Feature

Therapeutics could be available in the near term to help treat COVID-19 patients, according to President Donald Trump.

Courtesy CDC

During a March 19 press briefing, the president highlighted two drugs that could be put into play in the battle against the virus.

The first product is hydroxychloroquine (Plaquenil), a drug used to treat malaria and severe arthritis, is showing promise as a possible treatment for COVID-19.

“The nice part is it’s been around for a long time, so we know that if things go as planned, it’s not going to kill anybody,” President Trump said. “When you go with a brand-new drug, you don’t know that that’s going to happen,” adding that it has shown “very, very encouraging” results as a potential treatment for COVID-19.

He said this drug will be made available “almost immediately.” During the press conference, Food and Drug Administration Commissioner Stephen M. Hahn, MD, suggested the drug would be made available in the context of a large pragmatic clinical trial, enabling the FDA to collect data on it and make a long-term decision on its viability to treat COVID-19.

Dr. Hahn also pointed to the Gilead drug remdesivir – a drug originally developed to fight Ebola and currently undergoing clinical trials – as another possible candidate for a near-term therapeutic to help treat patients while vaccine development occurs.

Dr. Hahn noted that, while the agency is striving to provide regulatory flexibility, safety is paramount. “Let me make one thing clear: FDA’s responsibility to the American people is to ensure that products are safe and effective and that we are continuing to do that.”

He noted that if these and other experimental drugs show promise, physicians can request them under “compassionate use” provisions.

“We have criteria for that, and very speedy approval for that,” Dr. Hahn said. “The important thing about compassionate use ... this is even beyond ‘right to try.’ [We] get to collect the information about that.”

He noted that the FDA is looking at other drugs that are approved for other indications. The examinations of existing therapies are meant to be a bridge as companies work to develop new therapeutics as well as vaccines.

Dr. Hahn also highlighted a cross-agency effort on convalescent plasma, which uses the plasma from a patient who has recovered from COVID-19 infection to help patients fight the virus. “This is a possible treatment; this is not a proven treatment, “ Dr. Hahn said.

Takeda is working on an immunoglobulin treatment based on its intravenous immunoglobulin product Gammagard Liquid.

Julie Kim, president of plasma-derived therapies at Takeda, said the company should be able to go straight into testing efficacy of this approach, given the known safety profile of the treatment. She made the comments during a March 18 press briefing hosted by Pharmaceutical Research and Manufacturers of America (PhRMA). Ms. Kim did caution that this would not be a mass market kind of treatment, as supply would depend on plasma donations from individuals who have fully recovered from a COVID-19 infection. She estimated that the treatment could be available to a targeted group of high-risk patients in 9-18 months.

PhRMA president and CEO Stephen Ubl said the industry is “literally working around the clock” on four key areas: development of new diagnostics, identification of potential existing treatments to make available through trials and compassionate use, development of novel therapies, and development of a vaccine.

There are more than 80 clinical trials underway on existing treatments that could have approval to treat COVID-19 in a matter of months, he said.

Mikael Dolsten, MD, PhD, chief scientific officer at Pfizer, said that the company is working with Germany-based BioNTech SE to develop an mRNA-based vaccine for COVID-19, with testing expected to begin in Germany, China, and the United States by the end of April. The company also is screening antiviral compounds that were previously in development against other coronavirus diseases.

Clement Lewin, PhD, associate vice president of R&D strategy for vaccines at Sanofi, said the company has partnered with Regeneron to launch a trial of sarilumab (Kevzara), a drug approved to treat moderate to severe rheumatoid arthritis, to help treat COVID-19.

Meanwhile, Lilly Chief Scientific Officer Daniel Skovronsky, MD, PhD, noted that his company is collaborating with AbCellera to develop therapeutics using monoclonal antibodies isolated from one of the first U.S. patients who recovered from COVID-19. He said the goal is to begin testing within the next 4 months.

Separately, World Health Organization Director General Tedros Adhanom Ghebreyesus announced during a March 18 press conference that it is spearheading a large international study examining a number of different treatments in what has been dubbed the SOLIDARITY trial. Argentina, Bahrain, Canada, France, Iran, Norway, South Africa, Spain, Switzerland, and Thailand have signed on to be a part of the trial, with more countries expected to participate.

“I continue to be inspired by the many demonstrations of solidarity from all over the world,” he said. “These and other efforts give me hope that together, we can and will prevail. This virus is presenting us with an unprecedented threat. But it’s also an unprecedented opportunity to come together as one against a common enemy, an enemy against humanity.”

gtwachtman@mdedge.com

Therapeutics could be available in the near term to help treat COVID-19 patients, according to President Donald Trump.

Courtesy CDC

During a March 19 press briefing, the president highlighted two drugs that could be put into play in the battle against the virus.

The first product is hydroxychloroquine (Plaquenil), a drug used to treat malaria and severe arthritis, is showing promise as a possible treatment for COVID-19.

“The nice part is it’s been around for a long time, so we know that if things go as planned, it’s not going to kill anybody,” President Trump said. “When you go with a brand-new drug, you don’t know that that’s going to happen,” adding that it has shown “very, very encouraging” results as a potential treatment for COVID-19.

He said this drug will be made available “almost immediately.” During the press conference, Food and Drug Administration Commissioner Stephen M. Hahn, MD, suggested the drug would be made available in the context of a large pragmatic clinical trial, enabling the FDA to collect data on it and make a long-term decision on its viability to treat COVID-19.

Dr. Hahn also pointed to the Gilead drug remdesivir – a drug originally developed to fight Ebola and currently undergoing clinical trials – as another possible candidate for a near-term therapeutic to help treat patients while vaccine development occurs.

Dr. Hahn noted that, while the agency is striving to provide regulatory flexibility, safety is paramount. “Let me make one thing clear: FDA’s responsibility to the American people is to ensure that products are safe and effective and that we are continuing to do that.”

He noted that if these and other experimental drugs show promise, physicians can request them under “compassionate use” provisions.

“We have criteria for that, and very speedy approval for that,” Dr. Hahn said. “The important thing about compassionate use ... this is even beyond ‘right to try.’ [We] get to collect the information about that.”

He noted that the FDA is looking at other drugs that are approved for other indications. The examinations of existing therapies are meant to be a bridge as companies work to develop new therapeutics as well as vaccines.

Dr. Hahn also highlighted a cross-agency effort on convalescent plasma, which uses the plasma from a patient who has recovered from COVID-19 infection to help patients fight the virus. “This is a possible treatment; this is not a proven treatment, “ Dr. Hahn said.

Takeda is working on an immunoglobulin treatment based on its intravenous immunoglobulin product Gammagard Liquid.

Julie Kim, president of plasma-derived therapies at Takeda, said the company should be able to go straight into testing efficacy of this approach, given the known safety profile of the treatment. She made the comments during a March 18 press briefing hosted by Pharmaceutical Research and Manufacturers of America (PhRMA). Ms. Kim did caution that this would not be a mass market kind of treatment, as supply would depend on plasma donations from individuals who have fully recovered from a COVID-19 infection. She estimated that the treatment could be available to a targeted group of high-risk patients in 9-18 months.

PhRMA president and CEO Stephen Ubl said the industry is “literally working around the clock” on four key areas: development of new diagnostics, identification of potential existing treatments to make available through trials and compassionate use, development of novel therapies, and development of a vaccine.

There are more than 80 clinical trials underway on existing treatments that could have approval to treat COVID-19 in a matter of months, he said.

Mikael Dolsten, MD, PhD, chief scientific officer at Pfizer, said that the company is working with Germany-based BioNTech SE to develop an mRNA-based vaccine for COVID-19, with testing expected to begin in Germany, China, and the United States by the end of April. The company also is screening antiviral compounds that were previously in development against other coronavirus diseases.

Clement Lewin, PhD, associate vice president of R&D strategy for vaccines at Sanofi, said the company has partnered with Regeneron to launch a trial of sarilumab (Kevzara), a drug approved to treat moderate to severe rheumatoid arthritis, to help treat COVID-19.

Meanwhile, Lilly Chief Scientific Officer Daniel Skovronsky, MD, PhD, noted that his company is collaborating with AbCellera to develop therapeutics using monoclonal antibodies isolated from one of the first U.S. patients who recovered from COVID-19. He said the goal is to begin testing within the next 4 months.

Separately, World Health Organization Director General Tedros Adhanom Ghebreyesus announced during a March 18 press conference that it is spearheading a large international study examining a number of different treatments in what has been dubbed the SOLIDARITY trial. Argentina, Bahrain, Canada, France, Iran, Norway, South Africa, Spain, Switzerland, and Thailand have signed on to be a part of the trial, with more countries expected to participate.

“I continue to be inspired by the many demonstrations of solidarity from all over the world,” he said. “These and other efforts give me hope that together, we can and will prevail. This virus is presenting us with an unprecedented threat. But it’s also an unprecedented opportunity to come together as one against a common enemy, an enemy against humanity.”

gtwachtman@mdedge.com

Therapeutics could be available in the near term to help treat COVID-19 patients, according to President Donald Trump.

Courtesy CDC

During a March 19 press briefing, the president highlighted two drugs that could be put into play in the battle against the virus.

The first product is hydroxychloroquine (Plaquenil), a drug used to treat malaria and severe arthritis, is showing promise as a possible treatment for COVID-19.

“The nice part is it’s been around for a long time, so we know that if things go as planned, it’s not going to kill anybody,” President Trump said. “When you go with a brand-new drug, you don’t know that that’s going to happen,” adding that it has shown “very, very encouraging” results as a potential treatment for COVID-19.

He said this drug will be made available “almost immediately.” During the press conference, Food and Drug Administration Commissioner Stephen M. Hahn, MD, suggested the drug would be made available in the context of a large pragmatic clinical trial, enabling the FDA to collect data on it and make a long-term decision on its viability to treat COVID-19.

Dr. Hahn also pointed to the Gilead drug remdesivir – a drug originally developed to fight Ebola and currently undergoing clinical trials – as another possible candidate for a near-term therapeutic to help treat patients while vaccine development occurs.

Dr. Hahn noted that, while the agency is striving to provide regulatory flexibility, safety is paramount. “Let me make one thing clear: FDA’s responsibility to the American people is to ensure that products are safe and effective and that we are continuing to do that.”

He noted that if these and other experimental drugs show promise, physicians can request them under “compassionate use” provisions.

“We have criteria for that, and very speedy approval for that,” Dr. Hahn said. “The important thing about compassionate use ... this is even beyond ‘right to try.’ [We] get to collect the information about that.”

He noted that the FDA is looking at other drugs that are approved for other indications. The examinations of existing therapies are meant to be a bridge as companies work to develop new therapeutics as well as vaccines.

Dr. Hahn also highlighted a cross-agency effort on convalescent plasma, which uses the plasma from a patient who has recovered from COVID-19 infection to help patients fight the virus. “This is a possible treatment; this is not a proven treatment, “ Dr. Hahn said.

Takeda is working on an immunoglobulin treatment based on its intravenous immunoglobulin product Gammagard Liquid.

Julie Kim, president of plasma-derived therapies at Takeda, said the company should be able to go straight into testing efficacy of this approach, given the known safety profile of the treatment. She made the comments during a March 18 press briefing hosted by Pharmaceutical Research and Manufacturers of America (PhRMA). Ms. Kim did caution that this would not be a mass market kind of treatment, as supply would depend on plasma donations from individuals who have fully recovered from a COVID-19 infection. She estimated that the treatment could be available to a targeted group of high-risk patients in 9-18 months.

PhRMA president and CEO Stephen Ubl said the industry is “literally working around the clock” on four key areas: development of new diagnostics, identification of potential existing treatments to make available through trials and compassionate use, development of novel therapies, and development of a vaccine.

There are more than 80 clinical trials underway on existing treatments that could have approval to treat COVID-19 in a matter of months, he said.

Mikael Dolsten, MD, PhD, chief scientific officer at Pfizer, said that the company is working with Germany-based BioNTech SE to develop an mRNA-based vaccine for COVID-19, with testing expected to begin in Germany, China, and the United States by the end of April. The company also is screening antiviral compounds that were previously in development against other coronavirus diseases.

Clement Lewin, PhD, associate vice president of R&D strategy for vaccines at Sanofi, said the company has partnered with Regeneron to launch a trial of sarilumab (Kevzara), a drug approved to treat moderate to severe rheumatoid arthritis, to help treat COVID-19.

Meanwhile, Lilly Chief Scientific Officer Daniel Skovronsky, MD, PhD, noted that his company is collaborating with AbCellera to develop therapeutics using monoclonal antibodies isolated from one of the first U.S. patients who recovered from COVID-19. He said the goal is to begin testing within the next 4 months.

Separately, World Health Organization Director General Tedros Adhanom Ghebreyesus announced during a March 18 press conference that it is spearheading a large international study examining a number of different treatments in what has been dubbed the SOLIDARITY trial. Argentina, Bahrain, Canada, France, Iran, Norway, South Africa, Spain, Switzerland, and Thailand have signed on to be a part of the trial, with more countries expected to participate.

“I continue to be inspired by the many demonstrations of solidarity from all over the world,” he said. “These and other efforts give me hope that together, we can and will prevail. This virus is presenting us with an unprecedented threat. But it’s also an unprecedented opportunity to come together as one against a common enemy, an enemy against humanity.”

gtwachtman@mdedge.com

Sickle cell disease (SCD) is an incurable genetic blood disorder that reduces patients’ lifespan and quality of life. Many patients live into their 40s or 50s. Yet, throughout their lives, patients are plagued by lethargy, unpredictable painful crises, and frequent hospitalizations. For nearly 20 years, clinicians only had one drug to treat SCD. Since 2017, three new drugs have been approved, but their costs and lack of long-term data have spawned questions regarding access and benefit.

“SCD reduces lifespan by 30 years, and that’s very hard to quantify,” says Ifeyinwa Osunkwo, MD, professor of medicine and pediatrics and director of Sickle Cell Disease Enterprise at the Levine Cancer Institute at Atrium Health in Charlotte, N.C. “If you put a dollar amount on what someone would make working for 30 adult years, that would be more reflective of the true cost of treating the disease.”

In 1984, hydroxyurea (Hydrea, Droxia) became the first drug to treat SCD in adults.

Originally developed as a myelosuppressive antineoplastic, hydroxyurea is used to treat resistant chronic myeloid leukemia and certain head and neck cancers. In SCD, it increases levels of hemoglobin and fetal hemoglobin.

Despite its benefit, hydroxyurea has two major drawbacks: It is only effective in two genotypes – HbSS or HbS/Beta⁰thal.

HbSS or HbS/Beta⁰thal genotypes account for 60% of the SCD population, but further studies are required to elucidate hydroxyurea’s effect in other forms of SCD, according to Dr. Osunkwo.

Secondly, hydroxyurea only reduces the frequency of painful episodes by 50% – not enough to ameliorate the pain, said John J. Strouse, MD, associate professor of medicine at Duke University School of Medicine.

Newer therapies offer the potential to enhance the effects of hydroxyurea when used concomitantly. They also give clinicians additional options for patients who either fail hydroxyurea therapy or for whom it is inappropriate.

The amino acid L-glutamine (Endari) became the second drug approved for sickle cell in 2017. Indicated for patients 5 years of age and older, Dr. Osunkwo says many patients were thrilled to have a nonchemotherapeutic option available. However, the medical community received the drug with some skepticism. “The data show Endari is moderately effective at best,” said Dr. Strouse. “Also, the mechanism of action is unclear.”

Additionally, the drug’s powder form and twice-daily dosing regimen make adherence more challenging than swallowing a few hydroxyurea tablets or capsules once a day. In Dr. Osunkwo’s experience, patients who respond best to Endari tend to be those who are naturally motivated individuals who are intentional in their efforts at optimizing their nutrition and self-care.

“It takes a lot to be adherent to Endari,” she said. “You have to work at it.”

On Nov. 15, 2019, the FDA approved crizanlizumab-tmca (Adakveo) for patients 16 years of age and older to decrease the occurrence of vasoocclusive crises.

The drug works by blocking selectin – a protein involved in the painful vascular pathophysiology. Patients receive a loading dose of 5 mg/kg administered via intravenous infusion over 30 minutes at the initiation of therapy, as well as weeks 2 and 4. After that, patients undergo treatment once a month. Nausea, back pain, pyrexia, and arthralgia are the most frequently reported adverse reactions. Clinicians must monitor patients for signs and symptoms of infusion-related reactions.

Ten days later, the FDA approved voxelotor (Oxbryta) for patients ages 12 years and up. The drug inhibits hemoglobin S polymerization and increases hemoglobin levels. Like hydroxyurea, the drug offers the convenience of once-daily dosing, and the tablet can be taken without regard to food. The drug dose requires adjustment for patients with severe hepatic impairment. Headache, fatigue, rash, and gastrointestinal disturbances such as diarrhea, nausea, and abdominal pain fall among the most commonly reported side effects.

Endari, Adakveo, and Oxbryta can all be used as monotherapy. They also provide additional benefits in reducing pain and hospitalizations and improving anemia when used concomitantly with hydroxyurea.

Like so many drugs, these novel therapies are expensive. The cost of these novel treatments has raised some eyebrows.

Annual costs of generic hydroxyurea range in the neighborhood of $1,200. In a 2017 CNBC interview, Endari manufacturer Emmaus stated that it aimed to keep drug costs under $20,000 a year. Annual costs for Adakveo and Oxbryta costs are in the neighborhood of $100,000. Adakveo manufacturer Novartis reportedly priced vials at $2,347. Most patients will require at least three of the maximum four vials per treatment. In a press release, Global Therapeutics stated that Oxbyta would cost $10,417 a month.

However, Dr. Osunkwo says the benefits of these new drugs far exceed the costs from both monetary and quality of life standpoints.

“Sickle cell disease is costly to manage,” she said in an interview. “One hospitalization can cost $10,000.”

Additionally, many SCD patients are publicly insured because of the profound disability and loss of productive work they encounter as a direct consequence of their disease and its complications. Those too sick to complete their high school and postsecondary education find limited employment opportunities.

Those fortunate enough to secure employment face significantly fewer years they can work because their pain, fatigue, frequent hospitalizations, and cumulative organ damage result in permanent disability. Only a smaller number of patients with less severe disease manifestations can secure steady employment and pursue careers that allow them to obtain private insurance.

Even if the newer therapies can help cut some costs, clinicians should be aware that prior authorizations can delay patient access to Adakveo and Oxbyta.

“We wrote the first prescription for Oxbryta in November of 2019, but the prior authorization wasn’t approved until February of 2020,” she said. Adding Adakveo to her institution’s formulary required several months of navigation. Given the arduous process, Dr. Osunkwo anticipates it will take at least year after approval before Adakveo is available for all eligible patients.

The long-term impact of these drugs also remains to be seen, so hydroxyurea will likely remain the drug of choice for many patients, according to Dr. Strouse.

Dr. Osunkwo believes SCD needs more drugs in order to truly optimize outcomes, contain costs, and enhance the patient experience.

Dr. Osunkwo reports consultancy and being on the speaker’s bureau and participating in the advisory board for Novartis, which markets Adakveo, and relationships with a variety of other pharmaceutical companies. She is the editor in chief for Hematology News. Dr. Strouse reports consultancy for Global Therapeutics, which markets Oxbryta.

