Q) Many total joint replacements and other orthopedic procedures are performed at the surgical center where I work. To decrease the use of narcotics, the anesthesiology department often uses IV push ketorolac postop. Our nephrology colleagues in the community are unhappy about this—but we think they’re overreacting, since these patients are often generally healthy. Is there any data on the use of ketorolac and orthopedic surgery?

All medications have associated risks. For example, while therapeutic dosages for a limited time are considered safe and effective, prolonged use of any NSAID can increase the risk for acute kidney injury (AKI) or chronic kidney disease (CKD) progression. We tend to associate these issues only with patients who are at higher risk for CKD: those who are older or who have diabetes or hypertension.

Thus, it was shocking to read a clinical report on four previously healthy young adults who were admitted for AKI three to four days after postoperative administration of ketorolac. None of these patients had risk factors that would predispose them to kidney disease. All had complained of gastrointestinal symptoms along with mild dehydration and flank pain; one young man even required a kidney biopsy and dialysis. All four did eventually recover kidney function. ¹

Continue to: Ketorolac—like most NSAIDs...

Ketorolac—like most NSAIDs—can affect kidney function, decreasing renal plasma flow and causing a dysfunction in salt and water balance. Postoperative patients may have activity limitations (eg, the young healthy patient on crutches). Factor in kidney damage from presurgical/outpatient NSAID use (which is usually reversible) and dehydration due to decreased fluid intake and nausea, and AKI is a real danger.

With the opioid crisis at the forefront of national health news, nonnarcotic alternatives for pain control are much in demand. This puts a whole new population at risk for AKI. Educate patients and their families about preventive measures, such as controlling nausea, maintaining hydration, and monitoring urine output. Fever, flank pain, or any untoward symptoms should be reported. Remember, AKI may be more common in the older patient with diabetes—but it can occur in anyone.   —EA

Ellen Apple
Dickson Schools Family Clinic, Tennessee

Q) Many total joint replacements and other orthopedic procedures are performed at the surgical center where I work. To decrease the use of narcotics, the anesthesiology department often uses IV push ketorolac postop. Our nephrology colleagues in the community are unhappy about this—but we think they’re overreacting, since these patients are often generally healthy. Is there any data on the use of ketorolac and orthopedic surgery?

All medications have associated risks. For example, while therapeutic dosages for a limited time are considered safe and effective, prolonged use of any NSAID can increase the risk for acute kidney injury (AKI) or chronic kidney disease (CKD) progression. We tend to associate these issues only with patients who are at higher risk for CKD: those who are older or who have diabetes or hypertension.

Thus, it was shocking to read a clinical report on four previously healthy young adults who were admitted for AKI three to four days after postoperative administration of ketorolac. None of these patients had risk factors that would predispose them to kidney disease. All had complained of gastrointestinal symptoms along with mild dehydration and flank pain; one young man even required a kidney biopsy and dialysis. All four did eventually recover kidney function. ¹

Continue to: Ketorolac—like most NSAIDs...

Ketorolac—like most NSAIDs—can affect kidney function, decreasing renal plasma flow and causing a dysfunction in salt and water balance. Postoperative patients may have activity limitations (eg, the young healthy patient on crutches). Factor in kidney damage from presurgical/outpatient NSAID use (which is usually reversible) and dehydration due to decreased fluid intake and nausea, and AKI is a real danger.

With the opioid crisis at the forefront of national health news, nonnarcotic alternatives for pain control are much in demand. This puts a whole new population at risk for AKI. Educate patients and their families about preventive measures, such as controlling nausea, maintaining hydration, and monitoring urine output. Fever, flank pain, or any untoward symptoms should be reported. Remember, AKI may be more common in the older patient with diabetes—but it can occur in anyone.   —EA

Ellen Apple
Dickson Schools Family Clinic, Tennessee

Q) Many total joint replacements and other orthopedic procedures are performed at the surgical center where I work. To decrease the use of narcotics, the anesthesiology department often uses IV push ketorolac postop. Our nephrology colleagues in the community are unhappy about this—but we think they’re overreacting, since these patients are often generally healthy. Is there any data on the use of ketorolac and orthopedic surgery?

All medications have associated risks. For example, while therapeutic dosages for a limited time are considered safe and effective, prolonged use of any NSAID can increase the risk for acute kidney injury (AKI) or chronic kidney disease (CKD) progression. We tend to associate these issues only with patients who are at higher risk for CKD: those who are older or who have diabetes or hypertension.

Thus, it was shocking to read a clinical report on four previously healthy young adults who were admitted for AKI three to four days after postoperative administration of ketorolac. None of these patients had risk factors that would predispose them to kidney disease. All had complained of gastrointestinal symptoms along with mild dehydration and flank pain; one young man even required a kidney biopsy and dialysis. All four did eventually recover kidney function. ¹

Continue to: Ketorolac—like most NSAIDs...

Ketorolac—like most NSAIDs—can affect kidney function, decreasing renal plasma flow and causing a dysfunction in salt and water balance. Postoperative patients may have activity limitations (eg, the young healthy patient on crutches). Factor in kidney damage from presurgical/outpatient NSAID use (which is usually reversible) and dehydration due to decreased fluid intake and nausea, and AKI is a real danger.

With the opioid crisis at the forefront of national health news, nonnarcotic alternatives for pain control are much in demand. This puts a whole new population at risk for AKI. Educate patients and their families about preventive measures, such as controlling nausea, maintaining hydration, and monitoring urine output. Fever, flank pain, or any untoward symptoms should be reported. Remember, AKI may be more common in the older patient with diabetes—but it can occur in anyone.   —EA

Ellen Apple
Dickson Schools Family Clinic, Tennessee

The Food and Drug Administration has approved inotersen for treating polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR) in adults, the second treatment approved in 2 months for the rare genetic disorder.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Inotersen is a transthyretin-directed antisense oligonucleotide that inhibits production of the transthyretin (TTR) protein (amyloid), according to the FDA statement announcing the approval on Oct. 5. It is administered in a subcutaneous injection once a week and will be marketed as Tegsedi. In August, the FDA approved the first treatment for hATTR, patisiran (Onpattro).

The FDA statement described hATTR as a “rare, debilitating, and often fatal genetic disease characterized by the buildup of abnormal amyloid protein in peripheral nerves, the heart, and other organs,” with signs and symptoms that include effects on “sensation (pain and temperature), autonomic function (blood pressure changes and bowel and digestive problems), and muscle strength (weakness and immobility in the arms, legs, hands, and feet),” caused by amyloid deposition in the peripheral nervous system.

The mechanism-of-action section of the prescribing information states that inotersen “causes degradation of mutant and wild-type TTR mRNA through binding to the TTR mRNA, which results in a reduction of serum TTR protein and TTR protein deposits in tissues.”

A statement issued by the manufacturer, Ionis Pharmaceuticals, said that approval was based on a phase 3 study of patients with hATTR amyloidosis and polyneuropathy symptoms, which found significantly greater benefits among those treated with inotersen, compared with placebo, using primary endpoints that measured quality of life related to neuropathy and a measure of neuropathic disease progression.

