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FDA approves tezepelumab-ekko (Tezspire) for severe asthma
The Food and Drug Administration has approved tezepelumab-ekko (Tezspire) as a first-in-class treatment for severe asthma in adults and pediatric patients aged 12 years and older. It is not recommended for the relief of acute bronchospasm or status asthmaticus.
Tezepelumab-ekko is a human monoclonal antibody that acts as a thymic stromal lymphopoietin (TSLP) blocker. TSLP is an epithelial cell–derived cytokine implicated in the pathogenesis of asthma. Tezepelumab-ekko is administered by subcutaneous injection at a recommended dosage of 210 mg given once every 4 weeks.
“Tezspire represents a much-needed new treatment for the many patients who remain underserved and continue to struggle with severe, uncontrolled asthma,” said professor Andrew Menzies-Gow, MD, PhD, director of the lung division, Royal Brompton Hospital, London, and the principal investigator of the pivotal NAVIGATOR trial, in a Dec. 17 Amgen press release.
Trial results
The early approval of the treatment was based on the results of various clinical trials, primarily the NAVIGATOR phase 3 trial, results of which were published in the New England Journal of Medicine in May 2021.
In the NAVIGATOR trial, a total of 1,061 patients were randomly assigned to receive tezepelumab (529 patients) or placebo (532 patients).
With tezepelumab, the annualized rate of asthma exacerbations was 0.93; with placebo, the rate was 2.10 (P < .001).
“Patients with severe, uncontrolled asthma who received tezepelumab had fewer exacerbations and better lung function, asthma control, and health-related quality of life than those who received placebo,” according to the report of NAVIGATOR trial, which was funded by AstraZeneca and Amgen.
Tezepelumab details
The full prescribing information for tezepelumab-ekko is available, including specific warnings and areas of concern where information is not available. The drug should not be administered to individuals with known hypersensitivity to tezepelumab-ekko or excipients, and hypersensitivity reactions (e.g., rash and allergic conjunctivitis), can occur within hours of administration, but in some instances have a delayed onset (i.e., days).
The drug should not be used to treat acute asthma symptoms, acute exacerbations, acute bronchospasm, or status asthmaticus, and the use of live-attenuated vaccines in patients receiving tezepelumab-ekko should be avoided.
There is no available data regarding the use of tezepelumab-ekko in patients who are pregnant, although placental transfer of monoclonal antibodies such as tezepelumab-ekko is greater during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy, according to the company.
The most common adverse reactions for the drug, with a reported incidence of at least 3%, are pharyngitis, arthralgia, and back pain.
“The approval of Tezspire is long-awaited positive news for the asthma community,” said Tonya Winders, president and CEO at the Allergy & Asthma Network and president of the Global Allergy and Airways Patient Platform in the Amgen press release. “For the first time, many people living with severe asthma have the opportunity to receive treatment regardless of the cause of their inflammation.”
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved tezepelumab-ekko (Tezspire) as a first-in-class treatment for severe asthma in adults and pediatric patients aged 12 years and older. It is not recommended for the relief of acute bronchospasm or status asthmaticus.
Tezepelumab-ekko is a human monoclonal antibody that acts as a thymic stromal lymphopoietin (TSLP) blocker. TSLP is an epithelial cell–derived cytokine implicated in the pathogenesis of asthma. Tezepelumab-ekko is administered by subcutaneous injection at a recommended dosage of 210 mg given once every 4 weeks.
“Tezspire represents a much-needed new treatment for the many patients who remain underserved and continue to struggle with severe, uncontrolled asthma,” said professor Andrew Menzies-Gow, MD, PhD, director of the lung division, Royal Brompton Hospital, London, and the principal investigator of the pivotal NAVIGATOR trial, in a Dec. 17 Amgen press release.
Trial results
The early approval of the treatment was based on the results of various clinical trials, primarily the NAVIGATOR phase 3 trial, results of which were published in the New England Journal of Medicine in May 2021.
In the NAVIGATOR trial, a total of 1,061 patients were randomly assigned to receive tezepelumab (529 patients) or placebo (532 patients).
With tezepelumab, the annualized rate of asthma exacerbations was 0.93; with placebo, the rate was 2.10 (P < .001).
“Patients with severe, uncontrolled asthma who received tezepelumab had fewer exacerbations and better lung function, asthma control, and health-related quality of life than those who received placebo,” according to the report of NAVIGATOR trial, which was funded by AstraZeneca and Amgen.
Tezepelumab details
The full prescribing information for tezepelumab-ekko is available, including specific warnings and areas of concern where information is not available. The drug should not be administered to individuals with known hypersensitivity to tezepelumab-ekko or excipients, and hypersensitivity reactions (e.g., rash and allergic conjunctivitis), can occur within hours of administration, but in some instances have a delayed onset (i.e., days).
The drug should not be used to treat acute asthma symptoms, acute exacerbations, acute bronchospasm, or status asthmaticus, and the use of live-attenuated vaccines in patients receiving tezepelumab-ekko should be avoided.
There is no available data regarding the use of tezepelumab-ekko in patients who are pregnant, although placental transfer of monoclonal antibodies such as tezepelumab-ekko is greater during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy, according to the company.
The most common adverse reactions for the drug, with a reported incidence of at least 3%, are pharyngitis, arthralgia, and back pain.
“The approval of Tezspire is long-awaited positive news for the asthma community,” said Tonya Winders, president and CEO at the Allergy & Asthma Network and president of the Global Allergy and Airways Patient Platform in the Amgen press release. “For the first time, many people living with severe asthma have the opportunity to receive treatment regardless of the cause of their inflammation.”
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved tezepelumab-ekko (Tezspire) as a first-in-class treatment for severe asthma in adults and pediatric patients aged 12 years and older. It is not recommended for the relief of acute bronchospasm or status asthmaticus.
Tezepelumab-ekko is a human monoclonal antibody that acts as a thymic stromal lymphopoietin (TSLP) blocker. TSLP is an epithelial cell–derived cytokine implicated in the pathogenesis of asthma. Tezepelumab-ekko is administered by subcutaneous injection at a recommended dosage of 210 mg given once every 4 weeks.
“Tezspire represents a much-needed new treatment for the many patients who remain underserved and continue to struggle with severe, uncontrolled asthma,” said professor Andrew Menzies-Gow, MD, PhD, director of the lung division, Royal Brompton Hospital, London, and the principal investigator of the pivotal NAVIGATOR trial, in a Dec. 17 Amgen press release.
Trial results
The early approval of the treatment was based on the results of various clinical trials, primarily the NAVIGATOR phase 3 trial, results of which were published in the New England Journal of Medicine in May 2021.
In the NAVIGATOR trial, a total of 1,061 patients were randomly assigned to receive tezepelumab (529 patients) or placebo (532 patients).
With tezepelumab, the annualized rate of asthma exacerbations was 0.93; with placebo, the rate was 2.10 (P < .001).
“Patients with severe, uncontrolled asthma who received tezepelumab had fewer exacerbations and better lung function, asthma control, and health-related quality of life than those who received placebo,” according to the report of NAVIGATOR trial, which was funded by AstraZeneca and Amgen.
Tezepelumab details
The full prescribing information for tezepelumab-ekko is available, including specific warnings and areas of concern where information is not available. The drug should not be administered to individuals with known hypersensitivity to tezepelumab-ekko or excipients, and hypersensitivity reactions (e.g., rash and allergic conjunctivitis), can occur within hours of administration, but in some instances have a delayed onset (i.e., days).
The drug should not be used to treat acute asthma symptoms, acute exacerbations, acute bronchospasm, or status asthmaticus, and the use of live-attenuated vaccines in patients receiving tezepelumab-ekko should be avoided.
There is no available data regarding the use of tezepelumab-ekko in patients who are pregnant, although placental transfer of monoclonal antibodies such as tezepelumab-ekko is greater during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy, according to the company.
The most common adverse reactions for the drug, with a reported incidence of at least 3%, are pharyngitis, arthralgia, and back pain.
“The approval of Tezspire is long-awaited positive news for the asthma community,” said Tonya Winders, president and CEO at the Allergy & Asthma Network and president of the Global Allergy and Airways Patient Platform in the Amgen press release. “For the first time, many people living with severe asthma have the opportunity to receive treatment regardless of the cause of their inflammation.”
A version of this article first appeared on Medscape.com.
Blastomycosislike Pyoderma: Verrucous Hyperpigmented Plaques on the Pretibial Shins
To the Editor:
Blastomycosislike pyoderma (BLP), also commonly referred to as pyoderma vegetans, is a rare cutaneous bacterial infection that often mimics other fungal, inflammatory, or neoplastic disorders.1 It is characterized by a collection of neutrophilic abscesses with pseudoepitheliomatous hyperplasia that coalesce into crusted plaques.
A 15-year-old adolescent girl with a history of type 1 diabetes mellitus was admitted for diabetic ketoacidosis. The patient presented with bilateral pretibial lesions of 6 years’ duration that developed after swimming in a pool following reported trauma to the site. These pruritic plaques had grown slowly and were occasionally tender. Of note, with episodes of hyperglycemia, the lesions developed purulent drainage.
Upon admission to the hospital and subsequent dermatology consultation, physical examination revealed the right pretibial shin had a 15×5-cm, gray-brown, hyperpigmented, verrucous, tender plaque with purulent drainage and overlying crust (Figure 1). The left pretibial shin had a similar smaller lesion (Figure 2). Laboratory test results were notable for a white blood cell count of 41.84 cells/µL (reference range, 3.8–10.5 cells/µL), blood glucose level of 586 mg/dL (reference range, 70–99 mg/dL), and hemoglobin A1c of 11.7% (reference range, 4.0%–5.6%). A biopsy specimen from the right pretibial shin was stained with hematoxylin and eosin for dermatopathologic evaluation as well as sent for tissue culture. Tissue and wound cultures grew Staphylococcus aureus and group B Streptococcus with no fungal or acid-fast bacilli growth.
Blood cultures were negative for bacteria. Results of radiographic imaging were negative for osteomyelitis. Biopsy specimens from the right pretibial plaque showed a markedly inflamed, ruptured follicular unit with a dense dermal lympho-neutrophilic infiltrate and overlying pseudoepitheliomatous hyperplasia (Figure 3). Periodic acid–Schiff, Gomori methenamine-silver, acid-fast bacilli, and Giemsa stains were negative for organisms. No granules consistent with a Splendore-Hoeppli phenomenon were observed. These observations were consistent with a diagnosis of BLP.
Blastomycosislike pyoderma is a rare cutaneous bacterial infection that often mimics other fungal, inflammatory, or neoplastic disorders.1 Pediatric cases also are uncommon. Blastomycosislike pyoderma most commonly is caused by infection with S aureus or group A streptococci, but several other organisms have been implicated.2 Clinically, BLP is similar to cutaneous botryomycosis, as both are caused by similar organisms.3 However, while BLP is limited to the skin, botryomycosis may involve visceral organs.
Blastomycosislike pyoderma typically presents as verrucous, hyperkeratotic, purulent plaques with raised borders. It most commonly occurs on the face, scalp, axillae, trunk, and distal extremities. Predisposing factors include immunosuppressed states such as poor nutrition, HIV, malignancy, alcoholism, and diabetes mellitus.3,4 Hyperglycemia is thought to suppress helper T cell (TH1)–dependent immunity, which may explain why our patient’s lesions worsened with hyperglycemic episodes.5Histopathology revealed pseudoepitheliomatous hyperplasia with neutrophilic abscesses.1 The distinguishing feature between botryomycosis and BLP is the development of grains known as the Splendore-Hoeppli phenomenon in botryomycosis.6 The grains are eosinophilic and contain the causative infectious agent. The presence of these grains is consistent with botryomycosis but is not pathognomonic, as it also can be found in several bacterial, fungal, and parasitic infections.3,6
The differential diagnosis of BLP includes atypical mycobacterial infection, pyoderma gangrenosum, fungal infection, and tuberculosis verrucosa cutis.7
Although BLP is caused by bacteria, response to systemic antibiotics is variable. Other treatment modalities include dapsone, systemic and intralesional corticosteroids, retinoids, debridement, CO2 laser, and excision.6,8 Lesions typically start out localized, but it is not uncommon for them to spread to distal or vulnerable tissue, such as sites of trauma or inflammation. Our patient was started on oral trimethoprim-sulfamethoxazole and showed improvement, but she worsened with subsequent hyperglycemic episodes when antibiotics were discontinued.