Sickle cell disease (SCD) is an incurable genetic blood disorder that reduces patients’ lifespan and quality of life. Many patients live into their 40s or 50s. Yet, throughout their lives, patients are plagued by lethargy, unpredictable painful crises, and frequent hospitalizations. For nearly 20 years, clinicians only had one drug to treat SCD. Since 2017, three new drugs have been approved, but their costs and lack of long-term data have spawned questions regarding access and benefit.

“SCD reduces lifespan by 30 years, and that’s very hard to quantify,” says Ifeyinwa Osunkwo, MD, professor of medicine and pediatrics and director of Sickle Cell Disease Enterprise at the Levine Cancer Institute at Atrium Health in Charlotte, N.C. “If you put a dollar amount on what someone would make working for 30 adult years, that would be more reflective of the true cost of treating the disease.”

In 1984, hydroxyurea (Hydrea, Droxia) became the first drug to treat SCD in adults.

Originally developed as a myelosuppressive antineoplastic, hydroxyurea is used to treat resistant chronic myeloid leukemia and certain head and neck cancers. In SCD, it increases levels of hemoglobin and fetal hemoglobin.

Despite its benefit, hydroxyurea has two major drawbacks: It is only effective in two genotypes – HbSS or HbS/Beta⁰thal.

HbSS or HbS/Beta⁰thal genotypes account for 60% of the SCD population, but further studies are required to elucidate hydroxyurea’s effect in other forms of SCD, according to Dr. Osunkwo.

Secondly, hydroxyurea only reduces the frequency of painful episodes by 50% – not enough to ameliorate the pain, said John J. Strouse, MD, associate professor of medicine at Duke University School of Medicine.

Newer therapies offer the potential to enhance the effects of hydroxyurea when used concomitantly. They also give clinicians additional options for patients who either fail hydroxyurea therapy or for whom it is inappropriate.

The amino acid L-glutamine (Endari) became the second drug approved for sickle cell in 2017. Indicated for patients 5 years of age and older, Dr. Osunkwo says many patients were thrilled to have a nonchemotherapeutic option available. However, the medical community received the drug with some skepticism. “The data show Endari is moderately effective at best,” said Dr. Strouse. “Also, the mechanism of action is unclear.”

Additionally, the drug’s powder form and twice-daily dosing regimen make adherence more challenging than swallowing a few hydroxyurea tablets or capsules once a day. In Dr. Osunkwo’s experience, patients who respond best to Endari tend to be those who are naturally motivated individuals who are intentional in their efforts at optimizing their nutrition and self-care.

“It takes a lot to be adherent to Endari,” she said. “You have to work at it.”

On Nov. 15, 2019, the FDA approved crizanlizumab-tmca (Adakveo) for patients 16 years of age and older to decrease the occurrence of vasoocclusive crises.

The drug works by blocking selectin – a protein involved in the painful vascular pathophysiology. Patients receive a loading dose of 5 mg/kg administered via intravenous infusion over 30 minutes at the initiation of therapy, as well as weeks 2 and 4. After that, patients undergo treatment once a month. Nausea, back pain, pyrexia, and arthralgia are the most frequently reported adverse reactions. Clinicians must monitor patients for signs and symptoms of infusion-related reactions.

Ten days later, the FDA approved voxelotor (Oxbryta) for patients ages 12 years and up. The drug inhibits hemoglobin S polymerization and increases hemoglobin levels. Like hydroxyurea, the drug offers the convenience of once-daily dosing, and the tablet can be taken without regard to food. The drug dose requires adjustment for patients with severe hepatic impairment. Headache, fatigue, rash, and gastrointestinal disturbances such as diarrhea, nausea, and abdominal pain fall among the most commonly reported side effects.

Endari, Adakveo, and Oxbryta can all be used as monotherapy. They also provide additional benefits in reducing pain and hospitalizations and improving anemia when used concomitantly with hydroxyurea.

Like so many drugs, these novel therapies are expensive. The cost of these novel treatments has raised some eyebrows.

Annual costs of generic hydroxyurea range in the neighborhood of $1,200. In a 2017 CNBC interview, Endari manufacturer Emmaus stated that it aimed to keep drug costs under $20,000 a year. Annual costs for Adakveo and Oxbryta costs are in the neighborhood of $100,000. Adakveo manufacturer Novartis reportedly priced vials at $2,347. Most patients will require at least three of the maximum four vials per treatment. In a press release, Global Therapeutics stated that Oxbyta would cost $10,417 a month.

However, Dr. Osunkwo says the benefits of these new drugs far exceed the costs from both monetary and quality of life standpoints.

“Sickle cell disease is costly to manage,” she said in an interview. “One hospitalization can cost $10,000.”

Additionally, many SCD patients are publicly insured because of the profound disability and loss of productive work they encounter as a direct consequence of their disease and its complications. Those too sick to complete their high school and postsecondary education find limited employment opportunities.

Those fortunate enough to secure employment face significantly fewer years they can work because their pain, fatigue, frequent hospitalizations, and cumulative organ damage result in permanent disability. Only a smaller number of patients with less severe disease manifestations can secure steady employment and pursue careers that allow them to obtain private insurance.

Even if the newer therapies can help cut some costs, clinicians should be aware that prior authorizations can delay patient access to Adakveo and Oxbyta.

“We wrote the first prescription for Oxbryta in November of 2019, but the prior authorization wasn’t approved until February of 2020,” she said. Adding Adakveo to her institution’s formulary required several months of navigation. Given the arduous process, Dr. Osunkwo anticipates it will take at least year after approval before Adakveo is available for all eligible patients.

The long-term impact of these drugs also remains to be seen, so hydroxyurea will likely remain the drug of choice for many patients, according to Dr. Strouse.

Dr. Osunkwo believes SCD needs more drugs in order to truly optimize outcomes, contain costs, and enhance the patient experience.

Dr. Osunkwo reports consultancy and being on the speaker’s bureau and participating in the advisory board for Novartis, which markets Adakveo, and relationships with a variety of other pharmaceutical companies. She is the editor in chief for Hematology News. Dr. Strouse reports consultancy for Global Therapeutics, which markets Oxbryta.

Sickle cell disease (SCD) is an incurable genetic blood disorder that reduces patients’ lifespan and quality of life. Many patients live into their 40s or 50s. Yet, throughout their lives, patients are plagued by lethargy, unpredictable painful crises, and frequent hospitalizations. For nearly 20 years, clinicians only had one drug to treat SCD. Since 2017, three new drugs have been approved, but their costs and lack of long-term data have spawned questions regarding access and benefit.

“SCD reduces lifespan by 30 years, and that’s very hard to quantify,” says Ifeyinwa Osunkwo, MD, professor of medicine and pediatrics and director of Sickle Cell Disease Enterprise at the Levine Cancer Institute at Atrium Health in Charlotte, N.C. “If you put a dollar amount on what someone would make working for 30 adult years, that would be more reflective of the true cost of treating the disease.”

In 1984, hydroxyurea (Hydrea, Droxia) became the first drug to treat SCD in adults.

Originally developed as a myelosuppressive antineoplastic, hydroxyurea is used to treat resistant chronic myeloid leukemia and certain head and neck cancers. In SCD, it increases levels of hemoglobin and fetal hemoglobin.

Despite its benefit, hydroxyurea has two major drawbacks: It is only effective in two genotypes – HbSS or HbS/Beta⁰thal.

HbSS or HbS/Beta⁰thal genotypes account for 60% of the SCD population, but further studies are required to elucidate hydroxyurea’s effect in other forms of SCD, according to Dr. Osunkwo.

Secondly, hydroxyurea only reduces the frequency of painful episodes by 50% – not enough to ameliorate the pain, said John J. Strouse, MD, associate professor of medicine at Duke University School of Medicine.

Newer therapies offer the potential to enhance the effects of hydroxyurea when used concomitantly. They also give clinicians additional options for patients who either fail hydroxyurea therapy or for whom it is inappropriate.

The amino acid L-glutamine (Endari) became the second drug approved for sickle cell in 2017. Indicated for patients 5 years of age and older, Dr. Osunkwo says many patients were thrilled to have a nonchemotherapeutic option available. However, the medical community received the drug with some skepticism. “The data show Endari is moderately effective at best,” said Dr. Strouse. “Also, the mechanism of action is unclear.”

Additionally, the drug’s powder form and twice-daily dosing regimen make adherence more challenging than swallowing a few hydroxyurea tablets or capsules once a day. In Dr. Osunkwo’s experience, patients who respond best to Endari tend to be those who are naturally motivated individuals who are intentional in their efforts at optimizing their nutrition and self-care.

“It takes a lot to be adherent to Endari,” she said. “You have to work at it.”

On Nov. 15, 2019, the FDA approved crizanlizumab-tmca (Adakveo) for patients 16 years of age and older to decrease the occurrence of vasoocclusive crises.

The drug works by blocking selectin – a protein involved in the painful vascular pathophysiology. Patients receive a loading dose of 5 mg/kg administered via intravenous infusion over 30 minutes at the initiation of therapy, as well as weeks 2 and 4. After that, patients undergo treatment once a month. Nausea, back pain, pyrexia, and arthralgia are the most frequently reported adverse reactions. Clinicians must monitor patients for signs and symptoms of infusion-related reactions.

Ten days later, the FDA approved voxelotor (Oxbryta) for patients ages 12 years and up. The drug inhibits hemoglobin S polymerization and increases hemoglobin levels. Like hydroxyurea, the drug offers the convenience of once-daily dosing, and the tablet can be taken without regard to food. The drug dose requires adjustment for patients with severe hepatic impairment. Headache, fatigue, rash, and gastrointestinal disturbances such as diarrhea, nausea, and abdominal pain fall among the most commonly reported side effects.

Endari, Adakveo, and Oxbryta can all be used as monotherapy. They also provide additional benefits in reducing pain and hospitalizations and improving anemia when used concomitantly with hydroxyurea.

Like so many drugs, these novel therapies are expensive. The cost of these novel treatments has raised some eyebrows.

Annual costs of generic hydroxyurea range in the neighborhood of $1,200. In a 2017 CNBC interview, Endari manufacturer Emmaus stated that it aimed to keep drug costs under $20,000 a year. Annual costs for Adakveo and Oxbryta costs are in the neighborhood of $100,000. Adakveo manufacturer Novartis reportedly priced vials at $2,347. Most patients will require at least three of the maximum four vials per treatment. In a press release, Global Therapeutics stated that Oxbyta would cost $10,417 a month.

However, Dr. Osunkwo says the benefits of these new drugs far exceed the costs from both monetary and quality of life standpoints.

“Sickle cell disease is costly to manage,” she said in an interview. “One hospitalization can cost $10,000.”

Additionally, many SCD patients are publicly insured because of the profound disability and loss of productive work they encounter as a direct consequence of their disease and its complications. Those too sick to complete their high school and postsecondary education find limited employment opportunities.

Those fortunate enough to secure employment face significantly fewer years they can work because their pain, fatigue, frequent hospitalizations, and cumulative organ damage result in permanent disability. Only a smaller number of patients with less severe disease manifestations can secure steady employment and pursue careers that allow them to obtain private insurance.

Even if the newer therapies can help cut some costs, clinicians should be aware that prior authorizations can delay patient access to Adakveo and Oxbyta.

“We wrote the first prescription for Oxbryta in November of 2019, but the prior authorization wasn’t approved until February of 2020,” she said. Adding Adakveo to her institution’s formulary required several months of navigation. Given the arduous process, Dr. Osunkwo anticipates it will take at least year after approval before Adakveo is available for all eligible patients.

The long-term impact of these drugs also remains to be seen, so hydroxyurea will likely remain the drug of choice for many patients, according to Dr. Strouse.

Dr. Osunkwo believes SCD needs more drugs in order to truly optimize outcomes, contain costs, and enhance the patient experience.

Dr. Osunkwo reports consultancy and being on the speaker’s bureau and participating in the advisory board for Novartis, which markets Adakveo, and relationships with a variety of other pharmaceutical companies. She is the editor in chief for Hematology News. Dr. Strouse reports consultancy for Global Therapeutics, which markets Oxbryta.

Rheumatologists the world over are joining forces to create a COVID-19 rheumatology registry designed to help both patients and providers learn from each other regarding management of rheumatologic diseases and risk of infection among patients who are commonly on chronic immunosuppressive medications.

The COVID-19 Global Rheumatology Alliance, a consortium supported by more than 50 major clinical societies and foundations, quickly grew from messages on social media platforms to a multinational group focused on the common goal of helping to “guide rheumatology clinicians in assessing and treating patients with rheumatologic disease and in evaluating the risk of infection in patients on immunosuppression.”

As of this writing, the rheumatology registry is still being assembled, and organizers are currently seeking approvals from various authorities. As of March 17, 2020, the Institutional Review Board (IRB) at the University of California, San Francisco, has determined that the registry is exempt from IRB approval requirements, a finding that should apply elsewhere in the United States, according to the registry website.

When it is fully up and running, clinicians will be able to report to the secure website on any and all cases of patients with rheumatologic disorders who present with COVID-19 of any severity, including patients with mild disease or asymptomatic patients who test positive.

“We are aiming for 5 to 10 minutes to input the data. We don’t want to drag them away from their clinical duties too much, but if clinicians are able to spare a few minutes to put in details about a patient, then that’s going to help build our knowledge and it’s going to help them with other patients,” said Philip Robinson, MBChB, associate professor of medicine at the University of Queensland in Brisbane, Australia, and the chief architect of the registry.

The data will be deindentified, with no protected health care information required or included, and made available to the global rheumatology community, but the registry will not offer clinical advice, Dr. Robinson said in an interview.

“This is observational data, it’s not randomized, but our approach is that some data is better than no data,” he said.

He also cautioned that the data will need careful interpretation, because information about patients with mild symptoms may offer false reassurances about the severity or extent of infection.

“For example, the patients with severe cases may be in the ICU, and can’t tell their doctors that they’re on methotrexate, so you can see how we need to be really careful about the messages from that data and not misinterpret it,” he said.

The COVID-19 rheumatology registry was inspired by a similar effort in the gastroenterology community, the Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE-IBD) registry. Patients with inflammatory bowel disease are often treated with immunosuppressive biologic agents familiar to the rheumatology community, such as infliximab (Remicade and biosimilars) and adalimumab (Humira and biosimilars), and methotrexate.

Rheumatologists the world over are joining forces to create a COVID-19 rheumatology registry designed to help both patients and providers learn from each other regarding management of rheumatologic diseases and risk of infection among patients who are commonly on chronic immunosuppressive medications.

The COVID-19 Global Rheumatology Alliance, a consortium supported by more than 50 major clinical societies and foundations, quickly grew from messages on social media platforms to a multinational group focused on the common goal of helping to “guide rheumatology clinicians in assessing and treating patients with rheumatologic disease and in evaluating the risk of infection in patients on immunosuppression.”

As of this writing, the rheumatology registry is still being assembled, and organizers are currently seeking approvals from various authorities. As of March 17, 2020, the Institutional Review Board (IRB) at the University of California, San Francisco, has determined that the registry is exempt from IRB approval requirements, a finding that should apply elsewhere in the United States, according to the registry website.

When it is fully up and running, clinicians will be able to report to the secure website on any and all cases of patients with rheumatologic disorders who present with COVID-19 of any severity, including patients with mild disease or asymptomatic patients who test positive.

“We are aiming for 5 to 10 minutes to input the data. We don’t want to drag them away from their clinical duties too much, but if clinicians are able to spare a few minutes to put in details about a patient, then that’s going to help build our knowledge and it’s going to help them with other patients,” said Philip Robinson, MBChB, associate professor of medicine at the University of Queensland in Brisbane, Australia, and the chief architect of the registry.

The data will be deindentified, with no protected health care information required or included, and made available to the global rheumatology community, but the registry will not offer clinical advice, Dr. Robinson said in an interview.

“This is observational data, it’s not randomized, but our approach is that some data is better than no data,” he said.

He also cautioned that the data will need careful interpretation, because information about patients with mild symptoms may offer false reassurances about the severity or extent of infection.

“For example, the patients with severe cases may be in the ICU, and can’t tell their doctors that they’re on methotrexate, so you can see how we need to be really careful about the messages from that data and not misinterpret it,” he said.

The COVID-19 rheumatology registry was inspired by a similar effort in the gastroenterology community, the Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE-IBD) registry. Patients with inflammatory bowel disease are often treated with immunosuppressive biologic agents familiar to the rheumatology community, such as infliximab (Remicade and biosimilars) and adalimumab (Humira and biosimilars), and methotrexate.

Rheumatologists the world over are joining forces to create a COVID-19 rheumatology registry designed to help both patients and providers learn from each other regarding management of rheumatologic diseases and risk of infection among patients who are commonly on chronic immunosuppressive medications.

The COVID-19 Global Rheumatology Alliance, a consortium supported by more than 50 major clinical societies and foundations, quickly grew from messages on social media platforms to a multinational group focused on the common goal of helping to “guide rheumatology clinicians in assessing and treating patients with rheumatologic disease and in evaluating the risk of infection in patients on immunosuppression.”

As of this writing, the rheumatology registry is still being assembled, and organizers are currently seeking approvals from various authorities. As of March 17, 2020, the Institutional Review Board (IRB) at the University of California, San Francisco, has determined that the registry is exempt from IRB approval requirements, a finding that should apply elsewhere in the United States, according to the registry website.

When it is fully up and running, clinicians will be able to report to the secure website on any and all cases of patients with rheumatologic disorders who present with COVID-19 of any severity, including patients with mild disease or asymptomatic patients who test positive.

“We are aiming for 5 to 10 minutes to input the data. We don’t want to drag them away from their clinical duties too much, but if clinicians are able to spare a few minutes to put in details about a patient, then that’s going to help build our knowledge and it’s going to help them with other patients,” said Philip Robinson, MBChB, associate professor of medicine at the University of Queensland in Brisbane, Australia, and the chief architect of the registry.

The data will be deindentified, with no protected health care information required or included, and made available to the global rheumatology community, but the registry will not offer clinical advice, Dr. Robinson said in an interview.

“This is observational data, it’s not randomized, but our approach is that some data is better than no data,” he said.

He also cautioned that the data will need careful interpretation, because information about patients with mild symptoms may offer false reassurances about the severity or extent of infection.

“For example, the patients with severe cases may be in the ICU, and can’t tell their doctors that they’re on methotrexate, so you can see how we need to be really careful about the messages from that data and not misinterpret it,” he said.

The COVID-19 rheumatology registry was inspired by a similar effort in the gastroenterology community, the Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE-IBD) registry. Patients with inflammatory bowel disease are often treated with immunosuppressive biologic agents familiar to the rheumatology community, such as infliximab (Remicade and biosimilars) and adalimumab (Humira and biosimilars), and methotrexate.

Newly updated guidance on treating patients with the novel coronavirus (COVID-19) has been published by the World Health Organization.

While it can’t replace clinical judgment or specialist consultation, the new guidance may help strengthen the clinical management of patients when COVID-19 is suspected, according to its authors.

The guidance, adapted from an earlier edition focused on the management of suspected Middle East respiratory syndrome coronavirus (MERS-CoV), covers best practices for triage, infection prevention and control, and optimized supportive care for mild, severe, or critical coronavirus disease 2019 (COVID-19).