Contraindications to inotersen include a history of acute glomerulonephritis caused by inotersen, history of a hypersensitivity reaction to the agent, and a platelet count below 100 × 10⁹/L; the label includes a boxed warning about thrombocytopenia and glomerulonephritis associated with treatment. The drug also is being marketed with a risk evaluation and mitigation strategy (REMS).

Patisiran, the treatment approved in August, results in “degradation of mutant and wild-type TTR mRNA through RNA interference, which results in a reduction of serum TTR protein and TTR protein deposits in tissues,” according to its prescribing information.

[email protected]

The Food and Drug Administration has approved inotersen for treating polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR) in adults, the second treatment approved in 2 months for the rare genetic disorder.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Inotersen is a transthyretin-directed antisense oligonucleotide that inhibits production of the transthyretin (TTR) protein (amyloid), according to the FDA statement announcing the approval on Oct. 5. It is administered in a subcutaneous injection once a week and will be marketed as Tegsedi. In August, the FDA approved the first treatment for hATTR, patisiran (Onpattro).

The FDA statement described hATTR as a “rare, debilitating, and often fatal genetic disease characterized by the buildup of abnormal amyloid protein in peripheral nerves, the heart, and other organs,” with signs and symptoms that include effects on “sensation (pain and temperature), autonomic function (blood pressure changes and bowel and digestive problems), and muscle strength (weakness and immobility in the arms, legs, hands, and feet),” caused by amyloid deposition in the peripheral nervous system.

The mechanism-of-action section of the prescribing information states that inotersen “causes degradation of mutant and wild-type TTR mRNA through binding to the TTR mRNA, which results in a reduction of serum TTR protein and TTR protein deposits in tissues.”

A statement issued by the manufacturer, Ionis Pharmaceuticals, said that approval was based on a phase 3 study of patients with hATTR amyloidosis and polyneuropathy symptoms, which found significantly greater benefits among those treated with inotersen, compared with placebo, using primary endpoints that measured quality of life related to neuropathy and a measure of neuropathic disease progression.

Contraindications to inotersen include a history of acute glomerulonephritis caused by inotersen, history of a hypersensitivity reaction to the agent, and a platelet count below 100 × 10⁹/L; the label includes a boxed warning about thrombocytopenia and glomerulonephritis associated with treatment. The drug also is being marketed with a risk evaluation and mitigation strategy (REMS).

Patisiran, the treatment approved in August, results in “degradation of mutant and wild-type TTR mRNA through RNA interference, which results in a reduction of serum TTR protein and TTR protein deposits in tissues,” according to its prescribing information.

[email protected]

The Food and Drug Administration has approved inotersen for treating polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR) in adults, the second treatment approved in 2 months for the rare genetic disorder.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Inotersen is a transthyretin-directed antisense oligonucleotide that inhibits production of the transthyretin (TTR) protein (amyloid), according to the FDA statement announcing the approval on Oct. 5. It is administered in a subcutaneous injection once a week and will be marketed as Tegsedi. In August, the FDA approved the first treatment for hATTR, patisiran (Onpattro).

The FDA statement described hATTR as a “rare, debilitating, and often fatal genetic disease characterized by the buildup of abnormal amyloid protein in peripheral nerves, the heart, and other organs,” with signs and symptoms that include effects on “sensation (pain and temperature), autonomic function (blood pressure changes and bowel and digestive problems), and muscle strength (weakness and immobility in the arms, legs, hands, and feet),” caused by amyloid deposition in the peripheral nervous system.

The mechanism-of-action section of the prescribing information states that inotersen “causes degradation of mutant and wild-type TTR mRNA through binding to the TTR mRNA, which results in a reduction of serum TTR protein and TTR protein deposits in tissues.”

A statement issued by the manufacturer, Ionis Pharmaceuticals, said that approval was based on a phase 3 study of patients with hATTR amyloidosis and polyneuropathy symptoms, which found significantly greater benefits among those treated with inotersen, compared with placebo, using primary endpoints that measured quality of life related to neuropathy and a measure of neuropathic disease progression.

Contraindications to inotersen include a history of acute glomerulonephritis caused by inotersen, history of a hypersensitivity reaction to the agent, and a platelet count below 100 × 10⁹/L; the label includes a boxed warning about thrombocytopenia and glomerulonephritis associated with treatment. The drug also is being marketed with a risk evaluation and mitigation strategy (REMS).

Patisiran, the treatment approved in August, results in “degradation of mutant and wild-type TTR mRNA through RNA interference, which results in a reduction of serum TTR protein and TTR protein deposits in tissues,” according to its prescribing information.

[email protected]

SAN FRANCISCO – In a phase II study, Vaxart’s oral flu vaccine was compared with a commercial injectable quadrivalent flu vaccine or placebo. The study found rates of illness were comparable between the oral vaccine and quadrivalent vaccinated groups.*

Vidyard Video

The recombinant adenovirus-based vaccine expresses hemagglutinin. It elicited a mucosal immune response, hinting that the mechanism of protection in flu vaccines may be dependent on the route of administration. It is also believed that a strong mucosal response is key to preventing future infections.

In an interview at IDWeek 2018, an annual scientific meeting on infectious diseases, Nikita Kolhatkar, PhD, a salaried employee of Vaxart, which makes the drug, describes the results of the study and explains the potential advantages of an oral flu vaccine versus a traditional injectable one. The oral formulation is cell-based and so is not vulnerable to the mutation and genetic drift that can occur in egg-based vaccines.

It is also more stable and, of course, less invasive than injectable vaccines, according to Dr. Kolhatkar.

*Correction, 10/9/2018: An earlier vs. of this article did not stress the comparability.

SOURCE: Kolhatkar N. IDWeek 2018. Poster abstract 1947.

SAN FRANCISCO – In a phase II study, Vaxart’s oral flu vaccine was compared with a commercial injectable quadrivalent flu vaccine or placebo. The study found rates of illness were comparable between the oral vaccine and quadrivalent vaccinated groups.*

Vidyard Video

The recombinant adenovirus-based vaccine expresses hemagglutinin. It elicited a mucosal immune response, hinting that the mechanism of protection in flu vaccines may be dependent on the route of administration. It is also believed that a strong mucosal response is key to preventing future infections.

In an interview at IDWeek 2018, an annual scientific meeting on infectious diseases, Nikita Kolhatkar, PhD, a salaried employee of Vaxart, which makes the drug, describes the results of the study and explains the potential advantages of an oral flu vaccine versus a traditional injectable one. The oral formulation is cell-based and so is not vulnerable to the mutation and genetic drift that can occur in egg-based vaccines.

It is also more stable and, of course, less invasive than injectable vaccines, according to Dr. Kolhatkar.

*Correction, 10/9/2018: An earlier vs. of this article did not stress the comparability.