1. Adis¸en E, Tezel F, Gürer MA. Pyoderma vegetans: a case for discussion. Acta Derm Venereol. 2009;89:186-188.
2. Scuderi S, O’Brien B, Robertson I, et al. Heterogeneity of blastomycosis-like pyoderma: a selection of cases from the last 35 years. Australas J Dermatol. 2017;58:139-141.
3. Marschalko, M. Pyoderma vegetans: report on a case and review of data on pyoderma vegetans and cutaneous botryomycosis. Acta Dermatovenerol Alp Pannonica Adriat. 1995;4:55-59.
4. Cerullo L, Zussman J, Young L. An unusual presentation of blastomycosislike pyoderma (pyoderma vegetans) and a review of the literature. Cutis. 2009;84:201-204.
5. Tanaka Y. Immunosuppressive mechanisms in diabetes mellitus [in Japanese]. Nihon Rinsho. 2008;66:2233-2237.
6. Hussein MR. Mucocutaneous Splendore-Hoeppli phenomenon. J Cutan Pathol. 2008;35:979-988.
7. Lee YS, Jung SW, Sim HS, et al. Blastomycosis-like pyoderma with good response to acitretin. Ann Dermatol. 2011;23:365-368.
8. Kobraei KB, Wesson SK. Blastomycosis-like pyoderma: response to systemic retinoid therapy. Int J Dermatol. 2010;49:1336-1338.
To the Editor:
Blastomycosislike pyoderma (BLP), also commonly referred to as pyoderma vegetans, is a rare cutaneous bacterial infection that often mimics other fungal, inflammatory, or neoplastic disorders.1 It is characterized by a collection of neutrophilic abscesses with pseudoepitheliomatous hyperplasia that coalesce into crusted plaques.
A 15-year-old adolescent girl with a history of type 1 diabetes mellitus was admitted for diabetic ketoacidosis. The patient presented with bilateral pretibial lesions of 6 years’ duration that developed after swimming in a pool following reported trauma to the site. These pruritic plaques had grown slowly and were occasionally tender. Of note, with episodes of hyperglycemia, the lesions developed purulent drainage.
Upon admission to the hospital and subsequent dermatology consultation, physical examination revealed the right pretibial shin had a 15×5-cm, gray-brown, hyperpigmented, verrucous, tender plaque with purulent drainage and overlying crust (Figure 1). The left pretibial shin had a similar smaller lesion (Figure 2). Laboratory test results were notable for a white blood cell count of 41.84 cells/µL (reference range, 3.8–10.5 cells/µL), blood glucose level of 586 mg/dL (reference range, 70–99 mg/dL), and hemoglobin A1c of 11.7% (reference range, 4.0%–5.6%). A biopsy specimen from the right pretibial shin was stained with hematoxylin and eosin for dermatopathologic evaluation as well as sent for tissue culture. Tissue and wound cultures grew Staphylococcus aureus and group B Streptococcus with no fungal or acid-fast bacilli growth.
Blood cultures were negative for bacteria. Results of radiographic imaging were negative for osteomyelitis. Biopsy specimens from the right pretibial plaque showed a markedly inflamed, ruptured follicular unit with a dense dermal lympho-neutrophilic infiltrate and overlying pseudoepitheliomatous hyperplasia (Figure 3). Periodic acid–Schiff, Gomori methenamine-silver, acid-fast bacilli, and Giemsa stains were negative for organisms. No granules consistent with a Splendore-Hoeppli phenomenon were observed. These observations were consistent with a diagnosis of BLP.
Blastomycosislike pyoderma is a rare cutaneous bacterial infection that often mimics other fungal, inflammatory, or neoplastic disorders.1 Pediatric cases also are uncommon. Blastomycosislike pyoderma most commonly is caused by infection with S aureus or group A streptococci, but several other organisms have been implicated.2 Clinically, BLP is similar to cutaneous botryomycosis, as both are caused by similar organisms.3 However, while BLP is limited to the skin, botryomycosis may involve visceral organs.
Blastomycosislike pyoderma typically presents as verrucous, hyperkeratotic, purulent plaques with raised borders. It most commonly occurs on the face, scalp, axillae, trunk, and distal extremities. Predisposing factors include immunosuppressed states such as poor nutrition, HIV, malignancy, alcoholism, and diabetes mellitus.3,4 Hyperglycemia is thought to suppress helper T cell (TH1)–dependent immunity, which may explain why our patient’s lesions worsened with hyperglycemic episodes.5Histopathology revealed pseudoepitheliomatous hyperplasia with neutrophilic abscesses.1 The distinguishing feature between botryomycosis and BLP is the development of grains known as the Splendore-Hoeppli phenomenon in botryomycosis.6 The grains are eosinophilic and contain the causative infectious agent. The presence of these grains is consistent with botryomycosis but is not pathognomonic, as it also can be found in several bacterial, fungal, and parasitic infections.3,6
The differential diagnosis of BLP includes atypical mycobacterial infection, pyoderma gangrenosum, fungal infection, and tuberculosis verrucosa cutis.7
Although BLP is caused by bacteria, response to systemic antibiotics is variable. Other treatment modalities include dapsone, systemic and intralesional corticosteroids, retinoids, debridement, CO2 laser, and excision.6,8 Lesions typically start out localized, but it is not uncommon for them to spread to distal or vulnerable tissue, such as sites of trauma or inflammation. Our patient was started on oral trimethoprim-sulfamethoxazole and showed improvement, but she worsened with subsequent hyperglycemic episodes when antibiotics were discontinued.
To the Editor:
Blastomycosislike pyoderma (BLP), also commonly referred to as pyoderma vegetans, is a rare cutaneous bacterial infection that often mimics other fungal, inflammatory, or neoplastic disorders.1 It is characterized by a collection of neutrophilic abscesses with pseudoepitheliomatous hyperplasia that coalesce into crusted plaques.
A 15-year-old adolescent girl with a history of type 1 diabetes mellitus was admitted for diabetic ketoacidosis. The patient presented with bilateral pretibial lesions of 6 years’ duration that developed after swimming in a pool following reported trauma to the site. These pruritic plaques had grown slowly and were occasionally tender. Of note, with episodes of hyperglycemia, the lesions developed purulent drainage.
Upon admission to the hospital and subsequent dermatology consultation, physical examination revealed the right pretibial shin had a 15×5-cm, gray-brown, hyperpigmented, verrucous, tender plaque with purulent drainage and overlying crust (Figure 1). The left pretibial shin had a similar smaller lesion (Figure 2). Laboratory test results were notable for a white blood cell count of 41.84 cells/µL (reference range, 3.8–10.5 cells/µL), blood glucose level of 586 mg/dL (reference range, 70–99 mg/dL), and hemoglobin A1c of 11.7% (reference range, 4.0%–5.6%). A biopsy specimen from the right pretibial shin was stained with hematoxylin and eosin for dermatopathologic evaluation as well as sent for tissue culture. Tissue and wound cultures grew Staphylococcus aureus and group B Streptococcus with no fungal or acid-fast bacilli growth.
Blood cultures were negative for bacteria. Results of radiographic imaging were negative for osteomyelitis. Biopsy specimens from the right pretibial plaque showed a markedly inflamed, ruptured follicular unit with a dense dermal lympho-neutrophilic infiltrate and overlying pseudoepitheliomatous hyperplasia (Figure 3). Periodic acid–Schiff, Gomori methenamine-silver, acid-fast bacilli, and Giemsa stains were negative for organisms. No granules consistent with a Splendore-Hoeppli phenomenon were observed. These observations were consistent with a diagnosis of BLP.
Blastomycosislike pyoderma is a rare cutaneous bacterial infection that often mimics other fungal, inflammatory, or neoplastic disorders.1 Pediatric cases also are uncommon. Blastomycosislike pyoderma most commonly is caused by infection with S aureus or group A streptococci, but several other organisms have been implicated.2 Clinically, BLP is similar to cutaneous botryomycosis, as both are caused by similar organisms.3 However, while BLP is limited to the skin, botryomycosis may involve visceral organs.
Blastomycosislike pyoderma typically presents as verrucous, hyperkeratotic, purulent plaques with raised borders. It most commonly occurs on the face, scalp, axillae, trunk, and distal extremities. Predisposing factors include immunosuppressed states such as poor nutrition, HIV, malignancy, alcoholism, and diabetes mellitus.3,4 Hyperglycemia is thought to suppress helper T cell (TH1)–dependent immunity, which may explain why our patient’s lesions worsened with hyperglycemic episodes.5Histopathology revealed pseudoepitheliomatous hyperplasia with neutrophilic abscesses.1 The distinguishing feature between botryomycosis and BLP is the development of grains known as the Splendore-Hoeppli phenomenon in botryomycosis.6 The grains are eosinophilic and contain the causative infectious agent. The presence of these grains is consistent with botryomycosis but is not pathognomonic, as it also can be found in several bacterial, fungal, and parasitic infections.3,6
The differential diagnosis of BLP includes atypical mycobacterial infection, pyoderma gangrenosum, fungal infection, and tuberculosis verrucosa cutis.7
Although BLP is caused by bacteria, response to systemic antibiotics is variable. Other treatment modalities include dapsone, systemic and intralesional corticosteroids, retinoids, debridement, CO2 laser, and excision.6,8 Lesions typically start out localized, but it is not uncommon for them to spread to distal or vulnerable tissue, such as sites of trauma or inflammation. Our patient was started on oral trimethoprim-sulfamethoxazole and showed improvement, but she worsened with subsequent hyperglycemic episodes when antibiotics were discontinued.
1. Adis¸en E, Tezel F, Gürer MA. Pyoderma vegetans: a case for discussion. Acta Derm Venereol. 2009;89:186-188.
2. Scuderi S, O’Brien B, Robertson I, et al. Heterogeneity of blastomycosis-like pyoderma: a selection of cases from the last 35 years. Australas J Dermatol. 2017;58:139-141.
3. Marschalko, M. Pyoderma vegetans: report on a case and review of data on pyoderma vegetans and cutaneous botryomycosis. Acta Dermatovenerol Alp Pannonica Adriat. 1995;4:55-59.
4. Cerullo L, Zussman J, Young L. An unusual presentation of blastomycosislike pyoderma (pyoderma vegetans) and a review of the literature. Cutis. 2009;84:201-204.
5. Tanaka Y. Immunosuppressive mechanisms in diabetes mellitus [in Japanese]. Nihon Rinsho. 2008;66:2233-2237.
6. Hussein MR. Mucocutaneous Splendore-Hoeppli phenomenon. J Cutan Pathol. 2008;35:979-988.
7. Lee YS, Jung SW, Sim HS, et al. Blastomycosis-like pyoderma with good response to acitretin. Ann Dermatol. 2011;23:365-368.
8. Kobraei KB, Wesson SK. Blastomycosis-like pyoderma: response to systemic retinoid therapy. Int J Dermatol. 2010;49:1336-1338.
1. Adis¸en E, Tezel F, Gürer MA. Pyoderma vegetans: a case for discussion. Acta Derm Venereol. 2009;89:186-188.
2. Scuderi S, O’Brien B, Robertson I, et al. Heterogeneity of blastomycosis-like pyoderma: a selection of cases from the last 35 years. Australas J Dermatol. 2017;58:139-141.
3. Marschalko, M. Pyoderma vegetans: report on a case and review of data on pyoderma vegetans and cutaneous botryomycosis. Acta Dermatovenerol Alp Pannonica Adriat. 1995;4:55-59.
4. Cerullo L, Zussman J, Young L. An unusual presentation of blastomycosislike pyoderma (pyoderma vegetans) and a review of the literature. Cutis. 2009;84:201-204.
5. Tanaka Y. Immunosuppressive mechanisms in diabetes mellitus [in Japanese]. Nihon Rinsho. 2008;66:2233-2237.
6. Hussein MR. Mucocutaneous Splendore-Hoeppli phenomenon. J Cutan Pathol. 2008;35:979-988.
7. Lee YS, Jung SW, Sim HS, et al. Blastomycosis-like pyoderma with good response to acitretin. Ann Dermatol. 2011;23:365-368.