“This guidance should serve as a foundation for optimized supportive care to ensure the best possible chance for survival,” the authors wrote in the guidance.

Newly updated guidance on treating patients with the novel coronavirus (COVID-19) has been published by the World Health Organization.

While it can’t replace clinical judgment or specialist consultation, the new guidance may help strengthen the clinical management of patients when COVID-19 is suspected, according to its authors.

The guidance, adapted from an earlier edition focused on the management of suspected Middle East respiratory syndrome coronavirus (MERS-CoV), covers best practices for triage, infection prevention and control, and optimized supportive care for mild, severe, or critical coronavirus disease 2019 (COVID-19).

“This guidance should serve as a foundation for optimized supportive care to ensure the best possible chance for survival,” the authors wrote in the guidance.

Newly updated guidance on treating patients with the novel coronavirus (COVID-19) has been published by the World Health Organization.

While it can’t replace clinical judgment or specialist consultation, the new guidance may help strengthen the clinical management of patients when COVID-19 is suspected, according to its authors.

The guidance, adapted from an earlier edition focused on the management of suspected Middle East respiratory syndrome coronavirus (MERS-CoV), covers best practices for triage, infection prevention and control, and optimized supportive care for mild, severe, or critical coronavirus disease 2019 (COVID-19).

“This guidance should serve as a foundation for optimized supportive care to ensure the best possible chance for survival,” the authors wrote in the guidance.

For much of the past 50 years, many of the drugs used in dermatology have been adopted – and often adapted – from other specialties and used for dermatologic conditions.

“Almost every drug was more or less a hand-me-down” developed first for cancer or other diseases and found later, often serendipitously, to be useful for the skin, said William Eaglstein, MD, thinking back to the 1970s and recalling steroids, tetracyclines, methotrexate, and 5-flourouracil. “The perception always was that skin diseases weren’t serious, that the market was small.”

Much has changed. Knowledge about the pathophysiology of dermatologic diseases has exponentially increased, largely because of basic and translational research by dermatologist investigators, and “more and more companies are recognizing the importance of our diseases and the ability to get a return on investment,” said Dr. Eaglstein, past professor and chair of the departments of dermatology at the University of Miami and the University of Pittsburgh, who worked in industry after his academic career.

Psoriasis was a game changer, he and other dermatologists said in interviews. The tumor necrosis factor (TNF)–alpha blockers were first used for other indications, but their marked follow-on success in psoriasis “offered proof of concept clinically – showing that by targeting immune pathways in the skin we could achieve a clinical effect – and proof of concept commercially” that dermatology drugs are worth pursuing by pharmaceutical companies, said William Ju, MD, a cofounder and president of Advancing Innovation in Dermatology, a nonprofit organization that brings together stakeholders to develop novel dermatologic drugs and products.

This resulted in the approval of subsequent biologics, such as ustekinumab (Stelara) which inhibits the signaling of interleukin (IL)–12/IL-23, for psoriasis as their initial indication. Then, biologics targeting IL-17 followed this dermatology-first approach. “Researchers have continued further dissecting out the immunopathological pathways, and antibody drugs targeting IL-23p19 have been approved for psoriasis as the lead indication,” said Dr. Ju, a dermatologist who has worked in industry.

Seth Orlow, MD, PhD, who chairs the department of dermatology at NYU Langone Health, remembers the 1970s through the 1990s as the “era of topicals” developed for dermatologic conditions – topical antifungals, topical corticosteroids, and topical retinoids. The next decade was characterized by formulation tweaks and few novel treatments for dermatology, said Dr. Orlow, who is also professor of pediatric dermatology and director of the program in cutaneous biology at New York University.

Now, given the succession of psoriasis discoveries in the last decade, “large companies are interested in dermatology,” he said in an interview. “There’s an explosion of interest in atopic dermatitis. … and companies are dipping their toes in the water for alopecia areata and vitiligo. That’s amazing.”

Rare diseases like epidermolysis bullosa, ichthyosis, and basal cell nevus syndrome are getting attention as well, boosted by the Orphan Drug Act of 1983, in addition to increased research on disease pathways and growing appreciation of skin diseases. “There’s a lot under development, from small molecules to biologics to gene-based therapies,” Dr. Orlow commented.


 

The new frontier of atopic dermatitis

The approval in 2017 of dupilumab (Dupixent), a monoclonal antibody that inhibits the signaling of both IL-4 and IL-13) for moderate-severe atopic dermatitis (AD) in adults illustrates the new standing of dermatologic diseases in the field of drug development and commercialization. “Atopic dermatitis had always been the forgotten chronic disease in dermatology. … We’ve had no good treatments,” said Eric Simpson, MD, professor of dermatology at Oregon Health & Science University, Portland. “Dupilumab coming to the forefront [as a dermatology-first indication] has changed the entire perspective of the field. … Everyone is now trying to find the next best drug.”

As with psoriasis, a targeted therapy for AD was made possible by the development in the 1990s of monoclonal antibody technology and the ensuing ability to create biologics that target specific molecules in the body – as well as bedside-to-bench research that homed in on the involvement of particular cytokines.

But there also is a “new understanding of the burden of the disease,” Dr. Simpson observed. In the last 5 years, he said, research funded by the National Eczema Association documented that AD “not only causes inflammation of the skin … but that it affects people at school and in the workplace, that people have multiple mental health comorbidities and skin infections, and that the disease profoundly affects the entire patient in ways that weren’t really recognized or appreciated.”

Having evolved in the footsteps of psoriasis, AD is at a higher starting point in terms of the safety and efficacy of its first biologic, sources said. On the other hand, AD is a much more complex and heterogeneous disease, and researchers are trying to determine which immune pathways and cytokines are most important – and in which populations.

“We’re at the beginning. We’re trying to figure out how to get 80% of patients clear or almost clear [as we can now with psoriasis biologics] rather than almost 40% [as in the dupilumab pivotal trials],” said Dr. Simpson, former cochair of the National Eczema Association’s scientific committee. Public data from ongoing phase 2 and 3 trials of other Th2 cytokine inhibitors suggest that 25%-45% of enrolled patients achieve high levels of clearance, he noted.

Emma Guttman-Yassky, MD, PhD, Sol and Clara Kest Professor and vice-chair for research in the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, said that AD’s heterogeneity involves “many factors, like ethnicity, age … and whether they have an atopic background such as asthma.”

Bruce Jancin/MDedge News

Her research is showing, for instance, that AD in Asian and black patients is different than AD in European-American patients, and that the presence of comorbidities may well have treatment implications. She has also shown that children may have a different phenotype than adults, with greater activation of the Th17 axis that typifies psoriasis.

“For certain patients, we may need to target more than one pathway, or target a different pathway than the Th2 pathway. And treatment may be different in the setting of comorbidities,” said Dr. Guttman-Yassky, who is also director of the laboratory of inflammatory skin diseases at Mount Sinai. “We may think of one treatment – dupilumab, for example – for someone who has asthma and AD. But for patients who don’t have asthma and are Asian, for instance, or for children, we may need additional agents.”

Her research over the years on AD has taught her the importance of human studies over mouse model studies; it was in humans, she noted, that she and other investigators demonstrated “without doubt” that AD is an immune disease and not simply a barrier disease. The Th2 cytokine pathway appears to play the predominant role in AD, though “there still is a strong Th1 component,” she said.

“We’re in a better position to figure this out today [than in the past 20 or even 10 years],” said Dr. Guttman-Yassky, who recalls being told years ago that AD was a “dead end,” that it “would kill [her] career.” Given the evolution of science and the recognition of comorbidities and seriousness of dermatologic diseases, “the stars are aligned to get more [therapies] to these patients.”

Janus kinase (JAK) inhibitors are among these therapies. Three JAK inhibitors are in or have recently completed phase 3 studies for AD; two are currently approved for rheumatoid arthritis, and the other has been designed specifically for AD, Dr. Simpson pointed out. The drugs are oral small molecule drugs that block the JAK signaling pathways for certain proinflammatory cytokines.

“The JAK inhibitors are a real exciting story for dermatology,” he said. “Theoretically, by blocking more cytokines than biologics do, there could be some safety issues – that’s why we’re awaiting big phase 3 study results so we can figure out the risk-benefit balance and guide our patients as to which drug is best.”

Andrew Blauvelt, MD, MBA, president of Oregon Medical Research Center in Portland – a stand-alone dermatology clinical trial center founded in 1998 – likes to envision the evolution of drugs for dermatologic conditions as a funnel, with the most broad-acting drugs at the wide top of the funnel and the most targeted drugs at the bottom tip.

JAK inhibitors, he said, sit near the middle – more targeted and safer than cyclosporine and methotrexate, for instance, but not as targeted as the biologics now available for psoriasis and being developed for AD. “The oral medications that have been developed for psoriasis and those coming for AD are not quite as targeted to the disease,” he noted. “JAK inhibitors have great efficacy – it’s more a question of safety and being able to treat without causing collateral damage.”

Dr. Blauvelt expects the armamentarium of new drugs approved for AD to go from one (dupilumab) to seven within the next 2 years. This will include three new biologics and three new oral JAK inhibitors, he predicts. As the specialty sorts through and integrates these new drugs into practice, dermatologists will increasingly personalize treatment and will face the “nonscientific” challenge of the cost of new therapies and patient access to them, he noted.

In the meantime, said Dr. Simpson, recent drug discoveries have driven more non–pharmaceutical-funded translational research aimed at understanding the underlying biology of AD. The National Institutes of Health, for instance, “is interested in dupilumab and its impact on the skin barrier and skin defense mechanisms,” he said. “We’ll learn a lot more [in coming years].”
 

Spillover to other diseases

JAK inhibitors – some in oral and some in topical form – are showing efficacy in ongoing research for alopecia areata (AA) and vitiligo as well, Dr. Blauvelt said.

“We’re understanding more about the pathophysiology of these diseases, which historically have been tough diseases for dermatologists to treat,” he said. “The successes in alopecia areata and vitiligo are incredibly exciting actually – it’s very exciting to see hair and pigment coming back. And as we learn more, we should be able to develop [additional] drugs that are more disease targeted than the JAK inhibitors.”

Already, some of the biologics used to treat psoriasis have been studied in patients with hidradenitis suppurativa (HS), a disease in which painful lumps and sometimes tunnels form under the skin, with some success; adalimumab (Humira), a TNF-inhibitor, is now FDA approved for the treatment of moderate-severe HS, and studies are ongoing of IL-17 and IL-23 blockers for the disease.

“The pathophysiology [of HS] is very complex; it’s not nearly as straightforward as psoriasis, and there haven’t been any major breakthroughs yet,” Dr. Blauvelt said. “But the drugs seem to be working better than historical alternatives.”

Regarding AA, Dr. Guttman-Yassky, who is participating in a study of dupilumab for AA, recently found in a retrospective cross-sectional study that patients with the condition are more likely to have atopic comorbidities – asthma, allergic rhinitis, and AD, for instance. “The more comorbid conditions, the greater the risk of developing alopecia areata,” she said. “That could point to a potential pathogenic role of the Th2 axis in the disorder [challenging the traditional view of AA as a singularly Th1-centered disease.] The future will tell.”
 

Action on rare skin diseases

Both large and small companies have moved into the orphan drug space, investing in research and pursuing orphan drug indications for dermatologic conditions, because “it’s clear now in the marketplace that companies can develop effective drugs for rare disorders and be quite successful,” Dr. Orlow said.

According to a recent analysis, as a result of incentives for rare disease drug development contained in the Orphan Drug Act, 72 indications have been approved for rare skin disease, skin-related cancers, and hereditary disorders with prominent dermatologic manifestations since the law was passed in 1983 (J. Am. Acad. Dermatol. 2019;81[3]:867-77).

Epidermolysis bullosa (EB) is a good example, he and other sources said, of commercial interests merging with growing knowledge of disease pathogenesis as well as the tools needed to develop new treatments.

Research by dermatology scientists and others over the past 40 years, Dr. Ju explained, shed light on the molecular basis underlying the structure and function of the junction between the epidermis and dermis, including the pivotal role that type VII collagen plays in the normal adhesion of these two layers. Researchers then learned that, in EB, the family of genetic diseases characterized by skin fragility, “dystrophic types are caused by mutations in the gene encoding type VII collagen,” he said.

“Just as the advent of monoclonal antibodies allowed us to start attacking psoriasis and atopic dermatitis in unprecedented ways, the advent of gene therapy allows us to potentially address the fundamental molecular genetic defect of various types of EB,” Dr. Ju said.

While gene therapy is “still in its infancy,” companies have begun using the tools to address EB. One gene therapy in the pipeline – in phase 3 clinical trial testing – involves grafting back into patients with recessive dystrophic EB their skin cells that have been genetically modified to produce a correct (nonmutated) type VII collagen, he said.

Basal cell nevus syndrome, or Gorlin syndrome, a rare disease in which patients develop a multitude of basal cell carcinoma tumors, is another example of a “dermatology first” approach, Dr. Ju said. Research identified a genetic mutation that causes the hedgehog signaling pathway to be inappropriately activated in the disease, and a drug, vismodegib, was developed to inhibit this pathway. The drug was initially approved for patients with metastatic basal cell cancer and types of advanced basal cell cancer, and is now being tested in cancers affecting other organs, he said.

Basal cell cancer “is a huge market, but it was really unrecognized in the past,” Dr. Eaglstein said. “Seeing drugs come to market for basal cell cancer – this wouldn’t have happened [decades ago].”

Dr. Ju has worked in the pharmaceutical industry; all other sources in this story have worked with pharmaceutical manufacturers of treatments that are being developed or have been approved to treat dermatologic diseases mentioned in this story. In addition to Dr. Ju, Dr. Eaglstein and Dr. Orlow are cofounders of the Advancing Innovation in Dermatology group; Dr. Orlow is a member of the program committee for the organization’s dermatology summit conference.

 

For much of the past 50 years, many of the drugs used in dermatology have been adopted – and often adapted – from other specialties and used for dermatologic conditions.

“Almost every drug was more or less a hand-me-down” developed first for cancer or other diseases and found later, often serendipitously, to be useful for the skin, said William Eaglstein, MD, thinking back to the 1970s and recalling steroids, tetracyclines, methotrexate, and 5-flourouracil. “The perception always was that skin diseases weren’t serious, that the market was small.”

Much has changed. Knowledge about the pathophysiology of dermatologic diseases has exponentially increased, largely because of basic and translational research by dermatologist investigators, and “more and more companies are recognizing the importance of our diseases and the ability to get a return on investment,” said Dr. Eaglstein, past professor and chair of the departments of dermatology at the University of Miami and the University of Pittsburgh, who worked in industry after his academic career.

Psoriasis was a game changer, he and other dermatologists said in interviews. The tumor necrosis factor (TNF)–alpha blockers were first used for other indications, but their marked follow-on success in psoriasis “offered proof of concept clinically – showing that by targeting immune pathways in the skin we could achieve a clinical effect – and proof of concept commercially” that dermatology drugs are worth pursuing by pharmaceutical companies, said William Ju, MD, a cofounder and president of Advancing Innovation in Dermatology, a nonprofit organization that brings together stakeholders to develop novel dermatologic drugs and products.

This resulted in the approval of subsequent biologics, such as ustekinumab (Stelara) which inhibits the signaling of interleukin (IL)–12/IL-23, for psoriasis as their initial indication. Then, biologics targeting IL-17 followed this dermatology-first approach. “Researchers have continued further dissecting out the immunopathological pathways, and antibody drugs targeting IL-23p19 have been approved for psoriasis as the lead indication,” said Dr. Ju, a dermatologist who has worked in industry.

Seth Orlow, MD, PhD, who chairs the department of dermatology at NYU Langone Health, remembers the 1970s through the 1990s as the “era of topicals” developed for dermatologic conditions – topical antifungals, topical corticosteroids, and topical retinoids. The next decade was characterized by formulation tweaks and few novel treatments for dermatology, said Dr. Orlow, who is also professor of pediatric dermatology and director of the program in cutaneous biology at New York University.

Now, given the succession of psoriasis discoveries in the last decade, “large companies are interested in dermatology,” he said in an interview. “There’s an explosion of interest in atopic dermatitis. … and companies are dipping their toes in the water for alopecia areata and vitiligo. That’s amazing.”

Rare diseases like epidermolysis bullosa, ichthyosis, and basal cell nevus syndrome are getting attention as well, boosted by the Orphan Drug Act of 1983, in addition to increased research on disease pathways and growing appreciation of skin diseases. “There’s a lot under development, from small molecules to biologics to gene-based therapies,” Dr. Orlow commented.


 

The new frontier of atopic dermatitis

The approval in 2017 of dupilumab (Dupixent), a monoclonal antibody that inhibits the signaling of both IL-4 and IL-13) for moderate-severe atopic dermatitis (AD) in adults illustrates the new standing of dermatologic diseases in the field of drug development and commercialization. “Atopic dermatitis had always been the forgotten chronic disease in dermatology. … We’ve had no good treatments,” said Eric Simpson, MD, professor of dermatology at Oregon Health & Science University, Portland. “Dupilumab coming to the forefront [as a dermatology-first indication] has changed the entire perspective of the field. … Everyone is now trying to find the next best drug.”

As with psoriasis, a targeted therapy for AD was made possible by the development in the 1990s of monoclonal antibody technology and the ensuing ability to create biologics that target specific molecules in the body – as well as bedside-to-bench research that homed in on the involvement of particular cytokines.

But there also is a “new understanding of the burden of the disease,” Dr. Simpson observed. In the last 5 years, he said, research funded by the National Eczema Association documented that AD “not only causes inflammation of the skin … but that it affects people at school and in the workplace, that people have multiple mental health comorbidities and skin infections, and that the disease profoundly affects the entire patient in ways that weren’t really recognized or appreciated.”

Having evolved in the footsteps of psoriasis, AD is at a higher starting point in terms of the safety and efficacy of its first biologic, sources said. On the other hand, AD is a much more complex and heterogeneous disease, and researchers are trying to determine which immune pathways and cytokines are most important – and in which populations.

“We’re at the beginning. We’re trying to figure out how to get 80% of patients clear or almost clear [as we can now with psoriasis biologics] rather than almost 40% [as in the dupilumab pivotal trials],” said Dr. Simpson, former cochair of the National Eczema Association’s scientific committee. Public data from ongoing phase 2 and 3 trials of other Th2 cytokine inhibitors suggest that 25%-45% of enrolled patients achieve high levels of clearance, he noted.

Emma Guttman-Yassky, MD, PhD, Sol and Clara Kest Professor and vice-chair for research in the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, said that AD’s heterogeneity involves “many factors, like ethnicity, age … and whether they have an atopic background such as asthma.”

Bruce Jancin/MDedge News

Her research is showing, for instance, that AD in Asian and black patients is different than AD in European-American patients, and that the presence of comorbidities may well have treatment implications. She has also shown that children may have a different phenotype than adults, with greater activation of the Th17 axis that typifies psoriasis.

