SCOTTSDALE, ARIZ. – From enterocolitis to MRSA, serious infections are on the rise among inpatients with psoriasis, and psoriasis is an independent risk factor for serious infections, according to findings from large retrospective studies from the United States and the United Kingdom.

Inpatients with psoriasis in the United States also were at greater risk of serious infections, compared with nonpsoriatic inpatients at every time point studied, and serious infections were associated with increased hospital costs, length of stay, and risk of mortality, reported Derek Hsu, a medical student at Northwestern University, Chicago, and his associates. “Research is needed to determine how to reduce the risk of serious infections in patients with psoriasis,” the investigators emphasized.

©David Parr/ thinkstockphotos.com

Psoriasis affects some 7 million adults in the United States. Biologics, which are transforming the treatment landscape for moderate-to-severe psoriasis, “should reduce inherent infectious risk by controlling the inflammatory process and reducing disease severity, [but] these effects may be immunosuppressing and increase the risk of infection in other ways,” according to Mr. Hsu and his associates. For their study, they analyzed data for 2002-2012 from the Nationwide Inpatient Sample, which covers 20% of hospitalizations in the United States. They extracted validated ICD-9 codes for psoriasis and serious infections, and calculated costs of care after adjusting for 2014 inflation, based on the United States Consumer Price Index.

Overall rates of serious infection and rates of pneumonia, MRSA, septicemia, diverticulitis, enterocolitis, encephalitis, and any viral or fungal infection rose significantly among inpatients with psoriasis between 2002 and 2012 (all P-values less than .05). Predictors of serious infections among inpatients with psoriasis included diabetes mellitus, obesity, and being of non-Caucasian race or ethnicity, female, older than 60 years, and on Medicare or Medicaid, the researchers reported at the annual meeting of the Society for Investigative Dermatology.

Furthermore, after controlling for age, sex, and race, psoriasis was a significant risk factor for many different types of serious infections. Among these were cellulitis, herpes simplex virus, infectious arthritis, osteomyelitis, meningitis, influenza, encephalitis, septicemia, enterocolitis, MRSA, methicillin-sensitive Staphylococcus aureus infections, and Clostridium difficile. Further, inpatients with psoriasis were more prone to urinary tract infection, peritonitis or intestinal abscess, appendicitis, tuberculosis, and viral and fungal infections (all P-values less than .05). The average cost of hospital stay for inpatients with psoriasis was more than $2,200 greater when they were diagnosed with one or more serious infections than otherwise, and their average length of hospital stay was 2 days longer.

The study in the United Kingdom included nearly 200,000 patients with psoriasis and almost 1 million patients without psoriasis from The Health Improvement Network electronic medical record database. Between 2002 and 2013, patients without psoriasis developed an estimated 78.5 serious infections per 100,000 person-years, compared with 88.9, 85.7, and 145.7 serious infections per 100,000 person-years, respectively, for all psoriasis patients, patients with mild disease, and patients with severe disease requiring systemic or phototherapy, said Dr. Junko Takeshita and her colleagues at the University of Pennsylvania in Philadelphia. After controlling for many potential demographic and clinical confounders, psoriasis increased the risk of serious infection by about 21% (hazard ratio, 1.21; 95% confidence interval, 1.18-1.23). Patients with severe psoriasis had a 63% greater risk of infection than patients without psoriasis, compared with an 18% increase for patients with mild psoriasis.

The findings show “serious infection, particularly respiratory and skin or soft tissue infections, to be an important and common cause of morbidity among patients with psoriasis, especially those with more severe disease,” Dr. Takeshita and her associates said. Notably, the link between psoriasis and risk of serious infection persisted after excluding patients on immunosuppressive therapies, suggesting “that the greater infection risk is at least partially attributable to more severe psoriasis, itself,” they added.

The analysis of Nationwide Inpatient Sample data was funded by the Agency for Healthcare Research and Quality and by the Dermatology Foundation. The analysis of Health Improvement Network data was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, which is part of the National Institutes of Health, and by the Dermatology Foundation. None of the investigators reported conflicts of interest.

SCOTTSDALE, ARIZ. – From enterocolitis to MRSA, serious infections are on the rise among inpatients with psoriasis, and psoriasis is an independent risk factor for serious infections, according to findings from large retrospective studies from the United States and the United Kingdom.

Inpatients with psoriasis in the United States also were at greater risk of serious infections, compared with nonpsoriatic inpatients at every time point studied, and serious infections were associated with increased hospital costs, length of stay, and risk of mortality, reported Derek Hsu, a medical student at Northwestern University, Chicago, and his associates. “Research is needed to determine how to reduce the risk of serious infections in patients with psoriasis,” the investigators emphasized.

©David Parr/ thinkstockphotos.com

Psoriasis affects some 7 million adults in the United States. Biologics, which are transforming the treatment landscape for moderate-to-severe psoriasis, “should reduce inherent infectious risk by controlling the inflammatory process and reducing disease severity, [but] these effects may be immunosuppressing and increase the risk of infection in other ways,” according to Mr. Hsu and his associates. For their study, they analyzed data for 2002-2012 from the Nationwide Inpatient Sample, which covers 20% of hospitalizations in the United States. They extracted validated ICD-9 codes for psoriasis and serious infections, and calculated costs of care after adjusting for 2014 inflation, based on the United States Consumer Price Index.

Overall rates of serious infection and rates of pneumonia, MRSA, septicemia, diverticulitis, enterocolitis, encephalitis, and any viral or fungal infection rose significantly among inpatients with psoriasis between 2002 and 2012 (all P-values less than .05). Predictors of serious infections among inpatients with psoriasis included diabetes mellitus, obesity, and being of non-Caucasian race or ethnicity, female, older than 60 years, and on Medicare or Medicaid, the researchers reported at the annual meeting of the Society for Investigative Dermatology.

Furthermore, after controlling for age, sex, and race, psoriasis was a significant risk factor for many different types of serious infections. Among these were cellulitis, herpes simplex virus, infectious arthritis, osteomyelitis, meningitis, influenza, encephalitis, septicemia, enterocolitis, MRSA, methicillin-sensitive Staphylococcus aureus infections, and Clostridium difficile. Further, inpatients with psoriasis were more prone to urinary tract infection, peritonitis or intestinal abscess, appendicitis, tuberculosis, and viral and fungal infections (all P-values less than .05). The average cost of hospital stay for inpatients with psoriasis was more than $2,200 greater when they were diagnosed with one or more serious infections than otherwise, and their average length of hospital stay was 2 days longer.

The study in the United Kingdom included nearly 200,000 patients with psoriasis and almost 1 million patients without psoriasis from The Health Improvement Network electronic medical record database. Between 2002 and 2013, patients without psoriasis developed an estimated 78.5 serious infections per 100,000 person-years, compared with 88.9, 85.7, and 145.7 serious infections per 100,000 person-years, respectively, for all psoriasis patients, patients with mild disease, and patients with severe disease requiring systemic or phototherapy, said Dr. Junko Takeshita and her colleagues at the University of Pennsylvania in Philadelphia. After controlling for many potential demographic and clinical confounders, psoriasis increased the risk of serious infection by about 21% (hazard ratio, 1.21; 95% confidence interval, 1.18-1.23). Patients with severe psoriasis had a 63% greater risk of infection than patients without psoriasis, compared with an 18% increase for patients with mild psoriasis.

The findings show “serious infection, particularly respiratory and skin or soft tissue infections, to be an important and common cause of morbidity among patients with psoriasis, especially those with more severe disease,” Dr. Takeshita and her associates said. Notably, the link between psoriasis and risk of serious infection persisted after excluding patients on immunosuppressive therapies, suggesting “that the greater infection risk is at least partially attributable to more severe psoriasis, itself,” they added.

The analysis of Nationwide Inpatient Sample data was funded by the Agency for Healthcare Research and Quality and by the Dermatology Foundation. The analysis of Health Improvement Network data was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, which is part of the National Institutes of Health, and by the Dermatology Foundation. None of the investigators reported conflicts of interest.

SCOTTSDALE, ARIZ. – From enterocolitis to MRSA, serious infections are on the rise among inpatients with psoriasis, and psoriasis is an independent risk factor for serious infections, according to findings from large retrospective studies from the United States and the United Kingdom.

Inpatients with psoriasis in the United States also were at greater risk of serious infections, compared with nonpsoriatic inpatients at every time point studied, and serious infections were associated with increased hospital costs, length of stay, and risk of mortality, reported Derek Hsu, a medical student at Northwestern University, Chicago, and his associates. “Research is needed to determine how to reduce the risk of serious infections in patients with psoriasis,” the investigators emphasized.

©David Parr/ thinkstockphotos.com

Psoriasis affects some 7 million adults in the United States. Biologics, which are transforming the treatment landscape for moderate-to-severe psoriasis, “should reduce inherent infectious risk by controlling the inflammatory process and reducing disease severity, [but] these effects may be immunosuppressing and increase the risk of infection in other ways,” according to Mr. Hsu and his associates. For their study, they analyzed data for 2002-2012 from the Nationwide Inpatient Sample, which covers 20% of hospitalizations in the United States. They extracted validated ICD-9 codes for psoriasis and serious infections, and calculated costs of care after adjusting for 2014 inflation, based on the United States Consumer Price Index.

Overall rates of serious infection and rates of pneumonia, MRSA, septicemia, diverticulitis, enterocolitis, encephalitis, and any viral or fungal infection rose significantly among inpatients with psoriasis between 2002 and 2012 (all P-values less than .05). Predictors of serious infections among inpatients with psoriasis included diabetes mellitus, obesity, and being of non-Caucasian race or ethnicity, female, older than 60 years, and on Medicare or Medicaid, the researchers reported at the annual meeting of the Society for Investigative Dermatology.

