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Multiple linear subcutaneous nodules
A 34-year-old woman sought consultation at our clinic for an asymptomatic swelling on her right foot that had been growing very slowly over the last 15 years. She said she had presented to other healthcare facilities, but no diagnosis had been made and no treatment had been offered.
Examination revealed a linear swelling extending from the lower third to the mid-dorsal surface of the right foot (Figure 1). Palpation revealed multiple, closely set nodules arranged in a linear fashion. This finding along with the history raised the suspicion of neurofibroma and other conditions in the differential diagnosis, eg, pure neuritic Hansen disease, phaeohyphomycosis, and palisaded neutrophilic granulomatous dermatitis. The rest of the mucocutaneous examination results were normal. No café-au-lait spots, axillary freckling, or other swelling suggestive of neurofibroma was seen. She had no family history of mucocutaneous disease or other systemic disorder.
Because of the suspicion of neurofibromatosis, slit-lamp examination of the eyes was done to rule out Lisch nodules, a common feature of neurofibromatosis; the results were normal. Plain radiography of the right foot showed only soft-tissue swelling. Magnetic resonance imaging with contrast, done to determine the extent of the lesions, revealed multiple dumbbell-shaped lesions with homogeneous enhancement (Figure 2). Histopathologic study of a biopsy specimen of the lesions showed tumor cells in the dermis. The cells were long, with elongated nuclei with pointed ends, arranged in long and short fascicles—an appearance characteristic of neurofibroma. Areas of hypocellularity and hypercellularity were seen, and on S100 protein immunostaining, the tumor cells showed strong nuclear and cytoplasmic positivity (Figure 3).
The histologic evaluation confirmed neurofibroma. The specific diagnosis of sporadic solitary neurofibroma was made based on the onset of the lesions, the number of lesions (one in this patient), and the absence of features suggestive of neurofibromatosis.
SPORADIC SOLITARY NEUROFIBROMA
Neurofibroma is a common tumor of the peripheral nerve sheath and, when present with features such as café-au-lait spots, axillary freckling, and characteristic bone changes, it is pathognomic of neurofibromatosis type 1.1 But solitary neurofibromas can occur sporadically in the absence of other features of neurofibromatosis.
Sporadic solitary neurofibroma arises from small nerves, is benign in nature, and carries a lower rate of malignant transformation than its counterpart that occurs in the setting of neurofibromatosis.2 Though sporadic solitary neurofibroma can occur in any part of the body, it is commonly seen on the head and neck, and occasionally on the presacral and parasacral space, thigh, intrascrotal area,3 the ankle and foot,4,5 and the subungual region.6 A series of 397 peripheral neural sheath tumors examined over 30 years showed 55 sporadic solitary neurofibromas occurring in the brachial plexus region, 45 in the upper extremities, 10 in the pelvic plexus, and 31 in the lower extremities.7
Management of sporadic solitary neurofibroma depends on the patient’s discomfort. For asymptomatic lesions, serial observation is all that is required. Complete surgical excision including the parent nerve is the treatment for large lesions. More research is needed to define the potential role of drugs such as pirfenidone and tipifarnib.
THE DIFFERENTIAL DIAGNOSIS
Sporadic solitary neurofibroma can masquerade as pure neuritic Hansen disease (leprosy), phaeohyphomycosis, and palisaded neutrophilic granulomatous dermatitis. The absence of neural symptoms and no evidence of trophic changes exclude pure neuritic Hansen disease. Phaeohyphomycosis clinically presents as a single cyst that may evolve into pigmented plaques,8 and the diagnosis relies on the presence of fungus in tissue. The absence of cystic changes clinically and fungi histopathologically in this patient did not favor phaeohyphomycosis. Palisaded neutrophilic granulomatous dermatitis is characterized clinically by cordlike skin lesions (the “rope sign”) and is accompanied by extracutaneous, mostly articular features. Histopathologically, it shows intense neutrophilic infiltrate and interstitial histiocytic infiltrate along with collagen degeneration. The absence of extracutaneous and classical histologic features negated this possibility in this patient.
Though sporotrichosis and cutaneous atypical mycobacterial infections may present in linear fashion following the course of the lymphatic vessels, the absence of epidermal changes after a disease course of 15 years and the absence of granulomatous infiltrate in histopathology excluded these possibilities in this patient.
The patient was referred to a plastic surgeon, and the lesions were successfully resected. She did not return for additional review after that.
- Hirbe AC, Gutmann DH. Neurofibromatosis type 1: a multidisciplinary approach to care. Lancet Neurol 2014; 13:834–843.
- Pulathan Z, Imamoglu M, Cay A, Guven YK. Intermittent claudication due to right common femoral artery compression by a solitary neurofibroma. Eur J Pediatr 2005; 164:463–465.
- Hosseini MM, Geramizadeh B, Shakeri S, Karimi MH. Intrascrotal solitary neurofibroma: a case report and review of the literature. Urol Ann 2012; 4:119–121.
- Carvajal JA, Cuartas E, Qadir R, Levi AD, Temple HT. Peripheral nerve sheath tumors of the foot and ankle. Foot Ankle Int 2011; 32:163–167.
- Tahririan MA, Hekmatnia A, Ahrar H, Heidarpour M, Hekmatnia F. Solitary giant neurofibroma of thigh. Adv Biomed Res 2014; 3:158.
- Huajun J, Wei Q, Ming L, Chongyang F, Weiguo Z, Decheng L. Solitary subungual neurofibroma in the right first finger. Int J Dermatol 2012; 51:335–338.
- Kim DH, Murovic JA, Tiel RL, Moes G, Kline DG. A series of 397 peripheral neural sheath tumors: 30-year experience at Louisiana State University Health Sciences Center. J Neurosurg 2005; 102:246–255.
- Garnica M, Nucci M, Queiroz-Telles F. Difficult mycoses of the skin: advances in the epidemiology and management of eumycetoma, phaeohyphomycosis and chromoblastomycosis. Curr Opin Infect Dis 2009; 22:559–563.
A 34-year-old woman sought consultation at our clinic for an asymptomatic swelling on her right foot that had been growing very slowly over the last 15 years. She said she had presented to other healthcare facilities, but no diagnosis had been made and no treatment had been offered.
Examination revealed a linear swelling extending from the lower third to the mid-dorsal surface of the right foot (Figure 1). Palpation revealed multiple, closely set nodules arranged in a linear fashion. This finding along with the history raised the suspicion of neurofibroma and other conditions in the differential diagnosis, eg, pure neuritic Hansen disease, phaeohyphomycosis, and palisaded neutrophilic granulomatous dermatitis. The rest of the mucocutaneous examination results were normal. No café-au-lait spots, axillary freckling, or other swelling suggestive of neurofibroma was seen. She had no family history of mucocutaneous disease or other systemic disorder.
Because of the suspicion of neurofibromatosis, slit-lamp examination of the eyes was done to rule out Lisch nodules, a common feature of neurofibromatosis; the results were normal. Plain radiography of the right foot showed only soft-tissue swelling. Magnetic resonance imaging with contrast, done to determine the extent of the lesions, revealed multiple dumbbell-shaped lesions with homogeneous enhancement (Figure 2). Histopathologic study of a biopsy specimen of the lesions showed tumor cells in the dermis. The cells were long, with elongated nuclei with pointed ends, arranged in long and short fascicles—an appearance characteristic of neurofibroma. Areas of hypocellularity and hypercellularity were seen, and on S100 protein immunostaining, the tumor cells showed strong nuclear and cytoplasmic positivity (Figure 3).