“For certain patients, we may need to target more than one pathway, or target a different pathway than the Th2 pathway. And treatment may be different in the setting of comorbidities,” said Dr. Guttman-Yassky, who is also director of the laboratory of inflammatory skin diseases at Mount Sinai. “We may think of one treatment – dupilumab, for example – for someone who has asthma and AD. But for patients who don’t have asthma and are Asian, for instance, or for children, we may need additional agents.”

Her research over the years on AD has taught her the importance of human studies over mouse model studies; it was in humans, she noted, that she and other investigators demonstrated “without doubt” that AD is an immune disease and not simply a barrier disease. The Th2 cytokine pathway appears to play the predominant role in AD, though “there still is a strong Th1 component,” she said.

“We’re in a better position to figure this out today [than in the past 20 or even 10 years],” said Dr. Guttman-Yassky, who recalls being told years ago that AD was a “dead end,” that it “would kill [her] career.” Given the evolution of science and the recognition of comorbidities and seriousness of dermatologic diseases, “the stars are aligned to get more [therapies] to these patients.”

Janus kinase (JAK) inhibitors are among these therapies. Three JAK inhibitors are in or have recently completed phase 3 studies for AD; two are currently approved for rheumatoid arthritis, and the other has been designed specifically for AD, Dr. Simpson pointed out. The drugs are oral small molecule drugs that block the JAK signaling pathways for certain proinflammatory cytokines.

“The JAK inhibitors are a real exciting story for dermatology,” he said. “Theoretically, by blocking more cytokines than biologics do, there could be some safety issues – that’s why we’re awaiting big phase 3 study results so we can figure out the risk-benefit balance and guide our patients as to which drug is best.”

Andrew Blauvelt, MD, MBA, president of Oregon Medical Research Center in Portland – a stand-alone dermatology clinical trial center founded in 1998 – likes to envision the evolution of drugs for dermatologic conditions as a funnel, with the most broad-acting drugs at the wide top of the funnel and the most targeted drugs at the bottom tip.

JAK inhibitors, he said, sit near the middle – more targeted and safer than cyclosporine and methotrexate, for instance, but not as targeted as the biologics now available for psoriasis and being developed for AD. “The oral medications that have been developed for psoriasis and those coming for AD are not quite as targeted to the disease,” he noted. “JAK inhibitors have great efficacy – it’s more a question of safety and being able to treat without causing collateral damage.”

Dr. Blauvelt expects the armamentarium of new drugs approved for AD to go from one (dupilumab) to seven within the next 2 years. This will include three new biologics and three new oral JAK inhibitors, he predicts. As the specialty sorts through and integrates these new drugs into practice, dermatologists will increasingly personalize treatment and will face the “nonscientific” challenge of the cost of new therapies and patient access to them, he noted.

In the meantime, said Dr. Simpson, recent drug discoveries have driven more non–pharmaceutical-funded translational research aimed at understanding the underlying biology of AD. The National Institutes of Health, for instance, “is interested in dupilumab and its impact on the skin barrier and skin defense mechanisms,” he said. “We’ll learn a lot more [in coming years].”
 

Spillover to other diseases

JAK inhibitors – some in oral and some in topical form – are showing efficacy in ongoing research for alopecia areata (AA) and vitiligo as well, Dr. Blauvelt said.

“We’re understanding more about the pathophysiology of these diseases, which historically have been tough diseases for dermatologists to treat,” he said. “The successes in alopecia areata and vitiligo are incredibly exciting actually – it’s very exciting to see hair and pigment coming back. And as we learn more, we should be able to develop [additional] drugs that are more disease targeted than the JAK inhibitors.”

Already, some of the biologics used to treat psoriasis have been studied in patients with hidradenitis suppurativa (HS), a disease in which painful lumps and sometimes tunnels form under the skin, with some success; adalimumab (Humira), a TNF-inhibitor, is now FDA approved for the treatment of moderate-severe HS, and studies are ongoing of IL-17 and IL-23 blockers for the disease.

“The pathophysiology [of HS] is very complex; it’s not nearly as straightforward as psoriasis, and there haven’t been any major breakthroughs yet,” Dr. Blauvelt said. “But the drugs seem to be working better than historical alternatives.”

Regarding AA, Dr. Guttman-Yassky, who is participating in a study of dupilumab for AA, recently found in a retrospective cross-sectional study that patients with the condition are more likely to have atopic comorbidities – asthma, allergic rhinitis, and AD, for instance. “The more comorbid conditions, the greater the risk of developing alopecia areata,” she said. “That could point to a potential pathogenic role of the Th2 axis in the disorder [challenging the traditional view of AA as a singularly Th1-centered disease.] The future will tell.”
 

Action on rare skin diseases

Both large and small companies have moved into the orphan drug space, investing in research and pursuing orphan drug indications for dermatologic conditions, because “it’s clear now in the marketplace that companies can develop effective drugs for rare disorders and be quite successful,” Dr. Orlow said.

According to a recent analysis, as a result of incentives for rare disease drug development contained in the Orphan Drug Act, 72 indications have been approved for rare skin disease, skin-related cancers, and hereditary disorders with prominent dermatologic manifestations since the law was passed in 1983 (J. Am. Acad. Dermatol. 2019;81[3]:867-77).

Epidermolysis bullosa (EB) is a good example, he and other sources said, of commercial interests merging with growing knowledge of disease pathogenesis as well as the tools needed to develop new treatments.

Research by dermatology scientists and others over the past 40 years, Dr. Ju explained, shed light on the molecular basis underlying the structure and function of the junction between the epidermis and dermis, including the pivotal role that type VII collagen plays in the normal adhesion of these two layers. Researchers then learned that, in EB, the family of genetic diseases characterized by skin fragility, “dystrophic types are caused by mutations in the gene encoding type VII collagen,” he said.

“Just as the advent of monoclonal antibodies allowed us to start attacking psoriasis and atopic dermatitis in unprecedented ways, the advent of gene therapy allows us to potentially address the fundamental molecular genetic defect of various types of EB,” Dr. Ju said.

While gene therapy is “still in its infancy,” companies have begun using the tools to address EB. One gene therapy in the pipeline – in phase 3 clinical trial testing – involves grafting back into patients with recessive dystrophic EB their skin cells that have been genetically modified to produce a correct (nonmutated) type VII collagen, he said.

Basal cell nevus syndrome, or Gorlin syndrome, a rare disease in which patients develop a multitude of basal cell carcinoma tumors, is another example of a “dermatology first” approach, Dr. Ju said. Research identified a genetic mutation that causes the hedgehog signaling pathway to be inappropriately activated in the disease, and a drug, vismodegib, was developed to inhibit this pathway. The drug was initially approved for patients with metastatic basal cell cancer and types of advanced basal cell cancer, and is now being tested in cancers affecting other organs, he said.

Basal cell cancer “is a huge market, but it was really unrecognized in the past,” Dr. Eaglstein said. “Seeing drugs come to market for basal cell cancer – this wouldn’t have happened [decades ago].”

Dr. Ju has worked in the pharmaceutical industry; all other sources in this story have worked with pharmaceutical manufacturers of treatments that are being developed or have been approved to treat dermatologic diseases mentioned in this story. In addition to Dr. Ju, Dr. Eaglstein and Dr. Orlow are cofounders of the Advancing Innovation in Dermatology group; Dr. Orlow is a member of the program committee for the organization’s dermatology summit conference.

 

For much of the past 50 years, many of the drugs used in dermatology have been adopted – and often adapted – from other specialties and used for dermatologic conditions.

“Almost every drug was more or less a hand-me-down” developed first for cancer or other diseases and found later, often serendipitously, to be useful for the skin, said William Eaglstein, MD, thinking back to the 1970s and recalling steroids, tetracyclines, methotrexate, and 5-flourouracil. “The perception always was that skin diseases weren’t serious, that the market was small.”

Much has changed. Knowledge about the pathophysiology of dermatologic diseases has exponentially increased, largely because of basic and translational research by dermatologist investigators, and “more and more companies are recognizing the importance of our diseases and the ability to get a return on investment,” said Dr. Eaglstein, past professor and chair of the departments of dermatology at the University of Miami and the University of Pittsburgh, who worked in industry after his academic career.

Psoriasis was a game changer, he and other dermatologists said in interviews. The tumor necrosis factor (TNF)–alpha blockers were first used for other indications, but their marked follow-on success in psoriasis “offered proof of concept clinically – showing that by targeting immune pathways in the skin we could achieve a clinical effect – and proof of concept commercially” that dermatology drugs are worth pursuing by pharmaceutical companies, said William Ju, MD, a cofounder and president of Advancing Innovation in Dermatology, a nonprofit organization that brings together stakeholders to develop novel dermatologic drugs and products.

This resulted in the approval of subsequent biologics, such as ustekinumab (Stelara) which inhibits the signaling of interleukin (IL)–12/IL-23, for psoriasis as their initial indication. Then, biologics targeting IL-17 followed this dermatology-first approach. “Researchers have continued further dissecting out the immunopathological pathways, and antibody drugs targeting IL-23p19 have been approved for psoriasis as the lead indication,” said Dr. Ju, a dermatologist who has worked in industry.

Seth Orlow, MD, PhD, who chairs the department of dermatology at NYU Langone Health, remembers the 1970s through the 1990s as the “era of topicals” developed for dermatologic conditions – topical antifungals, topical corticosteroids, and topical retinoids. The next decade was characterized by formulation tweaks and few novel treatments for dermatology, said Dr. Orlow, who is also professor of pediatric dermatology and director of the program in cutaneous biology at New York University.

Now, given the succession of psoriasis discoveries in the last decade, “large companies are interested in dermatology,” he said in an interview. “There’s an explosion of interest in atopic dermatitis. … and companies are dipping their toes in the water for alopecia areata and vitiligo. That’s amazing.”

Rare diseases like epidermolysis bullosa, ichthyosis, and basal cell nevus syndrome are getting attention as well, boosted by the Orphan Drug Act of 1983, in addition to increased research on disease pathways and growing appreciation of skin diseases. “There’s a lot under development, from small molecules to biologics to gene-based therapies,” Dr. Orlow commented.


 

The new frontier of atopic dermatitis

The approval in 2017 of dupilumab (Dupixent), a monoclonal antibody that inhibits the signaling of both IL-4 and IL-13) for moderate-severe atopic dermatitis (AD) in adults illustrates the new standing of dermatologic diseases in the field of drug development and commercialization. “Atopic dermatitis had always been the forgotten chronic disease in dermatology. … We’ve had no good treatments,” said Eric Simpson, MD, professor of dermatology at Oregon Health & Science University, Portland. “Dupilumab coming to the forefront [as a dermatology-first indication] has changed the entire perspective of the field. … Everyone is now trying to find the next best drug.”

As with psoriasis, a targeted therapy for AD was made possible by the development in the 1990s of monoclonal antibody technology and the ensuing ability to create biologics that target specific molecules in the body – as well as bedside-to-bench research that homed in on the involvement of particular cytokines.

But there also is a “new understanding of the burden of the disease,” Dr. Simpson observed. In the last 5 years, he said, research funded by the National Eczema Association documented that AD “not only causes inflammation of the skin … but that it affects people at school and in the workplace, that people have multiple mental health comorbidities and skin infections, and that the disease profoundly affects the entire patient in ways that weren’t really recognized or appreciated.”

Having evolved in the footsteps of psoriasis, AD is at a higher starting point in terms of the safety and efficacy of its first biologic, sources said. On the other hand, AD is a much more complex and heterogeneous disease, and researchers are trying to determine which immune pathways and cytokines are most important – and in which populations.

“We’re at the beginning. We’re trying to figure out how to get 80% of patients clear or almost clear [as we can now with psoriasis biologics] rather than almost 40% [as in the dupilumab pivotal trials],” said Dr. Simpson, former cochair of the National Eczema Association’s scientific committee. Public data from ongoing phase 2 and 3 trials of other Th2 cytokine inhibitors suggest that 25%-45% of enrolled patients achieve high levels of clearance, he noted.

Emma Guttman-Yassky, MD, PhD, Sol and Clara Kest Professor and vice-chair for research in the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, said that AD’s heterogeneity involves “many factors, like ethnicity, age … and whether they have an atopic background such as asthma.”

Bruce Jancin/MDedge News

Her research is showing, for instance, that AD in Asian and black patients is different than AD in European-American patients, and that the presence of comorbidities may well have treatment implications. She has also shown that children may have a different phenotype than adults, with greater activation of the Th17 axis that typifies psoriasis.

“For certain patients, we may need to target more than one pathway, or target a different pathway than the Th2 pathway. And treatment may be different in the setting of comorbidities,” said Dr. Guttman-Yassky, who is also director of the laboratory of inflammatory skin diseases at Mount Sinai. “We may think of one treatment – dupilumab, for example – for someone who has asthma and AD. But for patients who don’t have asthma and are Asian, for instance, or for children, we may need additional agents.”

Her research over the years on AD has taught her the importance of human studies over mouse model studies; it was in humans, she noted, that she and other investigators demonstrated “without doubt” that AD is an immune disease and not simply a barrier disease. The Th2 cytokine pathway appears to play the predominant role in AD, though “there still is a strong Th1 component,” she said.

“We’re in a better position to figure this out today [than in the past 20 or even 10 years],” said Dr. Guttman-Yassky, who recalls being told years ago that AD was a “dead end,” that it “would kill [her] career.” Given the evolution of science and the recognition of comorbidities and seriousness of dermatologic diseases, “the stars are aligned to get more [therapies] to these patients.”

Janus kinase (JAK) inhibitors are among these therapies. Three JAK inhibitors are in or have recently completed phase 3 studies for AD; two are currently approved for rheumatoid arthritis, and the other has been designed specifically for AD, Dr. Simpson pointed out. The drugs are oral small molecule drugs that block the JAK signaling pathways for certain proinflammatory cytokines.

“The JAK inhibitors are a real exciting story for dermatology,” he said. “Theoretically, by blocking more cytokines than biologics do, there could be some safety issues – that’s why we’re awaiting big phase 3 study results so we can figure out the risk-benefit balance and guide our patients as to which drug is best.”

Andrew Blauvelt, MD, MBA, president of Oregon Medical Research Center in Portland – a stand-alone dermatology clinical trial center founded in 1998 – likes to envision the evolution of drugs for dermatologic conditions as a funnel, with the most broad-acting drugs at the wide top of the funnel and the most targeted drugs at the bottom tip.

JAK inhibitors, he said, sit near the middle – more targeted and safer than cyclosporine and methotrexate, for instance, but not as targeted as the biologics now available for psoriasis and being developed for AD. “The oral medications that have been developed for psoriasis and those coming for AD are not quite as targeted to the disease,” he noted. “JAK inhibitors have great efficacy – it’s more a question of safety and being able to treat without causing collateral damage.”

Dr. Blauvelt expects the armamentarium of new drugs approved for AD to go from one (dupilumab) to seven within the next 2 years. This will include three new biologics and three new oral JAK inhibitors, he predicts. As the specialty sorts through and integrates these new drugs into practice, dermatologists will increasingly personalize treatment and will face the “nonscientific” challenge of the cost of new therapies and patient access to them, he noted.

In the meantime, said Dr. Simpson, recent drug discoveries have driven more non–pharmaceutical-funded translational research aimed at understanding the underlying biology of AD. The National Institutes of Health, for instance, “is interested in dupilumab and its impact on the skin barrier and skin defense mechanisms,” he said. “We’ll learn a lot more [in coming years].”
 

Spillover to other diseases

JAK inhibitors – some in oral and some in topical form – are showing efficacy in ongoing research for alopecia areata (AA) and vitiligo as well, Dr. Blauvelt said.

“We’re understanding more about the pathophysiology of these diseases, which historically have been tough diseases for dermatologists to treat,” he said. “The successes in alopecia areata and vitiligo are incredibly exciting actually – it’s very exciting to see hair and pigment coming back. And as we learn more, we should be able to develop [additional] drugs that are more disease targeted than the JAK inhibitors.”

Already, some of the biologics used to treat psoriasis have been studied in patients with hidradenitis suppurativa (HS), a disease in which painful lumps and sometimes tunnels form under the skin, with some success; adalimumab (Humira), a TNF-inhibitor, is now FDA approved for the treatment of moderate-severe HS, and studies are ongoing of IL-17 and IL-23 blockers for the disease.

“The pathophysiology [of HS] is very complex; it’s not nearly as straightforward as psoriasis, and there haven’t been any major breakthroughs yet,” Dr. Blauvelt said. “But the drugs seem to be working better than historical alternatives.”

Regarding AA, Dr. Guttman-Yassky, who is participating in a study of dupilumab for AA, recently found in a retrospective cross-sectional study that patients with the condition are more likely to have atopic comorbidities – asthma, allergic rhinitis, and AD, for instance. “The more comorbid conditions, the greater the risk of developing alopecia areata,” she said. “That could point to a potential pathogenic role of the Th2 axis in the disorder [challenging the traditional view of AA as a singularly Th1-centered disease.] The future will tell.”
 

Action on rare skin diseases

Both large and small companies have moved into the orphan drug space, investing in research and pursuing orphan drug indications for dermatologic conditions, because “it’s clear now in the marketplace that companies can develop effective drugs for rare disorders and be quite successful,” Dr. Orlow said.

According to a recent analysis, as a result of incentives for rare disease drug development contained in the Orphan Drug Act, 72 indications have been approved for rare skin disease, skin-related cancers, and hereditary disorders with prominent dermatologic manifestations since the law was passed in 1983 (J. Am. Acad. Dermatol. 2019;81[3]:867-77).

Epidermolysis bullosa (EB) is a good example, he and other sources said, of commercial interests merging with growing knowledge of disease pathogenesis as well as the tools needed to develop new treatments.

Research by dermatology scientists and others over the past 40 years, Dr. Ju explained, shed light on the molecular basis underlying the structure and function of the junction between the epidermis and dermis, including the pivotal role that type VII collagen plays in the normal adhesion of these two layers. Researchers then learned that, in EB, the family of genetic diseases characterized by skin fragility, “dystrophic types are caused by mutations in the gene encoding type VII collagen,” he said.

“Just as the advent of monoclonal antibodies allowed us to start attacking psoriasis and atopic dermatitis in unprecedented ways, the advent of gene therapy allows us to potentially address the fundamental molecular genetic defect of various types of EB,” Dr. Ju said.

While gene therapy is “still in its infancy,” companies have begun using the tools to address EB. One gene therapy in the pipeline – in phase 3 clinical trial testing – involves grafting back into patients with recessive dystrophic EB their skin cells that have been genetically modified to produce a correct (nonmutated) type VII collagen, he said.

Basal cell nevus syndrome, or Gorlin syndrome, a rare disease in which patients develop a multitude of basal cell carcinoma tumors, is another example of a “dermatology first” approach, Dr. Ju said. Research identified a genetic mutation that causes the hedgehog signaling pathway to be inappropriately activated in the disease, and a drug, vismodegib, was developed to inhibit this pathway. The drug was initially approved for patients with metastatic basal cell cancer and types of advanced basal cell cancer, and is now being tested in cancers affecting other organs, he said.

Basal cell cancer “is a huge market, but it was really unrecognized in the past,” Dr. Eaglstein said. “Seeing drugs come to market for basal cell cancer – this wouldn’t have happened [decades ago].”