Furthermore, after controlling for age, sex, and race, psoriasis was a significant risk factor for many different types of serious infections. Among these were cellulitis, herpes simplex virus, infectious arthritis, osteomyelitis, meningitis, influenza, encephalitis, septicemia, enterocolitis, MRSA, methicillin-sensitive Staphylococcus aureus infections, and Clostridium difficile. Further, inpatients with psoriasis were more prone to urinary tract infection, peritonitis or intestinal abscess, appendicitis, tuberculosis, and viral and fungal infections (all P-values less than .05). The average cost of hospital stay for inpatients with psoriasis was more than $2,200 greater when they were diagnosed with one or more serious infections than otherwise, and their average length of hospital stay was 2 days longer.

The study in the United Kingdom included nearly 200,000 patients with psoriasis and almost 1 million patients without psoriasis from The Health Improvement Network electronic medical record database. Between 2002 and 2013, patients without psoriasis developed an estimated 78.5 serious infections per 100,000 person-years, compared with 88.9, 85.7, and 145.7 serious infections per 100,000 person-years, respectively, for all psoriasis patients, patients with mild disease, and patients with severe disease requiring systemic or phototherapy, said Dr. Junko Takeshita and her colleagues at the University of Pennsylvania in Philadelphia. After controlling for many potential demographic and clinical confounders, psoriasis increased the risk of serious infection by about 21% (hazard ratio, 1.21; 95% confidence interval, 1.18-1.23). Patients with severe psoriasis had a 63% greater risk of infection than patients without psoriasis, compared with an 18% increase for patients with mild psoriasis.

The findings show “serious infection, particularly respiratory and skin or soft tissue infections, to be an important and common cause of morbidity among patients with psoriasis, especially those with more severe disease,” Dr. Takeshita and her associates said. Notably, the link between psoriasis and risk of serious infection persisted after excluding patients on immunosuppressive therapies, suggesting “that the greater infection risk is at least partially attributable to more severe psoriasis, itself,” they added.

The analysis of Nationwide Inpatient Sample data was funded by the Agency for Healthcare Research and Quality and by the Dermatology Foundation. The analysis of Health Improvement Network data was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, which is part of the National Institutes of Health, and by the Dermatology Foundation. None of the investigators reported conflicts of interest.

Aedes aegypti mosquito

Photo courtesy of

Muhammad Mahdi Karim

The US Centers for Disease Control and Prevention (CDC) has announced that US states and territories can now apply for funds to fight Zika locally.

The agency said more than $85 million in redirected funds identified by the Department of Health and Human Services is being made available to support efforts to protect Americans from Zika infection and associated adverse health outcomes.

“These funds will allow states and territories to continue implementation of their Zika preparedness plans but are not enough to support a comprehensive Zika response and can only temporarily address what is needed,” said Stephen C. Redd, MD, director of the CDC’s Office of Public Health Preparedness and Response.

“Without the full amount of requested emergency supplemental funding, many activities that need to start now are being delayed or may have to be stopped within months.”

The more than $85 million in funds includes the more $60 million reported earlier this year (Funding opportunity number CDC-RFA-CK14-1401CONTPPHF16) as well as another $25 million that was just announced (Funding opportunity number CDC-RFA-TP16-1602).

Earlier this year, states and cities participating in the Epidemiology and Lab Capacity program became eligible for more than $60 million in funds to:

• Build laboratory capacity
• Enhance epidemiological surveillance and investigation
• Improve mosquito control and monitoring
• Keep blood supplies safe
• Contribute data to the US Zika Pregnancy registry.

Applications for these funds are due May 27, 2016, and will be disbursed during the summer.

Under the latest announcement, $25 million in FY 2016 preparedness and response funding will go to 53 states, cities, and territories at risk for outbreaks of Zika virus infection.‎

Recipients will receive funds based on the geographic locations of the two mosquitoes known to transmit Zika virus (Aedes aegypti and Aedes albopictus), history of mosquito-borne disease outbreaks, and size of population.

The funds are intended to strengthen incident management and emergency operations coordination, information management and sharing, and community recovery and resilience.

State, local, and territorial health officials can use the funds to identify and investigate a possible outbreak of Zika virus disease in their communities, coordinate a comprehensive response across all levels of government and non-governmental partners (including the healthcare sector), and identify and connect to community services families affected by Zika virus disease.

Applications for the funds are due June 13, 2016. Funds will be disbursed during the summer and remain available through July 2017.

Zika virus disease is caused by the Zika virus, which is spread to people primarily through the bite of infected Aedes aegypti and Aedes albopictus mosquitoes, though Aedes aegypti are more likely to spread Zika. Sexual transmission and transmission via blood transfusion have been documented as well.

There is currently no vaccine or treatment for Zika. The most common symptoms of Zika are fever, rash, joint pain, and conjunctivitis. In previous outbreaks, the illness has typically been mild, with symptoms lasting for several days to a week after a person is bitten by an infected mosquito.

Zika virus infection in pregnant women is a cause of microcephaly and other severe fetal brain defects. Zika has also been linked to Guillain-Barré syndrome.

Aedes aegypti mosquito

Photo courtesy of

Muhammad Mahdi Karim

The US Centers for Disease Control and Prevention (CDC) has announced that US states and territories can now apply for funds to fight Zika locally.

The agency said more than $85 million in redirected funds identified by the Department of Health and Human Services is being made available to support efforts to protect Americans from Zika infection and associated adverse health outcomes.

“These funds will allow states and territories to continue implementation of their Zika preparedness plans but are not enough to support a comprehensive Zika response and can only temporarily address what is needed,” said Stephen C. Redd, MD, director of the CDC’s Office of Public Health Preparedness and Response.

“Without the full amount of requested emergency supplemental funding, many activities that need to start now are being delayed or may have to be stopped within months.”

The more than $85 million in funds includes the more $60 million reported earlier this year (Funding opportunity number CDC-RFA-CK14-1401CONTPPHF16) as well as another $25 million that was just announced (Funding opportunity number CDC-RFA-TP16-1602).

Earlier this year, states and cities participating in the Epidemiology and Lab Capacity program became eligible for more than $60 million in funds to:

• Build laboratory capacity
• Enhance epidemiological surveillance and investigation
• Improve mosquito control and monitoring
• Keep blood supplies safe
• Contribute data to the US Zika Pregnancy registry.

Applications for these funds are due May 27, 2016, and will be disbursed during the summer.

Under the latest announcement, $25 million in FY 2016 preparedness and response funding will go to 53 states, cities, and territories at risk for outbreaks of Zika virus infection.‎

Recipients will receive funds based on the geographic locations of the two mosquitoes known to transmit Zika virus (Aedes aegypti and Aedes albopictus), history of mosquito-borne disease outbreaks, and size of population.

The funds are intended to strengthen incident management and emergency operations coordination, information management and sharing, and community recovery and resilience.

State, local, and territorial health officials can use the funds to identify and investigate a possible outbreak of Zika virus disease in their communities, coordinate a comprehensive response across all levels of government and non-governmental partners (including the healthcare sector), and identify and connect to community services families affected by Zika virus disease.

Applications for the funds are due June 13, 2016. Funds will be disbursed during the summer and remain available through July 2017.

Zika virus disease is caused by the Zika virus, which is spread to people primarily through the bite of infected Aedes aegypti and Aedes albopictus mosquitoes, though Aedes aegypti are more likely to spread Zika. Sexual transmission and transmission via blood transfusion have been documented as well.

There is currently no vaccine or treatment for Zika. The most common symptoms of Zika are fever, rash, joint pain, and conjunctivitis. In previous outbreaks, the illness has typically been mild, with symptoms lasting for several days to a week after a person is bitten by an infected mosquito.

Zika virus infection in pregnant women is a cause of microcephaly and other severe fetal brain defects. Zika has also been linked to Guillain-Barré syndrome.

Aedes aegypti mosquito

Photo courtesy of

Muhammad Mahdi Karim

The US Centers for Disease Control and Prevention (CDC) has announced that US states and territories can now apply for funds to fight Zika locally.

The agency said more than $85 million in redirected funds identified by the Department of Health and Human Services is being made available to support efforts to protect Americans from Zika infection and associated adverse health outcomes.

“These funds will allow states and territories to continue implementation of their Zika preparedness plans but are not enough to support a comprehensive Zika response and can only temporarily address what is needed,” said Stephen C. Redd, MD, director of the CDC’s Office of Public Health Preparedness and Response.

“Without the full amount of requested emergency supplemental funding, many activities that need to start now are being delayed or may have to be stopped within months.”

The more than $85 million in funds includes the more $60 million reported earlier this year (Funding opportunity number CDC-RFA-CK14-1401CONTPPHF16) as well as another $25 million that was just announced (Funding opportunity number CDC-RFA-TP16-1602).

Earlier this year, states and cities participating in the Epidemiology and Lab Capacity program became eligible for more than $60 million in funds to:

• Build laboratory capacity
• Enhance epidemiological surveillance and investigation
• Improve mosquito control and monitoring
• Keep blood supplies safe
• Contribute data to the US Zika Pregnancy registry.

Applications for these funds are due May 27, 2016, and will be disbursed during the summer.

Under the latest announcement, $25 million in FY 2016 preparedness and response funding will go to 53 states, cities, and territories at risk for outbreaks of Zika virus infection.‎

Recipients will receive funds based on the geographic locations of the two mosquitoes known to transmit Zika virus (Aedes aegypti and Aedes albopictus), history of mosquito-borne disease outbreaks, and size of population.

The funds are intended to strengthen incident management and emergency operations coordination, information management and sharing, and community recovery and resilience.

