Immunology

LOS ANGELES – Fungi might play a far larger role in asthma and chronic sinusitis than previously thought, according to investigators at Baylor College of Medicine in Houston.

With the help of a special culturing technique to wash antifungal elements out of sputum samples, six or more fungal colony-forming units grew out of the sputum of 112 of 134 patients (83.5%) at the Houston Veterans Affairs Medical Center; about a third of the patients had asthma, a third had chronic sinusitis, and a third had both. Although Aspergillus and Candida species were common, more than 30 fungal species were identified. Only a handful of patients had positive results on IgE testing.

Of 62 patients treated with standard-dose voriconazole or terbinafine, sometimes for more than a year, 54 (87%) reported symptomatic benefit including 31 (50%) with decreased sputum production, 24 (39%) with improved breathing, 20 (32%) with less cough, and nine (14.5%) with less rescue inhaler use.

At Baylor, prescribing antifungals for patients with recalcitrant asthma and chronic sinusitis “has evolved into something we pretty much do all the time now regardless of sensitivity results. I’m pretty certain we are the only institution that does this,” said allergy and immunology fellow Dr. Evan Li.

“Fungi, we think, are important initiating factors in many cases of asthma. They set up chronic mucosal infection. Our [treatment] experience is extremely positive; it may be in the future that if you have significant asthma or sinusitis, you just go on an antifungal, but more research and clinical trials are needed,” said senior investigator Dr. David Corry, professor and chief of medical immunology, allergy, and rheumatology at Baylor.

“The standard culture techniques that have been used for 100 years are inadequate when it comes to culturing fungi from sputum, and why results almost invariably come back negative,” Dr. Corry said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The problem is that “almost everything in sputum” – eosinophils, macrophages, cytokines, and so on – “is designed to kill fungi.” Those elements have to be removed before plating. At Baylor, “we solubilize [sputum] with the reducing agent dithiothreitol, and vigorously stir the mixture to disperse the organisms and wash away the cellular elements and the other things.” The process leaves behind “a sandy material that’s basically fibrin clots mixed with a lot of fungal elements. You spread that on a plate, and it grows like wildfire,” he said.

“It’s easy to do, but time consuming. People are actually shipping their samples to us now from around the country, and we are happy to do those cultures,” Dr. Corry said. There’s no patent on the technique because “we want the community to use it. We want people to be helped,” he said.

Voriconazole seems to be the most effective option, and the team opts for it when possible, Dr. Corry noted. Terbinafine is the go-to drug for patients who can’t tolerate voriconazole. Fluconazole is sometimes added when monotherapy doesn’t seem to be doing the trick.

The work began as a search for household proteases. “One of our first discoveries was that” most are fungal. “The twist is that you are not inhaling the proteases, you are inhaling the fungus,” Dr. Corry said.

There have been both positive and negative results from the few prior investigations of antifungals for asthma. The team suspects that negative findings were a result of patients not being treated long enough, among other reasons.

The Baylor team is looking for funding for a prospective trial. The investigators hope to develop a protocol for diagnosis and treatment of fungal airway disease, but “there’s a lot of work that needs to get done,” Dr. Corry said.

The investigators had no relevant financial disclosures, and there was no outside funding for the work.

aotto@frontlinemedcom.com

LOS ANGELES – Fungi might play a far larger role in asthma and chronic sinusitis than previously thought, according to investigators at Baylor College of Medicine in Houston.

With the help of a special culturing technique to wash antifungal elements out of sputum samples, six or more fungal colony-forming units grew out of the sputum of 112 of 134 patients (83.5%) at the Houston Veterans Affairs Medical Center; about a third of the patients had asthma, a third had chronic sinusitis, and a third had both. Although Aspergillus and Candida species were common, more than 30 fungal species were identified. Only a handful of patients had positive results on IgE testing.

Of 62 patients treated with standard-dose voriconazole or terbinafine, sometimes for more than a year, 54 (87%) reported symptomatic benefit including 31 (50%) with decreased sputum production, 24 (39%) with improved breathing, 20 (32%) with less cough, and nine (14.5%) with less rescue inhaler use.

At Baylor, prescribing antifungals for patients with recalcitrant asthma and chronic sinusitis “has evolved into something we pretty much do all the time now regardless of sensitivity results. I’m pretty certain we are the only institution that does this,” said allergy and immunology fellow Dr. Evan Li.

“Fungi, we think, are important initiating factors in many cases of asthma. They set up chronic mucosal infection. Our [treatment] experience is extremely positive; it may be in the future that if you have significant asthma or sinusitis, you just go on an antifungal, but more research and clinical trials are needed,” said senior investigator Dr. David Corry, professor and chief of medical immunology, allergy, and rheumatology at Baylor.

“The standard culture techniques that have been used for 100 years are inadequate when it comes to culturing fungi from sputum, and why results almost invariably come back negative,” Dr. Corry said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The problem is that “almost everything in sputum” – eosinophils, macrophages, cytokines, and so on – “is designed to kill fungi.” Those elements have to be removed before plating. At Baylor, “we solubilize [sputum] with the reducing agent dithiothreitol, and vigorously stir the mixture to disperse the organisms and wash away the cellular elements and the other things.” The process leaves behind “a sandy material that’s basically fibrin clots mixed with a lot of fungal elements. You spread that on a plate, and it grows like wildfire,” he said.

“It’s easy to do, but time consuming. People are actually shipping their samples to us now from around the country, and we are happy to do those cultures,” Dr. Corry said. There’s no patent on the technique because “we want the community to use it. We want people to be helped,” he said.

Voriconazole seems to be the most effective option, and the team opts for it when possible, Dr. Corry noted. Terbinafine is the go-to drug for patients who can’t tolerate voriconazole. Fluconazole is sometimes added when monotherapy doesn’t seem to be doing the trick.

