Immunology

Children who present with a severe anaphylactic reaction are two to three times more likely to develop a second delayed, or late-phase, reaction, Dr. Waleed Alqurashi and his colleagues reported.

Their retrospective study found that of 484 children who came to the emergency department for anaphylaxis, 15% developed a biphasic reaction. Most of these (69%) were respiratory and/or cardiovascular; half required epinephrine (Ann. Allerg. Asth. Immunol. 2015 [doi.org/10.1016/j.anai.2015.05.013]).

Michele Sullivan/Frontline Medical News

Dr. Alqurashi of the pediatric department at the University of Ottawa and his associates identified five independent predictors of a biphasic reaction: age 6-9 years (odds ratio, 3.6); a delay in presentation of more than 90 minutes after the onset of the initial reaction (OR, 2.58); wide pulse pressure at triage (OR, 2.92); requiring more than one epinephrine dose for initial reaction (OR, 2.7); and needing inhaled beta-agonists at the ED (OR, 2.39).

Children with these characteristics should stay for observation, rather than being discharged when their initial reactions are stabilized, the authors wrote.

“This period should be individualized and based primarily on the degree of severity of the initial anaphylactic reaction. Given the relatively high sensitivity of the present predictors, children with mild anaphylaxis who do not match any of these predictors could be considered for early disposition from the ED (less than 6 hours timed from the onset of the anaphylactic reaction) as long as an appropriate counseling has been provided,” the investigators said. Nonetheless, Dr. Alqurashi and his associates think large-scale prospective pediatric studies are necessary to validate these predictors.

Dr Alqurashi and his associates have no financial disclosures.

Children who present with a severe anaphylactic reaction are two to three times more likely to develop a second delayed, or late-phase, reaction, Dr. Waleed Alqurashi and his colleagues reported.

Their retrospective study found that of 484 children who came to the emergency department for anaphylaxis, 15% developed a biphasic reaction. Most of these (69%) were respiratory and/or cardiovascular; half required epinephrine (Ann. Allerg. Asth. Immunol. 2015 [doi.org/10.1016/j.anai.2015.05.013]).

Michele Sullivan/Frontline Medical News

Dr. Alqurashi of the pediatric department at the University of Ottawa and his associates identified five independent predictors of a biphasic reaction: age 6-9 years (odds ratio, 3.6); a delay in presentation of more than 90 minutes after the onset of the initial reaction (OR, 2.58); wide pulse pressure at triage (OR, 2.92); requiring more than one epinephrine dose for initial reaction (OR, 2.7); and needing inhaled beta-agonists at the ED (OR, 2.39).

Children with these characteristics should stay for observation, rather than being discharged when their initial reactions are stabilized, the authors wrote.

“This period should be individualized and based primarily on the degree of severity of the initial anaphylactic reaction. Given the relatively high sensitivity of the present predictors, children with mild anaphylaxis who do not match any of these predictors could be considered for early disposition from the ED (less than 6 hours timed from the onset of the anaphylactic reaction) as long as an appropriate counseling has been provided,” the investigators said. Nonetheless, Dr. Alqurashi and his associates think large-scale prospective pediatric studies are necessary to validate these predictors.

Dr Alqurashi and his associates have no financial disclosures.

Children who present with a severe anaphylactic reaction are two to three times more likely to develop a second delayed, or late-phase, reaction, Dr. Waleed Alqurashi and his colleagues reported.

Their retrospective study found that of 484 children who came to the emergency department for anaphylaxis, 15% developed a biphasic reaction. Most of these (69%) were respiratory and/or cardiovascular; half required epinephrine (Ann. Allerg. Asth. Immunol. 2015 [doi.org/10.1016/j.anai.2015.05.013]).

Michele Sullivan/Frontline Medical News

Dr. Alqurashi of the pediatric department at the University of Ottawa and his associates identified five independent predictors of a biphasic reaction: age 6-9 years (odds ratio, 3.6); a delay in presentation of more than 90 minutes after the onset of the initial reaction (OR, 2.58); wide pulse pressure at triage (OR, 2.92); requiring more than one epinephrine dose for initial reaction (OR, 2.7); and needing inhaled beta-agonists at the ED (OR, 2.39).

Children with these characteristics should stay for observation, rather than being discharged when their initial reactions are stabilized, the authors wrote.

“This period should be individualized and based primarily on the degree of severity of the initial anaphylactic reaction. Given the relatively high sensitivity of the present predictors, children with mild anaphylaxis who do not match any of these predictors could be considered for early disposition from the ED (less than 6 hours timed from the onset of the anaphylactic reaction) as long as an appropriate counseling has been provided,” the investigators said. Nonetheless, Dr. Alqurashi and his associates think large-scale prospective pediatric studies are necessary to validate these predictors.

Dr Alqurashi and his associates have no financial disclosures.

Children who present with a severe anaphylactic reaction are two to three times more likely to develop a second delayed, or late-phase, reaction, Dr. Waleed Alqurashi and his colleagues reported.

Their retrospective study found that of 484 children who came to the emergency department for anaphylaxis, 15% developed a biphasic reaction. Most of these (69%) were respiratory and/or cardiovascular; half required epinephrine (Ann. Allerg. Asth. Immunol. 2015 [doi.org/10.1016/j.anai.2015.05.013]).

Michele Sullivan/Frontline Medical News

Dr. Alqurashi of the pediatric department at the University of Ottawa and his associates identified five independent predictors of a biphasic reaction: age 6-9 years (odds ratio, 3.6); a delay in presentation of more than 90 minutes after the onset of the initial reaction (OR, 2.58); wide pulse pressure at triage (OR, 2.92); requiring more than one epinephrine dose for initial reaction (OR, 2.7); and needing inhaled beta-agonists at the ED (OR, 2.39).

Children with these characteristics should stay for observation, rather than being discharged when their initial reactions are stabilized, the authors wrote.

“This period should be individualized and based primarily on the degree of severity of the initial anaphylactic reaction. Given the relatively high sensitivity of the present predictors, children with mild anaphylaxis who do not match any of these predictors could be considered for early disposition from the ED (less than 6 hours timed from the onset of the anaphylactic reaction) as long as an appropriate counseling has been provided,” the investigators said. Nonetheless, Dr. Alqurashi and his associates think large-scale prospective pediatric studies are necessary to validate these predictors.

Dr Alqurashi and his associates have no financial disclosures.

[email protected]

On Twitter @Alz_Gal

Children who present with a severe anaphylactic reaction are two to three times more likely to develop a second delayed, or late-phase, reaction, Dr. Waleed Alqurashi and his colleagues reported.

Their retrospective study found that of 484 children who came to the emergency department for anaphylaxis, 15% developed a biphasic reaction. Most of these (69%) were respiratory and/or cardiovascular; half required epinephrine (Ann. Allerg. Asth. Immunol. 2015 [doi.org/10.1016/j.anai.2015.05.013]).

Michele Sullivan/Frontline Medical News

Dr. Alqurashi of the pediatric department at the University of Ottawa and his associates identified five independent predictors of a biphasic reaction: age 6-9 years (odds ratio, 3.6); a delay in presentation of more than 90 minutes after the onset of the initial reaction (OR, 2.58); wide pulse pressure at triage (OR, 2.92); requiring more than one epinephrine dose for initial reaction (OR, 2.7); and needing inhaled beta-agonists at the ED (OR, 2.39).

Children with these characteristics should stay for observation, rather than being discharged when their initial reactions are stabilized, the authors wrote.

“This period should be individualized and based primarily on the degree of severity of the initial anaphylactic reaction. Given the relatively high sensitivity of the present predictors, children with mild anaphylaxis who do not match any of these predictors could be considered for early disposition from the ED (less than 6 hours timed from the onset of the anaphylactic reaction) as long as an appropriate counseling has been provided,” the investigators said. Nonetheless, Dr. Alqurashi and his associates think large-scale prospective pediatric studies are necessary to validate these predictors.

Dr Alqurashi and his associates have no financial disclosures.

[email protected]

On Twitter @Alz_Gal

Children who present with a severe anaphylactic reaction are two to three times more likely to develop a second delayed, or late-phase, reaction, Dr. Waleed Alqurashi and his colleagues reported.