State, local, and territorial health officials can use the funds to identify and investigate a possible outbreak of Zika virus disease in their communities, coordinate a comprehensive response across all levels of government and non-governmental partners (including the healthcare sector), and identify and connect to community services families affected by Zika virus disease.

Applications for the funds are due June 13, 2016. Funds will be disbursed during the summer and remain available through July 2017.

Zika virus disease is caused by the Zika virus, which is spread to people primarily through the bite of infected Aedes aegypti and Aedes albopictus mosquitoes, though Aedes aegypti are more likely to spread Zika. Sexual transmission and transmission via blood transfusion have been documented as well.

There is currently no vaccine or treatment for Zika. The most common symptoms of Zika are fever, rash, joint pain, and conjunctivitis. In previous outbreaks, the illness has typically been mild, with symptoms lasting for several days to a week after a person is bitten by an infected mosquito.

Zika virus infection in pregnant women is a cause of microcephaly and other severe fetal brain defects. Zika has also been linked to Guillain-Barré syndrome.

Antihemophilic factor

Results of a meta-analysis suggest a pair of recombinant factor VIII (FVIII) products may not increase the risk of FVIII inhibitors in previously untreated patients with severe hemophilia A.

The European Medicines Agency’s Pharmacovigilance Risk Assessment Committee (PRAC) analyzed data from 3 observational studies and found that patients who received Kogenate or Helixate had a higher incidence of inhibitors than patients who received other recombinant FVIII products.

However, the difference was not significant, and the PRAC concluded that, overall, the evidence does not confirm an increased risk of inhibitors with Kogenate or Helixate.

This conclusion is consistent with the PRAC’s previous conclusions from a review carried out in 2013.

For the current analysis, the PRAC reviewed data from 3 studies, which were conducted by the RODIN study group, the UK Haemophilia Centre Doctors’ Organisation (UKHCDO), and the FranceCoag Network.

The analysis included 1102 previously untreated patients—481 in the RODIN study, 293 in the FranceCoag study, and 328 in the UKHCDO study—who received octocog alfa (Advate, Helixate, or Kogenate), moroctocog alfa (Refacto or Refacto AF), or other recombinant FVIII products.

Results suggested a trend toward an increase of high-titer inhibitor development and all inhibitor development with Kogenate or Helixate compared to Advate.

Overall, 37% of patients treated with Kogenate or Helixate (147/400) developed inhibitory antibodies, 22% of whom (n=88) had high-titer inhibitors. Twenty-six percent of patients who received Advate (100/385) developed inhibitors, 15% of whom (n=57) had high-titer inhibitors.

The PRAC said a similar trend was observed for other recombinant FVIII products, but the results were less pronounced due to sample size constraints.

The committee pointed out that there were several limitations with this meta-analysis, including the possibility of residual confounding. The group also said a number of parameters may have had an impact on the incidence of inhibitors in these previously untreated patients, and adjusting for all of these factors may not be possible.

In addition, the PRAC noted that there has been no signal for a similar trend of increases in inhibitor development with Kogenate in previously treated patients in other studies.

Finally, the committee recommended that companies marketing recombinant FVIII products monitor published studies on inhibitor development with the aim of keeping the product information up to date.

Antihemophilic factor

Results of a meta-analysis suggest a pair of recombinant factor VIII (FVIII) products may not increase the risk of FVIII inhibitors in previously untreated patients with severe hemophilia A.

The European Medicines Agency’s Pharmacovigilance Risk Assessment Committee (PRAC) analyzed data from 3 observational studies and found that patients who received Kogenate or Helixate had a higher incidence of inhibitors than patients who received other recombinant FVIII products.

However, the difference was not significant, and the PRAC concluded that, overall, the evidence does not confirm an increased risk of inhibitors with Kogenate or Helixate.

This conclusion is consistent with the PRAC’s previous conclusions from a review carried out in 2013.

For the current analysis, the PRAC reviewed data from 3 studies, which were conducted by the RODIN study group, the UK Haemophilia Centre Doctors’ Organisation (UKHCDO), and the FranceCoag Network.

The analysis included 1102 previously untreated patients—481 in the RODIN study, 293 in the FranceCoag study, and 328 in the UKHCDO study—who received octocog alfa (Advate, Helixate, or Kogenate), moroctocog alfa (Refacto or Refacto AF), or other recombinant FVIII products.

Results suggested a trend toward an increase of high-titer inhibitor development and all inhibitor development with Kogenate or Helixate compared to Advate.

Overall, 37% of patients treated with Kogenate or Helixate (147/400) developed inhibitory antibodies, 22% of whom (n=88) had high-titer inhibitors. Twenty-six percent of patients who received Advate (100/385) developed inhibitors, 15% of whom (n=57) had high-titer inhibitors.

The PRAC said a similar trend was observed for other recombinant FVIII products, but the results were less pronounced due to sample size constraints.

The committee pointed out that there were several limitations with this meta-analysis, including the possibility of residual confounding. The group also said a number of parameters may have had an impact on the incidence of inhibitors in these previously untreated patients, and adjusting for all of these factors may not be possible.

In addition, the PRAC noted that there has been no signal for a similar trend of increases in inhibitor development with Kogenate in previously treated patients in other studies.

Finally, the committee recommended that companies marketing recombinant FVIII products monitor published studies on inhibitor development with the aim of keeping the product information up to date.

Antihemophilic factor

Results of a meta-analysis suggest a pair of recombinant factor VIII (FVIII) products may not increase the risk of FVIII inhibitors in previously untreated patients with severe hemophilia A.

The European Medicines Agency’s Pharmacovigilance Risk Assessment Committee (PRAC) analyzed data from 3 observational studies and found that patients who received Kogenate or Helixate had a higher incidence of inhibitors than patients who received other recombinant FVIII products.

However, the difference was not significant, and the PRAC concluded that, overall, the evidence does not confirm an increased risk of inhibitors with Kogenate or Helixate.

This conclusion is consistent with the PRAC’s previous conclusions from a review carried out in 2013.

For the current analysis, the PRAC reviewed data from 3 studies, which were conducted by the RODIN study group, the UK Haemophilia Centre Doctors’ Organisation (UKHCDO), and the FranceCoag Network.

The analysis included 1102 previously untreated patients—481 in the RODIN study, 293 in the FranceCoag study, and 328 in the UKHCDO study—who received octocog alfa (Advate, Helixate, or Kogenate), moroctocog alfa (Refacto or Refacto AF), or other recombinant FVIII products.

Results suggested a trend toward an increase of high-titer inhibitor development and all inhibitor development with Kogenate or Helixate compared to Advate.

Overall, 37% of patients treated with Kogenate or Helixate (147/400) developed inhibitory antibodies, 22% of whom (n=88) had high-titer inhibitors. Twenty-six percent of patients who received Advate (100/385) developed inhibitors, 15% of whom (n=57) had high-titer inhibitors.

The PRAC said a similar trend was observed for other recombinant FVIII products, but the results were less pronounced due to sample size constraints.

The committee pointed out that there were several limitations with this meta-analysis, including the possibility of residual confounding. The group also said a number of parameters may have had an impact on the incidence of inhibitors in these previously untreated patients, and adjusting for all of these factors may not be possible.

In addition, the PRAC noted that there has been no signal for a similar trend of increases in inhibitor development with Kogenate in previously treated patients in other studies.

Finally, the committee recommended that companies marketing recombinant FVIII products monitor published studies on inhibitor development with the aim of keeping the product information up to date.

When in D.C., well, pay attention to politics! Especially in an election year ...

Attendees at the Vascular Annual Meeting will be treated to a political comedy show from 8:30 to 9:30 p.m. Friday, June 10. The “Capitol Steps” group will poke its traditional fun at politics, politicians and the world at large as it has since the Reagan administration.

The event is free and open to all registered attendees, guests and exhibitors.

The group mixes standup comedy with song parodies, exploring the hot topics of the day, from the Democratic debates to “Apple vs. the FBI” to “If There were No Rich Men” and “Kasich is the Hardest Rhyme.” With the conventions scheduled for later this year, who knows what the Capitol Steps will be talking about, come June?

Come and find out. And be prepared to laugh heartily.

When in D.C., well, pay attention to politics! Especially in an election year ...

Attendees at the Vascular Annual Meeting will be treated to a political comedy show from 8:30 to 9:30 p.m. Friday, June 10. The “Capitol Steps” group will poke its traditional fun at politics, politicians and the world at large as it has since the Reagan administration.

The event is free and open to all registered attendees, guests and exhibitors.

The group mixes standup comedy with song parodies, exploring the hot topics of the day, from the Democratic debates to “Apple vs. the FBI” to “If There were No Rich Men” and “Kasich is the Hardest Rhyme.” With the conventions scheduled for later this year, who knows what the Capitol Steps will be talking about, come June?

Come and find out. And be prepared to laugh heartily.

When in D.C., well, pay attention to politics! Especially in an election year ...

Attendees at the Vascular Annual Meeting will be treated to a political comedy show from 8:30 to 9:30 p.m. Friday, June 10. The “Capitol Steps” group will poke its traditional fun at politics, politicians and the world at large as it has since the Reagan administration.

The event is free and open to all registered attendees, guests and exhibitors.

The group mixes standup comedy with song parodies, exploring the hot topics of the day, from the Democratic debates to “Apple vs. the FBI” to “If There were No Rich Men” and “Kasich is the Hardest Rhyme.” With the conventions scheduled for later this year, who knows what the Capitol Steps will be talking about, come June?

Come and find out. And be prepared to laugh heartily.

Up to four $5,000 scholarships to attend the 2017 Vascular Annual Meeting in San Diego are available to qualified young vascular surgeons living outside of North America.

In addition to the meeting, scholars also will visit clinical, teaching and research programs in the United States and Canada. Applications can be completed online.