The histologic evaluation confirmed neurofibroma. The specific diagnosis of sporadic solitary neurofibroma was made based on the onset of the lesions, the number of lesions (one in this patient), and the absence of features suggestive of neurofibromatosis.
SPORADIC SOLITARY NEUROFIBROMA
Neurofibroma is a common tumor of the peripheral nerve sheath and, when present with features such as café-au-lait spots, axillary freckling, and characteristic bone changes, it is pathognomic of neurofibromatosis type 1.1 But solitary neurofibromas can occur sporadically in the absence of other features of neurofibromatosis.
Sporadic solitary neurofibroma arises from small nerves, is benign in nature, and carries a lower rate of malignant transformation than its counterpart that occurs in the setting of neurofibromatosis.2 Though sporadic solitary neurofibroma can occur in any part of the body, it is commonly seen on the head and neck, and occasionally on the presacral and parasacral space, thigh, intrascrotal area,3 the ankle and foot,4,5 and the subungual region.6 A series of 397 peripheral neural sheath tumors examined over 30 years showed 55 sporadic solitary neurofibromas occurring in the brachial plexus region, 45 in the upper extremities, 10 in the pelvic plexus, and 31 in the lower extremities.7
Management of sporadic solitary neurofibroma depends on the patient’s discomfort. For asymptomatic lesions, serial observation is all that is required. Complete surgical excision including the parent nerve is the treatment for large lesions. More research is needed to define the potential role of drugs such as pirfenidone and tipifarnib.
THE DIFFERENTIAL DIAGNOSIS
Sporadic solitary neurofibroma can masquerade as pure neuritic Hansen disease (leprosy), phaeohyphomycosis, and palisaded neutrophilic granulomatous dermatitis. The absence of neural symptoms and no evidence of trophic changes exclude pure neuritic Hansen disease. Phaeohyphomycosis clinically presents as a single cyst that may evolve into pigmented plaques,8 and the diagnosis relies on the presence of fungus in tissue. The absence of cystic changes clinically and fungi histopathologically in this patient did not favor phaeohyphomycosis. Palisaded neutrophilic granulomatous dermatitis is characterized clinically by cordlike skin lesions (the “rope sign”) and is accompanied by extracutaneous, mostly articular features. Histopathologically, it shows intense neutrophilic infiltrate and interstitial histiocytic infiltrate along with collagen degeneration. The absence of extracutaneous and classical histologic features negated this possibility in this patient.
Though sporotrichosis and cutaneous atypical mycobacterial infections may present in linear fashion following the course of the lymphatic vessels, the absence of epidermal changes after a disease course of 15 years and the absence of granulomatous infiltrate in histopathology excluded these possibilities in this patient.
The patient was referred to a plastic surgeon, and the lesions were successfully resected. She did not return for additional review after that.
A 34-year-old woman sought consultation at our clinic for an asymptomatic swelling on her right foot that had been growing very slowly over the last 15 years. She said she had presented to other healthcare facilities, but no diagnosis had been made and no treatment had been offered.
Examination revealed a linear swelling extending from the lower third to the mid-dorsal surface of the right foot (Figure 1). Palpation revealed multiple, closely set nodules arranged in a linear fashion. This finding along with the history raised the suspicion of neurofibroma and other conditions in the differential diagnosis, eg, pure neuritic Hansen disease, phaeohyphomycosis, and palisaded neutrophilic granulomatous dermatitis. The rest of the mucocutaneous examination results were normal. No café-au-lait spots, axillary freckling, or other swelling suggestive of neurofibroma was seen. She had no family history of mucocutaneous disease or other systemic disorder.
Because of the suspicion of neurofibromatosis, slit-lamp examination of the eyes was done to rule out Lisch nodules, a common feature of neurofibromatosis; the results were normal. Plain radiography of the right foot showed only soft-tissue swelling. Magnetic resonance imaging with contrast, done to determine the extent of the lesions, revealed multiple dumbbell-shaped lesions with homogeneous enhancement (Figure 2). Histopathologic study of a biopsy specimen of the lesions showed tumor cells in the dermis. The cells were long, with elongated nuclei with pointed ends, arranged in long and short fascicles—an appearance characteristic of neurofibroma. Areas of hypocellularity and hypercellularity were seen, and on S100 protein immunostaining, the tumor cells showed strong nuclear and cytoplasmic positivity (Figure 3).
The histologic evaluation confirmed neurofibroma. The specific diagnosis of sporadic solitary neurofibroma was made based on the onset of the lesions, the number of lesions (one in this patient), and the absence of features suggestive of neurofibromatosis.
SPORADIC SOLITARY NEUROFIBROMA
Neurofibroma is a common tumor of the peripheral nerve sheath and, when present with features such as café-au-lait spots, axillary freckling, and characteristic bone changes, it is pathognomic of neurofibromatosis type 1.1 But solitary neurofibromas can occur sporadically in the absence of other features of neurofibromatosis.
Sporadic solitary neurofibroma arises from small nerves, is benign in nature, and carries a lower rate of malignant transformation than its counterpart that occurs in the setting of neurofibromatosis.2 Though sporadic solitary neurofibroma can occur in any part of the body, it is commonly seen on the head and neck, and occasionally on the presacral and parasacral space, thigh, intrascrotal area,3 the ankle and foot,4,5 and the subungual region.6 A series of 397 peripheral neural sheath tumors examined over 30 years showed 55 sporadic solitary neurofibromas occurring in the brachial plexus region, 45 in the upper extremities, 10 in the pelvic plexus, and 31 in the lower extremities.7
Management of sporadic solitary neurofibroma depends on the patient’s discomfort. For asymptomatic lesions, serial observation is all that is required. Complete surgical excision including the parent nerve is the treatment for large lesions. More research is needed to define the potential role of drugs such as pirfenidone and tipifarnib.
THE DIFFERENTIAL DIAGNOSIS
Sporadic solitary neurofibroma can masquerade as pure neuritic Hansen disease (leprosy), phaeohyphomycosis, and palisaded neutrophilic granulomatous dermatitis. The absence of neural symptoms and no evidence of trophic changes exclude pure neuritic Hansen disease. Phaeohyphomycosis clinically presents as a single cyst that may evolve into pigmented plaques,8 and the diagnosis relies on the presence of fungus in tissue. The absence of cystic changes clinically and fungi histopathologically in this patient did not favor phaeohyphomycosis. Palisaded neutrophilic granulomatous dermatitis is characterized clinically by cordlike skin lesions (the “rope sign”) and is accompanied by extracutaneous, mostly articular features. Histopathologically, it shows intense neutrophilic infiltrate and interstitial histiocytic infiltrate along with collagen degeneration. The absence of extracutaneous and classical histologic features negated this possibility in this patient.
Though sporotrichosis and cutaneous atypical mycobacterial infections may present in linear fashion following the course of the lymphatic vessels, the absence of epidermal changes after a disease course of 15 years and the absence of granulomatous infiltrate in histopathology excluded these possibilities in this patient.
