsavir) (705; 584 for free acid)
This drug is an HIV-1–directed attachment inhibitor, in combination with other antiretrovirals. There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to the drug during pregnancy. Health care providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry at 1-800-258-4263.
Sogroya (somapacitan-beco) (23,305)
This is a human growth hormone analog indicated for replacement of endogenous growth hormone in adults with growth hormone deficiency. The drug was not teratogenic in animals.
Tepezza (teprotumumab-trbw) (148,000)
Drug is indicated for the treatment of thyroid eye disease. The drug was teratogenic in cynomolgus monkeys. The manufacturer states that because of the risk, the drug should not be used in pregnancy.
Tauvid (flortaucipir F-18) (262)
This drug is indicated for use with PET imaging of the brain to evaluate for Alzheimer’s disease. It is a radioactive drug and should not be used in pregnant women.
Uplizna (inebilizumab-cdon) (149,000)
Uplizna is indicated for the treatment of neuromyelitis optica spectrum disorder in adult patients who are anti-AQP4 antibody positive. It is a humanized IgG1 monoclonal antibody and immunoglobulins are known to cross the placental barrier. Based on animal data, the drug can cause fetal harm because of B-cell lymphopenia and reduce antibody response in offspring exposed to the drug. Women of childbearing potential should use contraception while receiving Uplizna and for 6 months after the last dose.
Winlevi (clascoterone) (403)
This cream is an androgen receptor inhibitor that is indicated for the topical treatment of acne vulgaris in patients aged 12 years and older. Subcutaneous use in animals was associated with fetal defects.
Xeglyze (abametapir) (1,840)
Xeglyze is indicated for the topical treatment of head lice infestation in patients aged 6 months and older. The drug was not teratogenic in animals.
Zokinvy (lonafarnib) (639)
Zokinvy is indicated in patients 12 months or older to reduce the risk of mortality in several conditions. Animal studies have found embryo-fetal harm.
Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at obnews@mdedge.com.
In 2020, the Food and Drug Administration approved 53 new drugs for humans. One of these agents, Annovera (segesterone and ethinyl estradiol), is a vaginal ring to prevent pregnancy and is not relevant in this article. A second drug, Asparlas (calaspargase pegol), indicated to treat acute lymphoblastic leukemia, has not yet been released by its manufacturer. Orgovyx (relugolix) is used for prostate cancer and Lampit (nifurtimox) is drug used in children – neither of these two agents will be covered. The remaining 49 are covered below. The agents with molecular weights less than 1,000 probably cross the placenta in the first half of pregnancy, but nearly all, regardless of MW, will cross in the second half of pregnancy.
No human pregnancy data for these agents has been found, but there are five drugs included in pregnancy registries. It will take some time before the outcomes of these drugs are published. The routine absence of pregnancy data for most drugs was pointed out in an article that I coauthored, “Should pregnant women be included in phase 4 clinical drug trials?”. The article makes a strong argument for including some pregnant women in these trials.
Anti-infectives
Artesunate (384)
The drug appears low risk when used in the second and third trimesters. There is inadequate information regarding its use in the first trimester, so the safest course for the embryo appears to be avoiding its use during this period. A single intravenous dose given to rats early in gestation resulted in embryolethality.
Ebanga (ansuvimab) (147,000)
Studies on its use in pregnant animals have not been conducted.
Inmazeb (atoltivimab, maftivimab, odesivimab) (144,000-146,000)
Inmazeb is a combination of the three agents. Studies on its use in pregnant animals have not been conducted.
Veklury (remdesivir) (603)
Veklury is indicated for the treatment of pregnant women hospitalized with COVID-19 who are at risk for serious morbidity and mortality. The drug should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus.
Antineoplastics
Ayvakit (avapritinib) (499)
The drug may cause fetal harm. The drug was teratogenic in animals.
Blenrep (belantamab mafodotin-blmf) (152,000)
A B-cell maturation antigen, it is indicated for the treatment of multiple myeloma. No human or animal pregnancy data have been located.
Danyelza (naxitamab-gqgk) (144,000)
This agent is used for the treatment of neuroblastoma. Based on its mechanism of action it may cause fetal harm if used in pregnancy.
Gavreto (pralsetinib) (534)
Gavreto is indicated for the treatment of small cell lung cancer. It may cause embryo-fetal harm if used in pregnancy.
Inqovi (cedazuridine + decitabine) (268,228)
The drug combination can cause fetal harm in human pregnancy. It is toxic in pregnant animals.
Margenza (margetuximab-cmkb) (149,000)
Although there are no data on the use of this drug in human pregnancy, the findings in animals and mechanism of action suggest that it will cause fetal harm.
Monjuvi (tafasitamab-cxix) (150,000)
This drug is a cytolytic antibody that is indicated in combination with lenalidomide. The combination may cause fetal harm.
Pemazyre (pemigatinib) (488)
It is indicated for the treatment of cholangiocarcinoma. In an animal study, the drug caused fetal defects, fetal growth retardation, and embryo-fetal death at maternal exposures lower than the human exposure.
Qinlock (ripretinib) (510)
This drug is used for the treatment of patients with advanced gastrointestinal stromal tumor. The drug was teratogenic in pregnant animals.
Retevmo (selpercatinib) (526)
This is a kinase inhibitor used for the treatment of small cell lung cancer. The drug is teratogenic in animals.
Sarclisa (isatuximab-irfc) (148,000)This drug is used in combination with pomalidomide and dexamethasone. The combination would probably cause major toxicity in an embryo or fetus.
Tabrecta (capmatinib) (412 – free base)Capmatinib is a kinase inhibitor used for the treatment of metastatic non–small cell lung cancer. It is teratogenic in animals.
Tazverik (tazemetostat) (654)Tazemetostat is indicated for the treatment of epithelioid sarcoma and follicular lymphoma, The drug is teratogenic in animals.
Trodelvy (sacituzumab govitecan-hziy) (1,602)This agent is used for the treatment of breast cancer. The drug has not been tested in pregnant animals. However, according to the manufacturer, there is a high possibility of human teratogenicity if it is given to a pregnant woman.
Tukysa (tucatinib) (481)
Tukysa is a tyrosine kinase inhibitor that is used in combination with trastuzumab and capecitabine for the treatment of breast cancer. The drug is teratogenic in animals.
Zeposia (ozanimod) (441)
Zeposia is indicated for the treatment of multiple sclerosis. The drug takes about 3 months to eliminate from the body. The drug is teratogenic in animals.
Zepzelca (lurbinectedin) (785)
This agent is used for the treatment of metastatic small cell lung cancer. The drug is teratogenic in animals.
Antiemetics
Barhemsys (amisulpride) (369)
This agent is Indicated to prevent nausea and vomiting. Animal data suggest low risk of embryo/fetal birth defects.
Antimigraine
Nurtec (rimegepant) (611)
Nurtec is indicated for acute treatment of migraine. Development toxicity was not observed in animals given doses similar to those used in humans.
Vyepti (eptinezumab-jjmr) (143,000)
A humanized monoclonal antibody that is given every 3 months to prevent migraine. There was no embryo-fetal harm in animals given the drug.
CNS
Byfavo (remimazolam) (493 – free base)
This drug is indicated for procedural sedation in adults undergoing procedures lasting 30 minutes or less. No defects were observed in animals.
Diagnostics
Cerianna (fluoroestradiol F 18) (289)
It is indicated for use with PET for characterization of estrogen receptor status in patients with ER-positive breast cancer. It has the potential to cause fetal harm depending on the fetal stage of development and the magnitude of radiation dose. There are no data on its use in pregnant women or animals.
Detectnet (copper CU-64 dotatate) (1,497)
All radiopharmaceuticals have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of the radiation dose. There are no pregnancy data in humans or animals
Miscellaneous
Dojolvi (triheptanoin) (429)
This agent is indicated as a source of calories and fatty acids for the treatment of pediatric and adult patients with molecularly confirmed long-chain fatty acid oxidation disorders. Advise patients that there is a pregnancy safety study that collects pregnancy outcome data in women taking Dojolvi during pregnancy. Pregnant patients can enroll in the study by calling 1-888-756-8657.
Enspryng (satralizumab-mwge) (143,000)
It is indicated for the treatment of neuromyelitis optica spectrum disorder in adult patients who are anti–aquaporin-4 (AQP4) antibody positive. No information is available on the risks, if any, in pregnancy. No adverse effects on maternal or fetal development were observed in pregnant monkeys and their offspring.
Evrysdi (risdiplam) (401)
This is a prescription medicine used to treat spinal muscular atrophy in adults and children aged 2 months and older. In pregnant animals the drug caused adverse effects on fetal development.
Gemtesa (vibegron) (445)
Gemtesa is used in adults to treat the symptoms of overactive bladder. The drug had no adverse effects on pregnant animals.
Imcivree (setmelanotide) (1,117)
This drug is indicated for chronic weight management in adult and pediatric patients aged 6 years and older with obesity because of proopiomelanocortin, proprotein convertase subtilisin/kexin type 1, or leptin receptor deficiency. The drug was not embryo toxic in animals.
Isturisa (osilodrostat) (325)
Isturisa is a cortisol synthesis inhibitor indicated for the treatment of adult patients with Cushing’s disease. No adverse fetal effects were observed in pregnant animals.
Klisyri (tirbanibulin) (431)
Tirbanibulin ointment is a microtubule inhibitor that is used to treat actinic keratosis. Information on its effects in pregnancy is not available.
Koselugo (selumetinib) (556)
This is a kinase inhibitor indicated for the treatment of pediatric patients aged 2 years and older. The drug is toxic in pregnant animals but its effects in human pregnancy are not known.
Nexletol (bempedoic acid) (344)
Nexletol is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of LDL cholesterol. The drug was not teratogenic in animals. Discontinue Nexletol when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus.
Olinvyk (oliceridine) (503)
Olinvyk injection is indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic. Prolonged use of Olinvyk during pregnancy can result in neonatal opioid withdrawal syndrome. The drug was not teratogenic in animals.
Ongentys (opicapone) (413)
Ongentys is indicated as adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease experiencing “off” episodes. The drug was teratogenic in rabbits but not in rats.
Orladeyo (berotralstat) (635)
This drug is a plasma kallikrein inhibitor indicated for prophylaxis to prevent attacks of hereditary angioedema. It was not teratogenic in animals.
Oxlumo (lumasiran) (17,286)
Oxlumo is a HAO1-directed small interfering ribonucleic acid indicated for the treatment of primary hyperoxaluria type 1 to lower urinary oxalate levels. No adverse effects on pregnancy or embryo-fetal development related to the drug were observed in animals.
Pizensy (lactitol) (344)
Lactitol is minimally absorbed systemically following oral administration. It is unknown whether maternal use will result in fetal exposure to the drug. No effects on embryo-fetal development were observed in animals at doses much higher than the maximum recommended human dosage.
Rukobia (fostemsavir) (705; 584 for free acid)
This drug is an HIV-1–directed attachment inhibitor, in combination with other antiretrovirals. There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to the drug during pregnancy. Health care providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry at 1-800-258-4263.
Sogroya (somapacitan-beco) (23,305)
This is a human growth hormone analog indicated for replacement of endogenous growth hormone in adults with growth hormone deficiency. The drug was not teratogenic in animals.
Tepezza (teprotumumab-trbw) (148,000)
Drug is indicated for the treatment of thyroid eye disease. The drug was teratogenic in cynomolgus monkeys. The manufacturer states that because of the risk, the drug should not be used in pregnancy.
Tauvid (flortaucipir F-18) (262)
This drug is indicated for use with PET imaging of the brain to evaluate for Alzheimer’s disease. It is a radioactive drug and should not be used in pregnant women.
Uplizna (inebilizumab-cdon) (149,000)
Uplizna is indicated for the treatment of neuromyelitis optica spectrum disorder in adult patients who are anti-AQP4 antibody positive. It is a humanized IgG1 monoclonal antibody and immunoglobulins are known to cross the placental barrier. Based on animal data, the drug can cause fetal harm because of B-cell lymphopenia and reduce antibody response in offspring exposed to the drug. Women of childbearing potential should use contraception while receiving Uplizna and for 6 months after the last dose.
Winlevi (clascoterone) (403)
This cream is an androgen receptor inhibitor that is indicated for the topical treatment of acne vulgaris in patients aged 12 years and older. Subcutaneous use in animals was associated with fetal defects.
Xeglyze (abametapir) (1,840)
Xeglyze is indicated for the topical treatment of head lice infestation in patients aged 6 months and older. The drug was not teratogenic in animals.
Zokinvy (lonafarnib) (639)
Zokinvy is indicated in patients 12 months or older to reduce the risk of mortality in several conditions. Animal studies have found embryo-fetal harm.
Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at obnews@mdedge.com.
Unhealthy drinking may worsen after weight loss surgery
Internal medicine primarily affords us the skill to cope with disorders of chronicity that rarely disappear. For every pneumococcal pneumonia we eradicate, we have multiple patients with HIV who will be treated indefinitely. Diabetes, once a lethal disease, is now a chronic condition for most patients, and even with treatment the trajectory is usually one of progression.
One gratifying exception in my professional lifetime has been the introduction of gastric surgeries that reduce morbidity and seem to extend the life span of those who successfully undergo these procedures. The Roux-en-Y gastric bypass and sleeve gastrectomy have kept thousands of patients in better health for many years, giving them a second chance. For a subset, however, this second chance comes with a stumbling block of substance use – most notably alcohol – that exceeds their preoperative use.
Increased alcohol use after surgery
A group affiliated with the Department of Veterans Affairs (VA) recently reviewed the large central database to identify changes in alcohol consumption among patients who had undergone successful bariatric surgery. The VA regularly administers the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), a survey validated as a reliable estimate of individual alcohol consumption. It is inserted into the VA electronic health record where it can be readily retrieved. By matching these survey results with individuals who underwent bariatric surgery at the VA and survived at least 8 years post op, the authors were able to follow trends in alcohol consumption, beginning 2 years before surgery through 8 years after.
Using the same database, the authors identified a larger number of nonoperative control patients with slightly less obesity but otherwise matched for several elements of comorbidity, such as hypertension, certain psychiatric disorders, and personal habits, including alcohol consumption.
Alcohol use was categorized as none, minor social use, and “unhealthy” use. Among those with no or minor social use preoperatively, 4% converted to unhealthy use at 3 years and about 5% at 8 years, significantly more than in the nonoperative control group. Those who had gastric bypass had somewhat more conversion than did those who had sleeve gastrectomy, though not significantly so.
Patients with an alcohol concern preoperatively took an interesting course. Consumption declined from 2 years pre op to the year of surgery, suggesting that curtailing its use may have been a surgical precondition. Postoperatively, they returned to unhealthy drinking levels. Those who underwent the sleeve gastrectomy consumed about the same amount of alcohol as did their matched nonoperative controls, but those who underwent bypass increased their baseline unhealthy use beyond that of the controls.
Because total abstinence is often the recommendation for treating alcoholism, the research group assessed how adherent the excessive drinkers were to abstinence. In anticipation of surgery, the rates of abstinence increased until the year of surgery, but by 3 years post op, consumption was often up to unhealthy levels, though no more than that of control participants with preexisting drinking problems.
Smoking and illicit drug use
Although increased alcohol consumption has generated the most studies, some attention has been given to smoking and illicit drug use, which may also increase over time.