Dr. Ju has worked in the pharmaceutical industry; all other sources in this story have worked with pharmaceutical manufacturers of treatments that are being developed or have been approved to treat dermatologic diseases mentioned in this story. In addition to Dr. Ju, Dr. Eaglstein and Dr. Orlow are cofounders of the Advancing Innovation in Dermatology group; Dr. Orlow is a member of the program committee for the organization’s dermatology summit conference.

 

In a JAMA Live Stream interview, Anthony S. Fauci, MD, a key member of the White House Coronavirus Task Force, urged resolve, rather than panic, as the coronavirus pandemic takes hold in the United States.

Dr. Fauci got into the details of what is known, what is unknown, what is being done in laboratories, and what clinical elements are still not understood about this disease.

The next several weeks, he said, are likely to tell the tale of whether our health care system is up to the challenge of care for the most ill among those who will be affected by COVID-19.

“It shouldn’t panic or frighten us, but we have to know we’re dealing with a very serious problem that we have to address, and we have to deal with it in a very bold way,” said Dr. Fauci, director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.

Speaking in an interview with JAMA Editor in Chief Howard Bauchner, MD, Dr. Fauci said the situation favors action over fear. “Let’s apply that energy to doing the things that we know can mitigate this.”

He added that he heard the message loud and clear from health care leaders in Italy and France during a World Health Organization coronavirus call earlier in the day. Officials in those countries, he said, were “almost pleading with the rest of the world to please take this very seriously, because it happens all of a sudden – very abruptly. ... The best time to mitigate is before that happens, because if you wait until after it happens you’re playing catch-up.”

Dr. Bauchner, noting that strict social distancing has been underway in many parts of the United States for several days, posited that, by early April, “We’ll really have a sense if we can manage in terms of serious illness.” Seattle, New York, Boston, and the San Francisco Bay Area may experience demand that outstrips ICU capacity at that point, but the rest of the country, he said, “is doing relatively well.”
 

Stress test on the health care system

Dr. Fauci agreed with this statement and added: “We’re going to know – for better or worse – whether we have enough of what it takes to be able to practice the kind of medicine that we optimally would want to practice.

In the matter of a week or 2 ... I think we’ll get a feel for whether or not we really have enough of the supplies that it takes.”

The well-publicized regional shortages in personal protective equipment (PPE) are forcing tough choices in some areas. As expedited – and even drive-through – testing begins, some of the demand for testing-related PPE may abate, especially if protocols include self-administration of nasal swabs, he noted.

Dr. Fauci added that the strategic national stockpile of medical supplies and equipment has not yet been tapped, “but you need to backfill that as quickly as you can once you start drawing from the strategic national stockpile.”
 

Returning to work after COVID-19 infection

Regarding the thorny question of when health care workers should be permitted to return to work after coronavirus infection, “it’s an evolving story,” said Dr. Fauci. Current guidance advises that health care providers stay away from work until two negative tests after resolution of fever and improvement of respiratory symptoms, or 3 fever-free days.

“We are approaching a point where you’re going to get enough people who are getting infected that we aren’t going to be able to do that,” he said. Depending on the stress to the health care system in a given locality, he said that facilities are going to have to “decide with good judgment” when health care workers go back on the job after coronavirus infection.

Asked how soon an individual would reliably test positive for COVID-19 after exposure, Dr. Fauci said, “We don’t know the answer to that. ... We can surmise it ...” He noted that it’s a median of about 5 days with a range of 2 to 14 days, before an infected individual becomes symptomatic. “I can say it’s not going to happen immediately,” he added, noting that he wouldn’t expect to see a positive test until about 2 days after exposure at the earliest. “When you get to the point where you are symptomatic, you’re almost certainly going to be positive then. ... This is just an extrapolation,” rather than conclusions drawn from solid data, he emphasized.
 

Higher risk reported in cardiac patients

Dr. Bauchner, who was relaying questions sent in from physicians during the live-streamed interview, asked about a newly issued joint statement from the American Heart Association, American College of Cardiology, and the Heart Failure Society of America, which on March 17 affirmed that individuals on ACE inhibitors and angiotensin receptor blockers (ARBs) continue that therapy if they should become ill with COVID-19. The European Society of Cardiology issued a similar recommendation a few days prior.

Despite these societies’ statements, Dr. Fauci pointed to population-level data in Italy as suggesting that the case isn’t yet closed. “We really need to get data, and we need to get data fast. There’s a mechanistic rationale for the concern. It’s there, and it’s firm,” he said. The theoretical concern is that ACE inhibitors can upregulate expression of the ACE-2 protein on cell membranes, which is the entry point for SARS-Cov-2 to enter cells.

He added that he remains concerned about the number of coronavirus fatalities of patients in Italy who had hypertension as their only, or primary, underlying health problem.“That to me was a bit of a red flag,” he said. “Patients with hypertension almost certainly had a physician, and the physician almost certainly treated that person with medication. Why should someone who has hypertension that was well controlled have a much greater chance of dying?” he asked, noting that “I look at a person with well-controlled hypertension as a relatively healthy person. I don’t know what the answer is, but somebody has to look very carefully,” ideally by means of a natural history study that identifies medications used by those who died from coronavirus.
 

Potential therapies

Regarding potential therapies for COVID-19, Dr. Fauci acknowledged the social media buzz and flurry of medical letters and case reports about the use of hydroxychloroquine (Plaquenil) to treat active infection. He said that he and other researchers are “in active discussion” about how best to study the efficacy and safety of hydroxychloroquine, but he also acknowledged that many treating clinicians will use hydroxychloroquine empirically in the absence of other treatments with proven efficacy.

Clinical trials underway in China for antiviral medication are facing some enrollment challenges currently “because people want to get the drug,” said Dr. Fauci. “They don’t want to be in the trial; they just want to get the drug.” Though each of two trials has targeted approximately 500 participants as the number needed for sufficient statistical power, Dr. Fauci urged Chinese data safety monitoring boards to “take a close look” at the data already accrued for the several hundred patients who have already enrolled for the studies “to see if there’s any hint of efficacy.”

koakes@mdedge.com

In a JAMA Live Stream interview, Anthony S. Fauci, MD, a key member of the White House Coronavirus Task Force, urged resolve, rather than panic, as the coronavirus pandemic takes hold in the United States.

Dr. Fauci got into the details of what is known, what is unknown, what is being done in laboratories, and what clinical elements are still not understood about this disease.

The next several weeks, he said, are likely to tell the tale of whether our health care system is up to the challenge of care for the most ill among those who will be affected by COVID-19.

“It shouldn’t panic or frighten us, but we have to know we’re dealing with a very serious problem that we have to address, and we have to deal with it in a very bold way,” said Dr. Fauci, director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.

Speaking in an interview with JAMA Editor in Chief Howard Bauchner, MD, Dr. Fauci said the situation favors action over fear. “Let’s apply that energy to doing the things that we know can mitigate this.”

He added that he heard the message loud and clear from health care leaders in Italy and France during a World Health Organization coronavirus call earlier in the day. Officials in those countries, he said, were “almost pleading with the rest of the world to please take this very seriously, because it happens all of a sudden – very abruptly. ... The best time to mitigate is before that happens, because if you wait until after it happens you’re playing catch-up.”

Dr. Bauchner, noting that strict social distancing has been underway in many parts of the United States for several days, posited that, by early April, “We’ll really have a sense if we can manage in terms of serious illness.” Seattle, New York, Boston, and the San Francisco Bay Area may experience demand that outstrips ICU capacity at that point, but the rest of the country, he said, “is doing relatively well.”
 

Stress test on the health care system

Dr. Fauci agreed with this statement and added: “We’re going to know – for better or worse – whether we have enough of what it takes to be able to practice the kind of medicine that we optimally would want to practice.

In the matter of a week or 2 ... I think we’ll get a feel for whether or not we really have enough of the supplies that it takes.”

The well-publicized regional shortages in personal protective equipment (PPE) are forcing tough choices in some areas. As expedited – and even drive-through – testing begins, some of the demand for testing-related PPE may abate, especially if protocols include self-administration of nasal swabs, he noted.

Dr. Fauci added that the strategic national stockpile of medical supplies and equipment has not yet been tapped, “but you need to backfill that as quickly as you can once you start drawing from the strategic national stockpile.”
 

Returning to work after COVID-19 infection

Regarding the thorny question of when health care workers should be permitted to return to work after coronavirus infection, “it’s an evolving story,” said Dr. Fauci. Current guidance advises that health care providers stay away from work until two negative tests after resolution of fever and improvement of respiratory symptoms, or 3 fever-free days.

“We are approaching a point where you’re going to get enough people who are getting infected that we aren’t going to be able to do that,” he said. Depending on the stress to the health care system in a given locality, he said that facilities are going to have to “decide with good judgment” when health care workers go back on the job after coronavirus infection.

Asked how soon an individual would reliably test positive for COVID-19 after exposure, Dr. Fauci said, “We don’t know the answer to that. ... We can surmise it ...” He noted that it’s a median of about 5 days with a range of 2 to 14 days, before an infected individual becomes symptomatic. “I can say it’s not going to happen immediately,” he added, noting that he wouldn’t expect to see a positive test until about 2 days after exposure at the earliest. “When you get to the point where you are symptomatic, you’re almost certainly going to be positive then. ... This is just an extrapolation,” rather than conclusions drawn from solid data, he emphasized.
 

Higher risk reported in cardiac patients

Dr. Bauchner, who was relaying questions sent in from physicians during the live-streamed interview, asked about a newly issued joint statement from the American Heart Association, American College of Cardiology, and the Heart Failure Society of America, which on March 17 affirmed that individuals on ACE inhibitors and angiotensin receptor blockers (ARBs) continue that therapy if they should become ill with COVID-19. The European Society of Cardiology issued a similar recommendation a few days prior.

Despite these societies’ statements, Dr. Fauci pointed to population-level data in Italy as suggesting that the case isn’t yet closed. “We really need to get data, and we need to get data fast. There’s a mechanistic rationale for the concern. It’s there, and it’s firm,” he said. The theoretical concern is that ACE inhibitors can upregulate expression of the ACE-2 protein on cell membranes, which is the entry point for SARS-Cov-2 to enter cells.

He added that he remains concerned about the number of coronavirus fatalities of patients in Italy who had hypertension as their only, or primary, underlying health problem.“That to me was a bit of a red flag,” he said. “Patients with hypertension almost certainly had a physician, and the physician almost certainly treated that person with medication. Why should someone who has hypertension that was well controlled have a much greater chance of dying?” he asked, noting that “I look at a person with well-controlled hypertension as a relatively healthy person. I don’t know what the answer is, but somebody has to look very carefully,” ideally by means of a natural history study that identifies medications used by those who died from coronavirus.
 

Potential therapies

Regarding potential therapies for COVID-19, Dr. Fauci acknowledged the social media buzz and flurry of medical letters and case reports about the use of hydroxychloroquine (Plaquenil) to treat active infection. He said that he and other researchers are “in active discussion” about how best to study the efficacy and safety of hydroxychloroquine, but he also acknowledged that many treating clinicians will use hydroxychloroquine empirically in the absence of other treatments with proven efficacy.

Clinical trials underway in China for antiviral medication are facing some enrollment challenges currently “because people want to get the drug,” said Dr. Fauci. “They don’t want to be in the trial; they just want to get the drug.” Though each of two trials has targeted approximately 500 participants as the number needed for sufficient statistical power, Dr. Fauci urged Chinese data safety monitoring boards to “take a close look” at the data already accrued for the several hundred patients who have already enrolled for the studies “to see if there’s any hint of efficacy.”

koakes@mdedge.com

In a JAMA Live Stream interview, Anthony S. Fauci, MD, a key member of the White House Coronavirus Task Force, urged resolve, rather than panic, as the coronavirus pandemic takes hold in the United States.

Dr. Fauci got into the details of what is known, what is unknown, what is being done in laboratories, and what clinical elements are still not understood about this disease.

The next several weeks, he said, are likely to tell the tale of whether our health care system is up to the challenge of care for the most ill among those who will be affected by COVID-19.

“It shouldn’t panic or frighten us, but we have to know we’re dealing with a very serious problem that we have to address, and we have to deal with it in a very bold way,” said Dr. Fauci, director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.

Speaking in an interview with JAMA Editor in Chief Howard Bauchner, MD, Dr. Fauci said the situation favors action over fear. “Let’s apply that energy to doing the things that we know can mitigate this.”

He added that he heard the message loud and clear from health care leaders in Italy and France during a World Health Organization coronavirus call earlier in the day. Officials in those countries, he said, were “almost pleading with the rest of the world to please take this very seriously, because it happens all of a sudden – very abruptly. ... The best time to mitigate is before that happens, because if you wait until after it happens you’re playing catch-up.”

Dr. Bauchner, noting that strict social distancing has been underway in many parts of the United States for several days, posited that, by early April, “We’ll really have a sense if we can manage in terms of serious illness.” Seattle, New York, Boston, and the San Francisco Bay Area may experience demand that outstrips ICU capacity at that point, but the rest of the country, he said, “is doing relatively well.”
 

Stress test on the health care system

Dr. Fauci agreed with this statement and added: “We’re going to know – for better or worse – whether we have enough of what it takes to be able to practice the kind of medicine that we optimally would want to practice.

In the matter of a week or 2 ... I think we’ll get a feel for whether or not we really have enough of the supplies that it takes.”

The well-publicized regional shortages in personal protective equipment (PPE) are forcing tough choices in some areas. As expedited – and even drive-through – testing begins, some of the demand for testing-related PPE may abate, especially if protocols include self-administration of nasal swabs, he noted.

Dr. Fauci added that the strategic national stockpile of medical supplies and equipment has not yet been tapped, “but you need to backfill that as quickly as you can once you start drawing from the strategic national stockpile.”
 

Returning to work after COVID-19 infection

Regarding the thorny question of when health care workers should be permitted to return to work after coronavirus infection, “it’s an evolving story,” said Dr. Fauci. Current guidance advises that health care providers stay away from work until two negative tests after resolution of fever and improvement of respiratory symptoms, or 3 fever-free days.

“We are approaching a point where you’re going to get enough people who are getting infected that we aren’t going to be able to do that,” he said. Depending on the stress to the health care system in a given locality, he said that facilities are going to have to “decide with good judgment” when health care workers go back on the job after coronavirus infection.

Asked how soon an individual would reliably test positive for COVID-19 after exposure, Dr. Fauci said, “We don’t know the answer to that. ... We can surmise it ...” He noted that it’s a median of about 5 days with a range of 2 to 14 days, before an infected individual becomes symptomatic. “I can say it’s not going to happen immediately,” he added, noting that he wouldn’t expect to see a positive test until about 2 days after exposure at the earliest. “When you get to the point where you are symptomatic, you’re almost certainly going to be positive then. ... This is just an extrapolation,” rather than conclusions drawn from solid data, he emphasized.
 

Higher risk reported in cardiac patients

Dr. Bauchner, who was relaying questions sent in from physicians during the live-streamed interview, asked about a newly issued joint statement from the American Heart Association, American College of Cardiology, and the Heart Failure Society of America, which on March 17 affirmed that individuals on ACE inhibitors and angiotensin receptor blockers (ARBs) continue that therapy if they should become ill with COVID-19. The European Society of Cardiology issued a similar recommendation a few days prior.

Despite these societies’ statements, Dr. Fauci pointed to population-level data in Italy as suggesting that the case isn’t yet closed. “We really need to get data, and we need to get data fast. There’s a mechanistic rationale for the concern. It’s there, and it’s firm,” he said. The theoretical concern is that ACE inhibitors can upregulate expression of the ACE-2 protein on cell membranes, which is the entry point for SARS-Cov-2 to enter cells.

He added that he remains concerned about the number of coronavirus fatalities of patients in Italy who had hypertension as their only, or primary, underlying health problem.“That to me was a bit of a red flag,” he said. “Patients with hypertension almost certainly had a physician, and the physician almost certainly treated that person with medication. Why should someone who has hypertension that was well controlled have a much greater chance of dying?” he asked, noting that “I look at a person with well-controlled hypertension as a relatively healthy person. I don’t know what the answer is, but somebody has to look very carefully,” ideally by means of a natural history study that identifies medications used by those who died from coronavirus.
 

Potential therapies

Regarding potential therapies for COVID-19, Dr. Fauci acknowledged the social media buzz and flurry of medical letters and case reports about the use of hydroxychloroquine (Plaquenil) to treat active infection. He said that he and other researchers are “in active discussion” about how best to study the efficacy and safety of hydroxychloroquine, but he also acknowledged that many treating clinicians will use hydroxychloroquine empirically in the absence of other treatments with proven efficacy.

Clinical trials underway in China for antiviral medication are facing some enrollment challenges currently “because people want to get the drug,” said Dr. Fauci. “They don’t want to be in the trial; they just want to get the drug.” Though each of two trials has targeted approximately 500 participants as the number needed for sufficient statistical power, Dr. Fauci urged Chinese data safety monitoring boards to “take a close look” at the data already accrued for the several hundred patients who have already enrolled for the studies “to see if there’s any hint of efficacy.”

koakes@mdedge.com

Clinicians across the United States are petitioning the federal government to follow the lead of South Korea, China, and other nations by imposing an immediate nationwide quarantine to slow the inevitable spread of COVID-19. Without federal action, the creators say, their lives and the lives of their colleagues, patients, and families are being put at increased risk.

In addition to the quarantine, the petition, posted on the website Change.org, calls on U.S. leaders to institute emergency production and distribution of personal protective equipment for healthcare workers and to rapidly increase access to testing.

The petition – which garnered more than 40,000 signatures in just 12 hours and as of this writing was approaching 94,000 – was started by an apolitical Facebook group to focus attention on what members see as the most critical issues for clinicians: slowing the spread of the virus through a coast-to-coast quarantine, protection of medical personnel with adequate supplies of essential equipment, and widespread testing.

“We started this group last Friday out of the realization that clinicians needed information about the outbreak and weren’t getting it,” said coadministrator Jessica McIntyre, MD, a pediatric hospitalist at Elliot Hospital in Manchester, N.H.

“We wanted to get ahead of it and connect with people before we were in the trenches experiencing it and to see what other programs were doing. From a local perspective, it has been really hard to see what people are doing in other states, especially when the protocols in our own states are changing every single day as we collect more information,” she said in an interview.
 

The Horse Has Bolted

A family medicine physician in Illinois helped launch the Facebook group. She asked that her name not be used but said in an interview that earlier actions may have prevented or at least delayed the need for the more draconian measures that her group is recommending.

“Clearly South Korea is one of the superstars as far as response has gone, but the concern we have in the United States is that we’re well beyond that point – we needed to be testing people over a month ago, in the hope of preventing a quarantine,” she said in an interview.

According to National Public Radio, as of March 13, South Korea had conducted 3,600 tests per million population, compared with five per million in the United States.

“I think the most concerning part is to see where Italy is now and where we are in comparison. Our ICUs have not yet overflowed, but I think we’re definitely looking at that in the next few weeks – hopefully longer, but I suspect that it will happen shortly,” she continued.

She cited work by Harvard University biostatistician Xihong Lin, PhD, that shows that when health authorities in Wuhan, China – widely cited as the epicenter of the global pandemic – cordoned off the city, the infection rate dropped from one person infecting 3.8 others to one infecting 1.25, thereby significantly slowing the rate of transmission.