The application deadline is June 17, 2016. For questions, email [email protected] or call 312-334-2300. Click here for more information.

Up to four $5,000 scholarships to attend the 2017 Vascular Annual Meeting in San Diego are available to qualified young vascular surgeons living outside of North America.

In addition to the meeting, scholars also will visit clinical, teaching and research programs in the United States and Canada. Applications can be completed online.

The application deadline is June 17, 2016. For questions, email [email protected] or call 312-334-2300. Click here for more information.

Up to four $5,000 scholarships to attend the 2017 Vascular Annual Meeting in San Diego are available to qualified young vascular surgeons living outside of North America.

In addition to the meeting, scholars also will visit clinical, teaching and research programs in the United States and Canada. Applications can be completed online.

The application deadline is June 17, 2016. For questions, email [email protected] or call 312-334-2300. Click here for more information.

BALTIMORE – The sutureless heart valve may now be a “necessity” for contemporary cardiothoracic surgeons, said an expert at the annual meeting of the American Association for Thoracic Surgery.

In an interview at the event, Niv Ad, MD, chief of cardiac surgery at Inova Heart and Vascular Institute, Falls Church, Va., discussed the results of an international trial evaluating clinical outcomes of two patient subgroups implanted with a sutureless valve prosthesis. He was enthusiastic about the trial’s results and the future promise of the sutureless valve.

The study, "Clinical Outcomes in Low and Intermediate-High Risk Groups with a Sutureless Heart Valve," will be presented at 7:30 a.m. on Wednesday.

“This study teaches us that the technology is safe,” he said. “This is really great news for surgeons, cardiologists, and patients. Complications associated with implantation of the valves were fairly low in their incidence, and the survival rates at 1 year were high.”

The study, led by Axel Haverich, MD, of Hannover Medical School in Germany, confirmed the safety and performance of the valve in both patient groups – high and low risk – regardless of the preoperative risk score. Dr. Ad said that sutureless valve technology would likely replace suture technology in all cases, although perhaps not in the near term.

Dr. Ad reported no relevant financial disclosures.

[email protected]

On Twitter @richpizzi

BALTIMORE – The sutureless heart valve may now be a “necessity” for contemporary cardiothoracic surgeons, said an expert at the annual meeting of the American Association for Thoracic Surgery.

In an interview at the event, Niv Ad, MD, chief of cardiac surgery at Inova Heart and Vascular Institute, Falls Church, Va., discussed the results of an international trial evaluating clinical outcomes of two patient subgroups implanted with a sutureless valve prosthesis. He was enthusiastic about the trial’s results and the future promise of the sutureless valve.

The study, "Clinical Outcomes in Low and Intermediate-High Risk Groups with a Sutureless Heart Valve," will be presented at 7:30 a.m. on Wednesday.

“This study teaches us that the technology is safe,” he said. “This is really great news for surgeons, cardiologists, and patients. Complications associated with implantation of the valves were fairly low in their incidence, and the survival rates at 1 year were high.”

The study, led by Axel Haverich, MD, of Hannover Medical School in Germany, confirmed the safety and performance of the valve in both patient groups – high and low risk – regardless of the preoperative risk score. Dr. Ad said that sutureless valve technology would likely replace suture technology in all cases, although perhaps not in the near term.

Dr. Ad reported no relevant financial disclosures.

[email protected]

On Twitter @richpizzi

BALTIMORE – The sutureless heart valve may now be a “necessity” for contemporary cardiothoracic surgeons, said an expert at the annual meeting of the American Association for Thoracic Surgery.

In an interview at the event, Niv Ad, MD, chief of cardiac surgery at Inova Heart and Vascular Institute, Falls Church, Va., discussed the results of an international trial evaluating clinical outcomes of two patient subgroups implanted with a sutureless valve prosthesis. He was enthusiastic about the trial’s results and the future promise of the sutureless valve.

The study, "Clinical Outcomes in Low and Intermediate-High Risk Groups with a Sutureless Heart Valve," will be presented at 7:30 a.m. on Wednesday.

“This study teaches us that the technology is safe,” he said. “This is really great news for surgeons, cardiologists, and patients. Complications associated with implantation of the valves were fairly low in their incidence, and the survival rates at 1 year were high.”

The study, led by Axel Haverich, MD, of Hannover Medical School in Germany, confirmed the safety and performance of the valve in both patient groups – high and low risk – regardless of the preoperative risk score. Dr. Ad said that sutureless valve technology would likely replace suture technology in all cases, although perhaps not in the near term.

Dr. Ad reported no relevant financial disclosures.

[email protected]

On Twitter @richpizzi

ATLANTA – Some patients experienced improvement in at least one neurocognitive domain up to 3 years after having bariatric surgery, a small, systematic review has shown.

The most significant improvements were reported in memory, with nine studies showing some statistically significant improvement in a post-bariatric surgery cohort. Four studies showed statistically significant improvement in attention and executive function, and two did so in language.

Dr. Gurneet S. Thiara, a psychiatry resident at the University of Toronto, presented the findings during a scientific session at this year’s annual meeting of the American Psychiatric Association.

Because the studies that form the basis of the analysis did not follow a standard pre-surgery neurocognitive assessment, the actual scope of bariatric surgery’s impact on neurocognition is hard to determine. This shortcoming provides evidence that instituting a standardized method of psychiatric assessment pre-bariatric surgery could help clinicians better anticipate overall neurocognitive outcomes, he said.

“It’s hard to pinpoint the one domain that affects [this cohort] most,” said Dr. Thiara.

One study included in the analysis showed no neurocognitive improvement, although Dr. Thiara noted this was possibly due to the under- or non-reporting of negative outcomes by researchers who conducted studies that might have met his inclusion criteria.

Dr. Thiara and his colleagues were not able to draw conclusions as to which patients would be affected in which domains and by what mechanism of action. Their analysis did suggest possible relationships between gastric bypass and changes in metabolism, levels of leptin and ghrelin, vascular function, hypoperfusion in the brain, and even shifts in the gut microbiome.

Dr. Thiara sought studies with bariatric surgery patients whose neurocognitive and psychological outcomes were followed anywhere from one to three years post-surgery. After analyzing 422 studies published between January 1990 and August 2015, only ten studies, with patient sample sizes ranging from 10 to 156, met the criteria.

The study was not intended to determine a relationship between neurocognitive outcomes and type of bypass surgery performed, but Dr. Thiara said the majority of the procedures analyzed tended to be Roux-en-Y rather than the gastric bypass sleeve.

[email protected]

On Twitter @whitneymcknight

ATLANTA – Some patients experienced improvement in at least one neurocognitive domain up to 3 years after having bariatric surgery, a small, systematic review has shown.

The most significant improvements were reported in memory, with nine studies showing some statistically significant improvement in a post-bariatric surgery cohort. Four studies showed statistically significant improvement in attention and executive function, and two did so in language.

Dr. Gurneet S. Thiara, a psychiatry resident at the University of Toronto, presented the findings during a scientific session at this year’s annual meeting of the American Psychiatric Association.

Because the studies that form the basis of the analysis did not follow a standard pre-surgery neurocognitive assessment, the actual scope of bariatric surgery’s impact on neurocognition is hard to determine. This shortcoming provides evidence that instituting a standardized method of psychiatric assessment pre-bariatric surgery could help clinicians better anticipate overall neurocognitive outcomes, he said.

“It’s hard to pinpoint the one domain that affects [this cohort] most,” said Dr. Thiara.

One study included in the analysis showed no neurocognitive improvement, although Dr. Thiara noted this was possibly due to the under- or non-reporting of negative outcomes by researchers who conducted studies that might have met his inclusion criteria.

Dr. Thiara and his colleagues were not able to draw conclusions as to which patients would be affected in which domains and by what mechanism of action. Their analysis did suggest possible relationships between gastric bypass and changes in metabolism, levels of leptin and ghrelin, vascular function, hypoperfusion in the brain, and even shifts in the gut microbiome.

Dr. Thiara sought studies with bariatric surgery patients whose neurocognitive and psychological outcomes were followed anywhere from one to three years post-surgery. After analyzing 422 studies published between January 1990 and August 2015, only ten studies, with patient sample sizes ranging from 10 to 156, met the criteria.

The study was not intended to determine a relationship between neurocognitive outcomes and type of bypass surgery performed, but Dr. Thiara said the majority of the procedures analyzed tended to be Roux-en-Y rather than the gastric bypass sleeve.

[email protected]

On Twitter @whitneymcknight

ATLANTA – Some patients experienced improvement in at least one neurocognitive domain up to 3 years after having bariatric surgery, a small, systematic review has shown.

The most significant improvements were reported in memory, with nine studies showing some statistically significant improvement in a post-bariatric surgery cohort. Four studies showed statistically significant improvement in attention and executive function, and two did so in language.

Dr. Gurneet S. Thiara, a psychiatry resident at the University of Toronto, presented the findings during a scientific session at this year’s annual meeting of the American Psychiatric Association.

Because the studies that form the basis of the analysis did not follow a standard pre-surgery neurocognitive assessment, the actual scope of bariatric surgery’s impact on neurocognition is hard to determine. This shortcoming provides evidence that instituting a standardized method of psychiatric assessment pre-bariatric surgery could help clinicians better anticipate overall neurocognitive outcomes, he said.

“It’s hard to pinpoint the one domain that affects [this cohort] most,” said Dr. Thiara.

One study included in the analysis showed no neurocognitive improvement, although Dr. Thiara noted this was possibly due to the under- or non-reporting of negative outcomes by researchers who conducted studies that might have met his inclusion criteria.