Their retrospective study found that of 484 children who came to the emergency department for anaphylaxis, 15% developed a biphasic reaction. Most of these (69%) were respiratory and/or cardiovascular; half required epinephrine (Ann. Allerg. Asth. Immunol. 2015 [doi.org/10.1016/j.anai.2015.05.013]).

Michele Sullivan/Frontline Medical News

Dr. Alqurashi of the pediatric department at the University of Ottawa and his associates identified five independent predictors of a biphasic reaction: age 6-9 years (odds ratio, 3.6); a delay in presentation of more than 90 minutes after the onset of the initial reaction (OR, 2.58); wide pulse pressure at triage (OR, 2.92); requiring more than one epinephrine dose for initial reaction (OR, 2.7); and needing inhaled beta-agonists at the ED (OR, 2.39).

Children with these characteristics should stay for observation, rather than being discharged when their initial reactions are stabilized, the authors wrote.

“This period should be individualized and based primarily on the degree of severity of the initial anaphylactic reaction. Given the relatively high sensitivity of the present predictors, children with mild anaphylaxis who do not match any of these predictors could be considered for early disposition from the ED (less than 6 hours timed from the onset of the anaphylactic reaction) as long as an appropriate counseling has been provided,” the investigators said. Nonetheless, Dr. Alqurashi and his associates think large-scale prospective pediatric studies are necessary to validate these predictors.

Dr Alqurashi and his associates have no financial disclosures.

[email protected]

On Twitter @Alz_Gal

VANCOUVER, B.C. – Topical tofacitinib shows promise as a novel treatment for atopic dermatitis on the basis of a highly positive phase II randomized clinical trial.

The topical Janus kinase inhibitor hit all of its efficacy endpoints and was well tolerated, with infrequent side effects, none of them serious, Dr. Robert Bissonnette reported at the World Congress of Dermatology.

An unmet need exists for additional topical therapies for atopic dermatitis, a condition whose prevalence has been estimated at up to 20%. Existing topical agents, including corticosteroids and calcineurin inhibitors, have limitations involving long-term safety concerns and application site reactions, noted Dr. Bissonnette, president of Innovaderm Research in Montreal.

The Janus kinases have been implicated in the pathogenesis of atopic dermatitis due to their effects upon the interleukin-4, IL-5, and IL-31 signaling pathways and the resultant dysregulation of the immune response.

Dr. Bissonnette presented a phase II, 4-week, double-blind, vehicle-controlled, multicenter Canadian study involving 65 adults with mild to moderate atopic dermatitis. They applied tofacitinib ointment 2% or its vehicle twice daily for 4 weeks. Participants averaged 31 years of age, with a median 21 years since receiving the diagnosis of atopic dermatitis. Roughly three-quarters of subjects had moderate disease based upon Physician Global Assessment.

The primary study endpoint was change in Eczema Area and Severity Index (EASI) total score after 4 weeks. From a baseline EASI score of 5.4, the topical tofacitinib group experienced a mean 82% reduction, significantly outperforming the control group, which showed a 30% reduction. The difference between the two study arms reached significance at the first assessment, at week 1.

Patients on the topical Janus kinase (JAK) inhibitor also showed significantly better outcomes than controls on all secondary endpoints, with the differences reaching statistical significance at week 1 with the exception of improvement in self-assessed Itch Severity Item, where topical tofacitinib’s advantage became significant on treatment day 2.

Two patients on topical tofacitinib and five controls developed treatment area adverse events, consisting of skin irritation and/or pain, which was mild in all cases. There were no cases of herpes simplex or zoster, no opportunistic infections, no laboratory abnormalities, and no one required a dose reduction or temporary discontinuation of the topical JAK inhibitor, according to the dermatologist.

Oral tofacitinib is Food and Drug Administration–approved as Xeljanz for the treatment of rheumatoid arthritis and is currently under FDA review as a potential treatment for moderate to severe chronic plaque psoriasis, with a regulatory decision anticipated in October 2015.

The atopic dermatitis study was funded by Pfizer. Dr. Bissonnette is a consultant to and recipient of research grants from more than a dozen pharmaceutical companies, including Pfizer.

[email protected]

VANCOUVER, B.C. – Topical tofacitinib shows promise as a novel treatment for atopic dermatitis on the basis of a highly positive phase II randomized clinical trial.

The topical Janus kinase inhibitor hit all of its efficacy endpoints and was well tolerated, with infrequent side effects, none of them serious, Dr. Robert Bissonnette reported at the World Congress of Dermatology.

An unmet need exists for additional topical therapies for atopic dermatitis, a condition whose prevalence has been estimated at up to 20%. Existing topical agents, including corticosteroids and calcineurin inhibitors, have limitations involving long-term safety concerns and application site reactions, noted Dr. Bissonnette, president of Innovaderm Research in Montreal.

The Janus kinases have been implicated in the pathogenesis of atopic dermatitis due to their effects upon the interleukin-4, IL-5, and IL-31 signaling pathways and the resultant dysregulation of the immune response.

Dr. Bissonnette presented a phase II, 4-week, double-blind, vehicle-controlled, multicenter Canadian study involving 65 adults with mild to moderate atopic dermatitis. They applied tofacitinib ointment 2% or its vehicle twice daily for 4 weeks. Participants averaged 31 years of age, with a median 21 years since receiving the diagnosis of atopic dermatitis. Roughly three-quarters of subjects had moderate disease based upon Physician Global Assessment.

The primary study endpoint was change in Eczema Area and Severity Index (EASI) total score after 4 weeks. From a baseline EASI score of 5.4, the topical tofacitinib group experienced a mean 82% reduction, significantly outperforming the control group, which showed a 30% reduction. The difference between the two study arms reached significance at the first assessment, at week 1.

Patients on the topical Janus kinase (JAK) inhibitor also showed significantly better outcomes than controls on all secondary endpoints, with the differences reaching statistical significance at week 1 with the exception of improvement in self-assessed Itch Severity Item, where topical tofacitinib’s advantage became significant on treatment day 2.

Two patients on topical tofacitinib and five controls developed treatment area adverse events, consisting of skin irritation and/or pain, which was mild in all cases. There were no cases of herpes simplex or zoster, no opportunistic infections, no laboratory abnormalities, and no one required a dose reduction or temporary discontinuation of the topical JAK inhibitor, according to the dermatologist.

Oral tofacitinib is Food and Drug Administration–approved as Xeljanz for the treatment of rheumatoid arthritis and is currently under FDA review as a potential treatment for moderate to severe chronic plaque psoriasis, with a regulatory decision anticipated in October 2015.

The atopic dermatitis study was funded by Pfizer. Dr. Bissonnette is a consultant to and recipient of research grants from more than a dozen pharmaceutical companies, including Pfizer.

[email protected]

VANCOUVER, B.C. – Topical tofacitinib shows promise as a novel treatment for atopic dermatitis on the basis of a highly positive phase II randomized clinical trial.

The topical Janus kinase inhibitor hit all of its efficacy endpoints and was well tolerated, with infrequent side effects, none of them serious, Dr. Robert Bissonnette reported at the World Congress of Dermatology.

An unmet need exists for additional topical therapies for atopic dermatitis, a condition whose prevalence has been estimated at up to 20%. Existing topical agents, including corticosteroids and calcineurin inhibitors, have limitations involving long-term safety concerns and application site reactions, noted Dr. Bissonnette, president of Innovaderm Research in Montreal.

The Janus kinases have been implicated in the pathogenesis of atopic dermatitis due to their effects upon the interleukin-4, IL-5, and IL-31 signaling pathways and the resultant dysregulation of the immune response.

Dr. Bissonnette presented a phase II, 4-week, double-blind, vehicle-controlled, multicenter Canadian study involving 65 adults with mild to moderate atopic dermatitis. They applied tofacitinib ointment 2% or its vehicle twice daily for 4 weeks. Participants averaged 31 years of age, with a median 21 years since receiving the diagnosis of atopic dermatitis. Roughly three-quarters of subjects had moderate disease based upon Physician Global Assessment.

The primary study endpoint was change in Eczema Area and Severity Index (EASI) total score after 4 weeks. From a baseline EASI score of 5.4, the topical tofacitinib group experienced a mean 82% reduction, significantly outperforming the control group, which showed a 30% reduction. The difference between the two study arms reached significance at the first assessment, at week 1.

