TORONTO – Neoadjuvant combined chemotherapy and immunotherapy (CT-IO) yielded high pathologic response rates for locally advanced, potentially resectable non-small cell lung cancer in the phase 2 multicenter study Nadim study.

Sharon Worcester/MDedge News

All 30 adults with stage IIIA N2 non-small cell lung cancer (NSCLC) who enrolled in the ongoing single-arm, open-label study and have undergone surgery to date, had resectable tumors following neoadjuvant treatment, Mariano Provencio, MD, of Hospital Puerta de Hierro, Madrid, Spain, reported at the World Conference on Lung Cancer.

The complete and partial response rates following the treatment were 10% and 60%, respectively, and the remaining patients had stable disease, Dr. Provencio said, noting that an additional 10 enrolled patients have completed treatment and are awaiting resection, and another 3 are still completing treatment.

The overall major pathologic response rate was 80%, including 75% with complete remission, he said at the conference, which was sponsored by the International Association for the Study of Lung Cancer.

“With a median follow-up of 4 months, no patients suffered any recurrence,” he said. “We have been unable to identify any significant factor related to the response, but we still do not have information about biomarkers.”

The study participants had a median age of 64 years, most (73%) were men, and all were current or former smokers. All received the planned neoadjuvant doses, which included 3 cycles of intravenous nivolumab at a dose of 360 mg every 3 weeks, plus 200 mg/m2 of paclitaxel and carboplatin at AUC 6 every 3 weeks.

“The most important toxicity was hematological toxicity related to chemotherapy; there were very few episodes of non-hematological toxicity,” he said.

Tumors were then assessed, and surgery–lobectomy in 90% of cases–was performed in the 3rd or 4th week after day 21 of the third neoadjuvant treatment cycle.

“There were no intraoperative complications, and 7 patients experienced some postoperative complications, but there was no postoperative mortality,” he said.

Adjuvant treatment included 240 mg of intravenous nivolumab every 2 weeks for 4 months and then 480 mg every 4 weeks for 8 months after resection.

The primary end-point of the study is 24-month progression-free survival.

CT-IO has a high response rate and longer survival in unselected patients with metastatic NSCLC, but there were previously no data about this combination in the neoadjuvant setting, Dr. Provencio said.

The findings of this ongoing study are limited by their preliminary nature and the related lack of information about overall survival and biomarkers, Dr. Provencio said.

Sharon Worcester/MDedge News

“But the higher complete remission and major pathological response rates make this a promising future treatment in stage 3 [NSCLC,] he said.

Indeed, the Nadim study thus far has shown “an amazing result that needs to be verified ... [there is] no prospective proof yet in this context that major pathologic response is parlayed with improved [progression-free survival] or [overall survival],” said discussant Corey Langer, MD, professor of medicine and director of thoracic oncology at the University of Pennsylvania, Philadelphia. “We need to track the late sequelae and [central nervous system] recurrences.”

Dr. Provencio reported relationships with AstraZeneca, Bristol-Meyers Squibb, Fabre, Merck, Pierre, Roche, and Bristol-Meyers Squibb. Dr. Langer reported relationships with numerous companies and organizations.

SOURCE: Provencio, Mario et al., WCLC 2018 Abstract OA01.05.

TORONTO – Neoadjuvant combined chemotherapy and immunotherapy (CT-IO) yielded high pathologic response rates for locally advanced, potentially resectable non-small cell lung cancer in the phase 2 multicenter study Nadim study.

Sharon Worcester/MDedge News

All 30 adults with stage IIIA N2 non-small cell lung cancer (NSCLC) who enrolled in the ongoing single-arm, open-label study and have undergone surgery to date, had resectable tumors following neoadjuvant treatment, Mariano Provencio, MD, of Hospital Puerta de Hierro, Madrid, Spain, reported at the World Conference on Lung Cancer.

The complete and partial response rates following the treatment were 10% and 60%, respectively, and the remaining patients had stable disease, Dr. Provencio said, noting that an additional 10 enrolled patients have completed treatment and are awaiting resection, and another 3 are still completing treatment.

The overall major pathologic response rate was 80%, including 75% with complete remission, he said at the conference, which was sponsored by the International Association for the Study of Lung Cancer.

“With a median follow-up of 4 months, no patients suffered any recurrence,” he said. “We have been unable to identify any significant factor related to the response, but we still do not have information about biomarkers.”

The study participants had a median age of 64 years, most (73%) were men, and all were current or former smokers. All received the planned neoadjuvant doses, which included 3 cycles of intravenous nivolumab at a dose of 360 mg every 3 weeks, plus 200 mg/m2 of paclitaxel and carboplatin at AUC 6 every 3 weeks.

“The most important toxicity was hematological toxicity related to chemotherapy; there were very few episodes of non-hematological toxicity,” he said.

Tumors were then assessed, and surgery–lobectomy in 90% of cases–was performed in the 3rd or 4th week after day 21 of the third neoadjuvant treatment cycle.

“There were no intraoperative complications, and 7 patients experienced some postoperative complications, but there was no postoperative mortality,” he said.

Adjuvant treatment included 240 mg of intravenous nivolumab every 2 weeks for 4 months and then 480 mg every 4 weeks for 8 months after resection.

The primary end-point of the study is 24-month progression-free survival.

CT-IO has a high response rate and longer survival in unselected patients with metastatic NSCLC, but there were previously no data about this combination in the neoadjuvant setting, Dr. Provencio said.

The findings of this ongoing study are limited by their preliminary nature and the related lack of information about overall survival and biomarkers, Dr. Provencio said.

Sharon Worcester/MDedge News

“But the higher complete remission and major pathological response rates make this a promising future treatment in stage 3 [NSCLC,] he said.

Indeed, the Nadim study thus far has shown “an amazing result that needs to be verified ... [there is] no prospective proof yet in this context that major pathologic response is parlayed with improved [progression-free survival] or [overall survival],” said discussant Corey Langer, MD, professor of medicine and director of thoracic oncology at the University of Pennsylvania, Philadelphia. “We need to track the late sequelae and [central nervous system] recurrences.”

Dr. Provencio reported relationships with AstraZeneca, Bristol-Meyers Squibb, Fabre, Merck, Pierre, Roche, and Bristol-Meyers Squibb. Dr. Langer reported relationships with numerous companies and organizations.

SOURCE: Provencio, Mario et al., WCLC 2018 Abstract OA01.05.

TORONTO – Neoadjuvant combined chemotherapy and immunotherapy (CT-IO) yielded high pathologic response rates for locally advanced, potentially resectable non-small cell lung cancer in the phase 2 multicenter study Nadim study.

Sharon Worcester/MDedge News

All 30 adults with stage IIIA N2 non-small cell lung cancer (NSCLC) who enrolled in the ongoing single-arm, open-label study and have undergone surgery to date, had resectable tumors following neoadjuvant treatment, Mariano Provencio, MD, of Hospital Puerta de Hierro, Madrid, Spain, reported at the World Conference on Lung Cancer.

The complete and partial response rates following the treatment were 10% and 60%, respectively, and the remaining patients had stable disease, Dr. Provencio said, noting that an additional 10 enrolled patients have completed treatment and are awaiting resection, and another 3 are still completing treatment.

The overall major pathologic response rate was 80%, including 75% with complete remission, he said at the conference, which was sponsored by the International Association for the Study of Lung Cancer.

“With a median follow-up of 4 months, no patients suffered any recurrence,” he said. “We have been unable to identify any significant factor related to the response, but we still do not have information about biomarkers.”

The study participants had a median age of 64 years, most (73%) were men, and all were current or former smokers. All received the planned neoadjuvant doses, which included 3 cycles of intravenous nivolumab at a dose of 360 mg every 3 weeks, plus 200 mg/m2 of paclitaxel and carboplatin at AUC 6 every 3 weeks.

“The most important toxicity was hematological toxicity related to chemotherapy; there were very few episodes of non-hematological toxicity,” he said.

Tumors were then assessed, and surgery–lobectomy in 90% of cases–was performed in the 3rd or 4th week after day 21 of the third neoadjuvant treatment cycle.

“There were no intraoperative complications, and 7 patients experienced some postoperative complications, but there was no postoperative mortality,” he said.

Adjuvant treatment included 240 mg of intravenous nivolumab every 2 weeks for 4 months and then 480 mg every 4 weeks for 8 months after resection.

The primary end-point of the study is 24-month progression-free survival.

CT-IO has a high response rate and longer survival in unselected patients with metastatic NSCLC, but there were previously no data about this combination in the neoadjuvant setting, Dr. Provencio said.

The findings of this ongoing study are limited by their preliminary nature and the related lack of information about overall survival and biomarkers, Dr. Provencio said.

Sharon Worcester/MDedge News

“But the higher complete remission and major pathological response rates make this a promising future treatment in stage 3 [NSCLC,] he said.

Indeed, the Nadim study thus far has shown “an amazing result that needs to be verified ... [there is] no prospective proof yet in this context that major pathologic response is parlayed with improved [progression-free survival] or [overall survival],” said discussant Corey Langer, MD, professor of medicine and director of thoracic oncology at the University of Pennsylvania, Philadelphia. “We need to track the late sequelae and [central nervous system] recurrences.”

Dr. Provencio reported relationships with AstraZeneca, Bristol-Meyers Squibb, Fabre, Merck, Pierre, Roche, and Bristol-Meyers Squibb. Dr. Langer reported relationships with numerous companies and organizations.

SOURCE: Provencio, Mario et al., WCLC 2018 Abstract OA01.05.

A protective effect was seen with regard to hepatitis C virus (HCV) transmission among individuals who “reversed transitioned” to noninjected drug use and in persons who used noninjected drugs in addition to injecting, according to an interview study of 846 drug users.

©andrewsafonov/Thinkstock

Data were collected between January 2007 and December 2017 as part of a long-running study of persons entering Mount Sinai Beth Israel drug detoxification and methadone maintenance programs, reported Don C. Des Jarlais, MD, of the Icahn School of Medicine at Mount Sinai, New York, and his colleagues.

Among the 846 individuals studied, men comprised 79%; 41% were white, 15% African American, and 40% Hispanic, with a mean age of 35 years. They were all currently persons who injected drugs (PWID), according to the report published in Drug and Alcohol Dependence.

A total of 97 persons (11%) “reverse transitioned” back to noninjected drug use, according to the researchers; this reverse transitioning was strongly associated with lower HCV positivity, compared with those who continued injecting (30% vs. 47%, respectively; P less than .005).

There was a substantial difference in the HCV prevalence between PWID who reported noninjected use of heroin (43%) versus PWID who did not report noninjected use of heroin (53%) (P = .005).

Distributive needle sharing was common in HCV seropositives who were injecting cocaine in the 6 months prior to the interview: 28% of the HCV seropositives injecting cocaine reported distributive sharing versus 14% of the HCV seropositives not injecting cocaine (P = .001).

“Harm reduction for PWID has been largely defined in terms of ‘safer injection,’ using sterile injection equipment, proper preparation of the injecting site, etc. We would like to suggest that harm reduction for PWID be broadened to include reverse transitions back to exclusive noninjecting use and frequent substitution of noninjecting for injecting use,” the investigators suggested.

The study was funded by the U.S. National Institute on Drug Abuse. The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Des Jarlais DC et al. Drug Alcohol Depend. 2018 Sep 12. doi: 10.1016/j.drugalcdep.2018.07.034.

A protective effect was seen with regard to hepatitis C virus (HCV) transmission among individuals who “reversed transitioned” to noninjected drug use and in persons who used noninjected drugs in addition to injecting, according to an interview study of 846 drug users.

©andrewsafonov/Thinkstock

Data were collected between January 2007 and December 2017 as part of a long-running study of persons entering Mount Sinai Beth Israel drug detoxification and methadone maintenance programs, reported Don C. Des Jarlais, MD, of the Icahn School of Medicine at Mount Sinai, New York, and his colleagues.

Among the 846 individuals studied, men comprised 79%; 41% were white, 15% African American, and 40% Hispanic, with a mean age of 35 years. They were all currently persons who injected drugs (PWID), according to the report published in Drug and Alcohol Dependence.

A total of 97 persons (11%) “reverse transitioned” back to noninjected drug use, according to the researchers; this reverse transitioning was strongly associated with lower HCV positivity, compared with those who continued injecting (30% vs. 47%, respectively; P less than .005).

There was a substantial difference in the HCV prevalence between PWID who reported noninjected use of heroin (43%) versus PWID who did not report noninjected use of heroin (53%) (P = .005).

Distributive needle sharing was common in HCV seropositives who were injecting cocaine in the 6 months prior to the interview: 28% of the HCV seropositives injecting cocaine reported distributive sharing versus 14% of the HCV seropositives not injecting cocaine (P = .001).

“Harm reduction for PWID has been largely defined in terms of ‘safer injection,’ using sterile injection equipment, proper preparation of the injecting site, etc. We would like to suggest that harm reduction for PWID be broadened to include reverse transitions back to exclusive noninjecting use and frequent substitution of noninjecting for injecting use,” the investigators suggested.

The study was funded by the U.S. National Institute on Drug Abuse. The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Des Jarlais DC et al. Drug Alcohol Depend. 2018 Sep 12. doi: 10.1016/j.drugalcdep.2018.07.034.

A protective effect was seen with regard to hepatitis C virus (HCV) transmission among individuals who “reversed transitioned” to noninjected drug use and in persons who used noninjected drugs in addition to injecting, according to an interview study of 846 drug users.

