Rheumatology News

Two recent articles in the medical literature provide new information on mucocutaneous manifestations of COVID-19 in children, which may help guide dermatologists in making accurate diagnoses and stratifying children at risk for serious, systemic illness due to the virus.

In a single-center descriptive study carried out over a 9-month period, researchers in Madrid found that of 50 hospitalized children infected with COVID-19, 21 (42%) had mucocutaneous symptoms, most commonly exanthem, followed by conjunctival hyperemia without secretion and red cracked lips or strawberry tongue. In addition, 18 (36%) fulfilled criteria for Multisystem Inflammatory Syndrome in Children (MIS-C).

“Based on findings in adult patients, the skin manifestations of COVID-19 have been classified under five categories: acral pseudo-chilblain, vesicular eruptions, urticarial lesions, maculopapular eruptions, and livedo or necrosis,” David Andina-Martinez, MD, of Hospital Infantil Universitario Niño Jesús, Madrid, and colleagues wrote in the study, which was published online on April 2 in the Journal of the American Academy of Dermatology.

“Chilblain lesions in healthy children and adolescents have received much attention; these lesions resolve without complications after a few weeks,” they added. “Besides, other cutaneous manifestations of COVID-19 in children have been the matter of case reports or small case series. Nevertheless, the mucocutaneous manifestations in hospitalized children infected with SARS-CoV-2 and their implications on the clinical course have not yet been extensively described.”

In an effort to describe the mucocutaneous manifestations in children hospitalized for COVID-19, the researchers evaluated 50 children up to 18 years of age who were admitted between March 1 and Nov. 30, 2020, to Hospital Infantil Universitario Niño Jesús, which was designated as a pediatric reference center during the peak of the pandemic. The main reasons for admission were respiratory illness (40%) and MIS-C (40%).

Of the 50 patients, 44 (88%) had a positive RT-PCR for SARS-CoV-2 and 6 (12%) met clinical suspicion criteria and had a negative RT-PCR with a positive IgG serology. In 34 patients (68%), a close contact with a suspected or confirmed case of COVID-19 was referred, while the source of the infection remained unknown in the remaining 16 patients (32%).

The researchers reported that 21 patients (42%) had mucocutaneous symptoms, most commonly maculopapular exanthem (86%), conjunctival hyperemia (81%), and red cracked lips or strawberry tongue (43%). In addition, 18 of the 21 patients (86%) fulfilled criteria for MIS-C.

“A tricky thing about MIS-C is that it often manifests 4-5 weeks after a child had COVID-19,” said Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn., who was asked to comment on the study. “MIS-C is associated with characteristic bright red lips and a red tongue that might resemble a strawberry. Such oral findings should prompt rapid evaluation for other signs and symptoms. There can be redness of the eyes or other more nonspecific skin findings (large or small areas of redness on the trunk or limbs, sometimes with surface change), but more importantly, fever, a rapid heartbeat, diarrhea, or breathing issues. The risk with MIS-C is a rapid decline in a child’s health, with admission to an intensive care unit.”

Dr. Andina-Martinez and his colleagues also contrast the skin findings of MIS-C, which are not generally on the hands or feet, with the so-called “COVID toe” or finger phenomenon, which has also been associated with SARS-CoV-2, particularly in children. “Only one of the patients in this series had skin involvement of a finger, and it only appeared after recovery from MIS-C,” Dr. Ko noted. “Distinguishing COVID toes from MIS-C is important, as COVID toes has a very good outcome, while MIS-C can have severe consequences, including protracted heart disease.”

In other findings, patients who presented with mucocutaneous signs tended to be older than those without skin signs and they presented at the emergency department with poor general status and extreme tachycardia. They also had higher C-reactive protein and D-dimer levels and lower lymphocyte counts and faced a more than a 10-fold increased risk of being admitted to the PICU, compared with patients who did not have skin signs (OR, 10.24; P = .003).

In a separate study published online on April 7 in JAMA Dermatology, Zachary E. Holcomb, MD, of the combined dermatology residency program at Massachusetts General Hospital, Boston, and colleagues presented what is believed to be the first case report of reactive infectious mucocutaneous eruption (RIME) triggered by SARS-CoV-2. RIME is the preferred term for pediatric patients who present with mucositis and rash (often a scant or even absent skin eruption) triggered by various infectious agents.

The patient, a 17-year-old male, presented to the emergency department with 3 days of mouth pain and nonpainful penile erosions. “One week prior, he experienced transient anosmia and ageusia that had since spontaneously resolved,” the researchers wrote. “At that time, he was tested for SARS-CoV-2 infection via nasopharyngeal polymerase chain reaction (PCR), the results of which were positive.”

At presentation, the patient had no fever, his vital signs were normal, and the physical exam revealed shallow erosions of the vermilion lips and hard palate, circumferential erythematous erosions of the periurethral glans penis, and five small vesicles on the trunk and upper extremities. Serum analysis revealed a normal white blood cell count with mild absolute lymphopenia, slightly elevated creatinine level, normal liver function, slightly elevated C-reactive protein level, and normal ferritin level.

Dr. Holcomb and colleagues made a diagnosis of SARS-CoV-2–associated RIME based on microbiological results, which revealed positive repeated SARS-CoV-2 nasopharyngeal PCR and negative nasopharyngeal PCR testing for Mycoplasma pneumoniae, adenovirus, Chlamydophila pneumoniae, human metapneumovirus, influenza A/B, parainfluenza 1 to 4, rhinovirus, and respiratory syncytial virus. In addition, titers of Mycoplasma pneumoniae IgM levels were negative, but Mycoplasma pneumoniae IgG levels were elevated.

The lesions resolved with 60 mg of oral prednisone taken daily for 4 days. A recurrence of oral mucositis 3 months later responded to 80 mg oral prednisone taken daily for 6 days.

“It’s not surprising that SARS-CoV-2 is yet another trigger for RIME,” said Anna Yasmine Kirkorian, MD, chief of the division of dermatology at Children’s National Hospital, Washington, who was asked to comment about the case report.

“The take-home message is for clinicians to be aware of this association and distinguish these patients from those with MIS-C, because patients with MIS-C require monitoring and urgent systemic treatment. RIME and MIS-C may potentially be distinguished clinically based on the nature of the mucositis (hemorrhagic and erosive in RIME, dry, cracked lips with ‘strawberry tongue’ in MIS-C) but more importantly patients with RIME lack laboratory evidence of severe systemic inflammation,” such as ESR, CRP, or ferritin, she said.

“A final interesting point in this article was the recurrence of mucositis in this patient, which could mean that recurrent mucositis/recurrent RIME might be yet another manifestation of ‘long-COVID’ (now called post-Acute Sequelae of SARS-CoV-2 infection) in some patients,” Dr. Kirkorian added. She noted that the American Academy of Dermatology–International League of Dermatologic Societies COVID-19 Dermatology Registry and articles like these “provide invaluable ‘hot off the presses’ information for clinicians who are facing the protean manifestations of a novel viral epidemic.”

The researchers reported having no financial disclosures.
 

dbrunk@mdedge.com

Two recent articles in the medical literature provide new information on mucocutaneous manifestations of COVID-19 in children, which may help guide dermatologists in making accurate diagnoses and stratifying children at risk for serious, systemic illness due to the virus.

In a single-center descriptive study carried out over a 9-month period, researchers in Madrid found that of 50 hospitalized children infected with COVID-19, 21 (42%) had mucocutaneous symptoms, most commonly exanthem, followed by conjunctival hyperemia without secretion and red cracked lips or strawberry tongue. In addition, 18 (36%) fulfilled criteria for Multisystem Inflammatory Syndrome in Children (MIS-C).

“Based on findings in adult patients, the skin manifestations of COVID-19 have been classified under five categories: acral pseudo-chilblain, vesicular eruptions, urticarial lesions, maculopapular eruptions, and livedo or necrosis,” David Andina-Martinez, MD, of Hospital Infantil Universitario Niño Jesús, Madrid, and colleagues wrote in the study, which was published online on April 2 in the Journal of the American Academy of Dermatology.

“Chilblain lesions in healthy children and adolescents have received much attention; these lesions resolve without complications after a few weeks,” they added. “Besides, other cutaneous manifestations of COVID-19 in children have been the matter of case reports or small case series. Nevertheless, the mucocutaneous manifestations in hospitalized children infected with SARS-CoV-2 and their implications on the clinical course have not yet been extensively described.”

In an effort to describe the mucocutaneous manifestations in children hospitalized for COVID-19, the researchers evaluated 50 children up to 18 years of age who were admitted between March 1 and Nov. 30, 2020, to Hospital Infantil Universitario Niño Jesús, which was designated as a pediatric reference center during the peak of the pandemic. The main reasons for admission were respiratory illness (40%) and MIS-C (40%).

Of the 50 patients, 44 (88%) had a positive RT-PCR for SARS-CoV-2 and 6 (12%) met clinical suspicion criteria and had a negative RT-PCR with a positive IgG serology. In 34 patients (68%), a close contact with a suspected or confirmed case of COVID-19 was referred, while the source of the infection remained unknown in the remaining 16 patients (32%).

The researchers reported that 21 patients (42%) had mucocutaneous symptoms, most commonly maculopapular exanthem (86%), conjunctival hyperemia (81%), and red cracked lips or strawberry tongue (43%). In addition, 18 of the 21 patients (86%) fulfilled criteria for MIS-C.

“A tricky thing about MIS-C is that it often manifests 4-5 weeks after a child had COVID-19,” said Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn., who was asked to comment on the study. “MIS-C is associated with characteristic bright red lips and a red tongue that might resemble a strawberry. Such oral findings should prompt rapid evaluation for other signs and symptoms. There can be redness of the eyes or other more nonspecific skin findings (large or small areas of redness on the trunk or limbs, sometimes with surface change), but more importantly, fever, a rapid heartbeat, diarrhea, or breathing issues. The risk with MIS-C is a rapid decline in a child’s health, with admission to an intensive care unit.”

Dr. Andina-Martinez and his colleagues also contrast the skin findings of MIS-C, which are not generally on the hands or feet, with the so-called “COVID toe” or finger phenomenon, which has also been associated with SARS-CoV-2, particularly in children. “Only one of the patients in this series had skin involvement of a finger, and it only appeared after recovery from MIS-C,” Dr. Ko noted. “Distinguishing COVID toes from MIS-C is important, as COVID toes has a very good outcome, while MIS-C can have severe consequences, including protracted heart disease.”

In other findings, patients who presented with mucocutaneous signs tended to be older than those without skin signs and they presented at the emergency department with poor general status and extreme tachycardia. They also had higher C-reactive protein and D-dimer levels and lower lymphocyte counts and faced a more than a 10-fold increased risk of being admitted to the PICU, compared with patients who did not have skin signs (OR, 10.24; P = .003).

In a separate study published online on April 7 in JAMA Dermatology, Zachary E. Holcomb, MD, of the combined dermatology residency program at Massachusetts General Hospital, Boston, and colleagues presented what is believed to be the first case report of reactive infectious mucocutaneous eruption (RIME) triggered by SARS-CoV-2. RIME is the preferred term for pediatric patients who present with mucositis and rash (often a scant or even absent skin eruption) triggered by various infectious agents.

The patient, a 17-year-old male, presented to the emergency department with 3 days of mouth pain and nonpainful penile erosions. “One week prior, he experienced transient anosmia and ageusia that had since spontaneously resolved,” the researchers wrote. “At that time, he was tested for SARS-CoV-2 infection via nasopharyngeal polymerase chain reaction (PCR), the results of which were positive.”

At presentation, the patient had no fever, his vital signs were normal, and the physical exam revealed shallow erosions of the vermilion lips and hard palate, circumferential erythematous erosions of the periurethral glans penis, and five small vesicles on the trunk and upper extremities. Serum analysis revealed a normal white blood cell count with mild absolute lymphopenia, slightly elevated creatinine level, normal liver function, slightly elevated C-reactive protein level, and normal ferritin level.

Dr. Holcomb and colleagues made a diagnosis of SARS-CoV-2–associated RIME based on microbiological results, which revealed positive repeated SARS-CoV-2 nasopharyngeal PCR and negative nasopharyngeal PCR testing for Mycoplasma pneumoniae, adenovirus, Chlamydophila pneumoniae, human metapneumovirus, influenza A/B, parainfluenza 1 to 4, rhinovirus, and respiratory syncytial virus. In addition, titers of Mycoplasma pneumoniae IgM levels were negative, but Mycoplasma pneumoniae IgG levels were elevated.

The lesions resolved with 60 mg of oral prednisone taken daily for 4 days. A recurrence of oral mucositis 3 months later responded to 80 mg oral prednisone taken daily for 6 days.