SOURCE: Kolhatkar N. IDWeek 2018. Poster abstract 1947.

SAN FRANCISCO – In a phase II study, Vaxart’s oral flu vaccine was compared with a commercial injectable quadrivalent flu vaccine or placebo. The study found rates of illness were comparable between the oral vaccine and quadrivalent vaccinated groups.*

Vidyard Video

The recombinant adenovirus-based vaccine expresses hemagglutinin. It elicited a mucosal immune response, hinting that the mechanism of protection in flu vaccines may be dependent on the route of administration. It is also believed that a strong mucosal response is key to preventing future infections.

In an interview at IDWeek 2018, an annual scientific meeting on infectious diseases, Nikita Kolhatkar, PhD, a salaried employee of Vaxart, which makes the drug, describes the results of the study and explains the potential advantages of an oral flu vaccine versus a traditional injectable one. The oral formulation is cell-based and so is not vulnerable to the mutation and genetic drift that can occur in egg-based vaccines.

It is also more stable and, of course, less invasive than injectable vaccines, according to Dr. Kolhatkar.

*Correction, 10/9/2018: An earlier vs. of this article did not stress the comparability.

SOURCE: Kolhatkar N. IDWeek 2018. Poster abstract 1947.

Acne vulgaris is significantly more common in people with hidradenitis suppurativa (HS) than in the general population, according to Sara Wertenteil and her colleagues in the department of dermatology at Hofstra University in Hempstead, N.Y.

Using data collected by IBM Watson Health, the study authors examined a total of 48,050 adults with HS and 16.9 million adults in the general U.S. population. In this study population, 15.2% of adults with HS had acne, compared with only 2.9% of adults in the general population (P less than .0001), the investigators wrote in the Journal of the American Academy of Dermatology.

After adjusting for age, sex, obesity, smoking status, and polycystic ovarian syndrome (PCOS) status, the odds ratio of adults with HS having acne was 4.51 over those without HS (95% confidence interval, 4.40-4.63). In all subgroups measured (male; female; adults aged 18-44 years, 45-64 years, and 65 years and older; white; nonwhite; obese; nonobese; smoker; nonsmoker; positive for PCOS; non-PCOS) adults with HS were significantly more likely to have acne. The strongest association was in patients who were aged 65 years and older (odds ratio, 10.14; 95% CI, 8.97-11.46).

“Patients with HS have an increased prevalence of [acne vulgaris]. Clinicians treating HS patients should be aware of this burden and its potential implications including a further impact on quality of life. Management strategies should include consideration of both conditions, either with treatments that have overlapping efficacy, or with concomitant therapies,” the authors concluded.

The study was sponsored in part by AbbVie. One coauthor reported having served as an advisor for AbbVie, Pfizer, Janssen, and Asana Biosciences.

[email protected]

SOURCE: Wertentiel S et al. J Am Acad Dermatol. 2018 Oct 1. doi: 10.1016/j.jaad.2018.09.040.

Acne vulgaris is significantly more common in people with hidradenitis suppurativa (HS) than in the general population, according to Sara Wertenteil and her colleagues in the department of dermatology at Hofstra University in Hempstead, N.Y.

Using data collected by IBM Watson Health, the study authors examined a total of 48,050 adults with HS and 16.9 million adults in the general U.S. population. In this study population, 15.2% of adults with HS had acne, compared with only 2.9% of adults in the general population (P less than .0001), the investigators wrote in the Journal of the American Academy of Dermatology.

After adjusting for age, sex, obesity, smoking status, and polycystic ovarian syndrome (PCOS) status, the odds ratio of adults with HS having acne was 4.51 over those without HS (95% confidence interval, 4.40-4.63). In all subgroups measured (male; female; adults aged 18-44 years, 45-64 years, and 65 years and older; white; nonwhite; obese; nonobese; smoker; nonsmoker; positive for PCOS; non-PCOS) adults with HS were significantly more likely to have acne. The strongest association was in patients who were aged 65 years and older (odds ratio, 10.14; 95% CI, 8.97-11.46).

“Patients with HS have an increased prevalence of [acne vulgaris]. Clinicians treating HS patients should be aware of this burden and its potential implications including a further impact on quality of life. Management strategies should include consideration of both conditions, either with treatments that have overlapping efficacy, or with concomitant therapies,” the authors concluded.

The study was sponsored in part by AbbVie. One coauthor reported having served as an advisor for AbbVie, Pfizer, Janssen, and Asana Biosciences.

[email protected]

SOURCE: Wertentiel S et al. J Am Acad Dermatol. 2018 Oct 1. doi: 10.1016/j.jaad.2018.09.040.

Acne vulgaris is significantly more common in people with hidradenitis suppurativa (HS) than in the general population, according to Sara Wertenteil and her colleagues in the department of dermatology at Hofstra University in Hempstead, N.Y.

Using data collected by IBM Watson Health, the study authors examined a total of 48,050 adults with HS and 16.9 million adults in the general U.S. population. In this study population, 15.2% of adults with HS had acne, compared with only 2.9% of adults in the general population (P less than .0001), the investigators wrote in the Journal of the American Academy of Dermatology.

After adjusting for age, sex, obesity, smoking status, and polycystic ovarian syndrome (PCOS) status, the odds ratio of adults with HS having acne was 4.51 over those without HS (95% confidence interval, 4.40-4.63). In all subgroups measured (male; female; adults aged 18-44 years, 45-64 years, and 65 years and older; white; nonwhite; obese; nonobese; smoker; nonsmoker; positive for PCOS; non-PCOS) adults with HS were significantly more likely to have acne. The strongest association was in patients who were aged 65 years and older (odds ratio, 10.14; 95% CI, 8.97-11.46).

“Patients with HS have an increased prevalence of [acne vulgaris]. Clinicians treating HS patients should be aware of this burden and its potential implications including a further impact on quality of life. Management strategies should include consideration of both conditions, either with treatments that have overlapping efficacy, or with concomitant therapies,” the authors concluded.

The study was sponsored in part by AbbVie. One coauthor reported having served as an advisor for AbbVie, Pfizer, Janssen, and Asana Biosciences.

[email protected]

SOURCE: Wertentiel S et al. J Am Acad Dermatol. 2018 Oct 1. doi: 10.1016/j.jaad.2018.09.040.

SAN FRANCISCO – The new herpes zoster subunit vaccine (Shingrix) is on the short list of essential vaccines for immunocompromised adults, including those on biologics.

Ongoing research is demonstrating efficacy and safety in renal transplants patients, as well as those with hematologic cancer and stem cell transplants, according to Lorry Rubin, MD, director of pediatric infectious diseases at Cohen Children’s Medical Center, Queens, and professor of pediatrics at Hofstra University, Hempstead, N.Y.

Immunocompromised people, including those on biologics, should be immunized against a variety of diseases just like everyone else, but it’s tricky. There’s considerable variability in how biologics affect the immune system and subsequent vaccine potency. Timing is important, and although live vaccines are generally a no-go, there’s one class of biologics with which they’re safe, he said.