The work began as a search for household proteases. “One of our first discoveries was that” most are fungal. “The twist is that you are not inhaling the proteases, you are inhaling the fungus,” Dr. Corry said.

There have been both positive and negative results from the few prior investigations of antifungals for asthma. The team suspects that negative findings were a result of patients not being treated long enough, among other reasons.

The Baylor team is looking for funding for a prospective trial. The investigators hope to develop a protocol for diagnosis and treatment of fungal airway disease, but “there’s a lot of work that needs to get done,” Dr. Corry said.

The investigators had no relevant financial disclosures, and there was no outside funding for the work.

aotto@frontlinemedcom.com

LOS ANGELES – Fungi might play a far larger role in asthma and chronic sinusitis than previously thought, according to investigators at Baylor College of Medicine in Houston.

With the help of a special culturing technique to wash antifungal elements out of sputum samples, six or more fungal colony-forming units grew out of the sputum of 112 of 134 patients (83.5%) at the Houston Veterans Affairs Medical Center; about a third of the patients had asthma, a third had chronic sinusitis, and a third had both. Although Aspergillus and Candida species were common, more than 30 fungal species were identified. Only a handful of patients had positive results on IgE testing.

Of 62 patients treated with standard-dose voriconazole or terbinafine, sometimes for more than a year, 54 (87%) reported symptomatic benefit including 31 (50%) with decreased sputum production, 24 (39%) with improved breathing, 20 (32%) with less cough, and nine (14.5%) with less rescue inhaler use.

At Baylor, prescribing antifungals for patients with recalcitrant asthma and chronic sinusitis “has evolved into something we pretty much do all the time now regardless of sensitivity results. I’m pretty certain we are the only institution that does this,” said allergy and immunology fellow Dr. Evan Li.

“Fungi, we think, are important initiating factors in many cases of asthma. They set up chronic mucosal infection. Our [treatment] experience is extremely positive; it may be in the future that if you have significant asthma or sinusitis, you just go on an antifungal, but more research and clinical trials are needed,” said senior investigator Dr. David Corry, professor and chief of medical immunology, allergy, and rheumatology at Baylor.

“The standard culture techniques that have been used for 100 years are inadequate when it comes to culturing fungi from sputum, and why results almost invariably come back negative,” Dr. Corry said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The problem is that “almost everything in sputum” – eosinophils, macrophages, cytokines, and so on – “is designed to kill fungi.” Those elements have to be removed before plating. At Baylor, “we solubilize [sputum] with the reducing agent dithiothreitol, and vigorously stir the mixture to disperse the organisms and wash away the cellular elements and the other things.” The process leaves behind “a sandy material that’s basically fibrin clots mixed with a lot of fungal elements. You spread that on a plate, and it grows like wildfire,” he said.

“It’s easy to do, but time consuming. People are actually shipping their samples to us now from around the country, and we are happy to do those cultures,” Dr. Corry said. There’s no patent on the technique because “we want the community to use it. We want people to be helped,” he said.

Voriconazole seems to be the most effective option, and the team opts for it when possible, Dr. Corry noted. Terbinafine is the go-to drug for patients who can’t tolerate voriconazole. Fluconazole is sometimes added when monotherapy doesn’t seem to be doing the trick.

The work began as a search for household proteases. “One of our first discoveries was that” most are fungal. “The twist is that you are not inhaling the proteases, you are inhaling the fungus,” Dr. Corry said.

There have been both positive and negative results from the few prior investigations of antifungals for asthma. The team suspects that negative findings were a result of patients not being treated long enough, among other reasons.

The Baylor team is looking for funding for a prospective trial. The investigators hope to develop a protocol for diagnosis and treatment of fungal airway disease, but “there’s a lot of work that needs to get done,” Dr. Corry said.

The investigators had no relevant financial disclosures, and there was no outside funding for the work.

aotto@frontlinemedcom.com

SCOTTSDALE, ARIZ. – The phosphodiesterase-4 inhibitor crisaborole was well tolerated over 6 to 12 months, yielding no major safety signals during a multicenter, open-label extension study of patients with mild-to-moderate atopic dermatitis.

These safety results held up across age groups and over time, said Dr. Lawrence Eichenfield, a dermatologist at Children’s Hospital, San Diego, and at the University of San Diego School of Medicine. “The majority of treatment-emergent adverse events were considered mild to moderate and not related to treatment. There were no reports of long-term cutaneous reactions, such as atrophy or telangiectasia,” he and his associates added.

Atopic dermatitis has lacked widely accepted treatment options. Despite attempts to educate patients and parents about topical steroids, many are afraid to use them, and topical calcineurin inhibitors have a black box warning for cancer risk. Not surprisingly, therefore, a 2% ointment of crisaborole made headlines in 2015 after meeting its efficacy and safety endpoints in two pivotal phase III trials of patients with mild-to-moderate atopic dermatitis. Based on those results, Anacor Pharmaceuticals filed a new drug application for the novel boron-based small molecule in January 2016.

The pivotal trials lasted just 28 days, so to assess long-term safety, Dr. Eichenfield and his associates enrolled a subgroup of 517 patients aged 2 to 72 years into a single-arm, open-label, 48-week extension study of crisaborole. About 31% of participants had received the control vehicle during the pivotal trials, while the rest had received crisaborole and tolerated it well enough to continue using it. Patients applied crisaborole twice daily during treatment cycles of 28 days, and were evaluated on days 1, 8, and 29 for up to 12 treatment cycles. Patients whose skin became clear or almost clear went off treatment, but they were still assessed for adverse effects at the same frequency.

In all, 396 patients used crisaborole for at least 6 months, and 271 completed 12 months of treatment, the researchers reported at the annual meeting of the Society for Investigative Dermatology. Only nine (1.7%) patients stopped treatment during the extension study because of treatment-emergent adverse effects. A total of 65% of patients had at least one treatment-emergent adverse event during the initial phase III trials, the extension study, or both. These were usually mildly or moderately severe and included nasopharyngitis, upper respiratory infections, cough, and/or fever, all of which were considered unrelated to treatment.