Patients on the topical Janus kinase (JAK) inhibitor also showed significantly better outcomes than controls on all secondary endpoints, with the differences reaching statistical significance at week 1 with the exception of improvement in self-assessed Itch Severity Item, where topical tofacitinib’s advantage became significant on treatment day 2.

Two patients on topical tofacitinib and five controls developed treatment area adverse events, consisting of skin irritation and/or pain, which was mild in all cases. There were no cases of herpes simplex or zoster, no opportunistic infections, no laboratory abnormalities, and no one required a dose reduction or temporary discontinuation of the topical JAK inhibitor, according to the dermatologist.

Oral tofacitinib is Food and Drug Administration–approved as Xeljanz for the treatment of rheumatoid arthritis and is currently under FDA review as a potential treatment for moderate to severe chronic plaque psoriasis, with a regulatory decision anticipated in October 2015.

The atopic dermatitis study was funded by Pfizer. Dr. Bissonnette is a consultant to and recipient of research grants from more than a dozen pharmaceutical companies, including Pfizer.

[email protected]

VANCOUVER – Atopic dermatitis arising de novo in patients in their 60s or older with no history of the disease poses a diagnostic challenge, and a low threshold for biopsy is warranted, Dr. Thomas Bieber said at the World Congress of Dermatology.

“The diagnosis is not very easy, and if you are not sure what you are facing, I urge you to take biopsies in order to exclude cutaneous T-cell lymphoma before treating the patient with any kind of active compound,” cautioned Dr. Bieber, professor and chair of the department of dermatology and allergy at the University of Bonn (Germany).

Bruce Jancin/Frontline Medical News

Very-late-onset atopic dermatitis and cutaneous T-cell lymphoma (CTCL) may look quite similar clinically. There is but a single exception: Primary CTCL usually doesn’t itch, while pruritus is a prominent feature of atopic dermatitis arising in seniors, he added.

New-onset atopic dermatitis at an advanced age is increasing in prevalence, as is true of atopic dermatitis across the rest of the age spectrum. Dr. Bieber said that statistic is certainly borne out in his own clinical practice, where with the graying of the population he is seeing more cases.

He credited Dr. Ryoji Tanei of Tokyo Metropolitan Geriatric Hospital with doing pioneering work in bringing this particular variant of atopic dermatitis to wider attention (J. Clin. Med. 2015;4:979-97). Roughly 30% of patients with atopic dermatitis in their 60s or older report they never had the disease before. Another 20% had atopic dermatitis in childhood, while it arose in early adulthood in the rest.

Atopic dermatitis arising de novo in seniors is a special form of the disease that characteristically involves the face, neck, and trunk while sparing the flexural areas which are so prominently involved in younger patients. The eczema is often erythrodermic. Older men are affected threefold more often than women.

The disorder is characterized by extraordinarily high serum IgE levels: a mean of 8,000 IU in one series reported by Dr. Tanei.

This very-late-onset form of atopic dermatitis tends not to fade away over time. Dr. Tanei has reported that many affected patients die with the inflammatory skin disease, never outgrowing it.

Very-late-onset atopic dermatitis is often resistant to topical therapies; repeated courses of oral corticosteroids may be required.

The differential diagnosis is quite different than in children, where genetic immunodeficiency syndromes are a real concern. While CTCL is the biggie in the differential diagnosis of very-late-onset atopic dermatitis, other conditions that need to be considered include psoriasis, contact dermatitis, pityriasis rubra pilaris, and pityriasis rosea.

Dr. Bieber is a consultant to and recipient of research grants from numerous pharmaceutical companies having an interest in dermatology.

bjancin@frontlinemedcom

VANCOUVER – Atopic dermatitis arising de novo in patients in their 60s or older with no history of the disease poses a diagnostic challenge, and a low threshold for biopsy is warranted, Dr. Thomas Bieber said at the World Congress of Dermatology.

“The diagnosis is not very easy, and if you are not sure what you are facing, I urge you to take biopsies in order to exclude cutaneous T-cell lymphoma before treating the patient with any kind of active compound,” cautioned Dr. Bieber, professor and chair of the department of dermatology and allergy at the University of Bonn (Germany).

Bruce Jancin/Frontline Medical News

Very-late-onset atopic dermatitis and cutaneous T-cell lymphoma (CTCL) may look quite similar clinically. There is but a single exception: Primary CTCL usually doesn’t itch, while pruritus is a prominent feature of atopic dermatitis arising in seniors, he added.

New-onset atopic dermatitis at an advanced age is increasing in prevalence, as is true of atopic dermatitis across the rest of the age spectrum. Dr. Bieber said that statistic is certainly borne out in his own clinical practice, where with the graying of the population he is seeing more cases.

He credited Dr. Ryoji Tanei of Tokyo Metropolitan Geriatric Hospital with doing pioneering work in bringing this particular variant of atopic dermatitis to wider attention (J. Clin. Med. 2015;4:979-97). Roughly 30% of patients with atopic dermatitis in their 60s or older report they never had the disease before. Another 20% had atopic dermatitis in childhood, while it arose in early adulthood in the rest.

Atopic dermatitis arising de novo in seniors is a special form of the disease that characteristically involves the face, neck, and trunk while sparing the flexural areas which are so prominently involved in younger patients. The eczema is often erythrodermic. Older men are affected threefold more often than women.

The disorder is characterized by extraordinarily high serum IgE levels: a mean of 8,000 IU in one series reported by Dr. Tanei.

This very-late-onset form of atopic dermatitis tends not to fade away over time. Dr. Tanei has reported that many affected patients die with the inflammatory skin disease, never outgrowing it.

Very-late-onset atopic dermatitis is often resistant to topical therapies; repeated courses of oral corticosteroids may be required.

The differential diagnosis is quite different than in children, where genetic immunodeficiency syndromes are a real concern. While CTCL is the biggie in the differential diagnosis of very-late-onset atopic dermatitis, other conditions that need to be considered include psoriasis, contact dermatitis, pityriasis rubra pilaris, and pityriasis rosea.

Dr. Bieber is a consultant to and recipient of research grants from numerous pharmaceutical companies having an interest in dermatology.

bjancin@frontlinemedcom

VANCOUVER – Atopic dermatitis arising de novo in patients in their 60s or older with no history of the disease poses a diagnostic challenge, and a low threshold for biopsy is warranted, Dr. Thomas Bieber said at the World Congress of Dermatology.

“The diagnosis is not very easy, and if you are not sure what you are facing, I urge you to take biopsies in order to exclude cutaneous T-cell lymphoma before treating the patient with any kind of active compound,” cautioned Dr. Bieber, professor and chair of the department of dermatology and allergy at the University of Bonn (Germany).

Bruce Jancin/Frontline Medical News

Very-late-onset atopic dermatitis and cutaneous T-cell lymphoma (CTCL) may look quite similar clinically. There is but a single exception: Primary CTCL usually doesn’t itch, while pruritus is a prominent feature of atopic dermatitis arising in seniors, he added.

New-onset atopic dermatitis at an advanced age is increasing in prevalence, as is true of atopic dermatitis across the rest of the age spectrum. Dr. Bieber said that statistic is certainly borne out in his own clinical practice, where with the graying of the population he is seeing more cases.

He credited Dr. Ryoji Tanei of Tokyo Metropolitan Geriatric Hospital with doing pioneering work in bringing this particular variant of atopic dermatitis to wider attention (J. Clin. Med. 2015;4:979-97). Roughly 30% of patients with atopic dermatitis in their 60s or older report they never had the disease before. Another 20% had atopic dermatitis in childhood, while it arose in early adulthood in the rest.

Atopic dermatitis arising de novo in seniors is a special form of the disease that characteristically involves the face, neck, and trunk while sparing the flexural areas which are so prominently involved in younger patients. The eczema is often erythrodermic. Older men are affected threefold more often than women.

The disorder is characterized by extraordinarily high serum IgE levels: a mean of 8,000 IU in one series reported by Dr. Tanei.

This very-late-onset form of atopic dermatitis tends not to fade away over time. Dr. Tanei has reported that many affected patients die with the inflammatory skin disease, never outgrowing it.

Very-late-onset atopic dermatitis is often resistant to topical therapies; repeated courses of oral corticosteroids may be required.