©andrewsafonov/Thinkstock

Data were collected between January 2007 and December 2017 as part of a long-running study of persons entering Mount Sinai Beth Israel drug detoxification and methadone maintenance programs, reported Don C. Des Jarlais, MD, of the Icahn School of Medicine at Mount Sinai, New York, and his colleagues.

Among the 846 individuals studied, men comprised 79%; 41% were white, 15% African American, and 40% Hispanic, with a mean age of 35 years. They were all currently persons who injected drugs (PWID), according to the report published in Drug and Alcohol Dependence.

A total of 97 persons (11%) “reverse transitioned” back to noninjected drug use, according to the researchers; this reverse transitioning was strongly associated with lower HCV positivity, compared with those who continued injecting (30% vs. 47%, respectively; P less than .005).

There was a substantial difference in the HCV prevalence between PWID who reported noninjected use of heroin (43%) versus PWID who did not report noninjected use of heroin (53%) (P = .005).

Distributive needle sharing was common in HCV seropositives who were injecting cocaine in the 6 months prior to the interview: 28% of the HCV seropositives injecting cocaine reported distributive sharing versus 14% of the HCV seropositives not injecting cocaine (P = .001).

“Harm reduction for PWID has been largely defined in terms of ‘safer injection,’ using sterile injection equipment, proper preparation of the injecting site, etc. We would like to suggest that harm reduction for PWID be broadened to include reverse transitions back to exclusive noninjecting use and frequent substitution of noninjecting for injecting use,” the investigators suggested.

The study was funded by the U.S. National Institute on Drug Abuse. The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Des Jarlais DC et al. Drug Alcohol Depend. 2018 Sep 12. doi: 10.1016/j.drugalcdep.2018.07.034.

A proposed rule from the White House would make it harder for legal immigrants to get green cards if they have received certain kinds of public assistance – including Medicaid, food stamps, and housing subsidies. Green cards allow them to live and work permanently in the United States.

“Those seeking to immigrate to the United States must show they can support themselves financially,” Homeland Security Secretary Kirstjen Nielsen said in a statement.

The proposal, announced Sept. 22, marks a new frontier in the administration’s long-term effort to curb immigration, both legal and illegal. It already has spurred intense criticism from Democrats, anti-poverty activists, health care organizations, and immigrants’ rights advocates, who call its restrictions unprecedented.

“We are operating in an overall climate of tremendous fear and anxiety as a result of the administration’s overall approach to immigration enforcement and immigration policy,” said Mark Greenberg, a senior fellow at the Migration Policy Institute, which studies migration and refugee policies at local, national, and international levels. He is also a former Obama administration official.

But what effect would this proposal have?

It’s a complicated question, touching upon vast government programs, with billions of dollars at stake. While the implications aren’t all immediately clear, Kaiser Health News breaks down some of the key elements.
 

1. First thing first: What is the White House proposing?

The Trump administration wants to redefine a status known as “public charge” – a category used to determine whether someone seeking permanent resident status is “likely to become primarily dependent on the government for subsistence.”

In the past, people have been at risk of being defined a “public charge” if they took cash welfare – known as Temporary Assistance for Needy Families, or Supplemental Security Income – or federal help paying for long-term care. (Immigrants must be in the country legally for 5 years before being eligible for TANF or SSI.)

And that “public charge” designation could undermine their applications for permanent residence.

The new rule would expand the list to include some health insurance, food, and housing programs. Specifically, it would penalize green-card applicants for using Medicaid, a federal-state health plan for low-income people. (Penalties would not apply for using Medicaid in certain emergencies or for some Medicaid services provided through schools and disability programs.)

Using food stamps, Section 8 rental assistance, and federal housing vouchers also would count against applicants. Enrollment in a Medicare Part D program subsidy to help low-income people buy prescription drugs would work against them, too.

The proposal “is definitely a dramatic change from how public charge works today,” said Kelly Whitener, an associate professor at Georgetown University’s Center for Children and Families who specializes in pediatric health benefits and managed-care systems.

A leaked version of the rule from March suggested officials then were also considering penalizing those who receive subsidies to buy health insurance on the Affordable Care Act marketplaces. But that idea was not in the proposal. The marketplace subsidies are aimed at people at a generally higher income bracket than the beneficiaries targeted in the Trump plan, Whitener noted.

“They’re really homing in on low-income immigrants,” she added.

Nielsen said the proposed rule is “intended to promote immigrant self-sufficiency and protect finite resources.”
 

2. Is this as unprecedented as critics say?

Yes.

Public charge is an old idea. In the 1990s, lawmakers expanded it to consider explicitly whether people had received cash-based welfare.

But including programs like Medicaid and food stamps, which are much wider in scope, is a significant change. It would more likely hit working people – the majority of people on Medicaid are themselves employed, and almost 80% live in families with at least one working member, according to data compiled by the Kaiser Family Foundation. (Kaiser Health News is an editorially independent program of the foundation.)

Children who are American citizens but whose parents are immigrants could be more likely to suffer repercussions, said some experts. When parents opt out of public assistance for fear of their own legal status, their kids are less likely to be enrolled in programs such as the Children’s Health Insurance Program, or CHIP, for which they would qualify.

To be clear, receiving public aid wouldn’t necessarily stop people from getting a green card. But it would tilt the odds against them.

“Another piece is the enormous discretion the administration will have under its proposal in making judgments about who gets admitted to the country and who gets a green card,” said the Migration Policy Institute’s Greenberg.
 

3. When will the policy shift take effect?

This is an early step in the complex federal rule-making process. And a lot could still change.

Once the proposed rule appears in the Federal Register, a 60-day countdown starts, during which anyone can weigh in with comments.

A final rule likely wouldn’t take effect until 2019.

And DHS is still seeking input on some details. For instance, it hasn’t decided whether CHIP would be counted as one of the “public charge” eligible programs.

In the interim, people who had received public benefits before the rule took effect would not be penalized for doing so.
 

4. Already, though, the proposal is having effects

DHS estimates that 2.5% of eligible immigrants would drop out of public benefits programs because of this change – which would tally about $1.5 billion worth of federal money per year. But others expect a much larger impact.

“The chilling effects will be vastly greater than the individuals directly affected,” Greenberg said. “There’s considerable reason to believe that [the White House estimate] may be a significant understatement.”

In the proposed rule, DHS notes that the changes could result in “worse health outcomes,” “increased use of emergency rooms,” “increased prevalence of communicable diseases,” “increased rates of poverty,” and other concerns.

Given the complexity of these programs and the proposed rule – and the high stakes at play – low-income immigrants would be much more likely to avoid public benefits altogether, immigration experts said. Millions of immigrants are likely to be affected directly or indirectly, according to the Center for Law and Social Policy, a D.C.-based nonprofit organization.

That could have stark health implications.

Take free vaccines, for which children are often eligible and which would not be subject to the public charge rule. Families afraid of jeopardizing a green card could still be more likely to opt out of that service, Whitener said.

Already, she added, there are reports of people declining federal assistance – even though nothing has yet happened.

“The fear factor cannot be underestimated,” she said.
 

5. Will people sue?

Legal action is likely.

Officials such as California Attorney General Xavier Becerra, who has frequently clashed with the White House, are weighing challenges to the rule.

“The Trump Administration’s proposal punishes hard-working immigrant families – even targeting children who are citizens – for utilizing programs that provide basic nutrition and healthcare. This is an assault on our families and our communities,” Becerra said in a statement.

But these actions depend on the final shape of the regulation, which could change through the rule-making process.

“They are likely to receive a very large number of sharply critical comments, and there is no way to know what changes they might make as a result,” Greenberg said.
 

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente. KHN’s coverage of children’s health care issues is supported in part by the Heising-Simons Foundation.

A proposed rule from the White House would make it harder for legal immigrants to get green cards if they have received certain kinds of public assistance – including Medicaid, food stamps, and housing subsidies. Green cards allow them to live and work permanently in the United States.

“Those seeking to immigrate to the United States must show they can support themselves financially,” Homeland Security Secretary Kirstjen Nielsen said in a statement.

The proposal, announced Sept. 22, marks a new frontier in the administration’s long-term effort to curb immigration, both legal and illegal. It already has spurred intense criticism from Democrats, anti-poverty activists, health care organizations, and immigrants’ rights advocates, who call its restrictions unprecedented.

“We are operating in an overall climate of tremendous fear and anxiety as a result of the administration’s overall approach to immigration enforcement and immigration policy,” said Mark Greenberg, a senior fellow at the Migration Policy Institute, which studies migration and refugee policies at local, national, and international levels. He is also a former Obama administration official.

But what effect would this proposal have?

It’s a complicated question, touching upon vast government programs, with billions of dollars at stake. While the implications aren’t all immediately clear, Kaiser Health News breaks down some of the key elements.
 

1. First thing first: What is the White House proposing?

The Trump administration wants to redefine a status known as “public charge” – a category used to determine whether someone seeking permanent resident status is “likely to become primarily dependent on the government for subsistence.”

In the past, people have been at risk of being defined a “public charge” if they took cash welfare – known as Temporary Assistance for Needy Families, or Supplemental Security Income – or federal help paying for long-term care. (Immigrants must be in the country legally for 5 years before being eligible for TANF or SSI.)

And that “public charge” designation could undermine their applications for permanent residence.

The new rule would expand the list to include some health insurance, food, and housing programs. Specifically, it would penalize green-card applicants for using Medicaid, a federal-state health plan for low-income people. (Penalties would not apply for using Medicaid in certain emergencies or for some Medicaid services provided through schools and disability programs.)

Using food stamps, Section 8 rental assistance, and federal housing vouchers also would count against applicants. Enrollment in a Medicare Part D program subsidy to help low-income people buy prescription drugs would work against them, too.

The proposal “is definitely a dramatic change from how public charge works today,” said Kelly Whitener, an associate professor at Georgetown University’s Center for Children and Families who specializes in pediatric health benefits and managed-care systems.

A leaked version of the rule from March suggested officials then were also considering penalizing those who receive subsidies to buy health insurance on the Affordable Care Act marketplaces. But that idea was not in the proposal. The marketplace subsidies are aimed at people at a generally higher income bracket than the beneficiaries targeted in the Trump plan, Whitener noted.

“They’re really homing in on low-income immigrants,” she added.

Nielsen said the proposed rule is “intended to promote immigrant self-sufficiency and protect finite resources.”
 

2. Is this as unprecedented as critics say?

Yes.

Public charge is an old idea. In the 1990s, lawmakers expanded it to consider explicitly whether people had received cash-based welfare.

But including programs like Medicaid and food stamps, which are much wider in scope, is a significant change. It would more likely hit working people – the majority of people on Medicaid are themselves employed, and almost 80% live in families with at least one working member, according to data compiled by the Kaiser Family Foundation. (Kaiser Health News is an editorially independent program of the foundation.)

Children who are American citizens but whose parents are immigrants could be more likely to suffer repercussions, said some experts. When parents opt out of public assistance for fear of their own legal status, their kids are less likely to be enrolled in programs such as the Children’s Health Insurance Program, or CHIP, for which they would qualify.

To be clear, receiving public aid wouldn’t necessarily stop people from getting a green card. But it would tilt the odds against them.

“Another piece is the enormous discretion the administration will have under its proposal in making judgments about who gets admitted to the country and who gets a green card,” said the Migration Policy Institute’s Greenberg.
 

3. When will the policy shift take effect?

This is an early step in the complex federal rule-making process. And a lot could still change.

Once the proposed rule appears in the Federal Register, a 60-day countdown starts, during which anyone can weigh in with comments.

A final rule likely wouldn’t take effect until 2019.

And DHS is still seeking input on some details. For instance, it hasn’t decided whether CHIP would be counted as one of the “public charge” eligible programs.

In the interim, people who had received public benefits before the rule took effect would not be penalized for doing so.
 

4. Already, though, the proposal is having effects

DHS estimates that 2.5% of eligible immigrants would drop out of public benefits programs because of this change – which would tally about $1.5 billion worth of federal money per year. But others expect a much larger impact.

“The chilling effects will be vastly greater than the individuals directly affected,” Greenberg said. “There’s considerable reason to believe that [the White House estimate] may be a significant understatement.”

In the proposed rule, DHS notes that the changes could result in “worse health outcomes,” “increased use of emergency rooms,” “increased prevalence of communicable diseases,” “increased rates of poverty,” and other concerns.

Given the complexity of these programs and the proposed rule – and the high stakes at play – low-income immigrants would be much more likely to avoid public benefits altogether, immigration experts said. Millions of immigrants are likely to be affected directly or indirectly, according to the Center for Law and Social Policy, a D.C.-based nonprofit organization.

That could have stark health implications.

Take free vaccines, for which children are often eligible and which would not be subject to the public charge rule. Families afraid of jeopardizing a green card could still be more likely to opt out of that service, Whitener said.

Already, she added, there are reports of people declining federal assistance – even though nothing has yet happened.

“The fear factor cannot be underestimated,” she said.
 

5. Will people sue?

Legal action is likely.

Officials such as California Attorney General Xavier Becerra, who has frequently clashed with the White House, are weighing challenges to the rule.

“The Trump Administration’s proposal punishes hard-working immigrant families – even targeting children who are citizens – for utilizing programs that provide basic nutrition and healthcare. This is an assault on our families and our communities,” Becerra said in a statement.

But these actions depend on the final shape of the regulation, which could change through the rule-making process.

“They are likely to receive a very large number of sharply critical comments, and there is no way to know what changes they might make as a result,” Greenberg said.
 

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente. KHN’s coverage of children’s health care issues is supported in part by the Heising-Simons Foundation.

A proposed rule from the White House would make it harder for legal immigrants to get green cards if they have received certain kinds of public assistance – including Medicaid, food stamps, and housing subsidies. Green cards allow them to live and work permanently in the United States.