In a wide-ranging interview at IDWeek 2018, an annual scientific meeting on infectious diseases, Dr. Rubin shared his advice on immunizing the immunocompromised, including the other vaccines on the short list. He also tackled the common concern that vaccinations might trigger rejection in transplant patients.

He’s well qualified to address the issues: Dr. Rubin was lead author on the 2013 Infectious Diseases Society of America guidelines on vaccinating immunocompromised patients.

[email protected]

SAN FRANCISCO – The new herpes zoster subunit vaccine (Shingrix) is on the short list of essential vaccines for immunocompromised adults, including those on biologics.

Ongoing research is demonstrating efficacy and safety in renal transplants patients, as well as those with hematologic cancer and stem cell transplants, according to Lorry Rubin, MD, director of pediatric infectious diseases at Cohen Children’s Medical Center, Queens, and professor of pediatrics at Hofstra University, Hempstead, N.Y.

Immunocompromised people, including those on biologics, should be immunized against a variety of diseases just like everyone else, but it’s tricky. There’s considerable variability in how biologics affect the immune system and subsequent vaccine potency. Timing is important, and although live vaccines are generally a no-go, there’s one class of biologics with which they’re safe, he said.

In a wide-ranging interview at IDWeek 2018, an annual scientific meeting on infectious diseases, Dr. Rubin shared his advice on immunizing the immunocompromised, including the other vaccines on the short list. He also tackled the common concern that vaccinations might trigger rejection in transplant patients.

He’s well qualified to address the issues: Dr. Rubin was lead author on the 2013 Infectious Diseases Society of America guidelines on vaccinating immunocompromised patients.

[email protected]

SAN FRANCISCO – The new herpes zoster subunit vaccine (Shingrix) is on the short list of essential vaccines for immunocompromised adults, including those on biologics.

Ongoing research is demonstrating efficacy and safety in renal transplants patients, as well as those with hematologic cancer and stem cell transplants, according to Lorry Rubin, MD, director of pediatric infectious diseases at Cohen Children’s Medical Center, Queens, and professor of pediatrics at Hofstra University, Hempstead, N.Y.

Immunocompromised people, including those on biologics, should be immunized against a variety of diseases just like everyone else, but it’s tricky. There’s considerable variability in how biologics affect the immune system and subsequent vaccine potency. Timing is important, and although live vaccines are generally a no-go, there’s one class of biologics with which they’re safe, he said.

In a wide-ranging interview at IDWeek 2018, an annual scientific meeting on infectious diseases, Dr. Rubin shared his advice on immunizing the immunocompromised, including the other vaccines on the short list. He also tackled the common concern that vaccinations might trigger rejection in transplant patients.

He’s well qualified to address the issues: Dr. Rubin was lead author on the 2013 Infectious Diseases Society of America guidelines on vaccinating immunocompromised patients.

[email protected]

SAN FRANCISCO – Direct-acting antiretrovirals are more effective than pegylated interferon/ribavirin in reducing cardiovascular risk in people with hepatitis C virus, according to a review of over 30,000 patients in the ERCHIVES (Electronically Retrieved Cohort of HCV Infected Veterans) database of the Veterans Health Administration system.

In the study, 12,667 patients were treated with direct-acting antiretrovirals (DAAs) and 4,436 with pegylated interferon/ribavirin (PEG/RBV). Each subject was matched to an untreated control based on alcohol use, diabetes, and other confounders. Patients with HIV, hepatitis B, or previously diagnosed cardiovascular disease were excluded.

Over a follow-up of about 10 years, there were 2,361 strokes, heart attacks, or other cardiovascular (CV) events among untreated patients, which translated to an incidence of 30.9 events per 1,000 patient years. In the PEG/RBV group, there were 804 events, yielding an incidence of 23.5 per 1,000 patient years. The DAA group fared better, with 435 events and an incident rate of 16.3.

Sustained virologic response also was associated with lower CV risk, and the odds of attaining it were about 25% greater with DAAs vs. PEG/RBV. That might have played a role in the findings, since hepatitis C is known to be associated with CV disease and the virus has been found in atherosclerotic plaques.

Past investigations have been mixed on whether or not hepatitis C virus treatment reduces CV risk, but lead investigator Adeel Ajwad Butt, MD, professor of medicine at Cornell University, New York, said that his study was stronger than what has come before. He explained why, and also why the findings matter, in an interview at ID Week 2018, an annual scientific meeting on infectious diseases.

Most of the subjects were men, about a quarter were black, and the median age at baseline was 58 years.

Dr. Butt disclosed institutional research grants from Merck and Gilead.

[email protected]

SOURCE: Butt AA et al. ID Week 2018 abstract 930.

SAN FRANCISCO – Direct-acting antiretrovirals are more effective than pegylated interferon/ribavirin in reducing cardiovascular risk in people with hepatitis C virus, according to a review of over 30,000 patients in the ERCHIVES (Electronically Retrieved Cohort of HCV Infected Veterans) database of the Veterans Health Administration system.

In the study, 12,667 patients were treated with direct-acting antiretrovirals (DAAs) and 4,436 with pegylated interferon/ribavirin (PEG/RBV). Each subject was matched to an untreated control based on alcohol use, diabetes, and other confounders. Patients with HIV, hepatitis B, or previously diagnosed cardiovascular disease were excluded.

Over a follow-up of about 10 years, there were 2,361 strokes, heart attacks, or other cardiovascular (CV) events among untreated patients, which translated to an incidence of 30.9 events per 1,000 patient years. In the PEG/RBV group, there were 804 events, yielding an incidence of 23.5 per 1,000 patient years. The DAA group fared better, with 435 events and an incident rate of 16.3.

Sustained virologic response also was associated with lower CV risk, and the odds of attaining it were about 25% greater with DAAs vs. PEG/RBV. That might have played a role in the findings, since hepatitis C is known to be associated with CV disease and the virus has been found in atherosclerotic plaques.

Past investigations have been mixed on whether or not hepatitis C virus treatment reduces CV risk, but lead investigator Adeel Ajwad Butt, MD, professor of medicine at Cornell University, New York, said that his study was stronger than what has come before. He explained why, and also why the findings matter, in an interview at ID Week 2018, an annual scientific meeting on infectious diseases.

Most of the subjects were men, about a quarter were black, and the median age at baseline was 58 years.

Dr. Butt disclosed institutional research grants from Merck and Gilead.

[email protected]

SOURCE: Butt AA et al. ID Week 2018 abstract 930.

SAN FRANCISCO – Direct-acting antiretrovirals are more effective than pegylated interferon/ribavirin in reducing cardiovascular risk in people with hepatitis C virus, according to a review of over 30,000 patients in the ERCHIVES (Electronically Retrieved Cohort of HCV Infected Veterans) database of the Veterans Health Administration system.