The patient was referred to a plastic surgeon, and the lesions were successfully resected. She did not return for additional review after that.
- Hirbe AC, Gutmann DH. Neurofibromatosis type 1: a multidisciplinary approach to care. Lancet Neurol 2014; 13:834–843.
- Pulathan Z, Imamoglu M, Cay A, Guven YK. Intermittent claudication due to right common femoral artery compression by a solitary neurofibroma. Eur J Pediatr 2005; 164:463–465.
- Hosseini MM, Geramizadeh B, Shakeri S, Karimi MH. Intrascrotal solitary neurofibroma: a case report and review of the literature. Urol Ann 2012; 4:119–121.
- Carvajal JA, Cuartas E, Qadir R, Levi AD, Temple HT. Peripheral nerve sheath tumors of the foot and ankle. Foot Ankle Int 2011; 32:163–167.
- Tahririan MA, Hekmatnia A, Ahrar H, Heidarpour M, Hekmatnia F. Solitary giant neurofibroma of thigh. Adv Biomed Res 2014; 3:158.
- Huajun J, Wei Q, Ming L, Chongyang F, Weiguo Z, Decheng L. Solitary subungual neurofibroma in the right first finger. Int J Dermatol 2012; 51:335–338.
- Kim DH, Murovic JA, Tiel RL, Moes G, Kline DG. A series of 397 peripheral neural sheath tumors: 30-year experience at Louisiana State University Health Sciences Center. J Neurosurg 2005; 102:246–255.
- Garnica M, Nucci M, Queiroz-Telles F. Difficult mycoses of the skin: advances in the epidemiology and management of eumycetoma, phaeohyphomycosis and chromoblastomycosis. Curr Opin Infect Dis 2009; 22:559–563.
- Hirbe AC, Gutmann DH. Neurofibromatosis type 1: a multidisciplinary approach to care. Lancet Neurol 2014; 13:834–843.
- Pulathan Z, Imamoglu M, Cay A, Guven YK. Intermittent claudication due to right common femoral artery compression by a solitary neurofibroma. Eur J Pediatr 2005; 164:463–465.
- Hosseini MM, Geramizadeh B, Shakeri S, Karimi MH. Intrascrotal solitary neurofibroma: a case report and review of the literature. Urol Ann 2012; 4:119–121.
- Carvajal JA, Cuartas E, Qadir R, Levi AD, Temple HT. Peripheral nerve sheath tumors of the foot and ankle. Foot Ankle Int 2011; 32:163–167.
- Tahririan MA, Hekmatnia A, Ahrar H, Heidarpour M, Hekmatnia F. Solitary giant neurofibroma of thigh. Adv Biomed Res 2014; 3:158.
- Huajun J, Wei Q, Ming L, Chongyang F, Weiguo Z, Decheng L. Solitary subungual neurofibroma in the right first finger. Int J Dermatol 2012; 51:335–338.
- Kim DH, Murovic JA, Tiel RL, Moes G, Kline DG. A series of 397 peripheral neural sheath tumors: 30-year experience at Louisiana State University Health Sciences Center. J Neurosurg 2005; 102:246–255.
- Garnica M, Nucci M, Queiroz-Telles F. Difficult mycoses of the skin: advances in the epidemiology and management of eumycetoma, phaeohyphomycosis and chromoblastomycosis. Curr Opin Infect Dis 2009; 22:559–563.
Lebrikizumab boosts lung function in asthma
LOS ANGELES – The investigational interleukin-13 inhibitor lebrikizumab provides a clinically meaningful improvement in measures of lung function within 1 week after the first dose in patients with moderate-to-severe uncontrolled asthma on standard-of-care therapy and a high baseline serum periostin level, Dr. Jonathan Corren reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.
He presented a post hoc analysis of three phase II randomized trials of lebrikizumab as add-on therapy in a total of 558 patients with uncontrolled asthma while on a moderate- or high-dose inhaled corticosteroid plus at least one other controller medication, most often a long-acting beta agonist. The post hoc analysis included 333 asthma patients who received lebrikizumab subcutaneously at 125 or 250 mg every 4 weeks for 12 weeks and 225 who got placebo. Baseline serum periostin levels were 50 ng/mL or higher in 252 participants.
One week after the first dose of lebrikizumab, the high serum periostin group demonstrated a placebo-subtracted mean 147-mL improvement from baseline in pre-bronchodilator forced expiratory volume in 1 second (FEV1). The week 1 improvement in FEV1 with lebrikizumab in the low serum periostin group was more modest: a placebo-subtracted 57 mL.
The response to lebrikizumab was maintained through 12 weeks of once-monthly therapy, with a mean placebo-subtracted week 12 improvement in FEV1 of 198 mL in the high-periostin group, compared with 74 mL in low-periostin patients. The lebrikizumab-treated group with high baseline periostin had a 16% improvement from baseline in FEV1 as compared with a 5% improvement in placebo-treated patients with high periostin.
The three trials were known by the acronyms MILLY, LUTE, and VERSE. Dr. Corren was first author of the MILLY study (N Engl J Med. 2011 Sep 22;365(12):1088-98), which was the initial report that lebrikizumab performed markedly better in patients with uncontrolled asthma and a high baseline serum periostin – a biomarker for IL-13 activity – and that periostin was a better predictor of response to lebrikizumab than either blood eosinophil count or serum IgE.
The new pooled post hoc analysis was performed to boost sample size and confirm the key MILLY findings, as well as to more closely examine the speed of improvement in airflow in response to therapy, said Dr. Corren of the University of California, Los Angeles.
Lebrikizumab is an IgG4 humanized monoclonal antibody that binds to IL-13 with high affinity. Its efficacy in the phase II trials confirms the importance of IL-13 as a mediator of disease activity in a subset of asthma patients with activation of Type 2 lymphocytes.
“We know specifically that IL-13 has some very important effects in asthma, including upregulation of adhesion molecules that allow eosinophils to stick in the lung, as well as promoting hyperplasia of smooth muscle and mucus cell hyperplasia with increased mucus secretion. Immunologically, it allows switching from IgM to IgE on the surface of B cells. So IL-13 is a cytokine that literally makes people atopic,” Dr. Corren explained in an interview.
Several ongoing phase III randomized trials of lebrikizumab in adults with uncontrolled asthma despite standard-of-care therapy are due to be completed in the first half of 2017. A phase III trial in adolescents is also underway.
Dr. Corren reported receiving research funding from Roche/Genentech, which sponsored the studies.
LOS ANGELES – The investigational interleukin-13 inhibitor lebrikizumab provides a clinically meaningful improvement in measures of lung function within 1 week after the first dose in patients with moderate-to-severe uncontrolled asthma on standard-of-care therapy and a high baseline serum periostin level, Dr. Jonathan Corren reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.
He presented a post hoc analysis of three phase II randomized trials of lebrikizumab as add-on therapy in a total of 558 patients with uncontrolled asthma while on a moderate- or high-dose inhaled corticosteroid plus at least one other controller medication, most often a long-acting beta agonist. The post hoc analysis included 333 asthma patients who received lebrikizumab subcutaneously at 125 or 250 mg every 4 weeks for 12 weeks and 225 who got placebo. Baseline serum periostin levels were 50 ng/mL or higher in 252 participants.