One small study looked at composite tobacco, alcohol, and drug use pre- and postoperatively over 2 years, using population data. The authors found a parallel pattern of users voluntarily reducing their substance use in anticipation of surgery but relapsing as the procedure made them more functional and perhaps more independent. Of the substances people resumed, alcohol by far involved the largest increase in use from the preoperative baseline.
These studies, as important as they are, reveal what happened more effectively than they disclose why it happened. The latter requires some clinical experience. Curtailing cigarettes and alcohol use preoperatively may have been done to stay in the good graces of the surgeon. Many patients may have seen this as their path to a second chance that they intended to maintain.
The incentive to proceed to surgical weight loss, which incurs a measure of risk and forces changes in long ingrained eating habits, involves avoiding future morbidity and promoting longevity. Thus, the postoperative behaviors that threaten the long-term goal need to become a component of ongoing follow-up.
The acquisition of adverse behaviors not present preoperatively seems more difficult to sort out, and obligates those of us following these patients to ask about changes in alcohol use and provide resources for them should they need intervention.
Dr. Plotzker is a retired endocrinologist with 40 years of experience treating patients in both private practice and hospital settings.
A version of this article first appeared on Medscape.com.
Internal medicine primarily affords us the skill to cope with disorders of chronicity that rarely disappear. For every pneumococcal pneumonia we eradicate, we have multiple patients with HIV who will be treated indefinitely. Diabetes, once a lethal disease, is now a chronic condition for most patients, and even with treatment the trajectory is usually one of progression.
One gratifying exception in my professional lifetime has been the introduction of gastric surgeries that reduce morbidity and seem to extend the life span of those who successfully undergo these procedures. The Roux-en-Y gastric bypass and sleeve gastrectomy have kept thousands of patients in better health for many years, giving them a second chance. For a subset, however, this second chance comes with a stumbling block of substance use – most notably alcohol – that exceeds their preoperative use.
Increased alcohol use after surgery
A group affiliated with the Department of Veterans Affairs (VA) recently reviewed the large central database to identify changes in alcohol consumption among patients who had undergone successful bariatric surgery. The VA regularly administers the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), a survey validated as a reliable estimate of individual alcohol consumption. It is inserted into the VA electronic health record where it can be readily retrieved. By matching these survey results with individuals who underwent bariatric surgery at the VA and survived at least 8 years post op, the authors were able to follow trends in alcohol consumption, beginning 2 years before surgery through 8 years after.
Using the same database, the authors identified a larger number of nonoperative control patients with slightly less obesity but otherwise matched for several elements of comorbidity, such as hypertension, certain psychiatric disorders, and personal habits, including alcohol consumption.
Alcohol use was categorized as none, minor social use, and “unhealthy” use. Among those with no or minor social use preoperatively, 4% converted to unhealthy use at 3 years and about 5% at 8 years, significantly more than in the nonoperative control group. Those who had gastric bypass had somewhat more conversion than did those who had sleeve gastrectomy, though not significantly so.
Patients with an alcohol concern preoperatively took an interesting course. Consumption declined from 2 years pre op to the year of surgery, suggesting that curtailing its use may have been a surgical precondition. Postoperatively, they returned to unhealthy drinking levels. Those who underwent the sleeve gastrectomy consumed about the same amount of alcohol as did their matched nonoperative controls, but those who underwent bypass increased their baseline unhealthy use beyond that of the controls.
Because total abstinence is often the recommendation for treating alcoholism, the research group assessed how adherent the excessive drinkers were to abstinence. In anticipation of surgery, the rates of abstinence increased until the year of surgery, but by 3 years post op, consumption was often up to unhealthy levels, though no more than that of control participants with preexisting drinking problems.
Smoking and illicit drug use
Although increased alcohol consumption has generated the most studies, some attention has been given to smoking and illicit drug use, which may also increase over time.
One small study looked at composite tobacco, alcohol, and drug use pre- and postoperatively over 2 years, using population data. The authors found a parallel pattern of users voluntarily reducing their substance use in anticipation of surgery but relapsing as the procedure made them more functional and perhaps more independent. Of the substances people resumed, alcohol by far involved the largest increase in use from the preoperative baseline.
These studies, as important as they are, reveal what happened more effectively than they disclose why it happened. The latter requires some clinical experience. Curtailing cigarettes and alcohol use preoperatively may have been done to stay in the good graces of the surgeon. Many patients may have seen this as their path to a second chance that they intended to maintain.
The incentive to proceed to surgical weight loss, which incurs a measure of risk and forces changes in long ingrained eating habits, involves avoiding future morbidity and promoting longevity. Thus, the postoperative behaviors that threaten the long-term goal need to become a component of ongoing follow-up.
The acquisition of adverse behaviors not present preoperatively seems more difficult to sort out, and obligates those of us following these patients to ask about changes in alcohol use and provide resources for them should they need intervention.
Dr. Plotzker is a retired endocrinologist with 40 years of experience treating patients in both private practice and hospital settings.
A version of this article first appeared on Medscape.com.
Internal medicine primarily affords us the skill to cope with disorders of chronicity that rarely disappear. For every pneumococcal pneumonia we eradicate, we have multiple patients with HIV who will be treated indefinitely. Diabetes, once a lethal disease, is now a chronic condition for most patients, and even with treatment the trajectory is usually one of progression.
One gratifying exception in my professional lifetime has been the introduction of gastric surgeries that reduce morbidity and seem to extend the life span of those who successfully undergo these procedures. The Roux-en-Y gastric bypass and sleeve gastrectomy have kept thousands of patients in better health for many years, giving them a second chance. For a subset, however, this second chance comes with a stumbling block of substance use – most notably alcohol – that exceeds their preoperative use.
Increased alcohol use after surgery
A group affiliated with the Department of Veterans Affairs (VA) recently reviewed the large central database to identify changes in alcohol consumption among patients who had undergone successful bariatric surgery. The VA regularly administers the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), a survey validated as a reliable estimate of individual alcohol consumption. It is inserted into the VA electronic health record where it can be readily retrieved. By matching these survey results with individuals who underwent bariatric surgery at the VA and survived at least 8 years post op, the authors were able to follow trends in alcohol consumption, beginning 2 years before surgery through 8 years after.
Using the same database, the authors identified a larger number of nonoperative control patients with slightly less obesity but otherwise matched for several elements of comorbidity, such as hypertension, certain psychiatric disorders, and personal habits, including alcohol consumption.
Alcohol use was categorized as none, minor social use, and “unhealthy” use. Among those with no or minor social use preoperatively, 4% converted to unhealthy use at 3 years and about 5% at 8 years, significantly more than in the nonoperative control group. Those who had gastric bypass had somewhat more conversion than did those who had sleeve gastrectomy, though not significantly so.
Patients with an alcohol concern preoperatively took an interesting course. Consumption declined from 2 years pre op to the year of surgery, suggesting that curtailing its use may have been a surgical precondition. Postoperatively, they returned to unhealthy drinking levels. Those who underwent the sleeve gastrectomy consumed about the same amount of alcohol as did their matched nonoperative controls, but those who underwent bypass increased their baseline unhealthy use beyond that of the controls.
Because total abstinence is often the recommendation for treating alcoholism, the research group assessed how adherent the excessive drinkers were to abstinence. In anticipation of surgery, the rates of abstinence increased until the year of surgery, but by 3 years post op, consumption was often up to unhealthy levels, though no more than that of control participants with preexisting drinking problems.
Smoking and illicit drug use
Although increased alcohol consumption has generated the most studies, some attention has been given to smoking and illicit drug use, which may also increase over time.
One small study looked at composite tobacco, alcohol, and drug use pre- and postoperatively over 2 years, using population data. The authors found a parallel pattern of users voluntarily reducing their substance use in anticipation of surgery but relapsing as the procedure made them more functional and perhaps more independent. Of the substances people resumed, alcohol by far involved the largest increase in use from the preoperative baseline.
These studies, as important as they are, reveal what happened more effectively than they disclose why it happened. The latter requires some clinical experience. Curtailing cigarettes and alcohol use preoperatively may have been done to stay in the good graces of the surgeon. Many patients may have seen this as their path to a second chance that they intended to maintain.
The incentive to proceed to surgical weight loss, which incurs a measure of risk and forces changes in long ingrained eating habits, involves avoiding future morbidity and promoting longevity. Thus, the postoperative behaviors that threaten the long-term goal need to become a component of ongoing follow-up.
The acquisition of adverse behaviors not present preoperatively seems more difficult to sort out, and obligates those of us following these patients to ask about changes in alcohol use and provide resources for them should they need intervention.
Dr. Plotzker is a retired endocrinologist with 40 years of experience treating patients in both private practice and hospital settings.
A version of this article first appeared on Medscape.com.
New targeted treatments are major advances for HER2-positive breast cancer
Before 2001, HER2/neu-positive breast cancer (HER2+) was one of the most dreaded diagnoses a woman could face, as treatment was largely ineffective. The discovery of trastuzumab changed that dramatically.
Over the next 20 years, two additional HER2-targeted therapies – lapatinib and trastuzumab emtansine (TDM-1) – earned approval from the Food and Drug Administration for selected patients with early and late HER2+ breast cancer.
Since 2019, four additional HER2-targeted therapies have been approved by the FDA for HER2+ metastatic breast cancer (MBC), changing the treatment paradigm for those patients substantially.
The new agents are especially useful in certain patient populations. The agents offer the promise of improved survival for patients with recurrent metastatic disease and the potential for further reductions in relapse rates in earlier settings.
Trastuzumab deruxtecan
Trastuzumab deruxtecan is an antibody-drug conjugate that links three components: an anti-HER2 monoclonal antibody, a highly potent topoisomerase I inhibitor payload, and a tetrapeptide-based cleavable linker.
Trastuzumab deruxtecan has a high drug-to-antibody ratio. A membrane-permeable payload offers the potential for activity against adjacent HER2-negative cells in heterogeneous tumors. It has a long half-life (6 days).
Trastuzumab deruxtecan received accelerated approval from the FDA in December 2019 to treat patients with HER2+ MBC who have received two or more prior HER2-targeted regimens, based on the results of the DESTINY-Breast 01 trial.
DESTINY-Breast 01 trial
In the phase 2 DESTINY-Breast 01 trial, 184 patients with a median of six previous treatments received trastuzumab deruxtecan (5.4 mg/kg) intravenously every 21 days. There were 24 patients with treated, asymptomatic brain metastases who participated. Patients with untreated or symptomatic brain metastases were excluded.
Overall, a response to therapy was reported in 112 patients (60.9%), with 6.0% complete and 54.9% partial responses. Most of the patients for whom both baseline and postbaseline data were available had a reduction in tumor size.
The median time until response was 1.6 months, an interval that corresponded to the time until the first scheduled imaging. Three patients (1.6%) had progressive disease, and two patients (1.1%) could not be evaluated.
The median duration of follow-up was 11.1 months, and the median response duration was 14.8 months.
The median progression-free survival (PFS) was 16.4 months, and the median overall survival (OS) was not reached. The median PFS in the patients with brain involvement was 18.1 months.
The most common adverse events of grade 3 or higher were a decreased neutrophil count (20.7%), anemia (8.7%), and nausea (7.6%). Most concerning was that trastuzumab deruxtecan was associated with interstitial lung disease in 13.6% of patients.
Tucatinib
Tucatinib is an oral, highly selective HER2 tyrosine kinase inhibitor (TKI). In April 2020, it was approved by the FDA, in combination with trastuzumab and capecitabine, for adult patients with advanced unresectable or metastatic HER2+ breast cancer who have received one or more prior anti-HER2–based regimens for MBC. The approval included patients with brain metastases.
The recommended tucatinib dose is 300 mg orally twice a day in combination with trastuzumab (at the standard dose) and capecitabine (1,000 mg/m2 given orally twice daily on days 1-14) on a 21-day cycle, until disease progression or unacceptable toxicity.
HER2CLIMB trial
The study that led to the approval of tucatinib was the HER2CLIMB trial. The trial enrolled 612 HER2+ MBC patients who had prior treatment with trastuzumab, pertuzumab, and T-DM1. Patients had received a median of 4 (range, 2-17) prior lines of HER2-targeted therapy.
The patients were randomized 2:1 to receive trastuzumab plus capecitabine and either tucatinib or an identical placebo twice daily.
The primary endpoint was PFS, evaluated in the initial 480 randomized patients. The median PFS was 7.8 months in the tucatinib arm and 5.6 months in the control arm (hazard ratio, 0.54; 95% confidence interval, 0.42-0.71; P < .001).
The confirmed overall response rate for patients with measurable disease was 40.6% in the tucatinib arm and 22.8% in the control arm (P = .001). The proportion of patients still in response at 12 months was 33.1% and 12.3%, respectively.
The median OS was 21.9 months in the tucatinib arm and 17.4 months in the placebo arm (HR, 0.66; 95% CI, 0.50-0.88; P = .005). At 24 months, 44.9% and 26.6% of patients, respectively, were still alive.
The most common grade 3 or higher adverse events (in the tucatinib and placebo arms, respectively) were palmar-plantar erythrodysesthesia syndrome (13.1% vs. 9.1%), diarrhea (12.9% vs. 8.6%), elevations in ALT and AST (approximately 5% vs. 0.5% for each), and fatigue (4.7% vs. 4.1%).
Tucatinib in patients with brain involvement
A unique feature of the HER2CLIMB study was that patients with MBC and untreated, symptomatic brain metastases were eligible. Patients with active, untreated central nervous system disease are excluded from virtually all other trials, especially drug-approval trials.
There were 291 patients with brain metastases in HER2CLIMB, 198 (48%) in the tucatinib arm and 93 (46%) in the control arm.
The risk of intracranial progression or death was reduced by 68% in the tucatinib arm (HR, 0.32; 95% CI, 0.22 to 0.48; P < .0001).
The 1-year CNS-PFS rate was 40.2% in the tucatinib arm and 0% in the placebo arm. The median duration of CNS-PFS was 9.9 months and 4.2 months, respectively.
The risk of death was reduced by 42% in the tucatinib arm (HR, 0.58; 95% CI, 0.40-0.85; P = .005). The median OS was 18.1 months and 12.0 months, respectively.
There were more objective responses in the brain with tucatinib (47.3%) than with placebo (20.0%; P = .03). The median duration of response was 6.8 months and 3.0 months, respectively.
Particularly because of its CNS activity and lack of serious, long-term toxicity, tucatinib combination therapy represents an attractive new option for patients with HER2+ MBC.
Neratinib
Neratinib is an irreversible pan-HER TKI that was approved by the FDA in July 2017 for extended adjuvant therapy in patients with early-stage HER2+ breast cancer, following the use of trastuzumab-based therapy.
Long-term results of the ExteNet study led to the approval for use as extended adjuvant therapy.
In February 2020, neratinib was FDA approved in combination with capecitabine for patients with HER2+ MBC after two or more prior anti-HER2–based regimens. The more recent FDA approval was based on results of the NALA trial.
NALA trial
The phase 3 NALA trial included 621 patients with HER2+ MBC who had received at least two prior anti-HER2 based regimens.
Patients were randomized 1:1 to receive neratinib at 240 mg orally once daily on days 1-21 with capecitabine at 750 mg/m2 orally twice daily on days 1-14 or lapatinib at 1,250 mg orally once daily on days 1-21 with capecitabine at 1,000 mg/m2 orally twice daily on days 1-14 for each 21-day cycle. Patients were treated until disease progression or unacceptable toxicity.