Treatment-related adverse events included flares of atopic dermatitis, burning or stinging at the application site, and application site infection, which affected 3.1%, 2.3%, and 1.2%, respectively, of patients in the extension study. None of these events were considered serious. Notably, 11% of patients experienced atopic dermatitis flares in the original phase III trials, the researchers reported. Patients who could not tolerate crisaborole were excluded from the extension study, which might help explain the lower flare rate (3%) with long-term treatment.

“Crisaborole topical ointment, 2%, demonstrated a favorable long-term safety profile for the treatment of patients aged 2 years and older with mild-to-moderate atopic dermatitis,” the researchers concluded. The Food and Drug Administration accepted the new drug application in March.

Anacor Pharmaceuticals makes crisaborole and funded the study. Dr. Eichenfield has served as an investigator and consultant to Anacor. Three coinvestigators also reported affiliations with Anacor.

SCOTTSDALE, ARIZ. – The phosphodiesterase-4 inhibitor crisaborole was well tolerated over 6 to 12 months, yielding no major safety signals during a multicenter, open-label extension study of patients with mild-to-moderate atopic dermatitis.

These safety results held up across age groups and over time, said Dr. Lawrence Eichenfield, a dermatologist at Children’s Hospital, San Diego, and at the University of San Diego School of Medicine. “The majority of treatment-emergent adverse events were considered mild to moderate and not related to treatment. There were no reports of long-term cutaneous reactions, such as atrophy or telangiectasia,” he and his associates added.

Atopic dermatitis has lacked widely accepted treatment options. Despite attempts to educate patients and parents about topical steroids, many are afraid to use them, and topical calcineurin inhibitors have a black box warning for cancer risk. Not surprisingly, therefore, a 2% ointment of crisaborole made headlines in 2015 after meeting its efficacy and safety endpoints in two pivotal phase III trials of patients with mild-to-moderate atopic dermatitis. Based on those results, Anacor Pharmaceuticals filed a new drug application for the novel boron-based small molecule in January 2016.

The pivotal trials lasted just 28 days, so to assess long-term safety, Dr. Eichenfield and his associates enrolled a subgroup of 517 patients aged 2 to 72 years into a single-arm, open-label, 48-week extension study of crisaborole. About 31% of participants had received the control vehicle during the pivotal trials, while the rest had received crisaborole and tolerated it well enough to continue using it. Patients applied crisaborole twice daily during treatment cycles of 28 days, and were evaluated on days 1, 8, and 29 for up to 12 treatment cycles. Patients whose skin became clear or almost clear went off treatment, but they were still assessed for adverse effects at the same frequency.

In all, 396 patients used crisaborole for at least 6 months, and 271 completed 12 months of treatment, the researchers reported at the annual meeting of the Society for Investigative Dermatology. Only nine (1.7%) patients stopped treatment during the extension study because of treatment-emergent adverse effects. A total of 65% of patients had at least one treatment-emergent adverse event during the initial phase III trials, the extension study, or both. These were usually mildly or moderately severe and included nasopharyngitis, upper respiratory infections, cough, and/or fever, all of which were considered unrelated to treatment.

Treatment-related adverse events included flares of atopic dermatitis, burning or stinging at the application site, and application site infection, which affected 3.1%, 2.3%, and 1.2%, respectively, of patients in the extension study. None of these events were considered serious. Notably, 11% of patients experienced atopic dermatitis flares in the original phase III trials, the researchers reported. Patients who could not tolerate crisaborole were excluded from the extension study, which might help explain the lower flare rate (3%) with long-term treatment.

“Crisaborole topical ointment, 2%, demonstrated a favorable long-term safety profile for the treatment of patients aged 2 years and older with mild-to-moderate atopic dermatitis,” the researchers concluded. The Food and Drug Administration accepted the new drug application in March.

Anacor Pharmaceuticals makes crisaborole and funded the study. Dr. Eichenfield has served as an investigator and consultant to Anacor. Three coinvestigators also reported affiliations with Anacor.

SCOTTSDALE, ARIZ. – The phosphodiesterase-4 inhibitor crisaborole was well tolerated over 6 to 12 months, yielding no major safety signals during a multicenter, open-label extension study of patients with mild-to-moderate atopic dermatitis.

These safety results held up across age groups and over time, said Dr. Lawrence Eichenfield, a dermatologist at Children’s Hospital, San Diego, and at the University of San Diego School of Medicine. “The majority of treatment-emergent adverse events were considered mild to moderate and not related to treatment. There were no reports of long-term cutaneous reactions, such as atrophy or telangiectasia,” he and his associates added.

Atopic dermatitis has lacked widely accepted treatment options. Despite attempts to educate patients and parents about topical steroids, many are afraid to use them, and topical calcineurin inhibitors have a black box warning for cancer risk. Not surprisingly, therefore, a 2% ointment of crisaborole made headlines in 2015 after meeting its efficacy and safety endpoints in two pivotal phase III trials of patients with mild-to-moderate atopic dermatitis. Based on those results, Anacor Pharmaceuticals filed a new drug application for the novel boron-based small molecule in January 2016.

The pivotal trials lasted just 28 days, so to assess long-term safety, Dr. Eichenfield and his associates enrolled a subgroup of 517 patients aged 2 to 72 years into a single-arm, open-label, 48-week extension study of crisaborole. About 31% of participants had received the control vehicle during the pivotal trials, while the rest had received crisaborole and tolerated it well enough to continue using it. Patients applied crisaborole twice daily during treatment cycles of 28 days, and were evaluated on days 1, 8, and 29 for up to 12 treatment cycles. Patients whose skin became clear or almost clear went off treatment, but they were still assessed for adverse effects at the same frequency.