“Those seeking to immigrate to the United States must show they can support themselves financially,” Homeland Security Secretary Kirstjen Nielsen said in a statement.

The proposal, announced Sept. 22, marks a new frontier in the administration’s long-term effort to curb immigration, both legal and illegal. It already has spurred intense criticism from Democrats, anti-poverty activists, health care organizations, and immigrants’ rights advocates, who call its restrictions unprecedented.

“We are operating in an overall climate of tremendous fear and anxiety as a result of the administration’s overall approach to immigration enforcement and immigration policy,” said Mark Greenberg, a senior fellow at the Migration Policy Institute, which studies migration and refugee policies at local, national, and international levels. He is also a former Obama administration official.

But what effect would this proposal have?

It’s a complicated question, touching upon vast government programs, with billions of dollars at stake. While the implications aren’t all immediately clear, Kaiser Health News breaks down some of the key elements.
 

1. First thing first: What is the White House proposing?

The Trump administration wants to redefine a status known as “public charge” – a category used to determine whether someone seeking permanent resident status is “likely to become primarily dependent on the government for subsistence.”

In the past, people have been at risk of being defined a “public charge” if they took cash welfare – known as Temporary Assistance for Needy Families, or Supplemental Security Income – or federal help paying for long-term care. (Immigrants must be in the country legally for 5 years before being eligible for TANF or SSI.)

And that “public charge” designation could undermine their applications for permanent residence.

The new rule would expand the list to include some health insurance, food, and housing programs. Specifically, it would penalize green-card applicants for using Medicaid, a federal-state health plan for low-income people. (Penalties would not apply for using Medicaid in certain emergencies or for some Medicaid services provided through schools and disability programs.)

Using food stamps, Section 8 rental assistance, and federal housing vouchers also would count against applicants. Enrollment in a Medicare Part D program subsidy to help low-income people buy prescription drugs would work against them, too.

The proposal “is definitely a dramatic change from how public charge works today,” said Kelly Whitener, an associate professor at Georgetown University’s Center for Children and Families who specializes in pediatric health benefits and managed-care systems.

A leaked version of the rule from March suggested officials then were also considering penalizing those who receive subsidies to buy health insurance on the Affordable Care Act marketplaces. But that idea was not in the proposal. The marketplace subsidies are aimed at people at a generally higher income bracket than the beneficiaries targeted in the Trump plan, Whitener noted.

“They’re really homing in on low-income immigrants,” she added.

Nielsen said the proposed rule is “intended to promote immigrant self-sufficiency and protect finite resources.”
 

2. Is this as unprecedented as critics say?

Yes.

Public charge is an old idea. In the 1990s, lawmakers expanded it to consider explicitly whether people had received cash-based welfare.

But including programs like Medicaid and food stamps, which are much wider in scope, is a significant change. It would more likely hit working people – the majority of people on Medicaid are themselves employed, and almost 80% live in families with at least one working member, according to data compiled by the Kaiser Family Foundation. (Kaiser Health News is an editorially independent program of the foundation.)

Children who are American citizens but whose parents are immigrants could be more likely to suffer repercussions, said some experts. When parents opt out of public assistance for fear of their own legal status, their kids are less likely to be enrolled in programs such as the Children’s Health Insurance Program, or CHIP, for which they would qualify.

To be clear, receiving public aid wouldn’t necessarily stop people from getting a green card. But it would tilt the odds against them.

“Another piece is the enormous discretion the administration will have under its proposal in making judgments about who gets admitted to the country and who gets a green card,” said the Migration Policy Institute’s Greenberg.
 

3. When will the policy shift take effect?

This is an early step in the complex federal rule-making process. And a lot could still change.

Once the proposed rule appears in the Federal Register, a 60-day countdown starts, during which anyone can weigh in with comments.

A final rule likely wouldn’t take effect until 2019.

And DHS is still seeking input on some details. For instance, it hasn’t decided whether CHIP would be counted as one of the “public charge” eligible programs.

In the interim, people who had received public benefits before the rule took effect would not be penalized for doing so.
 

4. Already, though, the proposal is having effects

DHS estimates that 2.5% of eligible immigrants would drop out of public benefits programs because of this change – which would tally about $1.5 billion worth of federal money per year. But others expect a much larger impact.

“The chilling effects will be vastly greater than the individuals directly affected,” Greenberg said. “There’s considerable reason to believe that [the White House estimate] may be a significant understatement.”

In the proposed rule, DHS notes that the changes could result in “worse health outcomes,” “increased use of emergency rooms,” “increased prevalence of communicable diseases,” “increased rates of poverty,” and other concerns.

Given the complexity of these programs and the proposed rule – and the high stakes at play – low-income immigrants would be much more likely to avoid public benefits altogether, immigration experts said. Millions of immigrants are likely to be affected directly or indirectly, according to the Center for Law and Social Policy, a D.C.-based nonprofit organization.

That could have stark health implications.

Take free vaccines, for which children are often eligible and which would not be subject to the public charge rule. Families afraid of jeopardizing a green card could still be more likely to opt out of that service, Whitener said.

Already, she added, there are reports of people declining federal assistance – even though nothing has yet happened.

“The fear factor cannot be underestimated,” she said.
 

5. Will people sue?

Legal action is likely.

Officials such as California Attorney General Xavier Becerra, who has frequently clashed with the White House, are weighing challenges to the rule.

“The Trump Administration’s proposal punishes hard-working immigrant families – even targeting children who are citizens – for utilizing programs that provide basic nutrition and healthcare. This is an assault on our families and our communities,” Becerra said in a statement.

But these actions depend on the final shape of the regulation, which could change through the rule-making process.

“They are likely to receive a very large number of sharply critical comments, and there is no way to know what changes they might make as a result,” Greenberg said.
 

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente. KHN’s coverage of children’s health care issues is supported in part by the Heising-Simons Foundation.

An adenine mutation in the MUTYH base repair excision gene increased the risk of developing hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV). The mutation was discovered in an analysis of 19 tagging single-nucleotide polymorphism (SNP) variants examined for multiple base repair excision genes (MUTYH, OGG1, and MTH1), according to the results of a retrospective analysis of patient genotypes reported in Free Radical Biology and Medicine (2018;129:88-96).

©Gio_tto/Thinkstock.com

In addition, the researchers examined MUTYH-null mice to assess the involvement of oxidative stress and DNA repair enzymes in hepatocarcinogenesis.

One significant SNP was found and confirmed from 93 Japanese patients with chronic HCV (38 with HCC and 55 controls), according to Akira Sakurada, MD, of Sapporo (Japan) Medical University, and his colleagues.

Patients diagnosed as having chronic HCV between 2007 and 2015 were enrolled. All patients were 45 years of age or older with detectable anti-HCV antibodies and HCV-RNA, as well as histopathological evidence of chronic hepatitis on liver biopsy. An exploratory cohort of 40 patients was first used before the 93 patient confirmatory analysis.

Genomic DNA was extracted from peripheral mononuclear cells of all of the patients studied.

Dr. Sakurada and his colleagues found significant associations for the single intron SNP (rs3219487) in the MUTYH gene. Human MutY homolog (MUTYH) protein is responsible for recognition and removal of an inappropriately inserted adenine (A).

The risk of developing HCC in patients with A/A or G/A genotypes was higher than in those with the G/G genotype (odds ratio = 9.27, 95% confidence interval = 2.39-32.1, P = .0005). In addition, they found that MUTYH mRNA levels were significantly lower in G/A or A/A genotyped subjects as compared with the wild type (G/G) (P = .0157 and P = .0108, respectively).

In their mouse model, the investigators found that liver tumors developed in MUTYH-null mice. As a physiological confirmation of their results, the researchers investigated a MUTYH-null mouse model. They found that decreased MUTYH activity in the null mice resulted in the development of HCC in these animals after 12 months of a high iron diet, but no tumors were observed when a dietary antioxidant (N-Acetyl-L-cysteine) was also provided.

“HCC may develop even in patients with an SVR [sustained virologic response]. This may be a problem especially for the numerous elderly patients. Our study suggests that SNP genotyping may predict the risk of developing HCC in such patients. We propose that in the setting of appropriate screening intervals, stratification of patients for whom antioxidant treatment would be appropriate could be achieved in this manner,” the researchers concluded.

The study was supported by grants from the Japan Society for Scientific Research. The authors reported they had nothing to disclose.

[email protected]

SOURCE: Sakurada A et al. Free Radic Biol Med. 2018;129:88-96.

An adenine mutation in the MUTYH base repair excision gene increased the risk of developing hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV). The mutation was discovered in an analysis of 19 tagging single-nucleotide polymorphism (SNP) variants examined for multiple base repair excision genes (MUTYH, OGG1, and MTH1), according to the results of a retrospective analysis of patient genotypes reported in Free Radical Biology and Medicine (2018;129:88-96).

©Gio_tto/Thinkstock.com

In addition, the researchers examined MUTYH-null mice to assess the involvement of oxidative stress and DNA repair enzymes in hepatocarcinogenesis.

One significant SNP was found and confirmed from 93 Japanese patients with chronic HCV (38 with HCC and 55 controls), according to Akira Sakurada, MD, of Sapporo (Japan) Medical University, and his colleagues.

Patients diagnosed as having chronic HCV between 2007 and 2015 were enrolled. All patients were 45 years of age or older with detectable anti-HCV antibodies and HCV-RNA, as well as histopathological evidence of chronic hepatitis on liver biopsy. An exploratory cohort of 40 patients was first used before the 93 patient confirmatory analysis.

Genomic DNA was extracted from peripheral mononuclear cells of all of the patients studied.

Dr. Sakurada and his colleagues found significant associations for the single intron SNP (rs3219487) in the MUTYH gene. Human MutY homolog (MUTYH) protein is responsible for recognition and removal of an inappropriately inserted adenine (A).

The risk of developing HCC in patients with A/A or G/A genotypes was higher than in those with the G/G genotype (odds ratio = 9.27, 95% confidence interval = 2.39-32.1, P = .0005). In addition, they found that MUTYH mRNA levels were significantly lower in G/A or A/A genotyped subjects as compared with the wild type (G/G) (P = .0157 and P = .0108, respectively).

In their mouse model, the investigators found that liver tumors developed in MUTYH-null mice. As a physiological confirmation of their results, the researchers investigated a MUTYH-null mouse model. They found that decreased MUTYH activity in the null mice resulted in the development of HCC in these animals after 12 months of a high iron diet, but no tumors were observed when a dietary antioxidant (N-Acetyl-L-cysteine) was also provided.

“HCC may develop even in patients with an SVR [sustained virologic response]. This may be a problem especially for the numerous elderly patients. Our study suggests that SNP genotyping may predict the risk of developing HCC in such patients. We propose that in the setting of appropriate screening intervals, stratification of patients for whom antioxidant treatment would be appropriate could be achieved in this manner,” the researchers concluded.

The study was supported by grants from the Japan Society for Scientific Research. The authors reported they had nothing to disclose.

[email protected]

SOURCE: Sakurada A et al. Free Radic Biol Med. 2018;129:88-96.

An adenine mutation in the MUTYH base repair excision gene increased the risk of developing hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV). The mutation was discovered in an analysis of 19 tagging single-nucleotide polymorphism (SNP) variants examined for multiple base repair excision genes (MUTYH, OGG1, and MTH1), according to the results of a retrospective analysis of patient genotypes reported in Free Radical Biology and Medicine (2018;129:88-96).

©Gio_tto/Thinkstock.com

In addition, the researchers examined MUTYH-null mice to assess the involvement of oxidative stress and DNA repair enzymes in hepatocarcinogenesis.

One significant SNP was found and confirmed from 93 Japanese patients with chronic HCV (38 with HCC and 55 controls), according to Akira Sakurada, MD, of Sapporo (Japan) Medical University, and his colleagues.

Patients diagnosed as having chronic HCV between 2007 and 2015 were enrolled. All patients were 45 years of age or older with detectable anti-HCV antibodies and HCV-RNA, as well as histopathological evidence of chronic hepatitis on liver biopsy. An exploratory cohort of 40 patients was first used before the 93 patient confirmatory analysis.

Genomic DNA was extracted from peripheral mononuclear cells of all of the patients studied.

Dr. Sakurada and his colleagues found significant associations for the single intron SNP (rs3219487) in the MUTYH gene. Human MutY homolog (MUTYH) protein is responsible for recognition and removal of an inappropriately inserted adenine (A).

The risk of developing HCC in patients with A/A or G/A genotypes was higher than in those with the G/G genotype (odds ratio = 9.27, 95% confidence interval = 2.39-32.1, P = .0005). In addition, they found that MUTYH mRNA levels were significantly lower in G/A or A/A genotyped subjects as compared with the wild type (G/G) (P = .0157 and P = .0108, respectively).

In their mouse model, the investigators found that liver tumors developed in MUTYH-null mice. As a physiological confirmation of their results, the researchers investigated a MUTYH-null mouse model. They found that decreased MUTYH activity in the null mice resulted in the development of HCC in these animals after 12 months of a high iron diet, but no tumors were observed when a dietary antioxidant (N-Acetyl-L-cysteine) was also provided.

“HCC may develop even in patients with an SVR [sustained virologic response]. This may be a problem especially for the numerous elderly patients. Our study suggests that SNP genotyping may predict the risk of developing HCC in such patients. We propose that in the setting of appropriate screening intervals, stratification of patients for whom antioxidant treatment would be appropriate could be achieved in this manner,” the researchers concluded.

The study was supported by grants from the Japan Society for Scientific Research. The authors reported they had nothing to disclose.