The primary endpoints were PFS and OS by blinded, independent, central review.
The median PFS was 5.6 months in the neratinib arm and 5.5 months in the lapatinib arm (HR, 0.76; 95% CI, 0.63-0.93; P = .0059). The PFS rate at 12 months was 28.8% and 14.8%, respectively.
The median OS was 21.0 months in the neratinib arm and 18.7 months in the lapatinib arm (HR, 0.88; 95% CI, 0.72-1.07; P = .2086). The ORR was 32.8% and 26.7%, respectively. The median response duration was 8.5 months and 5.6 months, respectively.
Fewer interventions for CNS disease were required in the neratinib arm than in the lapatinib arm (cumulative incidence, 22.8% vs. 29.2%; P = .043).
The most frequently reported grade 3-4 adverse reactions for the neratinib combination were diarrhea, nausea, vomiting, fatigue, and decreased appetite.
Grade 3 diarrhea occurred in 24.4% of those in the neratinib arm and 12.5% of those in the lapatinib arm. Antidiarrheal medication was used by 98.3% of patients receiving neratinib and 62.1% of patients receiving lapatinib.
Margetuximab-cmkb
Margetuximab is a chimeric Fc-engineered anti-HER2 monoclonal antibody that targets the same epitope as trastuzumab and exerts similar antiproliferative effects.
Compared with trastuzumab, margetuximab has higher affinity for both 158V (high-binding) and 158F (low-binding) alleles of the activating Fc receptor, CD16A. As a result, margetuximab enhances innate immunity, including CD16A-mediated antibody-dependent cellular cytotoxicity, more effectively than trastuzumab. Margetuximab also potentiates adaptive immunity, including enhanced clonality of the T-cell repertoire and induction of HER2-specific T- and B-cell responses.
In December 2020, margetuximab, in combination with chemotherapy, was approved by the FDA for patients with HER2+ MBC after two or more prior anti-HER2 regimens, at least one of which was for metastatic disease. The approved dose is 15 mg/kg IV every 3 weeks.
The study that led to margetuximab’s approval was the phase 3 SOPHIA trial.
SOPHIA trial
SOPHIA was a randomized trial of 536 patients with HER2+ MBC who had received prior treatment with other anti-HER2 therapies, including one to three lines of therapy for MBC.
Patients were randomly assigned 1:1 to receive margetuximab plus chemotherapy or trastuzumab plus chemotherapy. Assignment was stratified by chemotherapy choice (capecitabine, eribulin, gemcitabine, or vinorelbine), the number of previous lines of therapy for MBC, and disease extent.
Co–primary outcome measures were PFS by blinded, independent, central review and OS.
At the second interim analysis, the median PFS was 5.8 months in the margetuximab arm and 4.9 months in the trastuzumab arm (HR, 0.76; 95% CI, 0.59-0.98; P = .033). Results were more impressive in patients with CD16A genotypes containing a 158F allele. In this group, the median PFS was 6.9 months with margetuximab and 5.1 months with trastuzumab (HR, 0.68, 95% CI, 0.52-0.90; P = .005).
At the second interim analysis, the median OS was 21.6 months in the margetuximab arm and 19.8 months in the trastuzumab arm (HR, 0.89; 95% CI, 0.69-1.13; P = .33).
Subgroup data showed no differences in OS between the two arms for any subgroup except HER2+ MBC patients with an IHC score of 2 or higher. This is consistent with the postulated mechanism of action of margetuximab.
The confirmed ORR was 25% in the margetuximab arm and 14% in the trastuzumab arm, with similar durations of response between the study arms.
The most common adverse events in both arms (≥20%), regardless of causality, were fatigue, nausea, diarrhea, and neutropenia. Vomiting was common in the margetuximab arm, and anemia was common in the trastuzumab arm.
Grade 3 or higher adverse events occurred in 53.8% of patients receiving margetuximab and 52.6% of those receiving trastuzumab.
In view of margetuximab’s modest benefits in the SOPHIA trial, the ultimate role for margetuximab in HER2+ MBC may be restricted to patients with the CD16A-158F allele. A neoadjuvant trial is planned in that population.
Take-home messages
There are legitimate arguments regarding whether curing MBC is within reach for certain patient subsets, but there is no argument about whether the outlook for patients with HER2+ MBC has improved dramatically in recent years; it has.
The approval of four unique, new agents for the treatment of women with HER2+ MBC in relapse provides further improvements in outcome for these patients and distinctly different opportunities for tailoring treatment to the special circumstances of each patient (e.g., whether brain metastases are present, desire for oral therapy, comorbidities, experience with prior chemotherapy, etc).
When considered along with the potential for incorporating these drugs in earlier settings in well-designed clinical trials, these new drugs offer great promise to a group of patients who faced a dismal outcome just 2 decades ago.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
Before 2001, HER2/neu-positive breast cancer (HER2+) was one of the most dreaded diagnoses a woman could face, as treatment was largely ineffective. The discovery of trastuzumab changed that dramatically.
Over the next 20 years, two additional HER2-targeted therapies – lapatinib and trastuzumab emtansine (TDM-1) – earned approval from the Food and Drug Administration for selected patients with early and late HER2+ breast cancer.
Since 2019, four additional HER2-targeted therapies have been approved by the FDA for HER2+ metastatic breast cancer (MBC), changing the treatment paradigm for those patients substantially.
The new agents are especially useful in certain patient populations. The agents offer the promise of improved survival for patients with recurrent metastatic disease and the potential for further reductions in relapse rates in earlier settings.
Trastuzumab deruxtecan
Trastuzumab deruxtecan is an antibody-drug conjugate that links three components: an anti-HER2 monoclonal antibody, a highly potent topoisomerase I inhibitor payload, and a tetrapeptide-based cleavable linker.
Trastuzumab deruxtecan has a high drug-to-antibody ratio. A membrane-permeable payload offers the potential for activity against adjacent HER2-negative cells in heterogeneous tumors. It has a long half-life (6 days).
Trastuzumab deruxtecan received accelerated approval from the FDA in December 2019 to treat patients with HER2+ MBC who have received two or more prior HER2-targeted regimens, based on the results of the DESTINY-Breast 01 trial.
DESTINY-Breast 01 trial
In the phase 2 DESTINY-Breast 01 trial, 184 patients with a median of six previous treatments received trastuzumab deruxtecan (5.4 mg/kg) intravenously every 21 days. There were 24 patients with treated, asymptomatic brain metastases who participated. Patients with untreated or symptomatic brain metastases were excluded.
Overall, a response to therapy was reported in 112 patients (60.9%), with 6.0% complete and 54.9% partial responses. Most of the patients for whom both baseline and postbaseline data were available had a reduction in tumor size.
The median time until response was 1.6 months, an interval that corresponded to the time until the first scheduled imaging. Three patients (1.6%) had progressive disease, and two patients (1.1%) could not be evaluated.
The median duration of follow-up was 11.1 months, and the median response duration was 14.8 months.
The median progression-free survival (PFS) was 16.4 months, and the median overall survival (OS) was not reached. The median PFS in the patients with brain involvement was 18.1 months.
The most common adverse events of grade 3 or higher were a decreased neutrophil count (20.7%), anemia (8.7%), and nausea (7.6%). Most concerning was that trastuzumab deruxtecan was associated with interstitial lung disease in 13.6% of patients.
Tucatinib
Tucatinib is an oral, highly selective HER2 tyrosine kinase inhibitor (TKI). In April 2020, it was approved by the FDA, in combination with trastuzumab and capecitabine, for adult patients with advanced unresectable or metastatic HER2+ breast cancer who have received one or more prior anti-HER2–based regimens for MBC. The approval included patients with brain metastases.
The recommended tucatinib dose is 300 mg orally twice a day in combination with trastuzumab (at the standard dose) and capecitabine (1,000 mg/m2 given orally twice daily on days 1-14) on a 21-day cycle, until disease progression or unacceptable toxicity.
HER2CLIMB trial
The study that led to the approval of tucatinib was the HER2CLIMB trial. The trial enrolled 612 HER2+ MBC patients who had prior treatment with trastuzumab, pertuzumab, and T-DM1. Patients had received a median of 4 (range, 2-17) prior lines of HER2-targeted therapy.
The patients were randomized 2:1 to receive trastuzumab plus capecitabine and either tucatinib or an identical placebo twice daily.
The primary endpoint was PFS, evaluated in the initial 480 randomized patients. The median PFS was 7.8 months in the tucatinib arm and 5.6 months in the control arm (hazard ratio, 0.54; 95% confidence interval, 0.42-0.71; P < .001).
The confirmed overall response rate for patients with measurable disease was 40.6% in the tucatinib arm and 22.8% in the control arm (P = .001). The proportion of patients still in response at 12 months was 33.1% and 12.3%, respectively.
The median OS was 21.9 months in the tucatinib arm and 17.4 months in the placebo arm (HR, 0.66; 95% CI, 0.50-0.88; P = .005). At 24 months, 44.9% and 26.6% of patients, respectively, were still alive.
The most common grade 3 or higher adverse events (in the tucatinib and placebo arms, respectively) were palmar-plantar erythrodysesthesia syndrome (13.1% vs. 9.1%), diarrhea (12.9% vs. 8.6%), elevations in ALT and AST (approximately 5% vs. 0.5% for each), and fatigue (4.7% vs. 4.1%).
Tucatinib in patients with brain involvement
A unique feature of the HER2CLIMB study was that patients with MBC and untreated, symptomatic brain metastases were eligible. Patients with active, untreated central nervous system disease are excluded from virtually all other trials, especially drug-approval trials.
There were 291 patients with brain metastases in HER2CLIMB, 198 (48%) in the tucatinib arm and 93 (46%) in the control arm.
The risk of intracranial progression or death was reduced by 68% in the tucatinib arm (HR, 0.32; 95% CI, 0.22 to 0.48; P < .0001).
The 1-year CNS-PFS rate was 40.2% in the tucatinib arm and 0% in the placebo arm. The median duration of CNS-PFS was 9.9 months and 4.2 months, respectively.
The risk of death was reduced by 42% in the tucatinib arm (HR, 0.58; 95% CI, 0.40-0.85; P = .005). The median OS was 18.1 months and 12.0 months, respectively.
There were more objective responses in the brain with tucatinib (47.3%) than with placebo (20.0%; P = .03). The median duration of response was 6.8 months and 3.0 months, respectively.
Particularly because of its CNS activity and lack of serious, long-term toxicity, tucatinib combination therapy represents an attractive new option for patients with HER2+ MBC.
Neratinib
Neratinib is an irreversible pan-HER TKI that was approved by the FDA in July 2017 for extended adjuvant therapy in patients with early-stage HER2+ breast cancer, following the use of trastuzumab-based therapy.
Long-term results of the ExteNet study led to the approval for use as extended adjuvant therapy.
In February 2020, neratinib was FDA approved in combination with capecitabine for patients with HER2+ MBC after two or more prior anti-HER2–based regimens. The more recent FDA approval was based on results of the NALA trial.
NALA trial
The phase 3 NALA trial included 621 patients with HER2+ MBC who had received at least two prior anti-HER2 based regimens.
Patients were randomized 1:1 to receive neratinib at 240 mg orally once daily on days 1-21 with capecitabine at 750 mg/m2 orally twice daily on days 1-14 or lapatinib at 1,250 mg orally once daily on days 1-21 with capecitabine at 1,000 mg/m2 orally twice daily on days 1-14 for each 21-day cycle. Patients were treated until disease progression or unacceptable toxicity.
The primary endpoints were PFS and OS by blinded, independent, central review.
The median PFS was 5.6 months in the neratinib arm and 5.5 months in the lapatinib arm (HR, 0.76; 95% CI, 0.63-0.93; P = .0059). The PFS rate at 12 months was 28.8% and 14.8%, respectively.
The median OS was 21.0 months in the neratinib arm and 18.7 months in the lapatinib arm (HR, 0.88; 95% CI, 0.72-1.07; P = .2086). The ORR was 32.8% and 26.7%, respectively. The median response duration was 8.5 months and 5.6 months, respectively.
Fewer interventions for CNS disease were required in the neratinib arm than in the lapatinib arm (cumulative incidence, 22.8% vs. 29.2%; P = .043).
The most frequently reported grade 3-4 adverse reactions for the neratinib combination were diarrhea, nausea, vomiting, fatigue, and decreased appetite.
Grade 3 diarrhea occurred in 24.4% of those in the neratinib arm and 12.5% of those in the lapatinib arm. Antidiarrheal medication was used by 98.3% of patients receiving neratinib and 62.1% of patients receiving lapatinib.
Margetuximab-cmkb
Margetuximab is a chimeric Fc-engineered anti-HER2 monoclonal antibody that targets the same epitope as trastuzumab and exerts similar antiproliferative effects.
Compared with trastuzumab, margetuximab has higher affinity for both 158V (high-binding) and 158F (low-binding) alleles of the activating Fc receptor, CD16A. As a result, margetuximab enhances innate immunity, including CD16A-mediated antibody-dependent cellular cytotoxicity, more effectively than trastuzumab. Margetuximab also potentiates adaptive immunity, including enhanced clonality of the T-cell repertoire and induction of HER2-specific T- and B-cell responses.
In December 2020, margetuximab, in combination with chemotherapy, was approved by the FDA for patients with HER2+ MBC after two or more prior anti-HER2 regimens, at least one of which was for metastatic disease. The approved dose is 15 mg/kg IV every 3 weeks.
The study that led to margetuximab’s approval was the phase 3 SOPHIA trial.
SOPHIA trial
SOPHIA was a randomized trial of 536 patients with HER2+ MBC who had received prior treatment with other anti-HER2 therapies, including one to three lines of therapy for MBC.
Patients were randomly assigned 1:1 to receive margetuximab plus chemotherapy or trastuzumab plus chemotherapy. Assignment was stratified by chemotherapy choice (capecitabine, eribulin, gemcitabine, or vinorelbine), the number of previous lines of therapy for MBC, and disease extent.
Co–primary outcome measures were PFS by blinded, independent, central review and OS.
At the second interim analysis, the median PFS was 5.8 months in the margetuximab arm and 4.9 months in the trastuzumab arm (HR, 0.76; 95% CI, 0.59-0.98; P = .033). Results were more impressive in patients with CD16A genotypes containing a 158F allele. In this group, the median PFS was 6.9 months with margetuximab and 5.1 months with trastuzumab (HR, 0.68, 95% CI, 0.52-0.90; P = .005).
At the second interim analysis, the median OS was 21.6 months in the margetuximab arm and 19.8 months in the trastuzumab arm (HR, 0.89; 95% CI, 0.69-1.13; P = .33).
Subgroup data showed no differences in OS between the two arms for any subgroup except HER2+ MBC patients with an IHC score of 2 or higher. This is consistent with the postulated mechanism of action of margetuximab.
The confirmed ORR was 25% in the margetuximab arm and 14% in the trastuzumab arm, with similar durations of response between the study arms.
The most common adverse events in both arms (≥20%), regardless of causality, were fatigue, nausea, diarrhea, and neutropenia. Vomiting was common in the margetuximab arm, and anemia was common in the trastuzumab arm.
Grade 3 or higher adverse events occurred in 53.8% of patients receiving margetuximab and 52.6% of those receiving trastuzumab.