In all, 396 patients used crisaborole for at least 6 months, and 271 completed 12 months of treatment, the researchers reported at the annual meeting of the Society for Investigative Dermatology. Only nine (1.7%) patients stopped treatment during the extension study because of treatment-emergent adverse effects. A total of 65% of patients had at least one treatment-emergent adverse event during the initial phase III trials, the extension study, or both. These were usually mildly or moderately severe and included nasopharyngitis, upper respiratory infections, cough, and/or fever, all of which were considered unrelated to treatment.

Treatment-related adverse events included flares of atopic dermatitis, burning or stinging at the application site, and application site infection, which affected 3.1%, 2.3%, and 1.2%, respectively, of patients in the extension study. None of these events were considered serious. Notably, 11% of patients experienced atopic dermatitis flares in the original phase III trials, the researchers reported. Patients who could not tolerate crisaborole were excluded from the extension study, which might help explain the lower flare rate (3%) with long-term treatment.

“Crisaborole topical ointment, 2%, demonstrated a favorable long-term safety profile for the treatment of patients aged 2 years and older with mild-to-moderate atopic dermatitis,” the researchers concluded. The Food and Drug Administration accepted the new drug application in March.

Anacor Pharmaceuticals makes crisaborole and funded the study. Dr. Eichenfield has served as an investigator and consultant to Anacor. Three coinvestigators also reported affiliations with Anacor.

LOS ANGELES – A peanut protein–bearing skin patch known as the Viaskin Peanut gave a continued strong performance for treatment of peanut allergy in children during the second year of an international study of this novel form of epicutaneous immunotherapy.

The clinical response rate in 6- to 11-year-olds after 1 year of treatment with the 250-mcg dose of peanut protein in the medical device was 57% in the phase IIb, double-blind, 22-site, international VIPES trial, as reported last year.

©mates/Fotolia.com

After an additional year of treatment with the 250-mcg Viaskin Peanut in the open-label extension study known as OLFUS-VIPES, this rate climbed to 80%. Safety and tolerability of the device therapy remained excellent, Dr. Hugh A. Sampson said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In adolescents and adults, however, the clinical response – while significantly better than placebo in VIPES – was less robust than in children, and it remained stable from year 1 to year 2. This is believed to be due to the greater plasticity of the immune system in children, observed Dr. Sampson, director of the Jaffe Food Allergy Institute at Kravis Children’s Hospital at Mount Sinai in New York and chief scientific officer at DBV Technologies, which is developing the Viaskin Peanut.

The ongoing phase III trial uses the 250-mcg dose of peanut protein – the highest of several doses studied in VIPES and OLFUS-VIPES – and is restricted to peanut-allergic children ages 4-11 years. Doses of peanut protein greater than 250 mcg will be explored in separate studies of adolescents and adults.

The clinical response rate in children on the 250-mcg Viaskin Peanut rose from 57% after 1 year to 80% – that is, 16 of 20 subjects – after 2 years. A clinical response in VIPES and OLFUS-VIPES was defined as nonreactivity to a dose of at least 1,000 mg of peanut protein – the equivalent of four peanuts – during a formal double-blind food challenge or at least a tenfold increase in the eliciting dose, compared to the original eliciting dose.

In VIPES, one-third of children on the 250-mcg device therapy for 1 year could tolerate at least 1,000 mg of peanut protein; after an additional year of open-label therapy, 60% of children were able to do so.

Among 6- to 11-year-olds, the median cumulative reactive dose of peanut protein was 44 mg at baseline, 444 mg after 12 months of using the 250-mcg Viaskin Peanut, and 1,444 mg at 2 years.

The children’s immunologic response to the Viaskin Peanut was impressive: A 40% reduction from baseline in peanut IgE at 2 years, along with a ninefold increase in protective peanut-specific IgG4.

The skin patch consists of a dried allergen – in this case, peanut protein – which is made electrostatically adherent to a membrane on a Band-Aid–like chamber. A set of patches is placed on noneczematous skin on a child’s back and on the inner upper arm of older patients. Moisture emitted from the skin gradually causes the protein allergen to solubilize and get absorbed into the outer layer of the skin. It is then picked up by antigen-presenting Langerhans cells and transported to regional lymph nodes for deactivation. The patches are changed daily.

“It appears that we need to look at the skin as a tolerogenic organ when it’s uninflamed,” Dr. Sampson observed.

Compliance with treatment was in excess of 96% in both VIPES and OLFUS-VIPES. There have been no serious treatment-related adverse events and no need for the use of epinephrine. Side effects have been limited to occasional mild to moderate application site reactions easily managed with antihistamines and/or topical steroids, according to Dr. Sampson.

The double-blind VIPES study included 207 subjects with documented peanut allergy. OLFUS-VIPES, which will continue for 1 additional year of open-label therapy, includes 171 of the original 207, including 97 children, 49 adolescents, and 25 adults up to age 55 years.

“We’ll see if there’s continued improvement in children through the third year or it levels off, but based upon the immunologic parameters I think it’s having continued effect,” the pediatric allergist said.

bjancin@frontlinemedcom.com

LOS ANGELES – A peanut protein–bearing skin patch known as the Viaskin Peanut gave a continued strong performance for treatment of peanut allergy in children during the second year of an international study of this novel form of epicutaneous immunotherapy.

The clinical response rate in 6- to 11-year-olds after 1 year of treatment with the 250-mcg dose of peanut protein in the medical device was 57% in the phase IIb, double-blind, 22-site, international VIPES trial, as reported last year.

©mates/Fotolia.com

After an additional year of treatment with the 250-mcg Viaskin Peanut in the open-label extension study known as OLFUS-VIPES, this rate climbed to 80%. Safety and tolerability of the device therapy remained excellent, Dr. Hugh A. Sampson said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In adolescents and adults, however, the clinical response – while significantly better than placebo in VIPES – was less robust than in children, and it remained stable from year 1 to year 2. This is believed to be due to the greater plasticity of the immune system in children, observed Dr. Sampson, director of the Jaffe Food Allergy Institute at Kravis Children’s Hospital at Mount Sinai in New York and chief scientific officer at DBV Technologies, which is developing the Viaskin Peanut.