The differential diagnosis is quite different than in children, where genetic immunodeficiency syndromes are a real concern. While CTCL is the biggie in the differential diagnosis of very-late-onset atopic dermatitis, other conditions that need to be considered include psoriasis, contact dermatitis, pityriasis rubra pilaris, and pityriasis rosea.

Dr. Bieber is a consultant to and recipient of research grants from numerous pharmaceutical companies having an interest in dermatology.

bjancin@frontlinemedcom

GAITHERSBURG, MD. – The biologic agent mepolizumab was unanimously recommended for approval as a treatment for severe asthma in adults at a June 4 meeting of the Food and Drug Administration’s Pulmonary-Allergy Drugs Advisory Committee.

All 14 members of the advisory panel agreed that the efficacy data provide substantial evidence of a clinically meaningful benefit of mepolizumab for the treatment of severe asthma in adults; 13 of the 14 members agreed that the data adequately demonstrated safety in adults. However, only four panel members recommended approval for adolescents aged 12-17 years, with the majority of panel members citing concerns that the low number of adolescents studied to date did not allow safety to be adequately evaluated in a younger population, especially for a medication that would be taken for many years – perhaps for a lifetime.

If approved by the FDA, the biologic agent would be available as a once-monthly treatment that is injected subcutaneously by a health care professional. Mepolizumab would be marketed by Glaxo Smith Kline under the trade name Nucala. Mepolizumab is a first-in-class humanized monoclonal antibody that targets interleukin-5, a glycoprotein cytokine that mediates production of eosinophils. Elevation of eosinophils in blood and tissue is associated with an increase in cytokines and other inflammatory molecules that can trigger or exacerbate airway inflammation in asthma. One other monoclonal antibody, the anti-IgE biologic omulizimab (Xolair), has been approved to treat asthma. Glaxo Smith Kline brought mepolizumab to the FDA for use as an add-on therapy for the small subset of asthma patients whose disease remains uncontrolled despite the optimal use of inhaled corticosteroids and additional therapies such as leukotriene inhibitors or theophylline. This population experiences more frequent asthma exacerbations, has more emergency department visits and hospitalizations, and uses higher doses of oral corticosteroids. Approximately 60% of those with severe asthma have marked eosinophilia.Panel members uniformly cited the efficacy data for adults with severe asthma; several panelists also remarked on the importance of developing more steroid-sparing alternatives for this population.

The panel endorsed neither efficacy nor safety for those aged 12-17 years, with 9 of the 14 panelists voting not to endorse efficacy and 13 members voting not to endorse safety findings. Mepolizumab’s efficacy, many panelists said, was not clearly established from the data presented, which drew from small numbers of adolescents enrolled in the studies.

Dr. David Au, acting director of Health Services Research and Development at Seattle’s VA Puget Sound Health Care system, observed that “adolescents are not small adults – their lungs continue to mature over time.” Many panelists, however, also called for ongoing study, noting the significant unmet need for steroid alternatives in the adolescent population.

Several panelists advocated postmarketing surveillance for long-term use, with particular attention to those with parasitic disease, to monitoring any sign of malignancy, and to tracking opportunistic diseases such as herpes zoster.

An early clinical trial of mepolizumab, conducted in 1999, failed to show benefit for an undifferentiated population of patients with moderate to severe asthma. However, independent research later identified marked eosinophilia as a factor associated with more frequent asthma exacerbations and a series of clinical trials begun in 2011 targeted patients with severe asthma and eosinophilic inflammation. A global program was initiated, with 12% of patients overall coming from the United States.

Pivotal phase 2b/3, double blind, placebo-controlled clinical trials included a dose-ranging study tracking asthma exacerbations enrolling 616 patients for 52 weeks.

The recommended dose of 100 mg subcutaneously every 4 weeks, as well as a 75-mg IV dose, was used for an additional 576 patients for 32 weeks, with the primary outcome measure being the number of asthma exacerbations. A final 24-week study of 135 patients with severe asthma measured the reduction in oral corticosteroid use, compared with placebo, as well as the number of asthma exacerbations. In all of the studies, patients’ asthma treatment was optimized according to standard of care before adding mepolizumab.

In each study and in pooled data, mepolizumab approximately halved the number of asthma exacerbations for study participants when compared with those using placebo. A 24-week corticosteroid-sparing study showed significant reduction in oral corticosteroid use, without loss of asthma control, for the mepolizumab group. Prespecified subgroup analyses were hampered because of low participation numbers for African Americans and adolescents, and because confidence intervals for these subgroups often ranged over 1, limiting interpretation of benefit results for these groups. The overall safety profile was good, with adverse event rates similar in the treatment and placebo arms. Headache and injection-site reactions were the most commonly reported adverse events but were similar between treatment and placebo arms. No episodes of anaphylaxis were reported, and neutralizing antibodies developed in one patient total across all studies. Ongoing open-label studies continue.The FDA’s independent biostatistical analysis showed clear evidence of efficacy for mepolizumab, with demonstrated consistent, statistically significant decreases of about one exacerbation per year, according to the agency.In its analysis, the agency observed a positive association between higher eosinophil count and mepolizumab treatment effect, meaning that those with higher eosinophil counts saw a greater benefit from mepolizumab, as measured by a reduction in exacerbations.

The number of deaths was balanced across treatment arms, though a larger number of respiratory-related deaths than expected was seen overall. This higher number of deaths may reflect the severity of asthma in the study population. The respiratory-related serious adverse events, according to the FDA, favor treatment over placebo.

No treatment-related cardiovascular risks were identified.

The FDA usually follows the recommendations of its advisory panels. The FDA panelists reported no relevant conflicts of interest.

GAITHERSBURG, MD. – The biologic agent mepolizumab was unanimously recommended for approval as a treatment for severe asthma in adults at a June 4 meeting of the Food and Drug Administration’s Pulmonary-Allergy Drugs Advisory Committee.

All 14 members of the advisory panel agreed that the efficacy data provide substantial evidence of a clinically meaningful benefit of mepolizumab for the treatment of severe asthma in adults; 13 of the 14 members agreed that the data adequately demonstrated safety in adults. However, only four panel members recommended approval for adolescents aged 12-17 years, with the majority of panel members citing concerns that the low number of adolescents studied to date did not allow safety to be adequately evaluated in a younger population, especially for a medication that would be taken for many years – perhaps for a lifetime.

If approved by the FDA, the biologic agent would be available as a once-monthly treatment that is injected subcutaneously by a health care professional. Mepolizumab would be marketed by Glaxo Smith Kline under the trade name Nucala. Mepolizumab is a first-in-class humanized monoclonal antibody that targets interleukin-5, a glycoprotein cytokine that mediates production of eosinophils. Elevation of eosinophils in blood and tissue is associated with an increase in cytokines and other inflammatory molecules that can trigger or exacerbate airway inflammation in asthma. One other monoclonal antibody, the anti-IgE biologic omulizimab (Xolair), has been approved to treat asthma. Glaxo Smith Kline brought mepolizumab to the FDA for use as an add-on therapy for the small subset of asthma patients whose disease remains uncontrolled despite the optimal use of inhaled corticosteroids and additional therapies such as leukotriene inhibitors or theophylline. This population experiences more frequent asthma exacerbations, has more emergency department visits and hospitalizations, and uses higher doses of oral corticosteroids. Approximately 60% of those with severe asthma have marked eosinophilia.Panel members uniformly cited the efficacy data for adults with severe asthma; several panelists also remarked on the importance of developing more steroid-sparing alternatives for this population.

The panel endorsed neither efficacy nor safety for those aged 12-17 years, with 9 of the 14 panelists voting not to endorse efficacy and 13 members voting not to endorse safety findings. Mepolizumab’s efficacy, many panelists said, was not clearly established from the data presented, which drew from small numbers of adolescents enrolled in the studies.

Dr. David Au, acting director of Health Services Research and Development at Seattle’s VA Puget Sound Health Care system, observed that “adolescents are not small adults – their lungs continue to mature over time.” Many panelists, however, also called for ongoing study, noting the significant unmet need for steroid alternatives in the adolescent population.

Several panelists advocated postmarketing surveillance for long-term use, with particular attention to those with parasitic disease, to monitoring any sign of malignancy, and to tracking opportunistic diseases such as herpes zoster.