8. Kobraei KB, Wesson SK. Blastomycosis-like pyoderma: response to systemic retinoid therapy. Int J Dermatol. 2010;49:1336-1338.
Practice Points
- Blastomycosislike pyoderma is a rare condition secondary to bacterial infection, but as the name suggests, it also can resemble cutaneous blastomycosis.
- Blastomycosislike pyoderma most commonly occurs in immunocompromised patients.
- The most common histologic findings include suppurative and neutrophilic inflammation with pseudoepitheliomatous hyperplasia.
FDA grants new indication to lumateperone (Caplyta) for bipolar depression
The Food and Drug Administration has expanded approval of lumateperone (Caplyta) to include treatment of adults with depressive episodes associated with bipolar I and II disorder, as monotherapy or adjunctive therapy with lithium or valproate.
This makes lumateperone the only FDA-approved drug for this indication.
“The efficacy, and favorable safety and tolerability profile, make Caplyta an important treatment option for the millions of patients living with bipolar I or II depression and represents a major development for these patients,” Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, and head of the mood disorders psychopharmacology unit, said in a company news release.
Lumateperone was first approved by the FDA in 2019 for the treatment of adults with schizophrenia.
‘Positioned to launch immediately’
that showed treatment with lumateperone, alone or with lithium or valproate, significantly improved depressive symptoms for patients with major depressive episodes associated with bipolar I and bipolar II disorders.
In these studies, treatment with a 42-mg once-daily dose was associated with significantly greater improvement from baseline in Montgomery-Åsberg Depression Rating Scale score versus placebo.
Lumateperone also showed a statistically significant improvement in the key secondary endpoint relating to clinical global impression of bipolar disorder.
Somnolence/sedation, dizziness, nausea, and dry mouth were the most commonly reported adverse events associated with the medication. Minimal changes were observed in weight and vital signs and in results of metabolic or endocrine assessments. Incidence of extrapyramidal symptom–related events was low and was similar to those with placebo.
Sharon Mates, PhD, chairman and CEO of Intra-Cellular Therapies, noted in the same press release that the company is “positioned to launch immediately and are excited to offer Caplyta to the millions of patients living with bipolar depression.”
Full prescribing information is available online.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has expanded approval of lumateperone (Caplyta) to include treatment of adults with depressive episodes associated with bipolar I and II disorder, as monotherapy or adjunctive therapy with lithium or valproate.
This makes lumateperone the only FDA-approved drug for this indication.
“The efficacy, and favorable safety and tolerability profile, make Caplyta an important treatment option for the millions of patients living with bipolar I or II depression and represents a major development for these patients,” Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, and head of the mood disorders psychopharmacology unit, said in a company news release.
Lumateperone was first approved by the FDA in 2019 for the treatment of adults with schizophrenia.
‘Positioned to launch immediately’
that showed treatment with lumateperone, alone or with lithium or valproate, significantly improved depressive symptoms for patients with major depressive episodes associated with bipolar I and bipolar II disorders.
In these studies, treatment with a 42-mg once-daily dose was associated with significantly greater improvement from baseline in Montgomery-Åsberg Depression Rating Scale score versus placebo.
Lumateperone also showed a statistically significant improvement in the key secondary endpoint relating to clinical global impression of bipolar disorder.
Somnolence/sedation, dizziness, nausea, and dry mouth were the most commonly reported adverse events associated with the medication. Minimal changes were observed in weight and vital signs and in results of metabolic or endocrine assessments. Incidence of extrapyramidal symptom–related events was low and was similar to those with placebo.
Sharon Mates, PhD, chairman and CEO of Intra-Cellular Therapies, noted in the same press release that the company is “positioned to launch immediately and are excited to offer Caplyta to the millions of patients living with bipolar depression.”
Full prescribing information is available online.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has expanded approval of lumateperone (Caplyta) to include treatment of adults with depressive episodes associated with bipolar I and II disorder, as monotherapy or adjunctive therapy with lithium or valproate.
This makes lumateperone the only FDA-approved drug for this indication.
“The efficacy, and favorable safety and tolerability profile, make Caplyta an important treatment option for the millions of patients living with bipolar I or II depression and represents a major development for these patients,” Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, and head of the mood disorders psychopharmacology unit, said in a company news release.
Lumateperone was first approved by the FDA in 2019 for the treatment of adults with schizophrenia.
‘Positioned to launch immediately’
that showed treatment with lumateperone, alone or with lithium or valproate, significantly improved depressive symptoms for patients with major depressive episodes associated with bipolar I and bipolar II disorders.
In these studies, treatment with a 42-mg once-daily dose was associated with significantly greater improvement from baseline in Montgomery-Åsberg Depression Rating Scale score versus placebo.
Lumateperone also showed a statistically significant improvement in the key secondary endpoint relating to clinical global impression of bipolar disorder.
Somnolence/sedation, dizziness, nausea, and dry mouth were the most commonly reported adverse events associated with the medication. Minimal changes were observed in weight and vital signs and in results of metabolic or endocrine assessments. Incidence of extrapyramidal symptom–related events was low and was similar to those with placebo.
Sharon Mates, PhD, chairman and CEO of Intra-Cellular Therapies, noted in the same press release that the company is “positioned to launch immediately and are excited to offer Caplyta to the millions of patients living with bipolar depression.”
Full prescribing information is available online.
A version of this article first appeared on Medscape.com.
Pfizer COVID vaccine for younger children hits snag
Pfizer’s COVID-19 vaccine for children ages 2 to 5 years old fizzled in clinical trials, the company said on Friday, signaling a further delay in getting a vaccine to preschoolers just as Omicron bears down on the U.S.
In a news release, Pfizer reported that while its 3-microgram dose – which is less than one-third of the dose given to older children – generated a protective immune response in babies and toddlers ages 6 to 24 months, it didn’t generate adequate immunity in children ages 2 to 5.
The company plans to change its clinical trial to add a third dose for younger children in hopes of improving those results. It also plans to test a third dose of its 10-microgram vaccine for children ages 5 to 12.
If the trials are successful, Pfizer said it would submit data to the FDA for an emergency use authorization (EUA) in the first half of 2022.
That pushes the timeline of getting a vaccine to younger children back by several months. In November, Anthony Fauci, MD, head of the National Institute of Allergy Infectious Diseases, predicted a vaccine would be ready for preschoolers by spring.
“On one hand, parents are understandably disappointed,” said Jill Foster, MD, a pediatric infectious disease doctor at the University of Minnesota Medical School. “On the other, it shows that the system for testing vaccines is working. Children are not little adults and have complex immune systems, so it’s not just a matter of making the dose smaller and expecting that it will work,” she said, noting that data from Moderna’s KidCOVE study in preschoolers is pending.
Until there’s a vaccine, Dr. Foster says parents should protect babies and toddlers by making sure everyone around them is vaccinated, promote the use of face masks for everyone around them and for all children over age 2, and continue to avoid crowded gatherings, particularly those that are indoors.
“Hand sanitizer is important, but this virus, especially the Omicron variant, is very easily spread through the air, so keep the air clear of virus as much as possible,” she said.
While the youngest children are still waiting for an effective vaccine, there was reassuring news Dec. 16 about the safety of Pfizer’s vaccine for school-aged kids – those ages 5 through 11.
Out of more than 7 million doses given since this vaccine was authorized for emergency use in late October, most reactions to the vaccine – including arm pain, swelling, and fatigue – have been mild and gone away quickly, without the need to miss school or see a doctor, the CDC reported to a meeting of its Advisory Committee on Immunization Practices, or ACIP.
Many experts had been waiting to see if this vaccine would cause rare cases of heart inflammation called myocarditis, as a higher dose did in teens and young adults.
The news on this front was excellent. About 6 weeks after this vaccine became available, the CDC says there have been only eight confirmed cases of myocarditis in this age group. Six more cases are under investigation.
To put this risk into context, data collected by the American Academy of Pediatrics and the Children’s Hospital Association shows that about 1% of children who test positive for COVID-19 are hospitalized for their infections, while the risk of getting a case of myocarditis after vaccination is .0002%, making it about 5,000 times more likely that a child would need to be hospitalized for COVID-19 than for myocarditis after vaccination.
John Su, MD, who is a member of the CDC’s Vaccine Safety Team, reported there had been two deaths in children after a COVID-19 vaccination. Both were girls, ages 5 and 6. Both had complicated medical histories for several medical disorders. It’s not clear their deaths were linked to the vaccine, and the causes of their deaths are still under investigation.
A version of this article first appeared on WebMD.com.
Pfizer’s COVID-19 vaccine for children ages 2 to 5 years old fizzled in clinical trials, the company said on Friday, signaling a further delay in getting a vaccine to preschoolers just as Omicron bears down on the U.S.
In a news release, Pfizer reported that while its 3-microgram dose – which is less than one-third of the dose given to older children – generated a protective immune response in babies and toddlers ages 6 to 24 months, it didn’t generate adequate immunity in children ages 2 to 5.
The company plans to change its clinical trial to add a third dose for younger children in hopes of improving those results. It also plans to test a third dose of its 10-microgram vaccine for children ages 5 to 12.
If the trials are successful, Pfizer said it would submit data to the FDA for an emergency use authorization (EUA) in the first half of 2022.
That pushes the timeline of getting a vaccine to younger children back by several months. In November, Anthony Fauci, MD, head of the National Institute of Allergy Infectious Diseases, predicted a vaccine would be ready for preschoolers by spring.
“On one hand, parents are understandably disappointed,” said Jill Foster, MD, a pediatric infectious disease doctor at the University of Minnesota Medical School. “On the other, it shows that the system for testing vaccines is working. Children are not little adults and have complex immune systems, so it’s not just a matter of making the dose smaller and expecting that it will work,” she said, noting that data from Moderna’s KidCOVE study in preschoolers is pending.
Until there’s a vaccine, Dr. Foster says parents should protect babies and toddlers by making sure everyone around them is vaccinated, promote the use of face masks for everyone around them and for all children over age 2, and continue to avoid crowded gatherings, particularly those that are indoors.
“Hand sanitizer is important, but this virus, especially the Omicron variant, is very easily spread through the air, so keep the air clear of virus as much as possible,” she said.
While the youngest children are still waiting for an effective vaccine, there was reassuring news Dec. 16 about the safety of Pfizer’s vaccine for school-aged kids – those ages 5 through 11.
Out of more than 7 million doses given since this vaccine was authorized for emergency use in late October, most reactions to the vaccine – including arm pain, swelling, and fatigue – have been mild and gone away quickly, without the need to miss school or see a doctor, the CDC reported to a meeting of its Advisory Committee on Immunization Practices, or ACIP.
Many experts had been waiting to see if this vaccine would cause rare cases of heart inflammation called myocarditis, as a higher dose did in teens and young adults.
The news on this front was excellent. About 6 weeks after this vaccine became available, the CDC says there have been only eight confirmed cases of myocarditis in this age group. Six more cases are under investigation.
To put this risk into context, data collected by the American Academy of Pediatrics and the Children’s Hospital Association shows that about 1% of children who test positive for COVID-19 are hospitalized for their infections, while the risk of getting a case of myocarditis after vaccination is .0002%, making it about 5,000 times more likely that a child would need to be hospitalized for COVID-19 than for myocarditis after vaccination.
John Su, MD, who is a member of the CDC’s Vaccine Safety Team, reported there had been two deaths in children after a COVID-19 vaccination. Both were girls, ages 5 and 6. Both had complicated medical histories for several medical disorders. It’s not clear their deaths were linked to the vaccine, and the causes of their deaths are still under investigation.
A version of this article first appeared on WebMD.com.
Pfizer’s COVID-19 vaccine for children ages 2 to 5 years old fizzled in clinical trials, the company said on Friday, signaling a further delay in getting a vaccine to preschoolers just as Omicron bears down on the U.S.
In a news release, Pfizer reported that while its 3-microgram dose – which is less than one-third of the dose given to older children – generated a protective immune response in babies and toddlers ages 6 to 24 months, it didn’t generate adequate immunity in children ages 2 to 5.