In the study, 12,667 patients were treated with direct-acting antiretrovirals (DAAs) and 4,436 with pegylated interferon/ribavirin (PEG/RBV). Each subject was matched to an untreated control based on alcohol use, diabetes, and other confounders. Patients with HIV, hepatitis B, or previously diagnosed cardiovascular disease were excluded.

Over a follow-up of about 10 years, there were 2,361 strokes, heart attacks, or other cardiovascular (CV) events among untreated patients, which translated to an incidence of 30.9 events per 1,000 patient years. In the PEG/RBV group, there were 804 events, yielding an incidence of 23.5 per 1,000 patient years. The DAA group fared better, with 435 events and an incident rate of 16.3.

Sustained virologic response also was associated with lower CV risk, and the odds of attaining it were about 25% greater with DAAs vs. PEG/RBV. That might have played a role in the findings, since hepatitis C is known to be associated with CV disease and the virus has been found in atherosclerotic plaques.

Past investigations have been mixed on whether or not hepatitis C virus treatment reduces CV risk, but lead investigator Adeel Ajwad Butt, MD, professor of medicine at Cornell University, New York, said that his study was stronger than what has come before. He explained why, and also why the findings matter, in an interview at ID Week 2018, an annual scientific meeting on infectious diseases.

Most of the subjects were men, about a quarter were black, and the median age at baseline was 58 years.

Dr. Butt disclosed institutional research grants from Merck and Gilead.

[email protected]

SOURCE: Butt AA et al. ID Week 2018 abstract 930.

SAN FRANCISCO – In early October, the Food and Drug Administration approved omadacycline (Nuzyra) for the treatment of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections in adults.

The drug is a synthetic tetracycline designed to overcome some of the resistance mechanisms that can undermine traditional tetracycline drugs. It gained approval on the strength of the Oasis-1 (NCT03482011) and Oasis-2 (NCT03535194) trials, which demonstrated the drug’s noninferiority to linezolid.

At IDWeek 2018, researchers combined the data from the two pivotal trials to gain more power in some of the secondary endpoints, such as adverse events.

Paul McGovern, MD, vice president of clinical and medical affairs at Paratek, which markets omadacycline, discussed the results of the analysis at an annual scientific meeting on infectious diseases.

Combined, the two studies included 691 patients who received omadacycline and 689 who received linezolid. The two drugs achieved similar results for early clinical response, defined as at least a 20% reduction in lesion size 48-72 hours after the first dose. The mean reduction in baseline lesion area at day 3 was 53.4% in the omadacycline group and 53.0% in the linezolid group. At the end of the treatment period, those values were 93.9% and 93.7%, respectively, Dr. McGovern reported.

A total of 28.5% of patients receiving omadacycline reported drug-related treatment-emergent adverse events, compared with 16.1% of the linezolid group. The omadacycline group experienced higher frequency of nausea (21.9% vs. 8.7%) and vomiting (11.4% vs. 3.9%), he said.

The Oasis 1 and Oasis 2 studies were funded by Paratek. Dr. McGovern is an employee of Paratek.

SOURCE: McGovern P et al. IDWeek 2018, poster abstract 1347.

SAN FRANCISCO – In early October, the Food and Drug Administration approved omadacycline (Nuzyra) for the treatment of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections in adults.

The drug is a synthetic tetracycline designed to overcome some of the resistance mechanisms that can undermine traditional tetracycline drugs. It gained approval on the strength of the Oasis-1 (NCT03482011) and Oasis-2 (NCT03535194) trials, which demonstrated the drug’s noninferiority to linezolid.

At IDWeek 2018, researchers combined the data from the two pivotal trials to gain more power in some of the secondary endpoints, such as adverse events.

Paul McGovern, MD, vice president of clinical and medical affairs at Paratek, which markets omadacycline, discussed the results of the analysis at an annual scientific meeting on infectious diseases.

Combined, the two studies included 691 patients who received omadacycline and 689 who received linezolid. The two drugs achieved similar results for early clinical response, defined as at least a 20% reduction in lesion size 48-72 hours after the first dose. The mean reduction in baseline lesion area at day 3 was 53.4% in the omadacycline group and 53.0% in the linezolid group. At the end of the treatment period, those values were 93.9% and 93.7%, respectively, Dr. McGovern reported.

A total of 28.5% of patients receiving omadacycline reported drug-related treatment-emergent adverse events, compared with 16.1% of the linezolid group. The omadacycline group experienced higher frequency of nausea (21.9% vs. 8.7%) and vomiting (11.4% vs. 3.9%), he said.

The Oasis 1 and Oasis 2 studies were funded by Paratek. Dr. McGovern is an employee of Paratek.

SOURCE: McGovern P et al. IDWeek 2018, poster abstract 1347.

SAN FRANCISCO – In early October, the Food and Drug Administration approved omadacycline (Nuzyra) for the treatment of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections in adults.

The drug is a synthetic tetracycline designed to overcome some of the resistance mechanisms that can undermine traditional tetracycline drugs. It gained approval on the strength of the Oasis-1 (NCT03482011) and Oasis-2 (NCT03535194) trials, which demonstrated the drug’s noninferiority to linezolid.

At IDWeek 2018, researchers combined the data from the two pivotal trials to gain more power in some of the secondary endpoints, such as adverse events.

Paul McGovern, MD, vice president of clinical and medical affairs at Paratek, which markets omadacycline, discussed the results of the analysis at an annual scientific meeting on infectious diseases.

Combined, the two studies included 691 patients who received omadacycline and 689 who received linezolid. The two drugs achieved similar results for early clinical response, defined as at least a 20% reduction in lesion size 48-72 hours after the first dose. The mean reduction in baseline lesion area at day 3 was 53.4% in the omadacycline group and 53.0% in the linezolid group. At the end of the treatment period, those values were 93.9% and 93.7%, respectively, Dr. McGovern reported.

A total of 28.5% of patients receiving omadacycline reported drug-related treatment-emergent adverse events, compared with 16.1% of the linezolid group. The omadacycline group experienced higher frequency of nausea (21.9% vs. 8.7%) and vomiting (11.4% vs. 3.9%), he said.

The Oasis 1 and Oasis 2 studies were funded by Paratek. Dr. McGovern is an employee of Paratek.

SOURCE: McGovern P et al. IDWeek 2018, poster abstract 1347.

Photo from Novartis

The cost-effectiveness of tisagenlecleucel (Kymriah) depends on long-term clinical outcomes, which are presently unknown, according to investigators.

If the long-term outcomes are more modest than clinical trials suggest, then payers may be unwilling to cover the costly therapy, reported John K. Lin, MD, of Stanford University, and his colleagues.

Lowering the price or setting up an outcomes-based pricing structure may be necessary to get insurers to cover the therapy.

Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy that was approved by the U.S. Food and Drug Administration in August 2017 for relapsed or refractory pediatric B-cell acute lymphoblastic leukemia (ALL).

In 2018, the FDA expanded the indication for tisagenlecleucel to include adults with relapsed or refractory large B-cell lymphoma, though outcomes from lymphoma trials are not analyzed in the current study.