“It’s not surprising that SARS-CoV-2 is yet another trigger for RIME,” said Anna Yasmine Kirkorian, MD, chief of the division of dermatology at Children’s National Hospital, Washington, who was asked to comment about the case report.

“The take-home message is for clinicians to be aware of this association and distinguish these patients from those with MIS-C, because patients with MIS-C require monitoring and urgent systemic treatment. RIME and MIS-C may potentially be distinguished clinically based on the nature of the mucositis (hemorrhagic and erosive in RIME, dry, cracked lips with ‘strawberry tongue’ in MIS-C) but more importantly patients with RIME lack laboratory evidence of severe systemic inflammation,” such as ESR, CRP, or ferritin, she said.

“A final interesting point in this article was the recurrence of mucositis in this patient, which could mean that recurrent mucositis/recurrent RIME might be yet another manifestation of ‘long-COVID’ (now called post-Acute Sequelae of SARS-CoV-2 infection) in some patients,” Dr. Kirkorian added. She noted that the American Academy of Dermatology–International League of Dermatologic Societies COVID-19 Dermatology Registry and articles like these “provide invaluable ‘hot off the presses’ information for clinicians who are facing the protean manifestations of a novel viral epidemic.”

The researchers reported having no financial disclosures.
 

dbrunk@mdedge.com

Two recent articles in the medical literature provide new information on mucocutaneous manifestations of COVID-19 in children, which may help guide dermatologists in making accurate diagnoses and stratifying children at risk for serious, systemic illness due to the virus.

In a single-center descriptive study carried out over a 9-month period, researchers in Madrid found that of 50 hospitalized children infected with COVID-19, 21 (42%) had mucocutaneous symptoms, most commonly exanthem, followed by conjunctival hyperemia without secretion and red cracked lips or strawberry tongue. In addition, 18 (36%) fulfilled criteria for Multisystem Inflammatory Syndrome in Children (MIS-C).

“Based on findings in adult patients, the skin manifestations of COVID-19 have been classified under five categories: acral pseudo-chilblain, vesicular eruptions, urticarial lesions, maculopapular eruptions, and livedo or necrosis,” David Andina-Martinez, MD, of Hospital Infantil Universitario Niño Jesús, Madrid, and colleagues wrote in the study, which was published online on April 2 in the Journal of the American Academy of Dermatology.

“Chilblain lesions in healthy children and adolescents have received much attention; these lesions resolve without complications after a few weeks,” they added. “Besides, other cutaneous manifestations of COVID-19 in children have been the matter of case reports or small case series. Nevertheless, the mucocutaneous manifestations in hospitalized children infected with SARS-CoV-2 and their implications on the clinical course have not yet been extensively described.”

In an effort to describe the mucocutaneous manifestations in children hospitalized for COVID-19, the researchers evaluated 50 children up to 18 years of age who were admitted between March 1 and Nov. 30, 2020, to Hospital Infantil Universitario Niño Jesús, which was designated as a pediatric reference center during the peak of the pandemic. The main reasons for admission were respiratory illness (40%) and MIS-C (40%).

Of the 50 patients, 44 (88%) had a positive RT-PCR for SARS-CoV-2 and 6 (12%) met clinical suspicion criteria and had a negative RT-PCR with a positive IgG serology. In 34 patients (68%), a close contact with a suspected or confirmed case of COVID-19 was referred, while the source of the infection remained unknown in the remaining 16 patients (32%).

The researchers reported that 21 patients (42%) had mucocutaneous symptoms, most commonly maculopapular exanthem (86%), conjunctival hyperemia (81%), and red cracked lips or strawberry tongue (43%). In addition, 18 of the 21 patients (86%) fulfilled criteria for MIS-C.

“A tricky thing about MIS-C is that it often manifests 4-5 weeks after a child had COVID-19,” said Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn., who was asked to comment on the study. “MIS-C is associated with characteristic bright red lips and a red tongue that might resemble a strawberry. Such oral findings should prompt rapid evaluation for other signs and symptoms. There can be redness of the eyes or other more nonspecific skin findings (large or small areas of redness on the trunk or limbs, sometimes with surface change), but more importantly, fever, a rapid heartbeat, diarrhea, or breathing issues. The risk with MIS-C is a rapid decline in a child’s health, with admission to an intensive care unit.”

Dr. Andina-Martinez and his colleagues also contrast the skin findings of MIS-C, which are not generally on the hands or feet, with the so-called “COVID toe” or finger phenomenon, which has also been associated with SARS-CoV-2, particularly in children. “Only one of the patients in this series had skin involvement of a finger, and it only appeared after recovery from MIS-C,” Dr. Ko noted. “Distinguishing COVID toes from MIS-C is important, as COVID toes has a very good outcome, while MIS-C can have severe consequences, including protracted heart disease.”

In other findings, patients who presented with mucocutaneous signs tended to be older than those without skin signs and they presented at the emergency department with poor general status and extreme tachycardia. They also had higher C-reactive protein and D-dimer levels and lower lymphocyte counts and faced a more than a 10-fold increased risk of being admitted to the PICU, compared with patients who did not have skin signs (OR, 10.24; P = .003).

In a separate study published online on April 7 in JAMA Dermatology, Zachary E. Holcomb, MD, of the combined dermatology residency program at Massachusetts General Hospital, Boston, and colleagues presented what is believed to be the first case report of reactive infectious mucocutaneous eruption (RIME) triggered by SARS-CoV-2. RIME is the preferred term for pediatric patients who present with mucositis and rash (often a scant or even absent skin eruption) triggered by various infectious agents.

The patient, a 17-year-old male, presented to the emergency department with 3 days of mouth pain and nonpainful penile erosions. “One week prior, he experienced transient anosmia and ageusia that had since spontaneously resolved,” the researchers wrote. “At that time, he was tested for SARS-CoV-2 infection via nasopharyngeal polymerase chain reaction (PCR), the results of which were positive.”

At presentation, the patient had no fever, his vital signs were normal, and the physical exam revealed shallow erosions of the vermilion lips and hard palate, circumferential erythematous erosions of the periurethral glans penis, and five small vesicles on the trunk and upper extremities. Serum analysis revealed a normal white blood cell count with mild absolute lymphopenia, slightly elevated creatinine level, normal liver function, slightly elevated C-reactive protein level, and normal ferritin level.

Dr. Holcomb and colleagues made a diagnosis of SARS-CoV-2–associated RIME based on microbiological results, which revealed positive repeated SARS-CoV-2 nasopharyngeal PCR and negative nasopharyngeal PCR testing for Mycoplasma pneumoniae, adenovirus, Chlamydophila pneumoniae, human metapneumovirus, influenza A/B, parainfluenza 1 to 4, rhinovirus, and respiratory syncytial virus. In addition, titers of Mycoplasma pneumoniae IgM levels were negative, but Mycoplasma pneumoniae IgG levels were elevated.

The lesions resolved with 60 mg of oral prednisone taken daily for 4 days. A recurrence of oral mucositis 3 months later responded to 80 mg oral prednisone taken daily for 6 days.

“It’s not surprising that SARS-CoV-2 is yet another trigger for RIME,” said Anna Yasmine Kirkorian, MD, chief of the division of dermatology at Children’s National Hospital, Washington, who was asked to comment about the case report.

“The take-home message is for clinicians to be aware of this association and distinguish these patients from those with MIS-C, because patients with MIS-C require monitoring and urgent systemic treatment. RIME and MIS-C may potentially be distinguished clinically based on the nature of the mucositis (hemorrhagic and erosive in RIME, dry, cracked lips with ‘strawberry tongue’ in MIS-C) but more importantly patients with RIME lack laboratory evidence of severe systemic inflammation,” such as ESR, CRP, or ferritin, she said.

“A final interesting point in this article was the recurrence of mucositis in this patient, which could mean that recurrent mucositis/recurrent RIME might be yet another manifestation of ‘long-COVID’ (now called post-Acute Sequelae of SARS-CoV-2 infection) in some patients,” Dr. Kirkorian added. She noted that the American Academy of Dermatology–International League of Dermatologic Societies COVID-19 Dermatology Registry and articles like these “provide invaluable ‘hot off the presses’ information for clinicians who are facing the protean manifestations of a novel viral epidemic.”

The researchers reported having no financial disclosures.
 

dbrunk@mdedge.com

Seven years after concluding that evidence was insufficient to recommend screening for vitamin D deficiency in the general population, the United States Preventive Services Task Force (USPSTF) has revisited the issue – and come up with the same conclusion.

Overall, “the current evidence is inadequate to determine whether screening for and treatment of asymptomatic low 25(OH)D levels improve clinical outcomes in community dwelling adults,” the task force concluded in its statement, recommending an “I” for insufficient.

The statement was published online April 13 in JAMA.

In the absence of screening recommendations, clinicians may be best advised to instead focus on diet and supplementation for those considered at risk, said Anne R. Cappola, MD, of the University of Pennsylvania, Philadelphia.

“Rather than posing the question of screening the general population for vitamin D deficiency, let’s focus on ensuring that everyone consumes the age-based recommended daily allowance of vitamin D instead,” Dr. Cappola, a coauthor of the accompanying editorial, said in an interview.
 

No studies have directly evaluated benefits of screening

The latest USPSTF recommendation is based on a systematic review of the benefits and harms of screening and early treatment for vitamin D deficiency in asymptomatic, community-dwelling nonpregnant adults aged 18 or older in the primary care setting with no signs or symptoms of deficiency.

The review found no studies that directly evaluated the benefits of screening for vitamin D deficiency.

However, 26 randomized clinical trials and one nested case-control study evaluated the effectiveness of treatment of vitamin D deficiency with supplementation.

And while observational studies have linked lower vitamin D levels with a multitude of conditions and risks, evidence of any benefit was inconsistent, with none identified for most major outcomes in asymptomatic adults – the focus of the Task Force recommendation.

“Among asymptomatic, community-dwelling populations with low vitamin D levels, the evidence suggests that treatment with vitamin D has no effect on mortality or the incidence of fractures, falls, depression, diabetes, cardiovascular disease, cancer, or adverse events,” the review authors stress.

“The evidence is inconclusive about the effect of treatment on physical functioning and infection.”
 

One in four are vitamin D deficient

In terms of the further question of the potential harms of vitamin D screening of asymptomatic individuals, a key concern is the potential for misclassification and over- or underdiagnosis due to inconsistent cutoffs and variability of different screening assays, the review concluded.

However, with the rare exception of vitamin D toxicity from supplementation well above sufficient levels, treatment with vitamin D supplementation appears relatively safe.

With a lack of consensus even over the basic cutoff for vitamin D deficiency, the National Academy of Medicine determined in 2011 that hydroxyvitamin D (25[OH]D) levels below 20 ng/mL are deficient for bone health, with no evidence of different thresholds for any other health condition.

Based on that cutoff, the National Health and Nutrition Examination Survey (NHANES), reported in 2014 that 25% of the U.S. population over the age of 1 was vitamin D deficient, with 18% of the population having 25(OH)D levels of 12-19 ng/mL and 5% having very low levels (< 12 ng/mL).
 

More work needed to determine groups at risk

While the task force report did not delve into testing or treatment recommendations for symptomatic adults, key established risk factors that may help clinicians identify those who are vitamin D deficient include obesity, receiving little or no UVB light exposure, and older age.

In general, obesity is associated with a 1.3- to 2-fold risk of being vitamin D deficient based on the criteria used, while non-Hispanic Blacks are 2-10 times more likely to be deficient compared with non-Hispanic White patients, the task force noted.

However, the implications of vitamin D deficiency in certain populations can vary. For instance, non-Hispanic Black people, despite having a higher prevalence of lower vitamin D levels compared with White people, in fact, have lower reported rates of fractures.

To address the various issues and gain a better understanding of the complexities of vitamin D deficiency, the task force calls for further research in key areas.

“More research is needed to determine whether total serum 25(OH)D levels are the best measure of vitamin D deficiency and whether the best measure of vitamin D deficiency varies by subgroups defined by race, ethnicity, or sex,” the authors indicated.

Furthermore, “more research is needed to determine the cutoff that defines vitamin D deficiency and whether that cutoff varies by specific clinical outcome or by subgroups defined by race, ethnicity, or sex.”
 

No support for population-based screening in guidelines

With the lack of conclusive evidence, no organizations currently recommend population-based screening for vitamin D deficiency in asymptomatic patients, and the American Society for Clinical Pathology endorses this stance.

The Endocrine Society and the American Association of Clinical Endocrinologists meanwhile do recommend screening for vitamin D deficiency in patients considered at risk.

Data show there was as much as an 80-fold increase in Medicare reimbursement volumes for vitamin D testing among clinicians from 2000 to 2010; however, that rate may have leveled off after the National Academy of Medicine reported on set deficiency levels, said Sherri-Ann M. Burnett-Bowie, MD, MPH, Dr. Cappola’s editorial coauthor.