In view of margetuximab’s modest benefits in the SOPHIA trial, the ultimate role for margetuximab in HER2+ MBC may be restricted to patients with the CD16A-158F allele. A neoadjuvant trial is planned in that population.
Take-home messages
There are legitimate arguments regarding whether curing MBC is within reach for certain patient subsets, but there is no argument about whether the outlook for patients with HER2+ MBC has improved dramatically in recent years; it has.
The approval of four unique, new agents for the treatment of women with HER2+ MBC in relapse provides further improvements in outcome for these patients and distinctly different opportunities for tailoring treatment to the special circumstances of each patient (e.g., whether brain metastases are present, desire for oral therapy, comorbidities, experience with prior chemotherapy, etc).
When considered along with the potential for incorporating these drugs in earlier settings in well-designed clinical trials, these new drugs offer great promise to a group of patients who faced a dismal outcome just 2 decades ago.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
Before 2001, HER2/neu-positive breast cancer (HER2+) was one of the most dreaded diagnoses a woman could face, as treatment was largely ineffective. The discovery of trastuzumab changed that dramatically.
Over the next 20 years, two additional HER2-targeted therapies – lapatinib and trastuzumab emtansine (TDM-1) – earned approval from the Food and Drug Administration for selected patients with early and late HER2+ breast cancer.
Since 2019, four additional HER2-targeted therapies have been approved by the FDA for HER2+ metastatic breast cancer (MBC), changing the treatment paradigm for those patients substantially.
The new agents are especially useful in certain patient populations. The agents offer the promise of improved survival for patients with recurrent metastatic disease and the potential for further reductions in relapse rates in earlier settings.
Trastuzumab deruxtecan
Trastuzumab deruxtecan is an antibody-drug conjugate that links three components: an anti-HER2 monoclonal antibody, a highly potent topoisomerase I inhibitor payload, and a tetrapeptide-based cleavable linker.
Trastuzumab deruxtecan has a high drug-to-antibody ratio. A membrane-permeable payload offers the potential for activity against adjacent HER2-negative cells in heterogeneous tumors. It has a long half-life (6 days).
Trastuzumab deruxtecan received accelerated approval from the FDA in December 2019 to treat patients with HER2+ MBC who have received two or more prior HER2-targeted regimens, based on the results of the DESTINY-Breast 01 trial.
DESTINY-Breast 01 trial
In the phase 2 DESTINY-Breast 01 trial, 184 patients with a median of six previous treatments received trastuzumab deruxtecan (5.4 mg/kg) intravenously every 21 days. There were 24 patients with treated, asymptomatic brain metastases who participated. Patients with untreated or symptomatic brain metastases were excluded.
Overall, a response to therapy was reported in 112 patients (60.9%), with 6.0% complete and 54.9% partial responses. Most of the patients for whom both baseline and postbaseline data were available had a reduction in tumor size.
The median time until response was 1.6 months, an interval that corresponded to the time until the first scheduled imaging. Three patients (1.6%) had progressive disease, and two patients (1.1%) could not be evaluated.
The median duration of follow-up was 11.1 months, and the median response duration was 14.8 months.
The median progression-free survival (PFS) was 16.4 months, and the median overall survival (OS) was not reached. The median PFS in the patients with brain involvement was 18.1 months.
The most common adverse events of grade 3 or higher were a decreased neutrophil count (20.7%), anemia (8.7%), and nausea (7.6%). Most concerning was that trastuzumab deruxtecan was associated with interstitial lung disease in 13.6% of patients.
Tucatinib
Tucatinib is an oral, highly selective HER2 tyrosine kinase inhibitor (TKI). In April 2020, it was approved by the FDA, in combination with trastuzumab and capecitabine, for adult patients with advanced unresectable or metastatic HER2+ breast cancer who have received one or more prior anti-HER2–based regimens for MBC. The approval included patients with brain metastases.
The recommended tucatinib dose is 300 mg orally twice a day in combination with trastuzumab (at the standard dose) and capecitabine (1,000 mg/m2 given orally twice daily on days 1-14) on a 21-day cycle, until disease progression or unacceptable toxicity.
HER2CLIMB trial
The study that led to the approval of tucatinib was the HER2CLIMB trial. The trial enrolled 612 HER2+ MBC patients who had prior treatment with trastuzumab, pertuzumab, and T-DM1. Patients had received a median of 4 (range, 2-17) prior lines of HER2-targeted therapy.
The patients were randomized 2:1 to receive trastuzumab plus capecitabine and either tucatinib or an identical placebo twice daily.
The primary endpoint was PFS, evaluated in the initial 480 randomized patients. The median PFS was 7.8 months in the tucatinib arm and 5.6 months in the control arm (hazard ratio, 0.54; 95% confidence interval, 0.42-0.71; P < .001).
The confirmed overall response rate for patients with measurable disease was 40.6% in the tucatinib arm and 22.8% in the control arm (P = .001). The proportion of patients still in response at 12 months was 33.1% and 12.3%, respectively.
The median OS was 21.9 months in the tucatinib arm and 17.4 months in the placebo arm (HR, 0.66; 95% CI, 0.50-0.88; P = .005). At 24 months, 44.9% and 26.6% of patients, respectively, were still alive.
The most common grade 3 or higher adverse events (in the tucatinib and placebo arms, respectively) were palmar-plantar erythrodysesthesia syndrome (13.1% vs. 9.1%), diarrhea (12.9% vs. 8.6%), elevations in ALT and AST (approximately 5% vs. 0.5% for each), and fatigue (4.7% vs. 4.1%).
Tucatinib in patients with brain involvement
A unique feature of the HER2CLIMB study was that patients with MBC and untreated, symptomatic brain metastases were eligible. Patients with active, untreated central nervous system disease are excluded from virtually all other trials, especially drug-approval trials.
There were 291 patients with brain metastases in HER2CLIMB, 198 (48%) in the tucatinib arm and 93 (46%) in the control arm.
The risk of intracranial progression or death was reduced by 68% in the tucatinib arm (HR, 0.32; 95% CI, 0.22 to 0.48; P < .0001).
The 1-year CNS-PFS rate was 40.2% in the tucatinib arm and 0% in the placebo arm. The median duration of CNS-PFS was 9.9 months and 4.2 months, respectively.
The risk of death was reduced by 42% in the tucatinib arm (HR, 0.58; 95% CI, 0.40-0.85; P = .005). The median OS was 18.1 months and 12.0 months, respectively.
There were more objective responses in the brain with tucatinib (47.3%) than with placebo (20.0%; P = .03). The median duration of response was 6.8 months and 3.0 months, respectively.
Particularly because of its CNS activity and lack of serious, long-term toxicity, tucatinib combination therapy represents an attractive new option for patients with HER2+ MBC.
Neratinib
Neratinib is an irreversible pan-HER TKI that was approved by the FDA in July 2017 for extended adjuvant therapy in patients with early-stage HER2+ breast cancer, following the use of trastuzumab-based therapy.
Long-term results of the ExteNet study led to the approval for use as extended adjuvant therapy.
In February 2020, neratinib was FDA approved in combination with capecitabine for patients with HER2+ MBC after two or more prior anti-HER2–based regimens. The more recent FDA approval was based on results of the NALA trial.
NALA trial
The phase 3 NALA trial included 621 patients with HER2+ MBC who had received at least two prior anti-HER2 based regimens.
Patients were randomized 1:1 to receive neratinib at 240 mg orally once daily on days 1-21 with capecitabine at 750 mg/m2 orally twice daily on days 1-14 or lapatinib at 1,250 mg orally once daily on days 1-21 with capecitabine at 1,000 mg/m2 orally twice daily on days 1-14 for each 21-day cycle. Patients were treated until disease progression or unacceptable toxicity.
The primary endpoints were PFS and OS by blinded, independent, central review.
The median PFS was 5.6 months in the neratinib arm and 5.5 months in the lapatinib arm (HR, 0.76; 95% CI, 0.63-0.93; P = .0059). The PFS rate at 12 months was 28.8% and 14.8%, respectively.
The median OS was 21.0 months in the neratinib arm and 18.7 months in the lapatinib arm (HR, 0.88; 95% CI, 0.72-1.07; P = .2086). The ORR was 32.8% and 26.7%, respectively. The median response duration was 8.5 months and 5.6 months, respectively.
Fewer interventions for CNS disease were required in the neratinib arm than in the lapatinib arm (cumulative incidence, 22.8% vs. 29.2%; P = .043).
The most frequently reported grade 3-4 adverse reactions for the neratinib combination were diarrhea, nausea, vomiting, fatigue, and decreased appetite.
Grade 3 diarrhea occurred in 24.4% of those in the neratinib arm and 12.5% of those in the lapatinib arm. Antidiarrheal medication was used by 98.3% of patients receiving neratinib and 62.1% of patients receiving lapatinib.
Margetuximab-cmkb
Margetuximab is a chimeric Fc-engineered anti-HER2 monoclonal antibody that targets the same epitope as trastuzumab and exerts similar antiproliferative effects.
Compared with trastuzumab, margetuximab has higher affinity for both 158V (high-binding) and 158F (low-binding) alleles of the activating Fc receptor, CD16A. As a result, margetuximab enhances innate immunity, including CD16A-mediated antibody-dependent cellular cytotoxicity, more effectively than trastuzumab. Margetuximab also potentiates adaptive immunity, including enhanced clonality of the T-cell repertoire and induction of HER2-specific T- and B-cell responses.
In December 2020, margetuximab, in combination with chemotherapy, was approved by the FDA for patients with HER2+ MBC after two or more prior anti-HER2 regimens, at least one of which was for metastatic disease. The approved dose is 15 mg/kg IV every 3 weeks.
The study that led to margetuximab’s approval was the phase 3 SOPHIA trial.
SOPHIA trial
SOPHIA was a randomized trial of 536 patients with HER2+ MBC who had received prior treatment with other anti-HER2 therapies, including one to three lines of therapy for MBC.
Patients were randomly assigned 1:1 to receive margetuximab plus chemotherapy or trastuzumab plus chemotherapy. Assignment was stratified by chemotherapy choice (capecitabine, eribulin, gemcitabine, or vinorelbine), the number of previous lines of therapy for MBC, and disease extent.
Co–primary outcome measures were PFS by blinded, independent, central review and OS.
At the second interim analysis, the median PFS was 5.8 months in the margetuximab arm and 4.9 months in the trastuzumab arm (HR, 0.76; 95% CI, 0.59-0.98; P = .033). Results were more impressive in patients with CD16A genotypes containing a 158F allele. In this group, the median PFS was 6.9 months with margetuximab and 5.1 months with trastuzumab (HR, 0.68, 95% CI, 0.52-0.90; P = .005).
At the second interim analysis, the median OS was 21.6 months in the margetuximab arm and 19.8 months in the trastuzumab arm (HR, 0.89; 95% CI, 0.69-1.13; P = .33).
Subgroup data showed no differences in OS between the two arms for any subgroup except HER2+ MBC patients with an IHC score of 2 or higher. This is consistent with the postulated mechanism of action of margetuximab.
The confirmed ORR was 25% in the margetuximab arm and 14% in the trastuzumab arm, with similar durations of response between the study arms.
The most common adverse events in both arms (≥20%), regardless of causality, were fatigue, nausea, diarrhea, and neutropenia. Vomiting was common in the margetuximab arm, and anemia was common in the trastuzumab arm.
Grade 3 or higher adverse events occurred in 53.8% of patients receiving margetuximab and 52.6% of those receiving trastuzumab.
In view of margetuximab’s modest benefits in the SOPHIA trial, the ultimate role for margetuximab in HER2+ MBC may be restricted to patients with the CD16A-158F allele. A neoadjuvant trial is planned in that population.
Take-home messages
There are legitimate arguments regarding whether curing MBC is within reach for certain patient subsets, but there is no argument about whether the outlook for patients with HER2+ MBC has improved dramatically in recent years; it has.
The approval of four unique, new agents for the treatment of women with HER2+ MBC in relapse provides further improvements in outcome for these patients and distinctly different opportunities for tailoring treatment to the special circumstances of each patient (e.g., whether brain metastases are present, desire for oral therapy, comorbidities, experience with prior chemotherapy, etc).
When considered along with the potential for incorporating these drugs in earlier settings in well-designed clinical trials, these new drugs offer great promise to a group of patients who faced a dismal outcome just 2 decades ago.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
Coping with postpandemic school hesitancy
As the protective effect of the vaccines becomes increasingly apparent, a large number of school systems are beginning to return to prepandemic in-school learning. But anecdotal reports from around the country are making it clear that some children or their families are hesitant to return to the old norm of face to face learning (Goldstein D. “Schools Are Open, but Many Families Remain Hesitant to Return.” New York Times. 2021 May 9). The possible explanations for this hesitancy include a broad list that goes well beyond the obvious concern about the child contracting COVID-19.
I hear from my grandchildren that remote learning has for the most part been unpleasant and lacked the rigor of their in-class experiences. But, they admit that they have found that, in some situations, they prefer the environment at home because it is less distracting. They also acknowledge that, while they miss seeing their friends, at times the isolation has allowed them to be more efficient. Of course, their observations must be viewed in light of their personalities and the support provided by their parents. For these motivated teenagers, the bottom line is that they would prefer to be in school.
However, for the children who have always been a bit ambivalent about school either because they were anxious in social situations or because they found the academics too challenging, one can easily understand why they might prefer to remain in a less-intimidating home environment. For them, missing their friends may have little draw because they may not have had any friends. And, the negative feedback and bullying they have received at school is too overwhelming. A teenager for whom the pandemic has offered the out-of-school free time to explore her independence, feel more like an adult, and enjoy the benefits of having a job may be hesitant to return to the restrictions imposed by what she sees as the childishness of in-school learning.
Compounding the problem is the risk avoidance posture of some school systems and the hesitancy of some teachers to return to an environment that they continue to view as unsafe despite the evidence of the effectiveness of the vaccines and the minimal threat of in-school spread. It is going to be interesting to see how school administrators and politicians deal with this level of institutional hesitancy. Some schools may take what might be considered a hard-line approach and eliminate remote learning completely.
Regardless of how swiftly and thoughtfully schools return to in-class learning, a large number of children will eventually be faced with the stark reality of returning to a place in which they had felt painfully uncomfortable in the past. Pediatricians must be prepared to see this current wave of school hesitancy morph into a full-fledged tsunami of school refusals.
Successful management of a family whose child finds school too challenging emotionally has always required a combination of careful attention to the possible medical causes of the child’s complaints, consultation with a mental health practitioner, and thoughtful coordination with educators sensitive to the child’s school-generated distress.
It has never been easy to reassure the family of a child with frequent headaches or belly pain that his symptoms have no physical basis and then gently point out that the stress of school attendance may be a contributing factor. Some families who buy into the association may be fortunate enough to be able to offer their child home schooling as a solution to school refusal. But this strategy often requires that one parent remain home and has the temperament and the skills to teach.
Now that we have all seen that remote learning has the potential to work in a crisis, will some parents begin to demand it for their children with school refusal? Who will pay for it? I think you and I would prefer to see a solution that targeted therapeutic interventions aimed at getting the child back in school. But you and I also know those strategies don’t always work.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.
As the protective effect of the vaccines becomes increasingly apparent, a large number of school systems are beginning to return to prepandemic in-school learning. But anecdotal reports from around the country are making it clear that some children or their families are hesitant to return to the old norm of face to face learning (Goldstein D. “Schools Are Open, but Many Families Remain Hesitant to Return.” New York Times. 2021 May 9). The possible explanations for this hesitancy include a broad list that goes well beyond the obvious concern about the child contracting COVID-19.