The company plans to change its clinical trial to add a third dose for younger children in hopes of improving those results. It also plans to test a third dose of its 10-microgram vaccine for children ages 5 to 12.
If the trials are successful, Pfizer said it would submit data to the FDA for an emergency use authorization (EUA) in the first half of 2022.
That pushes the timeline of getting a vaccine to younger children back by several months. In November, Anthony Fauci, MD, head of the National Institute of Allergy Infectious Diseases, predicted a vaccine would be ready for preschoolers by spring.
“On one hand, parents are understandably disappointed,” said Jill Foster, MD, a pediatric infectious disease doctor at the University of Minnesota Medical School. “On the other, it shows that the system for testing vaccines is working. Children are not little adults and have complex immune systems, so it’s not just a matter of making the dose smaller and expecting that it will work,” she said, noting that data from Moderna’s KidCOVE study in preschoolers is pending.
Until there’s a vaccine, Dr. Foster says parents should protect babies and toddlers by making sure everyone around them is vaccinated, promote the use of face masks for everyone around them and for all children over age 2, and continue to avoid crowded gatherings, particularly those that are indoors.
“Hand sanitizer is important, but this virus, especially the Omicron variant, is very easily spread through the air, so keep the air clear of virus as much as possible,” she said.
While the youngest children are still waiting for an effective vaccine, there was reassuring news Dec. 16 about the safety of Pfizer’s vaccine for school-aged kids – those ages 5 through 11.
Out of more than 7 million doses given since this vaccine was authorized for emergency use in late October, most reactions to the vaccine – including arm pain, swelling, and fatigue – have been mild and gone away quickly, without the need to miss school or see a doctor, the CDC reported to a meeting of its Advisory Committee on Immunization Practices, or ACIP.
Many experts had been waiting to see if this vaccine would cause rare cases of heart inflammation called myocarditis, as a higher dose did in teens and young adults.
The news on this front was excellent. About 6 weeks after this vaccine became available, the CDC says there have been only eight confirmed cases of myocarditis in this age group. Six more cases are under investigation.
To put this risk into context, data collected by the American Academy of Pediatrics and the Children’s Hospital Association shows that about 1% of children who test positive for COVID-19 are hospitalized for their infections, while the risk of getting a case of myocarditis after vaccination is .0002%, making it about 5,000 times more likely that a child would need to be hospitalized for COVID-19 than for myocarditis after vaccination.
John Su, MD, who is a member of the CDC’s Vaccine Safety Team, reported there had been two deaths in children after a COVID-19 vaccination. Both were girls, ages 5 and 6. Both had complicated medical histories for several medical disorders. It’s not clear their deaths were linked to the vaccine, and the causes of their deaths are still under investigation.
A version of this article first appeared on WebMD.com.
Class I recall of percutaneous thrombolytic device
Arrow International, a subsidiary of Teleflex, has recalled a total of 3,241 Arrow-Trerotola over-the-wire 7FR percutaneous thrombolytic device (PTD) kits because of the risk of the orange inner lumen of the catheter’s tip component separating from the basket.
The U.S. Food and Drug Administration has identified this as a Class I recall, the most serious type, because of the potential for serious injury or death.
The recalled kits include a rotatable catheter with an outer sheath and an inner cable with a self-expanding basket. The Arrow-Trerotola PTD catheter is used with the Arrow rotator drive unit to remove clots in patients with arteriovenous fistulas and synthetic dialysis grafts.
“If the orange inner lumen separates from the basket, it may fracture and detach and block the blood vessel(s),” the FDA says in the recall notice posted on the FDA website.
“If the orange inner lumen detaches from the basket, health consequences depend upon where the fractured tip component embolizes. If the embolization is local to the treatment target site, retrieval may be attempted, requiring an additional intervention and consequent delay of therapy,” the agency notes.
“In some cases, the embolization could be central or possibly even to the heart or pulmonary arteries. This may lead to serious adverse events such as vessel damage, need for additional medical procedures, or possibly death,” the agency says.
To date, there have been seven complaints and no injuries or deaths reported for this device.
The recalled devices were distributed in the United States between Nov. 1, 2019, and July 31, 2021. Product codes and lot numbers pertaining to the devices are listed on the FDA website.
Teleflex has sent an urgent field safety notice to customers requesting that they check inventory for affected product and remove and quarantine all recalled product.
Customers are also asked to complete the enclosed acknowledgement form and fax it to 1-855-419-8507 (attention: customer service) or e-mail the form to [email protected].
Customers with recalled product service will be contacted by a company representative with instructions for returning any recalled products.
Customers who have questions about this recall should contact Teleflex customer service by phone at 1-866-396-2111, by fax at 1-855-419-8507, or by email at [email protected].
Health care providers can report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.
A version of this article first appeared on Medscape.com.
Arrow International, a subsidiary of Teleflex, has recalled a total of 3,241 Arrow-Trerotola over-the-wire 7FR percutaneous thrombolytic device (PTD) kits because of the risk of the orange inner lumen of the catheter’s tip component separating from the basket.
The U.S. Food and Drug Administration has identified this as a Class I recall, the most serious type, because of the potential for serious injury or death.
The recalled kits include a rotatable catheter with an outer sheath and an inner cable with a self-expanding basket. The Arrow-Trerotola PTD catheter is used with the Arrow rotator drive unit to remove clots in patients with arteriovenous fistulas and synthetic dialysis grafts.
“If the orange inner lumen separates from the basket, it may fracture and detach and block the blood vessel(s),” the FDA says in the recall notice posted on the FDA website.
“If the orange inner lumen detaches from the basket, health consequences depend upon where the fractured tip component embolizes. If the embolization is local to the treatment target site, retrieval may be attempted, requiring an additional intervention and consequent delay of therapy,” the agency notes.
“In some cases, the embolization could be central or possibly even to the heart or pulmonary arteries. This may lead to serious adverse events such as vessel damage, need for additional medical procedures, or possibly death,” the agency says.
To date, there have been seven complaints and no injuries or deaths reported for this device.
The recalled devices were distributed in the United States between Nov. 1, 2019, and July 31, 2021. Product codes and lot numbers pertaining to the devices are listed on the FDA website.
Teleflex has sent an urgent field safety notice to customers requesting that they check inventory for affected product and remove and quarantine all recalled product.
Customers are also asked to complete the enclosed acknowledgement form and fax it to 1-855-419-8507 (attention: customer service) or e-mail the form to [email protected].
Customers with recalled product service will be contacted by a company representative with instructions for returning any recalled products.
Customers who have questions about this recall should contact Teleflex customer service by phone at 1-866-396-2111, by fax at 1-855-419-8507, or by email at [email protected].
Health care providers can report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.
A version of this article first appeared on Medscape.com.
Arrow International, a subsidiary of Teleflex, has recalled a total of 3,241 Arrow-Trerotola over-the-wire 7FR percutaneous thrombolytic device (PTD) kits because of the risk of the orange inner lumen of the catheter’s tip component separating from the basket.
The U.S. Food and Drug Administration has identified this as a Class I recall, the most serious type, because of the potential for serious injury or death.
The recalled kits include a rotatable catheter with an outer sheath and an inner cable with a self-expanding basket. The Arrow-Trerotola PTD catheter is used with the Arrow rotator drive unit to remove clots in patients with arteriovenous fistulas and synthetic dialysis grafts.
“If the orange inner lumen separates from the basket, it may fracture and detach and block the blood vessel(s),” the FDA says in the recall notice posted on the FDA website.
“If the orange inner lumen detaches from the basket, health consequences depend upon where the fractured tip component embolizes. If the embolization is local to the treatment target site, retrieval may be attempted, requiring an additional intervention and consequent delay of therapy,” the agency notes.
“In some cases, the embolization could be central or possibly even to the heart or pulmonary arteries. This may lead to serious adverse events such as vessel damage, need for additional medical procedures, or possibly death,” the agency says.
To date, there have been seven complaints and no injuries or deaths reported for this device.
The recalled devices were distributed in the United States between Nov. 1, 2019, and July 31, 2021. Product codes and lot numbers pertaining to the devices are listed on the FDA website.
Teleflex has sent an urgent field safety notice to customers requesting that they check inventory for affected product and remove and quarantine all recalled product.
Customers are also asked to complete the enclosed acknowledgement form and fax it to 1-855-419-8507 (attention: customer service) or e-mail the form to [email protected].
Customers with recalled product service will be contacted by a company representative with instructions for returning any recalled products.
Customers who have questions about this recall should contact Teleflex customer service by phone at 1-866-396-2111, by fax at 1-855-419-8507, or by email at [email protected].
Health care providers can report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.
A version of this article first appeared on Medscape.com.
COVID cases spike as questions remain about Omicron’s threat
The best way to stay protected is by getting vaccinated and boosted, they said.
“For the unvaccinated, you’re looking at a winter of severe illness and death – for yourselves, families, and the hospitals who may soon overwhelm,” White House COVID-19 Response Coordinator Jeff Zients said at a news briefing Dec. 17. “We need the American people to do their part.”
The Omicron variant has been detected in at least 39 states and 75 countries, according to CDC director Rochelle Walensky, MD.
The strain is more transmissible than the already highly infectious Delta variant, and although there was early evidence that it caused more mild disease, she said that is likely because many of those infected have been vaccinated and boosted.
“Although Delta continues to circulate widely in the United States, Omicron is increasing rapidly and we expect it to become the dominant strain in the United States, as it has in other countries, in the coming weeks,” Dr. Walensky said.
The United States is averaging close to 1,300 deaths from COVID-19 each day. New cases, deaths, and hospitalizations are higher now than in the previous winter – before vaccines were so widely available. The New York Times reported on Dec. 17 that new infections in Connecticut and Maine have grown 150% in the past 2 weeks, and Ohio and Indiana are seeing hospitalization rates nearing the worst of 2020-2021’s winter surge.
Dueling reports released recently gave cause for relief and concern about Omicron.
A study from South Africa released on Dec. 14 shows lower hospitalizations during the first 3 weeks of the Omicron wave than during earlier waves from other variants. That’s the good news.
The concerning news is out of the United Kingdom, where Imperial College London reported Dec. 17 that the risk of reinfection with COVID-19 from Omicron is more than 5 times as high and that cases of Omicron-based COVID-19 are doubling every 2 days.
What’s more, the study “finds no evidence of Omicron having lower severity than Delta, judged by either the proportion of people testing positive who report symptoms, or by the proportion of cases seeking hospital care after infection. However, hospitalization data remains very limited at this time,” the researchers said.
“We have no evidence that the virus itself is more mild,” Eric Topol, MD, executive vice president of Scripps Research and editor-in-chief of Medscape, told PBS NewsHour. “Until we have that, we have to assume that people who don’t have any protection are highly vulnerable to getting very ill.”
The White House COVID-19 team continues to urge parents and guardians to get their children vaccinated, especially in anticipation of a post-holiday spike. Dr. Walensky said the CDC’s vaccine advisory board met on Dec. 16 to continue the safety discussion about COVID-19 vaccinations in children.
So far, 20 million children under 17 and 5 million under 11 have received their shots.
“Looking specifically at vaccine safety data from over 50,000 children 5-11 years old, we found no evidence of serious safety concerns,” Dr. Walensky said.
Top infectious disease expert Anthony S. Fauci, MD, highlighted the importance of getting vaccinated and boosted to avoid serious disease from Delta and Omicron.
“We’re in a situation where we are now facing a very important Delta surge and we are looking over our shoulder at an oncoming Omicron surge,” he said. “The optimum protection is fully vaccinated plus a boost.”
A version of this article first appeared on WebMD.com.
The best way to stay protected is by getting vaccinated and boosted, they said.
“For the unvaccinated, you’re looking at a winter of severe illness and death – for yourselves, families, and the hospitals who may soon overwhelm,” White House COVID-19 Response Coordinator Jeff Zients said at a news briefing Dec. 17. “We need the American people to do their part.”
The Omicron variant has been detected in at least 39 states and 75 countries, according to CDC director Rochelle Walensky, MD.
The strain is more transmissible than the already highly infectious Delta variant, and although there was early evidence that it caused more mild disease, she said that is likely because many of those infected have been vaccinated and boosted.