One week after the first dose of lebrikizumab, the high serum periostin group demonstrated a placebo-subtracted mean 147-mL improvement from baseline in pre-bronchodilator forced expiratory volume in 1 second (FEV1). The week 1 improvement in FEV1 with lebrikizumab in the low serum periostin group was more modest: a placebo-subtracted 57 mL.
The response to lebrikizumab was maintained through 12 weeks of once-monthly therapy, with a mean placebo-subtracted week 12 improvement in FEV1 of 198 mL in the high-periostin group, compared with 74 mL in low-periostin patients. The lebrikizumab-treated group with high baseline periostin had a 16% improvement from baseline in FEV1 as compared with a 5% improvement in placebo-treated patients with high periostin.
The three trials were known by the acronyms MILLY, LUTE, and VERSE. Dr. Corren was first author of the MILLY study (N Engl J Med. 2011 Sep 22;365(12):1088-98), which was the initial report that lebrikizumab performed markedly better in patients with uncontrolled asthma and a high baseline serum periostin – a biomarker for IL-13 activity – and that periostin was a better predictor of response to lebrikizumab than either blood eosinophil count or serum IgE.
The new pooled post hoc analysis was performed to boost sample size and confirm the key MILLY findings, as well as to more closely examine the speed of improvement in airflow in response to therapy, said Dr. Corren of the University of California, Los Angeles.
Lebrikizumab is an IgG4 humanized monoclonal antibody that binds to IL-13 with high affinity. Its efficacy in the phase II trials confirms the importance of IL-13 as a mediator of disease activity in a subset of asthma patients with activation of Type 2 lymphocytes.
“We know specifically that IL-13 has some very important effects in asthma, including upregulation of adhesion molecules that allow eosinophils to stick in the lung, as well as promoting hyperplasia of smooth muscle and mucus cell hyperplasia with increased mucus secretion. Immunologically, it allows switching from IgM to IgE on the surface of B cells. So IL-13 is a cytokine that literally makes people atopic,” Dr. Corren explained in an interview.
Several ongoing phase III randomized trials of lebrikizumab in adults with uncontrolled asthma despite standard-of-care therapy are due to be completed in the first half of 2017. A phase III trial in adolescents is also underway.
Dr. Corren reported receiving research funding from Roche/Genentech, which sponsored the studies.
LOS ANGELES – The investigational interleukin-13 inhibitor lebrikizumab provides a clinically meaningful improvement in measures of lung function within 1 week after the first dose in patients with moderate-to-severe uncontrolled asthma on standard-of-care therapy and a high baseline serum periostin level, Dr. Jonathan Corren reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.
He presented a post hoc analysis of three phase II randomized trials of lebrikizumab as add-on therapy in a total of 558 patients with uncontrolled asthma while on a moderate- or high-dose inhaled corticosteroid plus at least one other controller medication, most often a long-acting beta agonist. The post hoc analysis included 333 asthma patients who received lebrikizumab subcutaneously at 125 or 250 mg every 4 weeks for 12 weeks and 225 who got placebo. Baseline serum periostin levels were 50 ng/mL or higher in 252 participants.
One week after the first dose of lebrikizumab, the high serum periostin group demonstrated a placebo-subtracted mean 147-mL improvement from baseline in pre-bronchodilator forced expiratory volume in 1 second (FEV1). The week 1 improvement in FEV1 with lebrikizumab in the low serum periostin group was more modest: a placebo-subtracted 57 mL.
The response to lebrikizumab was maintained through 12 weeks of once-monthly therapy, with a mean placebo-subtracted week 12 improvement in FEV1 of 198 mL in the high-periostin group, compared with 74 mL in low-periostin patients. The lebrikizumab-treated group with high baseline periostin had a 16% improvement from baseline in FEV1 as compared with a 5% improvement in placebo-treated patients with high periostin.
The three trials were known by the acronyms MILLY, LUTE, and VERSE. Dr. Corren was first author of the MILLY study (N Engl J Med. 2011 Sep 22;365(12):1088-98), which was the initial report that lebrikizumab performed markedly better in patients with uncontrolled asthma and a high baseline serum periostin – a biomarker for IL-13 activity – and that periostin was a better predictor of response to lebrikizumab than either blood eosinophil count or serum IgE.
The new pooled post hoc analysis was performed to boost sample size and confirm the key MILLY findings, as well as to more closely examine the speed of improvement in airflow in response to therapy, said Dr. Corren of the University of California, Los Angeles.
Lebrikizumab is an IgG4 humanized monoclonal antibody that binds to IL-13 with high affinity. Its efficacy in the phase II trials confirms the importance of IL-13 as a mediator of disease activity in a subset of asthma patients with activation of Type 2 lymphocytes.
“We know specifically that IL-13 has some very important effects in asthma, including upregulation of adhesion molecules that allow eosinophils to stick in the lung, as well as promoting hyperplasia of smooth muscle and mucus cell hyperplasia with increased mucus secretion. Immunologically, it allows switching from IgM to IgE on the surface of B cells. So IL-13 is a cytokine that literally makes people atopic,” Dr. Corren explained in an interview.
Several ongoing phase III randomized trials of lebrikizumab in adults with uncontrolled asthma despite standard-of-care therapy are due to be completed in the first half of 2017. A phase III trial in adolescents is also underway.
Dr. Corren reported receiving research funding from Roche/Genentech, which sponsored the studies.
AT 2016 AAAAI ANNUAL MEETING
Key clinical point: Lebrikizumab shows promise for treatment of patients with moderate-to-severe type 2 lymphocyte-mediated asthma.
Major finding: One week after patients with uncontrolled asthma and a high baseline serum periostin level received their first dose of lebrikizumab, they demonstrated a mean 16% improvement over baseline in forced expiratory volume in 1 second.
Data source: This was a post hoc analysis of three phase II, randomized, placebo-controlled clinical trials totaling 558 patients with moderate-to-severe uncontrolled asthma while on standard of care therapy.
Disclosures: The study presenter reported receiving research funding from Roche/Genentech, which is developing lebrikizumab.
Fungi May Exacerbate Asthma, Chronic Sinusitis
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.
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.
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.
AT AAAAI
Fungi may exacerbate asthma, chronic sinusitis
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.
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.
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.
AT AAAAI
Key clinical point: Consider antifungal therapy if asthma or chronic sinusitis patients don’t respond well to conventional treatment.
Major finding: 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.
Data source: A single-center case review.
Disclosures: The investigators had no relevant financial disclosures, and there was no outside funding for the work.
Crisaborole’s safety holds up in long-term atopic dermatitis trial
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.
AT THE 2016 SID ANNUAL MEETING
Key clinical point: The topical phosphodiesterase-4 inhibitor crisaborole was safe and well tolerated for up to 48 weeks in patients with mild-to-moderate atopic dermatitis.
Major finding: The most common treatment–related adverse events were atopic dermatitis flare (3%), stinging and burning at the application site (2%), and application site infection (1%). None were serious.
Data source: A single-arm, multicenter, open-label, 48-week extension study of 517 patients with mild-to-moderate atopic dermatitis.
Disclosures: 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.
Yoga Improves Asthmatics’ Quality of Life, Data Review Suggests
Yoga seems to improve the quality of life and symptoms of people with asthma, suggests a review of 15 randomized controlled trials comprising 1,048 patients with varying degrees of asthma severity.