“This is absolutely what we need to be doing,” she said.
 

Real News

Within 3 days of its creation, the online group had accrued more than 80,000 members with advanced medical training, including MDs, DOs, physician assistants, nurse practitioners, and certified registered nurse anesthetists.

“A lot of us were already very busy with our day-to-day work outside of COVID-19, and I think a lot of us felt unsure about where to get the best information,” said coadministrator David Janssen, MD, a family medicine physician in group practice in Sioux Center, Iowa,

“If you turn on the TV, there’s a lot of politicizing of the issue, and there’s a lot of good information, but also a lot of bad information. When health care providers talk to other health care providers, that’s often how we get our information and how we learn,” he said in an interview.

The COVID-19 U.S. Physicians/APP Facebook group includes 20 volunteer moderators who handle hundreds of posts per hour from persons seeking information on the novel coronavirus, what to tell patients, and how to protect themselves.

“It’s been wonderful to see how providers have been helping other providers sort through issues. Teaching hospitals have their hands on the latest research, but a lot of people like myself are at small community hospitals, critical-access hospitals, where we may have a lot of questions but don’t necessarily have the answers readily available to us,” Dr. Janssen said.

Dr. Janssen said that his community of about 8,000 residents initially had only four COVID-19 testing kits, or one for every 2,000 people. The situation has since improved, and more tests are now available, he added.

Dr. McIntyre, Dr. Janssen, and the Illinois family physician have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Clinicians across the United States are petitioning the federal government to follow the lead of South Korea, China, and other nations by imposing an immediate nationwide quarantine to slow the inevitable spread of COVID-19. Without federal action, the creators say, their lives and the lives of their colleagues, patients, and families are being put at increased risk.

In addition to the quarantine, the petition, posted on the website Change.org, calls on U.S. leaders to institute emergency production and distribution of personal protective equipment for healthcare workers and to rapidly increase access to testing.

The petition – which garnered more than 40,000 signatures in just 12 hours and as of this writing was approaching 94,000 – was started by an apolitical Facebook group to focus attention on what members see as the most critical issues for clinicians: slowing the spread of the virus through a coast-to-coast quarantine, protection of medical personnel with adequate supplies of essential equipment, and widespread testing.

“We started this group last Friday out of the realization that clinicians needed information about the outbreak and weren’t getting it,” said coadministrator Jessica McIntyre, MD, a pediatric hospitalist at Elliot Hospital in Manchester, N.H.

“We wanted to get ahead of it and connect with people before we were in the trenches experiencing it and to see what other programs were doing. From a local perspective, it has been really hard to see what people are doing in other states, especially when the protocols in our own states are changing every single day as we collect more information,” she said in an interview.
 

The Horse Has Bolted

A family medicine physician in Illinois helped launch the Facebook group. She asked that her name not be used but said in an interview that earlier actions may have prevented or at least delayed the need for the more draconian measures that her group is recommending.

“Clearly South Korea is one of the superstars as far as response has gone, but the concern we have in the United States is that we’re well beyond that point – we needed to be testing people over a month ago, in the hope of preventing a quarantine,” she said in an interview.

According to National Public Radio, as of March 13, South Korea had conducted 3,600 tests per million population, compared with five per million in the United States.

“I think the most concerning part is to see where Italy is now and where we are in comparison. Our ICUs have not yet overflowed, but I think we’re definitely looking at that in the next few weeks – hopefully longer, but I suspect that it will happen shortly,” she continued.

She cited work by Harvard University biostatistician Xihong Lin, PhD, that shows that when health authorities in Wuhan, China – widely cited as the epicenter of the global pandemic – cordoned off the city, the infection rate dropped from one person infecting 3.8 others to one infecting 1.25, thereby significantly slowing the rate of transmission.

“This is absolutely what we need to be doing,” she said.
 

Real News

Within 3 days of its creation, the online group had accrued more than 80,000 members with advanced medical training, including MDs, DOs, physician assistants, nurse practitioners, and certified registered nurse anesthetists.

“A lot of us were already very busy with our day-to-day work outside of COVID-19, and I think a lot of us felt unsure about where to get the best information,” said coadministrator David Janssen, MD, a family medicine physician in group practice in Sioux Center, Iowa,

“If you turn on the TV, there’s a lot of politicizing of the issue, and there’s a lot of good information, but also a lot of bad information. When health care providers talk to other health care providers, that’s often how we get our information and how we learn,” he said in an interview.

The COVID-19 U.S. Physicians/APP Facebook group includes 20 volunteer moderators who handle hundreds of posts per hour from persons seeking information on the novel coronavirus, what to tell patients, and how to protect themselves.

“It’s been wonderful to see how providers have been helping other providers sort through issues. Teaching hospitals have their hands on the latest research, but a lot of people like myself are at small community hospitals, critical-access hospitals, where we may have a lot of questions but don’t necessarily have the answers readily available to us,” Dr. Janssen said.

Dr. Janssen said that his community of about 8,000 residents initially had only four COVID-19 testing kits, or one for every 2,000 people. The situation has since improved, and more tests are now available, he added.

Dr. McIntyre, Dr. Janssen, and the Illinois family physician have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Clinicians across the United States are petitioning the federal government to follow the lead of South Korea, China, and other nations by imposing an immediate nationwide quarantine to slow the inevitable spread of COVID-19. Without federal action, the creators say, their lives and the lives of their colleagues, patients, and families are being put at increased risk.

In addition to the quarantine, the petition, posted on the website Change.org, calls on U.S. leaders to institute emergency production and distribution of personal protective equipment for healthcare workers and to rapidly increase access to testing.

The petition – which garnered more than 40,000 signatures in just 12 hours and as of this writing was approaching 94,000 – was started by an apolitical Facebook group to focus attention on what members see as the most critical issues for clinicians: slowing the spread of the virus through a coast-to-coast quarantine, protection of medical personnel with adequate supplies of essential equipment, and widespread testing.

“We started this group last Friday out of the realization that clinicians needed information about the outbreak and weren’t getting it,” said coadministrator Jessica McIntyre, MD, a pediatric hospitalist at Elliot Hospital in Manchester, N.H.

“We wanted to get ahead of it and connect with people before we were in the trenches experiencing it and to see what other programs were doing. From a local perspective, it has been really hard to see what people are doing in other states, especially when the protocols in our own states are changing every single day as we collect more information,” she said in an interview.
 

The Horse Has Bolted

A family medicine physician in Illinois helped launch the Facebook group. She asked that her name not be used but said in an interview that earlier actions may have prevented or at least delayed the need for the more draconian measures that her group is recommending.

“Clearly South Korea is one of the superstars as far as response has gone, but the concern we have in the United States is that we’re well beyond that point – we needed to be testing people over a month ago, in the hope of preventing a quarantine,” she said in an interview.

According to National Public Radio, as of March 13, South Korea had conducted 3,600 tests per million population, compared with five per million in the United States.

“I think the most concerning part is to see where Italy is now and where we are in comparison. Our ICUs have not yet overflowed, but I think we’re definitely looking at that in the next few weeks – hopefully longer, but I suspect that it will happen shortly,” she continued.

She cited work by Harvard University biostatistician Xihong Lin, PhD, that shows that when health authorities in Wuhan, China – widely cited as the epicenter of the global pandemic – cordoned off the city, the infection rate dropped from one person infecting 3.8 others to one infecting 1.25, thereby significantly slowing the rate of transmission.

“This is absolutely what we need to be doing,” she said.
 

Real News

Within 3 days of its creation, the online group had accrued more than 80,000 members with advanced medical training, including MDs, DOs, physician assistants, nurse practitioners, and certified registered nurse anesthetists.

“A lot of us were already very busy with our day-to-day work outside of COVID-19, and I think a lot of us felt unsure about where to get the best information,” said coadministrator David Janssen, MD, a family medicine physician in group practice in Sioux Center, Iowa,

“If you turn on the TV, there’s a lot of politicizing of the issue, and there’s a lot of good information, but also a lot of bad information. When health care providers talk to other health care providers, that’s often how we get our information and how we learn,” he said in an interview.

The COVID-19 U.S. Physicians/APP Facebook group includes 20 volunteer moderators who handle hundreds of posts per hour from persons seeking information on the novel coronavirus, what to tell patients, and how to protect themselves.

“It’s been wonderful to see how providers have been helping other providers sort through issues. Teaching hospitals have their hands on the latest research, but a lot of people like myself are at small community hospitals, critical-access hospitals, where we may have a lot of questions but don’t necessarily have the answers readily available to us,” Dr. Janssen said.

Dr. Janssen said that his community of about 8,000 residents initially had only four COVID-19 testing kits, or one for every 2,000 people. The situation has since improved, and more tests are now available, he added.

Dr. McIntyre, Dr. Janssen, and the Illinois family physician have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Controversy continued over the potential effect of drugs that interfere with the renin-angiotensin-aldosterone system via the angiotensin-converting enzymes (ACE) may have on exacerbating infection with the SARS-CoV-2 virus that causes COVID-19.

A joint statement from the American Heart Association, American College of Cardiology, and the Heart Failure Society of America on March 17 gave full, unqualified support to maintaining patients on drugs that work this way, specifically the ACE inhibitors and angiotensin-receptor blockers (ARBs), which together form a long-standing cornerstone of treatment for hypertension, heart failure, and ischemic heart disease.

The three societies “recommend continuation” of ACE inhibitors or ARBs “for all patients already prescribed.” The statement went on to say that patients already diagnosed with a COVID-19 infection “should be fully evaluated before adding or removing any treatments, and any changes to their treatment should be based on the latest scientific evidence and shared decision making with their physician and health care team.”

“We understand the concern – as it has become clear that people with cardiovascular disease are at much higher risk of serious complications including death from COVID-19. However, we have reviewed the latest research – the evidence does not confirm the need to discontinue ACE inhibitors or ARBs, and we strongly recommend all physicians to consider the individual needs of each patient before making any changes to ACE-inhibitor or ARB treatment regimens,” said Robert A. Harrington, MD, president of the American Heart Association and professor and chair of medicine at Stanford (Calif.) University, in the statement.

“There are no experimental or clinical data demonstrating beneficial or adverse outcomes among COVID-19 patients using ACE-inhibitor or ARB medications,” added Richard J. Kovacs, MD, president of the American College of Cardiology and professor of cardiology at Indiana University in Indianapolis.

The “latest research” referred to in the statement likely focuses on a report that had appeared less than a week earlier in a British journal that hypothesized a possible increase in the susceptibility of human epithelial cells of the lungs, intestine, kidneys, and blood vessels exposed to these or certain other drugs, like the thiazolidinedione oral diabetes drugs or ibuprofen, because they cause up-regulation of the ACE2 protein in cell membranes, and ACE2 is the primary cell-surface receptor that allows the SARS-CoV-2 virus to enter.

“We therefore hypothesize that diabetes and hypertension treatment with ACE2-stimulating drugs increases the risk of developing severe and fatal COVID-19,” wrote Michael Roth, MD, and his associates in their recent article (Lancet Resp Med. 2020 Mar 11. doi: 10.1016/S2213-2600[20]30116-8). While the potential clinical impact of an increase in the number of ACE2 molecules in a cell’s surface membrane remains uninvestigated, the risk this phenomenon poses should mean that patients taking these drugs should receive heightened monitoring for COVID-19 disease, suggested Dr. Roth, a professor of biomedicine who specializes in studying inflammatory lung diseases including asthma, and associates.

However, others who have considered the impact that ACE inhibitors and ARBs might have on ACE2 and COVID-19 infections have noted that the picture is not simple. “Higher ACE2 expression following chronically medicating SARS‐CoV‐2 infected patients with AT1R [angiotensin receptor 1] blockers, while seemingly paradoxical, may protect them against acute lung injury rather than putting them at higher risk to develop SARS. This may be accounted for by two complementary mechanisms: blocking the excessive angiotensin‐mediated AT1R activation caused by the viral infection, as well as up-regulating ACE2, thereby reducing angiotensin production by ACE and increasing the production” of a vasodilating form of angiotensin, wrote David Gurwitz, PhD, in a recently published editorial (Drug Dev Res. 2020 Mar 4. doi: 10.1002/ddr.21656). A data-mining approach may allow researchers to determine whether patients who received drugs that interfere with angiotensin 1 function prior to being diagnosed with a COVID-19 infection had a better disease outcome, suggested Dr. Gurwitz, a molecular geneticist at Tel Aviv University in Jerusalem.

The statement from the three U.S. cardiology societies came a few days following a similar statement of support for ongoing use of ACE inhibitors and ARBs from the European Society of Cardiology’s Council on Hypertension.

Dr. Harrington, Dr. Kovacs, Dr. Roth, and Dr. Gurwitz had no relevant disclosures.

mzoler@mdedge.com

Controversy continued over the potential effect of drugs that interfere with the renin-angiotensin-aldosterone system via the angiotensin-converting enzymes (ACE) may have on exacerbating infection with the SARS-CoV-2 virus that causes COVID-19.

A joint statement from the American Heart Association, American College of Cardiology, and the Heart Failure Society of America on March 17 gave full, unqualified support to maintaining patients on drugs that work this way, specifically the ACE inhibitors and angiotensin-receptor blockers (ARBs), which together form a long-standing cornerstone of treatment for hypertension, heart failure, and ischemic heart disease.

The three societies “recommend continuation” of ACE inhibitors or ARBs “for all patients already prescribed.” The statement went on to say that patients already diagnosed with a COVID-19 infection “should be fully evaluated before adding or removing any treatments, and any changes to their treatment should be based on the latest scientific evidence and shared decision making with their physician and health care team.”

“We understand the concern – as it has become clear that people with cardiovascular disease are at much higher risk of serious complications including death from COVID-19. However, we have reviewed the latest research – the evidence does not confirm the need to discontinue ACE inhibitors or ARBs, and we strongly recommend all physicians to consider the individual needs of each patient before making any changes to ACE-inhibitor or ARB treatment regimens,” said Robert A. Harrington, MD, president of the American Heart Association and professor and chair of medicine at Stanford (Calif.) University, in the statement.

“There are no experimental or clinical data demonstrating beneficial or adverse outcomes among COVID-19 patients using ACE-inhibitor or ARB medications,” added Richard J. Kovacs, MD, president of the American College of Cardiology and professor of cardiology at Indiana University in Indianapolis.

The “latest research” referred to in the statement likely focuses on a report that had appeared less than a week earlier in a British journal that hypothesized a possible increase in the susceptibility of human epithelial cells of the lungs, intestine, kidneys, and blood vessels exposed to these or certain other drugs, like the thiazolidinedione oral diabetes drugs or ibuprofen, because they cause up-regulation of the ACE2 protein in cell membranes, and ACE2 is the primary cell-surface receptor that allows the SARS-CoV-2 virus to enter.

“We therefore hypothesize that diabetes and hypertension treatment with ACE2-stimulating drugs increases the risk of developing severe and fatal COVID-19,” wrote Michael Roth, MD, and his associates in their recent article (Lancet Resp Med. 2020 Mar 11. doi: 10.1016/S2213-2600[20]30116-8). While the potential clinical impact of an increase in the number of ACE2 molecules in a cell’s surface membrane remains uninvestigated, the risk this phenomenon poses should mean that patients taking these drugs should receive heightened monitoring for COVID-19 disease, suggested Dr. Roth, a professor of biomedicine who specializes in studying inflammatory lung diseases including asthma, and associates.

However, others who have considered the impact that ACE inhibitors and ARBs might have on ACE2 and COVID-19 infections have noted that the picture is not simple. “Higher ACE2 expression following chronically medicating SARS‐CoV‐2 infected patients with AT1R [angiotensin receptor 1] blockers, while seemingly paradoxical, may protect them against acute lung injury rather than putting them at higher risk to develop SARS. This may be accounted for by two complementary mechanisms: blocking the excessive angiotensin‐mediated AT1R activation caused by the viral infection, as well as up-regulating ACE2, thereby reducing angiotensin production by ACE and increasing the production” of a vasodilating form of angiotensin, wrote David Gurwitz, PhD, in a recently published editorial (Drug Dev Res. 2020 Mar 4. doi: 10.1002/ddr.21656). A data-mining approach may allow researchers to determine whether patients who received drugs that interfere with angiotensin 1 function prior to being diagnosed with a COVID-19 infection had a better disease outcome, suggested Dr. Gurwitz, a molecular geneticist at Tel Aviv University in Jerusalem.

The statement from the three U.S. cardiology societies came a few days following a similar statement of support for ongoing use of ACE inhibitors and ARBs from the European Society of Cardiology’s Council on Hypertension.

Dr. Harrington, Dr. Kovacs, Dr. Roth, and Dr. Gurwitz had no relevant disclosures.

mzoler@mdedge.com

Controversy continued over the potential effect of drugs that interfere with the renin-angiotensin-aldosterone system via the angiotensin-converting enzymes (ACE) may have on exacerbating infection with the SARS-CoV-2 virus that causes COVID-19.

A joint statement from the American Heart Association, American College of Cardiology, and the Heart Failure Society of America on March 17 gave full, unqualified support to maintaining patients on drugs that work this way, specifically the ACE inhibitors and angiotensin-receptor blockers (ARBs), which together form a long-standing cornerstone of treatment for hypertension, heart failure, and ischemic heart disease.

The three societies “recommend continuation” of ACE inhibitors or ARBs “for all patients already prescribed.” The statement went on to say that patients already diagnosed with a COVID-19 infection “should be fully evaluated before adding or removing any treatments, and any changes to their treatment should be based on the latest scientific evidence and shared decision making with their physician and health care team.”

“We understand the concern – as it has become clear that people with cardiovascular disease are at much higher risk of serious complications including death from COVID-19. However, we have reviewed the latest research – the evidence does not confirm the need to discontinue ACE inhibitors or ARBs, and we strongly recommend all physicians to consider the individual needs of each patient before making any changes to ACE-inhibitor or ARB treatment regimens,” said Robert A. Harrington, MD, president of the American Heart Association and professor and chair of medicine at Stanford (Calif.) University, in the statement.

“There are no experimental or clinical data demonstrating beneficial or adverse outcomes among COVID-19 patients using ACE-inhibitor or ARB medications,” added Richard J. Kovacs, MD, president of the American College of Cardiology and professor of cardiology at Indiana University in Indianapolis.

The “latest research” referred to in the statement likely focuses on a report that had appeared less than a week earlier in a British journal that hypothesized a possible increase in the susceptibility of human epithelial cells of the lungs, intestine, kidneys, and blood vessels exposed to these or certain other drugs, like the thiazolidinedione oral diabetes drugs or ibuprofen, because they cause up-regulation of the ACE2 protein in cell membranes, and ACE2 is the primary cell-surface receptor that allows the SARS-CoV-2 virus to enter.

“We therefore hypothesize that diabetes and hypertension treatment with ACE2-stimulating drugs increases the risk of developing severe and fatal COVID-19,” wrote Michael Roth, MD, and his associates in their recent article (Lancet Resp Med. 2020 Mar 11. doi: 10.1016/S2213-2600[20]30116-8). While the potential clinical impact of an increase in the number of ACE2 molecules in a cell’s surface membrane remains uninvestigated, the risk this phenomenon poses should mean that patients taking these drugs should receive heightened monitoring for COVID-19 disease, suggested Dr. Roth, a professor of biomedicine who specializes in studying inflammatory lung diseases including asthma, and associates.