Dr. Thiara and his colleagues were not able to draw conclusions as to which patients would be affected in which domains and by what mechanism of action. Their analysis did suggest possible relationships between gastric bypass and changes in metabolism, levels of leptin and ghrelin, vascular function, hypoperfusion in the brain, and even shifts in the gut microbiome.

Dr. Thiara sought studies with bariatric surgery patients whose neurocognitive and psychological outcomes were followed anywhere from one to three years post-surgery. After analyzing 422 studies published between January 1990 and August 2015, only ten studies, with patient sample sizes ranging from 10 to 156, met the criteria.

The study was not intended to determine a relationship between neurocognitive outcomes and type of bypass surgery performed, but Dr. Thiara said the majority of the procedures analyzed tended to be Roux-en-Y rather than the gastric bypass sleeve.

[email protected]

On Twitter @whitneymcknight

VANCOUVER – Three types of drugs commonly used to treat multiple sclerosis (MS) appear to have a generally good safety profile when administered before and during early pregnancy, suggest a trio of studies reported at the annual meeting of the American Academy of Neurology.

Exposure to interferon-beta during the first trimester did not increase the risks of miscarriage, congenital anomalies, or birth weight. And although use of natalizumab led to higher odds of spontaneous abortion as compared with interferon-beta or no therapy, the absolute rate still fell within that of the general population. Pregnancies occurring weeks to years after treatment with alemtuzumab also had rates of spontaneous abortion, birth defects, and stillbirth on par with population values.

All three drugs fall in a gray area when it comes to use in pregnancy, with a Food and Drug Administration designation of category C, indicating that animal studies have shown adverse effects on the fetus and adequate, quality human data are lacking, but potential benefits may outweigh potential harms in pregnancy. The studies’ findings are therefore likely to be informative to women of reproductive age, a group disproportionately affected by MS.

“It’s very important to collect as much data as possible about potential exposure risks with disease-modifying therapy in pregnancy,” session comoderator Dr. Jennifer Graves, a neurologist at the Multiple Sclerosis Center at University of California–San Francisco Medical Center and UCSF Benioff Children’s Hospital, San Francisco, said in an interview.

“However, all studies have the limitation of sample size,” she added. “The majority of serious adverse effects – teratogenicity, major birth defects – may be less than 1 in 500 [in frequency]. So this is something that puts all of these studies into context because we just don’t have that many pregnancies that have been exposed to some of these agents.” The method whereby miscarriages are ascertained can also influence findings.

Nonetheless, this research is critical for women and their physicians when it comes to making decisions about treatment, Dr. Graves maintained. “Although pregnancy may be protective for many women with MS, many do need treatment during their pregnancy to prevent severe relapses due to various factors. Collecting this type of information is important.”

Interferon-beta safety

In the first study, investigators led by Dr. Sandra Thiel of Ruhr University Bochum and the Heinrich Heine University Düsseldorf, both in Germany, analyzed data from the German Multiple Sclerosis and Pregnancy Registry.

They studied pregnancies among women who had at least 12 months of postpartum follow-up. Exposure to interferon-beta (brand names Rebif, Avonex, Betaseron, and Extavia) was defined as injection of the drug at any time after the last menstrual period.

In all, 251 pregnancies exposed to interferon-beta were compared with 194 pregnancies not exposed to any disease-modifying drugs. The median duration of exposure in the former group was 32 days, indicating that most women stopped the drug soon after discovering they were pregnant, Dr. Thiel noted.

Study results, reported at the meeting and recently published (Mult Scler. 2016 Feb 26. doi: 10.1177/1352458516634872), showed that the rate of miscarriage was 9.96% in the exposed group and 7.73% in the unexposed group, and the rate of congenital anomalies among live births was 3.08% and 5.52%.

In analyses using propensity score adjustment, there were no significant differences between groups in the odds of live birth, spontaneous abortion, congenital anomalies, preterm birth, cesarean section, or small for gestational age, or in mean infant birth weight.

Of note, the women whose pregnancies were not exposed to any disease-modifying therapy had a higher rate of relapse during pregnancy when compared with counterparts whose pregnancies were exposed to interferon-beta (27.3% vs. 14.3%).

“Taken together with the existing literature, our study provides further reassurance that interferon-beta treatment can be safely continued up until the time when women with MS become pregnant,” Dr. Thiel concluded. The safety profile seen “is consistent with the pharmacologically plausible safety of interferon-beta, as interferon-beta is a huge molecule that cannot pass the placental barrier.”

“Since the vast majority of women stopped the interferon-beta treatment during the first trimester of pregnancy, we cannot draw any conclusions about the safety of interferon-beta later in pregnancy,” she cautioned. “Another limitation is the variability in the gestational week of entry into the cohort, as later than first-trimester inclusion can lead to an underestimation of early events, particularly spontaneous abortions.”

Natalizumab safety

In the second study, Dr. Maria Pia Amato, Department of NEUROFARBA, Section of Neurosciences, University of Florence, Italy, and her colleagues with the Italian MS Study Group assessed pregnancy outcomes after exposure to natalizumab (Tysabri). This antibody targets alpha-4 integrins, which play a role in a variety of pregnancy processes and in fetal hematopoiesis and cardiac development, she noted.

They identified women for the study using two sources: the prospective Italian Pregnancy Dataset of consecutive female patients with MS referred to 25 centers and a cohort of women from an Italian interferon-beta study.

In all, they compared 65 pregnancies exposed to natalizumab (any treatment from 8 weeks before the start of the last menstrual period onward), 88 exposed to interferon-beta as a control, and 339 not exposed to either. The mean duration of natalizumab exposure was 1.16 weeks, and the mean duration of interferon-beta exposure was 4.6 weeks.

Results showed that the rate of spontaneous abortion was higher for natalizumab-exposed pregnancies, at 18.5%, than for interferon-beta–exposed pregnancies, at 8%, and for nonexposed pregnancies, at 6.5% (P = .006). But the timing of these abortions was similar, at about 8 weeks of gestation.

In adjusted analyses, natalizumab exposure was still associated with an elevated risk of spontaneous abortion when compared with interferon-beta or no exposure (odds ratio, 3.9). However, the 18.5% rate seen with the antibody fell within the range for the Italian general population of 4.8% to 21.1%.

Infants in the natalizumab group had the lowest birth weight and length, while infants in the interferon-beta group had the youngest gestational age. The groups did not differ significantly with respect to the incidence of birth defects; however, with a single defect seen in each, the study was underpowered to assess differences in this outcome.

Data additionally showed that discontinuation of natalizumab in advance of pregnancy led to an uptick in relapses, with 30% of women having a relapse, according to Dr. Amato. “This increase started during the first trimester of pregnancy and culminated in the second trimester of pregnancy. All the women were retreated soon after delivery with natalizumab, and disease activity returned to the pre-pregnancy period level with resumption of the drug.”

“Patients and clinicians should discuss together and balance the potential risks to the fetus with natalizumab exposure with the potential risks to the mother of disease reactivation during pregnancy,” she recommended, cautioning that the findings were based on first-trimester exposure of short duration. “Decisions should be made case by case on the basis of the disease activity in a specific patient and the availability of alternative treatment, and whether to use a conservative approach, stopping the drug and respecting the washout period, or in a few cases, an active approach, continuing the drug till conception or even discuss continuing the drug during pregnancy.”

Alemtuzumab safety

In the third study, investigators led by Dr. Jiwon Oh of the division of neurology at the University of Toronto analyzed outcomes of pregnancies among women who had been treated with alemtuzumab (Lemtrada), an antibody that targets CD52.

Treatment with alemtuzumab leads to depletion of lymphocytes followed by reconstitution of the immune system with a less inflammatory profile. “This is thought to contribute to the durable efficacy in the absence of continuous treatment with alemtuzumab,” she explained. “This durable efficacy and the fact that you may not need to redose is relevant when you are thinking about pregnancy in patients with MS, just because this is a drug that is given in two different cycles and may not need to be readministered.”

Although the antibody becomes undetectable in serum about 30 days after administration, it is unclear whether the ongoing immune reconstitution has any impact on subsequent pregnancy, Dr. Oh said.

The investigators pooled data from the phase II CAMMS223 trial and the phase III CARE-MS I and CARE-MS II trials of alemtuzumab and their extension phases. Women enrolled in the trials were required to use effective contraception during treatment and for the next 6 months.

Dr. Oh reported interim results based on 200 pregnancies among 137 women. Most pregnancies occurred at least 4 months after the last dose of alemtuzumab; only four occurred within 1 month and another four occurred 1 to 3 months after the last dose.

Among the 181 completed pregnancies with known outcomes, 67.4% resulted in live births. Another 21.5% ended in spontaneous abortion. “Although this is on the higher end of normal, it is still in keeping with what is seen in the general population,” Dr. Oh noted.

The rate of stillbirth was 0.6%, also at the upper end of the range seen for the general population. Finally, 10.5% of the pregnancies ended in elective abortion.

There were no congenital anomalies or birth defects among the live-born infants. One was seen in an electively terminated pregnancy (26 months after the last dose), and another was seen in a stillbirth (4 years after the last dose).

“Two out of 200 is 1%, and this is actually lower than what is normally seen in the general population, approximately 3% to 7%,” Dr. Oh commented.

“To date, there is no indication of an increased risk for congenital anomalies or birth defects in infants,” she summarized. “There has also been no indication of increased rates of spontaneous abortion in women who become pregnant, but obviously, these data are limited because we don’t necessarily have a control group.”

“Based on the pharmacokinetics of alemtuzumab and labeling guidelines, women of childbearing potential should continue to use contraception for 4 months after receiving a course of alemtuzumab,” Dr. Oh concluded. “There is an international Alemtuzumab Pregnancy Exposure Registry that is open and enrolling patients who become pregnant between the first dose of alemtuzumab and 4 months after the last infusion, and hopefully this will give us more information to confirm some of the observations that we see here.”