[email protected]

SOURCE: Sakurada A et al. Free Radic Biol Med. 2018;129:88-96.

Micrograph showing CLL

The U.S. Food and Drug Administration (FDA) has approved duvelisib (Copiktra™), a dual PI3K delta/gamma inhibitor, for two indications.

Duvelisib has full FDA approval to treat adults with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who have received at least two prior therapies.

Duvelisib also has accelerated approval to treat adults with relapsed or refractory follicular lymphoma (FL) who have received at least two prior systemic therapies.

Accelerated approval is based on a surrogate or intermediate endpoint—in this case, overall response rate—that is reasonably likely to predict clinical benefit. Continued approval of duvelisib in FL may be contingent upon results of confirmatory trials verifying that the drug provides a clinical benefit.

Duvelisib will be available in the U.S. immediately, according to Verastem Inc., the company marketing the drug.

Verastem said it will help patients access duvelisib through the Verastem Cares™ program, which is designed to provide information and assistance to patients who are prescribed duvelisib.

The prescribing information for duvelisib includes a boxed warning detailing four fatal and/or serious toxicities associated with the drug—infections, diarrhea or colitis, cutaneous reactions, and pneumonitis.

Verastem said it is implementing an informational risk evaluation and mitigation strategy to provide appropriate dosing and safety information for duvelisib.

The recommended dose of duvelisib is 25 mg orally twice daily, taken continuously in 28-day treatment cycles.

The FDA assessed the new drug application for duvelisib under priority review. The FDA also granted duvelisib fast track designation in CLL and FL as well as orphan drug designation for CLL/SLL and FL.

The FDA’s approval of duvelisib is supported by data from the phase 3 DUO trial and the phase 2 DYNAMO trial. Updated results from both studies are available in the prescribing information for duvelisib.

DUO trial

DUO included 319 patients with CLL (n=312) or SLL (n=7) who had received at least one prior therapy. They were randomized to receive either duvelisib (25 mg orally twice daily) or ofatumumab (initial infusion of 300 mg followed by 7 weekly infusions and 4 monthly infusions of 2000 mg).

The following efficacy results were observed in patients who had received at least two prior therapies, which includes 95 patients in the duvelisib arm and 101 in the ofatumumab arm.

The overall response rate was 78% in the duvelisib arm and 39% in the ofatumumab arm. All responses in both arms were partial responses.

The median progression-free survival was 16.4 months with duvelisib and 9.1 months with ofatumumab (hazard ratio=0.40).

The safety results include all patients treated with duvelisib or ofatumumab.

Twelve percent of patients in the duvelisib arm had fatal adverse events (AEs) within 30 days of the last dose. The same was true of 4% of patients treated with ofatumumab.

Serious AEs occurred in 73% of patients treated with duvelisib. The most common were infection (38%) and diarrhea/colitis (23%).

Thirty-six percent of patients discontinued duvelisib. Most discontinuations were due to diarrhea/ colitis, infection, and rash. Twenty-nine percent of patients in the duvelisib arm required dose reductions, most often due to diarrhea/colitis and rash.

DYNAMO trial

DYNAMO enrolled patients with indolent non-Hodgkin lymphoma whose disease was refractory to both rituximab and chemotherapy or radioimmunotherapy.

There were 83 patients with FL. They had a median of 3 prior anticancer regimens (range, 1-10).

The patients received duvelisib at 25 mg orally twice daily until disease progression or unacceptable toxicity.

The overall response rate was 42%. One patient achieved a complete response, and 34 had a partial response.

Forty-three percent of responders maintained their response at 6 months, and 17% maintained their response at 12 months.

Serious AEs occurred in 58% of FL patients. The most common were diarrhea/colitis, pneumonia, renal insufficiency, rash, and sepsis.

AEs occurring in at least 20% of FL patients included diarrhea/colitis, nausea, fatigue, musculoskeletal pain, rash, neutropenia, cough, anemia, pyrexia, headache, mucositis, abdominal pain, vomiting, transaminase elevation, and thrombocytopenia.

Twenty-nine percent of FL patients discontinued duvelisib, and 23% had dose reductions. Most discontinuations were due to diarrhea/colitis and rash, and most dose reductions were due to transaminase elevation, diarrhea/colitis, lipase increase, and infection.

Micrograph showing CLL

The U.S. Food and Drug Administration (FDA) has approved duvelisib (Copiktra™), a dual PI3K delta/gamma inhibitor, for two indications.

Duvelisib has full FDA approval to treat adults with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who have received at least two prior therapies.

Duvelisib also has accelerated approval to treat adults with relapsed or refractory follicular lymphoma (FL) who have received at least two prior systemic therapies.

Accelerated approval is based on a surrogate or intermediate endpoint—in this case, overall response rate—that is reasonably likely to predict clinical benefit. Continued approval of duvelisib in FL may be contingent upon results of confirmatory trials verifying that the drug provides a clinical benefit.

Duvelisib will be available in the U.S. immediately, according to Verastem Inc., the company marketing the drug.

Verastem said it will help patients access duvelisib through the Verastem Cares™ program, which is designed to provide information and assistance to patients who are prescribed duvelisib.

The prescribing information for duvelisib includes a boxed warning detailing four fatal and/or serious toxicities associated with the drug—infections, diarrhea or colitis, cutaneous reactions, and pneumonitis.

Verastem said it is implementing an informational risk evaluation and mitigation strategy to provide appropriate dosing and safety information for duvelisib.

The recommended dose of duvelisib is 25 mg orally twice daily, taken continuously in 28-day treatment cycles.

The FDA assessed the new drug application for duvelisib under priority review. The FDA also granted duvelisib fast track designation in CLL and FL as well as orphan drug designation for CLL/SLL and FL.

The FDA’s approval of duvelisib is supported by data from the phase 3 DUO trial and the phase 2 DYNAMO trial. Updated results from both studies are available in the prescribing information for duvelisib.

DUO trial

DUO included 319 patients with CLL (n=312) or SLL (n=7) who had received at least one prior therapy. They were randomized to receive either duvelisib (25 mg orally twice daily) or ofatumumab (initial infusion of 300 mg followed by 7 weekly infusions and 4 monthly infusions of 2000 mg).

The following efficacy results were observed in patients who had received at least two prior therapies, which includes 95 patients in the duvelisib arm and 101 in the ofatumumab arm.

The overall response rate was 78% in the duvelisib arm and 39% in the ofatumumab arm. All responses in both arms were partial responses.

The median progression-free survival was 16.4 months with duvelisib and 9.1 months with ofatumumab (hazard ratio=0.40).

The safety results include all patients treated with duvelisib or ofatumumab.

Twelve percent of patients in the duvelisib arm had fatal adverse events (AEs) within 30 days of the last dose. The same was true of 4% of patients treated with ofatumumab.

Serious AEs occurred in 73% of patients treated with duvelisib. The most common were infection (38%) and diarrhea/colitis (23%).

Thirty-six percent of patients discontinued duvelisib. Most discontinuations were due to diarrhea/ colitis, infection, and rash. Twenty-nine percent of patients in the duvelisib arm required dose reductions, most often due to diarrhea/colitis and rash.

DYNAMO trial

DYNAMO enrolled patients with indolent non-Hodgkin lymphoma whose disease was refractory to both rituximab and chemotherapy or radioimmunotherapy.

There were 83 patients with FL. They had a median of 3 prior anticancer regimens (range, 1-10).

The patients received duvelisib at 25 mg orally twice daily until disease progression or unacceptable toxicity.

The overall response rate was 42%. One patient achieved a complete response, and 34 had a partial response.

Forty-three percent of responders maintained their response at 6 months, and 17% maintained their response at 12 months.

Serious AEs occurred in 58% of FL patients. The most common were diarrhea/colitis, pneumonia, renal insufficiency, rash, and sepsis.

AEs occurring in at least 20% of FL patients included diarrhea/colitis, nausea, fatigue, musculoskeletal pain, rash, neutropenia, cough, anemia, pyrexia, headache, mucositis, abdominal pain, vomiting, transaminase elevation, and thrombocytopenia.

Twenty-nine percent of FL patients discontinued duvelisib, and 23% had dose reductions. Most discontinuations were due to diarrhea/colitis and rash, and most dose reductions were due to transaminase elevation, diarrhea/colitis, lipase increase, and infection.

Micrograph showing CLL

The U.S. Food and Drug Administration (FDA) has approved duvelisib (Copiktra™), a dual PI3K delta/gamma inhibitor, for two indications.

Duvelisib has full FDA approval to treat adults with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who have received at least two prior therapies.

Duvelisib also has accelerated approval to treat adults with relapsed or refractory follicular lymphoma (FL) who have received at least two prior systemic therapies.

Accelerated approval is based on a surrogate or intermediate endpoint—in this case, overall response rate—that is reasonably likely to predict clinical benefit. Continued approval of duvelisib in FL may be contingent upon results of confirmatory trials verifying that the drug provides a clinical benefit.

Duvelisib will be available in the U.S. immediately, according to Verastem Inc., the company marketing the drug.

Verastem said it will help patients access duvelisib through the Verastem Cares™ program, which is designed to provide information and assistance to patients who are prescribed duvelisib.

The prescribing information for duvelisib includes a boxed warning detailing four fatal and/or serious toxicities associated with the drug—infections, diarrhea or colitis, cutaneous reactions, and pneumonitis.

Verastem said it is implementing an informational risk evaluation and mitigation strategy to provide appropriate dosing and safety information for duvelisib.

The recommended dose of duvelisib is 25 mg orally twice daily, taken continuously in 28-day treatment cycles.

The FDA assessed the new drug application for duvelisib under priority review. The FDA also granted duvelisib fast track designation in CLL and FL as well as orphan drug designation for CLL/SLL and FL.

The FDA’s approval of duvelisib is supported by data from the phase 3 DUO trial and the phase 2 DYNAMO trial. Updated results from both studies are available in the prescribing information for duvelisib.

DUO trial

DUO included 319 patients with CLL (n=312) or SLL (n=7) who had received at least one prior therapy. They were randomized to receive either duvelisib (25 mg orally twice daily) or ofatumumab (initial infusion of 300 mg followed by 7 weekly infusions and 4 monthly infusions of 2000 mg).

The following efficacy results were observed in patients who had received at least two prior therapies, which includes 95 patients in the duvelisib arm and 101 in the ofatumumab arm.

The overall response rate was 78% in the duvelisib arm and 39% in the ofatumumab arm. All responses in both arms were partial responses.

The median progression-free survival was 16.4 months with duvelisib and 9.1 months with ofatumumab (hazard ratio=0.40).

The safety results include all patients treated with duvelisib or ofatumumab.

Twelve percent of patients in the duvelisib arm had fatal adverse events (AEs) within 30 days of the last dose. The same was true of 4% of patients treated with ofatumumab.

Serious AEs occurred in 73% of patients treated with duvelisib. The most common were infection (38%) and diarrhea/colitis (23%).

Thirty-six percent of patients discontinued duvelisib. Most discontinuations were due to diarrhea/ colitis, infection, and rash. Twenty-nine percent of patients in the duvelisib arm required dose reductions, most often due to diarrhea/colitis and rash.

DYNAMO trial

DYNAMO enrolled patients with indolent non-Hodgkin lymphoma whose disease was refractory to both rituximab and chemotherapy or radioimmunotherapy.

There were 83 patients with FL. They had a median of 3 prior anticancer regimens (range, 1-10).

The patients received duvelisib at 25 mg orally twice daily until disease progression or unacceptable toxicity.

The overall response rate was 42%. One patient achieved a complete response, and 34 had a partial response.

Forty-three percent of responders maintained their response at 6 months, and 17% maintained their response at 12 months.

Serious AEs occurred in 58% of FL patients. The most common were diarrhea/colitis, pneumonia, renal insufficiency, rash, and sepsis.

AEs occurring in at least 20% of FL patients included diarrhea/colitis, nausea, fatigue, musculoskeletal pain, rash, neutropenia, cough, anemia, pyrexia, headache, mucositis, abdominal pain, vomiting, transaminase elevation, and thrombocytopenia.

Twenty-nine percent of FL patients discontinued duvelisib, and 23% had dose reductions. Most discontinuations were due to diarrhea/colitis and rash, and most dose reductions were due to transaminase elevation, diarrhea/colitis, lipase increase, and infection.

Longer-term outcomes of treating uncomplicated acute appendicitis with antibiotics suggest it is a feasible alternative to appendectomy.

copyright decade3d/Thinkstock

Researchers have presented the 5-year follow-up data from the Appendicitis Acuta (APPAC) multicenter randomized clinical trial comparing appendectomy with antibiotic therapy in 530 patients.

They found that 39.1% (100) of the 257 patients randomized to antibiotic therapy – 3 days of intravenous ertapenem followed by 7 days of oral levofloxacin and metronidazole – experienced a recurrence of appendicitis within 5 years and subsequently had surgery.

However the authors noted that seven of these patients were later found not to have appendicitis, so the true success rate for antibiotic treatment was actually 63.7%.

Seventy of the patients who experienced a recurrence underwent surgery in the first year after randomization, 17 in the second year, 3 in the third year, 5 in the fourth year, and the remaining 5 patients in the fifth year, the authors wrote in an article published in JAMA.

However the overall complication rate was similar in patients who were randomized to undergo appendectomy and in those who were initially randomized to the antibiotic group but later experienced a recurrence and underwent surgery.