However, others who have considered the impact that ACE inhibitors and ARBs might have on ACE2 and COVID-19 infections have noted that the picture is not simple. “Higher ACE2 expression following chronically medicating SARS‐CoV‐2 infected patients with AT1R [angiotensin receptor 1] blockers, while seemingly paradoxical, may protect them against acute lung injury rather than putting them at higher risk to develop SARS. This may be accounted for by two complementary mechanisms: blocking the excessive angiotensin‐mediated AT1R activation caused by the viral infection, as well as up-regulating ACE2, thereby reducing angiotensin production by ACE and increasing the production” of a vasodilating form of angiotensin, wrote David Gurwitz, PhD, in a recently published editorial (Drug Dev Res. 2020 Mar 4. doi: 10.1002/ddr.21656). A data-mining approach may allow researchers to determine whether patients who received drugs that interfere with angiotensin 1 function prior to being diagnosed with a COVID-19 infection had a better disease outcome, suggested Dr. Gurwitz, a molecular geneticist at Tel Aviv University in Jerusalem.

The statement from the three U.S. cardiology societies came a few days following a similar statement of support for ongoing use of ACE inhibitors and ARBs from the European Society of Cardiology’s Council on Hypertension.

Dr. Harrington, Dr. Kovacs, Dr. Roth, and Dr. Gurwitz had no relevant disclosures.

mzoler@mdedge.com

This article is the first in a series on maternal mortality.

“You’re in really bad shape, kid. I don’t know if you’re gonna live through the night. I’m going to do everything I can to save your life, but the truth is you might die.”

If Timoria McQueen Saba imagined the words she would hear in the moments after she gave birth, those likely weren’t among them. But then she started to bleed. The energy around her shifted; she felt the urgency and intensity in the room, and she could see it – reflected from the television monitor over her bed – in the faces of her care team. After her husband and newborn daughter were led from the room, she did, in fact, hear those words.

They were spoken by a surgeon called in after efforts to control the bleeding failed – emetic words that joined forces with her hemorrhaging and confusion and fear, and as she began to vomit, her eyelids felt heavy. She fought to keep them open, sensing that if she closed them they might never open again.

In 2018 alone, similar words perhaps were spoken to the 658 U.S. women who suffered maternal complications and whose eyes never did open again. This is the latest official maternal mortality data from the Centers for Disease Control and Prevention.

Ms. Saba’s eyes, however, remained open through her birth trauma and through the PTSD that followed. A fierce advocate for maternal health, she shares her story often, as she did during a panel discussion at the American College of Obstetricians and Gynecologists’ annual meeting in May 2019, in an effort to improve outcomes for other women and families.

But her story unfolded nearly a decade ago and those eyes still are seeing women die from childbirth. Despite her efforts and the efforts of countless other individuals and organizations working to improve maternal outcomes, the new CDC data show that the United States has the highest maternal mortality rate of any similarly wealthy industrialized nation.

“I cannot believe I’m still talking about this issue,” Ms. Saba told a standing-room-only crowd and her copanelists Neel T. Shah, MD, and Charles S. Johnson IV, whose wife, Kira, died in 2016 during surgery for bleeding complications following the birth of their second child. “If all the people who I’d written to had just listened maybe once and tried to propel my message forward back then, Charles would be in a much better situation and so would his children.”

Mr. Johnson said that for 10 hours he and other family members pleaded for help for Kira, a healthy, vibrant women he described as “sunshine personified.”

She showed signs of postpartum bleeding after delivering a healthy baby boy by C-section, but a “STAT CT” order went unheeded for hours before she was finally taken for surgery.

“You’re walking down this corridor, you get to this point, these double doors open, and you just can’t go any further – and that was the last time I saw my wife alive,” he said. “When they took Kira back into the operating room, there were three-and-a-half liters of blood in her abdomen, and her heart stopped immediately.

Kira Johnson died April 13, 2016.

“I’m not here to tell you what I think, I’m here to tell you what I know, and that’s that Kira deserved so much better, and that Kira’s not alone, and that women all over this country deserve so much better.”

The U.S. maternal mortality crisis

Dr. Shah, an ob.gyn. at Beth Israel Deaconess Medical Center and director of the Delivery Decisions Initiative at Harvard Medical School’s Ariadne Labs, both in Boston, where he has “been on this mission to improve safety in childbirth for years now,” echoed Ms. Saba’s dismay regarding the pace of progress.

“It’s not just about the present, it’s about the future, it’s about the pact that every generation ought to have with the next one to leave things at least as well as they found them. And when it comes to the health of our moms in this country, we are not doing that,” he said. “An American mom today is 50% more likely to die in childbirth than her own mother was, and 3-4 times more likely to die if she’s black than if she’s white.”

Indeed, the data released Jan. 30 by the CDC’s National Center for Health Statistics (NCHS) – the first on maternal mortality released by the agency since 2007 – show a U.S. maternal mortality rate of 17.4 maternal deaths per 100,000 live births in 2018.

The rate is higher than the 12.7 per 100,000 live births reported in 2007, but the increase is attributable mostly to changes in data collection and reporting methods. In 2003, “a consensus process recommended that all states add a standardized ‘checkbox’ to improve the identification of maternal deaths,” and implementation wasn’t complete until 2017 as “funding, technology, and state laws allowed,” meaning 2018 was the first year that data were reported in a standardized fashion across states, the CDC explained in a press release.

The data demonstrate ongoing wide racial/ethnic disparities: the maternal mortality rates for non-Hispanic black women, non-Hispanic white women, and Hispanic women were 37.1, 14.7, and 11.8 per 100,000 live births, consistent with earlier data.

Further, the rates for women aged 40 years and over were nearly eightfold higher than for those under age 25 years (81.9 vs. 10.6 per 100,000 live births).

CDC officials noted, however, that inconsistencies in reporting still leave some question about the accuracy of the data, stating in the release that “NCHS has identified instances where application of the checkbox information according to coding rules led to misclassification of maternal deaths.”

The agency is making changes in rules and reporting to ensure greater accuracy, but the numbers nevertheless reveal a startling truth: “The United States is the most dangerous place to deliver a baby in the industrialized world.”

 

Progress and challenges

Rebekah Gee, MD, an ob.gyn. who served for 4 years as Secretary of the Louisiana Department of Health before leaving the position in January, made that statement during another panel discussion at ACOG 2019 – The President’s Panel: Maternal Mortality: Progress Toward Prevention – which was moderated by Lisa M. Hollier, MD, now the immediate past president of ACOG.

Texas Children's Hospital

That’s not to say progress hasn’t been or can’t be made, Dr. Gee said.

In fact, quality improvement measures she facilitated in Louisiana led to a 25% reduction in infant mortality and a 10% reduction in neonatal intensive care unit admissions, demonstrating the potential for improvement with such initiatives, but addressing maternal issues is a greater challenge, she said.

“I think part of the sad truth is that we really focus on babies first, not moms ... and that needs to change,” Dr. Gee said.

Dr. Hollier focused much of her attention during her tenure as ACOG president on doing just that, particularly through an emphasis on heart disease, which is the leading cause of U.S. maternal deaths in pregnancy and the postpartum period.

In an interview, she shared her thoughts on the progress achieved and the work that remains.

ACOG was instrumental in the enactment of the Preventing Maternal Deaths Act of 2018, which appropriated funding for Enhancing Reviews and Surveillance to Eliminate Maternal Mortality (ERASE MM), a CDC initiative to support state-based maternal mortality review committees, said Dr. Hollier, professor of obstetrics and gynecology at Baylor College of Medicine, Houston.

“The really great news is that almost immediately after passage of the legislation, the CDC put out the notice of the funding opportunity, and they were able to provide 24 awards supporting 25 states,” she said.

ERASE MM will enhance state data collection and availability and enable a level of data sharing that “will really add strength and depth to reporting from the maternal mortality review committees, which really provides us with the best information we have to truly understand the causes, the contributing factors, and the strategies that can be put in place to prevent future maternal deaths.”

Further, the Alliance for Innovation on Maternal Health (AIM) program, a cooperative agreement with the Health Resources and Services Administration (HRSA) Maternal and Child Health Bureau to improve safety and outcomes through evidence-based patient safety bundles, was extended, and in May 2019, ACOG updated its guidance on managing cardiac contributors to maternal mortality, releasing its “Pregnancy and Heart Disease” Practice Bulletin, she said.

Dr. Hollier continues in her quest for improved maternal outcomes. She is slated to deliver a keynote address at the American College of Cardiology/World Congress of Cardiology conference March 28 in Chicago.

“I’m so excited ... to talk about the new guidelines that we’ve put out and to really talk about how cardiologists and ob.gyns. can work together to improve women’s health outcomes,” she said, adding that she already is seeing a strengthening of such partnerships.

A number of academic institutions are developing “pregnancy heart teams” to identify and care for women who have or develop heart disease during pregnancy.

“This type of collaboration ... is going to be essential to address mortality from cardiovascular causes and from cardiomyopathy, which accounts for about 25% of all maternal mortality,” she said. “The next area where we really need some buy-in is from our emergency physicians.”

Enhanced collaboration with emergency physicians and other specialties present opportunities to better identify and address pregnancy-related complications and sequelae, she said.

“Women are dying because they’re not being diagnosed,” she added. “We have to raise that level of awareness – it’s just absolutely critical.”
 

Identifying and addressing drivers of the crisis

Dr. Gee further emphasized the importance of addressing maternal health, noting that for every woman who dies from maternal causes, 100 experience maternal morbidity.

“It’s startling and it’s scary,” she said. “We are looking at this not just as a problem of outcomes, but a problem of racial inequity and racial bias and implicit bias.”

When she and her team assessed maternal mortality in Louisiana, they looked specifically at whether each death could have been prevented if, for example, blood was given sooner, cardiomyopathy was recognized sooner, or hypertension was treated on time.

“When we looked at these numbers ... when we looked at white women, 9% of the time we could have done better with our medical care; with black women, 59% of the time we could have saved her life with better care,” said Dr Gee, who is a gratis assistant professor of obstetrics and gynecology at Louisiana State University, New Orleans. “And if that doesn’t convince you that racial bias is an incredibly important thing to address – that we need to have a conversation about and address at a national level – I don’t know what would.”

In fact, numerous health, societal, socioeconomic, and other factors – some known, some yet to be identified, and many inter-related – are among the drivers of the U.S. maternal mortality crisis. In the coming months, an Ob.Gyn. News team will examine several of these drivers in depth. We’ll look specifically at the role of racism and bias, and at urban-rural disparities in access and outcomes – especially for women of color and indigenous women. We’ll address the scope and impact of each, successes and failures in addressing the problems, and ongoing initiatives.

Follow us for insights from experts, researchers, practicing physicians, and patients and families affected by the maternal mortality crisis, and stay with us through coverage of ACOG 2020 for perspective on what, specifically, ob.gyns. can do about it.

Mr. Johnson proposed a starting point:

“Here’s the good news – you guys ready for this? We can fix this,” he said, adding that the solution starts with “speaking Timoria’s name ... speaking the name of Kira Dixon Johnson ... speaking the names of these women and then asking the people that are around you, ‘What are we prepared to do to make sure that this doesn’t happen to other women.’ ”

sworcester@mdedge.com

This article is the first in a series on maternal mortality.

“You’re in really bad shape, kid. I don’t know if you’re gonna live through the night. I’m going to do everything I can to save your life, but the truth is you might die.”

If Timoria McQueen Saba imagined the words she would hear in the moments after she gave birth, those likely weren’t among them. But then she started to bleed. The energy around her shifted; she felt the urgency and intensity in the room, and she could see it – reflected from the television monitor over her bed – in the faces of her care team. After her husband and newborn daughter were led from the room, she did, in fact, hear those words.

They were spoken by a surgeon called in after efforts to control the bleeding failed – emetic words that joined forces with her hemorrhaging and confusion and fear, and as she began to vomit, her eyelids felt heavy. She fought to keep them open, sensing that if she closed them they might never open again.

In 2018 alone, similar words perhaps were spoken to the 658 U.S. women who suffered maternal complications and whose eyes never did open again. This is the latest official maternal mortality data from the Centers for Disease Control and Prevention.

Ms. Saba’s eyes, however, remained open through her birth trauma and through the PTSD that followed. A fierce advocate for maternal health, she shares her story often, as she did during a panel discussion at the American College of Obstetricians and Gynecologists’ annual meeting in May 2019, in an effort to improve outcomes for other women and families.

But her story unfolded nearly a decade ago and those eyes still are seeing women die from childbirth. Despite her efforts and the efforts of countless other individuals and organizations working to improve maternal outcomes, the new CDC data show that the United States has the highest maternal mortality rate of any similarly wealthy industrialized nation.

“I cannot believe I’m still talking about this issue,” Ms. Saba told a standing-room-only crowd and her copanelists Neel T. Shah, MD, and Charles S. Johnson IV, whose wife, Kira, died in 2016 during surgery for bleeding complications following the birth of their second child. “If all the people who I’d written to had just listened maybe once and tried to propel my message forward back then, Charles would be in a much better situation and so would his children.”

Mr. Johnson said that for 10 hours he and other family members pleaded for help for Kira, a healthy, vibrant women he described as “sunshine personified.”

She showed signs of postpartum bleeding after delivering a healthy baby boy by C-section, but a “STAT CT” order went unheeded for hours before she was finally taken for surgery.

“You’re walking down this corridor, you get to this point, these double doors open, and you just can’t go any further – and that was the last time I saw my wife alive,” he said. “When they took Kira back into the operating room, there were three-and-a-half liters of blood in her abdomen, and her heart stopped immediately.

Kira Johnson died April 13, 2016.

“I’m not here to tell you what I think, I’m here to tell you what I know, and that’s that Kira deserved so much better, and that Kira’s not alone, and that women all over this country deserve so much better.”

The U.S. maternal mortality crisis

Dr. Shah, an ob.gyn. at Beth Israel Deaconess Medical Center and director of the Delivery Decisions Initiative at Harvard Medical School’s Ariadne Labs, both in Boston, where he has “been on this mission to improve safety in childbirth for years now,” echoed Ms. Saba’s dismay regarding the pace of progress.

“It’s not just about the present, it’s about the future, it’s about the pact that every generation ought to have with the next one to leave things at least as well as they found them. And when it comes to the health of our moms in this country, we are not doing that,” he said. “An American mom today is 50% more likely to die in childbirth than her own mother was, and 3-4 times more likely to die if she’s black than if she’s white.”

Indeed, the data released Jan. 30 by the CDC’s National Center for Health Statistics (NCHS) – the first on maternal mortality released by the agency since 2007 – show a U.S. maternal mortality rate of 17.4 maternal deaths per 100,000 live births in 2018.

The rate is higher than the 12.7 per 100,000 live births reported in 2007, but the increase is attributable mostly to changes in data collection and reporting methods. In 2003, “a consensus process recommended that all states add a standardized ‘checkbox’ to improve the identification of maternal deaths,” and implementation wasn’t complete until 2017 as “funding, technology, and state laws allowed,” meaning 2018 was the first year that data were reported in a standardized fashion across states, the CDC explained in a press release.

The data demonstrate ongoing wide racial/ethnic disparities: the maternal mortality rates for non-Hispanic black women, non-Hispanic white women, and Hispanic women were 37.1, 14.7, and 11.8 per 100,000 live births, consistent with earlier data.

Further, the rates for women aged 40 years and over were nearly eightfold higher than for those under age 25 years (81.9 vs. 10.6 per 100,000 live births).

CDC officials noted, however, that inconsistencies in reporting still leave some question about the accuracy of the data, stating in the release that “NCHS has identified instances where application of the checkbox information according to coding rules led to misclassification of maternal deaths.”

The agency is making changes in rules and reporting to ensure greater accuracy, but the numbers nevertheless reveal a startling truth: “The United States is the most dangerous place to deliver a baby in the industrialized world.”

 

Progress and challenges

Rebekah Gee, MD, an ob.gyn. who served for 4 years as Secretary of the Louisiana Department of Health before leaving the position in January, made that statement during another panel discussion at ACOG 2019 – The President’s Panel: Maternal Mortality: Progress Toward Prevention – which was moderated by Lisa M. Hollier, MD, now the immediate past president of ACOG.

Texas Children's Hospital

That’s not to say progress hasn’t been or can’t be made, Dr. Gee said.

In fact, quality improvement measures she facilitated in Louisiana led to a 25% reduction in infant mortality and a 10% reduction in neonatal intensive care unit admissions, demonstrating the potential for improvement with such initiatives, but addressing maternal issues is a greater challenge, she said.

“I think part of the sad truth is that we really focus on babies first, not moms ... and that needs to change,” Dr. Gee said.

Dr. Hollier focused much of her attention during her tenure as ACOG president on doing just that, particularly through an emphasis on heart disease, which is the leading cause of U.S. maternal deaths in pregnancy and the postpartum period.

In an interview, she shared her thoughts on the progress achieved and the work that remains.

ACOG was instrumental in the enactment of the Preventing Maternal Deaths Act of 2018, which appropriated funding for Enhancing Reviews and Surveillance to Eliminate Maternal Mortality (ERASE MM), a CDC initiative to support state-based maternal mortality review committees, said Dr. Hollier, professor of obstetrics and gynecology at Baylor College of Medicine, Houston.

“The really great news is that almost immediately after passage of the legislation, the CDC put out the notice of the funding opportunity, and they were able to provide 24 awards supporting 25 states,” she said.

ERASE MM will enhance state data collection and availability and enable a level of data sharing that “will really add strength and depth to reporting from the maternal mortality review committees, which really provides us with the best information we have to truly understand the causes, the contributing factors, and the strategies that can be put in place to prevent future maternal deaths.”

Further, the Alliance for Innovation on Maternal Health (AIM) program, a cooperative agreement with the Health Resources and Services Administration (HRSA) Maternal and Child Health Bureau to improve safety and outcomes through evidence-based patient safety bundles, was extended, and in May 2019, ACOG updated its guidance on managing cardiac contributors to maternal mortality, releasing its “Pregnancy and Heart Disease” Practice Bulletin, she said.

Dr. Hollier continues in her quest for improved maternal outcomes. She is slated to deliver a keynote address at the American College of Cardiology/World Congress of Cardiology conference March 28 in Chicago.

“I’m so excited ... to talk about the new guidelines that we’ve put out and to really talk about how cardiologists and ob.gyns. can work together to improve women’s health outcomes,” she said, adding that she already is seeing a strengthening of such partnerships.

A number of academic institutions are developing “pregnancy heart teams” to identify and care for women who have or develop heart disease during pregnancy.

“This type of collaboration ... is going to be essential to address mortality from cardiovascular causes and from cardiomyopathy, which accounts for about 25% of all maternal mortality,” she said. “The next area where we really need some buy-in is from our emergency physicians.”

Enhanced collaboration with emergency physicians and other specialties present opportunities to better identify and address pregnancy-related complications and sequelae, she said.

“Women are dying because they’re not being diagnosed,” she added. “We have to raise that level of awareness – it’s just absolutely critical.”
 