“Although Delta continues to circulate widely in the United States, Omicron is increasing rapidly and we expect it to become the dominant strain in the United States, as it has in other countries, in the coming weeks,” Dr. Walensky said.
The United States is averaging close to 1,300 deaths from COVID-19 each day. New cases, deaths, and hospitalizations are higher now than in the previous winter – before vaccines were so widely available. The New York Times reported on Dec. 17 that new infections in Connecticut and Maine have grown 150% in the past 2 weeks, and Ohio and Indiana are seeing hospitalization rates nearing the worst of 2020-2021’s winter surge.
Dueling reports released recently gave cause for relief and concern about Omicron.
A study from South Africa released on Dec. 14 shows lower hospitalizations during the first 3 weeks of the Omicron wave than during earlier waves from other variants. That’s the good news.
The concerning news is out of the United Kingdom, where Imperial College London reported Dec. 17 that the risk of reinfection with COVID-19 from Omicron is more than 5 times as high and that cases of Omicron-based COVID-19 are doubling every 2 days.
What’s more, the study “finds no evidence of Omicron having lower severity than Delta, judged by either the proportion of people testing positive who report symptoms, or by the proportion of cases seeking hospital care after infection. However, hospitalization data remains very limited at this time,” the researchers said.
“We have no evidence that the virus itself is more mild,” Eric Topol, MD, executive vice president of Scripps Research and editor-in-chief of Medscape, told PBS NewsHour. “Until we have that, we have to assume that people who don’t have any protection are highly vulnerable to getting very ill.”
The White House COVID-19 team continues to urge parents and guardians to get their children vaccinated, especially in anticipation of a post-holiday spike. Dr. Walensky said the CDC’s vaccine advisory board met on Dec. 16 to continue the safety discussion about COVID-19 vaccinations in children.
So far, 20 million children under 17 and 5 million under 11 have received their shots.
“Looking specifically at vaccine safety data from over 50,000 children 5-11 years old, we found no evidence of serious safety concerns,” Dr. Walensky said.
Top infectious disease expert Anthony S. Fauci, MD, highlighted the importance of getting vaccinated and boosted to avoid serious disease from Delta and Omicron.
“We’re in a situation where we are now facing a very important Delta surge and we are looking over our shoulder at an oncoming Omicron surge,” he said. “The optimum protection is fully vaccinated plus a boost.”
A version of this article first appeared on WebMD.com.
The best way to stay protected is by getting vaccinated and boosted, they said.
“For the unvaccinated, you’re looking at a winter of severe illness and death – for yourselves, families, and the hospitals who may soon overwhelm,” White House COVID-19 Response Coordinator Jeff Zients said at a news briefing Dec. 17. “We need the American people to do their part.”
The Omicron variant has been detected in at least 39 states and 75 countries, according to CDC director Rochelle Walensky, MD.
The strain is more transmissible than the already highly infectious Delta variant, and although there was early evidence that it caused more mild disease, she said that is likely because many of those infected have been vaccinated and boosted.
“Although Delta continues to circulate widely in the United States, Omicron is increasing rapidly and we expect it to become the dominant strain in the United States, as it has in other countries, in the coming weeks,” Dr. Walensky said.
The United States is averaging close to 1,300 deaths from COVID-19 each day. New cases, deaths, and hospitalizations are higher now than in the previous winter – before vaccines were so widely available. The New York Times reported on Dec. 17 that new infections in Connecticut and Maine have grown 150% in the past 2 weeks, and Ohio and Indiana are seeing hospitalization rates nearing the worst of 2020-2021’s winter surge.
Dueling reports released recently gave cause for relief and concern about Omicron.
A study from South Africa released on Dec. 14 shows lower hospitalizations during the first 3 weeks of the Omicron wave than during earlier waves from other variants. That’s the good news.
The concerning news is out of the United Kingdom, where Imperial College London reported Dec. 17 that the risk of reinfection with COVID-19 from Omicron is more than 5 times as high and that cases of Omicron-based COVID-19 are doubling every 2 days.
What’s more, the study “finds no evidence of Omicron having lower severity than Delta, judged by either the proportion of people testing positive who report symptoms, or by the proportion of cases seeking hospital care after infection. However, hospitalization data remains very limited at this time,” the researchers said.
“We have no evidence that the virus itself is more mild,” Eric Topol, MD, executive vice president of Scripps Research and editor-in-chief of Medscape, told PBS NewsHour. “Until we have that, we have to assume that people who don’t have any protection are highly vulnerable to getting very ill.”
The White House COVID-19 team continues to urge parents and guardians to get their children vaccinated, especially in anticipation of a post-holiday spike. Dr. Walensky said the CDC’s vaccine advisory board met on Dec. 16 to continue the safety discussion about COVID-19 vaccinations in children.
So far, 20 million children under 17 and 5 million under 11 have received their shots.
“Looking specifically at vaccine safety data from over 50,000 children 5-11 years old, we found no evidence of serious safety concerns,” Dr. Walensky said.
Top infectious disease expert Anthony S. Fauci, MD, highlighted the importance of getting vaccinated and boosted to avoid serious disease from Delta and Omicron.
“We’re in a situation where we are now facing a very important Delta surge and we are looking over our shoulder at an oncoming Omicron surge,” he said. “The optimum protection is fully vaccinated plus a boost.”
A version of this article first appeared on WebMD.com.
FDA approves new myasthenia gravis drug
“There are significant unmet medical needs for people living with myasthenia gravis, as with many other rare diseases,” Billy Dunn, MD, director, office of neuroscience, FDA Center for Drug Evaluation and Research, said in a news release.
This approval represents “an important step in providing a novel therapy option for patients and underscores the agency’s commitment to help make new treatment options available for people living with rare diseases,” Dr. Dunn added.
Effective, well tolerated
The rare and chronic autoimmune neuromuscular disorder of gMG causes debilitating and potentially life-threatening muscle weakness and significantly impaired independence and quality of life. Most patients with gMG have IgG antibodies, which are most often directed against skeletal muscle nicotinic acetylcholine receptors.
Efgartigimod is an antibody fragment designed to reduce pathogenic IgG antibodies and block the IgG recycling process in patients with gMG.
The novel agent binds to the neonatal Fc receptor (FcRn), which is widely expressed throughout the body and plays a central role in rescuing IgG antibodies from degradation. Blocking FcRn reduces IgG antibody levels.
As previously reported, efgartigimod was effective and well tolerated in the phase 3, randomized, placebo-controlled ADAPT trial, which enrolled 187 adults with gMG regardless of acetylcholine receptor antibody status. All had a Myasthenia Gravis–Activities of Daily Living score of at least 5 (>50% nonocular) on a background of a stable dose of at least one MG drug.
For 26 weeks, 84 patients were randomly assigned to receive efgartigimod 10 mg/kg and 83 to receive matching placebo. Both treatments were administered as four infusions per cycle at one infusion per week. The process was repeated as needed, depending on clinical response no sooner than 8 weeks after initiation of the previous cycle.
Treatment with efgartigimod reduced disease burden and improved strength and quality of life in patients with gMG across four MG-specific scales. In addition, these benefits were observed early and were reproducible and durable.
The results were published in Lancet Neurology.
‘Important new advance’
Efgartigimod is a “very rapidly acting drug relative to other treatments that may take 4, 6, sometimes 10 months before they start to work; and the side-effect profile is much like placebo,” said principal investigator James Howard Jr., MD, department of neurology, University of North Carolina at Chapel Hill.
The FDA granted efgartigimod fast track and orphan drug designation.
“People living with gMG have been in need of new treatment options that are targeted to the underlying pathogenesis of the disease and supported by clinical data,” Dr. Howard said in a company news release issued upon approval.
This approval “represents an important new advance for gMG patients and families affected by this debilitating disease. This therapy has the potential to reduce the disease burden of gMG and transform the way we treat this disease,” Dr. Howard added.
A version of this article first appeared on Medscape.com.
“There are significant unmet medical needs for people living with myasthenia gravis, as with many other rare diseases,” Billy Dunn, MD, director, office of neuroscience, FDA Center for Drug Evaluation and Research, said in a news release.
This approval represents “an important step in providing a novel therapy option for patients and underscores the agency’s commitment to help make new treatment options available for people living with rare diseases,” Dr. Dunn added.
Effective, well tolerated
The rare and chronic autoimmune neuromuscular disorder of gMG causes debilitating and potentially life-threatening muscle weakness and significantly impaired independence and quality of life. Most patients with gMG have IgG antibodies, which are most often directed against skeletal muscle nicotinic acetylcholine receptors.
Efgartigimod is an antibody fragment designed to reduce pathogenic IgG antibodies and block the IgG recycling process in patients with gMG.
The novel agent binds to the neonatal Fc receptor (FcRn), which is widely expressed throughout the body and plays a central role in rescuing IgG antibodies from degradation. Blocking FcRn reduces IgG antibody levels.
As previously reported, efgartigimod was effective and well tolerated in the phase 3, randomized, placebo-controlled ADAPT trial, which enrolled 187 adults with gMG regardless of acetylcholine receptor antibody status. All had a Myasthenia Gravis–Activities of Daily Living score of at least 5 (>50% nonocular) on a background of a stable dose of at least one MG drug.
For 26 weeks, 84 patients were randomly assigned to receive efgartigimod 10 mg/kg and 83 to receive matching placebo. Both treatments were administered as four infusions per cycle at one infusion per week. The process was repeated as needed, depending on clinical response no sooner than 8 weeks after initiation of the previous cycle.
Treatment with efgartigimod reduced disease burden and improved strength and quality of life in patients with gMG across four MG-specific scales. In addition, these benefits were observed early and were reproducible and durable.
The results were published in Lancet Neurology.
‘Important new advance’
Efgartigimod is a “very rapidly acting drug relative to other treatments that may take 4, 6, sometimes 10 months before they start to work; and the side-effect profile is much like placebo,” said principal investigator James Howard Jr., MD, department of neurology, University of North Carolina at Chapel Hill.
The FDA granted efgartigimod fast track and orphan drug designation.
“People living with gMG have been in need of new treatment options that are targeted to the underlying pathogenesis of the disease and supported by clinical data,” Dr. Howard said in a company news release issued upon approval.
This approval “represents an important new advance for gMG patients and families affected by this debilitating disease. This therapy has the potential to reduce the disease burden of gMG and transform the way we treat this disease,” Dr. Howard added.
A version of this article first appeared on Medscape.com.
“There are significant unmet medical needs for people living with myasthenia gravis, as with many other rare diseases,” Billy Dunn, MD, director, office of neuroscience, FDA Center for Drug Evaluation and Research, said in a news release.
This approval represents “an important step in providing a novel therapy option for patients and underscores the agency’s commitment to help make new treatment options available for people living with rare diseases,” Dr. Dunn added.
Effective, well tolerated
The rare and chronic autoimmune neuromuscular disorder of gMG causes debilitating and potentially life-threatening muscle weakness and significantly impaired independence and quality of life. Most patients with gMG have IgG antibodies, which are most often directed against skeletal muscle nicotinic acetylcholine receptors.
Efgartigimod is an antibody fragment designed to reduce pathogenic IgG antibodies and block the IgG recycling process in patients with gMG.
The novel agent binds to the neonatal Fc receptor (FcRn), which is widely expressed throughout the body and plays a central role in rescuing IgG antibodies from degradation. Blocking FcRn reduces IgG antibody levels.
As previously reported, efgartigimod was effective and well tolerated in the phase 3, randomized, placebo-controlled ADAPT trial, which enrolled 187 adults with gMG regardless of acetylcholine receptor antibody status. All had a Myasthenia Gravis–Activities of Daily Living score of at least 5 (>50% nonocular) on a background of a stable dose of at least one MG drug.
For 26 weeks, 84 patients were randomly assigned to receive efgartigimod 10 mg/kg and 83 to receive matching placebo. Both treatments were administered as four infusions per cycle at one infusion per week. The process was repeated as needed, depending on clinical response no sooner than 8 weeks after initiation of the previous cycle.
Treatment with efgartigimod reduced disease burden and improved strength and quality of life in patients with gMG across four MG-specific scales. In addition, these benefits were observed early and were reproducible and durable.
The results were published in Lancet Neurology.