Dr. Burnett-Bowie noted that she regularly tests her patients’ vitamin D levels, however most of her patients have osteoporosis or fractures.

“I do screen them for vitamin D deficiency since optimizing their vitamin D will improve calcium absorption, which is important for treating their osteoporosis,” Dr. Burnett-Bowie, of the endocrine division, department of medicine, Massachusetts General Hospital, Boston, said in an interview.

In terms of broader testing of asymptomatic patients in the general population, however, any changes in screening will likely be contingent on developments in the effects of treatment, she said.

“Given the challenge in finding benefits of vitamin D supplementation in those who are deficient, it will likely be more challenging to find benefits from wider screening,” she concluded.

The USPSTF and editorialists reported having no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Seven years after concluding that evidence was insufficient to recommend screening for vitamin D deficiency in the general population, the United States Preventive Services Task Force (USPSTF) has revisited the issue – and come up with the same conclusion.

Overall, “the current evidence is inadequate to determine whether screening for and treatment of asymptomatic low 25(OH)D levels improve clinical outcomes in community dwelling adults,” the task force concluded in its statement, recommending an “I” for insufficient.

The statement was published online April 13 in JAMA.

In the absence of screening recommendations, clinicians may be best advised to instead focus on diet and supplementation for those considered at risk, said Anne R. Cappola, MD, of the University of Pennsylvania, Philadelphia.

“Rather than posing the question of screening the general population for vitamin D deficiency, let’s focus on ensuring that everyone consumes the age-based recommended daily allowance of vitamin D instead,” Dr. Cappola, a coauthor of the accompanying editorial, said in an interview.
 

No studies have directly evaluated benefits of screening

The latest USPSTF recommendation is based on a systematic review of the benefits and harms of screening and early treatment for vitamin D deficiency in asymptomatic, community-dwelling nonpregnant adults aged 18 or older in the primary care setting with no signs or symptoms of deficiency.

The review found no studies that directly evaluated the benefits of screening for vitamin D deficiency.

However, 26 randomized clinical trials and one nested case-control study evaluated the effectiveness of treatment of vitamin D deficiency with supplementation.

And while observational studies have linked lower vitamin D levels with a multitude of conditions and risks, evidence of any benefit was inconsistent, with none identified for most major outcomes in asymptomatic adults – the focus of the Task Force recommendation.

“Among asymptomatic, community-dwelling populations with low vitamin D levels, the evidence suggests that treatment with vitamin D has no effect on mortality or the incidence of fractures, falls, depression, diabetes, cardiovascular disease, cancer, or adverse events,” the review authors stress.

“The evidence is inconclusive about the effect of treatment on physical functioning and infection.”
 

One in four are vitamin D deficient

In terms of the further question of the potential harms of vitamin D screening of asymptomatic individuals, a key concern is the potential for misclassification and over- or underdiagnosis due to inconsistent cutoffs and variability of different screening assays, the review concluded.

However, with the rare exception of vitamin D toxicity from supplementation well above sufficient levels, treatment with vitamin D supplementation appears relatively safe.

With a lack of consensus even over the basic cutoff for vitamin D deficiency, the National Academy of Medicine determined in 2011 that hydroxyvitamin D (25[OH]D) levels below 20 ng/mL are deficient for bone health, with no evidence of different thresholds for any other health condition.

Based on that cutoff, the National Health and Nutrition Examination Survey (NHANES), reported in 2014 that 25% of the U.S. population over the age of 1 was vitamin D deficient, with 18% of the population having 25(OH)D levels of 12-19 ng/mL and 5% having very low levels (< 12 ng/mL).
 

More work needed to determine groups at risk

While the task force report did not delve into testing or treatment recommendations for symptomatic adults, key established risk factors that may help clinicians identify those who are vitamin D deficient include obesity, receiving little or no UVB light exposure, and older age.

In general, obesity is associated with a 1.3- to 2-fold risk of being vitamin D deficient based on the criteria used, while non-Hispanic Blacks are 2-10 times more likely to be deficient compared with non-Hispanic White patients, the task force noted.

However, the implications of vitamin D deficiency in certain populations can vary. For instance, non-Hispanic Black people, despite having a higher prevalence of lower vitamin D levels compared with White people, in fact, have lower reported rates of fractures.

To address the various issues and gain a better understanding of the complexities of vitamin D deficiency, the task force calls for further research in key areas.

“More research is needed to determine whether total serum 25(OH)D levels are the best measure of vitamin D deficiency and whether the best measure of vitamin D deficiency varies by subgroups defined by race, ethnicity, or sex,” the authors indicated.

Furthermore, “more research is needed to determine the cutoff that defines vitamin D deficiency and whether that cutoff varies by specific clinical outcome or by subgroups defined by race, ethnicity, or sex.”
 

No support for population-based screening in guidelines

With the lack of conclusive evidence, no organizations currently recommend population-based screening for vitamin D deficiency in asymptomatic patients, and the American Society for Clinical Pathology endorses this stance.

The Endocrine Society and the American Association of Clinical Endocrinologists meanwhile do recommend screening for vitamin D deficiency in patients considered at risk.

Data show there was as much as an 80-fold increase in Medicare reimbursement volumes for vitamin D testing among clinicians from 2000 to 2010; however, that rate may have leveled off after the National Academy of Medicine reported on set deficiency levels, said Sherri-Ann M. Burnett-Bowie, MD, MPH, Dr. Cappola’s editorial coauthor.

Dr. Burnett-Bowie noted that she regularly tests her patients’ vitamin D levels, however most of her patients have osteoporosis or fractures.

“I do screen them for vitamin D deficiency since optimizing their vitamin D will improve calcium absorption, which is important for treating their osteoporosis,” Dr. Burnett-Bowie, of the endocrine division, department of medicine, Massachusetts General Hospital, Boston, said in an interview.

In terms of broader testing of asymptomatic patients in the general population, however, any changes in screening will likely be contingent on developments in the effects of treatment, she said.

“Given the challenge in finding benefits of vitamin D supplementation in those who are deficient, it will likely be more challenging to find benefits from wider screening,” she concluded.

The USPSTF and editorialists reported having no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Seven years after concluding that evidence was insufficient to recommend screening for vitamin D deficiency in the general population, the United States Preventive Services Task Force (USPSTF) has revisited the issue – and come up with the same conclusion.

Overall, “the current evidence is inadequate to determine whether screening for and treatment of asymptomatic low 25(OH)D levels improve clinical outcomes in community dwelling adults,” the task force concluded in its statement, recommending an “I” for insufficient.

The statement was published online April 13 in JAMA.

In the absence of screening recommendations, clinicians may be best advised to instead focus on diet and supplementation for those considered at risk, said Anne R. Cappola, MD, of the University of Pennsylvania, Philadelphia.

“Rather than posing the question of screening the general population for vitamin D deficiency, let’s focus on ensuring that everyone consumes the age-based recommended daily allowance of vitamin D instead,” Dr. Cappola, a coauthor of the accompanying editorial, said in an interview.
 

No studies have directly evaluated benefits of screening

The latest USPSTF recommendation is based on a systematic review of the benefits and harms of screening and early treatment for vitamin D deficiency in asymptomatic, community-dwelling nonpregnant adults aged 18 or older in the primary care setting with no signs or symptoms of deficiency.

The review found no studies that directly evaluated the benefits of screening for vitamin D deficiency.

However, 26 randomized clinical trials and one nested case-control study evaluated the effectiveness of treatment of vitamin D deficiency with supplementation.

And while observational studies have linked lower vitamin D levels with a multitude of conditions and risks, evidence of any benefit was inconsistent, with none identified for most major outcomes in asymptomatic adults – the focus of the Task Force recommendation.

“Among asymptomatic, community-dwelling populations with low vitamin D levels, the evidence suggests that treatment with vitamin D has no effect on mortality or the incidence of fractures, falls, depression, diabetes, cardiovascular disease, cancer, or adverse events,” the review authors stress.

“The evidence is inconclusive about the effect of treatment on physical functioning and infection.”
 

One in four are vitamin D deficient

In terms of the further question of the potential harms of vitamin D screening of asymptomatic individuals, a key concern is the potential for misclassification and over- or underdiagnosis due to inconsistent cutoffs and variability of different screening assays, the review concluded.

However, with the rare exception of vitamin D toxicity from supplementation well above sufficient levels, treatment with vitamin D supplementation appears relatively safe.

With a lack of consensus even over the basic cutoff for vitamin D deficiency, the National Academy of Medicine determined in 2011 that hydroxyvitamin D (25[OH]D) levels below 20 ng/mL are deficient for bone health, with no evidence of different thresholds for any other health condition.

Based on that cutoff, the National Health and Nutrition Examination Survey (NHANES), reported in 2014 that 25% of the U.S. population over the age of 1 was vitamin D deficient, with 18% of the population having 25(OH)D levels of 12-19 ng/mL and 5% having very low levels (< 12 ng/mL).
 

More work needed to determine groups at risk

While the task force report did not delve into testing or treatment recommendations for symptomatic adults, key established risk factors that may help clinicians identify those who are vitamin D deficient include obesity, receiving little or no UVB light exposure, and older age.

In general, obesity is associated with a 1.3- to 2-fold risk of being vitamin D deficient based on the criteria used, while non-Hispanic Blacks are 2-10 times more likely to be deficient compared with non-Hispanic White patients, the task force noted.

However, the implications of vitamin D deficiency in certain populations can vary. For instance, non-Hispanic Black people, despite having a higher prevalence of lower vitamin D levels compared with White people, in fact, have lower reported rates of fractures.

To address the various issues and gain a better understanding of the complexities of vitamin D deficiency, the task force calls for further research in key areas.

“More research is needed to determine whether total serum 25(OH)D levels are the best measure of vitamin D deficiency and whether the best measure of vitamin D deficiency varies by subgroups defined by race, ethnicity, or sex,” the authors indicated.

Furthermore, “more research is needed to determine the cutoff that defines vitamin D deficiency and whether that cutoff varies by specific clinical outcome or by subgroups defined by race, ethnicity, or sex.”
 

No support for population-based screening in guidelines

With the lack of conclusive evidence, no organizations currently recommend population-based screening for vitamin D deficiency in asymptomatic patients, and the American Society for Clinical Pathology endorses this stance.

The Endocrine Society and the American Association of Clinical Endocrinologists meanwhile do recommend screening for vitamin D deficiency in patients considered at risk.

Data show there was as much as an 80-fold increase in Medicare reimbursement volumes for vitamin D testing among clinicians from 2000 to 2010; however, that rate may have leveled off after the National Academy of Medicine reported on set deficiency levels, said Sherri-Ann M. Burnett-Bowie, MD, MPH, Dr. Cappola’s editorial coauthor.

Dr. Burnett-Bowie noted that she regularly tests her patients’ vitamin D levels, however most of her patients have osteoporosis or fractures.

“I do screen them for vitamin D deficiency since optimizing their vitamin D will improve calcium absorption, which is important for treating their osteoporosis,” Dr. Burnett-Bowie, of the endocrine division, department of medicine, Massachusetts General Hospital, Boston, said in an interview.

In terms of broader testing of asymptomatic patients in the general population, however, any changes in screening will likely be contingent on developments in the effects of treatment, she said.

“Given the challenge in finding benefits of vitamin D supplementation in those who are deficient, it will likely be more challenging to find benefits from wider screening,” she concluded.

The USPSTF and editorialists reported having no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Early use of tocilizumab (Actemra) does not reduce myocardial infarct size but modestly increases myocardial salvage in patients with acute ST-segment elevation MI (STEMI), results of the ASSAIL-MI trial suggest.

“We’re among the first to show that you can actually affect the reperfusion injury through anti-inflammatory treatment – it’s sort of a new attack point for treatments in STEMI,” lead author Kaspar Broch, MD, PhD, Oslo University Hospital Rikshospitalet, said in an interview. “What we do now is reperfuse as soon as we can and then add drugs in order to prevent new events, but we don’t really attack the reperfusion injury that occurs when you perform PCI [percutaneous coronary intervention], which has been shown to actually account for some 50% of the final injury.”

The phase 2, proof-of-concept study was prompted by the team’s earlier work in non-STEMI patients, in which a single dose of the interleukin-6 receptor antagonist cut C-reactive protein (CRP) levels by more than 50% during hospitalization and reduced troponin T release after PCI.

For ASSAIL-MI, Dr. Broch and colleagues randomly assigned 199 patients presenting with acute STEMI within 6 hours of symptom onset to a single intravenous injection of 280 mg tocilizumab or placebo during PCI. Patients, study personnel, and caretakers were blinded to treatment. Data were available for 195 patients for the primary endpoint of myocardial salvage index.