At a wholesale acquisition cost of $475,000 per infusion, it is the most expensive existing oncology therapy to date, and can be accompanied by expensive, potentially fatal adverse effects.

However, clinical trials suggest that tisagenlecleucel can offer years of relapse-free remission, thereby allowing patients to forgo other expensive therapies such as hematopoietic stem cell transplantation (HSCT).

“Although tisagenlecleucel-induced remission rates are promising, compared with those of established therapies (greater than 80% vs. less than 50%), only short-term follow-up data currently exist,” the investigators wrote in the Journal of Clinical Oncology.

“Given the high cost and broad applicability in other malignancies of tisagenlecleucel, a pressing question for policy makers, payers, patients, and clinicians is whether the cost of therapy represents reasonable value.”

The study used a Markov model to assess various long-term clinical outcome rates and cost thresholds of tisagenlecleucel. The lifetime cost of therapy was assessed and compared with costs of existing therapies.

The results showed that a 5-year relapse free survival rate of 40% would make the present cost ($475,000) of tisagenlecleucel economically reasonable. In this scenario, the increased life expectancy would be 12.1 years and would result in an additional 5.07 quality-adjusted life years (QALY) gained at a cost of $61,000 per QALY, compared with blinatumomab.

But if long-term outcomes are less favorable, tisagenlecleucel becomes much less cost effective. A 5-year relapse-free survival rate of 20% would drop increased life expectancy to 3.8 years, resulting in 1.80 QALYs gained and raising the cost to $151,000 per QALY.

“Our results suggest that at tisagenlecleucel’s current price and payment structure, its economic value is uncertain,” the investigators wrote.

They suggested a price drop to $200,000 or $350,000, which would allow the drug to remain cost effective even in a worse-case scenario, in which patients relapse and tisagenlecleucel is a bridge to transplant.

Another option is to move to outcomes-based pricing. Making payment conditional on 7 months of remission would make the treatment cost effective, according to the analysis.

“Price reductions of tisagenlecleucel or payment only for longer-term remissions would favorably influence cost-effectiveness, even if long-term clinical outcomes are modest,” the investigators wrote.

The study was funded by a Veterans Affairs Office of Academic Affiliations advanced fellowship in health service and research development, and a National Center for Advancing Translational Science Clinical and Translational Science Award.

One of the study coauthors reported consulting and research funding from Novartis. 

Photo from Novartis

The cost-effectiveness of tisagenlecleucel (Kymriah) depends on long-term clinical outcomes, which are presently unknown, according to investigators.

If the long-term outcomes are more modest than clinical trials suggest, then payers may be unwilling to cover the costly therapy, reported John K. Lin, MD, of Stanford University, and his colleagues.

Lowering the price or setting up an outcomes-based pricing structure may be necessary to get insurers to cover the therapy.

Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy that was approved by the U.S. Food and Drug Administration in August 2017 for relapsed or refractory pediatric B-cell acute lymphoblastic leukemia (ALL).

In 2018, the FDA expanded the indication for tisagenlecleucel to include adults with relapsed or refractory large B-cell lymphoma, though outcomes from lymphoma trials are not analyzed in the current study.

At a wholesale acquisition cost of $475,000 per infusion, it is the most expensive existing oncology therapy to date, and can be accompanied by expensive, potentially fatal adverse effects.

However, clinical trials suggest that tisagenlecleucel can offer years of relapse-free remission, thereby allowing patients to forgo other expensive therapies such as hematopoietic stem cell transplantation (HSCT).

“Although tisagenlecleucel-induced remission rates are promising, compared with those of established therapies (greater than 80% vs. less than 50%), only short-term follow-up data currently exist,” the investigators wrote in the Journal of Clinical Oncology.

“Given the high cost and broad applicability in other malignancies of tisagenlecleucel, a pressing question for policy makers, payers, patients, and clinicians is whether the cost of therapy represents reasonable value.”

The study used a Markov model to assess various long-term clinical outcome rates and cost thresholds of tisagenlecleucel. The lifetime cost of therapy was assessed and compared with costs of existing therapies.

The results showed that a 5-year relapse free survival rate of 40% would make the present cost ($475,000) of tisagenlecleucel economically reasonable. In this scenario, the increased life expectancy would be 12.1 years and would result in an additional 5.07 quality-adjusted life years (QALY) gained at a cost of $61,000 per QALY, compared with blinatumomab.

But if long-term outcomes are less favorable, tisagenlecleucel becomes much less cost effective. A 5-year relapse-free survival rate of 20% would drop increased life expectancy to 3.8 years, resulting in 1.80 QALYs gained and raising the cost to $151,000 per QALY.

“Our results suggest that at tisagenlecleucel’s current price and payment structure, its economic value is uncertain,” the investigators wrote.

They suggested a price drop to $200,000 or $350,000, which would allow the drug to remain cost effective even in a worse-case scenario, in which patients relapse and tisagenlecleucel is a bridge to transplant.

Another option is to move to outcomes-based pricing. Making payment conditional on 7 months of remission would make the treatment cost effective, according to the analysis.

“Price reductions of tisagenlecleucel or payment only for longer-term remissions would favorably influence cost-effectiveness, even if long-term clinical outcomes are modest,” the investigators wrote.

The study was funded by a Veterans Affairs Office of Academic Affiliations advanced fellowship in health service and research development, and a National Center for Advancing Translational Science Clinical and Translational Science Award.

One of the study coauthors reported consulting and research funding from Novartis. 

Photo from Novartis

The cost-effectiveness of tisagenlecleucel (Kymriah) depends on long-term clinical outcomes, which are presently unknown, according to investigators.

If the long-term outcomes are more modest than clinical trials suggest, then payers may be unwilling to cover the costly therapy, reported John K. Lin, MD, of Stanford University, and his colleagues.

Lowering the price or setting up an outcomes-based pricing structure may be necessary to get insurers to cover the therapy.

Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy that was approved by the U.S. Food and Drug Administration in August 2017 for relapsed or refractory pediatric B-cell acute lymphoblastic leukemia (ALL).

In 2018, the FDA expanded the indication for tisagenlecleucel to include adults with relapsed or refractory large B-cell lymphoma, though outcomes from lymphoma trials are not analyzed in the current study.

At a wholesale acquisition cost of $475,000 per infusion, it is the most expensive existing oncology therapy to date, and can be accompanied by expensive, potentially fatal adverse effects.

However, clinical trials suggest that tisagenlecleucel can offer years of relapse-free remission, thereby allowing patients to forgo other expensive therapies such as hematopoietic stem cell transplantation (HSCT).

“Although tisagenlecleucel-induced remission rates are promising, compared with those of established therapies (greater than 80% vs. less than 50%), only short-term follow-up data currently exist,” the investigators wrote in the Journal of Clinical Oncology.

“Given the high cost and broad applicability in other malignancies of tisagenlecleucel, a pressing question for policy makers, payers, patients, and clinicians is whether the cost of therapy represents reasonable value.”