The studies generally compared the outcomes for asthma patients participating in at least 2 weeks of yoga with the outcomes for those who were treated with usual care for asthma, a sham intervention, or no intervention.
Average improvements in the Asthma Quality of Life Questionnaire scores of 0.57 units per item on a 7-point scale were found through an analysis of responses from 375 individuals, with each person having participated in one of the five randomized controlled trials (RCTs). While the average increase exceeded the minimal clinically important difference (MCID) for this questionnaire, outcomes of two of the trials raise questions about whether the reported improvements in patients’ quality of life can be attributed to yoga. In those two trials, which included a placebo or sham intervention for some of the participants, no differences in these questionnaire scores were found following the interventions.
For 243 asthma patients who participated in three of the RCTs, on average, yoga improved their symptoms by 0.37 standard deviation units of the disease severity scores used.
“Our findings are preliminary and suggestive, rather than conclusive, and therefore should be interpreted cautiously. Yoga probably improves quality of life and symptoms in people with asthma to some extent. However, whether or not the improvements in symptoms exceed the MCID is uncertain due to lack of an established MCID for the severity scores used in the included studies,” noted Zu-Yao Yang of the Chinese University of Hong Kong, and colleagues.
They used various methods to collect data, including searching the Cochrane Airways Group Register of Trials, which is derived from systematic searches of bibliographic databases, and hand-searching respiratory journals and meeting abstracts. They searched all databases from their inception to July 22, 2015, and placed no restriction on language of publication. All studies were parallel-group trials, except for one cross-over trial.
While two of the studies reported adverse events, four of the studies reported having investigated the occurrences of such types of incidents. One of the studies said three participants in its control group required oral steroids because of acute exacerbations of their asthma, but that these adverse events could not be counted as having been caused by yoga. Another study showed that one participant in its yoga group, who used the Pink City Lung Exerciser (a medical device used to mimic the typical patterns of yoga breathing), reported mild dyspnea during the exercise.
“[As] the included studies were mostly small in sample size and at high risk of bias, high-quality RCTs with large sample sizes are needed to confirm the effects of yoga,” the researchers said.
They reported that they had no known declarations of interest. The project was supported by the National Institute for Health Research, via Cochrane Infrastructure funding to the Cochrane Airways Group.
The full review is available in the Cochrane Database of Systematic Reviews (doi: 10.1002/14651858.CD010346.pub2).
Yoga seems to improve the quality of life and symptoms of people with asthma, suggests a review of 15 randomized controlled trials comprising 1,048 patients with varying degrees of asthma severity.
The studies generally compared the outcomes for asthma patients participating in at least 2 weeks of yoga with the outcomes for those who were treated with usual care for asthma, a sham intervention, or no intervention.
Average improvements in the Asthma Quality of Life Questionnaire scores of 0.57 units per item on a 7-point scale were found through an analysis of responses from 375 individuals, with each person having participated in one of the five randomized controlled trials (RCTs). While the average increase exceeded the minimal clinically important difference (MCID) for this questionnaire, outcomes of two of the trials raise questions about whether the reported improvements in patients’ quality of life can be attributed to yoga. In those two trials, which included a placebo or sham intervention for some of the participants, no differences in these questionnaire scores were found following the interventions.
For 243 asthma patients who participated in three of the RCTs, on average, yoga improved their symptoms by 0.37 standard deviation units of the disease severity scores used.
“Our findings are preliminary and suggestive, rather than conclusive, and therefore should be interpreted cautiously. Yoga probably improves quality of life and symptoms in people with asthma to some extent. However, whether or not the improvements in symptoms exceed the MCID is uncertain due to lack of an established MCID for the severity scores used in the included studies,” noted Zu-Yao Yang of the Chinese University of Hong Kong, and colleagues.
They used various methods to collect data, including searching the Cochrane Airways Group Register of Trials, which is derived from systematic searches of bibliographic databases, and hand-searching respiratory journals and meeting abstracts. They searched all databases from their inception to July 22, 2015, and placed no restriction on language of publication. All studies were parallel-group trials, except for one cross-over trial.
While two of the studies reported adverse events, four of the studies reported having investigated the occurrences of such types of incidents. One of the studies said three participants in its control group required oral steroids because of acute exacerbations of their asthma, but that these adverse events could not be counted as having been caused by yoga. Another study showed that one participant in its yoga group, who used the Pink City Lung Exerciser (a medical device used to mimic the typical patterns of yoga breathing), reported mild dyspnea during the exercise.
“[As] the included studies were mostly small in sample size and at high risk of bias, high-quality RCTs with large sample sizes are needed to confirm the effects of yoga,” the researchers said.
They reported that they had no known declarations of interest. The project was supported by the National Institute for Health Research, via Cochrane Infrastructure funding to the Cochrane Airways Group.
The full review is available in the Cochrane Database of Systematic Reviews (doi: 10.1002/14651858.CD010346.pub2).
Yoga seems to improve the quality of life and symptoms of people with asthma, suggests a review of 15 randomized controlled trials comprising 1,048 patients with varying degrees of asthma severity.
The studies generally compared the outcomes for asthma patients participating in at least 2 weeks of yoga with the outcomes for those who were treated with usual care for asthma, a sham intervention, or no intervention.
Average improvements in the Asthma Quality of Life Questionnaire scores of 0.57 units per item on a 7-point scale were found through an analysis of responses from 375 individuals, with each person having participated in one of the five randomized controlled trials (RCTs). While the average increase exceeded the minimal clinically important difference (MCID) for this questionnaire, outcomes of two of the trials raise questions about whether the reported improvements in patients’ quality of life can be attributed to yoga. In those two trials, which included a placebo or sham intervention for some of the participants, no differences in these questionnaire scores were found following the interventions.
For 243 asthma patients who participated in three of the RCTs, on average, yoga improved their symptoms by 0.37 standard deviation units of the disease severity scores used.
“Our findings are preliminary and suggestive, rather than conclusive, and therefore should be interpreted cautiously. Yoga probably improves quality of life and symptoms in people with asthma to some extent. However, whether or not the improvements in symptoms exceed the MCID is uncertain due to lack of an established MCID for the severity scores used in the included studies,” noted Zu-Yao Yang of the Chinese University of Hong Kong, and colleagues.
They used various methods to collect data, including searching the Cochrane Airways Group Register of Trials, which is derived from systematic searches of bibliographic databases, and hand-searching respiratory journals and meeting abstracts. They searched all databases from their inception to July 22, 2015, and placed no restriction on language of publication. All studies were parallel-group trials, except for one cross-over trial.
While two of the studies reported adverse events, four of the studies reported having investigated the occurrences of such types of incidents. One of the studies said three participants in its control group required oral steroids because of acute exacerbations of their asthma, but that these adverse events could not be counted as having been caused by yoga. Another study showed that one participant in its yoga group, who used the Pink City Lung Exerciser (a medical device used to mimic the typical patterns of yoga breathing), reported mild dyspnea during the exercise.
“[As] the included studies were mostly small in sample size and at high risk of bias, high-quality RCTs with large sample sizes are needed to confirm the effects of yoga,” the researchers said.
They reported that they had no known declarations of interest. The project was supported by the National Institute for Health Research, via Cochrane Infrastructure funding to the Cochrane Airways Group.