As reported in the Journal of the American College of Cardiology, tocilizumab was associated with a higher adjusted myocardial salvage index on cardiac MRI 3-7 days after PCI than placebo (69.3% vs. 63.6%; P = .04).

The extent of microvascular obstruction was less with tocilizumab (0% vs. 4%; P = .03), as was the area under the curve of CRP during hospitalization (1.9 vs. 8.6 mg/L per hour; P < .001).

The final infarct size at 6 months was 21% lower in the tocilizumab group but the difference did not reach statistical significance (7.2% vs. 9.1% of left ventricular mass; P = .08).

There were no between-group differences in troponin T area under the curve during hospitalization (1,614 vs. 2,357 ng/L per hour; P = .13), N-terminal of the prohormone brain natriuretic peptide concentrations at 6 months (79 vs. 63 ng/L; P = .25), or baseline-adjusted left ventricular end-diastolic volume at 6 months (157 vs. 160 mL; P = .54).

Subgroup analyses suggested the positive effect of tocilizumab on myocardial salvage index is limited to patients presenting at least 3 hours after symptom onset versus 3 hours or less (P = .034), with a trend for greater benefit among men versus women (P = .053).

Dr. Broch noted that the absolute effect of tocilizumab on myocardial necrosis was smaller than anticipated when the trial was designed, which may explain the lack of significant reduction in infarct size.

“We were aiming for patients with larger infarctions than we actually ended up with, which is partly due to the strict inclusion criteria and the fact that, with modern treatments, patients don’t end up with large myocardial infarctions,” he said. “But if they had been larger, I think that 20% absolute reduction would have meant a lot in terms of clinical events.”

The study also used a very modest dose of tocilizumab, compared with that used for inflammatory diseases, to minimize a potential negative effect on myocardial healing, for instance, myocardial ruptures, Dr. Broch said. “I’m not sure whether you gain anything by giving a larger dose.”

Serious adverse events were similar in the tocilizumab and placebo groups (19 vs. 15; P = .57). There were no myocardial ruptures, and no patient died or developed heart failure. LDL cholesterol, triglycerides, and liver enzymes increased in the tocilizumab group but were similar at 3 and 6 months.

Frontline Medical News

“IL-6 is a central cytokine involved in all stages of plaque growth, progression, and rupture,” Paul Ridker, MD, MPH, of the Brigham and Women’s Hospital in Boston, and a long-standing investigator in inflammation and atherothrombosis, said in an interview. “These preliminary data in STEMI, like the authors’ prior data in non-STEMI, are consistent with the idea that inhibiting IL-6 could have clinical benefit, a concept that will be taken into a major cardiovascular outcomes trial later this year.”

The cardiovascular outcomes trial, known as ZEUS, will test the novel IL-6 inhibitor ziltivekimab among more than 6,000 very-high-risk atherosclerosis patients who have moderate to severe chronic kidney disease and high sensitivity CRP greater than 2 mg/L, he noted.

Moving beyond IL-1b blockade as done in CANTOS to direct downstream inhibition of IL-6 represents a “logical next scientific step” in the development of anti-inflammatory therapies for acute ischemia and chronic atherosclerosis, Dr. Ridker, who led the CANTOS trial, noted in an accompanying editorial.

“Preventive cardiologists, however, need not wait until outcome trials are complete to use this evolving biological knowledge to their patient’s advantage,” he wrote. “As recently confirmed in the pages of the Journal, exercise, smoking cessation, and a healthy diet reduce both C-reactive protein and IL-6, and clearly have lifelong benefits. Our immediate task is thus to incorporate inflammation inhibition through lifestyle management into our daily practice.”

The study was supported by the South-Eastern Norway Regional Health Authority, Central Norway Regional Health Authority, and Roche, which provided the medicinal products and an unrestricted grant. Dr. Broch has disclosed no relevant financial relationships. Dr. Ridker has received investigator-initiated research grant support from Kowa, Novartis, Amarin, Pfizer, and the National Heart, Lung, and Blood Institute; and has served as a consultant to Novartis, Janssen, Agepha, Flame, Civi Biopharma, Inflazome, Corvidia, Novo Nordisk, SOCAR, IQVIA, and AstraZeneca.

A version of this article first appeared on Medscape.com.

Early use of tocilizumab (Actemra) does not reduce myocardial infarct size but modestly increases myocardial salvage in patients with acute ST-segment elevation MI (STEMI), results of the ASSAIL-MI trial suggest.

“We’re among the first to show that you can actually affect the reperfusion injury through anti-inflammatory treatment – it’s sort of a new attack point for treatments in STEMI,” lead author Kaspar Broch, MD, PhD, Oslo University Hospital Rikshospitalet, said in an interview. “What we do now is reperfuse as soon as we can and then add drugs in order to prevent new events, but we don’t really attack the reperfusion injury that occurs when you perform PCI [percutaneous coronary intervention], which has been shown to actually account for some 50% of the final injury.”

The phase 2, proof-of-concept study was prompted by the team’s earlier work in non-STEMI patients, in which a single dose of the interleukin-6 receptor antagonist cut C-reactive protein (CRP) levels by more than 50% during hospitalization and reduced troponin T release after PCI.

For ASSAIL-MI, Dr. Broch and colleagues randomly assigned 199 patients presenting with acute STEMI within 6 hours of symptom onset to a single intravenous injection of 280 mg tocilizumab or placebo during PCI. Patients, study personnel, and caretakers were blinded to treatment. Data were available for 195 patients for the primary endpoint of myocardial salvage index.

As reported in the Journal of the American College of Cardiology, tocilizumab was associated with a higher adjusted myocardial salvage index on cardiac MRI 3-7 days after PCI than placebo (69.3% vs. 63.6%; P = .04).

The extent of microvascular obstruction was less with tocilizumab (0% vs. 4%; P = .03), as was the area under the curve of CRP during hospitalization (1.9 vs. 8.6 mg/L per hour; P < .001).

The final infarct size at 6 months was 21% lower in the tocilizumab group but the difference did not reach statistical significance (7.2% vs. 9.1% of left ventricular mass; P = .08).

There were no between-group differences in troponin T area under the curve during hospitalization (1,614 vs. 2,357 ng/L per hour; P = .13), N-terminal of the prohormone brain natriuretic peptide concentrations at 6 months (79 vs. 63 ng/L; P = .25), or baseline-adjusted left ventricular end-diastolic volume at 6 months (157 vs. 160 mL; P = .54).

Subgroup analyses suggested the positive effect of tocilizumab on myocardial salvage index is limited to patients presenting at least 3 hours after symptom onset versus 3 hours or less (P = .034), with a trend for greater benefit among men versus women (P = .053).

Dr. Broch noted that the absolute effect of tocilizumab on myocardial necrosis was smaller than anticipated when the trial was designed, which may explain the lack of significant reduction in infarct size.

“We were aiming for patients with larger infarctions than we actually ended up with, which is partly due to the strict inclusion criteria and the fact that, with modern treatments, patients don’t end up with large myocardial infarctions,” he said. “But if they had been larger, I think that 20% absolute reduction would have meant a lot in terms of clinical events.”

The study also used a very modest dose of tocilizumab, compared with that used for inflammatory diseases, to minimize a potential negative effect on myocardial healing, for instance, myocardial ruptures, Dr. Broch said. “I’m not sure whether you gain anything by giving a larger dose.”

Serious adverse events were similar in the tocilizumab and placebo groups (19 vs. 15; P = .57). There were no myocardial ruptures, and no patient died or developed heart failure. LDL cholesterol, triglycerides, and liver enzymes increased in the tocilizumab group but were similar at 3 and 6 months.

Frontline Medical News

“IL-6 is a central cytokine involved in all stages of plaque growth, progression, and rupture,” Paul Ridker, MD, MPH, of the Brigham and Women’s Hospital in Boston, and a long-standing investigator in inflammation and atherothrombosis, said in an interview. “These preliminary data in STEMI, like the authors’ prior data in non-STEMI, are consistent with the idea that inhibiting IL-6 could have clinical benefit, a concept that will be taken into a major cardiovascular outcomes trial later this year.”

The cardiovascular outcomes trial, known as ZEUS, will test the novel IL-6 inhibitor ziltivekimab among more than 6,000 very-high-risk atherosclerosis patients who have moderate to severe chronic kidney disease and high sensitivity CRP greater than 2 mg/L, he noted.

Moving beyond IL-1b blockade as done in CANTOS to direct downstream inhibition of IL-6 represents a “logical next scientific step” in the development of anti-inflammatory therapies for acute ischemia and chronic atherosclerosis, Dr. Ridker, who led the CANTOS trial, noted in an accompanying editorial.

“Preventive cardiologists, however, need not wait until outcome trials are complete to use this evolving biological knowledge to their patient’s advantage,” he wrote. “As recently confirmed in the pages of the Journal, exercise, smoking cessation, and a healthy diet reduce both C-reactive protein and IL-6, and clearly have lifelong benefits. Our immediate task is thus to incorporate inflammation inhibition through lifestyle management into our daily practice.”

The study was supported by the South-Eastern Norway Regional Health Authority, Central Norway Regional Health Authority, and Roche, which provided the medicinal products and an unrestricted grant. Dr. Broch has disclosed no relevant financial relationships. Dr. Ridker has received investigator-initiated research grant support from Kowa, Novartis, Amarin, Pfizer, and the National Heart, Lung, and Blood Institute; and has served as a consultant to Novartis, Janssen, Agepha, Flame, Civi Biopharma, Inflazome, Corvidia, Novo Nordisk, SOCAR, IQVIA, and AstraZeneca.

A version of this article first appeared on Medscape.com.

Early use of tocilizumab (Actemra) does not reduce myocardial infarct size but modestly increases myocardial salvage in patients with acute ST-segment elevation MI (STEMI), results of the ASSAIL-MI trial suggest.

“We’re among the first to show that you can actually affect the reperfusion injury through anti-inflammatory treatment – it’s sort of a new attack point for treatments in STEMI,” lead author Kaspar Broch, MD, PhD, Oslo University Hospital Rikshospitalet, said in an interview. “What we do now is reperfuse as soon as we can and then add drugs in order to prevent new events, but we don’t really attack the reperfusion injury that occurs when you perform PCI [percutaneous coronary intervention], which has been shown to actually account for some 50% of the final injury.”

The phase 2, proof-of-concept study was prompted by the team’s earlier work in non-STEMI patients, in which a single dose of the interleukin-6 receptor antagonist cut C-reactive protein (CRP) levels by more than 50% during hospitalization and reduced troponin T release after PCI.

For ASSAIL-MI, Dr. Broch and colleagues randomly assigned 199 patients presenting with acute STEMI within 6 hours of symptom onset to a single intravenous injection of 280 mg tocilizumab or placebo during PCI. Patients, study personnel, and caretakers were blinded to treatment. Data were available for 195 patients for the primary endpoint of myocardial salvage index.

As reported in the Journal of the American College of Cardiology, tocilizumab was associated with a higher adjusted myocardial salvage index on cardiac MRI 3-7 days after PCI than placebo (69.3% vs. 63.6%; P = .04).

The extent of microvascular obstruction was less with tocilizumab (0% vs. 4%; P = .03), as was the area under the curve of CRP during hospitalization (1.9 vs. 8.6 mg/L per hour; P < .001).

The final infarct size at 6 months was 21% lower in the tocilizumab group but the difference did not reach statistical significance (7.2% vs. 9.1% of left ventricular mass; P = .08).

There were no between-group differences in troponin T area under the curve during hospitalization (1,614 vs. 2,357 ng/L per hour; P = .13), N-terminal of the prohormone brain natriuretic peptide concentrations at 6 months (79 vs. 63 ng/L; P = .25), or baseline-adjusted left ventricular end-diastolic volume at 6 months (157 vs. 160 mL; P = .54).

Subgroup analyses suggested the positive effect of tocilizumab on myocardial salvage index is limited to patients presenting at least 3 hours after symptom onset versus 3 hours or less (P = .034), with a trend for greater benefit among men versus women (P = .053).

Dr. Broch noted that the absolute effect of tocilizumab on myocardial necrosis was smaller than anticipated when the trial was designed, which may explain the lack of significant reduction in infarct size.

“We were aiming for patients with larger infarctions than we actually ended up with, which is partly due to the strict inclusion criteria and the fact that, with modern treatments, patients don’t end up with large myocardial infarctions,” he said. “But if they had been larger, I think that 20% absolute reduction would have meant a lot in terms of clinical events.”

The study also used a very modest dose of tocilizumab, compared with that used for inflammatory diseases, to minimize a potential negative effect on myocardial healing, for instance, myocardial ruptures, Dr. Broch said. “I’m not sure whether you gain anything by giving a larger dose.”