The ongoing phase III trial uses the 250-mcg dose of peanut protein – the highest of several doses studied in VIPES and OLFUS-VIPES – and is restricted to peanut-allergic children ages 4-11 years. Doses of peanut protein greater than 250 mcg will be explored in separate studies of adolescents and adults.

The clinical response rate in children on the 250-mcg Viaskin Peanut rose from 57% after 1 year to 80% – that is, 16 of 20 subjects – after 2 years. A clinical response in VIPES and OLFUS-VIPES was defined as nonreactivity to a dose of at least 1,000 mg of peanut protein – the equivalent of four peanuts – during a formal double-blind food challenge or at least a tenfold increase in the eliciting dose, compared to the original eliciting dose.

In VIPES, one-third of children on the 250-mcg device therapy for 1 year could tolerate at least 1,000 mg of peanut protein; after an additional year of open-label therapy, 60% of children were able to do so.

Among 6- to 11-year-olds, the median cumulative reactive dose of peanut protein was 44 mg at baseline, 444 mg after 12 months of using the 250-mcg Viaskin Peanut, and 1,444 mg at 2 years.

The children’s immunologic response to the Viaskin Peanut was impressive: A 40% reduction from baseline in peanut IgE at 2 years, along with a ninefold increase in protective peanut-specific IgG4.

The skin patch consists of a dried allergen – in this case, peanut protein – which is made electrostatically adherent to a membrane on a Band-Aid–like chamber. A set of patches is placed on noneczematous skin on a child’s back and on the inner upper arm of older patients. Moisture emitted from the skin gradually causes the protein allergen to solubilize and get absorbed into the outer layer of the skin. It is then picked up by antigen-presenting Langerhans cells and transported to regional lymph nodes for deactivation. The patches are changed daily.

“It appears that we need to look at the skin as a tolerogenic organ when it’s uninflamed,” Dr. Sampson observed.

Compliance with treatment was in excess of 96% in both VIPES and OLFUS-VIPES. There have been no serious treatment-related adverse events and no need for the use of epinephrine. Side effects have been limited to occasional mild to moderate application site reactions easily managed with antihistamines and/or topical steroids, according to Dr. Sampson.

The double-blind VIPES study included 207 subjects with documented peanut allergy. OLFUS-VIPES, which will continue for 1 additional year of open-label therapy, includes 171 of the original 207, including 97 children, 49 adolescents, and 25 adults up to age 55 years.

“We’ll see if there’s continued improvement in children through the third year or it levels off, but based upon the immunologic parameters I think it’s having continued effect,” the pediatric allergist said.

bjancin@frontlinemedcom.com

LOS ANGELES – A peanut protein–bearing skin patch known as the Viaskin Peanut gave a continued strong performance for treatment of peanut allergy in children during the second year of an international study of this novel form of epicutaneous immunotherapy.

The clinical response rate in 6- to 11-year-olds after 1 year of treatment with the 250-mcg dose of peanut protein in the medical device was 57% in the phase IIb, double-blind, 22-site, international VIPES trial, as reported last year.

©mates/Fotolia.com

After an additional year of treatment with the 250-mcg Viaskin Peanut in the open-label extension study known as OLFUS-VIPES, this rate climbed to 80%. Safety and tolerability of the device therapy remained excellent, Dr. Hugh A. Sampson said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In adolescents and adults, however, the clinical response – while significantly better than placebo in VIPES – was less robust than in children, and it remained stable from year 1 to year 2. This is believed to be due to the greater plasticity of the immune system in children, observed Dr. Sampson, director of the Jaffe Food Allergy Institute at Kravis Children’s Hospital at Mount Sinai in New York and chief scientific officer at DBV Technologies, which is developing the Viaskin Peanut.

The ongoing phase III trial uses the 250-mcg dose of peanut protein – the highest of several doses studied in VIPES and OLFUS-VIPES – and is restricted to peanut-allergic children ages 4-11 years. Doses of peanut protein greater than 250 mcg will be explored in separate studies of adolescents and adults.

The clinical response rate in children on the 250-mcg Viaskin Peanut rose from 57% after 1 year to 80% – that is, 16 of 20 subjects – after 2 years. A clinical response in VIPES and OLFUS-VIPES was defined as nonreactivity to a dose of at least 1,000 mg of peanut protein – the equivalent of four peanuts – during a formal double-blind food challenge or at least a tenfold increase in the eliciting dose, compared to the original eliciting dose.

In VIPES, one-third of children on the 250-mcg device therapy for 1 year could tolerate at least 1,000 mg of peanut protein; after an additional year of open-label therapy, 60% of children were able to do so.

Among 6- to 11-year-olds, the median cumulative reactive dose of peanut protein was 44 mg at baseline, 444 mg after 12 months of using the 250-mcg Viaskin Peanut, and 1,444 mg at 2 years.

The children’s immunologic response to the Viaskin Peanut was impressive: A 40% reduction from baseline in peanut IgE at 2 years, along with a ninefold increase in protective peanut-specific IgG4.

The skin patch consists of a dried allergen – in this case, peanut protein – which is made electrostatically adherent to a membrane on a Band-Aid–like chamber. A set of patches is placed on noneczematous skin on a child’s back and on the inner upper arm of older patients. Moisture emitted from the skin gradually causes the protein allergen to solubilize and get absorbed into the outer layer of the skin. It is then picked up by antigen-presenting Langerhans cells and transported to regional lymph nodes for deactivation. The patches are changed daily.

“It appears that we need to look at the skin as a tolerogenic organ when it’s uninflamed,” Dr. Sampson observed.