“No patient initially treated with antibiotics, who ultimately developed recurrent appendicitis, had any complications related to the delay in surgery,” wrote Paulina Salminen, MD, from Turku (Finland) University Hospital and coauthors. “Nearly two-thirds of all patients who initially presented with uncomplicated appendicitis were successfully treated with antibiotics alone, and those who ultimately developed recurrent disease did not experience any adverse outcomes related to the delay in appendectomy.”

Of the 100 patients randomized to antibiotics who underwent appendectomy after a recurrence, 15 were operated on when they were first hospitalized at study admission.

The authors commented that the study design allowed for surgeons to exercise their clinical judgment in choosing when to perform an appendectomy on patients in the antibiotic group, because antibiotics alone was not considered acceptable treatment for appendicitis.

“This led to some patients undergoing appendectomy who did not have appendicitis or who might have been successfully treated with antibiotics or an another course of antibiotics,” they wrote. “Future studies should investigate protocols for further imaging or antibiotic treatment for patients who develop recurrent appendicitis after they were initially treated with antibiotics.”

In the recurrence group, the majority were found to have uncomplicated appendicitis, but complicated appendicitis was seen in two patients between 2 and 5 years after the index admission.

There was a significant 17.9% higher complication rate in the appendectomy group, compared with the antibiotic group – 24.4% versus 6.5% – at 5 years and two patients in the appendectomy group had severe complications requiring reoperation.

They suggested that the higher complication rate with surgery, which was mostly attributable to infections, could be reduced by the use of laparoscopic appendectomy, which is also associated with faster recovery.

The median length of hospital stay was 3 days for both the appendectomy group and the antibiotics-only group, but patients randomized to appendectomy took a median of 22 days of sick leave, compared with 11 days for those randomized to antibiotics (P less than .001).

In the absence of standard protocol on treating appendicitis with antibiotics, the authors noted that they took a conservative approach, using broad-spectrum antibiotics and keeping patients in hospital for 3 days for observation.

“The success of antibiotic treatment for appendicitis calls into question prior beliefs that appendicitis inevitably results in serious intra-abdominal infection if appendectomy is not performed.”

The study was supported by the Mary and Georg C. Ehrnrooth Foundation, the EVO Foundation, and Turku University. One author declared lecture fees from three pharmaceutical companies but no other conflicts of interest were declared.

SOURCE: Salminen P et al. JAMA 2018;320:1259-65. doi: 10.1001/jama.2018.13201.

Longer-term outcomes of treating uncomplicated acute appendicitis with antibiotics suggest it is a feasible alternative to appendectomy.

copyright decade3d/Thinkstock

Researchers have presented the 5-year follow-up data from the Appendicitis Acuta (APPAC) multicenter randomized clinical trial comparing appendectomy with antibiotic therapy in 530 patients.

They found that 39.1% (100) of the 257 patients randomized to antibiotic therapy – 3 days of intravenous ertapenem followed by 7 days of oral levofloxacin and metronidazole – experienced a recurrence of appendicitis within 5 years and subsequently had surgery.

However the authors noted that seven of these patients were later found not to have appendicitis, so the true success rate for antibiotic treatment was actually 63.7%.

Seventy of the patients who experienced a recurrence underwent surgery in the first year after randomization, 17 in the second year, 3 in the third year, 5 in the fourth year, and the remaining 5 patients in the fifth year, the authors wrote in an article published in JAMA.

However the overall complication rate was similar in patients who were randomized to undergo appendectomy and in those who were initially randomized to the antibiotic group but later experienced a recurrence and underwent surgery.

“No patient initially treated with antibiotics, who ultimately developed recurrent appendicitis, had any complications related to the delay in surgery,” wrote Paulina Salminen, MD, from Turku (Finland) University Hospital and coauthors. “Nearly two-thirds of all patients who initially presented with uncomplicated appendicitis were successfully treated with antibiotics alone, and those who ultimately developed recurrent disease did not experience any adverse outcomes related to the delay in appendectomy.”

Of the 100 patients randomized to antibiotics who underwent appendectomy after a recurrence, 15 were operated on when they were first hospitalized at study admission.

The authors commented that the study design allowed for surgeons to exercise their clinical judgment in choosing when to perform an appendectomy on patients in the antibiotic group, because antibiotics alone was not considered acceptable treatment for appendicitis.

“This led to some patients undergoing appendectomy who did not have appendicitis or who might have been successfully treated with antibiotics or an another course of antibiotics,” they wrote. “Future studies should investigate protocols for further imaging or antibiotic treatment for patients who develop recurrent appendicitis after they were initially treated with antibiotics.”

In the recurrence group, the majority were found to have uncomplicated appendicitis, but complicated appendicitis was seen in two patients between 2 and 5 years after the index admission.

There was a significant 17.9% higher complication rate in the appendectomy group, compared with the antibiotic group – 24.4% versus 6.5% – at 5 years and two patients in the appendectomy group had severe complications requiring reoperation.

They suggested that the higher complication rate with surgery, which was mostly attributable to infections, could be reduced by the use of laparoscopic appendectomy, which is also associated with faster recovery.

The median length of hospital stay was 3 days for both the appendectomy group and the antibiotics-only group, but patients randomized to appendectomy took a median of 22 days of sick leave, compared with 11 days for those randomized to antibiotics (P less than .001).

In the absence of standard protocol on treating appendicitis with antibiotics, the authors noted that they took a conservative approach, using broad-spectrum antibiotics and keeping patients in hospital for 3 days for observation.

“The success of antibiotic treatment for appendicitis calls into question prior beliefs that appendicitis inevitably results in serious intra-abdominal infection if appendectomy is not performed.”

The study was supported by the Mary and Georg C. Ehrnrooth Foundation, the EVO Foundation, and Turku University. One author declared lecture fees from three pharmaceutical companies but no other conflicts of interest were declared.

SOURCE: Salminen P et al. JAMA 2018;320:1259-65. doi: 10.1001/jama.2018.13201.

Longer-term outcomes of treating uncomplicated acute appendicitis with antibiotics suggest it is a feasible alternative to appendectomy.

copyright decade3d/Thinkstock

Researchers have presented the 5-year follow-up data from the Appendicitis Acuta (APPAC) multicenter randomized clinical trial comparing appendectomy with antibiotic therapy in 530 patients.

They found that 39.1% (100) of the 257 patients randomized to antibiotic therapy – 3 days of intravenous ertapenem followed by 7 days of oral levofloxacin and metronidazole – experienced a recurrence of appendicitis within 5 years and subsequently had surgery.

However the authors noted that seven of these patients were later found not to have appendicitis, so the true success rate for antibiotic treatment was actually 63.7%.

Seventy of the patients who experienced a recurrence underwent surgery in the first year after randomization, 17 in the second year, 3 in the third year, 5 in the fourth year, and the remaining 5 patients in the fifth year, the authors wrote in an article published in JAMA.

However the overall complication rate was similar in patients who were randomized to undergo appendectomy and in those who were initially randomized to the antibiotic group but later experienced a recurrence and underwent surgery.

“No patient initially treated with antibiotics, who ultimately developed recurrent appendicitis, had any complications related to the delay in surgery,” wrote Paulina Salminen, MD, from Turku (Finland) University Hospital and coauthors. “Nearly two-thirds of all patients who initially presented with uncomplicated appendicitis were successfully treated with antibiotics alone, and those who ultimately developed recurrent disease did not experience any adverse outcomes related to the delay in appendectomy.”

Of the 100 patients randomized to antibiotics who underwent appendectomy after a recurrence, 15 were operated on when they were first hospitalized at study admission.

The authors commented that the study design allowed for surgeons to exercise their clinical judgment in choosing when to perform an appendectomy on patients in the antibiotic group, because antibiotics alone was not considered acceptable treatment for appendicitis.

“This led to some patients undergoing appendectomy who did not have appendicitis or who might have been successfully treated with antibiotics or an another course of antibiotics,” they wrote. “Future studies should investigate protocols for further imaging or antibiotic treatment for patients who develop recurrent appendicitis after they were initially treated with antibiotics.”

In the recurrence group, the majority were found to have uncomplicated appendicitis, but complicated appendicitis was seen in two patients between 2 and 5 years after the index admission.

There was a significant 17.9% higher complication rate in the appendectomy group, compared with the antibiotic group – 24.4% versus 6.5% – at 5 years and two patients in the appendectomy group had severe complications requiring reoperation.

They suggested that the higher complication rate with surgery, which was mostly attributable to infections, could be reduced by the use of laparoscopic appendectomy, which is also associated with faster recovery.

The median length of hospital stay was 3 days for both the appendectomy group and the antibiotics-only group, but patients randomized to appendectomy took a median of 22 days of sick leave, compared with 11 days for those randomized to antibiotics (P less than .001).

In the absence of standard protocol on treating appendicitis with antibiotics, the authors noted that they took a conservative approach, using broad-spectrum antibiotics and keeping patients in hospital for 3 days for observation.

“The success of antibiotic treatment for appendicitis calls into question prior beliefs that appendicitis inevitably results in serious intra-abdominal infection if appendectomy is not performed.”

The study was supported by the Mary and Georg C. Ehrnrooth Foundation, the EVO Foundation, and Turku University. One author declared lecture fees from three pharmaceutical companies but no other conflicts of interest were declared.

SOURCE: Salminen P et al. JAMA 2018;320:1259-65. doi: 10.1001/jama.2018.13201.

Digitally delivered cognitive-behavioral therapy not only improved insomnia, but also provided “around-the-clock” health, psychological, and quality-of-life improvements, according to investigators.

Hocus Focus Studio/iStockphoto

Compared with control subjects, patients who used a cognitive-behavioral therapy (CBT) program and associated iPhone app had small improvements in functional health and psychological well-being and large improvements in sleep-related quality of life, the investigators reported.

Those changes were mediated by a large improvement in insomnia, according to Colin A. Espie, PhD, professor of sleep medicine at the University of Oxford (England), and his colleagues.

“These findings indicate that digital CBT improves both daytime and nighttime aspects of insomnia, lending further weight to the clinical guideline recommendation of CBT as the treatment of choice for insomnia,” Dr. Espie and his colleagues reported in JAMA Psychiatry.

Their study included 1,711 adults with symptoms of insomnia that were self-reported and a score of 16 or less on the Sleep Condition Indicator (SCI), which has a range of 0-32. A total of 853 were randomized to receive digital CBT, of whom 413 completed six scheduled 20-minute sessions; an additional 276 adults completed at least one session. The control arm included 858 individuals randomized to sleep hygiene education, of whom 759 went on to receive that intervention.

Small but significant improvements were seen in self-reported measures of functional health, Dr. Espie and his colleagues reported. The adjusted differences in mean scores on the Patient-Reported Outcomes Measurement Information System: Global Health Scale were 0.90 in a midtreatment evaluation at 4 weeks after baseline, 1.76 in a posttreatment evaluation at 8 weeks, and 1.76 at a 24-week follow-up assessment (P less than 0.001 for all comparisons).

Likewise, adjusted differences in the Warwick-Edinburgh Mental Wellbeing Scale were 1.04, 2.68, and 2.95 at 4, 8, and 24 weeks, respectively.

Adjusted differences in the Glasgow Sleep Impact Index, which measures sleep-related quality of life, were –8.76, –17.60, and –18.72 at 4, 8, and 24 weeks, respectively, indicating a benefit of the digital CBT intervention over the control intervention, the investigators said.

About 45%-84% of these effects were attributable to changes in insomnia symptoms, results of a mediation analysis showed.

Insomnia scores as measured by the eight-item SCI scale were 6.5 and 6.6 at baseline for the digital CBT and control groups, respectively. By week 4, SCI scores were 9.96 and 13.00 for the two groups (P less than 0.001), with significant differences also reported at the 8- and 24-week evaluations.

The investigators noted that their findings might not be generalizable because participants were not drawn from patient populations. In addition, although 58% of the participants completed 4 weeks or more of the digital CBT sessions, the dropout rate was “substantial.”

Nevertheless, they wrote, these findings, together with results of a recently reported parallel study looking at the effects of sleep on mental health, affirm CBT as the treatment of choice for insomnia. “The mediation analyses in these two studies, with a total of 5,466 participants, provide novel and convincing evidence that insomnia may be a legitimate and important target for mental health and well-being.”

Dr. Espie reported that he is cofounder and chief medical officer of Big Health. He is a shareholder and receives a salary from the company, which was involved in the design and conduct of the study, interpretation of data, and development of the manuscript appearing in JAMA Psychiatry. The study was funded by Big Health and other sources, including the National Institute for Health Research Oxford Biomedical Research Centre.

SOURCE: Espie CA et al. JAMA Psychiatry. 2018 Sep 25. doi: 10.1001/jamapsychiatry.2018.2745.

Digitally delivered cognitive-behavioral therapy not only improved insomnia, but also provided “around-the-clock” health, psychological, and quality-of-life improvements, according to investigators.

Hocus Focus Studio/iStockphoto

Compared with control subjects, patients who used a cognitive-behavioral therapy (CBT) program and associated iPhone app had small improvements in functional health and psychological well-being and large improvements in sleep-related quality of life, the investigators reported.

Those changes were mediated by a large improvement in insomnia, according to Colin A. Espie, PhD, professor of sleep medicine at the University of Oxford (England), and his colleagues.

“These findings indicate that digital CBT improves both daytime and nighttime aspects of insomnia, lending further weight to the clinical guideline recommendation of CBT as the treatment of choice for insomnia,” Dr. Espie and his colleagues reported in JAMA Psychiatry.

Their study included 1,711 adults with symptoms of insomnia that were self-reported and a score of 16 or less on the Sleep Condition Indicator (SCI), which has a range of 0-32. A total of 853 were randomized to receive digital CBT, of whom 413 completed six scheduled 20-minute sessions; an additional 276 adults completed at least one session. The control arm included 858 individuals randomized to sleep hygiene education, of whom 759 went on to receive that intervention.