Serious adverse events were similar in the tocilizumab and placebo groups (19 vs. 15; P = .57). There were no myocardial ruptures, and no patient died or developed heart failure. LDL cholesterol, triglycerides, and liver enzymes increased in the tocilizumab group but were similar at 3 and 6 months.

Frontline Medical News

“IL-6 is a central cytokine involved in all stages of plaque growth, progression, and rupture,” Paul Ridker, MD, MPH, of the Brigham and Women’s Hospital in Boston, and a long-standing investigator in inflammation and atherothrombosis, said in an interview. “These preliminary data in STEMI, like the authors’ prior data in non-STEMI, are consistent with the idea that inhibiting IL-6 could have clinical benefit, a concept that will be taken into a major cardiovascular outcomes trial later this year.”

The cardiovascular outcomes trial, known as ZEUS, will test the novel IL-6 inhibitor ziltivekimab among more than 6,000 very-high-risk atherosclerosis patients who have moderate to severe chronic kidney disease and high sensitivity CRP greater than 2 mg/L, he noted.

Moving beyond IL-1b blockade as done in CANTOS to direct downstream inhibition of IL-6 represents a “logical next scientific step” in the development of anti-inflammatory therapies for acute ischemia and chronic atherosclerosis, Dr. Ridker, who led the CANTOS trial, noted in an accompanying editorial.

“Preventive cardiologists, however, need not wait until outcome trials are complete to use this evolving biological knowledge to their patient’s advantage,” he wrote. “As recently confirmed in the pages of the Journal, exercise, smoking cessation, and a healthy diet reduce both C-reactive protein and IL-6, and clearly have lifelong benefits. Our immediate task is thus to incorporate inflammation inhibition through lifestyle management into our daily practice.”

The study was supported by the South-Eastern Norway Regional Health Authority, Central Norway Regional Health Authority, and Roche, which provided the medicinal products and an unrestricted grant. Dr. Broch has disclosed no relevant financial relationships. Dr. Ridker has received investigator-initiated research grant support from Kowa, Novartis, Amarin, Pfizer, and the National Heart, Lung, and Blood Institute; and has served as a consultant to Novartis, Janssen, Agepha, Flame, Civi Biopharma, Inflazome, Corvidia, Novo Nordisk, SOCAR, IQVIA, and AstraZeneca.

A version of this article first appeared on Medscape.com.

It’s likely the United States will see another surge of COVID-19 this winter, warned Christopher Murray, MD, director of the Institute for Health Metrics and Evaluation (IHME) at the University of Washington in Seattle.

Speaking at the national conference of State of Reform on April 8, Dr. Murray cited the seasonality of the SARS-CoV-2 virus, which wanes in the summer and waxes in the winter. The “optimistic forecast” of IHME, which has modeled the course of the pandemic for the past 13 months, is that daily deaths will rise a bit in the next month, then decline from May through August, he said.

“Summer should be fairly quiet in terms of COVID, if vaccinations rise and people don’t stop wearing masks,” Dr. Murray said.

But he added that “a considerable surge will occur over next winter,” because the new variants are more transmissible, and people will likely relax social distancing and mask wearing. The IHME predicts that the percentage of Americans who usually don masks will decline from 73% today to 21% by Aug. 1.

With a rapid decline in mask use and a rise in mobility, there will still be more than 1,000 deaths each day by July 1, Dr. Murray said. In a forecast released the day after Dr. Murray spoke, the IHME predicted that by Aug. 1, there will be a total of 618,523 U.S. deaths from COVID-19. Deaths could be as high as 696,651 if mobility among the vaccinated returns to prepandemic levels, the institute forecasts.

Based on cell phone data, Dr. Murray said, the amount of mobility in the United States has already risen to the level of March 2020, when the pandemic was just getting underway.
 

Decreased infections

If there’s one piece of good news in the latest IHME report, it’s that the estimated number of people infected (including those not tested) will drop from 111,581 today to a projected 17,502 on Aug. 1. But in a worst-case scenario, with sharply higher mobility among vaccinated people, the case count on that date would only fall to 73,842.

The SARS-CoV-2 variants are another factor of concern. Dr. Murray distinguished between variants like the one first identified in the U.K. (B.1.1.7) and other “escape variants.”

B.1.1.7, which is now the dominant strain in the United States, increases transmission but doesn’t necessarily escape the immune system or vaccines, he explained.

In contrast, if someone is infected with a variant such as the South African or the Brazilian mutations, he said, a previous COVID-19 infection might not protect the person, and vaccines are less effective against those variants.

Cross-variant immunity may range from 0% to 60% for escape variants, based on the slim amount of data now available, Dr. Murray said. In his view, these variants will be the long-term driver of the pandemic in the United States, while the United Kingdom variant is the short-term driver.

The latest data, he said, show that the Pfizer/BioNTech and Moderna vaccines are 75% effective against the escape variants, with lower efficacy for other vaccines. But booster shots may still be required to protect people against some variants.
 

Human factors

Human behavior will also help determine the course of the pandemic, he noted. Vaccine hesitancy, for example, is still high in the United States.

By the end of May, he predicted, about 180 million people will have received about two doses of vaccine. After that, he said, “vaccination will flatline due to lack of demand.” The two unknowns are how much campaigns to promote vaccination will increase vaccine confidence, and when children will be vaccinated.

In the United States, he said, 69% of adults have been vaccinated or want to get a shot. But that percentage has dropped 5 points since February, and vaccine confidence varies by state.

Dr. Murray emphasized that the winter surge he predicts can be blocked if people change their behaviors. These include a rise in vaccine confidence to 80% and continued mask wearing by most people.

However, if vaccine confidence and mask wearing decline, state governments continue to drop social distancing rules, and the uptake of boosters is low, the winter surge could be more serious, he said.
 

Double surge

Murray also raised the possibility of a double surge of COVID-19 and influenza this winter. Widely expected last winter, this double surge never materialized here or elsewhere, partly because of mask wearing. But Dr. Murray said it could happen this year: History shows that the flu tends to be stronger in years after weak outbreaks.

He advised hospitals to prepare now for whatever might come later this year. Public health authorities, he said, should speed up vaccination, monitor variants closely with additional sequencing, and try to modify behavior in high-risk groups.

Asked to explain the recent surge of COVID-19 cases in Michigan, Dr. Murray attributed it partly to the spread of the B.1.1.7 (U.K.) variant. But he noted that the U.K. variant has expanded even more widely in some other states that haven’t had an explosive surge like Michigan’s.

Moreover, he noted, Michigan doesn’t have low mask use or high mobility. So the upward spiral of COVID-19 infections there is very concerning, he said.

In regard to the role of children as reservoirs of the virus, Dr. Murray pointed out that views on this have changed around the world. For a while, people thought kids didn’t spread COVID-19 very much. That view shifted when U.K. data showed that child transmission of the B.1.1.7 variant increased by half to 9% of contacts in comparison with the original virus strain.

Dutch data, similarly, showed schools contributing to the latest outbreaks, and some European nations have closed schools. In the United States, the trend is to open them.

A version of this article first appeared on Medscape.com.

It’s likely the United States will see another surge of COVID-19 this winter, warned Christopher Murray, MD, director of the Institute for Health Metrics and Evaluation (IHME) at the University of Washington in Seattle.

Speaking at the national conference of State of Reform on April 8, Dr. Murray cited the seasonality of the SARS-CoV-2 virus, which wanes in the summer and waxes in the winter. The “optimistic forecast” of IHME, which has modeled the course of the pandemic for the past 13 months, is that daily deaths will rise a bit in the next month, then decline from May through August, he said.

“Summer should be fairly quiet in terms of COVID, if vaccinations rise and people don’t stop wearing masks,” Dr. Murray said.

But he added that “a considerable surge will occur over next winter,” because the new variants are more transmissible, and people will likely relax social distancing and mask wearing. The IHME predicts that the percentage of Americans who usually don masks will decline from 73% today to 21% by Aug. 1.

With a rapid decline in mask use and a rise in mobility, there will still be more than 1,000 deaths each day by July 1, Dr. Murray said. In a forecast released the day after Dr. Murray spoke, the IHME predicted that by Aug. 1, there will be a total of 618,523 U.S. deaths from COVID-19. Deaths could be as high as 696,651 if mobility among the vaccinated returns to prepandemic levels, the institute forecasts.

Based on cell phone data, Dr. Murray said, the amount of mobility in the United States has already risen to the level of March 2020, when the pandemic was just getting underway.
 

Decreased infections

If there’s one piece of good news in the latest IHME report, it’s that the estimated number of people infected (including those not tested) will drop from 111,581 today to a projected 17,502 on Aug. 1. But in a worst-case scenario, with sharply higher mobility among vaccinated people, the case count on that date would only fall to 73,842.

The SARS-CoV-2 variants are another factor of concern. Dr. Murray distinguished between variants like the one first identified in the U.K. (B.1.1.7) and other “escape variants.”

B.1.1.7, which is now the dominant strain in the United States, increases transmission but doesn’t necessarily escape the immune system or vaccines, he explained.

In contrast, if someone is infected with a variant such as the South African or the Brazilian mutations, he said, a previous COVID-19 infection might not protect the person, and vaccines are less effective against those variants.

Cross-variant immunity may range from 0% to 60% for escape variants, based on the slim amount of data now available, Dr. Murray said. In his view, these variants will be the long-term driver of the pandemic in the United States, while the United Kingdom variant is the short-term driver.

The latest data, he said, show that the Pfizer/BioNTech and Moderna vaccines are 75% effective against the escape variants, with lower efficacy for other vaccines. But booster shots may still be required to protect people against some variants.
 

Human factors

Human behavior will also help determine the course of the pandemic, he noted. Vaccine hesitancy, for example, is still high in the United States.

By the end of May, he predicted, about 180 million people will have received about two doses of vaccine. After that, he said, “vaccination will flatline due to lack of demand.” The two unknowns are how much campaigns to promote vaccination will increase vaccine confidence, and when children will be vaccinated.

In the United States, he said, 69% of adults have been vaccinated or want to get a shot. But that percentage has dropped 5 points since February, and vaccine confidence varies by state.

Dr. Murray emphasized that the winter surge he predicts can be blocked if people change their behaviors. These include a rise in vaccine confidence to 80% and continued mask wearing by most people.

However, if vaccine confidence and mask wearing decline, state governments continue to drop social distancing rules, and the uptake of boosters is low, the winter surge could be more serious, he said.
 

Double surge

Murray also raised the possibility of a double surge of COVID-19 and influenza this winter. Widely expected last winter, this double surge never materialized here or elsewhere, partly because of mask wearing. But Dr. Murray said it could happen this year: History shows that the flu tends to be stronger in years after weak outbreaks.

He advised hospitals to prepare now for whatever might come later this year. Public health authorities, he said, should speed up vaccination, monitor variants closely with additional sequencing, and try to modify behavior in high-risk groups.

Asked to explain the recent surge of COVID-19 cases in Michigan, Dr. Murray attributed it partly to the spread of the B.1.1.7 (U.K.) variant. But he noted that the U.K. variant has expanded even more widely in some other states that haven’t had an explosive surge like Michigan’s.

Moreover, he noted, Michigan doesn’t have low mask use or high mobility. So the upward spiral of COVID-19 infections there is very concerning, he said.

In regard to the role of children as reservoirs of the virus, Dr. Murray pointed out that views on this have changed around the world. For a while, people thought kids didn’t spread COVID-19 very much. That view shifted when U.K. data showed that child transmission of the B.1.1.7 variant increased by half to 9% of contacts in comparison with the original virus strain.

Dutch data, similarly, showed schools contributing to the latest outbreaks, and some European nations have closed schools. In the United States, the trend is to open them.

A version of this article first appeared on Medscape.com.

It’s likely the United States will see another surge of COVID-19 this winter, warned Christopher Murray, MD, director of the Institute for Health Metrics and Evaluation (IHME) at the University of Washington in Seattle.

Speaking at the national conference of State of Reform on April 8, Dr. Murray cited the seasonality of the SARS-CoV-2 virus, which wanes in the summer and waxes in the winter. The “optimistic forecast” of IHME, which has modeled the course of the pandemic for the past 13 months, is that daily deaths will rise a bit in the next month, then decline from May through August, he said.

“Summer should be fairly quiet in terms of COVID, if vaccinations rise and people don’t stop wearing masks,” Dr. Murray said.

But he added that “a considerable surge will occur over next winter,” because the new variants are more transmissible, and people will likely relax social distancing and mask wearing. The IHME predicts that the percentage of Americans who usually don masks will decline from 73% today to 21% by Aug. 1.

With a rapid decline in mask use and a rise in mobility, there will still be more than 1,000 deaths each day by July 1, Dr. Murray said. In a forecast released the day after Dr. Murray spoke, the IHME predicted that by Aug. 1, there will be a total of 618,523 U.S. deaths from COVID-19. Deaths could be as high as 696,651 if mobility among the vaccinated returns to prepandemic levels, the institute forecasts.