Dr. Thiel disclosed that she had no relevant conflicts of interest; the German Multiple Sclerosis and Pregnancy registry was partly supported by Bayer Healthcare, Biogen Idec Germany, Merck Serono, Novartis Pharma, Teva Pharma, and Sanofi-Aventis/Genzyme Pharmaceuticals. Dr. Amato disclosed that she has received research grants and honoraria as a speaker from and is a member of advisory boards for Bayer, Biogen Idec, Merck Serono, Novartis, Sanofi Genzyme, Teva, Almirall, and Roche; the study did not receive any financial support. Dr. Oh disclosed that she serves on the scientific advisory boards or is a speaker for Biogen Idec, EMD Serono, Genzyme, Novartis, Roche, and Teva; the study was supported by Genzyme and Bayer Healthcare.

VANCOUVER – Three types of drugs commonly used to treat multiple sclerosis (MS) appear to have a generally good safety profile when administered before and during early pregnancy, suggest a trio of studies reported at the annual meeting of the American Academy of Neurology.

Exposure to interferon-beta during the first trimester did not increase the risks of miscarriage, congenital anomalies, or birth weight. And although use of natalizumab led to higher odds of spontaneous abortion as compared with interferon-beta or no therapy, the absolute rate still fell within that of the general population. Pregnancies occurring weeks to years after treatment with alemtuzumab also had rates of spontaneous abortion, birth defects, and stillbirth on par with population values.

All three drugs fall in a gray area when it comes to use in pregnancy, with a Food and Drug Administration designation of category C, indicating that animal studies have shown adverse effects on the fetus and adequate, quality human data are lacking, but potential benefits may outweigh potential harms in pregnancy. The studies’ findings are therefore likely to be informative to women of reproductive age, a group disproportionately affected by MS.

“It’s very important to collect as much data as possible about potential exposure risks with disease-modifying therapy in pregnancy,” session comoderator Dr. Jennifer Graves, a neurologist at the Multiple Sclerosis Center at University of California–San Francisco Medical Center and UCSF Benioff Children’s Hospital, San Francisco, said in an interview.

“However, all studies have the limitation of sample size,” she added. “The majority of serious adverse effects – teratogenicity, major birth defects – may be less than 1 in 500 [in frequency]. So this is something that puts all of these studies into context because we just don’t have that many pregnancies that have been exposed to some of these agents.” The method whereby miscarriages are ascertained can also influence findings.

Nonetheless, this research is critical for women and their physicians when it comes to making decisions about treatment, Dr. Graves maintained. “Although pregnancy may be protective for many women with MS, many do need treatment during their pregnancy to prevent severe relapses due to various factors. Collecting this type of information is important.”

Interferon-beta safety

In the first study, investigators led by Dr. Sandra Thiel of Ruhr University Bochum and the Heinrich Heine University Düsseldorf, both in Germany, analyzed data from the German Multiple Sclerosis and Pregnancy Registry.

They studied pregnancies among women who had at least 12 months of postpartum follow-up. Exposure to interferon-beta (brand names Rebif, Avonex, Betaseron, and Extavia) was defined as injection of the drug at any time after the last menstrual period.

In all, 251 pregnancies exposed to interferon-beta were compared with 194 pregnancies not exposed to any disease-modifying drugs. The median duration of exposure in the former group was 32 days, indicating that most women stopped the drug soon after discovering they were pregnant, Dr. Thiel noted.

Study results, reported at the meeting and recently published (Mult Scler. 2016 Feb 26. doi: 10.1177/1352458516634872), showed that the rate of miscarriage was 9.96% in the exposed group and 7.73% in the unexposed group, and the rate of congenital anomalies among live births was 3.08% and 5.52%.

In analyses using propensity score adjustment, there were no significant differences between groups in the odds of live birth, spontaneous abortion, congenital anomalies, preterm birth, cesarean section, or small for gestational age, or in mean infant birth weight.

Of note, the women whose pregnancies were not exposed to any disease-modifying therapy had a higher rate of relapse during pregnancy when compared with counterparts whose pregnancies were exposed to interferon-beta (27.3% vs. 14.3%).

“Taken together with the existing literature, our study provides further reassurance that interferon-beta treatment can be safely continued up until the time when women with MS become pregnant,” Dr. Thiel concluded. The safety profile seen “is consistent with the pharmacologically plausible safety of interferon-beta, as interferon-beta is a huge molecule that cannot pass the placental barrier.”

“Since the vast majority of women stopped the interferon-beta treatment during the first trimester of pregnancy, we cannot draw any conclusions about the safety of interferon-beta later in pregnancy,” she cautioned. “Another limitation is the variability in the gestational week of entry into the cohort, as later than first-trimester inclusion can lead to an underestimation of early events, particularly spontaneous abortions.”

Natalizumab safety

In the second study, Dr. Maria Pia Amato, Department of NEUROFARBA, Section of Neurosciences, University of Florence, Italy, and her colleagues with the Italian MS Study Group assessed pregnancy outcomes after exposure to natalizumab (Tysabri). This antibody targets alpha-4 integrins, which play a role in a variety of pregnancy processes and in fetal hematopoiesis and cardiac development, she noted.

They identified women for the study using two sources: the prospective Italian Pregnancy Dataset of consecutive female patients with MS referred to 25 centers and a cohort of women from an Italian interferon-beta study.

In all, they compared 65 pregnancies exposed to natalizumab (any treatment from 8 weeks before the start of the last menstrual period onward), 88 exposed to interferon-beta as a control, and 339 not exposed to either. The mean duration of natalizumab exposure was 1.16 weeks, and the mean duration of interferon-beta exposure was 4.6 weeks.

Results showed that the rate of spontaneous abortion was higher for natalizumab-exposed pregnancies, at 18.5%, than for interferon-beta–exposed pregnancies, at 8%, and for nonexposed pregnancies, at 6.5% (P = .006). But the timing of these abortions was similar, at about 8 weeks of gestation.

In adjusted analyses, natalizumab exposure was still associated with an elevated risk of spontaneous abortion when compared with interferon-beta or no exposure (odds ratio, 3.9). However, the 18.5% rate seen with the antibody fell within the range for the Italian general population of 4.8% to 21.1%.

Infants in the natalizumab group had the lowest birth weight and length, while infants in the interferon-beta group had the youngest gestational age. The groups did not differ significantly with respect to the incidence of birth defects; however, with a single defect seen in each, the study was underpowered to assess differences in this outcome.

Data additionally showed that discontinuation of natalizumab in advance of pregnancy led to an uptick in relapses, with 30% of women having a relapse, according to Dr. Amato. “This increase started during the first trimester of pregnancy and culminated in the second trimester of pregnancy. All the women were retreated soon after delivery with natalizumab, and disease activity returned to the pre-pregnancy period level with resumption of the drug.”

“Patients and clinicians should discuss together and balance the potential risks to the fetus with natalizumab exposure with the potential risks to the mother of disease reactivation during pregnancy,” she recommended, cautioning that the findings were based on first-trimester exposure of short duration. “Decisions should be made case by case on the basis of the disease activity in a specific patient and the availability of alternative treatment, and whether to use a conservative approach, stopping the drug and respecting the washout period, or in a few cases, an active approach, continuing the drug till conception or even discuss continuing the drug during pregnancy.”

Alemtuzumab safety

In the third study, investigators led by Dr. Jiwon Oh of the division of neurology at the University of Toronto analyzed outcomes of pregnancies among women who had been treated with alemtuzumab (Lemtrada), an antibody that targets CD52.

Treatment with alemtuzumab leads to depletion of lymphocytes followed by reconstitution of the immune system with a less inflammatory profile. “This is thought to contribute to the durable efficacy in the absence of continuous treatment with alemtuzumab,” she explained. “This durable efficacy and the fact that you may not need to redose is relevant when you are thinking about pregnancy in patients with MS, just because this is a drug that is given in two different cycles and may not need to be readministered.”

Although the antibody becomes undetectable in serum about 30 days after administration, it is unclear whether the ongoing immune reconstitution has any impact on subsequent pregnancy, Dr. Oh said.

The investigators pooled data from the phase II CAMMS223 trial and the phase III CARE-MS I and CARE-MS II trials of alemtuzumab and their extension phases. Women enrolled in the trials were required to use effective contraception during treatment and for the next 6 months.

Dr. Oh reported interim results based on 200 pregnancies among 137 women. Most pregnancies occurred at least 4 months after the last dose of alemtuzumab; only four occurred within 1 month and another four occurred 1 to 3 months after the last dose.

Among the 181 completed pregnancies with known outcomes, 67.4% resulted in live births. Another 21.5% ended in spontaneous abortion. “Although this is on the higher end of normal, it is still in keeping with what is seen in the general population,” Dr. Oh noted.

The rate of stillbirth was 0.6%, also at the upper end of the range seen for the general population. Finally, 10.5% of the pregnancies ended in elective abortion.

There were no congenital anomalies or birth defects among the live-born infants. One was seen in an electively terminated pregnancy (26 months after the last dose), and another was seen in a stillbirth (4 years after the last dose).

“Two out of 200 is 1%, and this is actually lower than what is normally seen in the general population, approximately 3% to 7%,” Dr. Oh commented.

“To date, there is no indication of an increased risk for congenital anomalies or birth defects in infants,” she summarized. “There has also been no indication of increased rates of spontaneous abortion in women who become pregnant, but obviously, these data are limited because we don’t necessarily have a control group.”