‘Important new advance’
Efgartigimod is a “very rapidly acting drug relative to other treatments that may take 4, 6, sometimes 10 months before they start to work; and the side-effect profile is much like placebo,” said principal investigator James Howard Jr., MD, department of neurology, University of North Carolina at Chapel Hill.
The FDA granted efgartigimod fast track and orphan drug designation.
“People living with gMG have been in need of new treatment options that are targeted to the underlying pathogenesis of the disease and supported by clinical data,” Dr. Howard said in a company news release issued upon approval.
This approval “represents an important new advance for gMG patients and families affected by this debilitating disease. This therapy has the potential to reduce the disease burden of gMG and transform the way we treat this disease,” Dr. Howard added.
A version of this article first appeared on Medscape.com.
Small myocarditis risk now seen for adenovirus-based COVID-19 vaccine
The first large population study to investigate the association between different COVID-19 vaccines types and cardiac effects and adverse events shows a small increase in the risk for acute myocarditis with both the mRNA-based vaccines and – in what may a first in the literature – an adenovirus-vector vaccine.
The excess risk was seen following the first dose of the ChAdOc1 (AstraZeneca/Oxford), the adenovirus-based vaccine, and the mRNA-based BNT162b2 (Pfizer/BioNTech). It was observed after first and second doses of the mRNA-1273 (Moderna) vaccine.
The incidence rate ratios for myocarditis 1-7 days after the first AstraZeneca, Pfizer, and Moderna injections were 1.76, 1.45, and 8.38, respectively, and 23.1 after the second dose of the Moderna vaccine.
“There’s a bit more uncertainty and worry about mRNA vaccines because it’s quite a new vector for vaccination and, therefore, there’s been more focus on the potential side effects,” said Nicholas Mills, MD.
“But it doesn’t surprise me the signal is present for all types of vaccines because they’re designed to generate a systemic immune response and that is, unfortunately, where you can cause small risks for immune-mediated illnesses like myocarditis,” Dr. Mills, from the University of Edinburgh, told this news organization. Dr. Mills is a coauthor on the study, published Dec. 14 in Nature Medicine.
To put the risks in context, the group estimated between 1 and 10 additional myocarditis hospitalizations or deaths per 1 million people vaccinated, but 40 excess myocarditis events per million following a positive SARS-CoV-2 test result.
As reported, rates of excess myocarditis events associated with a first dose were 2 per million injections of the AstraZeneca vaccine, 1 per million for the Pfizer vaccine, and 6 per million with the Moderna vaccine.
Following a second dose, there were 10 additional myocarditis events per million people receiving the Moderna vaccine and none among recipients of the AstraZeneca or Pfizer vaccines.
“It was particularly seen within the first 7 days of the first dose, which is very consistent with what we see in people who have viral myocarditis,” Dr. Mills said. “So it looks like a real signal but it’s very small.”
The results are in line with previous studies of the Pfizer vaccine in Israel and studies of the Moderna vaccine in the United States, Biykem Bozkurt, MD, PhD, professor of medicine at Baylor College of Medicine, Houston, told this news organization.
“What this paper does is confirm that cardiovascular complications – and they are only looking at a small component of those cardiovascular complications – are markedly higher with the COVID-19 infection than with the vaccines,” she said.
It also adds a new twist to the search for the mechanisms of myocarditis, which has focused on the immunogenicity of the RNA in the Pfizer and Moderna vaccines but also hypothesized that molecular mimicry between the SARS-CoV-2 spike glycoprotein and cell antigens, antibody production against cardiac proteins, and testosterone may play a role.
“But now it doesn’t look like the risk is solely confined to the mRNA vaccine platform because it’s also happening with the adenovirus,” Dr. Bozkurt said. “The mechanisms require future experimental and clinical research and we’ll need more granular data with cohorts that are closely followed up as well as subclinical follow-up.”
James de Lemos, MD, professor of medicine at the University of Texas Southwestern Medical Center, Dallas, and cochair of the American Heart Association’s COVID-19 CVD Registry, said he was also not surprised by a myocarditis signal with AstraZeneca’s adenovirus vaccine.
“Looking at relative risks has biological implications, but the clinical and public health implications are that the absolute risk with the adenovirus is trivial. And you see that with their estimations of absolute risk where it’s literally sort of a needle in the haystack of 1 or 2 per million,” he said in an interview.
Large-scale data
The investigators examined the rates of hospital admission or death from myocarditis, pericarditis, and cardiac arrhythmia in the 28 days following SARS-CoV-2 vaccination or infection by linking the English National Immunisation Database of COVID-19 vaccination with a national patient-level health care database of 38.6 million people, aged 16 years or older, vaccinated from Dec.1, 2020, to Aug. 24, 2021.
The number of people admitted to the hospital or who died during the study period was 1,615 for myocarditis, 1,574 for pericarditis, and 385,508 for cardiac arrhythmia.
There was no evidence of an increased risk for pericarditis or cardiac arrhythmia following vaccination, except for arrhythmia in the 28 days following a second dose of the Moderna vaccine (IRR, 1.46).
In contrast, the risk was increased for pericarditis (IRR, 2.79) and cardiac arrhythmia (IRR, 5.35) in the 28 days following a positive SARS-CoV-2 test result.
Although the scale of the analysis allows for more precise estimates than what’s been possible in smaller data sets, there is the challenge of diagnosing COVID-19 from billing codes and the potential for ascertainment bias, noted Dr. de Lemos.
“Having said that, I think it’s a really important study, because it’s the first study to put the incidence in context in the same general population the risks of myocarditis with various vaccines and with COVID-19,” he said.
“That’s really important and provides a lot of reassurance for those who are trying to balance the risks and benefits of vaccination.”
Analyses by sex and age
A subgroup analysis by age showed increased risks for myocarditis with the mRNA vaccines only in those younger than 40, whereas no association was found with the Oxford adenovirus vaccine.
“We’re not seeing any signal here that would make us change the recommendation for vaccination in children as a consequence of this risk,” Dr. Mills said during a press briefing.
Dr. Bozkurt pointed out, however, that the estimated excess in myocarditis events following a second dose of the Moderna vaccine in these younger adults reportedly exceeded that for SARS-CoV-2 infection (15 per million vs. 10 per million).
“For that age group, it’s concerning and needs further clarification. This hasn’t been seen before,” she said.
The average age was 39 years for those receiving two doses of the Moderna vaccine and 55 for recipients of the Pfizer and Oxford vaccines. The Moderna vaccine wasn’t rolled out until April 2021 in the United Kingdom, the authors noted, so the number of patients who received this vaccine is lower.
Although reports have suggested young males are at greater risk for myocarditis after vaccination, an analysis by sex found that women had an increased risk for myocarditis after a first dose of the AstraZeneca (IRR, 1.40) and Pfizer (IRR, 1.54) vaccines and following a positive COVID-19 test result (IRR, 11.00).
“Women being at increased risk is rather a new message,” Dr. Bozkurt said. “But the incidence rate ratios are being compared against the unvaccinated, so when you see the increase in women, it doesn’t mean it’s increased against men. It would be helpful for sex-specific incidence rate ratios to be reported for younger age subgroups, such as ages 16-20 and 20-30, to determine whether there’s an increased risk for males compared to females at younger ages.”
Age and sex differences are huge questions, but “I think we’ll learn a lot about myocarditis in general from what is going to be an explosion of research into the vaccine-associated causes,” Dr. de Lemos said.
“That will help us understand myocarditis more broadly and prepare us for the next generation of vaccines, which inevitably will be mRNA based.”
Dr. Mills reported having no relevant disclosures. Dr. Bozkurt reported consulting for Bayer and scPharmaceuticals and serving on a clinical-events committee for a trial supported by Abbott Pharmaceuticals and on a data and safety monitoring board for a trial supported by Liva Nova Pharmaceuticals. Dr. De Lemos reported having no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
The first large population study to investigate the association between different COVID-19 vaccines types and cardiac effects and adverse events shows a small increase in the risk for acute myocarditis with both the mRNA-based vaccines and – in what may a first in the literature – an adenovirus-vector vaccine.
The excess risk was seen following the first dose of the ChAdOc1 (AstraZeneca/Oxford), the adenovirus-based vaccine, and the mRNA-based BNT162b2 (Pfizer/BioNTech). It was observed after first and second doses of the mRNA-1273 (Moderna) vaccine.
The incidence rate ratios for myocarditis 1-7 days after the first AstraZeneca, Pfizer, and Moderna injections were 1.76, 1.45, and 8.38, respectively, and 23.1 after the second dose of the Moderna vaccine.
“There’s a bit more uncertainty and worry about mRNA vaccines because it’s quite a new vector for vaccination and, therefore, there’s been more focus on the potential side effects,” said Nicholas Mills, MD.
“But it doesn’t surprise me the signal is present for all types of vaccines because they’re designed to generate a systemic immune response and that is, unfortunately, where you can cause small risks for immune-mediated illnesses like myocarditis,” Dr. Mills, from the University of Edinburgh, told this news organization. Dr. Mills is a coauthor on the study, published Dec. 14 in Nature Medicine.
To put the risks in context, the group estimated between 1 and 10 additional myocarditis hospitalizations or deaths per 1 million people vaccinated, but 40 excess myocarditis events per million following a positive SARS-CoV-2 test result.
As reported, rates of excess myocarditis events associated with a first dose were 2 per million injections of the AstraZeneca vaccine, 1 per million for the Pfizer vaccine, and 6 per million with the Moderna vaccine.
Following a second dose, there were 10 additional myocarditis events per million people receiving the Moderna vaccine and none among recipients of the AstraZeneca or Pfizer vaccines.
“It was particularly seen within the first 7 days of the first dose, which is very consistent with what we see in people who have viral myocarditis,” Dr. Mills said. “So it looks like a real signal but it’s very small.”
The results are in line with previous studies of the Pfizer vaccine in Israel and studies of the Moderna vaccine in the United States, Biykem Bozkurt, MD, PhD, professor of medicine at Baylor College of Medicine, Houston, told this news organization.
“What this paper does is confirm that cardiovascular complications – and they are only looking at a small component of those cardiovascular complications – are markedly higher with the COVID-19 infection than with the vaccines,” she said.
It also adds a new twist to the search for the mechanisms of myocarditis, which has focused on the immunogenicity of the RNA in the Pfizer and Moderna vaccines but also hypothesized that molecular mimicry between the SARS-CoV-2 spike glycoprotein and cell antigens, antibody production against cardiac proteins, and testosterone may play a role.
“But now it doesn’t look like the risk is solely confined to the mRNA vaccine platform because it’s also happening with the adenovirus,” Dr. Bozkurt said. “The mechanisms require future experimental and clinical research and we’ll need more granular data with cohorts that are closely followed up as well as subclinical follow-up.”
James de Lemos, MD, professor of medicine at the University of Texas Southwestern Medical Center, Dallas, and cochair of the American Heart Association’s COVID-19 CVD Registry, said he was also not surprised by a myocarditis signal with AstraZeneca’s adenovirus vaccine.
“Looking at relative risks has biological implications, but the clinical and public health implications are that the absolute risk with the adenovirus is trivial. And you see that with their estimations of absolute risk where it’s literally sort of a needle in the haystack of 1 or 2 per million,” he said in an interview.
Large-scale data
The investigators examined the rates of hospital admission or death from myocarditis, pericarditis, and cardiac arrhythmia in the 28 days following SARS-CoV-2 vaccination or infection by linking the English National Immunisation Database of COVID-19 vaccination with a national patient-level health care database of 38.6 million people, aged 16 years or older, vaccinated from Dec.1, 2020, to Aug. 24, 2021.
The number of people admitted to the hospital or who died during the study period was 1,615 for myocarditis, 1,574 for pericarditis, and 385,508 for cardiac arrhythmia.
There was no evidence of an increased risk for pericarditis or cardiac arrhythmia following vaccination, except for arrhythmia in the 28 days following a second dose of the Moderna vaccine (IRR, 1.46).
In contrast, the risk was increased for pericarditis (IRR, 2.79) and cardiac arrhythmia (IRR, 5.35) in the 28 days following a positive SARS-CoV-2 test result.
Although the scale of the analysis allows for more precise estimates than what’s been possible in smaller data sets, there is the challenge of diagnosing COVID-19 from billing codes and the potential for ascertainment bias, noted Dr. de Lemos.