I hear from my grandchildren that remote learning has for the most part been unpleasant and lacked the rigor of their in-class experiences. But, they admit that they have found that, in some situations, they prefer the environment at home because it is less distracting. They also acknowledge that, while they miss seeing their friends, at times the isolation has allowed them to be more efficient. Of course, their observations must be viewed in light of their personalities and the support provided by their parents. For these motivated teenagers, the bottom line is that they would prefer to be in school.
However, for the children who have always been a bit ambivalent about school either because they were anxious in social situations or because they found the academics too challenging, one can easily understand why they might prefer to remain in a less-intimidating home environment. For them, missing their friends may have little draw because they may not have had any friends. And, the negative feedback and bullying they have received at school is too overwhelming. A teenager for whom the pandemic has offered the out-of-school free time to explore her independence, feel more like an adult, and enjoy the benefits of having a job may be hesitant to return to the restrictions imposed by what she sees as the childishness of in-school learning.
Compounding the problem is the risk avoidance posture of some school systems and the hesitancy of some teachers to return to an environment that they continue to view as unsafe despite the evidence of the effectiveness of the vaccines and the minimal threat of in-school spread. It is going to be interesting to see how school administrators and politicians deal with this level of institutional hesitancy. Some schools may take what might be considered a hard-line approach and eliminate remote learning completely.
Regardless of how swiftly and thoughtfully schools return to in-class learning, a large number of children will eventually be faced with the stark reality of returning to a place in which they had felt painfully uncomfortable in the past. Pediatricians must be prepared to see this current wave of school hesitancy morph into a full-fledged tsunami of school refusals.
Successful management of a family whose child finds school too challenging emotionally has always required a combination of careful attention to the possible medical causes of the child’s complaints, consultation with a mental health practitioner, and thoughtful coordination with educators sensitive to the child’s school-generated distress.
It has never been easy to reassure the family of a child with frequent headaches or belly pain that his symptoms have no physical basis and then gently point out that the stress of school attendance may be a contributing factor. Some families who buy into the association may be fortunate enough to be able to offer their child home schooling as a solution to school refusal. But this strategy often requires that one parent remain home and has the temperament and the skills to teach.
Now that we have all seen that remote learning has the potential to work in a crisis, will some parents begin to demand it for their children with school refusal? Who will pay for it? I think you and I would prefer to see a solution that targeted therapeutic interventions aimed at getting the child back in school. But you and I also know those strategies don’t always work.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.
As the protective effect of the vaccines becomes increasingly apparent, a large number of school systems are beginning to return to prepandemic in-school learning. But anecdotal reports from around the country are making it clear that some children or their families are hesitant to return to the old norm of face to face learning (Goldstein D. “Schools Are Open, but Many Families Remain Hesitant to Return.” New York Times. 2021 May 9). The possible explanations for this hesitancy include a broad list that goes well beyond the obvious concern about the child contracting COVID-19.
I hear from my grandchildren that remote learning has for the most part been unpleasant and lacked the rigor of their in-class experiences. But, they admit that they have found that, in some situations, they prefer the environment at home because it is less distracting. They also acknowledge that, while they miss seeing their friends, at times the isolation has allowed them to be more efficient. Of course, their observations must be viewed in light of their personalities and the support provided by their parents. For these motivated teenagers, the bottom line is that they would prefer to be in school.
However, for the children who have always been a bit ambivalent about school either because they were anxious in social situations or because they found the academics too challenging, one can easily understand why they might prefer to remain in a less-intimidating home environment. For them, missing their friends may have little draw because they may not have had any friends. And, the negative feedback and bullying they have received at school is too overwhelming. A teenager for whom the pandemic has offered the out-of-school free time to explore her independence, feel more like an adult, and enjoy the benefits of having a job may be hesitant to return to the restrictions imposed by what she sees as the childishness of in-school learning.
Compounding the problem is the risk avoidance posture of some school systems and the hesitancy of some teachers to return to an environment that they continue to view as unsafe despite the evidence of the effectiveness of the vaccines and the minimal threat of in-school spread. It is going to be interesting to see how school administrators and politicians deal with this level of institutional hesitancy. Some schools may take what might be considered a hard-line approach and eliminate remote learning completely.
Regardless of how swiftly and thoughtfully schools return to in-class learning, a large number of children will eventually be faced with the stark reality of returning to a place in which they had felt painfully uncomfortable in the past. Pediatricians must be prepared to see this current wave of school hesitancy morph into a full-fledged tsunami of school refusals.
Successful management of a family whose child finds school too challenging emotionally has always required a combination of careful attention to the possible medical causes of the child’s complaints, consultation with a mental health practitioner, and thoughtful coordination with educators sensitive to the child’s school-generated distress.
It has never been easy to reassure the family of a child with frequent headaches or belly pain that his symptoms have no physical basis and then gently point out that the stress of school attendance may be a contributing factor. Some families who buy into the association may be fortunate enough to be able to offer their child home schooling as a solution to school refusal. But this strategy often requires that one parent remain home and has the temperament and the skills to teach.
Now that we have all seen that remote learning has the potential to work in a crisis, will some parents begin to demand it for their children with school refusal? Who will pay for it? I think you and I would prefer to see a solution that targeted therapeutic interventions aimed at getting the child back in school. But you and I also know those strategies don’t always work.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.
Race or income: What’s really at play with health disparities?
In February, an article published by the American Medical Association pointed out that income inequality is likely the cause for health disparity among races.1 The topic of health disparities was also the subject of the editorial published in the January/February issue, “Systemic racism and health disparities: a statement from editors of family medicine journals” (J Fam Pract. 2021;70:3-5).
It would be interesting to compare health outcomes among Blacks, Latinos, and Whites stratified by income/poverty levels. I suspect that much of the racial inequality would fade with that. There are so many questions to ask in relation to these issues rather than chalk everything up to racism. Does education, dietary choices, exercise, substance abuse, or cultural priorities factor into the differences? If everyone suddenly had equal access to care and equal financial resources, would there be any difference, or would behavior patterns remain unchanged?
I would hope we could avoid groupthink and be willing to intelligently and critically evaluate these issues so that the underlying problems can be effectively addressed.
Steven Mull, MD
Rockford, IL
1. Robeznieks A. COVID-19’s unequal impact tied to another inequality—of income. American Medical Association. Published February 16, 2021. Accessed March 17, 2021. ww.ama-assn.org/ delivering-care/health-equity/covid-19-s-unequal-impact-tiedanother-inequality-income
In February, an article published by the American Medical Association pointed out that income inequality is likely the cause for health disparity among races.1 The topic of health disparities was also the subject of the editorial published in the January/February issue, “Systemic racism and health disparities: a statement from editors of family medicine journals” (J Fam Pract. 2021;70:3-5).
It would be interesting to compare health outcomes among Blacks, Latinos, and Whites stratified by income/poverty levels. I suspect that much of the racial inequality would fade with that. There are so many questions to ask in relation to these issues rather than chalk everything up to racism. Does education, dietary choices, exercise, substance abuse, or cultural priorities factor into the differences? If everyone suddenly had equal access to care and equal financial resources, would there be any difference, or would behavior patterns remain unchanged?
I would hope we could avoid groupthink and be willing to intelligently and critically evaluate these issues so that the underlying problems can be effectively addressed.
Steven Mull, MD
Rockford, IL
In February, an article published by the American Medical Association pointed out that income inequality is likely the cause for health disparity among races.1 The topic of health disparities was also the subject of the editorial published in the January/February issue, “Systemic racism and health disparities: a statement from editors of family medicine journals” (J Fam Pract. 2021;70:3-5).
It would be interesting to compare health outcomes among Blacks, Latinos, and Whites stratified by income/poverty levels. I suspect that much of the racial inequality would fade with that. There are so many questions to ask in relation to these issues rather than chalk everything up to racism. Does education, dietary choices, exercise, substance abuse, or cultural priorities factor into the differences? If everyone suddenly had equal access to care and equal financial resources, would there be any difference, or would behavior patterns remain unchanged?
I would hope we could avoid groupthink and be willing to intelligently and critically evaluate these issues so that the underlying problems can be effectively addressed.
Steven Mull, MD
Rockford, IL
1. Robeznieks A. COVID-19’s unequal impact tied to another inequality—of income. American Medical Association. Published February 16, 2021. Accessed March 17, 2021. ww.ama-assn.org/ delivering-care/health-equity/covid-19-s-unequal-impact-tiedanother-inequality-income
1. Robeznieks A. COVID-19’s unequal impact tied to another inequality—of income. American Medical Association. Published February 16, 2021. Accessed March 17, 2021. ww.ama-assn.org/ delivering-care/health-equity/covid-19-s-unequal-impact-tiedanother-inequality-income
Look at health disparities by zip codes
It was encouraging to see your editorial, “Systemic racism and health disparities: a statement from editors of family medicine journals” (J Fam Pract. 2021;70:3-5), because to solve a problem you must first recognize the problem exists. There was a publication several years ago that went deeply into this subject.1 I worked with the Medicaid population for 20 years, and I observed things similar to what was described in that paper.
Health disparities should be looked at as if structured around zip codes. People who live in low-income/poverty areas usually have to deal with at least 3 main problems. The first issue involves lack of healthy food options. In low-income areas, food choice is often limited, forcing many to purchase their meals from fast food restaurants, dollar stores, or a “corner store.” In addition to being a food desert, a low-income area may have a poor public school system, and studies have shown that good health outcomes are linked to higher education. Poor medical intelligence is another problem connected to low-income patients. These patients tend to have a hard time keeping up with what medicine they are taking and cannot offer much insight into their medical condition. Furthermore, it is possible that in a busy practice, patient education is not what it should be, and a patient’s silence during a visit should not be accepted as an understanding of what a doctor has told them.
Hopefully, recognizing these issues will help provide a starting point for each doctor to gain better awareness into this problem.
Robert W. Sessoms, MD
Daytona Beach, FL
1. Institute of Medicine. How Far Have We Come in Eliminating Health Disparities? Progress Since 2000. National Academies Press; 2012.
It was encouraging to see your editorial, “Systemic racism and health disparities: a statement from editors of family medicine journals” (J Fam Pract. 2021;70:3-5), because to solve a problem you must first recognize the problem exists. There was a publication several years ago that went deeply into this subject.1 I worked with the Medicaid population for 20 years, and I observed things similar to what was described in that paper.
Health disparities should be looked at as if structured around zip codes. People who live in low-income/poverty areas usually have to deal with at least 3 main problems. The first issue involves lack of healthy food options. In low-income areas, food choice is often limited, forcing many to purchase their meals from fast food restaurants, dollar stores, or a “corner store.” In addition to being a food desert, a low-income area may have a poor public school system, and studies have shown that good health outcomes are linked to higher education. Poor medical intelligence is another problem connected to low-income patients. These patients tend to have a hard time keeping up with what medicine they are taking and cannot offer much insight into their medical condition. Furthermore, it is possible that in a busy practice, patient education is not what it should be, and a patient’s silence during a visit should not be accepted as an understanding of what a doctor has told them.
Hopefully, recognizing these issues will help provide a starting point for each doctor to gain better awareness into this problem.
Robert W. Sessoms, MD
Daytona Beach, FL
It was encouraging to see your editorial, “Systemic racism and health disparities: a statement from editors of family medicine journals” (J Fam Pract. 2021;70:3-5), because to solve a problem you must first recognize the problem exists. There was a publication several years ago that went deeply into this subject.1 I worked with the Medicaid population for 20 years, and I observed things similar to what was described in that paper.
Health disparities should be looked at as if structured around zip codes. People who live in low-income/poverty areas usually have to deal with at least 3 main problems. The first issue involves lack of healthy food options. In low-income areas, food choice is often limited, forcing many to purchase their meals from fast food restaurants, dollar stores, or a “corner store.” In addition to being a food desert, a low-income area may have a poor public school system, and studies have shown that good health outcomes are linked to higher education. Poor medical intelligence is another problem connected to low-income patients. These patients tend to have a hard time keeping up with what medicine they are taking and cannot offer much insight into their medical condition. Furthermore, it is possible that in a busy practice, patient education is not what it should be, and a patient’s silence during a visit should not be accepted as an understanding of what a doctor has told them.
Hopefully, recognizing these issues will help provide a starting point for each doctor to gain better awareness into this problem.
Robert W. Sessoms, MD
Daytona Beach, FL
1. Institute of Medicine. How Far Have We Come in Eliminating Health Disparities? Progress Since 2000. National Academies Press; 2012.
1. Institute of Medicine. How Far Have We Come in Eliminating Health Disparities? Progress Since 2000. National Academies Press; 2012.
Acts of kindness, empathy bolster mental health
Sigmund Freud said, “Out of your vulnerabilities will come greatest strength.” What exactly did Dr. Freud mean by this?
Many aspects of mental health treatment include cognitive restructuring, behavioral changes, emotion processing, and setting boundaries. These are all critical aspects of treatment, but what about kindness and compassion?
We often forget that kindness requires us to be vulnerable and take a risk at times. Being kind to others is not always easy, and it is not always an automatic reaction. Vulnerability often involves risk, but the outcomes often outweigh fear.
Dr. Freud was highlighting that being kind, open, and honest will often result in strong character and resilience. In turn, it will help others. Psychology and psychiatry have proved time and time again that empathy, compassion, and kindness have numerous benefits for mental and physical health for both the giver and the receiver.
From a biological perspective, we know that acts of kindness signal the brain to release serotonin and dopamine, known as “feel good transmitters,” and endorphins, which in turn lessen pain, depression, and anxiety. According to Waguih W. Ishak, MD, a psychiatrist affiliated with Cedars-Sinai in Los Angeles,1 in addition to boosting oxytocin and dopamine, being kind can increase serotonin, a neurotransmitter that helps regulate mood. Kindness and compassion have been shown to release oxytocin, known as the “love hormone,” which increases self-esteem, trust, connection, and optimism. Oxytocin also reduces blood pressure and has been dubbed the “cardioprotective” hormone. According to Kelli Harding, MD, MPH, a psychiatrist affiliated with Columbia University in New York,2 kindness can extend the lifespan. Research from Emory University in Atlanta has shown that, when an individual is kind to another, the brain’s reward centers light up – resulting in a “helper’s high.” Thus, kindness is self-reinforcing.3
Kindness leads to a greater sense of connection to others and a lessening in feelings of isolation. Small acts of kindness build up compassion in oneself. Research indicates that kindness doesn’t just positively affect the giver and receiver but can also benefit onlookers. An article in Psychology Today,4 suggests that those who witness acts of kindness are also more likely to “pay it forward,” resulting in a domino effect. Along these same lines, altruistic people, specifically those who engage in charitable donations, expressed higher levels of overall happiness according to a 2010 Harvard Business School survey.5
“You can’t pour from an empty cup” is a trendy quote making its way around social media. Before we can be kind and compassionate to others, we must first be kind and compassionate to ourselves. In today’s world, productivity and pressure-filled environments consume us daily. We often find ourselves skipping meals, forgetting to connect with loved ones, missing breaks, and even neglecting our sleep. It is virtually impossible to care for others when we are depleted ourselves. Sometimes not prioritizing ourselves can result in collateral damage. We may become short-tempered, irritable, moody, and overwhelmed. At this point kindness, compassion, and empathy toward others are likely to be absent. Once we replenish ourselves, by taking time off, indulging in a nice meal, exercising, we are more likely to respond as opposed to react, ask others about themselves, and engage in overall positive interactions throughout our day. Kindness is best fostered by being kind to ourselves to sustain our own well-being and by being kind to others in order to maintain the cycle. For clinicians who have been pushed to respond to various aspects of the COVID-19 pandemic, self-care has never been more important.