The study used a Markov model to assess various long-term clinical outcome rates and cost thresholds of tisagenlecleucel. The lifetime cost of therapy was assessed and compared with costs of existing therapies.

The results showed that a 5-year relapse free survival rate of 40% would make the present cost ($475,000) of tisagenlecleucel economically reasonable. In this scenario, the increased life expectancy would be 12.1 years and would result in an additional 5.07 quality-adjusted life years (QALY) gained at a cost of $61,000 per QALY, compared with blinatumomab.

But if long-term outcomes are less favorable, tisagenlecleucel becomes much less cost effective. A 5-year relapse-free survival rate of 20% would drop increased life expectancy to 3.8 years, resulting in 1.80 QALYs gained and raising the cost to $151,000 per QALY.

“Our results suggest that at tisagenlecleucel’s current price and payment structure, its economic value is uncertain,” the investigators wrote.

They suggested a price drop to $200,000 or $350,000, which would allow the drug to remain cost effective even in a worse-case scenario, in which patients relapse and tisagenlecleucel is a bridge to transplant.

Another option is to move to outcomes-based pricing. Making payment conditional on 7 months of remission would make the treatment cost effective, according to the analysis.

“Price reductions of tisagenlecleucel or payment only for longer-term remissions would favorably influence cost-effectiveness, even if long-term clinical outcomes are modest,” the investigators wrote.

The study was funded by a Veterans Affairs Office of Academic Affiliations advanced fellowship in health service and research development, and a National Center for Advancing Translational Science Clinical and Translational Science Award.

One of the study coauthors reported consulting and research funding from Novartis. 

The approval of the 9-valent human papillomavirus (HPV) vaccine has been expanded to include an older age group, men and women aged 27-45 years, the Food and Drug Administration announced on Oct. 5.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The vaccine (Gardasil 9) was previously approved for those aged 9-26 years.

The approval “represents an important opportunity to help prevent HPV-related diseases and cancers in a broader age range,” Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research, said in the FDA statement announcing the approval.

“The Centers for Disease Control and Prevention has stated that HPV vaccination prior to becoming infected with the HPV types covered by the vaccine has the potential to prevent more than 90 percent of these cancers, or 31,200 cases every year, from ever developing,” he added.

Gardasil 9, approved in 2014, covers the four HPV types included in the original Gardasil vaccine approved in 2006, plus five additional HPV types.

The approval is based on the results of a study and follow-up of about 3,200 women aged 27-45 years, followed for an average of 3.5 years, which found that the vaccine was 88% percent effective “in the prevention of a combined endpoint of persistent infection, genital warts, vulvar and vaginal precancerous lesions, cervical precancerous lesions, and cervical cancer related to HPV types covered by the vaccine,” according to the FDA. The vaccine’s effectiveness in men in this age group is “inferred” from these results and from data on Gardasil in men aged 16-26 years, as well as “immunogenicity data from a clinical trial in which 150 men, 27 through 45 years of age, received a 3-dose regimen of Gardasil over 6 months,” the FDA statement noted.

Based on safety data in about 13,000 men and women, injection-site pain, swelling, redness, and headaches are the most common adverse reactions associated with Gardasil 9, the statement said. Gardasil 9 is manufactured by Merck.

[email protected]

The approval of the 9-valent human papillomavirus (HPV) vaccine has been expanded to include an older age group, men and women aged 27-45 years, the Food and Drug Administration announced on Oct. 5.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The vaccine (Gardasil 9) was previously approved for those aged 9-26 years.

The approval “represents an important opportunity to help prevent HPV-related diseases and cancers in a broader age range,” Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research, said in the FDA statement announcing the approval.

“The Centers for Disease Control and Prevention has stated that HPV vaccination prior to becoming infected with the HPV types covered by the vaccine has the potential to prevent more than 90 percent of these cancers, or 31,200 cases every year, from ever developing,” he added.

Gardasil 9, approved in 2014, covers the four HPV types included in the original Gardasil vaccine approved in 2006, plus five additional HPV types.

The approval is based on the results of a study and follow-up of about 3,200 women aged 27-45 years, followed for an average of 3.5 years, which found that the vaccine was 88% percent effective “in the prevention of a combined endpoint of persistent infection, genital warts, vulvar and vaginal precancerous lesions, cervical precancerous lesions, and cervical cancer related to HPV types covered by the vaccine,” according to the FDA. The vaccine’s effectiveness in men in this age group is “inferred” from these results and from data on Gardasil in men aged 16-26 years, as well as “immunogenicity data from a clinical trial in which 150 men, 27 through 45 years of age, received a 3-dose regimen of Gardasil over 6 months,” the FDA statement noted.

Based on safety data in about 13,000 men and women, injection-site pain, swelling, redness, and headaches are the most common adverse reactions associated with Gardasil 9, the statement said. Gardasil 9 is manufactured by Merck.

[email protected]

The approval of the 9-valent human papillomavirus (HPV) vaccine has been expanded to include an older age group, men and women aged 27-45 years, the Food and Drug Administration announced on Oct. 5.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The vaccine (Gardasil 9) was previously approved for those aged 9-26 years.

The approval “represents an important opportunity to help prevent HPV-related diseases and cancers in a broader age range,” Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research, said in the FDA statement announcing the approval.

“The Centers for Disease Control and Prevention has stated that HPV vaccination prior to becoming infected with the HPV types covered by the vaccine has the potential to prevent more than 90 percent of these cancers, or 31,200 cases every year, from ever developing,” he added.

Gardasil 9, approved in 2014, covers the four HPV types included in the original Gardasil vaccine approved in 2006, plus five additional HPV types.

The approval is based on the results of a study and follow-up of about 3,200 women aged 27-45 years, followed for an average of 3.5 years, which found that the vaccine was 88% percent effective “in the prevention of a combined endpoint of persistent infection, genital warts, vulvar and vaginal precancerous lesions, cervical precancerous lesions, and cervical cancer related to HPV types covered by the vaccine,” according to the FDA. The vaccine’s effectiveness in men in this age group is “inferred” from these results and from data on Gardasil in men aged 16-26 years, as well as “immunogenicity data from a clinical trial in which 150 men, 27 through 45 years of age, received a 3-dose regimen of Gardasil over 6 months,” the FDA statement noted.

Based on safety data in about 13,000 men and women, injection-site pain, swelling, redness, and headaches are the most common adverse reactions associated with Gardasil 9, the statement said. Gardasil 9 is manufactured by Merck.

[email protected]

SAN FRANCISCO – For the first time, the World Health Organization’s Monitored Emergency Use of Unregistered and Investigational Interventions (MEURI) protocol is being field tested in the Democratic Republic of Congo (DRC), where four different therapeutics are being delivered to Ebola patients. MEURI was created after controversy surrounding the 2014-2016 Ebola outbreak in West Africa, which ultimately led to the decision to integrate research into outbreak responses.

gl0ck/Thinkstock

MEURI is broadly designed for pathogens that have no proven intervention, on the premise that in a disease with high mortality, it can be ethically appropriate to provide experimental therapies during a response, as long as a set of criteria are met that ensure patient autonomy and give patients a reasonable opportunity to improve their condition.