The full review is available in the Cochrane Database of Systematic Reviews (doi: 10.1002/14651858.CD010346.pub2).
FROM THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS
Yoga improves asthmatics’ quality of life, data review suggests
Yoga seems to improve the quality of life and symptoms of people with asthma, suggests a review of 15 randomized controlled trials comprising 1,048 patients with varying degrees of asthma severity.
The studies generally compared the outcomes for asthma patients participating in at least 2 weeks of yoga with the outcomes for those who were treated with usual care for asthma, a sham intervention, or no intervention.
Average improvements in the Asthma Quality of Life Questionnaire scores of 0.57 units per item on a 7-point scale were found through an analysis of responses from 375 individuals, with each person having participated in one of the five randomized controlled trials (RCTs). While the average increase exceeded the minimal clinically important difference (MCID) for this questionnaire, outcomes of two of the trials raise questions about whether the reported improvements in patients’ quality of life can be attributed to yoga. In those two trials, which included a placebo or sham intervention for some of the participants, no differences in these questionnaire scores were found following the interventions.
For 243 asthma patients who participated in three of the RCTs, on average, yoga improved their symptoms by 0.37 standard deviation units of the disease severity scores used.
“Our findings are preliminary and suggestive, rather than conclusive, and therefore should be interpreted cautiously. Yoga probably improves quality of life and symptoms in people with asthma to some extent. However, whether or not the improvements in symptoms exceed the MCID is uncertain due to lack of an established MCID for the severity scores used in the included studies,” noted Zu-Yao Yang of the Chinese University of Hong Kong, and colleagues.
They used various methods to collect data, including searching the Cochrane Airways Group Register of Trials, which is derived from systematic searches of bibliographic databases, and hand-searching respiratory journals and meeting abstracts. They searched all databases from their inception to July 22, 2015, and placed no restriction on language of publication. All studies were parallel-group trials, except for one cross-over trial.
While two of the studies reported adverse events, four of the studies reported having investigated the occurrences of such types of incidents. One of the studies said three participants in its control group required oral steroids because of acute exacerbations of their asthma, but that these adverse events could not be counted as having been caused by yoga. Another study showed that one participant in its yoga group, who used the Pink City Lung Exerciser (a medical device used to mimic the typical patterns of yoga breathing), reported mild dyspnea during the exercise.
“[As] the included studies were mostly small in sample size and at high risk of bias, high-quality RCTs with large sample sizes are needed to confirm the effects of yoga,” the researchers said.
They reported that they had no known declarations of interest. The project was supported by the National Institute for Health Research, via Cochrane Infrastructure funding to the Cochrane Airways Group.
The full review is available in the Cochrane Database of Systematic Reviews (doi: 10.1002/14651858.CD010346.pub2).
Yoga seems to improve the quality of life and symptoms of people with asthma, suggests a review of 15 randomized controlled trials comprising 1,048 patients with varying degrees of asthma severity.
The studies generally compared the outcomes for asthma patients participating in at least 2 weeks of yoga with the outcomes for those who were treated with usual care for asthma, a sham intervention, or no intervention.
Average improvements in the Asthma Quality of Life Questionnaire scores of 0.57 units per item on a 7-point scale were found through an analysis of responses from 375 individuals, with each person having participated in one of the five randomized controlled trials (RCTs). While the average increase exceeded the minimal clinically important difference (MCID) for this questionnaire, outcomes of two of the trials raise questions about whether the reported improvements in patients’ quality of life can be attributed to yoga. In those two trials, which included a placebo or sham intervention for some of the participants, no differences in these questionnaire scores were found following the interventions.
For 243 asthma patients who participated in three of the RCTs, on average, yoga improved their symptoms by 0.37 standard deviation units of the disease severity scores used.
“Our findings are preliminary and suggestive, rather than conclusive, and therefore should be interpreted cautiously. Yoga probably improves quality of life and symptoms in people with asthma to some extent. However, whether or not the improvements in symptoms exceed the MCID is uncertain due to lack of an established MCID for the severity scores used in the included studies,” noted Zu-Yao Yang of the Chinese University of Hong Kong, and colleagues.
They used various methods to collect data, including searching the Cochrane Airways Group Register of Trials, which is derived from systematic searches of bibliographic databases, and hand-searching respiratory journals and meeting abstracts. They searched all databases from their inception to July 22, 2015, and placed no restriction on language of publication. All studies were parallel-group trials, except for one cross-over trial.
While two of the studies reported adverse events, four of the studies reported having investigated the occurrences of such types of incidents. One of the studies said three participants in its control group required oral steroids because of acute exacerbations of their asthma, but that these adverse events could not be counted as having been caused by yoga. Another study showed that one participant in its yoga group, who used the Pink City Lung Exerciser (a medical device used to mimic the typical patterns of yoga breathing), reported mild dyspnea during the exercise.
“[As] the included studies were mostly small in sample size and at high risk of bias, high-quality RCTs with large sample sizes are needed to confirm the effects of yoga,” the researchers said.
They reported that they had no known declarations of interest. The project was supported by the National Institute for Health Research, via Cochrane Infrastructure funding to the Cochrane Airways Group.
The full review is available in the Cochrane Database of Systematic Reviews (doi: 10.1002/14651858.CD010346.pub2).
Yoga seems to improve the quality of life and symptoms of people with asthma, suggests a review of 15 randomized controlled trials comprising 1,048 patients with varying degrees of asthma severity.
The studies generally compared the outcomes for asthma patients participating in at least 2 weeks of yoga with the outcomes for those who were treated with usual care for asthma, a sham intervention, or no intervention.
Average improvements in the Asthma Quality of Life Questionnaire scores of 0.57 units per item on a 7-point scale were found through an analysis of responses from 375 individuals, with each person having participated in one of the five randomized controlled trials (RCTs). While the average increase exceeded the minimal clinically important difference (MCID) for this questionnaire, outcomes of two of the trials raise questions about whether the reported improvements in patients’ quality of life can be attributed to yoga. In those two trials, which included a placebo or sham intervention for some of the participants, no differences in these questionnaire scores were found following the interventions.
For 243 asthma patients who participated in three of the RCTs, on average, yoga improved their symptoms by 0.37 standard deviation units of the disease severity scores used.
“Our findings are preliminary and suggestive, rather than conclusive, and therefore should be interpreted cautiously. Yoga probably improves quality of life and symptoms in people with asthma to some extent. However, whether or not the improvements in symptoms exceed the MCID is uncertain due to lack of an established MCID for the severity scores used in the included studies,” noted Zu-Yao Yang of the Chinese University of Hong Kong, and colleagues.
They used various methods to collect data, including searching the Cochrane Airways Group Register of Trials, which is derived from systematic searches of bibliographic databases, and hand-searching respiratory journals and meeting abstracts. They searched all databases from their inception to July 22, 2015, and placed no restriction on language of publication. All studies were parallel-group trials, except for one cross-over trial.
While two of the studies reported adverse events, four of the studies reported having investigated the occurrences of such types of incidents. One of the studies said three participants in its control group required oral steroids because of acute exacerbations of their asthma, but that these adverse events could not be counted as having been caused by yoga. Another study showed that one participant in its yoga group, who used the Pink City Lung Exerciser (a medical device used to mimic the typical patterns of yoga breathing), reported mild dyspnea during the exercise.