COVID-19 has been difficult for everyone, particularly the elderly and vulnerable populations. However, kindness has proved to be an overwhelming response as many businesses and individuals have taken to volunteering time and resources for those in need. Even big corporations have chipped in. For example, Lyft and Uber – in a partnership with the White House – are now offering free rides to vaccine sites, and several local businesses have donated personal protective equipment to hospitals and assisted living facilities.
Kindness and empathy are ever present in the field of mental health, medicine, and substance use treatment. The very act of caring for another involves kindness. In medicine, empathy has been defined as “an emotional experience between an observer and a subject in which the observer, based on visual and auditory cues, identifies and transiently experiences the subject’s emotional state.”6
As mental health professionals, we receive empathy training early on in our schooling – increasingly so over the last decade. Research has indicated that trusting relationships between clinicians and patients result in optimal care. Evidence-based communication styles are being widely implemented. This entails using nonjudgmental language, open-ended questions, and active listening skills, for example. In addition, the mental health professionals have our conscious and unconscious judgments. If empathy training is provided, we can learn to acknowledge our biases and mitigate them. Lastly, empathy training has been proven to assist with destigmatization, increase in treatment seeking, and overall better outcomes.
Substance use treatment, which often focuses on cognition and behavior changing, boundaries, and family dynamics, also requires support and kindness. Although it is not an empirically based “treatment,” Alcoholics Anonymous (AA) has used kindness for decades.
Step 12 of AA’s 12-step program, which was developed by two people with alcohol use disorder in 1935 in Akron, Ohio, is as follows: “Having had a spiritual awakening as the result of these steps, we tried to carry this message to alcoholics, and to practice these principles in all our affairs.”
Once AA members are on solid ground with their sobriety, they are urged to help others in their recovery. This process provides many benefits. When individuals are concerned about someone else, they are less focused on themselves. This helps the individuals in recovery to decrease their rumination and “get out of themselves.” It also allows for the AA member to be kind and helpful to an individual who is suffering, thereby expressing kindness, compassion, and empathy. This act of “paying it forward” produces a domino effect that has withstood the test of time as evidenced by the ever-growing fellowship of Alcoholics Anonymous.
Several small acts of kindness can help us as clinicians and our patients:
1. Practice self-care.
2. Take a half day off from your practice.
3. Give staff a half day off.
4. Call a family member or friend and ask them how they are doing. Then engage in active listening and refrain from giving advice.
5. Donate to a homeless shelter or volunteer your time at a charity.
6. Give a stranger a compliment.
7. Surprise someone with a small gift.
8. Send a loved one a letter instead of a text.
9. Pick up litter.
10. Acknowledge family and friends who gave you extra support during the pandemic.
11. Take baked goods to your office.
12. Help a neighbor with groceries.
13. Leave a generous tip.
14. Play soft music in your office.
In conclusion, kindness, empathy, and compassion are vital concepts that are not just fluffy theories. They have vast mental, physical, and social benefits for us and our patients.
References
1. Cedars-Sinai staff. The Science of Kindness. 2019 Feb 13. Cedars-Sinai blog.
2. Harding K. The Rabbit Effect: Live Longer, Happier, and Healthier with the Groundbreaking Science of Kindness. Atria Books, 2019.
3. Ritvo E. BeKindr. Momosa Publishing, 2017.
4. Svoboda E. “Pay it Forward.” Psychology Today. Last reviewed 2016 Jun 9.
5. Aknin LB et al. “Prosocial spending and well-being: Cross-Cultural Evidence for a Psychological Universal.” Harvard Business School. Working Paper 11-038. 2010.
6. Hirsch EM. AMA J Ethics. Virtual Mentor. 2007;9(6):423-7.
Dr. Haji is a licensed clinical psychologist specializing in psychodiagnostic assessment, forensic assessment, dual diagnosis, serious and persistent mental illness, depression, anxiety, personality disorders, and substance abuse treatment. She practices in Miami and has no conflicts of interest.
Sigmund Freud said, “Out of your vulnerabilities will come greatest strength.” What exactly did Dr. Freud mean by this?
Many aspects of mental health treatment include cognitive restructuring, behavioral changes, emotion processing, and setting boundaries. These are all critical aspects of treatment, but what about kindness and compassion?
We often forget that kindness requires us to be vulnerable and take a risk at times. Being kind to others is not always easy, and it is not always an automatic reaction. Vulnerability often involves risk, but the outcomes often outweigh fear.
Dr. Freud was highlighting that being kind, open, and honest will often result in strong character and resilience. In turn, it will help others. Psychology and psychiatry have proved time and time again that empathy, compassion, and kindness have numerous benefits for mental and physical health for both the giver and the receiver.
From a biological perspective, we know that acts of kindness signal the brain to release serotonin and dopamine, known as “feel good transmitters,” and endorphins, which in turn lessen pain, depression, and anxiety. According to Waguih W. Ishak, MD, a psychiatrist affiliated with Cedars-Sinai in Los Angeles,1 in addition to boosting oxytocin and dopamine, being kind can increase serotonin, a neurotransmitter that helps regulate mood. Kindness and compassion have been shown to release oxytocin, known as the “love hormone,” which increases self-esteem, trust, connection, and optimism. Oxytocin also reduces blood pressure and has been dubbed the “cardioprotective” hormone. According to Kelli Harding, MD, MPH, a psychiatrist affiliated with Columbia University in New York,2 kindness can extend the lifespan. Research from Emory University in Atlanta has shown that, when an individual is kind to another, the brain’s reward centers light up – resulting in a “helper’s high.” Thus, kindness is self-reinforcing.3
Kindness leads to a greater sense of connection to others and a lessening in feelings of isolation. Small acts of kindness build up compassion in oneself. Research indicates that kindness doesn’t just positively affect the giver and receiver but can also benefit onlookers. An article in Psychology Today,4 suggests that those who witness acts of kindness are also more likely to “pay it forward,” resulting in a domino effect. Along these same lines, altruistic people, specifically those who engage in charitable donations, expressed higher levels of overall happiness according to a 2010 Harvard Business School survey.5
“You can’t pour from an empty cup” is a trendy quote making its way around social media. Before we can be kind and compassionate to others, we must first be kind and compassionate to ourselves. In today’s world, productivity and pressure-filled environments consume us daily. We often find ourselves skipping meals, forgetting to connect with loved ones, missing breaks, and even neglecting our sleep. It is virtually impossible to care for others when we are depleted ourselves. Sometimes not prioritizing ourselves can result in collateral damage. We may become short-tempered, irritable, moody, and overwhelmed. At this point kindness, compassion, and empathy toward others are likely to be absent. Once we replenish ourselves, by taking time off, indulging in a nice meal, exercising, we are more likely to respond as opposed to react, ask others about themselves, and engage in overall positive interactions throughout our day. Kindness is best fostered by being kind to ourselves to sustain our own well-being and by being kind to others in order to maintain the cycle. For clinicians who have been pushed to respond to various aspects of the COVID-19 pandemic, self-care has never been more important.
COVID-19 has been difficult for everyone, particularly the elderly and vulnerable populations. However, kindness has proved to be an overwhelming response as many businesses and individuals have taken to volunteering time and resources for those in need. Even big corporations have chipped in. For example, Lyft and Uber – in a partnership with the White House – are now offering free rides to vaccine sites, and several local businesses have donated personal protective equipment to hospitals and assisted living facilities.
Kindness and empathy are ever present in the field of mental health, medicine, and substance use treatment. The very act of caring for another involves kindness. In medicine, empathy has been defined as “an emotional experience between an observer and a subject in which the observer, based on visual and auditory cues, identifies and transiently experiences the subject’s emotional state.”6
As mental health professionals, we receive empathy training early on in our schooling – increasingly so over the last decade. Research has indicated that trusting relationships between clinicians and patients result in optimal care. Evidence-based communication styles are being widely implemented. This entails using nonjudgmental language, open-ended questions, and active listening skills, for example. In addition, the mental health professionals have our conscious and unconscious judgments. If empathy training is provided, we can learn to acknowledge our biases and mitigate them. Lastly, empathy training has been proven to assist with destigmatization, increase in treatment seeking, and overall better outcomes.
Substance use treatment, which often focuses on cognition and behavior changing, boundaries, and family dynamics, also requires support and kindness. Although it is not an empirically based “treatment,” Alcoholics Anonymous (AA) has used kindness for decades.
Step 12 of AA’s 12-step program, which was developed by two people with alcohol use disorder in 1935 in Akron, Ohio, is as follows: “Having had a spiritual awakening as the result of these steps, we tried to carry this message to alcoholics, and to practice these principles in all our affairs.”
Once AA members are on solid ground with their sobriety, they are urged to help others in their recovery. This process provides many benefits. When individuals are concerned about someone else, they are less focused on themselves. This helps the individuals in recovery to decrease their rumination and “get out of themselves.” It also allows for the AA member to be kind and helpful to an individual who is suffering, thereby expressing kindness, compassion, and empathy. This act of “paying it forward” produces a domino effect that has withstood the test of time as evidenced by the ever-growing fellowship of Alcoholics Anonymous.
Several small acts of kindness can help us as clinicians and our patients:
1. Practice self-care.
2. Take a half day off from your practice.
3. Give staff a half day off.
4. Call a family member or friend and ask them how they are doing. Then engage in active listening and refrain from giving advice.
5. Donate to a homeless shelter or volunteer your time at a charity.
6. Give a stranger a compliment.
7. Surprise someone with a small gift.
8. Send a loved one a letter instead of a text.
9. Pick up litter.
10. Acknowledge family and friends who gave you extra support during the pandemic.
11. Take baked goods to your office.
12. Help a neighbor with groceries.
13. Leave a generous tip.
14. Play soft music in your office.
In conclusion, kindness, empathy, and compassion are vital concepts that are not just fluffy theories. They have vast mental, physical, and social benefits for us and our patients.
References
1. Cedars-Sinai staff. The Science of Kindness. 2019 Feb 13. Cedars-Sinai blog.
2. Harding K. The Rabbit Effect: Live Longer, Happier, and Healthier with the Groundbreaking Science of Kindness. Atria Books, 2019.
3. Ritvo E. BeKindr. Momosa Publishing, 2017.
4. Svoboda E. “Pay it Forward.” Psychology Today. Last reviewed 2016 Jun 9.
5. Aknin LB et al. “Prosocial spending and well-being: Cross-Cultural Evidence for a Psychological Universal.” Harvard Business School. Working Paper 11-038. 2010.
6. Hirsch EM. AMA J Ethics. Virtual Mentor. 2007;9(6):423-7.
Dr. Haji is a licensed clinical psychologist specializing in psychodiagnostic assessment, forensic assessment, dual diagnosis, serious and persistent mental illness, depression, anxiety, personality disorders, and substance abuse treatment. She practices in Miami and has no conflicts of interest.
Sigmund Freud said, “Out of your vulnerabilities will come greatest strength.” What exactly did Dr. Freud mean by this?
Many aspects of mental health treatment include cognitive restructuring, behavioral changes, emotion processing, and setting boundaries. These are all critical aspects of treatment, but what about kindness and compassion?
We often forget that kindness requires us to be vulnerable and take a risk at times. Being kind to others is not always easy, and it is not always an automatic reaction. Vulnerability often involves risk, but the outcomes often outweigh fear.
Dr. Freud was highlighting that being kind, open, and honest will often result in strong character and resilience. In turn, it will help others. Psychology and psychiatry have proved time and time again that empathy, compassion, and kindness have numerous benefits for mental and physical health for both the giver and the receiver.
From a biological perspective, we know that acts of kindness signal the brain to release serotonin and dopamine, known as “feel good transmitters,” and endorphins, which in turn lessen pain, depression, and anxiety. According to Waguih W. Ishak, MD, a psychiatrist affiliated with Cedars-Sinai in Los Angeles,1 in addition to boosting oxytocin and dopamine, being kind can increase serotonin, a neurotransmitter that helps regulate mood. Kindness and compassion have been shown to release oxytocin, known as the “love hormone,” which increases self-esteem, trust, connection, and optimism. Oxytocin also reduces blood pressure and has been dubbed the “cardioprotective” hormone. According to Kelli Harding, MD, MPH, a psychiatrist affiliated with Columbia University in New York,2 kindness can extend the lifespan. Research from Emory University in Atlanta has shown that, when an individual is kind to another, the brain’s reward centers light up – resulting in a “helper’s high.” Thus, kindness is self-reinforcing.3
Kindness leads to a greater sense of connection to others and a lessening in feelings of isolation. Small acts of kindness build up compassion in oneself. Research indicates that kindness doesn’t just positively affect the giver and receiver but can also benefit onlookers. An article in Psychology Today,4 suggests that those who witness acts of kindness are also more likely to “pay it forward,” resulting in a domino effect. Along these same lines, altruistic people, specifically those who engage in charitable donations, expressed higher levels of overall happiness according to a 2010 Harvard Business School survey.5
“You can’t pour from an empty cup” is a trendy quote making its way around social media. Before we can be kind and compassionate to others, we must first be kind and compassionate to ourselves. In today’s world, productivity and pressure-filled environments consume us daily. We often find ourselves skipping meals, forgetting to connect with loved ones, missing breaks, and even neglecting our sleep. It is virtually impossible to care for others when we are depleted ourselves. Sometimes not prioritizing ourselves can result in collateral damage. We may become short-tempered, irritable, moody, and overwhelmed. At this point kindness, compassion, and empathy toward others are likely to be absent. Once we replenish ourselves, by taking time off, indulging in a nice meal, exercising, we are more likely to respond as opposed to react, ask others about themselves, and engage in overall positive interactions throughout our day. Kindness is best fostered by being kind to ourselves to sustain our own well-being and by being kind to others in order to maintain the cycle. For clinicians who have been pushed to respond to various aspects of the COVID-19 pandemic, self-care has never been more important.
COVID-19 has been difficult for everyone, particularly the elderly and vulnerable populations. However, kindness has proved to be an overwhelming response as many businesses and individuals have taken to volunteering time and resources for those in need. Even big corporations have chipped in. For example, Lyft and Uber – in a partnership with the White House – are now offering free rides to vaccine sites, and several local businesses have donated personal protective equipment to hospitals and assisted living facilities.
Kindness and empathy are ever present in the field of mental health, medicine, and substance use treatment. The very act of caring for another involves kindness. In medicine, empathy has been defined as “an emotional experience between an observer and a subject in which the observer, based on visual and auditory cues, identifies and transiently experiences the subject’s emotional state.”6
As mental health professionals, we receive empathy training early on in our schooling – increasingly so over the last decade. Research has indicated that trusting relationships between clinicians and patients result in optimal care. Evidence-based communication styles are being widely implemented. This entails using nonjudgmental language, open-ended questions, and active listening skills, for example. In addition, the mental health professionals have our conscious and unconscious judgments. If empathy training is provided, we can learn to acknowledge our biases and mitigate them. Lastly, empathy training has been proven to assist with destigmatization, increase in treatment seeking, and overall better outcomes.