“Based on the pharmacokinetics of alemtuzumab and labeling guidelines, women of childbearing potential should continue to use contraception for 4 months after receiving a course of alemtuzumab,” Dr. Oh concluded. “There is an international Alemtuzumab Pregnancy Exposure Registry that is open and enrolling patients who become pregnant between the first dose of alemtuzumab and 4 months after the last infusion, and hopefully this will give us more information to confirm some of the observations that we see here.”

Dr. Thiel disclosed that she had no relevant conflicts of interest; the German Multiple Sclerosis and Pregnancy registry was partly supported by Bayer Healthcare, Biogen Idec Germany, Merck Serono, Novartis Pharma, Teva Pharma, and Sanofi-Aventis/Genzyme Pharmaceuticals. Dr. Amato disclosed that she has received research grants and honoraria as a speaker from and is a member of advisory boards for Bayer, Biogen Idec, Merck Serono, Novartis, Sanofi Genzyme, Teva, Almirall, and Roche; the study did not receive any financial support. Dr. Oh disclosed that she serves on the scientific advisory boards or is a speaker for Biogen Idec, EMD Serono, Genzyme, Novartis, Roche, and Teva; the study was supported by Genzyme and Bayer Healthcare.

VANCOUVER – Three types of drugs commonly used to treat multiple sclerosis (MS) appear to have a generally good safety profile when administered before and during early pregnancy, suggest a trio of studies reported at the annual meeting of the American Academy of Neurology.

Exposure to interferon-beta during the first trimester did not increase the risks of miscarriage, congenital anomalies, or birth weight. And although use of natalizumab led to higher odds of spontaneous abortion as compared with interferon-beta or no therapy, the absolute rate still fell within that of the general population. Pregnancies occurring weeks to years after treatment with alemtuzumab also had rates of spontaneous abortion, birth defects, and stillbirth on par with population values.

All three drugs fall in a gray area when it comes to use in pregnancy, with a Food and Drug Administration designation of category C, indicating that animal studies have shown adverse effects on the fetus and adequate, quality human data are lacking, but potential benefits may outweigh potential harms in pregnancy. The studies’ findings are therefore likely to be informative to women of reproductive age, a group disproportionately affected by MS.

“It’s very important to collect as much data as possible about potential exposure risks with disease-modifying therapy in pregnancy,” session comoderator Dr. Jennifer Graves, a neurologist at the Multiple Sclerosis Center at University of California–San Francisco Medical Center and UCSF Benioff Children’s Hospital, San Francisco, said in an interview.

“However, all studies have the limitation of sample size,” she added. “The majority of serious adverse effects – teratogenicity, major birth defects – may be less than 1 in 500 [in frequency]. So this is something that puts all of these studies into context because we just don’t have that many pregnancies that have been exposed to some of these agents.” The method whereby miscarriages are ascertained can also influence findings.

Nonetheless, this research is critical for women and their physicians when it comes to making decisions about treatment, Dr. Graves maintained. “Although pregnancy may be protective for many women with MS, many do need treatment during their pregnancy to prevent severe relapses due to various factors. Collecting this type of information is important.”

Interferon-beta safety

In the first study, investigators led by Dr. Sandra Thiel of Ruhr University Bochum and the Heinrich Heine University Düsseldorf, both in Germany, analyzed data from the German Multiple Sclerosis and Pregnancy Registry.

They studied pregnancies among women who had at least 12 months of postpartum follow-up. Exposure to interferon-beta (brand names Rebif, Avonex, Betaseron, and Extavia) was defined as injection of the drug at any time after the last menstrual period.

In all, 251 pregnancies exposed to interferon-beta were compared with 194 pregnancies not exposed to any disease-modifying drugs. The median duration of exposure in the former group was 32 days, indicating that most women stopped the drug soon after discovering they were pregnant, Dr. Thiel noted.

Study results, reported at the meeting and recently published (Mult Scler. 2016 Feb 26. doi: 10.1177/1352458516634872), showed that the rate of miscarriage was 9.96% in the exposed group and 7.73% in the unexposed group, and the rate of congenital anomalies among live births was 3.08% and 5.52%.

In analyses using propensity score adjustment, there were no significant differences between groups in the odds of live birth, spontaneous abortion, congenital anomalies, preterm birth, cesarean section, or small for gestational age, or in mean infant birth weight.

Of note, the women whose pregnancies were not exposed to any disease-modifying therapy had a higher rate of relapse during pregnancy when compared with counterparts whose pregnancies were exposed to interferon-beta (27.3% vs. 14.3%).

“Taken together with the existing literature, our study provides further reassurance that interferon-beta treatment can be safely continued up until the time when women with MS become pregnant,” Dr. Thiel concluded. The safety profile seen “is consistent with the pharmacologically plausible safety of interferon-beta, as interferon-beta is a huge molecule that cannot pass the placental barrier.”

“Since the vast majority of women stopped the interferon-beta treatment during the first trimester of pregnancy, we cannot draw any conclusions about the safety of interferon-beta later in pregnancy,” she cautioned. “Another limitation is the variability in the gestational week of entry into the cohort, as later than first-trimester inclusion can lead to an underestimation of early events, particularly spontaneous abortions.”

Natalizumab safety

In the second study, Dr. Maria Pia Amato, Department of NEUROFARBA, Section of Neurosciences, University of Florence, Italy, and her colleagues with the Italian MS Study Group assessed pregnancy outcomes after exposure to natalizumab (Tysabri). This antibody targets alpha-4 integrins, which play a role in a variety of pregnancy processes and in fetal hematopoiesis and cardiac development, she noted.

They identified women for the study using two sources: the prospective Italian Pregnancy Dataset of consecutive female patients with MS referred to 25 centers and a cohort of women from an Italian interferon-beta study.

In all, they compared 65 pregnancies exposed to natalizumab (any treatment from 8 weeks before the start of the last menstrual period onward), 88 exposed to interferon-beta as a control, and 339 not exposed to either. The mean duration of natalizumab exposure was 1.16 weeks, and the mean duration of interferon-beta exposure was 4.6 weeks.

Results showed that the rate of spontaneous abortion was higher for natalizumab-exposed pregnancies, at 18.5%, than for interferon-beta–exposed pregnancies, at 8%, and for nonexposed pregnancies, at 6.5% (P = .006). But the timing of these abortions was similar, at about 8 weeks of gestation.

In adjusted analyses, natalizumab exposure was still associated with an elevated risk of spontaneous abortion when compared with interferon-beta or no exposure (odds ratio, 3.9). However, the 18.5% rate seen with the antibody fell within the range for the Italian general population of 4.8% to 21.1%.

Infants in the natalizumab group had the lowest birth weight and length, while infants in the interferon-beta group had the youngest gestational age. The groups did not differ significantly with respect to the incidence of birth defects; however, with a single defect seen in each, the study was underpowered to assess differences in this outcome.

Data additionally showed that discontinuation of natalizumab in advance of pregnancy led to an uptick in relapses, with 30% of women having a relapse, according to Dr. Amato. “This increase started during the first trimester of pregnancy and culminated in the second trimester of pregnancy. All the women were retreated soon after delivery with natalizumab, and disease activity returned to the pre-pregnancy period level with resumption of the drug.”

“Patients and clinicians should discuss together and balance the potential risks to the fetus with natalizumab exposure with the potential risks to the mother of disease reactivation during pregnancy,” she recommended, cautioning that the findings were based on first-trimester exposure of short duration. “Decisions should be made case by case on the basis of the disease activity in a specific patient and the availability of alternative treatment, and whether to use a conservative approach, stopping the drug and respecting the washout period, or in a few cases, an active approach, continuing the drug till conception or even discuss continuing the drug during pregnancy.”

Alemtuzumab safety

In the third study, investigators led by Dr. Jiwon Oh of the division of neurology at the University of Toronto analyzed outcomes of pregnancies among women who had been treated with alemtuzumab (Lemtrada), an antibody that targets CD52.

Treatment with alemtuzumab leads to depletion of lymphocytes followed by reconstitution of the immune system with a less inflammatory profile. “This is thought to contribute to the durable efficacy in the absence of continuous treatment with alemtuzumab,” she explained. “This durable efficacy and the fact that you may not need to redose is relevant when you are thinking about pregnancy in patients with MS, just because this is a drug that is given in two different cycles and may not need to be readministered.”

Although the antibody becomes undetectable in serum about 30 days after administration, it is unclear whether the ongoing immune reconstitution has any impact on subsequent pregnancy, Dr. Oh said.

The investigators pooled data from the phase II CAMMS223 trial and the phase III CARE-MS I and CARE-MS II trials of alemtuzumab and their extension phases. Women enrolled in the trials were required to use effective contraception during treatment and for the next 6 months.

Dr. Oh reported interim results based on 200 pregnancies among 137 women. Most pregnancies occurred at least 4 months after the last dose of alemtuzumab; only four occurred within 1 month and another four occurred 1 to 3 months after the last dose.

Among the 181 completed pregnancies with known outcomes, 67.4% resulted in live births. Another 21.5% ended in spontaneous abortion. “Although this is on the higher end of normal, it is still in keeping with what is seen in the general population,” Dr. Oh noted.

The rate of stillbirth was 0.6%, also at the upper end of the range seen for the general population. Finally, 10.5% of the pregnancies ended in elective abortion.

There were no congenital anomalies or birth defects among the live-born infants. One was seen in an electively terminated pregnancy (26 months after the last dose), and another was seen in a stillbirth (4 years after the last dose).

“Two out of 200 is 1%, and this is actually lower than what is normally seen in the general population, approximately 3% to 7%,” Dr. Oh commented.

“To date, there is no indication of an increased risk for congenital anomalies or birth defects in infants,” she summarized. “There has also been no indication of increased rates of spontaneous abortion in women who become pregnant, but obviously, these data are limited because we don’t necessarily have a control group.”