Based on cell phone data, Dr. Murray said, the amount of mobility in the United States has already risen to the level of March 2020, when the pandemic was just getting underway.
 

Decreased infections

If there’s one piece of good news in the latest IHME report, it’s that the estimated number of people infected (including those not tested) will drop from 111,581 today to a projected 17,502 on Aug. 1. But in a worst-case scenario, with sharply higher mobility among vaccinated people, the case count on that date would only fall to 73,842.

The SARS-CoV-2 variants are another factor of concern. Dr. Murray distinguished between variants like the one first identified in the U.K. (B.1.1.7) and other “escape variants.”

B.1.1.7, which is now the dominant strain in the United States, increases transmission but doesn’t necessarily escape the immune system or vaccines, he explained.

In contrast, if someone is infected with a variant such as the South African or the Brazilian mutations, he said, a previous COVID-19 infection might not protect the person, and vaccines are less effective against those variants.

Cross-variant immunity may range from 0% to 60% for escape variants, based on the slim amount of data now available, Dr. Murray said. In his view, these variants will be the long-term driver of the pandemic in the United States, while the United Kingdom variant is the short-term driver.

The latest data, he said, show that the Pfizer/BioNTech and Moderna vaccines are 75% effective against the escape variants, with lower efficacy for other vaccines. But booster shots may still be required to protect people against some variants.
 

Human factors

Human behavior will also help determine the course of the pandemic, he noted. Vaccine hesitancy, for example, is still high in the United States.

By the end of May, he predicted, about 180 million people will have received about two doses of vaccine. After that, he said, “vaccination will flatline due to lack of demand.” The two unknowns are how much campaigns to promote vaccination will increase vaccine confidence, and when children will be vaccinated.

In the United States, he said, 69% of adults have been vaccinated or want to get a shot. But that percentage has dropped 5 points since February, and vaccine confidence varies by state.

Dr. Murray emphasized that the winter surge he predicts can be blocked if people change their behaviors. These include a rise in vaccine confidence to 80% and continued mask wearing by most people.

However, if vaccine confidence and mask wearing decline, state governments continue to drop social distancing rules, and the uptake of boosters is low, the winter surge could be more serious, he said.
 

Double surge

Murray also raised the possibility of a double surge of COVID-19 and influenza this winter. Widely expected last winter, this double surge never materialized here or elsewhere, partly because of mask wearing. But Dr. Murray said it could happen this year: History shows that the flu tends to be stronger in years after weak outbreaks.

He advised hospitals to prepare now for whatever might come later this year. Public health authorities, he said, should speed up vaccination, monitor variants closely with additional sequencing, and try to modify behavior in high-risk groups.

Asked to explain the recent surge of COVID-19 cases in Michigan, Dr. Murray attributed it partly to the spread of the B.1.1.7 (U.K.) variant. But he noted that the U.K. variant has expanded even more widely in some other states that haven’t had an explosive surge like Michigan’s.

Moreover, he noted, Michigan doesn’t have low mask use or high mobility. So the upward spiral of COVID-19 infections there is very concerning, he said.

In regard to the role of children as reservoirs of the virus, Dr. Murray pointed out that views on this have changed around the world. For a while, people thought kids didn’t spread COVID-19 very much. That view shifted when U.K. data showed that child transmission of the B.1.1.7 variant increased by half to 9% of contacts in comparison with the original virus strain.

Dutch data, similarly, showed schools contributing to the latest outbreaks, and some European nations have closed schools. In the United States, the trend is to open them.

A version of this article first appeared on Medscape.com.

A version of this article first appeared on WebMD.com.

This article was updated 4/13/21.

A version of this article first appeared on WebMD.com.

This article was updated 4/13/21.

A version of this article first appeared on WebMD.com.

This article was updated 4/13/21.

Secukinumab proved highly effective at improving skin symptoms and quality of life in 6- to 17-year-old patients with moderate to severe plaque psoriasis at 24 weeks of follow-up in an ongoing 4-year phase 2 clinical trial, Adam Reich, MD, PhD, reported at Innovations in Dermatology: Virtual Spring Conference 2021.

Secukinumab (Cosentyx), a fully human monoclonal antibody that inhibits interleukin-17A, is widely approved for treatment of psoriasis in adults. In August 2020, the biologic received an expanded indication in Europe for treatment of 6- to 17-year-olds. Two phase 3 clinical trials are underway in an effort to gain a similar broadened indication in the United States to help address the high unmet need for new treatments for psoriasis in the pediatric population, said Dr. Reich, professor and head of the department of dermatology at the University of Rzeszow (Poland).

He reported on 84 pediatric patients participating in the open-label, phase 2, international study. They were randomized to one of two weight-based dosing regimens. Those in the low-dose arm received secukinumab dosed at 75 mg if they weighed less than 50 kg and 150 mg if they weighed more. In the high-dose arm, patients got secukinumab 75 mg if they weighed less than 25 kg, 150 mg if they weighed 25-50 kg, and 300 mg if they tipped the scales in excess of 50 kg.

The primary endpoint in the study was the week-12 rate of at least a 75% improvement from baseline in the Psoriasis Area and Severity Index score, or PASI 75. The rates were similar: 92.9% of patients in the high-dose arm achieved this endpoint, as did 90.5% in the low-dose arm. The PASI 90 rates were 83.3% and 78%, the PASI 100 rates were 61.9% and 54.8%, and clear or almost clear skin, as measured by the Investigator Global Assessment, was achieved in 88.7% of the high- and 85.7% of the low-dose groups. In addition,61.9% of those in the high-dose secukinumab group and 50% in the low-dose group had a score of 0 or 1 on the Children’s Dermatology Life Quality Index – indicating psoriasis has no impact on daily quality of life, he said at the conference sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.

At week 24, roughly 95% of patients in both the low- and high-dose secukinumab groups had achieved PASI 75s, 88% reached a PASI 90 response, and 67% were at PASI 100. Nearly 60% of the low-dose and 70% of the high-dose groups had a score of 0 or 1 on the Children’s Dermatology Life Quality Index.

Treatment-emergent adverse event rates were similar in the two study arms. Of note, there was one case of new-onset inflammatory bowel disease in the high-dose group, and one case of vulvovaginal candidiasis as well.

Discussant Bruce E. Strober, MD, PhD, said that, if secukinumab gets a pediatric indication from the Food and Drug Administration, as seems likely, it won’t alter his biologic treatment hierarchy.

“I treat a lot of kids with psoriasis. We have three approved drugs now in etanercept [Enbrel], ustekinumab [Stelara], and ixekizumab [Taltz]. My bias is still towards ustekinumab because it’s infrequently dosed and that’s a huge issue for children. You want to expose them to as few injections as possible, for obvious reasons: It’s easier for parents and other caregivers,” explained Dr. Strober, a dermatologist at Yale University, New Haven, Conn., and Central Connecticut Dermatology, Cromwell, Conn.

“The other issue is in IL-17 inhibition there has been a slight signal of inflammatory bowel disease popping up in children getting these drugs, and therefore you need to screen patients in this age group very carefully – not only the patients themselves, but their family – for IBD risk. If there is any sign of that I would move the IL-17 inhibitors to the back of the line, compared to ustekinumab and etanercept. Ustekinumab is still clearly the one that I think has to be used first line,” he said.

Dr. Strober offered a final word of advice for his colleagues: “You can’t be afraid to treat children with biologic therapies. In fact, preferentially I would use a biologic therapy over methotrexate or light therapy, which is really difficult for children.”

Dr. Reich and Dr. Strober reported receiving research grants from and serving as a consultant to numerous pharmaceutical companies, including Novartis, which markets secukinumab and funded the study.

MedscapeLIVE! and this news organization are owned by the same parent company.

Secukinumab proved highly effective at improving skin symptoms and quality of life in 6- to 17-year-old patients with moderate to severe plaque psoriasis at 24 weeks of follow-up in an ongoing 4-year phase 2 clinical trial, Adam Reich, MD, PhD, reported at Innovations in Dermatology: Virtual Spring Conference 2021.

Secukinumab (Cosentyx), a fully human monoclonal antibody that inhibits interleukin-17A, is widely approved for treatment of psoriasis in adults. In August 2020, the biologic received an expanded indication in Europe for treatment of 6- to 17-year-olds. Two phase 3 clinical trials are underway in an effort to gain a similar broadened indication in the United States to help address the high unmet need for new treatments for psoriasis in the pediatric population, said Dr. Reich, professor and head of the department of dermatology at the University of Rzeszow (Poland).

He reported on 84 pediatric patients participating in the open-label, phase 2, international study. They were randomized to one of two weight-based dosing regimens. Those in the low-dose arm received secukinumab dosed at 75 mg if they weighed less than 50 kg and 150 mg if they weighed more. In the high-dose arm, patients got secukinumab 75 mg if they weighed less than 25 kg, 150 mg if they weighed 25-50 kg, and 300 mg if they tipped the scales in excess of 50 kg.

The primary endpoint in the study was the week-12 rate of at least a 75% improvement from baseline in the Psoriasis Area and Severity Index score, or PASI 75. The rates were similar: 92.9% of patients in the high-dose arm achieved this endpoint, as did 90.5% in the low-dose arm. The PASI 90 rates were 83.3% and 78%, the PASI 100 rates were 61.9% and 54.8%, and clear or almost clear skin, as measured by the Investigator Global Assessment, was achieved in 88.7% of the high- and 85.7% of the low-dose groups. In addition,61.9% of those in the high-dose secukinumab group and 50% in the low-dose group had a score of 0 or 1 on the Children’s Dermatology Life Quality Index – indicating psoriasis has no impact on daily quality of life, he said at the conference sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.

At week 24, roughly 95% of patients in both the low- and high-dose secukinumab groups had achieved PASI 75s, 88% reached a PASI 90 response, and 67% were at PASI 100. Nearly 60% of the low-dose and 70% of the high-dose groups had a score of 0 or 1 on the Children’s Dermatology Life Quality Index.

Treatment-emergent adverse event rates were similar in the two study arms. Of note, there was one case of new-onset inflammatory bowel disease in the high-dose group, and one case of vulvovaginal candidiasis as well.

Discussant Bruce E. Strober, MD, PhD, said that, if secukinumab gets a pediatric indication from the Food and Drug Administration, as seems likely, it won’t alter his biologic treatment hierarchy.

“I treat a lot of kids with psoriasis. We have three approved drugs now in etanercept [Enbrel], ustekinumab [Stelara], and ixekizumab [Taltz]. My bias is still towards ustekinumab because it’s infrequently dosed and that’s a huge issue for children. You want to expose them to as few injections as possible, for obvious reasons: It’s easier for parents and other caregivers,” explained Dr. Strober, a dermatologist at Yale University, New Haven, Conn., and Central Connecticut Dermatology, Cromwell, Conn.

“The other issue is in IL-17 inhibition there has been a slight signal of inflammatory bowel disease popping up in children getting these drugs, and therefore you need to screen patients in this age group very carefully – not only the patients themselves, but their family – for IBD risk. If there is any sign of that I would move the IL-17 inhibitors to the back of the line, compared to ustekinumab and etanercept. Ustekinumab is still clearly the one that I think has to be used first line,” he said.

Dr. Strober offered a final word of advice for his colleagues: “You can’t be afraid to treat children with biologic therapies. In fact, preferentially I would use a biologic therapy over methotrexate or light therapy, which is really difficult for children.”

Dr. Reich and Dr. Strober reported receiving research grants from and serving as a consultant to numerous pharmaceutical companies, including Novartis, which markets secukinumab and funded the study.

MedscapeLIVE! and this news organization are owned by the same parent company.

Secukinumab proved highly effective at improving skin symptoms and quality of life in 6- to 17-year-old patients with moderate to severe plaque psoriasis at 24 weeks of follow-up in an ongoing 4-year phase 2 clinical trial, Adam Reich, MD, PhD, reported at Innovations in Dermatology: Virtual Spring Conference 2021.

Secukinumab (Cosentyx), a fully human monoclonal antibody that inhibits interleukin-17A, is widely approved for treatment of psoriasis in adults. In August 2020, the biologic received an expanded indication in Europe for treatment of 6- to 17-year-olds. Two phase 3 clinical trials are underway in an effort to gain a similar broadened indication in the United States to help address the high unmet need for new treatments for psoriasis in the pediatric population, said Dr. Reich, professor and head of the department of dermatology at the University of Rzeszow (Poland).