Substance use treatment, which often focuses on cognition and behavior changing, boundaries, and family dynamics, also requires support and kindness. Although it is not an empirically based “treatment,” Alcoholics Anonymous (AA) has used kindness for decades.
Step 12 of AA’s 12-step program, which was developed by two people with alcohol use disorder in 1935 in Akron, Ohio, is as follows: “Having had a spiritual awakening as the result of these steps, we tried to carry this message to alcoholics, and to practice these principles in all our affairs.”
Once AA members are on solid ground with their sobriety, they are urged to help others in their recovery. This process provides many benefits. When individuals are concerned about someone else, they are less focused on themselves. This helps the individuals in recovery to decrease their rumination and “get out of themselves.” It also allows for the AA member to be kind and helpful to an individual who is suffering, thereby expressing kindness, compassion, and empathy. This act of “paying it forward” produces a domino effect that has withstood the test of time as evidenced by the ever-growing fellowship of Alcoholics Anonymous.
Several small acts of kindness can help us as clinicians and our patients:
1. Practice self-care.
2. Take a half day off from your practice.
3. Give staff a half day off.
4. Call a family member or friend and ask them how they are doing. Then engage in active listening and refrain from giving advice.
5. Donate to a homeless shelter or volunteer your time at a charity.
6. Give a stranger a compliment.
7. Surprise someone with a small gift.
8. Send a loved one a letter instead of a text.
9. Pick up litter.
10. Acknowledge family and friends who gave you extra support during the pandemic.
11. Take baked goods to your office.
12. Help a neighbor with groceries.
13. Leave a generous tip.
14. Play soft music in your office.
In conclusion, kindness, empathy, and compassion are vital concepts that are not just fluffy theories. They have vast mental, physical, and social benefits for us and our patients.
References
1. Cedars-Sinai staff. The Science of Kindness. 2019 Feb 13. Cedars-Sinai blog.
2. Harding K. The Rabbit Effect: Live Longer, Happier, and Healthier with the Groundbreaking Science of Kindness. Atria Books, 2019.
3. Ritvo E. BeKindr. Momosa Publishing, 2017.
4. Svoboda E. “Pay it Forward.” Psychology Today. Last reviewed 2016 Jun 9.
5. Aknin LB et al. “Prosocial spending and well-being: Cross-Cultural Evidence for a Psychological Universal.” Harvard Business School. Working Paper 11-038. 2010.
6. Hirsch EM. AMA J Ethics. Virtual Mentor. 2007;9(6):423-7.
Dr. Haji is a licensed clinical psychologist specializing in psychodiagnostic assessment, forensic assessment, dual diagnosis, serious and persistent mental illness, depression, anxiety, personality disorders, and substance abuse treatment. She practices in Miami and has no conflicts of interest.
Fall prevention advice for patients with Parkinson’s
A 75-year-old man with Parkinson’s disease has had three falls over the past 4 weeks. He has been compliant with his Parkinson’s treatment. Which of the following options would most help decrease his fall risk?
A. Vitamin D supplementation
B. Vitamin B12 supplementation
C. Calcium supplementation
D. Tai chi
There has been recent evidence that vitamin D supplementation is not helpful in preventing falls in most community-dwelling older adults. Bolland and colleagues performed a meta-analysis of 81 randomized, controlled trials and found that vitamin D supplementation does not prevent fractures or falls.1 They found no difference or benefit in high-dose versus low-dose vitamin D supplementation.
The U.S. Preventive Services Task Force recommends against vitamin D supplementation for the purpose of preventing falls in community-dwelling adults over the age of 65.2 The same USPSTF report recommends exercise intervention, as having the strongest evidence for fall prevention in community-dwelling adults age 65 or older who are at risk for falls.
The benefits of tai chi
Tai chi with it’s emphasis on balance, strength training as well as stress reduction is an excellent option for older adults.
Lui and colleagues performed a meta-analyses of five randomized, controlled trials (355 patients) of tai chi in patients with Parkinson disease.3 Tai chi significantly decreased fall rates (odds ratio, 0.47; 95% confidence interval, 0.30-0.74; P = .001) and significantly improved balance and functional mobility (P < .001) in people with Parkinson disease, compared with no training.
Tai chi can also help prevent falls in a more general population of elderly patients. Lomas-Vega and colleagues performed a meta-analysis of 10 high-quality studies that met inclusion criteria evaluating tai chi for fall prevention.4 Fall risk was reduced over short-term follow-up (incident rate ratio, 0.57; 95% CI, 0.46-0.70) and a small protective effect was seen over long-term follow-up (IRR, 0.87; 95% CI, 0.77-0.98).
Pearl: Consider tai chi in your elderly patients with fall risk to increase their balance and reduce risks of falls.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.
References
1. Bolland MJ et al. Lancet Diabetes Endocrinol. 2018;6(11):847.
2. U.S. Preventive Services Task Force. JAMA. 2018;319(16):1696.
3. Liu HH et al. Parkinsons Dis. 2019 Feb 21;2019:9626934
4. Lomas-Vega R et al. J Am Geriatr Soc. 2017;65(9):2037.
A 75-year-old man with Parkinson’s disease has had three falls over the past 4 weeks. He has been compliant with his Parkinson’s treatment. Which of the following options would most help decrease his fall risk?
A. Vitamin D supplementation
B. Vitamin B12 supplementation
C. Calcium supplementation
D. Tai chi
There has been recent evidence that vitamin D supplementation is not helpful in preventing falls in most community-dwelling older adults. Bolland and colleagues performed a meta-analysis of 81 randomized, controlled trials and found that vitamin D supplementation does not prevent fractures or falls.1 They found no difference or benefit in high-dose versus low-dose vitamin D supplementation.
The U.S. Preventive Services Task Force recommends against vitamin D supplementation for the purpose of preventing falls in community-dwelling adults over the age of 65.2 The same USPSTF report recommends exercise intervention, as having the strongest evidence for fall prevention in community-dwelling adults age 65 or older who are at risk for falls.
The benefits of tai chi
Tai chi with it’s emphasis on balance, strength training as well as stress reduction is an excellent option for older adults.
Lui and colleagues performed a meta-analyses of five randomized, controlled trials (355 patients) of tai chi in patients with Parkinson disease.3 Tai chi significantly decreased fall rates (odds ratio, 0.47; 95% confidence interval, 0.30-0.74; P = .001) and significantly improved balance and functional mobility (P < .001) in people with Parkinson disease, compared with no training.
Tai chi can also help prevent falls in a more general population of elderly patients. Lomas-Vega and colleagues performed a meta-analysis of 10 high-quality studies that met inclusion criteria evaluating tai chi for fall prevention.4 Fall risk was reduced over short-term follow-up (incident rate ratio, 0.57; 95% CI, 0.46-0.70) and a small protective effect was seen over long-term follow-up (IRR, 0.87; 95% CI, 0.77-0.98).
Pearl: Consider tai chi in your elderly patients with fall risk to increase their balance and reduce risks of falls.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.
References
1. Bolland MJ et al. Lancet Diabetes Endocrinol. 2018;6(11):847.
2. U.S. Preventive Services Task Force. JAMA. 2018;319(16):1696.
3. Liu HH et al. Parkinsons Dis. 2019 Feb 21;2019:9626934
4. Lomas-Vega R et al. J Am Geriatr Soc. 2017;65(9):2037.
A 75-year-old man with Parkinson’s disease has had three falls over the past 4 weeks. He has been compliant with his Parkinson’s treatment. Which of the following options would most help decrease his fall risk?
A. Vitamin D supplementation
B. Vitamin B12 supplementation
C. Calcium supplementation
D. Tai chi
There has been recent evidence that vitamin D supplementation is not helpful in preventing falls in most community-dwelling older adults. Bolland and colleagues performed a meta-analysis of 81 randomized, controlled trials and found that vitamin D supplementation does not prevent fractures or falls.1 They found no difference or benefit in high-dose versus low-dose vitamin D supplementation.
The U.S. Preventive Services Task Force recommends against vitamin D supplementation for the purpose of preventing falls in community-dwelling adults over the age of 65.2 The same USPSTF report recommends exercise intervention, as having the strongest evidence for fall prevention in community-dwelling adults age 65 or older who are at risk for falls.
The benefits of tai chi
Tai chi with it’s emphasis on balance, strength training as well as stress reduction is an excellent option for older adults.
Lui and colleagues performed a meta-analyses of five randomized, controlled trials (355 patients) of tai chi in patients with Parkinson disease.3 Tai chi significantly decreased fall rates (odds ratio, 0.47; 95% confidence interval, 0.30-0.74; P = .001) and significantly improved balance and functional mobility (P < .001) in people with Parkinson disease, compared with no training.
Tai chi can also help prevent falls in a more general population of elderly patients. Lomas-Vega and colleagues performed a meta-analysis of 10 high-quality studies that met inclusion criteria evaluating tai chi for fall prevention.4 Fall risk was reduced over short-term follow-up (incident rate ratio, 0.57; 95% CI, 0.46-0.70) and a small protective effect was seen over long-term follow-up (IRR, 0.87; 95% CI, 0.77-0.98).
Pearl: Consider tai chi in your elderly patients with fall risk to increase their balance and reduce risks of falls.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.
References
1. Bolland MJ et al. Lancet Diabetes Endocrinol. 2018;6(11):847.
2. U.S. Preventive Services Task Force. JAMA. 2018;319(16):1696.
3. Liu HH et al. Parkinsons Dis. 2019 Feb 21;2019:9626934
4. Lomas-Vega R et al. J Am Geriatr Soc. 2017;65(9):2037.
Botulinum toxin and depression
. But confounding factors, such as medications, injection/acupuncture effect, physician interaction or touch, or other life scenarios, have made it difficult to discern botulinum toxin type A’s true effect on mood or psychiatric diagnosis. Now a systematic review and meta-analysis of randomized controlled trials examining botulinum toxin versus placebo provides evidence that botulinum toxin type A (BTX-A) injections are associated with statistically significant improvement in depressive symptoms.
Qian et al. analyzed all randomized controlled trials that investigated the efficacy and safety of facial BTX-A injections on patients with a diagnosis of major depressive disorder in PubMed and Web of Science from inception to June 17, 2020. A meta-analysis of the changes in depressive symptoms 6 weeks after BTX-A injections compared with placebo were the primary outcome of the report, while the safety of injections were also assessed.
A total of 417 patients from five randomized controlled trials (189 patients who received BTX-A injections and 228 in the placebo group) were deemed eligible. There was a statistically significant improvement in depressive symptoms in the BTX-A injections compared with placebo (Hedges’ g, –0.82; 95% confidence interval, –1.38 to 0.27). BTX-A injections were well tolerated with mild and temporary adverse events (headache, eyelid ptosis, and upper respiratory tract infection) reported in three of the five studies.
Limitations to the analysis include publication bias due to the limited number of studies in the analysis, the difficulty of being able to reliably blind participants because of potential noticeable cosmetic effects of BTX-A treatment, and the heterogeneity of symptom severity associated with major depressive disorder.
The authors referred to the Global Burden of Disease Study, which estimated that approximately 216 million people experienced major depressive disorder in 2015, the latest data available. MDD symptoms of sadness, fatigue, and loss of interest or pleasure, “incur a tremendous burden on health and finances,” they wrote. According to the Department of Health and Human Services, it is estimated that about 60% of people who commit suicide have had a mood disorder (major depression, bipolar disorder, dysthymia). The high rate of suicide associated with severe depression is also a serious public health concern. While further analysis is clearly warranted, cosmetic BTX-A injections may provide an alternative option in the treatment of depression.
Dr. Wesley and Dr. Lily Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. Write to them at dermnews@mdedge.com. They had no relevant disclosures.
. But confounding factors, such as medications, injection/acupuncture effect, physician interaction or touch, or other life scenarios, have made it difficult to discern botulinum toxin type A’s true effect on mood or psychiatric diagnosis. Now a systematic review and meta-analysis of randomized controlled trials examining botulinum toxin versus placebo provides evidence that botulinum toxin type A (BTX-A) injections are associated with statistically significant improvement in depressive symptoms.
Qian et al. analyzed all randomized controlled trials that investigated the efficacy and safety of facial BTX-A injections on patients with a diagnosis of major depressive disorder in PubMed and Web of Science from inception to June 17, 2020. A meta-analysis of the changes in depressive symptoms 6 weeks after BTX-A injections compared with placebo were the primary outcome of the report, while the safety of injections were also assessed.
A total of 417 patients from five randomized controlled trials (189 patients who received BTX-A injections and 228 in the placebo group) were deemed eligible. There was a statistically significant improvement in depressive symptoms in the BTX-A injections compared with placebo (Hedges’ g, –0.82; 95% confidence interval, –1.38 to 0.27). BTX-A injections were well tolerated with mild and temporary adverse events (headache, eyelid ptosis, and upper respiratory tract infection) reported in three of the five studies.
Limitations to the analysis include publication bias due to the limited number of studies in the analysis, the difficulty of being able to reliably blind participants because of potential noticeable cosmetic effects of BTX-A treatment, and the heterogeneity of symptom severity associated with major depressive disorder.
The authors referred to the Global Burden of Disease Study, which estimated that approximately 216 million people experienced major depressive disorder in 2015, the latest data available. MDD symptoms of sadness, fatigue, and loss of interest or pleasure, “incur a tremendous burden on health and finances,” they wrote. According to the Department of Health and Human Services, it is estimated that about 60% of people who commit suicide have had a mood disorder (major depression, bipolar disorder, dysthymia). The high rate of suicide associated with severe depression is also a serious public health concern. While further analysis is clearly warranted, cosmetic BTX-A injections may provide an alternative option in the treatment of depression.
Dr. Wesley and Dr. Lily Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. Write to them at dermnews@mdedge.com. They had no relevant disclosures.
. But confounding factors, such as medications, injection/acupuncture effect, physician interaction or touch, or other life scenarios, have made it difficult to discern botulinum toxin type A’s true effect on mood or psychiatric diagnosis. Now a systematic review and meta-analysis of randomized controlled trials examining botulinum toxin versus placebo provides evidence that botulinum toxin type A (BTX-A) injections are associated with statistically significant improvement in depressive symptoms.
Qian et al. analyzed all randomized controlled trials that investigated the efficacy and safety of facial BTX-A injections on patients with a diagnosis of major depressive disorder in PubMed and Web of Science from inception to June 17, 2020. A meta-analysis of the changes in depressive symptoms 6 weeks after BTX-A injections compared with placebo were the primary outcome of the report, while the safety of injections were also assessed.
A total of 417 patients from five randomized controlled trials (189 patients who received BTX-A injections and 228 in the placebo group) were deemed eligible. There was a statistically significant improvement in depressive symptoms in the BTX-A injections compared with placebo (Hedges’ g, –0.82; 95% confidence interval, –1.38 to 0.27). BTX-A injections were well tolerated with mild and temporary adverse events (headache, eyelid ptosis, and upper respiratory tract infection) reported in three of the five studies.
Limitations to the analysis include publication bias due to the limited number of studies in the analysis, the difficulty of being able to reliably blind participants because of potential noticeable cosmetic effects of BTX-A treatment, and the heterogeneity of symptom severity associated with major depressive disorder.