An early clinical trial of mepolizumab, conducted in 1999, failed to show benefit for an undifferentiated population of patients with moderate to severe asthma. However, independent research later identified marked eosinophilia as a factor associated with more frequent asthma exacerbations and a series of clinical trials begun in 2011 targeted patients with severe asthma and eosinophilic inflammation. A global program was initiated, with 12% of patients overall coming from the United States.

Pivotal phase 2b/3, double blind, placebo-controlled clinical trials included a dose-ranging study tracking asthma exacerbations enrolling 616 patients for 52 weeks.

The recommended dose of 100 mg subcutaneously every 4 weeks, as well as a 75-mg IV dose, was used for an additional 576 patients for 32 weeks, with the primary outcome measure being the number of asthma exacerbations. A final 24-week study of 135 patients with severe asthma measured the reduction in oral corticosteroid use, compared with placebo, as well as the number of asthma exacerbations. In all of the studies, patients’ asthma treatment was optimized according to standard of care before adding mepolizumab.

In each study and in pooled data, mepolizumab approximately halved the number of asthma exacerbations for study participants when compared with those using placebo. A 24-week corticosteroid-sparing study showed significant reduction in oral corticosteroid use, without loss of asthma control, for the mepolizumab group. Prespecified subgroup analyses were hampered because of low participation numbers for African Americans and adolescents, and because confidence intervals for these subgroups often ranged over 1, limiting interpretation of benefit results for these groups. The overall safety profile was good, with adverse event rates similar in the treatment and placebo arms. Headache and injection-site reactions were the most commonly reported adverse events but were similar between treatment and placebo arms. No episodes of anaphylaxis were reported, and neutralizing antibodies developed in one patient total across all studies. Ongoing open-label studies continue.The FDA’s independent biostatistical analysis showed clear evidence of efficacy for mepolizumab, with demonstrated consistent, statistically significant decreases of about one exacerbation per year, according to the agency.In its analysis, the agency observed a positive association between higher eosinophil count and mepolizumab treatment effect, meaning that those with higher eosinophil counts saw a greater benefit from mepolizumab, as measured by a reduction in exacerbations.

The number of deaths was balanced across treatment arms, though a larger number of respiratory-related deaths than expected was seen overall. This higher number of deaths may reflect the severity of asthma in the study population. The respiratory-related serious adverse events, according to the FDA, favor treatment over placebo.

No treatment-related cardiovascular risks were identified.

The FDA usually follows the recommendations of its advisory panels. The FDA panelists reported no relevant conflicts of interest.

GAITHERSBURG, MD. – The biologic agent mepolizumab was unanimously recommended for approval as a treatment for severe asthma in adults at a June 4 meeting of the Food and Drug Administration’s Pulmonary-Allergy Drugs Advisory Committee.

All 14 members of the advisory panel agreed that the efficacy data provide substantial evidence of a clinically meaningful benefit of mepolizumab for the treatment of severe asthma in adults; 13 of the 14 members agreed that the data adequately demonstrated safety in adults. However, only four panel members recommended approval for adolescents aged 12-17 years, with the majority of panel members citing concerns that the low number of adolescents studied to date did not allow safety to be adequately evaluated in a younger population, especially for a medication that would be taken for many years – perhaps for a lifetime.

If approved by the FDA, the biologic agent would be available as a once-monthly treatment that is injected subcutaneously by a health care professional. Mepolizumab would be marketed by Glaxo Smith Kline under the trade name Nucala. Mepolizumab is a first-in-class humanized monoclonal antibody that targets interleukin-5, a glycoprotein cytokine that mediates production of eosinophils. Elevation of eosinophils in blood and tissue is associated with an increase in cytokines and other inflammatory molecules that can trigger or exacerbate airway inflammation in asthma. One other monoclonal antibody, the anti-IgE biologic omulizimab (Xolair), has been approved to treat asthma. Glaxo Smith Kline brought mepolizumab to the FDA for use as an add-on therapy for the small subset of asthma patients whose disease remains uncontrolled despite the optimal use of inhaled corticosteroids and additional therapies such as leukotriene inhibitors or theophylline. This population experiences more frequent asthma exacerbations, has more emergency department visits and hospitalizations, and uses higher doses of oral corticosteroids. Approximately 60% of those with severe asthma have marked eosinophilia.Panel members uniformly cited the efficacy data for adults with severe asthma; several panelists also remarked on the importance of developing more steroid-sparing alternatives for this population.

The panel endorsed neither efficacy nor safety for those aged 12-17 years, with 9 of the 14 panelists voting not to endorse efficacy and 13 members voting not to endorse safety findings. Mepolizumab’s efficacy, many panelists said, was not clearly established from the data presented, which drew from small numbers of adolescents enrolled in the studies.

Dr. David Au, acting director of Health Services Research and Development at Seattle’s VA Puget Sound Health Care system, observed that “adolescents are not small adults – their lungs continue to mature over time.” Many panelists, however, also called for ongoing study, noting the significant unmet need for steroid alternatives in the adolescent population.

Several panelists advocated postmarketing surveillance for long-term use, with particular attention to those with parasitic disease, to monitoring any sign of malignancy, and to tracking opportunistic diseases such as herpes zoster.

An early clinical trial of mepolizumab, conducted in 1999, failed to show benefit for an undifferentiated population of patients with moderate to severe asthma. However, independent research later identified marked eosinophilia as a factor associated with more frequent asthma exacerbations and a series of clinical trials begun in 2011 targeted patients with severe asthma and eosinophilic inflammation. A global program was initiated, with 12% of patients overall coming from the United States.

Pivotal phase 2b/3, double blind, placebo-controlled clinical trials included a dose-ranging study tracking asthma exacerbations enrolling 616 patients for 52 weeks.

The recommended dose of 100 mg subcutaneously every 4 weeks, as well as a 75-mg IV dose, was used for an additional 576 patients for 32 weeks, with the primary outcome measure being the number of asthma exacerbations. A final 24-week study of 135 patients with severe asthma measured the reduction in oral corticosteroid use, compared with placebo, as well as the number of asthma exacerbations. In all of the studies, patients’ asthma treatment was optimized according to standard of care before adding mepolizumab.

In each study and in pooled data, mepolizumab approximately halved the number of asthma exacerbations for study participants when compared with those using placebo. A 24-week corticosteroid-sparing study showed significant reduction in oral corticosteroid use, without loss of asthma control, for the mepolizumab group. Prespecified subgroup analyses were hampered because of low participation numbers for African Americans and adolescents, and because confidence intervals for these subgroups often ranged over 1, limiting interpretation of benefit results for these groups. The overall safety profile was good, with adverse event rates similar in the treatment and placebo arms. Headache and injection-site reactions were the most commonly reported adverse events but were similar between treatment and placebo arms. No episodes of anaphylaxis were reported, and neutralizing antibodies developed in one patient total across all studies. Ongoing open-label studies continue.The FDA’s independent biostatistical analysis showed clear evidence of efficacy for mepolizumab, with demonstrated consistent, statistically significant decreases of about one exacerbation per year, according to the agency.In its analysis, the agency observed a positive association between higher eosinophil count and mepolizumab treatment effect, meaning that those with higher eosinophil counts saw a greater benefit from mepolizumab, as measured by a reduction in exacerbations.

The number of deaths was balanced across treatment arms, though a larger number of respiratory-related deaths than expected was seen overall. This higher number of deaths may reflect the severity of asthma in the study population. The respiratory-related serious adverse events, according to the FDA, favor treatment over placebo.

No treatment-related cardiovascular risks were identified.

The FDA usually follows the recommendations of its advisory panels. The FDA panelists reported no relevant conflicts of interest.

GAITHERSBURG, MD. – The biologic agent mepolizumab was unanimously recommended for approval as a treatment for severe asthma in adults at a June 4 meeting of the Food and Drug Administration’s Pulmonary-Allergy Drugs Advisory Committee.

All 14 members of the advisory panel agreed that the efficacy data provide substantial evidence of a clinically meaningful benefit of mepolizumab for the treatment of severe asthma in adults; 13 of the 14 members agreed that the data adequately demonstrated safety in adults. However, only four panel members recommended approval for adolescents aged 12-17 years, with the majority of panel members citing concerns that the low number of adolescents studied to date did not allow safety to be adequately evaluated in a younger population, especially for a medication that would be taken for many years – perhaps for a lifetime.