Compliance with treatment was in excess of 96% in both VIPES and OLFUS-VIPES. There have been no serious treatment-related adverse events and no need for the use of epinephrine. Side effects have been limited to occasional mild to moderate application site reactions easily managed with antihistamines and/or topical steroids, according to Dr. Sampson.

The double-blind VIPES study included 207 subjects with documented peanut allergy. OLFUS-VIPES, which will continue for 1 additional year of open-label therapy, includes 171 of the original 207, including 97 children, 49 adolescents, and 25 adults up to age 55 years.

“We’ll see if there’s continued improvement in children through the third year or it levels off, but based upon the immunologic parameters I think it’s having continued effect,” the pediatric allergist said.

bjancin@frontlinemedcom.com

The percentage of emergency department (ED) visits due to anaphylaxis more than doubled from 2011 to 2015 at one Canadian children’s hospital, according to a Research Letter to the Editor published in the Journal of Allergy and Clinical Immunology.

“Our results are limited to one pediatric center, but they suggest a worrisome increase in anaphylaxis rate that is consistent with the worldwide reported increase,” said Dr. Elana Hochstadter of the Hospital for Sick Children, University of Toronto, and her associates. The investigators analyzed longitudinal data in a national registry of anaphylaxis cases to track time trends for the disorder at their hospital. They identified 965 cases presenting to their ED during a 4-year period. The percentage of all ED visits accounted for by anaphylaxis rose from 0.20% to 0.41%. The overall volume of ED visits and the volume of specific ED diagnoses did not change during this interval.

EPG_europhotographics/ThinkStock

As in other studies of anaphylaxis around the world, food was the most common trigger in this series, responsible for 82% of cases. Peanut was the most common food allergen, accounting for 22% of cases. Most reactions were of moderate severity, and the percentages of mild, moderate, and severe reactions remained relatively stable throughout the study period. The presence of asthma was associated with increased severity of anaphylaxis (odds ratio, 2.3), as was the presence of eczema (OR, 2.1). Only half of the patients who had an epinephrine autoinjector used it before presenting to the ED, Dr. Hochstadter and her associates said (J Allergy Clin Immunol. 2016 doi: 10.1016/j.jaci.2016.02.016). The median age of the patients was 6 years.

The reason for this rapid increase is unknown, but it parallels that reported in studies of anaphylaxis throughout North America and Europe. “An important observation in our study is that administration of epinephrine before arrival in the ED is independently associated with a decreased likelihood of requiring multiple doses of epinephrine in the ED, suggesting that prompt epinephrine administration is beneficial,” they noted.

The Allergy, Genes, and Environment Network Centres of Excellence, Health Canada, and Sanofi funded the study. Dr. Hochstadter and her associates reported having no relevant disclosures.

fpnews@frontlinemedcom.com

The percentage of emergency department (ED) visits due to anaphylaxis more than doubled from 2011 to 2015 at one Canadian children’s hospital, according to a Research Letter to the Editor published in the Journal of Allergy and Clinical Immunology.

“Our results are limited to one pediatric center, but they suggest a worrisome increase in anaphylaxis rate that is consistent with the worldwide reported increase,” said Dr. Elana Hochstadter of the Hospital for Sick Children, University of Toronto, and her associates. The investigators analyzed longitudinal data in a national registry of anaphylaxis cases to track time trends for the disorder at their hospital. They identified 965 cases presenting to their ED during a 4-year period. The percentage of all ED visits accounted for by anaphylaxis rose from 0.20% to 0.41%. The overall volume of ED visits and the volume of specific ED diagnoses did not change during this interval.

EPG_europhotographics/ThinkStock

As in other studies of anaphylaxis around the world, food was the most common trigger in this series, responsible for 82% of cases. Peanut was the most common food allergen, accounting for 22% of cases. Most reactions were of moderate severity, and the percentages of mild, moderate, and severe reactions remained relatively stable throughout the study period. The presence of asthma was associated with increased severity of anaphylaxis (odds ratio, 2.3), as was the presence of eczema (OR, 2.1). Only half of the patients who had an epinephrine autoinjector used it before presenting to the ED, Dr. Hochstadter and her associates said (J Allergy Clin Immunol. 2016 doi: 10.1016/j.jaci.2016.02.016). The median age of the patients was 6 years.

The reason for this rapid increase is unknown, but it parallels that reported in studies of anaphylaxis throughout North America and Europe. “An important observation in our study is that administration of epinephrine before arrival in the ED is independently associated with a decreased likelihood of requiring multiple doses of epinephrine in the ED, suggesting that prompt epinephrine administration is beneficial,” they noted.

The Allergy, Genes, and Environment Network Centres of Excellence, Health Canada, and Sanofi funded the study. Dr. Hochstadter and her associates reported having no relevant disclosures.

fpnews@frontlinemedcom.com

The percentage of emergency department (ED) visits due to anaphylaxis more than doubled from 2011 to 2015 at one Canadian children’s hospital, according to a Research Letter to the Editor published in the Journal of Allergy and Clinical Immunology.

“Our results are limited to one pediatric center, but they suggest a worrisome increase in anaphylaxis rate that is consistent with the worldwide reported increase,” said Dr. Elana Hochstadter of the Hospital for Sick Children, University of Toronto, and her associates. The investigators analyzed longitudinal data in a national registry of anaphylaxis cases to track time trends for the disorder at their hospital. They identified 965 cases presenting to their ED during a 4-year period. The percentage of all ED visits accounted for by anaphylaxis rose from 0.20% to 0.41%. The overall volume of ED visits and the volume of specific ED diagnoses did not change during this interval.