“Having said that, I think it’s a really important study, because it’s the first study to put the incidence in context in the same general population the risks of myocarditis with various vaccines and with COVID-19,” he said.
“That’s really important and provides a lot of reassurance for those who are trying to balance the risks and benefits of vaccination.”
Analyses by sex and age
A subgroup analysis by age showed increased risks for myocarditis with the mRNA vaccines only in those younger than 40, whereas no association was found with the Oxford adenovirus vaccine.
“We’re not seeing any signal here that would make us change the recommendation for vaccination in children as a consequence of this risk,” Dr. Mills said during a press briefing.
Dr. Bozkurt pointed out, however, that the estimated excess in myocarditis events following a second dose of the Moderna vaccine in these younger adults reportedly exceeded that for SARS-CoV-2 infection (15 per million vs. 10 per million).
“For that age group, it’s concerning and needs further clarification. This hasn’t been seen before,” she said.
The average age was 39 years for those receiving two doses of the Moderna vaccine and 55 for recipients of the Pfizer and Oxford vaccines. The Moderna vaccine wasn’t rolled out until April 2021 in the United Kingdom, the authors noted, so the number of patients who received this vaccine is lower.
Although reports have suggested young males are at greater risk for myocarditis after vaccination, an analysis by sex found that women had an increased risk for myocarditis after a first dose of the AstraZeneca (IRR, 1.40) and Pfizer (IRR, 1.54) vaccines and following a positive COVID-19 test result (IRR, 11.00).
“Women being at increased risk is rather a new message,” Dr. Bozkurt said. “But the incidence rate ratios are being compared against the unvaccinated, so when you see the increase in women, it doesn’t mean it’s increased against men. It would be helpful for sex-specific incidence rate ratios to be reported for younger age subgroups, such as ages 16-20 and 20-30, to determine whether there’s an increased risk for males compared to females at younger ages.”
Age and sex differences are huge questions, but “I think we’ll learn a lot about myocarditis in general from what is going to be an explosion of research into the vaccine-associated causes,” Dr. de Lemos said.
“That will help us understand myocarditis more broadly and prepare us for the next generation of vaccines, which inevitably will be mRNA based.”
Dr. Mills reported having no relevant disclosures. Dr. Bozkurt reported consulting for Bayer and scPharmaceuticals and serving on a clinical-events committee for a trial supported by Abbott Pharmaceuticals and on a data and safety monitoring board for a trial supported by Liva Nova Pharmaceuticals. Dr. De Lemos reported having no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
The first large population study to investigate the association between different COVID-19 vaccines types and cardiac effects and adverse events shows a small increase in the risk for acute myocarditis with both the mRNA-based vaccines and – in what may a first in the literature – an adenovirus-vector vaccine.
The excess risk was seen following the first dose of the ChAdOc1 (AstraZeneca/Oxford), the adenovirus-based vaccine, and the mRNA-based BNT162b2 (Pfizer/BioNTech). It was observed after first and second doses of the mRNA-1273 (Moderna) vaccine.
The incidence rate ratios for myocarditis 1-7 days after the first AstraZeneca, Pfizer, and Moderna injections were 1.76, 1.45, and 8.38, respectively, and 23.1 after the second dose of the Moderna vaccine.
“There’s a bit more uncertainty and worry about mRNA vaccines because it’s quite a new vector for vaccination and, therefore, there’s been more focus on the potential side effects,” said Nicholas Mills, MD.
“But it doesn’t surprise me the signal is present for all types of vaccines because they’re designed to generate a systemic immune response and that is, unfortunately, where you can cause small risks for immune-mediated illnesses like myocarditis,” Dr. Mills, from the University of Edinburgh, told this news organization. Dr. Mills is a coauthor on the study, published Dec. 14 in Nature Medicine.
To put the risks in context, the group estimated between 1 and 10 additional myocarditis hospitalizations or deaths per 1 million people vaccinated, but 40 excess myocarditis events per million following a positive SARS-CoV-2 test result.
As reported, rates of excess myocarditis events associated with a first dose were 2 per million injections of the AstraZeneca vaccine, 1 per million for the Pfizer vaccine, and 6 per million with the Moderna vaccine.
Following a second dose, there were 10 additional myocarditis events per million people receiving the Moderna vaccine and none among recipients of the AstraZeneca or Pfizer vaccines.
“It was particularly seen within the first 7 days of the first dose, which is very consistent with what we see in people who have viral myocarditis,” Dr. Mills said. “So it looks like a real signal but it’s very small.”
The results are in line with previous studies of the Pfizer vaccine in Israel and studies of the Moderna vaccine in the United States, Biykem Bozkurt, MD, PhD, professor of medicine at Baylor College of Medicine, Houston, told this news organization.
“What this paper does is confirm that cardiovascular complications – and they are only looking at a small component of those cardiovascular complications – are markedly higher with the COVID-19 infection than with the vaccines,” she said.
It also adds a new twist to the search for the mechanisms of myocarditis, which has focused on the immunogenicity of the RNA in the Pfizer and Moderna vaccines but also hypothesized that molecular mimicry between the SARS-CoV-2 spike glycoprotein and cell antigens, antibody production against cardiac proteins, and testosterone may play a role.
“But now it doesn’t look like the risk is solely confined to the mRNA vaccine platform because it’s also happening with the adenovirus,” Dr. Bozkurt said. “The mechanisms require future experimental and clinical research and we’ll need more granular data with cohorts that are closely followed up as well as subclinical follow-up.”
James de Lemos, MD, professor of medicine at the University of Texas Southwestern Medical Center, Dallas, and cochair of the American Heart Association’s COVID-19 CVD Registry, said he was also not surprised by a myocarditis signal with AstraZeneca’s adenovirus vaccine.
“Looking at relative risks has biological implications, but the clinical and public health implications are that the absolute risk with the adenovirus is trivial. And you see that with their estimations of absolute risk where it’s literally sort of a needle in the haystack of 1 or 2 per million,” he said in an interview.
Large-scale data
The investigators examined the rates of hospital admission or death from myocarditis, pericarditis, and cardiac arrhythmia in the 28 days following SARS-CoV-2 vaccination or infection by linking the English National Immunisation Database of COVID-19 vaccination with a national patient-level health care database of 38.6 million people, aged 16 years or older, vaccinated from Dec.1, 2020, to Aug. 24, 2021.
The number of people admitted to the hospital or who died during the study period was 1,615 for myocarditis, 1,574 for pericarditis, and 385,508 for cardiac arrhythmia.
There was no evidence of an increased risk for pericarditis or cardiac arrhythmia following vaccination, except for arrhythmia in the 28 days following a second dose of the Moderna vaccine (IRR, 1.46).
In contrast, the risk was increased for pericarditis (IRR, 2.79) and cardiac arrhythmia (IRR, 5.35) in the 28 days following a positive SARS-CoV-2 test result.
Although the scale of the analysis allows for more precise estimates than what’s been possible in smaller data sets, there is the challenge of diagnosing COVID-19 from billing codes and the potential for ascertainment bias, noted Dr. de Lemos.
“Having said that, I think it’s a really important study, because it’s the first study to put the incidence in context in the same general population the risks of myocarditis with various vaccines and with COVID-19,” he said.
“That’s really important and provides a lot of reassurance for those who are trying to balance the risks and benefits of vaccination.”
Analyses by sex and age
A subgroup analysis by age showed increased risks for myocarditis with the mRNA vaccines only in those younger than 40, whereas no association was found with the Oxford adenovirus vaccine.
“We’re not seeing any signal here that would make us change the recommendation for vaccination in children as a consequence of this risk,” Dr. Mills said during a press briefing.
Dr. Bozkurt pointed out, however, that the estimated excess in myocarditis events following a second dose of the Moderna vaccine in these younger adults reportedly exceeded that for SARS-CoV-2 infection (15 per million vs. 10 per million).
“For that age group, it’s concerning and needs further clarification. This hasn’t been seen before,” she said.
The average age was 39 years for those receiving two doses of the Moderna vaccine and 55 for recipients of the Pfizer and Oxford vaccines. The Moderna vaccine wasn’t rolled out until April 2021 in the United Kingdom, the authors noted, so the number of patients who received this vaccine is lower.
Although reports have suggested young males are at greater risk for myocarditis after vaccination, an analysis by sex found that women had an increased risk for myocarditis after a first dose of the AstraZeneca (IRR, 1.40) and Pfizer (IRR, 1.54) vaccines and following a positive COVID-19 test result (IRR, 11.00).
“Women being at increased risk is rather a new message,” Dr. Bozkurt said. “But the incidence rate ratios are being compared against the unvaccinated, so when you see the increase in women, it doesn’t mean it’s increased against men. It would be helpful for sex-specific incidence rate ratios to be reported for younger age subgroups, such as ages 16-20 and 20-30, to determine whether there’s an increased risk for males compared to females at younger ages.”
Age and sex differences are huge questions, but “I think we’ll learn a lot about myocarditis in general from what is going to be an explosion of research into the vaccine-associated causes,” Dr. de Lemos said.
“That will help us understand myocarditis more broadly and prepare us for the next generation of vaccines, which inevitably will be mRNA based.”
Dr. Mills reported having no relevant disclosures. Dr. Bozkurt reported consulting for Bayer and scPharmaceuticals and serving on a clinical-events committee for a trial supported by Abbott Pharmaceuticals and on a data and safety monitoring board for a trial supported by Liva Nova Pharmaceuticals. Dr. De Lemos reported having no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM NATURE MEDICINE
Prurigo nodularis has two disease endotypes, a cluster analysis shows
A cluster analysis of circulating plasma biomarkers in prurigo nodularis (PN) has identified two disease endotypes with inflammatory and noninflammatory biomarker profiles.
said senior author Shawn G. Kwatra, MD, of the department of dermatology at Johns Hopkins University, Baltimore. “This is the beginning of personalized medicine in prurigo nodularis.”
He and others have long observed significant clinical heterogeneity both in the presentation of PN – with the nodules in African American patients, for instance, appearing larger, thicker, and more fibrotic – and in patients’ response to immunomodulating and neuromodulating therapies.
To avoid the introduction of bias, the researchers used an unsupervised machine-learning approach to analyze the levels of 12 inflammatory biomarkers in 20 patients with PN and in matched healthy controls. The biomarkers were chosen based on their demonstrated dysregulation in PN and other inflammatory dermatoses.
The researchers then conducted a population-level analysis using multicenter electronic medical record data to explore inflammatory markers and verify findings from the cluster analysis. The study was published online Oct. 27, 2021, in the Journal of Investigative Dermatology.
One cluster of the 20 patients had higher levels of nine inflammatory biomarkers representing multiple immune axes: Higher interleukin-1 alpha, IL-4, IL-5, IL-6, IL-10, IL-17A, IL-22, and IL-25. This cluster had a higher percentage of Black patients, a higher severity of itch, and lower quality of life scores, the authors report in the preprint.
The other cluster – without such an inflammatory profile – had fewer Black patients and a higher percentage of patients with myelopathy (e.g. spinal stenosis, spinal trauma, degenerative disc disease). The rates of inflammatory comorbidities and of immune- and neuromodulating treatments at the time of blood draw were relatively equivalent between the two clusters.
In the subsequent population-level analysis, using data from a global health research network of EMRs from almost 50 health care organizations, Black patients with PN were found to have higher erythrocyte sedimentation rate, C-reactive protein, ferritin, and eosinophils, and lower transferrin, than White patients with PN. (The analysis included only Black and White patients.)
There are no Food and Drug Administration–approved therapies for PN, and “clinicians need to be really creative in managing these patients,” Dr. Kwatra said.
“There may be suggestions at the bedside that patients have more immune dysregulation, or maybe I’ll see increased circulating blood eosinophils,” he said. “And there are those who don’t seem to have any immune dysregulation and have more features of neurosensitization ... who may have a history of neck pain or back injury.”
The existence of endotypes in PN suggests that patients may benefit from personalized therapies with either immunomodulating or neuromodulating treatments, he and his colleagues wrote. “Further neuroimmune phenotyping studies of PN may pave the way for a future precision medicine management approach.”