If approved by the FDA, the biologic agent would be available as a once-monthly treatment that is injected subcutaneously by a health care professional. Mepolizumab would be marketed by Glaxo Smith Kline under the trade name Nucala. Mepolizumab is a first-in-class humanized monoclonal antibody that targets interleukin-5, a glycoprotein cytokine that mediates production of eosinophils. Elevation of eosinophils in blood and tissue is associated with an increase in cytokines and other inflammatory molecules that can trigger or exacerbate airway inflammation in asthma. One other monoclonal antibody, the anti-IgE biologic omulizimab (Xolair), has been approved to treat asthma. Glaxo Smith Kline brought mepolizumab to the FDA for use as an add-on therapy for the small subset of asthma patients whose disease remains uncontrolled despite the optimal use of inhaled corticosteroids and additional therapies such as leukotriene inhibitors or theophylline. This population experiences more frequent asthma exacerbations, has more emergency department visits and hospitalizations, and uses higher doses of oral corticosteroids. Approximately 60% of those with severe asthma have marked eosinophilia.Panel members uniformly cited the efficacy data for adults with severe asthma; several panelists also remarked on the importance of developing more steroid-sparing alternatives for this population.

The panel endorsed neither efficacy nor safety for those aged 12-17 years, with 9 of the 14 panelists voting not to endorse efficacy and 13 members voting not to endorse safety findings. Mepolizumab’s efficacy, many panelists said, was not clearly established from the data presented, which drew from small numbers of adolescents enrolled in the studies.

Dr. David Au, acting director of Health Services Research and Development at Seattle’s VA Puget Sound Health Care system, observed that “adolescents are not small adults – their lungs continue to mature over time.” Many panelists, however, also called for ongoing study, noting the significant unmet need for steroid alternatives in the adolescent population.

Several panelists advocated postmarketing surveillance for long-term use, with particular attention to those with parasitic disease, to monitoring any sign of malignancy, and to tracking opportunistic diseases such as herpes zoster.

An early clinical trial of mepolizumab, conducted in 1999, failed to show benefit for an undifferentiated population of patients with moderate to severe asthma. However, independent research later identified marked eosinophilia as a factor associated with more frequent asthma exacerbations and a series of clinical trials begun in 2011 targeted patients with severe asthma and eosinophilic inflammation. A global program was initiated, with 12% of patients overall coming from the United States.

Pivotal phase 2b/3, double blind, placebo-controlled clinical trials included a dose-ranging study tracking asthma exacerbations enrolling 616 patients for 52 weeks.

The recommended dose of 100 mg subcutaneously every 4 weeks, as well as a 75-mg IV dose, was used for an additional 576 patients for 32 weeks, with the primary outcome measure being the number of asthma exacerbations. A final 24-week study of 135 patients with severe asthma measured the reduction in oral corticosteroid use, compared with placebo, as well as the number of asthma exacerbations. In all of the studies, patients’ asthma treatment was optimized according to standard of care before adding mepolizumab.

In each study and in pooled data, mepolizumab approximately halved the number of asthma exacerbations for study participants when compared with those using placebo. A 24-week corticosteroid-sparing study showed significant reduction in oral corticosteroid use, without loss of asthma control, for the mepolizumab group. Prespecified subgroup analyses were hampered because of low participation numbers for African Americans and adolescents, and because confidence intervals for these subgroups often ranged over 1, limiting interpretation of benefit results for these groups. The overall safety profile was good, with adverse event rates similar in the treatment and placebo arms. Headache and injection-site reactions were the most commonly reported adverse events but were similar between treatment and placebo arms. No episodes of anaphylaxis were reported, and neutralizing antibodies developed in one patient total across all studies. Ongoing open-label studies continue.The FDA’s independent biostatistical analysis showed clear evidence of efficacy for mepolizumab, with demonstrated consistent, statistically significant decreases of about one exacerbation per year, according to the agency.In its analysis, the agency observed a positive association between higher eosinophil count and mepolizumab treatment effect, meaning that those with higher eosinophil counts saw a greater benefit from mepolizumab, as measured by a reduction in exacerbations.

The number of deaths was balanced across treatment arms, though a larger number of respiratory-related deaths than expected was seen overall. This higher number of deaths may reflect the severity of asthma in the study population. The respiratory-related serious adverse events, according to the FDA, favor treatment over placebo.

No treatment-related cardiovascular risks were identified.

The FDA usually follows the recommendations of its advisory panels. The FDA panelists reported no relevant conflicts of interest.

GAITHERSBURG, MD. – The biologic agent mepolizumab was unanimously recommended for approval as a treatment for severe asthma in adults at a June 4 meeting of the Food and Drug Administration’s Pulmonary-Allergy Drugs Advisory Committee.

All 14 members of the advisory panel agreed that the efficacy data provide substantial evidence of a clinically meaningful benefit of mepolizumab for the treatment of severe asthma in adults; 13 of the 14 members agreed that the data adequately demonstrated safety in adults. However, only four panel members recommended approval for adolescents aged 12-17 years, with the majority of panel members citing concerns that the low number of adolescents studied to date did not allow safety to be adequately evaluated in a younger population, especially for a medication that would be taken for many years – perhaps for a lifetime.

If approved by the FDA, the biologic agent would be available as a once-monthly treatment that is injected subcutaneously by a health care professional. Mepolizumab would be marketed by Glaxo Smith Kline under the trade name Nucala. Mepolizumab is a first-in-class humanized monoclonal antibody that targets interleukin-5, a glycoprotein cytokine that mediates production of eosinophils. Elevation of eosinophils in blood and tissue is associated with an increase in cytokines and other inflammatory molecules that can trigger or exacerbate airway inflammation in asthma. One other monoclonal antibody, the anti-IgE biologic omulizimab (Xolair), has been approved to treat asthma. Glaxo Smith Kline brought mepolizumab to the FDA for use as an add-on therapy for the small subset of asthma patients whose disease remains uncontrolled despite the optimal use of inhaled corticosteroids and additional therapies such as leukotriene inhibitors or theophylline. This population experiences more frequent asthma exacerbations, has more emergency department visits and hospitalizations, and uses higher doses of oral corticosteroids. Approximately 60% of those with severe asthma have marked eosinophilia.Panel members uniformly cited the efficacy data for adults with severe asthma; several panelists also remarked on the importance of developing more steroid-sparing alternatives for this population.

The panel endorsed neither efficacy nor safety for those aged 12-17 years, with 9 of the 14 panelists voting not to endorse efficacy and 13 members voting not to endorse safety findings. Mepolizumab’s efficacy, many panelists said, was not clearly established from the data presented, which drew from small numbers of adolescents enrolled in the studies.

Dr. David Au, acting director of Health Services Research and Development at Seattle’s VA Puget Sound Health Care system, observed that “adolescents are not small adults – their lungs continue to mature over time.” Many panelists, however, also called for ongoing study, noting the significant unmet need for steroid alternatives in the adolescent population.

Several panelists advocated postmarketing surveillance for long-term use, with particular attention to those with parasitic disease, to monitoring any sign of malignancy, and to tracking opportunistic diseases such as herpes zoster.

An early clinical trial of mepolizumab, conducted in 1999, failed to show benefit for an undifferentiated population of patients with moderate to severe asthma. However, independent research later identified marked eosinophilia as a factor associated with more frequent asthma exacerbations and a series of clinical trials begun in 2011 targeted patients with severe asthma and eosinophilic inflammation. A global program was initiated, with 12% of patients overall coming from the United States.

Pivotal phase 2b/3, double blind, placebo-controlled clinical trials included a dose-ranging study tracking asthma exacerbations enrolling 616 patients for 52 weeks.

The recommended dose of 100 mg subcutaneously every 4 weeks, as well as a 75-mg IV dose, was used for an additional 576 patients for 32 weeks, with the primary outcome measure being the number of asthma exacerbations. A final 24-week study of 135 patients with severe asthma measured the reduction in oral corticosteroid use, compared with placebo, as well as the number of asthma exacerbations. In all of the studies, patients’ asthma treatment was optimized according to standard of care before adding mepolizumab.