“[As] the included studies were mostly small in sample size and at high risk of bias, high-quality RCTs with large sample sizes are needed to confirm the effects of yoga,” the researchers said.
They reported that they had no known declarations of interest. The project was supported by the National Institute for Health Research, via Cochrane Infrastructure funding to the Cochrane Airways Group.
The full review is available in the Cochrane Database of Systematic Reviews (doi: 10.1002/14651858.CD010346.pub2).
FROM THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS
Azithromycin Fails to Ameliorate Treatment-resistant Cough
Azithromycin does not appear to be an effective agent for those with treatment-resistant cough, but may be useful in treating those with comorbid asthma, according to the results of a study published in Chest.
David Hodgson, Ph.D., from the Nottingham Respiratory Research Unit at the University of Nottingham (England), and colleagues conducted an 8-week randomized, double-blind, placebo-controlled parallel group trial with follow-up visits at 4, 8, and 12 weeks to determine whether treatment with low-dose azithromycin would affect the Leicester Cough Questionnaire (LCQ) score, cough severity on a visual analog scale, and fraction of exhaled nitric oxide (FENO) in patients with treatment-resistant chronic cough. (Chest. 2016 Apr;149[4]:1052-60. doi: 10.1016/j.chest.2015.12.036).
The study included 40 nonsmoking patients who were being investigated for chronic cough in respiratory clinics at Nottingham University Hospitals National Health Service Trust in the United Kingdom. Twenty patients were randomized to receive azithromycin capsules 500 mg daily for 3 days, followed by 250 mg three times a week for 8 weeks, and 20 received lactose-containing placebo capsules taken according to the same dosing schedule. The primary outcome measure was change from baseline in LCQ score at week 8.
The study results suggested differences in the primary endpoint in response to treatment with azithromycin; however, statistical significance was not detected after adjusting for baseline values. Ancillary analyses suggested that study subjects with asthma treated with azithromycin exhibited a large and statistically significant improvement in LCQ score when compared with those treated with placebo. This difference was detected at 4 weeks and was statistically significant at the end of the 8-week trial and at all follow-ups. There were no significant changes in FENO levels between any groups in this study, and treatment was considered to be well tolerated.
Based on their data, Dr. Hodgson and colleagues said that their results were not supportive of the routine use of low-dose macrolides in patients with treatment-resistant chronic cough. They also noted that data from their ancillary analyses were suggestive of an association between azithromycin treatment and improvement in LCQ in those with chronic cough and coexisting asthma that could be a focus of additional research.
Funding for this project was provided by a National Institute for Health Research Biomedical Research Fellowship. The authors reported no conflicts of interest.
Azithromycin does not appear to be an effective agent for those with treatment-resistant cough, but may be useful in treating those with comorbid asthma, according to the results of a study published in Chest.
David Hodgson, Ph.D., from the Nottingham Respiratory Research Unit at the University of Nottingham (England), and colleagues conducted an 8-week randomized, double-blind, placebo-controlled parallel group trial with follow-up visits at 4, 8, and 12 weeks to determine whether treatment with low-dose azithromycin would affect the Leicester Cough Questionnaire (LCQ) score, cough severity on a visual analog scale, and fraction of exhaled nitric oxide (FENO) in patients with treatment-resistant chronic cough. (Chest. 2016 Apr;149[4]:1052-60. doi: 10.1016/j.chest.2015.12.036).
The study included 40 nonsmoking patients who were being investigated for chronic cough in respiratory clinics at Nottingham University Hospitals National Health Service Trust in the United Kingdom. Twenty patients were randomized to receive azithromycin capsules 500 mg daily for 3 days, followed by 250 mg three times a week for 8 weeks, and 20 received lactose-containing placebo capsules taken according to the same dosing schedule. The primary outcome measure was change from baseline in LCQ score at week 8.
The study results suggested differences in the primary endpoint in response to treatment with azithromycin; however, statistical significance was not detected after adjusting for baseline values. Ancillary analyses suggested that study subjects with asthma treated with azithromycin exhibited a large and statistically significant improvement in LCQ score when compared with those treated with placebo. This difference was detected at 4 weeks and was statistically significant at the end of the 8-week trial and at all follow-ups. There were no significant changes in FENO levels between any groups in this study, and treatment was considered to be well tolerated.
Based on their data, Dr. Hodgson and colleagues said that their results were not supportive of the routine use of low-dose macrolides in patients with treatment-resistant chronic cough. They also noted that data from their ancillary analyses were suggestive of an association between azithromycin treatment and improvement in LCQ in those with chronic cough and coexisting asthma that could be a focus of additional research.
Funding for this project was provided by a National Institute for Health Research Biomedical Research Fellowship. The authors reported no conflicts of interest.
Azithromycin does not appear to be an effective agent for those with treatment-resistant cough, but may be useful in treating those with comorbid asthma, according to the results of a study published in Chest.
David Hodgson, Ph.D., from the Nottingham Respiratory Research Unit at the University of Nottingham (England), and colleagues conducted an 8-week randomized, double-blind, placebo-controlled parallel group trial with follow-up visits at 4, 8, and 12 weeks to determine whether treatment with low-dose azithromycin would affect the Leicester Cough Questionnaire (LCQ) score, cough severity on a visual analog scale, and fraction of exhaled nitric oxide (FENO) in patients with treatment-resistant chronic cough. (Chest. 2016 Apr;149[4]:1052-60. doi: 10.1016/j.chest.2015.12.036).
The study included 40 nonsmoking patients who were being investigated for chronic cough in respiratory clinics at Nottingham University Hospitals National Health Service Trust in the United Kingdom. Twenty patients were randomized to receive azithromycin capsules 500 mg daily for 3 days, followed by 250 mg three times a week for 8 weeks, and 20 received lactose-containing placebo capsules taken according to the same dosing schedule. The primary outcome measure was change from baseline in LCQ score at week 8.
The study results suggested differences in the primary endpoint in response to treatment with azithromycin; however, statistical significance was not detected after adjusting for baseline values. Ancillary analyses suggested that study subjects with asthma treated with azithromycin exhibited a large and statistically significant improvement in LCQ score when compared with those treated with placebo. This difference was detected at 4 weeks and was statistically significant at the end of the 8-week trial and at all follow-ups. There were no significant changes in FENO levels between any groups in this study, and treatment was considered to be well tolerated.
Based on their data, Dr. Hodgson and colleagues said that their results were not supportive of the routine use of low-dose macrolides in patients with treatment-resistant chronic cough. They also noted that data from their ancillary analyses were suggestive of an association between azithromycin treatment and improvement in LCQ in those with chronic cough and coexisting asthma that could be a focus of additional research.
Funding for this project was provided by a National Institute for Health Research Biomedical Research Fellowship. The authors reported no conflicts of interest.
FROM CHEST
Azithromycin fails to ameliorate treatment-resistant cough
Azithromycin does not appear to be an effective agent for those with treatment-resistant cough, but may be useful in treating those with comorbid asthma, according to the results of a study published in Chest.