The original plan was to employ experimental drugs under the MEURI umbrella during an Ebola outbreak in the DRC that began in May, but an effective response contained it so quickly that the program was canceled. However, when another Ebola outbreak occurred on Aug. 27, the material was still in the country and ready to be deployed. “That made it very easy to begin using them,” said Elizabeth Higgs, MD, global health science advisor for the division of clinical research at the National Institute for Allergy and Infectious Disease.

Dr. Higgs spoke about the developments during a late-breakers session at IDWeek 2018, an annual scientific meeting on infectious disease.

The therapies under consideration are Zmapp (Leaf Biopharmaceutical), which includes three chimeric monoclonal antibodies that target the main surface protein of the Ebola virus; mAb114 (NIAID), which was isolated in 1995 from a human survivor of Ebola and binds to the core of the Ebola surface protein; Remdesivir (Gilead), a small molecule that is believed to interfere with viral replication; and Regeneron’s Ebola triple monoclonal antibody cocktail, which also targets the surface protein.

Through Oct. 2, 43 Ebola patients have received one of the four drugs: 19 are cured and have been discharged, 12 have died, and 12 are still in recovery. Dr. Higgs cautioned against reading anything into those numbers, however, since no randomization was involved.

Although compassionate use is the primary aim of MEURI, it may be lead to some scientific benefit. The most that can be hoped for is to glean some insight into the safety of the interventions, although even that information is limited. “A colleague and I were talking about this the other day. After the first X number of patients, they were all still alive. What can you say from that? I think what you can say is that it didn’t kill them,” Dr. Higgs said.

Still, researchers are collecting laboratory data from patients to monitor their responses. “With Remdesivir we’re closely examining their transaminase, for example, so I think it will be helpful,” said Dr. Higgs.

SOURCE: Higgs E et al. IDWeek 2018.

SAN FRANCISCO – For the first time, the World Health Organization’s Monitored Emergency Use of Unregistered and Investigational Interventions (MEURI) protocol is being field tested in the Democratic Republic of Congo (DRC), where four different therapeutics are being delivered to Ebola patients. MEURI was created after controversy surrounding the 2014-2016 Ebola outbreak in West Africa, which ultimately led to the decision to integrate research into outbreak responses.

gl0ck/Thinkstock

MEURI is broadly designed for pathogens that have no proven intervention, on the premise that in a disease with high mortality, it can be ethically appropriate to provide experimental therapies during a response, as long as a set of criteria are met that ensure patient autonomy and give patients a reasonable opportunity to improve their condition.

The original plan was to employ experimental drugs under the MEURI umbrella during an Ebola outbreak in the DRC that began in May, but an effective response contained it so quickly that the program was canceled. However, when another Ebola outbreak occurred on Aug. 27, the material was still in the country and ready to be deployed. “That made it very easy to begin using them,” said Elizabeth Higgs, MD, global health science advisor for the division of clinical research at the National Institute for Allergy and Infectious Disease.

Dr. Higgs spoke about the developments during a late-breakers session at IDWeek 2018, an annual scientific meeting on infectious disease.

The therapies under consideration are Zmapp (Leaf Biopharmaceutical), which includes three chimeric monoclonal antibodies that target the main surface protein of the Ebola virus; mAb114 (NIAID), which was isolated in 1995 from a human survivor of Ebola and binds to the core of the Ebola surface protein; Remdesivir (Gilead), a small molecule that is believed to interfere with viral replication; and Regeneron’s Ebola triple monoclonal antibody cocktail, which also targets the surface protein.

Through Oct. 2, 43 Ebola patients have received one of the four drugs: 19 are cured and have been discharged, 12 have died, and 12 are still in recovery. Dr. Higgs cautioned against reading anything into those numbers, however, since no randomization was involved.

Although compassionate use is the primary aim of MEURI, it may be lead to some scientific benefit. The most that can be hoped for is to glean some insight into the safety of the interventions, although even that information is limited. “A colleague and I were talking about this the other day. After the first X number of patients, they were all still alive. What can you say from that? I think what you can say is that it didn’t kill them,” Dr. Higgs said.

Still, researchers are collecting laboratory data from patients to monitor their responses. “With Remdesivir we’re closely examining their transaminase, for example, so I think it will be helpful,” said Dr. Higgs.

SOURCE: Higgs E et al. IDWeek 2018.

SAN FRANCISCO – For the first time, the World Health Organization’s Monitored Emergency Use of Unregistered and Investigational Interventions (MEURI) protocol is being field tested in the Democratic Republic of Congo (DRC), where four different therapeutics are being delivered to Ebola patients. MEURI was created after controversy surrounding the 2014-2016 Ebola outbreak in West Africa, which ultimately led to the decision to integrate research into outbreak responses.

gl0ck/Thinkstock

MEURI is broadly designed for pathogens that have no proven intervention, on the premise that in a disease with high mortality, it can be ethically appropriate to provide experimental therapies during a response, as long as a set of criteria are met that ensure patient autonomy and give patients a reasonable opportunity to improve their condition.

The original plan was to employ experimental drugs under the MEURI umbrella during an Ebola outbreak in the DRC that began in May, but an effective response contained it so quickly that the program was canceled. However, when another Ebola outbreak occurred on Aug. 27, the material was still in the country and ready to be deployed. “That made it very easy to begin using them,” said Elizabeth Higgs, MD, global health science advisor for the division of clinical research at the National Institute for Allergy and Infectious Disease.

Dr. Higgs spoke about the developments during a late-breakers session at IDWeek 2018, an annual scientific meeting on infectious disease.

The therapies under consideration are Zmapp (Leaf Biopharmaceutical), which includes three chimeric monoclonal antibodies that target the main surface protein of the Ebola virus; mAb114 (NIAID), which was isolated in 1995 from a human survivor of Ebola and binds to the core of the Ebola surface protein; Remdesivir (Gilead), a small molecule that is believed to interfere with viral replication; and Regeneron’s Ebola triple monoclonal antibody cocktail, which also targets the surface protein.

Through Oct. 2, 43 Ebola patients have received one of the four drugs: 19 are cured and have been discharged, 12 have died, and 12 are still in recovery. Dr. Higgs cautioned against reading anything into those numbers, however, since no randomization was involved.

Although compassionate use is the primary aim of MEURI, it may be lead to some scientific benefit. The most that can be hoped for is to glean some insight into the safety of the interventions, although even that information is limited. “A colleague and I were talking about this the other day. After the first X number of patients, they were all still alive. What can you say from that? I think what you can say is that it didn’t kill them,” Dr. Higgs said.

Still, researchers are collecting laboratory data from patients to monitor their responses. “With Remdesivir we’re closely examining their transaminase, for example, so I think it will be helpful,” said Dr. Higgs.

SOURCE: Higgs E et al. IDWeek 2018.