In each study and in pooled data, mepolizumab approximately halved the number of asthma exacerbations for study participants when compared with those using placebo. A 24-week corticosteroid-sparing study showed significant reduction in oral corticosteroid use, without loss of asthma control, for the mepolizumab group. Prespecified subgroup analyses were hampered because of low participation numbers for African Americans and adolescents, and because confidence intervals for these subgroups often ranged over 1, limiting interpretation of benefit results for these groups. The overall safety profile was good, with adverse event rates similar in the treatment and placebo arms. Headache and injection-site reactions were the most commonly reported adverse events but were similar between treatment and placebo arms. No episodes of anaphylaxis were reported, and neutralizing antibodies developed in one patient total across all studies. Ongoing open-label studies continue.The FDA’s independent biostatistical analysis showed clear evidence of efficacy for mepolizumab, with demonstrated consistent, statistically significant decreases of about one exacerbation per year, according to the agency.In its analysis, the agency observed a positive association between higher eosinophil count and mepolizumab treatment effect, meaning that those with higher eosinophil counts saw a greater benefit from mepolizumab, as measured by a reduction in exacerbations.

The number of deaths was balanced across treatment arms, though a larger number of respiratory-related deaths than expected was seen overall. This higher number of deaths may reflect the severity of asthma in the study population. The respiratory-related serious adverse events, according to the FDA, favor treatment over placebo.

No treatment-related cardiovascular risks were identified.

The FDA usually follows the recommendations of its advisory panels. The FDA panelists reported no relevant conflicts of interest.

GAITHERSBURG, MD. – The biologic agent mepolizumab was unanimously recommended for approval as a treatment for severe asthma in adults at a June 4 meeting of the Food and Drug Administration’s Pulmonary-Allergy Drugs Advisory Committee.

All 14 members of the advisory panel agreed that the efficacy data provide substantial evidence of a clinically meaningful benefit of mepolizumab for the treatment of severe asthma in adults; 13 of the 14 members agreed that the data adequately demonstrated safety in adults. However, only four panel members recommended approval for adolescents aged 12-17 years, with the majority of panel members citing concerns that the low number of adolescents studied to date did not allow safety to be adequately evaluated in a younger population, especially for a medication that would be taken for many years – perhaps for a lifetime.

If approved by the FDA, the biologic agent would be available as a once-monthly treatment that is injected subcutaneously by a health care professional. Mepolizumab would be marketed by Glaxo Smith Kline under the trade name Nucala. Mepolizumab is a first-in-class humanized monoclonal antibody that targets interleukin-5, a glycoprotein cytokine that mediates production of eosinophils. Elevation of eosinophils in blood and tissue is associated with an increase in cytokines and other inflammatory molecules that can trigger or exacerbate airway inflammation in asthma. One other monoclonal antibody, the anti-IgE biologic omulizimab (Xolair), has been approved to treat asthma. Glaxo Smith Kline brought mepolizumab to the FDA for use as an add-on therapy for the small subset of asthma patients whose disease remains uncontrolled despite the optimal use of inhaled corticosteroids and additional therapies such as leukotriene inhibitors or theophylline. This population experiences more frequent asthma exacerbations, has more emergency department visits and hospitalizations, and uses higher doses of oral corticosteroids. Approximately 60% of those with severe asthma have marked eosinophilia.Panel members uniformly cited the efficacy data for adults with severe asthma; several panelists also remarked on the importance of developing more steroid-sparing alternatives for this population.

The panel endorsed neither efficacy nor safety for those aged 12-17 years, with 9 of the 14 panelists voting not to endorse efficacy and 13 members voting not to endorse safety findings. Mepolizumab’s efficacy, many panelists said, was not clearly established from the data presented, which drew from small numbers of adolescents enrolled in the studies.

Dr. David Au, acting director of Health Services Research and Development at Seattle’s VA Puget Sound Health Care system, observed that “adolescents are not small adults – their lungs continue to mature over time.” Many panelists, however, also called for ongoing study, noting the significant unmet need for steroid alternatives in the adolescent population.

Several panelists advocated postmarketing surveillance for long-term use, with particular attention to those with parasitic disease, to monitoring any sign of malignancy, and to tracking opportunistic diseases such as herpes zoster.

An early clinical trial of mepolizumab, conducted in 1999, failed to show benefit for an undifferentiated population of patients with moderate to severe asthma. However, independent research later identified marked eosinophilia as a factor associated with more frequent asthma exacerbations and a series of clinical trials begun in 2011 targeted patients with severe asthma and eosinophilic inflammation. A global program was initiated, with 12% of patients overall coming from the United States.

Pivotal phase 2b/3, double blind, placebo-controlled clinical trials included a dose-ranging study tracking asthma exacerbations enrolling 616 patients for 52 weeks.

The recommended dose of 100 mg subcutaneously every 4 weeks, as well as a 75-mg IV dose, was used for an additional 576 patients for 32 weeks, with the primary outcome measure being the number of asthma exacerbations. A final 24-week study of 135 patients with severe asthma measured the reduction in oral corticosteroid use, compared with placebo, as well as the number of asthma exacerbations. In all of the studies, patients’ asthma treatment was optimized according to standard of care before adding mepolizumab.

In each study and in pooled data, mepolizumab approximately halved the number of asthma exacerbations for study participants when compared with those using placebo. A 24-week corticosteroid-sparing study showed significant reduction in oral corticosteroid use, without loss of asthma control, for the mepolizumab group. Prespecified subgroup analyses were hampered because of low participation numbers for African Americans and adolescents, and because confidence intervals for these subgroups often ranged over 1, limiting interpretation of benefit results for these groups. The overall safety profile was good, with adverse event rates similar in the treatment and placebo arms. Headache and injection-site reactions were the most commonly reported adverse events but were similar between treatment and placebo arms. No episodes of anaphylaxis were reported, and neutralizing antibodies developed in one patient total across all studies. Ongoing open-label studies continue.The FDA’s independent biostatistical analysis showed clear evidence of efficacy for mepolizumab, with demonstrated consistent, statistically significant decreases of about one exacerbation per year, according to the agency.In its analysis, the agency observed a positive association between higher eosinophil count and mepolizumab treatment effect, meaning that those with higher eosinophil counts saw a greater benefit from mepolizumab, as measured by a reduction in exacerbations.

The number of deaths was balanced across treatment arms, though a larger number of respiratory-related deaths than expected was seen overall. This higher number of deaths may reflect the severity of asthma in the study population. The respiratory-related serious adverse events, according to the FDA, favor treatment over placebo.

No treatment-related cardiovascular risks were identified.

The FDA usually follows the recommendations of its advisory panels. The FDA panelists reported no relevant conflicts of interest.

DENVER – The rate of asthma exacerbations was reduced more among elderly patients than among younger patients treated with mepolizumab vs. placebo as part of the Mepolizumab as Adjunctive Therapy in Patients with Severe Asthma (MENSA) trial, according to a post hoc analysis of the trial data.

The analysis also demonstrated that mepolizumab improved quality of life, compared with standard care, in both older and younger patients, although little differentiation was seen with respect to asthma control, Dr. Hector Ortega reported in a poster at an international conference of the American Thoracic Society.

A 76% greater reduction in clinically significant exacerbations was seen in 54 mepolizumab-treated patients aged 65 years and older in the trial, compared with 26 in that age group who received placebo (mean exacerbation rate per year, 0.92 vs. 1.65); a 44% greater reduction was seen in 331 mepolizumab-treated patients under age 65 years, compared with 165 in that age group who received placebo (mean exacerbation rate per year, 0.42 vs. 1.78), said Dr. Ortega, medical director at GlaxoSmithKline, Research Triangle Park, N.C.

The adjusted mean difference vs. placebo in change in St. George’s Respiratory Questionnaire scores from baseline to 32 weeks was -4.5 in the older patients, and -7.3 in the younger patients, and the adjusted mean difference vs. placebo in change in Asthma Control Questionnaire scores from baseline to 32 weeks was -0.1 and -0.5 in the older and younger patients, respectively, he noted.

The older patients, as expected, suffered more frequently from comorbidities, and this may have been accentuated by the chronic use of inhaled and oral corticosteroids in the older patients.

However, comorbidities had no impact on the response to treatment, and the safety profile of mepolizumab was similar to placebo in both age groups, he said.