David Hodgson, Ph.D., from the Nottingham Respiratory Research Unit at the University of Nottingham (England), and colleagues conducted an 8-week randomized, double-blind, placebo-controlled parallel group trial with follow-up visits at 4, 8, and 12 weeks to determine whether treatment with low-dose azithromycin would affect the Leicester Cough Questionnaire (LCQ) score, cough severity on a visual analog scale, and fraction of exhaled nitric oxide (FENO) in patients with treatment-resistant chronic cough. (Chest. 2016 Apr;149[4]:1052-60. doi: 10.1016/j.chest.2015.12.036).
The study included 40 nonsmoking patients who were being investigated for chronic cough in respiratory clinics at Nottingham University Hospitals National Health Service Trust in the United Kingdom. Twenty patients were randomized to receive azithromycin capsules 500 mg daily for 3 days, followed by 250 mg three times a week for 8 weeks, and 20 received lactose-containing placebo capsules taken according to the same dosing schedule. The primary outcome measure was change from baseline in LCQ score at week 8.
The study results suggested differences in the primary endpoint in response to treatment with azithromycin; however, statistical significance was not detected after adjusting for baseline values. Ancillary analyses suggested that study subjects with asthma treated with azithromycin exhibited a large and statistically significant improvement in LCQ score when compared with those treated with placebo. This difference was detected at 4 weeks and was statistically significant at the end of the 8-week trial and at all follow-ups. There were no significant changes in FENO levels between any groups in this study, and treatment was considered to be well tolerated.
Based on their data, Dr. Hodgson and colleagues said that their results were not supportive of the routine use of low-dose macrolides in patients with treatment-resistant chronic cough. They also noted that data from their ancillary analyses were suggestive of an association between azithromycin treatment and improvement in LCQ in those with chronic cough and coexisting asthma that could be a focus of additional research.
Funding for this project was provided by a National Institute for Health Research Biomedical Research Fellowship. The authors reported no conflicts of interest.
Azithromycin does not appear to be an effective agent for those with treatment-resistant cough, but may be useful in treating those with comorbid asthma, according to the results of a study published in Chest.
David Hodgson, Ph.D., from the Nottingham Respiratory Research Unit at the University of Nottingham (England), and colleagues conducted an 8-week randomized, double-blind, placebo-controlled parallel group trial with follow-up visits at 4, 8, and 12 weeks to determine whether treatment with low-dose azithromycin would affect the Leicester Cough Questionnaire (LCQ) score, cough severity on a visual analog scale, and fraction of exhaled nitric oxide (FENO) in patients with treatment-resistant chronic cough. (Chest. 2016 Apr;149[4]:1052-60. doi: 10.1016/j.chest.2015.12.036).
The study included 40 nonsmoking patients who were being investigated for chronic cough in respiratory clinics at Nottingham University Hospitals National Health Service Trust in the United Kingdom. Twenty patients were randomized to receive azithromycin capsules 500 mg daily for 3 days, followed by 250 mg three times a week for 8 weeks, and 20 received lactose-containing placebo capsules taken according to the same dosing schedule. The primary outcome measure was change from baseline in LCQ score at week 8.
The study results suggested differences in the primary endpoint in response to treatment with azithromycin; however, statistical significance was not detected after adjusting for baseline values. Ancillary analyses suggested that study subjects with asthma treated with azithromycin exhibited a large and statistically significant improvement in LCQ score when compared with those treated with placebo. This difference was detected at 4 weeks and was statistically significant at the end of the 8-week trial and at all follow-ups. There were no significant changes in FENO levels between any groups in this study, and treatment was considered to be well tolerated.
Based on their data, Dr. Hodgson and colleagues said that their results were not supportive of the routine use of low-dose macrolides in patients with treatment-resistant chronic cough. They also noted that data from their ancillary analyses were suggestive of an association between azithromycin treatment and improvement in LCQ in those with chronic cough and coexisting asthma that could be a focus of additional research.
Funding for this project was provided by a National Institute for Health Research Biomedical Research Fellowship. The authors reported no conflicts of interest.
Azithromycin does not appear to be an effective agent for those with treatment-resistant cough, but may be useful in treating those with comorbid asthma, according to the results of a study published in Chest.
David Hodgson, Ph.D., from the Nottingham Respiratory Research Unit at the University of Nottingham (England), and colleagues conducted an 8-week randomized, double-blind, placebo-controlled parallel group trial with follow-up visits at 4, 8, and 12 weeks to determine whether treatment with low-dose azithromycin would affect the Leicester Cough Questionnaire (LCQ) score, cough severity on a visual analog scale, and fraction of exhaled nitric oxide (FENO) in patients with treatment-resistant chronic cough. (Chest. 2016 Apr;149[4]:1052-60. doi: 10.1016/j.chest.2015.12.036).
The study included 40 nonsmoking patients who were being investigated for chronic cough in respiratory clinics at Nottingham University Hospitals National Health Service Trust in the United Kingdom. Twenty patients were randomized to receive azithromycin capsules 500 mg daily for 3 days, followed by 250 mg three times a week for 8 weeks, and 20 received lactose-containing placebo capsules taken according to the same dosing schedule. The primary outcome measure was change from baseline in LCQ score at week 8.
The study results suggested differences in the primary endpoint in response to treatment with azithromycin; however, statistical significance was not detected after adjusting for baseline values. Ancillary analyses suggested that study subjects with asthma treated with azithromycin exhibited a large and statistically significant improvement in LCQ score when compared with those treated with placebo. This difference was detected at 4 weeks and was statistically significant at the end of the 8-week trial and at all follow-ups. There were no significant changes in FENO levels between any groups in this study, and treatment was considered to be well tolerated.
Based on their data, Dr. Hodgson and colleagues said that their results were not supportive of the routine use of low-dose macrolides in patients with treatment-resistant chronic cough. They also noted that data from their ancillary analyses were suggestive of an association between azithromycin treatment and improvement in LCQ in those with chronic cough and coexisting asthma that could be a focus of additional research.
Funding for this project was provided by a National Institute for Health Research Biomedical Research Fellowship. The authors reported no conflicts of interest.
FROM CHEST
Key clinical point: This study did not support the clinical efficacy of low-dose macrolides for patients with treatment-resistant chronic cough.
Major finding: Leicester Cough Questionnaire scores did not differ significantly between the azithromycin and placebo groups after 8 weeks of treatment.
Data sources: Patients being investigated for chronic cough identified from respiratory clinics at Nottingham University Hospitals National Health Service Trust in the United Kingdom between July 2009 and August 2012.
Disclosures: Funding for this project was provided by a National Institute for Health Research Biomedical Research Fellowship. The authors reported no conflicts of interest.
Novel device therapy shows continued benefits in pediatric peanut allergy
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.
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.
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.
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.
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.
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.
AT 2016 AAAAI ANNUAL MEETING
Key clinical point: A peanut protein–bearing skin patch shows favorable efficacy and safety as a treatment for peanut allergy, especially in children.
Major finding: After 1 year using the Viaskin Peanut device at the 250-mcg dose, one-third of formerly peanut-allergic children tolerated at least 1,000 mg of peanut protein in an oral food challenge; after 2 years using the patch, the rate increased to 60%.
Data source: Ongoing 2-year, open-label extension of the yearlong, double-blind, randomized VIPES trial of 171 peanut-allergic subjects aged 6-55 years.
Disclosures: The study was funded by DBV Technologies and presented by the company’s chief scientific officer.