“Based on the pharmacokinetics of alemtuzumab and labeling guidelines, women of childbearing potential should continue to use contraception for 4 months after receiving a course of alemtuzumab,” Dr. Oh concluded. “There is an international Alemtuzumab Pregnancy Exposure Registry that is open and enrolling patients who become pregnant between the first dose of alemtuzumab and 4 months after the last infusion, and hopefully this will give us more information to confirm some of the observations that we see here.”

Dr. Thiel disclosed that she had no relevant conflicts of interest; the German Multiple Sclerosis and Pregnancy registry was partly supported by Bayer Healthcare, Biogen Idec Germany, Merck Serono, Novartis Pharma, Teva Pharma, and Sanofi-Aventis/Genzyme Pharmaceuticals. Dr. Amato disclosed that she has received research grants and honoraria as a speaker from and is a member of advisory boards for Bayer, Biogen Idec, Merck Serono, Novartis, Sanofi Genzyme, Teva, Almirall, and Roche; the study did not receive any financial support. Dr. Oh disclosed that she serves on the scientific advisory boards or is a speaker for Biogen Idec, EMD Serono, Genzyme, Novartis, Roche, and Teva; the study was supported by Genzyme and Bayer Healthcare.

The U.S. Food and Drug Administration has issued a warning to health care providers against the routine prescribing of fluoroquinolone antibiotics to those patients with sinusitis, bronchitis, and uncomplicated urinary tract infections who have other treatment options.

After conducting a safety review of the drugs, the FDA concluded that fluoroquinolone should be reserved for those patients who do not have alternative treatment options, in light of the findings that the antibiotics – when used systemically in either tablet, capsule, or injectable form – are associated with “disabling and potentially permanent serious side effects” that can occur together. These side effects can involve the tendons, muscles, joints, nerves, and central nervous system, according to the agency.

The FDA says health care providers should stop systemic fluoroquinolone treatment immediately in patients reporting serious side effects and switch to a non-fluoroquinolone antibacterial drug to complete the patient’s treatment course. The drug labels and medication guides for all fluoroquinolone antibiotics will be updated to reflect the new safety information.

The FDA had previously communicated safety information associated with systemic fluoroquinolone antibacterial drugs in August 2013 and July 2008, and the safety issues described in the current warning were discussed at an FDA Advisory Committee meeting in November 2015.

[email protected]

On Twitter @richpizzi

The U.S. Food and Drug Administration has issued a warning to health care providers against the routine prescribing of fluoroquinolone antibiotics to those patients with sinusitis, bronchitis, and uncomplicated urinary tract infections who have other treatment options.

After conducting a safety review of the drugs, the FDA concluded that fluoroquinolone should be reserved for those patients who do not have alternative treatment options, in light of the findings that the antibiotics – when used systemically in either tablet, capsule, or injectable form – are associated with “disabling and potentially permanent serious side effects” that can occur together. These side effects can involve the tendons, muscles, joints, nerves, and central nervous system, according to the agency.

The FDA says health care providers should stop systemic fluoroquinolone treatment immediately in patients reporting serious side effects and switch to a non-fluoroquinolone antibacterial drug to complete the patient’s treatment course. The drug labels and medication guides for all fluoroquinolone antibiotics will be updated to reflect the new safety information.

The FDA had previously communicated safety information associated with systemic fluoroquinolone antibacterial drugs in August 2013 and July 2008, and the safety issues described in the current warning were discussed at an FDA Advisory Committee meeting in November 2015.

[email protected]

On Twitter @richpizzi

The U.S. Food and Drug Administration has issued a warning to health care providers against the routine prescribing of fluoroquinolone antibiotics to those patients with sinusitis, bronchitis, and uncomplicated urinary tract infections who have other treatment options.

After conducting a safety review of the drugs, the FDA concluded that fluoroquinolone should be reserved for those patients who do not have alternative treatment options, in light of the findings that the antibiotics – when used systemically in either tablet, capsule, or injectable form – are associated with “disabling and potentially permanent serious side effects” that can occur together. These side effects can involve the tendons, muscles, joints, nerves, and central nervous system, according to the agency.

The FDA says health care providers should stop systemic fluoroquinolone treatment immediately in patients reporting serious side effects and switch to a non-fluoroquinolone antibacterial drug to complete the patient’s treatment course. The drug labels and medication guides for all fluoroquinolone antibiotics will be updated to reflect the new safety information.

The FDA had previously communicated safety information associated with systemic fluoroquinolone antibacterial drugs in August 2013 and July 2008, and the safety issues described in the current warning were discussed at an FDA Advisory Committee meeting in November 2015.

[email protected]

On Twitter @richpizzi

A vial of authentic BiCNU

shown on the left and a

counterfeit vial on the right

Photo courtesy of the FDA

The US Food and Drug Administration (FDA) is warning healthcare professionals that a counterfeit version of BiCNU (carmustine for injection) 100 mg has been detected in some foreign countries.

The agency said there is no indication that counterfeit BiCNU has entered the legitimate US drug supply chain and no indication that any US patients have received counterfeit BiCNU.

Still, the FDA is advising that healthcare professionals inspect BiCNU vials as an added precaution to ensure the product administered to patients is authentic.

BiCNU is approved to treat brain cancers, multiple myeloma, and lymphoma. It is manufactured by Emcure Pharmaceuticals Ltd. and distributed in the US by Heritage Pharmaceuticals Inc.

Heritage previously announced that counterfeit BiCNU had been found in India, Ireland, and Israel.

How to identify counterfeit BiCNU

BiCNU is available as a vial of BiCNU and dehydrated alcohol co-packaged together.

While the NDC on the outer package of the authentic and counterfeit versions might match, the best way to distinguish a counterfeit is to look at the BiCNU vial inside the packaging. The authentic product has a blue flip top, while the counterfeit product may have a gray flip top.

The product may also be counterfeit if the vial displays the following lot numbers, batch numbers, manufacturing dates, and expiration dates.

The FDA urges healthcare professionals to purchase drug products only from legitimate suppliers.

Healthcare professionals are encouraged to report sales solicitation of suspect drug products by calling the FDA’s Office of Criminal Investigations (OCI) at 800-551-3989, reporting via OCI’s website, or emailing [email protected].

Healthcare professionals and patients should report adverse events related to the use of any suspect medications to the FDA’s MedWatch Adverse Event Reporting Program.

A vial of authentic BiCNU

shown on the left and a

counterfeit vial on the right

Photo courtesy of the FDA

The US Food and Drug Administration (FDA) is warning healthcare professionals that a counterfeit version of BiCNU (carmustine for injection) 100 mg has been detected in some foreign countries.

The agency said there is no indication that counterfeit BiCNU has entered the legitimate US drug supply chain and no indication that any US patients have received counterfeit BiCNU.

Still, the FDA is advising that healthcare professionals inspect BiCNU vials as an added precaution to ensure the product administered to patients is authentic.

BiCNU is approved to treat brain cancers, multiple myeloma, and lymphoma. It is manufactured by Emcure Pharmaceuticals Ltd. and distributed in the US by Heritage Pharmaceuticals Inc.

Heritage previously announced that counterfeit BiCNU had been found in India, Ireland, and Israel.

How to identify counterfeit BiCNU

BiCNU is available as a vial of BiCNU and dehydrated alcohol co-packaged together.

While the NDC on the outer package of the authentic and counterfeit versions might match, the best way to distinguish a counterfeit is to look at the BiCNU vial inside the packaging. The authentic product has a blue flip top, while the counterfeit product may have a gray flip top.

The product may also be counterfeit if the vial displays the following lot numbers, batch numbers, manufacturing dates, and expiration dates.

The FDA urges healthcare professionals to purchase drug products only from legitimate suppliers.

Healthcare professionals are encouraged to report sales solicitation of suspect drug products by calling the FDA’s Office of Criminal Investigations (OCI) at 800-551-3989, reporting via OCI’s website, or emailing [email protected].

Healthcare professionals and patients should report adverse events related to the use of any suspect medications to the FDA’s MedWatch Adverse Event Reporting Program.

A vial of authentic BiCNU

shown on the left and a

counterfeit vial on the right

Photo courtesy of the FDA

The US Food and Drug Administration (FDA) is warning healthcare professionals that a counterfeit version of BiCNU (carmustine for injection) 100 mg has been detected in some foreign countries.

The agency said there is no indication that counterfeit BiCNU has entered the legitimate US drug supply chain and no indication that any US patients have received counterfeit BiCNU.

Still, the FDA is advising that healthcare professionals inspect BiCNU vials as an added precaution to ensure the product administered to patients is authentic.

BiCNU is approved to treat brain cancers, multiple myeloma, and lymphoma. It is manufactured by Emcure Pharmaceuticals Ltd. and distributed in the US by Heritage Pharmaceuticals Inc.

Heritage previously announced that counterfeit BiCNU had been found in India, Ireland, and Israel.

How to identify counterfeit BiCNU

BiCNU is available as a vial of BiCNU and dehydrated alcohol co-packaged together.

While the NDC on the outer package of the authentic and counterfeit versions might match, the best way to distinguish a counterfeit is to look at the BiCNU vial inside the packaging. The authentic product has a blue flip top, while the counterfeit product may have a gray flip top.

The product may also be counterfeit if the vial displays the following lot numbers, batch numbers, manufacturing dates, and expiration dates.

The FDA urges healthcare professionals to purchase drug products only from legitimate suppliers.

Healthcare professionals are encouraged to report sales solicitation of suspect drug products by calling the FDA’s Office of Criminal Investigations (OCI) at 800-551-3989, reporting via OCI’s website, or emailing [email protected].

Healthcare professionals and patients should report adverse events related to the use of any suspect medications to the FDA’s MedWatch Adverse Event Reporting Program.