EPG_europhotographics/ThinkStock

As in other studies of anaphylaxis around the world, food was the most common trigger in this series, responsible for 82% of cases. Peanut was the most common food allergen, accounting for 22% of cases. Most reactions were of moderate severity, and the percentages of mild, moderate, and severe reactions remained relatively stable throughout the study period. The presence of asthma was associated with increased severity of anaphylaxis (odds ratio, 2.3), as was the presence of eczema (OR, 2.1). Only half of the patients who had an epinephrine autoinjector used it before presenting to the ED, Dr. Hochstadter and her associates said (J Allergy Clin Immunol. 2016 doi: 10.1016/j.jaci.2016.02.016). The median age of the patients was 6 years.

The reason for this rapid increase is unknown, but it parallels that reported in studies of anaphylaxis throughout North America and Europe. “An important observation in our study is that administration of epinephrine before arrival in the ED is independently associated with a decreased likelihood of requiring multiple doses of epinephrine in the ED, suggesting that prompt epinephrine administration is beneficial,” they noted.

The Allergy, Genes, and Environment Network Centres of Excellence, Health Canada, and Sanofi funded the study. Dr. Hochstadter and her associates reported having no relevant disclosures.

fpnews@frontlinemedcom.com

BALTIMORE – Four out of five children with asthma didn’t have access to their medication at school because the proper paperwork was missing, according to a survey of 10 inner-city Milwaukee elementary schools.

The number of students who had the required physician-signed authorization forms remained low throughout the school year, said Dr. Santiago Encalada, a pulmonary fellow at the Medical College of Wisconsin, Milwaukee.

Dr. Encalada cited administrative hurdles, lack of standardization, and challenges in school-physician-family communication as barriers to children’s access to asthma medication at school. Although school nurses in Milwaukee have standing orders for emergency albuterol administration, they otherwise need physician signatures on school-generated forms to administer both rescue and prophylactic asthma administration.

Kari Oakes/Frontline Medical News

In a study whose purpose was to assess the percentage of children with asthma who had appropriate orders on file in a sample of 10 Milwaukee inner-city schools, the schools had orders on file for just 11% of students, on average, at the beginning of the 2014-2015 school year. At the second assessment in January 2015, the average number of students with orders on file at each school had risen to 22%, with schools that had performed better earlier also showing greater gains at mid-year. However, the June 2015 assessment showed that the gains did not continue, with the schools’ aggregate average of 21% of students with appropriate orders showing no improvement from mid-year.

The number of students with asthma in schools varied from about 40 to nearly 200. Numbers varied through the school year as enrollments shifted in these high-need schools, said Dr. Encalada, who presented his findings during a poster session at the annual meeting of the Pediatric Academic Societies. In general, the schools with lower enrollments tended to do better with having orders on file, although statistical analysis was not performed for this variable.

“On average, 80% of asthmatic students in the inner city schools we studied did not have school forms or orders available for life-saving asthma rescue medications, with significant variation between schools. Our findings show that access to even basic asthma care necessities are lagging for this vulnerable population, and a significant disparity exists even within this population,” said senior author Nicholas Antos*, associate director of the Cystic Fibrosis Center at Milwaukee’s Children’s Hospital of Wisconsin.

In interviews and discussion with school nurses and physicians’ offices, Dr. Antos* and Dr. Encalada found that there were often simple but fundamental misunderstandings that impeded the proper flow of paperwork. For example, schools in Milwaukee do not have standardized forms that authorize administration of prescription medications at school, so forms may be confusing to providers and their staff. Privacy concerns sometimes impeded the ability of clinic staff to authorize treatment for students. Also, the inevitable shuffle of paperwork in school-aged families meant that the forms sometimes were simply lost on the way to school.

Understanding the barriers in the process both on the school side and in physician offices has helped Dr. Antos*, Dr. Encalada, and their colleagues to start to build a better pathway. For example, a module has been built into the EHR asthma visit template that allows easy generation of a school form and asks for patient consent for release of information to the schools.

Dr. Antos* said in an interview that the work is ongoing: “To help address these problems, we have devised interventions to improve the way school nurses can contact clinicians, and helped design innovative standardized Asthma Action Plans that can double as school orders.”

In addition to working with local providers and schools, Dr. Encalada and Dr. Antos* have reached out to pediatric societies and the American Academy of Asthma, Allergy, and Immunology (AAAAI). Emphasizing the need for “education of stakeholders of all types,” Dr. Antos* said that change “may be difficult, but we hope with the support of pediatric organizations, the AAAAI, and school administrators, we can begin to break down the barriers preventing quality and timely communication with school nurses.”

The authors had no financial disclosures. The study was funded by the Centers for Disease Control and Prevention through the Wisconsin Asthma Coalition (WAC).

koakes@frontlinemedcom.com

On Twitter @karioakes

*In a previous version, Dr. Antos' name was misspelled.

BALTIMORE – Four out of five children with asthma didn’t have access to their medication at school because the proper paperwork was missing, according to a survey of 10 inner-city Milwaukee elementary schools.

The number of students who had the required physician-signed authorization forms remained low throughout the school year, said Dr. Santiago Encalada, a pulmonary fellow at the Medical College of Wisconsin, Milwaukee.

Dr. Encalada cited administrative hurdles, lack of standardization, and challenges in school-physician-family communication as barriers to children’s access to asthma medication at school. Although school nurses in Milwaukee have standing orders for emergency albuterol administration, they otherwise need physician signatures on school-generated forms to administer both rescue and prophylactic asthma administration.

Kari Oakes/Frontline Medical News

In a study whose purpose was to assess the percentage of children with asthma who had appropriate orders on file in a sample of 10 Milwaukee inner-city schools, the schools had orders on file for just 11% of students, on average, at the beginning of the 2014-2015 school year. At the second assessment in January 2015, the average number of students with orders on file at each school had risen to 22%, with schools that had performed better earlier also showing greater gains at mid-year. However, the June 2015 assessment showed that the gains did not continue, with the schools’ aggregate average of 21% of students with appropriate orders showing no improvement from mid-year.