Patients in the multicenter, randomized, placebo-controlled MENSA trial received high dose inhaled corticosteroids plus at least one additional controller, had a history of frequent exacerbations and a predefined eosinophilic threshold, and were randomized to receive add-on therapy with either 75 mg of intravenous mepolizumab, 100 mg subcutaneous mepolizumab, or corresponding placebo every 4 weeks for 32 weeks. In the primary planned analysis, the responses to the two doses of mepolizumab were similar, but efficacy in older patients had not been previously reported.

The MENSA trial and post hoc analysis were funded by GSK. Dr. Ortega is employed by GSK.

[email protected]

DENVER – The rate of asthma exacerbations was reduced more among elderly patients than among younger patients treated with mepolizumab vs. placebo as part of the Mepolizumab as Adjunctive Therapy in Patients with Severe Asthma (MENSA) trial, according to a post hoc analysis of the trial data.

The analysis also demonstrated that mepolizumab improved quality of life, compared with standard care, in both older and younger patients, although little differentiation was seen with respect to asthma control, Dr. Hector Ortega reported in a poster at an international conference of the American Thoracic Society.

A 76% greater reduction in clinically significant exacerbations was seen in 54 mepolizumab-treated patients aged 65 years and older in the trial, compared with 26 in that age group who received placebo (mean exacerbation rate per year, 0.92 vs. 1.65); a 44% greater reduction was seen in 331 mepolizumab-treated patients under age 65 years, compared with 165 in that age group who received placebo (mean exacerbation rate per year, 0.42 vs. 1.78), said Dr. Ortega, medical director at GlaxoSmithKline, Research Triangle Park, N.C.

The adjusted mean difference vs. placebo in change in St. George’s Respiratory Questionnaire scores from baseline to 32 weeks was -4.5 in the older patients, and -7.3 in the younger patients, and the adjusted mean difference vs. placebo in change in Asthma Control Questionnaire scores from baseline to 32 weeks was -0.1 and -0.5 in the older and younger patients, respectively, he noted.

The older patients, as expected, suffered more frequently from comorbidities, and this may have been accentuated by the chronic use of inhaled and oral corticosteroids in the older patients.

However, comorbidities had no impact on the response to treatment, and the safety profile of mepolizumab was similar to placebo in both age groups, he said.

Patients in the multicenter, randomized, placebo-controlled MENSA trial received high dose inhaled corticosteroids plus at least one additional controller, had a history of frequent exacerbations and a predefined eosinophilic threshold, and were randomized to receive add-on therapy with either 75 mg of intravenous mepolizumab, 100 mg subcutaneous mepolizumab, or corresponding placebo every 4 weeks for 32 weeks. In the primary planned analysis, the responses to the two doses of mepolizumab were similar, but efficacy in older patients had not been previously reported.

The MENSA trial and post hoc analysis were funded by GSK. Dr. Ortega is employed by GSK.

[email protected]

DENVER – The rate of asthma exacerbations was reduced more among elderly patients than among younger patients treated with mepolizumab vs. placebo as part of the Mepolizumab as Adjunctive Therapy in Patients with Severe Asthma (MENSA) trial, according to a post hoc analysis of the trial data.

The analysis also demonstrated that mepolizumab improved quality of life, compared with standard care, in both older and younger patients, although little differentiation was seen with respect to asthma control, Dr. Hector Ortega reported in a poster at an international conference of the American Thoracic Society.

A 76% greater reduction in clinically significant exacerbations was seen in 54 mepolizumab-treated patients aged 65 years and older in the trial, compared with 26 in that age group who received placebo (mean exacerbation rate per year, 0.92 vs. 1.65); a 44% greater reduction was seen in 331 mepolizumab-treated patients under age 65 years, compared with 165 in that age group who received placebo (mean exacerbation rate per year, 0.42 vs. 1.78), said Dr. Ortega, medical director at GlaxoSmithKline, Research Triangle Park, N.C.

The adjusted mean difference vs. placebo in change in St. George’s Respiratory Questionnaire scores from baseline to 32 weeks was -4.5 in the older patients, and -7.3 in the younger patients, and the adjusted mean difference vs. placebo in change in Asthma Control Questionnaire scores from baseline to 32 weeks was -0.1 and -0.5 in the older and younger patients, respectively, he noted.

The older patients, as expected, suffered more frequently from comorbidities, and this may have been accentuated by the chronic use of inhaled and oral corticosteroids in the older patients.

However, comorbidities had no impact on the response to treatment, and the safety profile of mepolizumab was similar to placebo in both age groups, he said.

Patients in the multicenter, randomized, placebo-controlled MENSA trial received high dose inhaled corticosteroids plus at least one additional controller, had a history of frequent exacerbations and a predefined eosinophilic threshold, and were randomized to receive add-on therapy with either 75 mg of intravenous mepolizumab, 100 mg subcutaneous mepolizumab, or corresponding placebo every 4 weeks for 32 weeks. In the primary planned analysis, the responses to the two doses of mepolizumab were similar, but efficacy in older patients had not been previously reported.

The MENSA trial and post hoc analysis were funded by GSK. Dr. Ortega is employed by GSK.

[email protected]

The Advisory Committee on Immunization Practices (ACIP) recommends the serogroup B meningitis (MenB) vaccine for individuals at increased risk for meningococcal disease aged 10 years or older, according to a report published in the June 12 Morbidity and Mortality Weekly Report.

The guideline recommends the MenB vaccine for persons with persistent complement component deficiencies, persons with anatomic or functional asplenia, microbiologists regularly exposed to isolates of Neisseria meningitidis, and persons identified at increased risk because of a serogroup B meningococcal disease outbreak.

The recommendations were revised following recent Food and Drug Administration approval of two MenB vaccines: Trumenba, approved in October 2014, and Bexsero, approved in January 2015. Both MenB vaccines are approved for use in people aged 10-25 years, but are not currently recommended for routine use in first-year college students living in residence halls, in adolescents, or in military recruits.

MenB vaccine should be administered as either a three-dose series of Trumenba or a two-dose series of Bexsero. The same vaccine product should be used for all doses, according to ACIP.

“Recommendations for broader use of MenB vaccines in adolescents and college students will be considered separately by the ACIP,” the report said.

Read more in this week’s MMWR.

The Advisory Committee on Immunization Practices (ACIP) recommends the serogroup B meningitis (MenB) vaccine for individuals at increased risk for meningococcal disease aged 10 years or older, according to a report published in the June 12 Morbidity and Mortality Weekly Report.

The guideline recommends the MenB vaccine for persons with persistent complement component deficiencies, persons with anatomic or functional asplenia, microbiologists regularly exposed to isolates of Neisseria meningitidis, and persons identified at increased risk because of a serogroup B meningococcal disease outbreak.

The recommendations were revised following recent Food and Drug Administration approval of two MenB vaccines: Trumenba, approved in October 2014, and Bexsero, approved in January 2015. Both MenB vaccines are approved for use in people aged 10-25 years, but are not currently recommended for routine use in first-year college students living in residence halls, in adolescents, or in military recruits.

MenB vaccine should be administered as either a three-dose series of Trumenba or a two-dose series of Bexsero. The same vaccine product should be used for all doses, according to ACIP.

“Recommendations for broader use of MenB vaccines in adolescents and college students will be considered separately by the ACIP,” the report said.

Read more in this week’s MMWR.

The Advisory Committee on Immunization Practices (ACIP) recommends the serogroup B meningitis (MenB) vaccine for individuals at increased risk for meningococcal disease aged 10 years or older, according to a report published in the June 12 Morbidity and Mortality Weekly Report.

The guideline recommends the MenB vaccine for persons with persistent complement component deficiencies, persons with anatomic or functional asplenia, microbiologists regularly exposed to isolates of Neisseria meningitidis, and persons identified at increased risk because of a serogroup B meningococcal disease outbreak.

The recommendations were revised following recent Food and Drug Administration approval of two MenB vaccines: Trumenba, approved in October 2014, and Bexsero, approved in January 2015. Both MenB vaccines are approved for use in people aged 10-25 years, but are not currently recommended for routine use in first-year college students living in residence halls, in adolescents, or in military recruits.

MenB vaccine should be administered as either a three-dose series of Trumenba or a two-dose series of Bexsero. The same vaccine product should be used for all doses, according to ACIP.

“Recommendations for broader use of MenB vaccines in adolescents and college students will be considered separately by the ACIP,” the report said.

Read more in this week’s MMWR.