Small but significant improvements were seen in self-reported measures of functional health, Dr. Espie and his colleagues reported. The adjusted differences in mean scores on the Patient-Reported Outcomes Measurement Information System: Global Health Scale were 0.90 in a midtreatment evaluation at 4 weeks after baseline, 1.76 in a posttreatment evaluation at 8 weeks, and 1.76 at a 24-week follow-up assessment (P less than 0.001 for all comparisons).

Likewise, adjusted differences in the Warwick-Edinburgh Mental Wellbeing Scale were 1.04, 2.68, and 2.95 at 4, 8, and 24 weeks, respectively.

Adjusted differences in the Glasgow Sleep Impact Index, which measures sleep-related quality of life, were –8.76, –17.60, and –18.72 at 4, 8, and 24 weeks, respectively, indicating a benefit of the digital CBT intervention over the control intervention, the investigators said.

About 45%-84% of these effects were attributable to changes in insomnia symptoms, results of a mediation analysis showed.

Insomnia scores as measured by the eight-item SCI scale were 6.5 and 6.6 at baseline for the digital CBT and control groups, respectively. By week 4, SCI scores were 9.96 and 13.00 for the two groups (P less than 0.001), with significant differences also reported at the 8- and 24-week evaluations.

The investigators noted that their findings might not be generalizable because participants were not drawn from patient populations. In addition, although 58% of the participants completed 4 weeks or more of the digital CBT sessions, the dropout rate was “substantial.”

Nevertheless, they wrote, these findings, together with results of a recently reported parallel study looking at the effects of sleep on mental health, affirm CBT as the treatment of choice for insomnia. “The mediation analyses in these two studies, with a total of 5,466 participants, provide novel and convincing evidence that insomnia may be a legitimate and important target for mental health and well-being.”

Dr. Espie reported that he is cofounder and chief medical officer of Big Health. He is a shareholder and receives a salary from the company, which was involved in the design and conduct of the study, interpretation of data, and development of the manuscript appearing in JAMA Psychiatry. The study was funded by Big Health and other sources, including the National Institute for Health Research Oxford Biomedical Research Centre.

SOURCE: Espie CA et al. JAMA Psychiatry. 2018 Sep 25. doi: 10.1001/jamapsychiatry.2018.2745.

Digitally delivered cognitive-behavioral therapy not only improved insomnia, but also provided “around-the-clock” health, psychological, and quality-of-life improvements, according to investigators.

Hocus Focus Studio/iStockphoto

Compared with control subjects, patients who used a cognitive-behavioral therapy (CBT) program and associated iPhone app had small improvements in functional health and psychological well-being and large improvements in sleep-related quality of life, the investigators reported.

Those changes were mediated by a large improvement in insomnia, according to Colin A. Espie, PhD, professor of sleep medicine at the University of Oxford (England), and his colleagues.

“These findings indicate that digital CBT improves both daytime and nighttime aspects of insomnia, lending further weight to the clinical guideline recommendation of CBT as the treatment of choice for insomnia,” Dr. Espie and his colleagues reported in JAMA Psychiatry.

Their study included 1,711 adults with symptoms of insomnia that were self-reported and a score of 16 or less on the Sleep Condition Indicator (SCI), which has a range of 0-32. A total of 853 were randomized to receive digital CBT, of whom 413 completed six scheduled 20-minute sessions; an additional 276 adults completed at least one session. The control arm included 858 individuals randomized to sleep hygiene education, of whom 759 went on to receive that intervention.

Small but significant improvements were seen in self-reported measures of functional health, Dr. Espie and his colleagues reported. The adjusted differences in mean scores on the Patient-Reported Outcomes Measurement Information System: Global Health Scale were 0.90 in a midtreatment evaluation at 4 weeks after baseline, 1.76 in a posttreatment evaluation at 8 weeks, and 1.76 at a 24-week follow-up assessment (P less than 0.001 for all comparisons).

Likewise, adjusted differences in the Warwick-Edinburgh Mental Wellbeing Scale were 1.04, 2.68, and 2.95 at 4, 8, and 24 weeks, respectively.

Adjusted differences in the Glasgow Sleep Impact Index, which measures sleep-related quality of life, were –8.76, –17.60, and –18.72 at 4, 8, and 24 weeks, respectively, indicating a benefit of the digital CBT intervention over the control intervention, the investigators said.

About 45%-84% of these effects were attributable to changes in insomnia symptoms, results of a mediation analysis showed.

Insomnia scores as measured by the eight-item SCI scale were 6.5 and 6.6 at baseline for the digital CBT and control groups, respectively. By week 4, SCI scores were 9.96 and 13.00 for the two groups (P less than 0.001), with significant differences also reported at the 8- and 24-week evaluations.

The investigators noted that their findings might not be generalizable because participants were not drawn from patient populations. In addition, although 58% of the participants completed 4 weeks or more of the digital CBT sessions, the dropout rate was “substantial.”

Nevertheless, they wrote, these findings, together with results of a recently reported parallel study looking at the effects of sleep on mental health, affirm CBT as the treatment of choice for insomnia. “The mediation analyses in these two studies, with a total of 5,466 participants, provide novel and convincing evidence that insomnia may be a legitimate and important target for mental health and well-being.”

Dr. Espie reported that he is cofounder and chief medical officer of Big Health. He is a shareholder and receives a salary from the company, which was involved in the design and conduct of the study, interpretation of data, and development of the manuscript appearing in JAMA Psychiatry. The study was funded by Big Health and other sources, including the National Institute for Health Research Oxford Biomedical Research Centre.

SOURCE: Espie CA et al. JAMA Psychiatry. 2018 Sep 25. doi: 10.1001/jamapsychiatry.2018.2745.

The Diagnosis: Herpes Simplex Virus Infection

Viral culture of the ulcer was positive for herpes simplex virus type 2 (HHV-2). Bacterial culture grew enteric flora. The patient was started on intravenous acyclovir 5 mg/kg every 8 hours for 7 days and then transitioned to oral acyclovir for chronic suppressive therapy. One month later, there was near-complete reepithelialization with 2 remaining 1-cm shallow ulcers. The verrucous lesions had dried up and were flaking off (Figure). At 6-month follow-up, the ulcers and verrucous lesions had completely resolved.

Herpes simplex virus type 2 is the most common cause of genital and perianal ulcers in immunocompromised individuals.¹ Patients classically present with painful grouped vesicles followed by painful superficial ulcers that may rapidly progress to extensive confluent ulceration. A hypertrophic variant of genital herpes characterized by anogenital verrucous lesions, similar to condyloma acuminata, also can be seen in immunocompromised individuals.² This form has almost exclusively been observed in patients with human immunodeficiency virus and may occur in isolation or together with the ulcerative form.^1-5 A case of vegetative HHV infection of the genital area in a patient with common variable immunodeficiency has been reported.⁶ Verrucous lesions of the mouth secondary to HHV have been observed in Hodgkin lymphoma, acute myelogenous leukemia, and individuals on immunosuppressive medications.^7-10

Perianal involvement of Crohn disease typically presents with fistulas, ulcers, abscesses, strictures, and skin tags in some cases. Invasive squamous cell carcinoma may arise within a chronic ulcer of the anogenital area or may itself manifest as an ulcer or anal fissure. Perianal ulcerative skin tuberculosis has been reported in the literature as a rare manifestation of extrapulmonary tuberculosis and should be considered in a patient with an appropriate clinical history. Pyoderma gangrenosum classically pre-sents as a large ulcer with irregular rolled borders, though a rare variant of vegetative pyoderma gangrenosum may manifest as a nodular or verrucous plaque.

Studies to diagnose HHV include viral cell culture, HHV polymerase chain reaction testing, HHV serology, and direct fluorescent antibody testing. Skin biopsy may be necessary to rule out underlying malignancy. Treatment of perianal HHV infection includes acyclovir, valacyclovir, or famciclovir.^1,5,6 Hypertrophic lesions often are refractory to first-line antiviral therapy and may require surgical resection or treatment with alternative medications such as imiquimod, a topical immunomodulator.^3,5,6,11

The Diagnosis: Herpes Simplex Virus Infection

Viral culture of the ulcer was positive for herpes simplex virus type 2 (HHV-2). Bacterial culture grew enteric flora. The patient was started on intravenous acyclovir 5 mg/kg every 8 hours for 7 days and then transitioned to oral acyclovir for chronic suppressive therapy. One month later, there was near-complete reepithelialization with 2 remaining 1-cm shallow ulcers. The verrucous lesions had dried up and were flaking off (Figure). At 6-month follow-up, the ulcers and verrucous lesions had completely resolved.

Herpes simplex virus type 2 is the most common cause of genital and perianal ulcers in immunocompromised individuals.¹ Patients classically present with painful grouped vesicles followed by painful superficial ulcers that may rapidly progress to extensive confluent ulceration. A hypertrophic variant of genital herpes characterized by anogenital verrucous lesions, similar to condyloma acuminata, also can be seen in immunocompromised individuals.² This form has almost exclusively been observed in patients with human immunodeficiency virus and may occur in isolation or together with the ulcerative form.^1-5 A case of vegetative HHV infection of the genital area in a patient with common variable immunodeficiency has been reported.⁶ Verrucous lesions of the mouth secondary to HHV have been observed in Hodgkin lymphoma, acute myelogenous leukemia, and individuals on immunosuppressive medications.^7-10

Perianal involvement of Crohn disease typically presents with fistulas, ulcers, abscesses, strictures, and skin tags in some cases. Invasive squamous cell carcinoma may arise within a chronic ulcer of the anogenital area or may itself manifest as an ulcer or anal fissure. Perianal ulcerative skin tuberculosis has been reported in the literature as a rare manifestation of extrapulmonary tuberculosis and should be considered in a patient with an appropriate clinical history. Pyoderma gangrenosum classically pre-sents as a large ulcer with irregular rolled borders, though a rare variant of vegetative pyoderma gangrenosum may manifest as a nodular or verrucous plaque.

Studies to diagnose HHV include viral cell culture, HHV polymerase chain reaction testing, HHV serology, and direct fluorescent antibody testing. Skin biopsy may be necessary to rule out underlying malignancy. Treatment of perianal HHV infection includes acyclovir, valacyclovir, or famciclovir.^1,5,6 Hypertrophic lesions often are refractory to first-line antiviral therapy and may require surgical resection or treatment with alternative medications such as imiquimod, a topical immunomodulator.^3,5,6,11

The Diagnosis: Herpes Simplex Virus Infection

Viral culture of the ulcer was positive for herpes simplex virus type 2 (HHV-2). Bacterial culture grew enteric flora. The patient was started on intravenous acyclovir 5 mg/kg every 8 hours for 7 days and then transitioned to oral acyclovir for chronic suppressive therapy. One month later, there was near-complete reepithelialization with 2 remaining 1-cm shallow ulcers. The verrucous lesions had dried up and were flaking off (Figure). At 6-month follow-up, the ulcers and verrucous lesions had completely resolved.

Herpes simplex virus type 2 is the most common cause of genital and perianal ulcers in immunocompromised individuals.¹ Patients classically present with painful grouped vesicles followed by painful superficial ulcers that may rapidly progress to extensive confluent ulceration. A hypertrophic variant of genital herpes characterized by anogenital verrucous lesions, similar to condyloma acuminata, also can be seen in immunocompromised individuals.² This form has almost exclusively been observed in patients with human immunodeficiency virus and may occur in isolation or together with the ulcerative form.^1-5 A case of vegetative HHV infection of the genital area in a patient with common variable immunodeficiency has been reported.⁶ Verrucous lesions of the mouth secondary to HHV have been observed in Hodgkin lymphoma, acute myelogenous leukemia, and individuals on immunosuppressive medications.^7-10

Perianal involvement of Crohn disease typically presents with fistulas, ulcers, abscesses, strictures, and skin tags in some cases. Invasive squamous cell carcinoma may arise within a chronic ulcer of the anogenital area or may itself manifest as an ulcer or anal fissure. Perianal ulcerative skin tuberculosis has been reported in the literature as a rare manifestation of extrapulmonary tuberculosis and should be considered in a patient with an appropriate clinical history. Pyoderma gangrenosum classically pre-sents as a large ulcer with irregular rolled borders, though a rare variant of vegetative pyoderma gangrenosum may manifest as a nodular or verrucous plaque.

Studies to diagnose HHV include viral cell culture, HHV polymerase chain reaction testing, HHV serology, and direct fluorescent antibody testing. Skin biopsy may be necessary to rule out underlying malignancy. Treatment of perianal HHV infection includes acyclovir, valacyclovir, or famciclovir.^1,5,6 Hypertrophic lesions often are refractory to first-line antiviral therapy and may require surgical resection or treatment with alternative medications such as imiquimod, a topical immunomodulator.^3,5,6,11

LAS VEGAS – Up to 22% of opioid abusers also abuse gabapentin, taking high doses of the antiepileptic for its psychoactive effects, or to potentiate the effect of opioids.

ah_designs/Getty Images

The drug – the 10th most commonly prescribed in the United States – is increasingly implicated in overdose deaths. In response, several states have recently reclassified the antiepileptic as a Schedule V controlled substance. Other states have declined to go that far, but have added gabapentin (Neurontin and others) to the drugs that must be reported to state prescription monitoring programs.