Studies of PN conducted in Europe have been almost exclusively in White patients, Dr. Kwatra noted, even though PN has been shown to disproportionately affect Black and other racial/ethnic-minority patients.
Black patients with PN were found to have the highest all-cause mortality over 20 years post diagnosis in a separate analysis of over 22,000 patients with PN. Using data from the same health research network, Dr. Kwatra and coinvestigators stratified patients by race/ethnicity and compared each subgroup with a corresponding subgroup of similar race/ethnicity to control for inherent differences in mortality.
Overall, patients with PN had higher all-cause mortality than controls (hazard ratio, 1.70), likely because of a high comorbidity burden, they wrote in their research letter. Black patients with PN had the highest mortality (HR, 2.07), followed by White (HR, 1.74) and Hispanic (HR, 1.62) patients.
PN may exacerbate existing racial disparities in the social determinants of health, and Black patients may suffer from greater systemic inflammation, Dr. Kwatra and coauthors wrote. Certainly, he said, these findings, as well as the finding of a distinct inflammatory signature in Black patients with PN, support “that the disease burden is much higher” in these patients.
Dr Kwatra disclosed that he is an advisory board member/consultant for Celldex Therapeutics, Galderma, Incyte, Pfizer, Regeneron, and Kiniksa Pharmaceuticals and has received grant funding from several companies. His research is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Grants from the Dermatology Foundation and the Skin of Color Society also helped fund the cluster analysis.
A cluster analysis of circulating plasma biomarkers in prurigo nodularis (PN) has identified two disease endotypes with inflammatory and noninflammatory biomarker profiles.
said senior author Shawn G. Kwatra, MD, of the department of dermatology at Johns Hopkins University, Baltimore. “This is the beginning of personalized medicine in prurigo nodularis.”
He and others have long observed significant clinical heterogeneity both in the presentation of PN – with the nodules in African American patients, for instance, appearing larger, thicker, and more fibrotic – and in patients’ response to immunomodulating and neuromodulating therapies.
To avoid the introduction of bias, the researchers used an unsupervised machine-learning approach to analyze the levels of 12 inflammatory biomarkers in 20 patients with PN and in matched healthy controls. The biomarkers were chosen based on their demonstrated dysregulation in PN and other inflammatory dermatoses.
The researchers then conducted a population-level analysis using multicenter electronic medical record data to explore inflammatory markers and verify findings from the cluster analysis. The study was published online Oct. 27, 2021, in the Journal of Investigative Dermatology.
One cluster of the 20 patients had higher levels of nine inflammatory biomarkers representing multiple immune axes: Higher interleukin-1 alpha, IL-4, IL-5, IL-6, IL-10, IL-17A, IL-22, and IL-25. This cluster had a higher percentage of Black patients, a higher severity of itch, and lower quality of life scores, the authors report in the preprint.
The other cluster – without such an inflammatory profile – had fewer Black patients and a higher percentage of patients with myelopathy (e.g. spinal stenosis, spinal trauma, degenerative disc disease). The rates of inflammatory comorbidities and of immune- and neuromodulating treatments at the time of blood draw were relatively equivalent between the two clusters.
In the subsequent population-level analysis, using data from a global health research network of EMRs from almost 50 health care organizations, Black patients with PN were found to have higher erythrocyte sedimentation rate, C-reactive protein, ferritin, and eosinophils, and lower transferrin, than White patients with PN. (The analysis included only Black and White patients.)
There are no Food and Drug Administration–approved therapies for PN, and “clinicians need to be really creative in managing these patients,” Dr. Kwatra said.
“There may be suggestions at the bedside that patients have more immune dysregulation, or maybe I’ll see increased circulating blood eosinophils,” he said. “And there are those who don’t seem to have any immune dysregulation and have more features of neurosensitization ... who may have a history of neck pain or back injury.”
The existence of endotypes in PN suggests that patients may benefit from personalized therapies with either immunomodulating or neuromodulating treatments, he and his colleagues wrote. “Further neuroimmune phenotyping studies of PN may pave the way for a future precision medicine management approach.”
Studies of PN conducted in Europe have been almost exclusively in White patients, Dr. Kwatra noted, even though PN has been shown to disproportionately affect Black and other racial/ethnic-minority patients.
Black patients with PN were found to have the highest all-cause mortality over 20 years post diagnosis in a separate analysis of over 22,000 patients with PN. Using data from the same health research network, Dr. Kwatra and coinvestigators stratified patients by race/ethnicity and compared each subgroup with a corresponding subgroup of similar race/ethnicity to control for inherent differences in mortality.
Overall, patients with PN had higher all-cause mortality than controls (hazard ratio, 1.70), likely because of a high comorbidity burden, they wrote in their research letter. Black patients with PN had the highest mortality (HR, 2.07), followed by White (HR, 1.74) and Hispanic (HR, 1.62) patients.
PN may exacerbate existing racial disparities in the social determinants of health, and Black patients may suffer from greater systemic inflammation, Dr. Kwatra and coauthors wrote. Certainly, he said, these findings, as well as the finding of a distinct inflammatory signature in Black patients with PN, support “that the disease burden is much higher” in these patients.
Dr Kwatra disclosed that he is an advisory board member/consultant for Celldex Therapeutics, Galderma, Incyte, Pfizer, Regeneron, and Kiniksa Pharmaceuticals and has received grant funding from several companies. His research is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Grants from the Dermatology Foundation and the Skin of Color Society also helped fund the cluster analysis.
A cluster analysis of circulating plasma biomarkers in prurigo nodularis (PN) has identified two disease endotypes with inflammatory and noninflammatory biomarker profiles.
said senior author Shawn G. Kwatra, MD, of the department of dermatology at Johns Hopkins University, Baltimore. “This is the beginning of personalized medicine in prurigo nodularis.”
He and others have long observed significant clinical heterogeneity both in the presentation of PN – with the nodules in African American patients, for instance, appearing larger, thicker, and more fibrotic – and in patients’ response to immunomodulating and neuromodulating therapies.
To avoid the introduction of bias, the researchers used an unsupervised machine-learning approach to analyze the levels of 12 inflammatory biomarkers in 20 patients with PN and in matched healthy controls. The biomarkers were chosen based on their demonstrated dysregulation in PN and other inflammatory dermatoses.
The researchers then conducted a population-level analysis using multicenter electronic medical record data to explore inflammatory markers and verify findings from the cluster analysis. The study was published online Oct. 27, 2021, in the Journal of Investigative Dermatology.
One cluster of the 20 patients had higher levels of nine inflammatory biomarkers representing multiple immune axes: Higher interleukin-1 alpha, IL-4, IL-5, IL-6, IL-10, IL-17A, IL-22, and IL-25. This cluster had a higher percentage of Black patients, a higher severity of itch, and lower quality of life scores, the authors report in the preprint.
The other cluster – without such an inflammatory profile – had fewer Black patients and a higher percentage of patients with myelopathy (e.g. spinal stenosis, spinal trauma, degenerative disc disease). The rates of inflammatory comorbidities and of immune- and neuromodulating treatments at the time of blood draw were relatively equivalent between the two clusters.
In the subsequent population-level analysis, using data from a global health research network of EMRs from almost 50 health care organizations, Black patients with PN were found to have higher erythrocyte sedimentation rate, C-reactive protein, ferritin, and eosinophils, and lower transferrin, than White patients with PN. (The analysis included only Black and White patients.)
There are no Food and Drug Administration–approved therapies for PN, and “clinicians need to be really creative in managing these patients,” Dr. Kwatra said.
“There may be suggestions at the bedside that patients have more immune dysregulation, or maybe I’ll see increased circulating blood eosinophils,” he said. “And there are those who don’t seem to have any immune dysregulation and have more features of neurosensitization ... who may have a history of neck pain or back injury.”
The existence of endotypes in PN suggests that patients may benefit from personalized therapies with either immunomodulating or neuromodulating treatments, he and his colleagues wrote. “Further neuroimmune phenotyping studies of PN may pave the way for a future precision medicine management approach.”
Studies of PN conducted in Europe have been almost exclusively in White patients, Dr. Kwatra noted, even though PN has been shown to disproportionately affect Black and other racial/ethnic-minority patients.
Black patients with PN were found to have the highest all-cause mortality over 20 years post diagnosis in a separate analysis of over 22,000 patients with PN. Using data from the same health research network, Dr. Kwatra and coinvestigators stratified patients by race/ethnicity and compared each subgroup with a corresponding subgroup of similar race/ethnicity to control for inherent differences in mortality.
Overall, patients with PN had higher all-cause mortality than controls (hazard ratio, 1.70), likely because of a high comorbidity burden, they wrote in their research letter. Black patients with PN had the highest mortality (HR, 2.07), followed by White (HR, 1.74) and Hispanic (HR, 1.62) patients.
PN may exacerbate existing racial disparities in the social determinants of health, and Black patients may suffer from greater systemic inflammation, Dr. Kwatra and coauthors wrote. Certainly, he said, these findings, as well as the finding of a distinct inflammatory signature in Black patients with PN, support “that the disease burden is much higher” in these patients.
Dr Kwatra disclosed that he is an advisory board member/consultant for Celldex Therapeutics, Galderma, Incyte, Pfizer, Regeneron, and Kiniksa Pharmaceuticals and has received grant funding from several companies. His research is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Grants from the Dermatology Foundation and the Skin of Color Society also helped fund the cluster analysis.
FROM THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
No negative effect of palbociclib dose reduction in advanced breast cancer
Key clinical point: Palbociclib dose reduction occurs in real-world practice among patients with advanced breast cancer (BC) and has no negative clinical outcomes. It is more common in older patients, with no effect on survival.
Major finding: Overall, palbociclib dose reduction occurred in 33% of patients, with median time-to-next treatment (P < .001) and median overall survival (OS; P = .003) significantly longer in patients with vs without dose reduction. Dose reductions were more common in patients aged ≥70 years vs <70 years (P = .041), with no effect observed on median OS (P = .051).
Study details: This real-world analysis included 598 patients (median age, 64 years) with hormone receptor-positive, human epidermal growth factor receptor 2-negative, advanced BC who were treated with palbociclib combined with either fulvestrant or aromatase inhibitors.
Disclosures: This study was funded by Dutch health insurer VGZ. The authors declared no conflict of interests.
Source: Ismail RK et al. Breast. 2021 Nov 17. doi: 10.1016/j.breast.2021.11.013.
Key clinical point: Palbociclib dose reduction occurs in real-world practice among patients with advanced breast cancer (BC) and has no negative clinical outcomes. It is more common in older patients, with no effect on survival.
Major finding: Overall, palbociclib dose reduction occurred in 33% of patients, with median time-to-next treatment (P < .001) and median overall survival (OS; P = .003) significantly longer in patients with vs without dose reduction. Dose reductions were more common in patients aged ≥70 years vs <70 years (P = .041), with no effect observed on median OS (P = .051).
Study details: This real-world analysis included 598 patients (median age, 64 years) with hormone receptor-positive, human epidermal growth factor receptor 2-negative, advanced BC who were treated with palbociclib combined with either fulvestrant or aromatase inhibitors.
Disclosures: This study was funded by Dutch health insurer VGZ. The authors declared no conflict of interests.
Source: Ismail RK et al. Breast. 2021 Nov 17. doi: 10.1016/j.breast.2021.11.013.
Key clinical point: Palbociclib dose reduction occurs in real-world practice among patients with advanced breast cancer (BC) and has no negative clinical outcomes. It is more common in older patients, with no effect on survival.
Major finding: Overall, palbociclib dose reduction occurred in 33% of patients, with median time-to-next treatment (P < .001) and median overall survival (OS; P = .003) significantly longer in patients with vs without dose reduction. Dose reductions were more common in patients aged ≥70 years vs <70 years (P = .041), with no effect observed on median OS (P = .051).
Study details: This real-world analysis included 598 patients (median age, 64 years) with hormone receptor-positive, human epidermal growth factor receptor 2-negative, advanced BC who were treated with palbociclib combined with either fulvestrant or aromatase inhibitors.
Disclosures: This study was funded by Dutch health insurer VGZ. The authors declared no conflict of interests.
Source: Ismail RK et al. Breast. 2021 Nov 17. doi: 10.1016/j.breast.2021.11.013.