He reported on 84 pediatric patients participating in the open-label, phase 2, international study. They were randomized to one of two weight-based dosing regimens. Those in the low-dose arm received secukinumab dosed at 75 mg if they weighed less than 50 kg and 150 mg if they weighed more. In the high-dose arm, patients got secukinumab 75 mg if they weighed less than 25 kg, 150 mg if they weighed 25-50 kg, and 300 mg if they tipped the scales in excess of 50 kg.

The primary endpoint in the study was the week-12 rate of at least a 75% improvement from baseline in the Psoriasis Area and Severity Index score, or PASI 75. The rates were similar: 92.9% of patients in the high-dose arm achieved this endpoint, as did 90.5% in the low-dose arm. The PASI 90 rates were 83.3% and 78%, the PASI 100 rates were 61.9% and 54.8%, and clear or almost clear skin, as measured by the Investigator Global Assessment, was achieved in 88.7% of the high- and 85.7% of the low-dose groups. In addition,61.9% of those in the high-dose secukinumab group and 50% in the low-dose group had a score of 0 or 1 on the Children’s Dermatology Life Quality Index – indicating psoriasis has no impact on daily quality of life, he said at the conference sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.

At week 24, roughly 95% of patients in both the low- and high-dose secukinumab groups had achieved PASI 75s, 88% reached a PASI 90 response, and 67% were at PASI 100. Nearly 60% of the low-dose and 70% of the high-dose groups had a score of 0 or 1 on the Children’s Dermatology Life Quality Index.

Treatment-emergent adverse event rates were similar in the two study arms. Of note, there was one case of new-onset inflammatory bowel disease in the high-dose group, and one case of vulvovaginal candidiasis as well.

Discussant Bruce E. Strober, MD, PhD, said that, if secukinumab gets a pediatric indication from the Food and Drug Administration, as seems likely, it won’t alter his biologic treatment hierarchy.

“I treat a lot of kids with psoriasis. We have three approved drugs now in etanercept [Enbrel], ustekinumab [Stelara], and ixekizumab [Taltz]. My bias is still towards ustekinumab because it’s infrequently dosed and that’s a huge issue for children. You want to expose them to as few injections as possible, for obvious reasons: It’s easier for parents and other caregivers,” explained Dr. Strober, a dermatologist at Yale University, New Haven, Conn., and Central Connecticut Dermatology, Cromwell, Conn.

“The other issue is in IL-17 inhibition there has been a slight signal of inflammatory bowel disease popping up in children getting these drugs, and therefore you need to screen patients in this age group very carefully – not only the patients themselves, but their family – for IBD risk. If there is any sign of that I would move the IL-17 inhibitors to the back of the line, compared to ustekinumab and etanercept. Ustekinumab is still clearly the one that I think has to be used first line,” he said.

Dr. Strober offered a final word of advice for his colleagues: “You can’t be afraid to treat children with biologic therapies. In fact, preferentially I would use a biologic therapy over methotrexate or light therapy, which is really difficult for children.”

Dr. Reich and Dr. Strober reported receiving research grants from and serving as a consultant to numerous pharmaceutical companies, including Novartis, which markets secukinumab and funded the study.

MedscapeLIVE! and this news organization are owned by the same parent company.

Adults with knee osteoarthritis (OA) who participated in a self-directed, web-based exercise program with automated text-message reminders and encouragement for 6 months showed significant improvement in overall knee pain and physical function, compared with patients who received web-based OA information alone, in a randomized trial of 180 individuals.

copyright Nandyphotos/Thinkstock

The results support a role for web-based exercise intervention to improve knee OA patients’ access to recommended exercises and to assist clinicians in managing patients on a population level, according to the first author of the study, Rachel Kate Nelligan, of the University of Melbourne, and colleagues. Their report is in JAMA Internal Medicine.

“Our free-to-access, unsupervised program could serve as an entry-level intervention, with participants who do not experience clinical benefits progressing to subsequent steps for more intensive, personalized management,” they said. “Such an approach has the potential to better distribute limited health care resources and reduce demand for contact with health professionals, thus improving access for those requiring it.”

Only two other randomized, clinical trials have evaluated web-based interventions for OA without contact from health professionals, according to the authors. While one of those did not find any differences in outcomes at 4 months when comparing a self-directed progressive lower-limb strength, flexibility, and walking program to being on a wait list, a separate trial evaluating a 9-module physical activity program in adults with knee and/or hip OA vs. a wait-list control group found evidence for efficacy for physical function at 3 months, but not quality of life or function in sport and recreation.

For the current study, researchers recruited 206 adults in Australia with clinically diagnosed knee OA via online advertisements and a volunteer database. Participants were aged 45 years or older, and reported activity-related knee pain and morning knee stiffness lasting at least 30 minutes; knee pain on most days for at least 3 months; and average knee pain severity of 4 or higher on an 11-point numeric rating scale in the previous week. In addition, participants were required to own a cell phone with text messaging, have Internet access, and be able to complete assessments.

Patients randomized to the intervention of the My Knee Exercise website received web-based information about OA and the value of exercise, with a 24-week self-directed program of strengthening exercises plus automated text messages to motivate behavior changes and encourage adherence to the exercise program. Controls received access to web-based information about OA and the value of exercise, but without the prescribed exercises or texts. Patients in the intervention group received an average of 60 text messages during the study period, and the average reply rate was 73%.

The primary study outcomes were changes in overall knee pain based on a numeric 0-10 rating scale and changes in physical function based on the Western Ontario and McMaster Universities Osteoarthritis Index 0-68 scale. A total of 180 participants completed both primary outcome measures at 24 weeks. The average age of the participants was 60 years, and 61% were women.

After 24 weeks, the intervention group averaged significantly greater improvement of 1.6 units for overall knee pain (P < .001) and 5.2 units for physical function (P = .002), compared with controls.

In addition, the proportion of patients who exceeded the minimal clinically important difference in pain improvement of at least 1.8 units was significantly higher in the intervention group, compared with controls (72.1% vs. 42.0%; P < .001). Similarly, more intervention-group patients achieved the minimal clinically important difference in WOMAC physical function of improvement of at least 6 units (68.0% vs. 40.8%; P < .001).

Secondary outcomes included additional measures of knee pain, knee function for sport and recreation, quality of life, physical activity, self-efficacy, overall improvement, and treatment satisfaction. Between-group differences favored the intervention on most measures, including Knee Injury and Osteoarthritis Outcome Score subscales for pain, sports/recreation, and quality of life; health-related quality of life; Arthritis Self-Efficacy Scale (ASES) pain subscale, individual change since baseline, and overall patient satisfaction. “Changes in PASE [Physical Activity Scale for the Elderly], ASES function, and SEE [Self Efficacy Exercise] were similar in both groups,” the researchers said.

No serious adverse events were reported by any study participants. Eight patients in the intervention group reported knee pain during the study, compared with one of the controls, and use of pain medications was similar between the groups, except that more control participants used massage, heat or cold, and topical anti-inflammatories.

The results suggest that a majority of participants in the intervention group improved pain and function without the need for in-person contact with a health professional, the researchers noted. However, more intensive management may be needed to support the 30% who did not benefit from the unsupervised approach, they said.

The study findings were limited by several factors, including the potential bias of a volunteer study population, possible lack of generalizability to individuals with lower levels of education or self-efficacy, and lack of direct comparison between web-based intervention and clinician-delivered intervention, the researchers noted.

The study was funded by the National Health and Medical Research Council, whose fellowships supported two of the authors. Lead author Ms. Nelligan disclosed a PhD scholarship from the Australian Government Research Training Program and personal fees from the University of Melbourne unrelated to the current study.

Adults with knee osteoarthritis (OA) who participated in a self-directed, web-based exercise program with automated text-message reminders and encouragement for 6 months showed significant improvement in overall knee pain and physical function, compared with patients who received web-based OA information alone, in a randomized trial of 180 individuals.

copyright Nandyphotos/Thinkstock

The results support a role for web-based exercise intervention to improve knee OA patients’ access to recommended exercises and to assist clinicians in managing patients on a population level, according to the first author of the study, Rachel Kate Nelligan, of the University of Melbourne, and colleagues. Their report is in JAMA Internal Medicine.

“Our free-to-access, unsupervised program could serve as an entry-level intervention, with participants who do not experience clinical benefits progressing to subsequent steps for more intensive, personalized management,” they said. “Such an approach has the potential to better distribute limited health care resources and reduce demand for contact with health professionals, thus improving access for those requiring it.”

Only two other randomized, clinical trials have evaluated web-based interventions for OA without contact from health professionals, according to the authors. While one of those did not find any differences in outcomes at 4 months when comparing a self-directed progressive lower-limb strength, flexibility, and walking program to being on a wait list, a separate trial evaluating a 9-module physical activity program in adults with knee and/or hip OA vs. a wait-list control group found evidence for efficacy for physical function at 3 months, but not quality of life or function in sport and recreation.

For the current study, researchers recruited 206 adults in Australia with clinically diagnosed knee OA via online advertisements and a volunteer database. Participants were aged 45 years or older, and reported activity-related knee pain and morning knee stiffness lasting at least 30 minutes; knee pain on most days for at least 3 months; and average knee pain severity of 4 or higher on an 11-point numeric rating scale in the previous week. In addition, participants were required to own a cell phone with text messaging, have Internet access, and be able to complete assessments.

Patients randomized to the intervention of the My Knee Exercise website received web-based information about OA and the value of exercise, with a 24-week self-directed program of strengthening exercises plus automated text messages to motivate behavior changes and encourage adherence to the exercise program. Controls received access to web-based information about OA and the value of exercise, but without the prescribed exercises or texts. Patients in the intervention group received an average of 60 text messages during the study period, and the average reply rate was 73%.

The primary study outcomes were changes in overall knee pain based on a numeric 0-10 rating scale and changes in physical function based on the Western Ontario and McMaster Universities Osteoarthritis Index 0-68 scale. A total of 180 participants completed both primary outcome measures at 24 weeks. The average age of the participants was 60 years, and 61% were women.

After 24 weeks, the intervention group averaged significantly greater improvement of 1.6 units for overall knee pain (P < .001) and 5.2 units for physical function (P = .002), compared with controls.

In addition, the proportion of patients who exceeded the minimal clinically important difference in pain improvement of at least 1.8 units was significantly higher in the intervention group, compared with controls (72.1% vs. 42.0%; P < .001). Similarly, more intervention-group patients achieved the minimal clinically important difference in WOMAC physical function of improvement of at least 6 units (68.0% vs. 40.8%; P < .001).

Secondary outcomes included additional measures of knee pain, knee function for sport and recreation, quality of life, physical activity, self-efficacy, overall improvement, and treatment satisfaction. Between-group differences favored the intervention on most measures, including Knee Injury and Osteoarthritis Outcome Score subscales for pain, sports/recreation, and quality of life; health-related quality of life; Arthritis Self-Efficacy Scale (ASES) pain subscale, individual change since baseline, and overall patient satisfaction. “Changes in PASE [Physical Activity Scale for the Elderly], ASES function, and SEE [Self Efficacy Exercise] were similar in both groups,” the researchers said.

No serious adverse events were reported by any study participants. Eight patients in the intervention group reported knee pain during the study, compared with one of the controls, and use of pain medications was similar between the groups, except that more control participants used massage, heat or cold, and topical anti-inflammatories.

The results suggest that a majority of participants in the intervention group improved pain and function without the need for in-person contact with a health professional, the researchers noted. However, more intensive management may be needed to support the 30% who did not benefit from the unsupervised approach, they said.

The study findings were limited by several factors, including the potential bias of a volunteer study population, possible lack of generalizability to individuals with lower levels of education or self-efficacy, and lack of direct comparison between web-based intervention and clinician-delivered intervention, the researchers noted.

The study was funded by the National Health and Medical Research Council, whose fellowships supported two of the authors. Lead author Ms. Nelligan disclosed a PhD scholarship from the Australian Government Research Training Program and personal fees from the University of Melbourne unrelated to the current study.

Adults with knee osteoarthritis (OA) who participated in a self-directed, web-based exercise program with automated text-message reminders and encouragement for 6 months showed significant improvement in overall knee pain and physical function, compared with patients who received web-based OA information alone, in a randomized trial of 180 individuals.

copyright Nandyphotos/Thinkstock

The results support a role for web-based exercise intervention to improve knee OA patients’ access to recommended exercises and to assist clinicians in managing patients on a population level, according to the first author of the study, Rachel Kate Nelligan, of the University of Melbourne, and colleagues. Their report is in JAMA Internal Medicine.

“Our free-to-access, unsupervised program could serve as an entry-level intervention, with participants who do not experience clinical benefits progressing to subsequent steps for more intensive, personalized management,” they said. “Such an approach has the potential to better distribute limited health care resources and reduce demand for contact with health professionals, thus improving access for those requiring it.”