“Gabapentin and pregabalin [Lyrica] are versatile and important drugs that are widely prescribed and used off label for a number of conditions from seizure disorder to fibromyalgia,” said Joseph Pergolizzi Jr., MD, who discussed the issue during the annual PAINWeek. “Abuse patterns differ somewhat from abuse patterns with prescription opioids. People who misuse gabapentinoids tend to already use other drugs inappropriately. It’s rare to find a person who only takes them recreationally, but it is increasingly common to find polydrug abusers who take gabapentinoids.”

Gabapentin abuse appears to be more common in Europe than in the United States, where it’s just beginning to emerge, Dr. Pergolizzi said. And the picture is more nuanced than it might first appear: Many of those who are misusing the drug are using it as a “do-it-yourself” opioid withdrawal aid, he said in an interview.

At the meeting, he presented a literature review comprising 46 papers on pregabalin abuse and 263 on gabapentin abuse. Several important themes arose from these papers, said Dr. Pergolizzi, cofounder and chief operating officer of NEMA Research Inc., Naples, Fla.:

• Gabapentin and pregabalin are being prescribed off label for numerous conditions, including bipolar disorder, neuropathic pain, diabetic neuropathy, complex regional pain syndrome, attention deficit disorder, restless leg syndrome, trigeminal neuralgia, periodic limb movement disorder of sleep, migraine, drug and alcohol withdrawal seizures, chronic low back pain, and even menopausal symptoms.
• About a one-third of users experience withdrawal symptoms with sudden discontinuation. Symptoms include disorientation, anxiety, insomnia, heart palpitations, diaphoresis, and abdominal cramps.
• Risk factors for abuse are emerging. These include opioid use disorders, mental illnesses, and a history of taking supratherapeutic doses of the drugs. Age and sex don’t seem to be a consistent risk factor for abuse.
• Abusers can obtain nonprescription gabapentinoids more easily each year, including street sales and online orders, Dr. Pergolizzi said. “A Google search conducted in July for ‘buy gabapentin without a prescription’ yielded 4.48 million results and ‘buy pregabalin without a prescription,’ 622,000. A similar search conducted in September 2017 yielded 1.19 million and 352,000 results, respectively.”
• Few urine drug assays screen for gabapentinoids, which makes them easy to conceal in random drug testing.

Reports of gabapentin-involved drug overdoses and even deaths have recently emerged in the United States, particularly in the opioid abuse-plagued Appalachian states. An article in May in Drug and Alcohol Dependence examined the prevalence of gabapentin in postmortem toxicology in drug overdose deaths in four Appalachian states in 2015 (Drug Alcohol Depend. 2018;186:80-5). Rates were 4% in eastern Tennessee, 15% in West Virginia, 20% in North Carolina, and 41% in Kentucky.

Three states have now added gabapentin to their list of Schedule V controlled substances: Kentucky in 2017, West Virginia this May, and Tennessee in July.

Ohio, Minnesota, Virginia, and Massachusetts have taken a different tack to controlling dispensing. In those states, all pharmacies, prescribers, and wholesalers must report all dispensing and sales of gabapentin to their prescription monitoring databases.

Dr. Pergolizzi disclosed financial relationships with numerous pharmaceutical companies.

[email protected]

SOURCE: Pergolizzi J et al. PAINWeek 2018, Poster 55.

LAS VEGAS – Up to 22% of opioid abusers also abuse gabapentin, taking high doses of the antiepileptic for its psychoactive effects, or to potentiate the effect of opioids.

ah_designs/Getty Images

The drug – the 10th most commonly prescribed in the United States – is increasingly implicated in overdose deaths. In response, several states have recently reclassified the antiepileptic as a Schedule V controlled substance. Other states have declined to go that far, but have added gabapentin (Neurontin and others) to the drugs that must be reported to state prescription monitoring programs.

“Gabapentin and pregabalin [Lyrica] are versatile and important drugs that are widely prescribed and used off label for a number of conditions from seizure disorder to fibromyalgia,” said Joseph Pergolizzi Jr., MD, who discussed the issue during the annual PAINWeek. “Abuse patterns differ somewhat from abuse patterns with prescription opioids. People who misuse gabapentinoids tend to already use other drugs inappropriately. It’s rare to find a person who only takes them recreationally, but it is increasingly common to find polydrug abusers who take gabapentinoids.”

Gabapentin abuse appears to be more common in Europe than in the United States, where it’s just beginning to emerge, Dr. Pergolizzi said. And the picture is more nuanced than it might first appear: Many of those who are misusing the drug are using it as a “do-it-yourself” opioid withdrawal aid, he said in an interview.

At the meeting, he presented a literature review comprising 46 papers on pregabalin abuse and 263 on gabapentin abuse. Several important themes arose from these papers, said Dr. Pergolizzi, cofounder and chief operating officer of NEMA Research Inc., Naples, Fla.:

• Gabapentin and pregabalin are being prescribed off label for numerous conditions, including bipolar disorder, neuropathic pain, diabetic neuropathy, complex regional pain syndrome, attention deficit disorder, restless leg syndrome, trigeminal neuralgia, periodic limb movement disorder of sleep, migraine, drug and alcohol withdrawal seizures, chronic low back pain, and even menopausal symptoms.
• About a one-third of users experience withdrawal symptoms with sudden discontinuation. Symptoms include disorientation, anxiety, insomnia, heart palpitations, diaphoresis, and abdominal cramps.
• Risk factors for abuse are emerging. These include opioid use disorders, mental illnesses, and a history of taking supratherapeutic doses of the drugs. Age and sex don’t seem to be a consistent risk factor for abuse.
• Abusers can obtain nonprescription gabapentinoids more easily each year, including street sales and online orders, Dr. Pergolizzi said. “A Google search conducted in July for ‘buy gabapentin without a prescription’ yielded 4.48 million results and ‘buy pregabalin without a prescription,’ 622,000. A similar search conducted in September 2017 yielded 1.19 million and 352,000 results, respectively.”
• Few urine drug assays screen for gabapentinoids, which makes them easy to conceal in random drug testing.

Reports of gabapentin-involved drug overdoses and even deaths have recently emerged in the United States, particularly in the opioid abuse-plagued Appalachian states. An article in May in Drug and Alcohol Dependence examined the prevalence of gabapentin in postmortem toxicology in drug overdose deaths in four Appalachian states in 2015 (Drug Alcohol Depend. 2018;186:80-5). Rates were 4% in eastern Tennessee, 15% in West Virginia, 20% in North Carolina, and 41% in Kentucky.

Three states have now added gabapentin to their list of Schedule V controlled substances: Kentucky in 2017, West Virginia this May, and Tennessee in July.

Ohio, Minnesota, Virginia, and Massachusetts have taken a different tack to controlling dispensing. In those states, all pharmacies, prescribers, and wholesalers must report all dispensing and sales of gabapentin to their prescription monitoring databases.

Dr. Pergolizzi disclosed financial relationships with numerous pharmaceutical companies.

[email protected]

SOURCE: Pergolizzi J et al. PAINWeek 2018, Poster 55.

LAS VEGAS – Up to 22% of opioid abusers also abuse gabapentin, taking high doses of the antiepileptic for its psychoactive effects, or to potentiate the effect of opioids.

ah_designs/Getty Images

The drug – the 10th most commonly prescribed in the United States – is increasingly implicated in overdose deaths. In response, several states have recently reclassified the antiepileptic as a Schedule V controlled substance. Other states have declined to go that far, but have added gabapentin (Neurontin and others) to the drugs that must be reported to state prescription monitoring programs.

“Gabapentin and pregabalin [Lyrica] are versatile and important drugs that are widely prescribed and used off label for a number of conditions from seizure disorder to fibromyalgia,” said Joseph Pergolizzi Jr., MD, who discussed the issue during the annual PAINWeek. “Abuse patterns differ somewhat from abuse patterns with prescription opioids. People who misuse gabapentinoids tend to already use other drugs inappropriately. It’s rare to find a person who only takes them recreationally, but it is increasingly common to find polydrug abusers who take gabapentinoids.”

Gabapentin abuse appears to be more common in Europe than in the United States, where it’s just beginning to emerge, Dr. Pergolizzi said. And the picture is more nuanced than it might first appear: Many of those who are misusing the drug are using it as a “do-it-yourself” opioid withdrawal aid, he said in an interview.

At the meeting, he presented a literature review comprising 46 papers on pregabalin abuse and 263 on gabapentin abuse. Several important themes arose from these papers, said Dr. Pergolizzi, cofounder and chief operating officer of NEMA Research Inc., Naples, Fla.:

• Gabapentin and pregabalin are being prescribed off label for numerous conditions, including bipolar disorder, neuropathic pain, diabetic neuropathy, complex regional pain syndrome, attention deficit disorder, restless leg syndrome, trigeminal neuralgia, periodic limb movement disorder of sleep, migraine, drug and alcohol withdrawal seizures, chronic low back pain, and even menopausal symptoms.
• About a one-third of users experience withdrawal symptoms with sudden discontinuation. Symptoms include disorientation, anxiety, insomnia, heart palpitations, diaphoresis, and abdominal cramps.
• Risk factors for abuse are emerging. These include opioid use disorders, mental illnesses, and a history of taking supratherapeutic doses of the drugs. Age and sex don’t seem to be a consistent risk factor for abuse.
• Abusers can obtain nonprescription gabapentinoids more easily each year, including street sales and online orders, Dr. Pergolizzi said. “A Google search conducted in July for ‘buy gabapentin without a prescription’ yielded 4.48 million results and ‘buy pregabalin without a prescription,’ 622,000. A similar search conducted in September 2017 yielded 1.19 million and 352,000 results, respectively.”
• Few urine drug assays screen for gabapentinoids, which makes them easy to conceal in random drug testing.

Reports of gabapentin-involved drug overdoses and even deaths have recently emerged in the United States, particularly in the opioid abuse-plagued Appalachian states. An article in May in Drug and Alcohol Dependence examined the prevalence of gabapentin in postmortem toxicology in drug overdose deaths in four Appalachian states in 2015 (Drug Alcohol Depend. 2018;186:80-5). Rates were 4% in eastern Tennessee, 15% in West Virginia, 20% in North Carolina, and 41% in Kentucky.

Three states have now added gabapentin to their list of Schedule V controlled substances: Kentucky in 2017, West Virginia this May, and Tennessee in July.

Ohio, Minnesota, Virginia, and Massachusetts have taken a different tack to controlling dispensing. In those states, all pharmacies, prescribers, and wholesalers must report all dispensing and sales of gabapentin to their prescription monitoring databases.

Dr. Pergolizzi disclosed financial relationships with numerous pharmaceutical companies.

[email protected]

SOURCE: Pergolizzi J et al. PAINWeek 2018, Poster 55.

A computer-based decision aid aims to facilitate the complex discussions and decisions that face patients with lupus nephritis.

Under development at the University of Alabama at Birmingham, the Shared Decision-Making in Lupus Electronic tool (SMILE) describes in easy-to-understand modules the pathology of the disease, and what can happen if it progresses untreated. The tool also identifies treatment options and discusses the potential benefits of each one, as well as the risks. It can be folded into office visits, accessed during waiting times, or viewed at the patient’s leisure. Its creators hope that patients will experience more fruitful discussions with their physicians by learning more about these complicated concepts as they co-navigate the difficult decisions both must make.

UAB Photo

“Our intent was to figure out how best to offer the education about lupus and its treatments that women need when coming into a busy clinic,” said Jasvinder Singh, MD, who is leading the developmental team. “Everyone’s time is limited, and patients want information delivered quickly, but in a way they can understand.”

SMILE is the first tool of its kind for patients with lupus nephritis, said Alexa Meara, MD, one of the rheumatologists investigating it.

“There is just nothing out there like this for either lupus, or lupus nephritis,” said Dr. Meara, a rheumatologist at Ohio State University, Columbus. “Lupus nephritis is a heterogeneous relapsing-remitting disease with complex medical regimens. It can have cognitive impacts and affect fertility, but these are things that may happen over decades. Patients may not be ready to talk about them early on, but they must understand them. We would like to enable the conversation between physician and patient, so they’re on the same page with everyone’s values and concerns addressed on both sides.”

But getting everyone on the same page at the same time is challenging, said Dr. Singh, a rheumatologist and professor of medicine and epidemiology at the University of Alabama at Birmingham. “This is a bit of a dilemma and a challenge. What’s great about the lupus decision aid is that it is culturally and linguistically appropriate for patients of all backgrounds, races, ages, literacy levels, and socioeconomic statuses. This levels the playing field for patients who are trying to understand their diagnosis and options to the best of their abilities.”

Three years in the making, SMILE comprises several modules addressing different facets of lupus nephritis. In simple words and concepts, the tool informs patients about what lupus is and what it can do to the kidneys, the information gleaned from blood and urine tests and what it means, and the potential consequences of not treating lupus kidney disease. The heart of the program is its breakdown of treatment options.

“It helps patients understand why they may be getting these cancer medications, and what their side effects are,” Dr. Singh said. “The tool also walks them through a comparison of the medications, with one slide on each medication and its risks and benefits. We really focus on that – about 60%-70% of the tool is comparing the drugs.”

The decision aid also contains optional modules that patients can bypass or explore. “There are separate sections on the risks and benefits of corticosteroids, on pregnancy and lactation, and on preserving fertility.”

A complete click-through of the basic information takes about 20 minutes, Dr. Singh said. An ideal time for a patient to do so would be before the initial visit to discuss treatment options, which can be an overwhelming experience. The tool could be presented in several ways. In the office, preloaded iPads could be one vehicle. These could be standalone, or linked to the patient’s electronic health record, so that any entered information could be directly transferred. At home, patients could navigate to a web link for an online version.

The first visit is a crucial moment, he said, where patients can evolve into management partners, or leave even more confused than when they arrived.