The authors referred to the Global Burden of Disease Study, which estimated that approximately 216 million people experienced major depressive disorder in 2015, the latest data available. MDD symptoms of sadness, fatigue, and loss of interest or pleasure, “incur a tremendous burden on health and finances,” they wrote. According to the Department of Health and Human Services, it is estimated that about 60% of people who commit suicide have had a mood disorder (major depression, bipolar disorder, dysthymia). The high rate of suicide associated with severe depression is also a serious public health concern. While further analysis is clearly warranted, cosmetic BTX-A injections may provide an alternative option in the treatment of depression.
Dr. Wesley and Dr. Lily Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. Write to them at dermnews@mdedge.com. They had no relevant disclosures.
COVID-19 fallout makes case for promoting the mental health czar
When the Biden administration announced who would serve on its COVID-19 task force, some asked why a mental health expert had not been included. I have a broader question: In light of the magnitude of the pandemic’s fallout, why doesn’t the administration create a mental health post parallel to the surgeon general?
I have been making the case for creation of a high-level mental health post for quite some time. In fact, in the late 1970s, toward the end of then-President Jimmy Carter’s term, I wrote and talked about the need for a special cabinet post of mental health. At the time I realized that, besides chronic mental disorders, the amount of mental distress people experienced from a myriad of life issues leading to anxiety, depression, even posttraumatic stress disorder (although not labeled as such then), needed focused and informed leadership.
Before the pandemic, the World Health Organization reported that depression was the leading cause of disability worldwide. In the prepandemic United States, mental and substance use disorders were the top cause of disability among younger people.
We’ve lost almost 600,000 people to COVID-19, and people have been unable to grieve properly. More than 2 million women have left the labor force to care for children and sick family members. As we continue to learn about the mental health–related devastation wrought by SARS-CoV-2 – particularly long-haul COVID-19 – it’s time to dust off my proposal, update it, and implement it.
Building on a good decision
Back in 2017, President Trump appointed Elinore F. McCance-Katz, MD, PhD, to a new post officially called “assistant secretary for mental health and substance use” and unofficially called the “mental health czar.” This was a groundbreaking step, because Dr. McCance-Katz, a psychiatrist, is known for developing innovative approaches to addressing the opioid crisis in her home state of Rhode Island. She resigned from her post on Jan. 7, 2021, citing her concerns about the Jan. 6 insurrection on the U.S. Capitol.
As of this writing, President Biden has nominated psychologist Miriam Delphin-Rittmon, PhD, who is commissioner of Connecticut Department of Mental Health and Addiction Services, as mental health czar. I’m glad to see that the new administration wants a new czar, but I would prefer to see a more expansive role for a mental health professional at the federal level. The reason is because
Processing the current crisis
Americans managed to recover emotionally from the ravages of death and dying from World War II; we lived through the “atomic age” of mutual destruction, sometimes calling it the age of anxiety. But nothing has come close to the overwhelming devastation that COVID-19 has brought to the world – and to this country.
A recent Government Accountability Office report shows 38% of U.S. adults reported symptoms of anxiety or depression from April 2020 through February 2021. That was up from 11% from January to June 2019, the report said, citing data from the Centers for Disease Control and Prevention. Meanwhile, the report cites data from the Substance Abuse and Mental Health Services Administration showing that opioid deaths were 25%-50% higher during the pandemic than a year earlier.
My sense is that people generally have opened up regarding their emotional problems in a freer manner, thus allowing us to speak about and accept mental health problems as part of our human reality – just as we accept physical disorders and search for treatment and care.
In terms of talk therapy, I still believe that the “thinking” therapies, that is, cognitive therapies that involved getting a new perspective on problems, are most effective in dealing with the myriad of emotional issues people experience as well as those that have arisen because of COVID-19, and the tremendous fear of severe illness and death that the virus can bring. Besides anxiety, depression, and fear, the psychological toll of a fractured lifestyle, coupled with social isolation, will lead many into a variety of PTSD-related conditions. Many of those conditions, including PTSD, might lift when COVID-19 is controlled, but the time frame for resolution is far from clear and will vary, depending on each person. National leadership, as well as therapists, need to be ready to work with the many mental health problems COVID-19 will leave in its wake.
Therapeutically, as we develop our cognitive approaches to the problems this pandemic has brought, whether affecting people with no past psychiatric history or those with a previous or ongoing problems, we are in a unique position ourselves to offer even more support based on our own experiences during the pandemic. Our patients have seen us wear masks and work remotely, and just as we know about their suffering, they know we have been affected as well. These shared experiences with patients can allow us to express even greater empathy and offer even greater support – which I believe enhances the cognitive process and adds more humanism to the therapeutic process.
The therapists I’ve talked with believe that sharing coping skills – even generally sharing anxieties – can be very therapeutic. They compared these exchanges to what is done in support or educational groups.
As a psychiatrist who has been treating patients using cognitive-behavioral therapy – the thinking therapy – for more than 40 years, I agree that sharing our experiences in this worldwide pandemic with those we are helping can be extremely beneficial. Using this approach would not distract from other cognitive work. CBT, after all, is a far cry from dynamic or psychoanalytic talking or listening.
Change is in the air. More and more Americans are getting vaccinated, and the CDC is constantly updating its guidance on COVID-19. That guidance should have a mental health component.
I urge the president to put mental health at the forefront by nominating an expert who could offer mental health solutions on a daily basis. This person should be on equal footing with the surgeon general. Taking this step would help destigmatize mental suffering and despair – and create greater awareness about how to address those conditions.
Dr. London has been a practicing psychiatrist for 4 decades and a newspaper columnist for almost as long. He has a private practice in New York and is author of “Find Freedom Fast: Short-Term Therapy That Works” (New York: Kettlehole Publishing, 2019). Dr. London has no conflicts of interest.
When the Biden administration announced who would serve on its COVID-19 task force, some asked why a mental health expert had not been included. I have a broader question: In light of the magnitude of the pandemic’s fallout, why doesn’t the administration create a mental health post parallel to the surgeon general?
I have been making the case for creation of a high-level mental health post for quite some time. In fact, in the late 1970s, toward the end of then-President Jimmy Carter’s term, I wrote and talked about the need for a special cabinet post of mental health. At the time I realized that, besides chronic mental disorders, the amount of mental distress people experienced from a myriad of life issues leading to anxiety, depression, even posttraumatic stress disorder (although not labeled as such then), needed focused and informed leadership.
Before the pandemic, the World Health Organization reported that depression was the leading cause of disability worldwide. In the prepandemic United States, mental and substance use disorders were the top cause of disability among younger people.
We’ve lost almost 600,000 people to COVID-19, and people have been unable to grieve properly. More than 2 million women have left the labor force to care for children and sick family members. As we continue to learn about the mental health–related devastation wrought by SARS-CoV-2 – particularly long-haul COVID-19 – it’s time to dust off my proposal, update it, and implement it.
Building on a good decision
Back in 2017, President Trump appointed Elinore F. McCance-Katz, MD, PhD, to a new post officially called “assistant secretary for mental health and substance use” and unofficially called the “mental health czar.” This was a groundbreaking step, because Dr. McCance-Katz, a psychiatrist, is known for developing innovative approaches to addressing the opioid crisis in her home state of Rhode Island. She resigned from her post on Jan. 7, 2021, citing her concerns about the Jan. 6 insurrection on the U.S. Capitol.
As of this writing, President Biden has nominated psychologist Miriam Delphin-Rittmon, PhD, who is commissioner of Connecticut Department of Mental Health and Addiction Services, as mental health czar. I’m glad to see that the new administration wants a new czar, but I would prefer to see a more expansive role for a mental health professional at the federal level. The reason is because
Processing the current crisis
Americans managed to recover emotionally from the ravages of death and dying from World War II; we lived through the “atomic age” of mutual destruction, sometimes calling it the age of anxiety. But nothing has come close to the overwhelming devastation that COVID-19 has brought to the world – and to this country.
A recent Government Accountability Office report shows 38% of U.S. adults reported symptoms of anxiety or depression from April 2020 through February 2021. That was up from 11% from January to June 2019, the report said, citing data from the Centers for Disease Control and Prevention. Meanwhile, the report cites data from the Substance Abuse and Mental Health Services Administration showing that opioid deaths were 25%-50% higher during the pandemic than a year earlier.
My sense is that people generally have opened up regarding their emotional problems in a freer manner, thus allowing us to speak about and accept mental health problems as part of our human reality – just as we accept physical disorders and search for treatment and care.
In terms of talk therapy, I still believe that the “thinking” therapies, that is, cognitive therapies that involved getting a new perspective on problems, are most effective in dealing with the myriad of emotional issues people experience as well as those that have arisen because of COVID-19, and the tremendous fear of severe illness and death that the virus can bring. Besides anxiety, depression, and fear, the psychological toll of a fractured lifestyle, coupled with social isolation, will lead many into a variety of PTSD-related conditions. Many of those conditions, including PTSD, might lift when COVID-19 is controlled, but the time frame for resolution is far from clear and will vary, depending on each person. National leadership, as well as therapists, need to be ready to work with the many mental health problems COVID-19 will leave in its wake.
Therapeutically, as we develop our cognitive approaches to the problems this pandemic has brought, whether affecting people with no past psychiatric history or those with a previous or ongoing problems, we are in a unique position ourselves to offer even more support based on our own experiences during the pandemic. Our patients have seen us wear masks and work remotely, and just as we know about their suffering, they know we have been affected as well. These shared experiences with patients can allow us to express even greater empathy and offer even greater support – which I believe enhances the cognitive process and adds more humanism to the therapeutic process.
The therapists I’ve talked with believe that sharing coping skills – even generally sharing anxieties – can be very therapeutic. They compared these exchanges to what is done in support or educational groups.
As a psychiatrist who has been treating patients using cognitive-behavioral therapy – the thinking therapy – for more than 40 years, I agree that sharing our experiences in this worldwide pandemic with those we are helping can be extremely beneficial. Using this approach would not distract from other cognitive work. CBT, after all, is a far cry from dynamic or psychoanalytic talking or listening.
Change is in the air. More and more Americans are getting vaccinated, and the CDC is constantly updating its guidance on COVID-19. That guidance should have a mental health component.
I urge the president to put mental health at the forefront by nominating an expert who could offer mental health solutions on a daily basis. This person should be on equal footing with the surgeon general. Taking this step would help destigmatize mental suffering and despair – and create greater awareness about how to address those conditions.
Dr. London has been a practicing psychiatrist for 4 decades and a newspaper columnist for almost as long. He has a private practice in New York and is author of “Find Freedom Fast: Short-Term Therapy That Works” (New York: Kettlehole Publishing, 2019). Dr. London has no conflicts of interest.
When the Biden administration announced who would serve on its COVID-19 task force, some asked why a mental health expert had not been included. I have a broader question: In light of the magnitude of the pandemic’s fallout, why doesn’t the administration create a mental health post parallel to the surgeon general?
I have been making the case for creation of a high-level mental health post for quite some time. In fact, in the late 1970s, toward the end of then-President Jimmy Carter’s term, I wrote and talked about the need for a special cabinet post of mental health. At the time I realized that, besides chronic mental disorders, the amount of mental distress people experienced from a myriad of life issues leading to anxiety, depression, even posttraumatic stress disorder (although not labeled as such then), needed focused and informed leadership.
Before the pandemic, the World Health Organization reported that depression was the leading cause of disability worldwide. In the prepandemic United States, mental and substance use disorders were the top cause of disability among younger people.
We’ve lost almost 600,000 people to COVID-19, and people have been unable to grieve properly. More than 2 million women have left the labor force to care for children and sick family members. As we continue to learn about the mental health–related devastation wrought by SARS-CoV-2 – particularly long-haul COVID-19 – it’s time to dust off my proposal, update it, and implement it.
Building on a good decision
Back in 2017, President Trump appointed Elinore F. McCance-Katz, MD, PhD, to a new post officially called “assistant secretary for mental health and substance use” and unofficially called the “mental health czar.” This was a groundbreaking step, because Dr. McCance-Katz, a psychiatrist, is known for developing innovative approaches to addressing the opioid crisis in her home state of Rhode Island. She resigned from her post on Jan. 7, 2021, citing her concerns about the Jan. 6 insurrection on the U.S. Capitol.
As of this writing, President Biden has nominated psychologist Miriam Delphin-Rittmon, PhD, who is commissioner of Connecticut Department of Mental Health and Addiction Services, as mental health czar. I’m glad to see that the new administration wants a new czar, but I would prefer to see a more expansive role for a mental health professional at the federal level. The reason is because
Processing the current crisis
Americans managed to recover emotionally from the ravages of death and dying from World War II; we lived through the “atomic age” of mutual destruction, sometimes calling it the age of anxiety. But nothing has come close to the overwhelming devastation that COVID-19 has brought to the world – and to this country.
A recent Government Accountability Office report shows 38% of U.S. adults reported symptoms of anxiety or depression from April 2020 through February 2021. That was up from 11% from January to June 2019, the report said, citing data from the Centers for Disease Control and Prevention. Meanwhile, the report cites data from the Substance Abuse and Mental Health Services Administration showing that opioid deaths were 25%-50% higher during the pandemic than a year earlier.
My sense is that people generally have opened up regarding their emotional problems in a freer manner, thus allowing us to speak about and accept mental health problems as part of our human reality – just as we accept physical disorders and search for treatment and care.
In terms of talk therapy, I still believe that the “thinking” therapies, that is, cognitive therapies that involved getting a new perspective on problems, are most effective in dealing with the myriad of emotional issues people experience as well as those that have arisen because of COVID-19, and the tremendous fear of severe illness and death that the virus can bring. Besides anxiety, depression, and fear, the psychological toll of a fractured lifestyle, coupled with social isolation, will lead many into a variety of PTSD-related conditions. Many of those conditions, including PTSD, might lift when COVID-19 is controlled, but the time frame for resolution is far from clear and will vary, depending on each person. National leadership, as well as therapists, need to be ready to work with the many mental health problems COVID-19 will leave in its wake.
Therapeutically, as we develop our cognitive approaches to the problems this pandemic has brought, whether affecting people with no past psychiatric history or those with a previous or ongoing problems, we are in a unique position ourselves to offer even more support based on our own experiences during the pandemic. Our patients have seen us wear masks and work remotely, and just as we know about their suffering, they know we have been affected as well. These shared experiences with patients can allow us to express even greater empathy and offer even greater support – which I believe enhances the cognitive process and adds more humanism to the therapeutic process.
The therapists I’ve talked with believe that sharing coping skills – even generally sharing anxieties – can be very therapeutic. They compared these exchanges to what is done in support or educational groups.
As a psychiatrist who has been treating patients using cognitive-behavioral therapy – the thinking therapy – for more than 40 years, I agree that sharing our experiences in this worldwide pandemic with those we are helping can be extremely beneficial. Using this approach would not distract from other cognitive work. CBT, after all, is a far cry from dynamic or psychoanalytic talking or listening.
Change is in the air. More and more Americans are getting vaccinated, and the CDC is constantly updating its guidance on COVID-19. That guidance should have a mental health component.
I urge the president to put mental health at the forefront by nominating an expert who could offer mental health solutions on a daily basis. This person should be on equal footing with the surgeon general. Taking this step would help destigmatize mental suffering and despair – and create greater awareness about how to address those conditions.
Dr. London has been a practicing psychiatrist for 4 decades and a newspaper columnist for almost as long. He has a private practice in New York and is author of “Find Freedom Fast: Short-Term Therapy That Works” (New York: Kettlehole Publishing, 2019). Dr. London has no conflicts of interest.