Identifying and addressing drivers of the crisis

Dr. Gee further emphasized the importance of addressing maternal health, noting that for every woman who dies from maternal causes, 100 experience maternal morbidity.

“It’s startling and it’s scary,” she said. “We are looking at this not just as a problem of outcomes, but a problem of racial inequity and racial bias and implicit bias.”

When she and her team assessed maternal mortality in Louisiana, they looked specifically at whether each death could have been prevented if, for example, blood was given sooner, cardiomyopathy was recognized sooner, or hypertension was treated on time.

“When we looked at these numbers ... when we looked at white women, 9% of the time we could have done better with our medical care; with black women, 59% of the time we could have saved her life with better care,” said Dr Gee, who is a gratis assistant professor of obstetrics and gynecology at Louisiana State University, New Orleans. “And if that doesn’t convince you that racial bias is an incredibly important thing to address – that we need to have a conversation about and address at a national level – I don’t know what would.”

In fact, numerous health, societal, socioeconomic, and other factors – some known, some yet to be identified, and many inter-related – are among the drivers of the U.S. maternal mortality crisis. In the coming months, an Ob.Gyn. News team will examine several of these drivers in depth. We’ll look specifically at the role of racism and bias, and at urban-rural disparities in access and outcomes – especially for women of color and indigenous women. We’ll address the scope and impact of each, successes and failures in addressing the problems, and ongoing initiatives.

Follow us for insights from experts, researchers, practicing physicians, and patients and families affected by the maternal mortality crisis, and stay with us through coverage of ACOG 2020 for perspective on what, specifically, ob.gyns. can do about it.

Mr. Johnson proposed a starting point:

“Here’s the good news – you guys ready for this? We can fix this,” he said, adding that the solution starts with “speaking Timoria’s name ... speaking the name of Kira Dixon Johnson ... speaking the names of these women and then asking the people that are around you, ‘What are we prepared to do to make sure that this doesn’t happen to other women.’ ”

sworcester@mdedge.com

This article is the first in a series on maternal mortality.

“You’re in really bad shape, kid. I don’t know if you’re gonna live through the night. I’m going to do everything I can to save your life, but the truth is you might die.”

If Timoria McQueen Saba imagined the words she would hear in the moments after she gave birth, those likely weren’t among them. But then she started to bleed. The energy around her shifted; she felt the urgency and intensity in the room, and she could see it – reflected from the television monitor over her bed – in the faces of her care team. After her husband and newborn daughter were led from the room, she did, in fact, hear those words.

They were spoken by a surgeon called in after efforts to control the bleeding failed – emetic words that joined forces with her hemorrhaging and confusion and fear, and as she began to vomit, her eyelids felt heavy. She fought to keep them open, sensing that if she closed them they might never open again.

In 2018 alone, similar words perhaps were spoken to the 658 U.S. women who suffered maternal complications and whose eyes never did open again. This is the latest official maternal mortality data from the Centers for Disease Control and Prevention.

Ms. Saba’s eyes, however, remained open through her birth trauma and through the PTSD that followed. A fierce advocate for maternal health, she shares her story often, as she did during a panel discussion at the American College of Obstetricians and Gynecologists’ annual meeting in May 2019, in an effort to improve outcomes for other women and families.

But her story unfolded nearly a decade ago and those eyes still are seeing women die from childbirth. Despite her efforts and the efforts of countless other individuals and organizations working to improve maternal outcomes, the new CDC data show that the United States has the highest maternal mortality rate of any similarly wealthy industrialized nation.

“I cannot believe I’m still talking about this issue,” Ms. Saba told a standing-room-only crowd and her copanelists Neel T. Shah, MD, and Charles S. Johnson IV, whose wife, Kira, died in 2016 during surgery for bleeding complications following the birth of their second child. “If all the people who I’d written to had just listened maybe once and tried to propel my message forward back then, Charles would be in a much better situation and so would his children.”

Mr. Johnson said that for 10 hours he and other family members pleaded for help for Kira, a healthy, vibrant women he described as “sunshine personified.”

She showed signs of postpartum bleeding after delivering a healthy baby boy by C-section, but a “STAT CT” order went unheeded for hours before she was finally taken for surgery.

“You’re walking down this corridor, you get to this point, these double doors open, and you just can’t go any further – and that was the last time I saw my wife alive,” he said. “When they took Kira back into the operating room, there were three-and-a-half liters of blood in her abdomen, and her heart stopped immediately.

Kira Johnson died April 13, 2016.

“I’m not here to tell you what I think, I’m here to tell you what I know, and that’s that Kira deserved so much better, and that Kira’s not alone, and that women all over this country deserve so much better.”

The U.S. maternal mortality crisis

Dr. Shah, an ob.gyn. at Beth Israel Deaconess Medical Center and director of the Delivery Decisions Initiative at Harvard Medical School’s Ariadne Labs, both in Boston, where he has “been on this mission to improve safety in childbirth for years now,” echoed Ms. Saba’s dismay regarding the pace of progress.

“It’s not just about the present, it’s about the future, it’s about the pact that every generation ought to have with the next one to leave things at least as well as they found them. And when it comes to the health of our moms in this country, we are not doing that,” he said. “An American mom today is 50% more likely to die in childbirth than her own mother was, and 3-4 times more likely to die if she’s black than if she’s white.”

Indeed, the data released Jan. 30 by the CDC’s National Center for Health Statistics (NCHS) – the first on maternal mortality released by the agency since 2007 – show a U.S. maternal mortality rate of 17.4 maternal deaths per 100,000 live births in 2018.

The rate is higher than the 12.7 per 100,000 live births reported in 2007, but the increase is attributable mostly to changes in data collection and reporting methods. In 2003, “a consensus process recommended that all states add a standardized ‘checkbox’ to improve the identification of maternal deaths,” and implementation wasn’t complete until 2017 as “funding, technology, and state laws allowed,” meaning 2018 was the first year that data were reported in a standardized fashion across states, the CDC explained in a press release.

The data demonstrate ongoing wide racial/ethnic disparities: the maternal mortality rates for non-Hispanic black women, non-Hispanic white women, and Hispanic women were 37.1, 14.7, and 11.8 per 100,000 live births, consistent with earlier data.

Further, the rates for women aged 40 years and over were nearly eightfold higher than for those under age 25 years (81.9 vs. 10.6 per 100,000 live births).

CDC officials noted, however, that inconsistencies in reporting still leave some question about the accuracy of the data, stating in the release that “NCHS has identified instances where application of the checkbox information according to coding rules led to misclassification of maternal deaths.”

The agency is making changes in rules and reporting to ensure greater accuracy, but the numbers nevertheless reveal a startling truth: “The United States is the most dangerous place to deliver a baby in the industrialized world.”

 

Progress and challenges

Rebekah Gee, MD, an ob.gyn. who served for 4 years as Secretary of the Louisiana Department of Health before leaving the position in January, made that statement during another panel discussion at ACOG 2019 – The President’s Panel: Maternal Mortality: Progress Toward Prevention – which was moderated by Lisa M. Hollier, MD, now the immediate past president of ACOG.

Texas Children's Hospital

That’s not to say progress hasn’t been or can’t be made, Dr. Gee said.

In fact, quality improvement measures she facilitated in Louisiana led to a 25% reduction in infant mortality and a 10% reduction in neonatal intensive care unit admissions, demonstrating the potential for improvement with such initiatives, but addressing maternal issues is a greater challenge, she said.

“I think part of the sad truth is that we really focus on babies first, not moms ... and that needs to change,” Dr. Gee said.

Dr. Hollier focused much of her attention during her tenure as ACOG president on doing just that, particularly through an emphasis on heart disease, which is the leading cause of U.S. maternal deaths in pregnancy and the postpartum period.

In an interview, she shared her thoughts on the progress achieved and the work that remains.

ACOG was instrumental in the enactment of the Preventing Maternal Deaths Act of 2018, which appropriated funding for Enhancing Reviews and Surveillance to Eliminate Maternal Mortality (ERASE MM), a CDC initiative to support state-based maternal mortality review committees, said Dr. Hollier, professor of obstetrics and gynecology at Baylor College of Medicine, Houston.

“The really great news is that almost immediately after passage of the legislation, the CDC put out the notice of the funding opportunity, and they were able to provide 24 awards supporting 25 states,” she said.

ERASE MM will enhance state data collection and availability and enable a level of data sharing that “will really add strength and depth to reporting from the maternal mortality review committees, which really provides us with the best information we have to truly understand the causes, the contributing factors, and the strategies that can be put in place to prevent future maternal deaths.”

Further, the Alliance for Innovation on Maternal Health (AIM) program, a cooperative agreement with the Health Resources and Services Administration (HRSA) Maternal and Child Health Bureau to improve safety and outcomes through evidence-based patient safety bundles, was extended, and in May 2019, ACOG updated its guidance on managing cardiac contributors to maternal mortality, releasing its “Pregnancy and Heart Disease” Practice Bulletin, she said.

Dr. Hollier continues in her quest for improved maternal outcomes. She is slated to deliver a keynote address at the American College of Cardiology/World Congress of Cardiology conference March 28 in Chicago.

“I’m so excited ... to talk about the new guidelines that we’ve put out and to really talk about how cardiologists and ob.gyns. can work together to improve women’s health outcomes,” she said, adding that she already is seeing a strengthening of such partnerships.

A number of academic institutions are developing “pregnancy heart teams” to identify and care for women who have or develop heart disease during pregnancy.

“This type of collaboration ... is going to be essential to address mortality from cardiovascular causes and from cardiomyopathy, which accounts for about 25% of all maternal mortality,” she said. “The next area where we really need some buy-in is from our emergency physicians.”

Enhanced collaboration with emergency physicians and other specialties present opportunities to better identify and address pregnancy-related complications and sequelae, she said.

“Women are dying because they’re not being diagnosed,” she added. “We have to raise that level of awareness – it’s just absolutely critical.”
 

Identifying and addressing drivers of the crisis

Dr. Gee further emphasized the importance of addressing maternal health, noting that for every woman who dies from maternal causes, 100 experience maternal morbidity.

“It’s startling and it’s scary,” she said. “We are looking at this not just as a problem of outcomes, but a problem of racial inequity and racial bias and implicit bias.”

When she and her team assessed maternal mortality in Louisiana, they looked specifically at whether each death could have been prevented if, for example, blood was given sooner, cardiomyopathy was recognized sooner, or hypertension was treated on time.

“When we looked at these numbers ... when we looked at white women, 9% of the time we could have done better with our medical care; with black women, 59% of the time we could have saved her life with better care,” said Dr Gee, who is a gratis assistant professor of obstetrics and gynecology at Louisiana State University, New Orleans. “And if that doesn’t convince you that racial bias is an incredibly important thing to address – that we need to have a conversation about and address at a national level – I don’t know what would.”

In fact, numerous health, societal, socioeconomic, and other factors – some known, some yet to be identified, and many inter-related – are among the drivers of the U.S. maternal mortality crisis. In the coming months, an Ob.Gyn. News team will examine several of these drivers in depth. We’ll look specifically at the role of racism and bias, and at urban-rural disparities in access and outcomes – especially for women of color and indigenous women. We’ll address the scope and impact of each, successes and failures in addressing the problems, and ongoing initiatives.

Follow us for insights from experts, researchers, practicing physicians, and patients and families affected by the maternal mortality crisis, and stay with us through coverage of ACOG 2020 for perspective on what, specifically, ob.gyns. can do about it.

Mr. Johnson proposed a starting point:

“Here’s the good news – you guys ready for this? We can fix this,” he said, adding that the solution starts with “speaking Timoria’s name ... speaking the name of Kira Dixon Johnson ... speaking the names of these women and then asking the people that are around you, ‘What are we prepared to do to make sure that this doesn’t happen to other women.’ ”

sworcester@mdedge.com

The Trump Administration is looking to telehealth services to play a more prominent role in helping mitigate the spread of COVID-19 by expanding existing benefits for Medicare beneficiaries.

“Medicare can pay for office, hospital, and other visits furnished via telehealth across the country and including in patients’ places of residence, starting March 6, 2020,” the Centers for Medicare & Medicaid Services said in a fact sheet issued March 17.

Some of the existing benefits were previously limited to rural communities.

“Medicare beneficiaries across the nation, no matter where they live, will now be able to receive a wide range of services via telehealth without ever having to leave home,” CMS Administrator Seema Verma said during a March 17 White House press briefing on administration actions to contain the spread of COVID-19. “These services can also be provided in a variety of settings, including nursing homes, hospital outpatient departments, and more.”

That means that seniors can continue to receive their routine care without having to leave the home and risk infection, or they can get medical guidance if they have mild symptoms, which would help mitigate the spread to others.

“This shift is very important for clinicians and providers who, over the coming weeks, will face considerable strain on their time and resources,” Dr. Verma said. “[It] allows the health care system to prioritize care for those who have more needs or who are in dire need, and it also preserves protective equipment.”

A range of providers will be able to deliver telehealth services, including doctors, nurse practitioners, clinical psychologists, and licensed clinical social workers. Visits using the telehealth services will be considered the same as in-person visits and will be paid as if the patient were seen in the office.

This expansion of Medicare telehealth services will continue for the duration of the COVID-19 public health emergency.

“In addition, the [Health and Human Services’] office of inspector general is providing flexibility for health care providers to reduce or waive cost-sharing for telehealth visits paid by federal health care programs,” the fact sheet states. CMS also said it will not conduct audits to ensure that an established relationship exists between the provider and the patient – a prior requirement for telehealth billing – during this public health emergency.

Billing for virtual check-ins, which are essentially brief conversations that may not require a full visit to the physician office, needs an established relationship between the practice and the patient. Likewise, for e-visits, which include non–face-to-face communications through online patient portals, billing can occur only when there is an established patient relationship.

Key to the expansion is that it will cover the entire United States and will not be limited to rural areas.

Dr. Verma also noted that the administration “will be temporarily suspending certain HIPAA requirements so that doctors can provide telehealth with their own phones.”

She noted this was all a part of mitigation efforts to limit the spread of COVID-19.

“As we are encouraging Americans to stay home whenever possible, we don’t want our Medicare policies getting in the way,” she said, adding that state Medicaid agencies can expand their telehealth services without the approval of CMS during this emergency.

gtwachtman@mdedge.com

The Trump Administration is looking to telehealth services to play a more prominent role in helping mitigate the spread of COVID-19 by expanding existing benefits for Medicare beneficiaries.

“Medicare can pay for office, hospital, and other visits furnished via telehealth across the country and including in patients’ places of residence, starting March 6, 2020,” the Centers for Medicare & Medicaid Services said in a fact sheet issued March 17.

Some of the existing benefits were previously limited to rural communities.

“Medicare beneficiaries across the nation, no matter where they live, will now be able to receive a wide range of services via telehealth without ever having to leave home,” CMS Administrator Seema Verma said during a March 17 White House press briefing on administration actions to contain the spread of COVID-19. “These services can also be provided in a variety of settings, including nursing homes, hospital outpatient departments, and more.”

That means that seniors can continue to receive their routine care without having to leave the home and risk infection, or they can get medical guidance if they have mild symptoms, which would help mitigate the spread to others.

“This shift is very important for clinicians and providers who, over the coming weeks, will face considerable strain on their time and resources,” Dr. Verma said. “[It] allows the health care system to prioritize care for those who have more needs or who are in dire need, and it also preserves protective equipment.”

A range of providers will be able to deliver telehealth services, including doctors, nurse practitioners, clinical psychologists, and licensed clinical social workers. Visits using the telehealth services will be considered the same as in-person visits and will be paid as if the patient were seen in the office.

This expansion of Medicare telehealth services will continue for the duration of the COVID-19 public health emergency.

“In addition, the [Health and Human Services’] office of inspector general is providing flexibility for health care providers to reduce or waive cost-sharing for telehealth visits paid by federal health care programs,” the fact sheet states. CMS also said it will not conduct audits to ensure that an established relationship exists between the provider and the patient – a prior requirement for telehealth billing – during this public health emergency.

Billing for virtual check-ins, which are essentially brief conversations that may not require a full visit to the physician office, needs an established relationship between the practice and the patient. Likewise, for e-visits, which include non–face-to-face communications through online patient portals, billing can occur only when there is an established patient relationship.

Key to the expansion is that it will cover the entire United States and will not be limited to rural areas.

Dr. Verma also noted that the administration “will be temporarily suspending certain HIPAA requirements so that doctors can provide telehealth with their own phones.”

She noted this was all a part of mitigation efforts to limit the spread of COVID-19.

“As we are encouraging Americans to stay home whenever possible, we don’t want our Medicare policies getting in the way,” she said, adding that state Medicaid agencies can expand their telehealth services without the approval of CMS during this emergency.

gtwachtman@mdedge.com

The Trump Administration is looking to telehealth services to play a more prominent role in helping mitigate the spread of COVID-19 by expanding existing benefits for Medicare beneficiaries.

“Medicare can pay for office, hospital, and other visits furnished via telehealth across the country and including in patients’ places of residence, starting March 6, 2020,” the Centers for Medicare & Medicaid Services said in a fact sheet issued March 17.

Some of the existing benefits were previously limited to rural communities.

“Medicare beneficiaries across the nation, no matter where they live, will now be able to receive a wide range of services via telehealth without ever having to leave home,” CMS Administrator Seema Verma said during a March 17 White House press briefing on administration actions to contain the spread of COVID-19. “These services can also be provided in a variety of settings, including nursing homes, hospital outpatient departments, and more.”

That means that seniors can continue to receive their routine care without having to leave the home and risk infection, or they can get medical guidance if they have mild symptoms, which would help mitigate the spread to others.

“This shift is very important for clinicians and providers who, over the coming weeks, will face considerable strain on their time and resources,” Dr. Verma said. “[It] allows the health care system to prioritize care for those who have more needs or who are in dire need, and it also preserves protective equipment.”

A range of providers will be able to deliver telehealth services, including doctors, nurse practitioners, clinical psychologists, and licensed clinical social workers. Visits using the telehealth services will be considered the same as in-person visits and will be paid as if the patient were seen in the office.

This expansion of Medicare telehealth services will continue for the duration of the COVID-19 public health emergency.

“In addition, the [Health and Human Services’] office of inspector general is providing flexibility for health care providers to reduce or waive cost-sharing for telehealth visits paid by federal health care programs,” the fact sheet states. CMS also said it will not conduct audits to ensure that an established relationship exists between the provider and the patient – a prior requirement for telehealth billing – during this public health emergency.

Billing for virtual check-ins, which are essentially brief conversations that may not require a full visit to the physician office, needs an established relationship between the practice and the patient. Likewise, for e-visits, which include non–face-to-face communications through online patient portals, billing can occur only when there is an established patient relationship.

Key to the expansion is that it will cover the entire United States and will not be limited to rural areas.

Dr. Verma also noted that the administration “will be temporarily suspending certain HIPAA requirements so that doctors can provide telehealth with their own phones.”

She noted this was all a part of mitigation efforts to limit the spread of COVID-19.

“As we are encouraging Americans to stay home whenever possible, we don’t want our Medicare policies getting in the way,” she said, adding that state Medicaid agencies can expand their telehealth services without the approval of CMS during this emergency.

gtwachtman@mdedge.com