“We aim to motivate and provide tools to the patient, so that the conversation isn’t just, ‘You have the disease and we can put you on this or that drug,’ ” Dr. Singh said. “You can lose the patient right away in this scenario, while you’re talking about so many things the patient isn’t even hearing you, because she’s thinking about other issues that are important in her life, completely overwhelmed with the shock of the diagnosis and with fear.”

The Patient-Centered Outcomes Research Institute (PCORI) has funded much of the work getting SMILE up and running, including a soon-to-be-published trial that favorably compared it against the educational standard: a paper pamphlet on lupus nephritis prepared by the American College of Rheumatology.

In this study, 301 high‐risk women with lupus kidney disease, including racial/ethnic minorities with low socioeconomic status, either received the pamphlet or the SMILE tool. The group was demographically diverse: 47% black, 26% Hispanic, 15% white, and 7% Asian. Other groups made up the remainder.

More patients rated the information in the decision aid to be excellent for understanding the impact of lupus (49% vs. 33%), risk factors (43% vs. 27%), medication options (50% vs. 33%), and evidence about medications (47% vs. 24%). About half of the tool users rated the ease of use of materials as excellent (51% vs. 38%). Women who used the tool also reported much less decisional conflict for immunosuppressive drugs and were much more likely to choose the treatment option most consistent with their values, having viewed information that mattered the most for the treatment decision.

PCORI continues to support the project, too. Dr. Singh just received a $2.2 million grant to investigate the tool in 16 clinics. The 2-year observational study has three aims:

• Identify physician attitudes and patient barriers toward the tool, to guide decisions about how to best implement it in its final form.

• Track changes in subjective and objective measures of implementation effectiveness.

• Identify opportunities for disseminating the tool and develop a step‐by‐step implementation guide for incorporating the decision aid tool into regular lupus clinic visits and care pathways.

The study will also look at some patient‐centered outcomes, including decision conflict, emergency department and inpatient visits, patient‐physician communication, and implementation success. Some practice-level outcomes will be assessed, including potential barriers to implementation. “The team will focus on context and strategy as facilitators and barriers to effective implementation of the lupus decision aid in busy, clinical practices of various types – for example, private versus academic, urban versus suburban, large versus small group practice,” according to the PCORI study description.

“This study can’t solve the entire problem about patients choosing treatment or no treatment, but it can provide a start to the conversation,” Dr. Singh said. “And my hope is that once it’s available, people will modify it to fit their needs, make adaptations and modifications to keep it relevant and valuable.”

[email protected]

A computer-based decision aid aims to facilitate the complex discussions and decisions that face patients with lupus nephritis.

Under development at the University of Alabama at Birmingham, the Shared Decision-Making in Lupus Electronic tool (SMILE) describes in easy-to-understand modules the pathology of the disease, and what can happen if it progresses untreated. The tool also identifies treatment options and discusses the potential benefits of each one, as well as the risks. It can be folded into office visits, accessed during waiting times, or viewed at the patient’s leisure. Its creators hope that patients will experience more fruitful discussions with their physicians by learning more about these complicated concepts as they co-navigate the difficult decisions both must make.

UAB Photo

“Our intent was to figure out how best to offer the education about lupus and its treatments that women need when coming into a busy clinic,” said Jasvinder Singh, MD, who is leading the developmental team. “Everyone’s time is limited, and patients want information delivered quickly, but in a way they can understand.”

SMILE is the first tool of its kind for patients with lupus nephritis, said Alexa Meara, MD, one of the rheumatologists investigating it.

“There is just nothing out there like this for either lupus, or lupus nephritis,” said Dr. Meara, a rheumatologist at Ohio State University, Columbus. “Lupus nephritis is a heterogeneous relapsing-remitting disease with complex medical regimens. It can have cognitive impacts and affect fertility, but these are things that may happen over decades. Patients may not be ready to talk about them early on, but they must understand them. We would like to enable the conversation between physician and patient, so they’re on the same page with everyone’s values and concerns addressed on both sides.”

But getting everyone on the same page at the same time is challenging, said Dr. Singh, a rheumatologist and professor of medicine and epidemiology at the University of Alabama at Birmingham. “This is a bit of a dilemma and a challenge. What’s great about the lupus decision aid is that it is culturally and linguistically appropriate for patients of all backgrounds, races, ages, literacy levels, and socioeconomic statuses. This levels the playing field for patients who are trying to understand their diagnosis and options to the best of their abilities.”

Three years in the making, SMILE comprises several modules addressing different facets of lupus nephritis. In simple words and concepts, the tool informs patients about what lupus is and what it can do to the kidneys, the information gleaned from blood and urine tests and what it means, and the potential consequences of not treating lupus kidney disease. The heart of the program is its breakdown of treatment options.

“It helps patients understand why they may be getting these cancer medications, and what their side effects are,” Dr. Singh said. “The tool also walks them through a comparison of the medications, with one slide on each medication and its risks and benefits. We really focus on that – about 60%-70% of the tool is comparing the drugs.”

The decision aid also contains optional modules that patients can bypass or explore. “There are separate sections on the risks and benefits of corticosteroids, on pregnancy and lactation, and on preserving fertility.”

A complete click-through of the basic information takes about 20 minutes, Dr. Singh said. An ideal time for a patient to do so would be before the initial visit to discuss treatment options, which can be an overwhelming experience. The tool could be presented in several ways. In the office, preloaded iPads could be one vehicle. These could be standalone, or linked to the patient’s electronic health record, so that any entered information could be directly transferred. At home, patients could navigate to a web link for an online version.

The first visit is a crucial moment, he said, where patients can evolve into management partners, or leave even more confused than when they arrived.

“We aim to motivate and provide tools to the patient, so that the conversation isn’t just, ‘You have the disease and we can put you on this or that drug,’ ” Dr. Singh said. “You can lose the patient right away in this scenario, while you’re talking about so many things the patient isn’t even hearing you, because she’s thinking about other issues that are important in her life, completely overwhelmed with the shock of the diagnosis and with fear.”

The Patient-Centered Outcomes Research Institute (PCORI) has funded much of the work getting SMILE up and running, including a soon-to-be-published trial that favorably compared it against the educational standard: a paper pamphlet on lupus nephritis prepared by the American College of Rheumatology.

In this study, 301 high‐risk women with lupus kidney disease, including racial/ethnic minorities with low socioeconomic status, either received the pamphlet or the SMILE tool. The group was demographically diverse: 47% black, 26% Hispanic, 15% white, and 7% Asian. Other groups made up the remainder.

More patients rated the information in the decision aid to be excellent for understanding the impact of lupus (49% vs. 33%), risk factors (43% vs. 27%), medication options (50% vs. 33%), and evidence about medications (47% vs. 24%). About half of the tool users rated the ease of use of materials as excellent (51% vs. 38%). Women who used the tool also reported much less decisional conflict for immunosuppressive drugs and were much more likely to choose the treatment option most consistent with their values, having viewed information that mattered the most for the treatment decision.

PCORI continues to support the project, too. Dr. Singh just received a $2.2 million grant to investigate the tool in 16 clinics. The 2-year observational study has three aims:

• Identify physician attitudes and patient barriers toward the tool, to guide decisions about how to best implement it in its final form.

• Track changes in subjective and objective measures of implementation effectiveness.

• Identify opportunities for disseminating the tool and develop a step‐by‐step implementation guide for incorporating the decision aid tool into regular lupus clinic visits and care pathways.

The study will also look at some patient‐centered outcomes, including decision conflict, emergency department and inpatient visits, patient‐physician communication, and implementation success. Some practice-level outcomes will be assessed, including potential barriers to implementation. “The team will focus on context and strategy as facilitators and barriers to effective implementation of the lupus decision aid in busy, clinical practices of various types – for example, private versus academic, urban versus suburban, large versus small group practice,” according to the PCORI study description.

“This study can’t solve the entire problem about patients choosing treatment or no treatment, but it can provide a start to the conversation,” Dr. Singh said. “And my hope is that once it’s available, people will modify it to fit their needs, make adaptations and modifications to keep it relevant and valuable.”

[email protected]

A computer-based decision aid aims to facilitate the complex discussions and decisions that face patients with lupus nephritis.

Under development at the University of Alabama at Birmingham, the Shared Decision-Making in Lupus Electronic tool (SMILE) describes in easy-to-understand modules the pathology of the disease, and what can happen if it progresses untreated. The tool also identifies treatment options and discusses the potential benefits of each one, as well as the risks. It can be folded into office visits, accessed during waiting times, or viewed at the patient’s leisure. Its creators hope that patients will experience more fruitful discussions with their physicians by learning more about these complicated concepts as they co-navigate the difficult decisions both must make.

UAB Photo

“Our intent was to figure out how best to offer the education about lupus and its treatments that women need when coming into a busy clinic,” said Jasvinder Singh, MD, who is leading the developmental team. “Everyone’s time is limited, and patients want information delivered quickly, but in a way they can understand.”

SMILE is the first tool of its kind for patients with lupus nephritis, said Alexa Meara, MD, one of the rheumatologists investigating it.

“There is just nothing out there like this for either lupus, or lupus nephritis,” said Dr. Meara, a rheumatologist at Ohio State University, Columbus. “Lupus nephritis is a heterogeneous relapsing-remitting disease with complex medical regimens. It can have cognitive impacts and affect fertility, but these are things that may happen over decades. Patients may not be ready to talk about them early on, but they must understand them. We would like to enable the conversation between physician and patient, so they’re on the same page with everyone’s values and concerns addressed on both sides.”

But getting everyone on the same page at the same time is challenging, said Dr. Singh, a rheumatologist and professor of medicine and epidemiology at the University of Alabama at Birmingham. “This is a bit of a dilemma and a challenge. What’s great about the lupus decision aid is that it is culturally and linguistically appropriate for patients of all backgrounds, races, ages, literacy levels, and socioeconomic statuses. This levels the playing field for patients who are trying to understand their diagnosis and options to the best of their abilities.”

Three years in the making, SMILE comprises several modules addressing different facets of lupus nephritis. In simple words and concepts, the tool informs patients about what lupus is and what it can do to the kidneys, the information gleaned from blood and urine tests and what it means, and the potential consequences of not treating lupus kidney disease. The heart of the program is its breakdown of treatment options.

“It helps patients understand why they may be getting these cancer medications, and what their side effects are,” Dr. Singh said. “The tool also walks them through a comparison of the medications, with one slide on each medication and its risks and benefits. We really focus on that – about 60%-70% of the tool is comparing the drugs.”

The decision aid also contains optional modules that patients can bypass or explore. “There are separate sections on the risks and benefits of corticosteroids, on pregnancy and lactation, and on preserving fertility.”

A complete click-through of the basic information takes about 20 minutes, Dr. Singh said. An ideal time for a patient to do so would be before the initial visit to discuss treatment options, which can be an overwhelming experience. The tool could be presented in several ways. In the office, preloaded iPads could be one vehicle. These could be standalone, or linked to the patient’s electronic health record, so that any entered information could be directly transferred. At home, patients could navigate to a web link for an online version.

The first visit is a crucial moment, he said, where patients can evolve into management partners, or leave even more confused than when they arrived.

“We aim to motivate and provide tools to the patient, so that the conversation isn’t just, ‘You have the disease and we can put you on this or that drug,’ ” Dr. Singh said. “You can lose the patient right away in this scenario, while you’re talking about so many things the patient isn’t even hearing you, because she’s thinking about other issues that are important in her life, completely overwhelmed with the shock of the diagnosis and with fear.”

The Patient-Centered Outcomes Research Institute (PCORI) has funded much of the work getting SMILE up and running, including a soon-to-be-published trial that favorably compared it against the educational standard: a paper pamphlet on lupus nephritis prepared by the American College of Rheumatology.

In this study, 301 high‐risk women with lupus kidney disease, including racial/ethnic minorities with low socioeconomic status, either received the pamphlet or the SMILE tool. The group was demographically diverse: 47% black, 26% Hispanic, 15% white, and 7% Asian. Other groups made up the remainder.

More patients rated the information in the decision aid to be excellent for understanding the impact of lupus (49% vs. 33%), risk factors (43% vs. 27%), medication options (50% vs. 33%), and evidence about medications (47% vs. 24%). About half of the tool users rated the ease of use of materials as excellent (51% vs. 38%). Women who used the tool also reported much less decisional conflict for immunosuppressive drugs and were much more likely to choose the treatment option most consistent with their values, having viewed information that mattered the most for the treatment decision.

PCORI continues to support the project, too. Dr. Singh just received a $2.2 million grant to investigate the tool in 16 clinics. The 2-year observational study has three aims:

• Identify physician attitudes and patient barriers toward the tool, to guide decisions about how to best implement it in its final form.

• Track changes in subjective and objective measures of implementation effectiveness.

• Identify opportunities for disseminating the tool and develop a step‐by‐step implementation guide for incorporating the decision aid tool into regular lupus clinic visits and care pathways.

The study will also look at some patient‐centered outcomes, including decision conflict, emergency department and inpatient visits, patient‐physician communication, and implementation success. Some practice-level outcomes will be assessed, including potential barriers to implementation. “The team will focus on context and strategy as facilitators and barriers to effective implementation of the lupus decision aid in busy, clinical practices of various types – for example, private versus academic, urban versus suburban, large versus small group practice,” according to the PCORI study description.

“This study can’t solve the entire problem about patients choosing treatment or no treatment, but it can provide a start to the conversation,” Dr. Singh said. “And my hope is that once it’s available, people will modify it to fit their needs, make adaptations and modifications to keep it relevant and valuable.”

[email protected]