The number of students with asthma in schools varied from about 40 to nearly 200. Numbers varied through the school year as enrollments shifted in these high-need schools, said Dr. Encalada, who presented his findings during a poster session at the annual meeting of the Pediatric Academic Societies. In general, the schools with lower enrollments tended to do better with having orders on file, although statistical analysis was not performed for this variable.

“On average, 80% of asthmatic students in the inner city schools we studied did not have school forms or orders available for life-saving asthma rescue medications, with significant variation between schools. Our findings show that access to even basic asthma care necessities are lagging for this vulnerable population, and a significant disparity exists even within this population,” said senior author Nicholas Antos*, associate director of the Cystic Fibrosis Center at Milwaukee’s Children’s Hospital of Wisconsin.

In interviews and discussion with school nurses and physicians’ offices, Dr. Antos* and Dr. Encalada found that there were often simple but fundamental misunderstandings that impeded the proper flow of paperwork. For example, schools in Milwaukee do not have standardized forms that authorize administration of prescription medications at school, so forms may be confusing to providers and their staff. Privacy concerns sometimes impeded the ability of clinic staff to authorize treatment for students. Also, the inevitable shuffle of paperwork in school-aged families meant that the forms sometimes were simply lost on the way to school.

Understanding the barriers in the process both on the school side and in physician offices has helped Dr. Antos*, Dr. Encalada, and their colleagues to start to build a better pathway. For example, a module has been built into the EHR asthma visit template that allows easy generation of a school form and asks for patient consent for release of information to the schools.

Dr. Antos* said in an interview that the work is ongoing: “To help address these problems, we have devised interventions to improve the way school nurses can contact clinicians, and helped design innovative standardized Asthma Action Plans that can double as school orders.”

In addition to working with local providers and schools, Dr. Encalada and Dr. Antos* have reached out to pediatric societies and the American Academy of Asthma, Allergy, and Immunology (AAAAI). Emphasizing the need for “education of stakeholders of all types,” Dr. Antos* said that change “may be difficult, but we hope with the support of pediatric organizations, the AAAAI, and school administrators, we can begin to break down the barriers preventing quality and timely communication with school nurses.”

The authors had no financial disclosures. The study was funded by the Centers for Disease Control and Prevention through the Wisconsin Asthma Coalition (WAC).

koakes@frontlinemedcom.com

On Twitter @karioakes

*In a previous version, Dr. Antos' name was misspelled.

BALTIMORE – Four out of five children with asthma didn’t have access to their medication at school because the proper paperwork was missing, according to a survey of 10 inner-city Milwaukee elementary schools.

The number of students who had the required physician-signed authorization forms remained low throughout the school year, said Dr. Santiago Encalada, a pulmonary fellow at the Medical College of Wisconsin, Milwaukee.

Dr. Encalada cited administrative hurdles, lack of standardization, and challenges in school-physician-family communication as barriers to children’s access to asthma medication at school. Although school nurses in Milwaukee have standing orders for emergency albuterol administration, they otherwise need physician signatures on school-generated forms to administer both rescue and prophylactic asthma administration.

Kari Oakes/Frontline Medical News

In a study whose purpose was to assess the percentage of children with asthma who had appropriate orders on file in a sample of 10 Milwaukee inner-city schools, the schools had orders on file for just 11% of students, on average, at the beginning of the 2014-2015 school year. At the second assessment in January 2015, the average number of students with orders on file at each school had risen to 22%, with schools that had performed better earlier also showing greater gains at mid-year. However, the June 2015 assessment showed that the gains did not continue, with the schools’ aggregate average of 21% of students with appropriate orders showing no improvement from mid-year.

The number of students with asthma in schools varied from about 40 to nearly 200. Numbers varied through the school year as enrollments shifted in these high-need schools, said Dr. Encalada, who presented his findings during a poster session at the annual meeting of the Pediatric Academic Societies. In general, the schools with lower enrollments tended to do better with having orders on file, although statistical analysis was not performed for this variable.

“On average, 80% of asthmatic students in the inner city schools we studied did not have school forms or orders available for life-saving asthma rescue medications, with significant variation between schools. Our findings show that access to even basic asthma care necessities are lagging for this vulnerable population, and a significant disparity exists even within this population,” said senior author Nicholas Antos*, associate director of the Cystic Fibrosis Center at Milwaukee’s Children’s Hospital of Wisconsin.

In interviews and discussion with school nurses and physicians’ offices, Dr. Antos* and Dr. Encalada found that there were often simple but fundamental misunderstandings that impeded the proper flow of paperwork. For example, schools in Milwaukee do not have standardized forms that authorize administration of prescription medications at school, so forms may be confusing to providers and their staff. Privacy concerns sometimes impeded the ability of clinic staff to authorize treatment for students. Also, the inevitable shuffle of paperwork in school-aged families meant that the forms sometimes were simply lost on the way to school.

Understanding the barriers in the process both on the school side and in physician offices has helped Dr. Antos*, Dr. Encalada, and their colleagues to start to build a better pathway. For example, a module has been built into the EHR asthma visit template that allows easy generation of a school form and asks for patient consent for release of information to the schools.

Dr. Antos* said in an interview that the work is ongoing: “To help address these problems, we have devised interventions to improve the way school nurses can contact clinicians, and helped design innovative standardized Asthma Action Plans that can double as school orders.”

In addition to working with local providers and schools, Dr. Encalada and Dr. Antos* have reached out to pediatric societies and the American Academy of Asthma, Allergy, and Immunology (AAAAI). Emphasizing the need for “education of stakeholders of all types,” Dr. Antos* said that change “may be difficult, but we hope with the support of pediatric organizations, the AAAAI, and school administrators, we can begin to break down the barriers preventing quality and timely communication with school nurses.”

The authors had no financial disclosures. The study was funded by the Centers for Disease Control and Prevention through the Wisconsin Asthma Coalition (WAC).

koakes@frontlinemedcom.com

On Twitter @karioakes

*In a previous version, Dr. Antos' name was misspelled.