Only two other randomized, clinical trials have evaluated web-based interventions for OA without contact from health professionals, according to the authors. While one of those did not find any differences in outcomes at 4 months when comparing a self-directed progressive lower-limb strength, flexibility, and walking program to being on a wait list, a separate trial evaluating a 9-module physical activity program in adults with knee and/or hip OA vs. a wait-list control group found evidence for efficacy for physical function at 3 months, but not quality of life or function in sport and recreation.

For the current study, researchers recruited 206 adults in Australia with clinically diagnosed knee OA via online advertisements and a volunteer database. Participants were aged 45 years or older, and reported activity-related knee pain and morning knee stiffness lasting at least 30 minutes; knee pain on most days for at least 3 months; and average knee pain severity of 4 or higher on an 11-point numeric rating scale in the previous week. In addition, participants were required to own a cell phone with text messaging, have Internet access, and be able to complete assessments.

Patients randomized to the intervention of the My Knee Exercise website received web-based information about OA and the value of exercise, with a 24-week self-directed program of strengthening exercises plus automated text messages to motivate behavior changes and encourage adherence to the exercise program. Controls received access to web-based information about OA and the value of exercise, but without the prescribed exercises or texts. Patients in the intervention group received an average of 60 text messages during the study period, and the average reply rate was 73%.

The primary study outcomes were changes in overall knee pain based on a numeric 0-10 rating scale and changes in physical function based on the Western Ontario and McMaster Universities Osteoarthritis Index 0-68 scale. A total of 180 participants completed both primary outcome measures at 24 weeks. The average age of the participants was 60 years, and 61% were women.

After 24 weeks, the intervention group averaged significantly greater improvement of 1.6 units for overall knee pain (P < .001) and 5.2 units for physical function (P = .002), compared with controls.

In addition, the proportion of patients who exceeded the minimal clinically important difference in pain improvement of at least 1.8 units was significantly higher in the intervention group, compared with controls (72.1% vs. 42.0%; P < .001). Similarly, more intervention-group patients achieved the minimal clinically important difference in WOMAC physical function of improvement of at least 6 units (68.0% vs. 40.8%; P < .001).

Secondary outcomes included additional measures of knee pain, knee function for sport and recreation, quality of life, physical activity, self-efficacy, overall improvement, and treatment satisfaction. Between-group differences favored the intervention on most measures, including Knee Injury and Osteoarthritis Outcome Score subscales for pain, sports/recreation, and quality of life; health-related quality of life; Arthritis Self-Efficacy Scale (ASES) pain subscale, individual change since baseline, and overall patient satisfaction. “Changes in PASE [Physical Activity Scale for the Elderly], ASES function, and SEE [Self Efficacy Exercise] were similar in both groups,” the researchers said.

No serious adverse events were reported by any study participants. Eight patients in the intervention group reported knee pain during the study, compared with one of the controls, and use of pain medications was similar between the groups, except that more control participants used massage, heat or cold, and topical anti-inflammatories.

The results suggest that a majority of participants in the intervention group improved pain and function without the need for in-person contact with a health professional, the researchers noted. However, more intensive management may be needed to support the 30% who did not benefit from the unsupervised approach, they said.

The study findings were limited by several factors, including the potential bias of a volunteer study population, possible lack of generalizability to individuals with lower levels of education or self-efficacy, and lack of direct comparison between web-based intervention and clinician-delivered intervention, the researchers noted.

The study was funded by the National Health and Medical Research Council, whose fellowships supported two of the authors. Lead author Ms. Nelligan disclosed a PhD scholarship from the Australian Government Research Training Program and personal fees from the University of Melbourne unrelated to the current study.

Each afternoon, Cyrus Shahpar, MD, the data guru for the White House COVID-19 Response Team, sends an email to staffers with the daily count of COVID-19 vaccinations delivered in the United States.

The numbers, collected from states ahead of the final figures being posted on the Centers for Disease Control and Prevention website, act as a report card of sorts on the team’s efforts.

On Saturday, April 3, it was a new record: 4.1 million vaccinations delivered in a single day, more than the total population of some states.

While the United States has a long way to go before it is done with COVID-19, there’s finally some good news in the nation’s long and blundering slog through the pandemic.

After a rocky start in December 2020 and January 2021, vaccination is happening faster than nearly anyone thought possible. As more people see their friends and family roll up their sleeves, hesitancy is dropping, too.

In settings where large numbers of people are vaccinated, such as nursing homes, COVID-19 cases and deaths have plunged.

Those gains, however, haven’t been shared equally. According to CDC data, 69% of people who are fully vaccinated are White, while just 8% are Black and about 9% are Hispanic, a group that now represents most new COVID-19 cases. 

Officials say that’s partly because the vaccines were rolled out to the elderly first. The average life expectancy for Black people in the United States is now age 72, which means there were fewer people of color represented in the first groups to become eligible. Experts are hopeful that underrepresented groups will start to catch up as more states open up vaccinations to younger people.

Based on overall numbers of daily vaccine doses, the United States ranks third, behind China and India. America ranks fourth – behind Israel, the United Kingdom, and Chile – in the total share of the population that’s been vaccinated, according to the website Our World in Data.
 

A positive development

It’s a stunning turnaround for a country that failed for months to develop effective tests, and still struggles in some quarters to investigate new cases and quarantine their contacts.

The 7-day rolling average of vaccines administered in the United States is currently more than 3 million a day.

“We knew that we needed to get to 3 million a day at some point, if we were going to get most people vaccinated this year, but I don’t think that most people expected it to happen this early,” said Eric Toner, MD, a senior scholar with the Johns Hopkins Center for Health Security in Baltimore.

Before taking office, President Joe Biden pledged to get 100 million shots in arms within his first 100 days in office. After hitting that goal in late March, he doubled it, to 200 million vaccinations by April 30. After first saying all adults should be eligible to get in line for the vaccine by May 1, on April 6, he bumped up that date to April 19. 

Some media reports have seen this repeated moving of the goalposts as calculated – an unstated strategy of underpromising and overdelivering with the aim of rebuilding public trust.

But others pointed out that, even if that’s true, the goals being set aren’t easy, and hitting them has never been a given.

“I think the Biden administration really gets a lot of credit for pushing the companies to get more vaccine out faster than they had planned to,” Dr. Toner said. “And the states have really responded as well as the federal government in terms of getting vaccination sites going. So we’re not only getting the vaccines, we’re getting it into people’s arms faster than expected.”

Others agree.

“We’re doing an amazing job, and I think the U.S. is really beginning to bend the curve,” said Carlos del Rio, MD, an infectious disease specialist and distinguished professor of medicine at Emory University, Atlanta.

“I think overall it’s just that everybody’s putting in a ton of work to get it done,” he said.

On April 3, the day the United States hit its vaccination record, he was volunteering to give vaccinations.

“I mean, of all the bad things we do to people as clinicians, this is one thing that people are very happy about, right?” Dr. del Rio said.

He said he vaccinated a young woman who asked if she could video chat with her mom, who was feeling nervous about getting the shot. He answered her mom’s questions, and later that day, she came down to be vaccinated herself.
 

‘We view it as a war’

The White House COVID-19 Response Team has worked hard to better coordinate the work of so many people at both the federal and state levels, Andy Slavitt, senior adviser for the team, said in an interview.

“We view it as a war, and in a war, you do everything: You bring experienced personnel; you bring all the resources to bear; you create multiple routes,” Mr. Slavitt said. “You don’t leave anything to chance.”

Among the levers the administration has pulled, using the Defense Production Act has helped vaccine manufacturers get needed supplies, Mr. Slavitt said.

The administration has set up an array of Federal Emergency Management Agency–run community vaccination centers and mobile vaccination sites to complement state-led efforts, and it’s activated a federal health law called the Public Readiness and Emergency Preparedness Act, which provides immunity from liability for retired doctors and nurses, among others, who sign up to help give vaccinations. That’s helped get more people into the field giving shots. 

The administration also canceled a plan to allocate vaccines to states based on their pace of administration, which would have punished underperforming states. Instead, doses are allocated based on population. 

In a media call on April 7, when asked whether the administration would send additional vaccines to Michigan, a state that’s seeing a surge of COVID-19 cases with more transmissible variants, Mr. Slavitt said they weren’t managing vaccine supply “according to some formula.”

He said they were distributing based on population “because that’s fundamental,” but were also locating vaccines “surgically in places that have had the greatest disease and where people have the greatest exposure.”

He said sites like community health centers and retail pharmacies have the power to order vaccines directly from the federal government, which helps get more supply to harder-hit areas.

Mr. Slavitt said hitting 4.1 million daily vaccinations on April 3 was gratifying.

“I’ve seen photographs ... of people breaking down in tears when they get their vaccine, people who are giving standing ovations to active military for taking care of them,” he said, “and I think about people who have gone for a long time without hope, or who have been very scared.

“It’s incredibly encouraging to think about maybe a few million people taking a step back to normal life again,” he said.

A version of this article first appeared on Medscape.com.

Each afternoon, Cyrus Shahpar, MD, the data guru for the White House COVID-19 Response Team, sends an email to staffers with the daily count of COVID-19 vaccinations delivered in the United States.

The numbers, collected from states ahead of the final figures being posted on the Centers for Disease Control and Prevention website, act as a report card of sorts on the team’s efforts.

On Saturday, April 3, it was a new record: 4.1 million vaccinations delivered in a single day, more than the total population of some states.

While the United States has a long way to go before it is done with COVID-19, there’s finally some good news in the nation’s long and blundering slog through the pandemic.

After a rocky start in December 2020 and January 2021, vaccination is happening faster than nearly anyone thought possible. As more people see their friends and family roll up their sleeves, hesitancy is dropping, too.

In settings where large numbers of people are vaccinated, such as nursing homes, COVID-19 cases and deaths have plunged.

Those gains, however, haven’t been shared equally. According to CDC data, 69% of people who are fully vaccinated are White, while just 8% are Black and about 9% are Hispanic, a group that now represents most new COVID-19 cases. 

Officials say that’s partly because the vaccines were rolled out to the elderly first. The average life expectancy for Black people in the United States is now age 72, which means there were fewer people of color represented in the first groups to become eligible. Experts are hopeful that underrepresented groups will start to catch up as more states open up vaccinations to younger people.

Based on overall numbers of daily vaccine doses, the United States ranks third, behind China and India. America ranks fourth – behind Israel, the United Kingdom, and Chile – in the total share of the population that’s been vaccinated, according to the website Our World in Data.
 

A positive development

It’s a stunning turnaround for a country that failed for months to develop effective tests, and still struggles in some quarters to investigate new cases and quarantine their contacts.

The 7-day rolling average of vaccines administered in the United States is currently more than 3 million a day.

“We knew that we needed to get to 3 million a day at some point, if we were going to get most people vaccinated this year, but I don’t think that most people expected it to happen this early,” said Eric Toner, MD, a senior scholar with the Johns Hopkins Center for Health Security in Baltimore.

Before taking office, President Joe Biden pledged to get 100 million shots in arms within his first 100 days in office. After hitting that goal in late March, he doubled it, to 200 million vaccinations by April 30. After first saying all adults should be eligible to get in line for the vaccine by May 1, on April 6, he bumped up that date to April 19. 

Some media reports have seen this repeated moving of the goalposts as calculated – an unstated strategy of underpromising and overdelivering with the aim of rebuilding public trust.

But others pointed out that, even if that’s true, the goals being set aren’t easy, and hitting them has never been a given.

“I think the Biden administration really gets a lot of credit for pushing the companies to get more vaccine out faster than they had planned to,” Dr. Toner said. “And the states have really responded as well as the federal government in terms of getting vaccination sites going. So we’re not only getting the vaccines, we’re getting it into people’s arms faster than expected.”

Others agree.

“We’re doing an amazing job, and I think the U.S. is really beginning to bend the curve,” said Carlos del Rio, MD, an infectious disease specialist and distinguished professor of medicine at Emory University, Atlanta.

“I think overall it’s just that everybody’s putting in a ton of work to get it done,” he said.

On April 3, the day the United States hit its vaccination record, he was volunteering to give vaccinations.

“I mean, of all the bad things we do to people as clinicians, this is one thing that people are very happy about, right?” Dr. del Rio said.

He said he vaccinated a young woman who asked if she could video chat with her mom, who was feeling nervous about getting the shot. He answered her mom’s questions, and later that day, she came down to be vaccinated herself.
 

‘We view it as a war’

The White House COVID-19 Response Team has worked hard to better coordinate the work of so many people at both the federal and state levels, Andy Slavitt, senior adviser for the team, said in an interview.

“We view it as a war, and in a war, you do everything: You bring experienced personnel; you bring all the resources to bear; you create multiple routes,” Mr. Slavitt said. “You don’t leave anything to chance.”

Among the levers the administration has pulled, using the Defense Production Act has helped vaccine manufacturers get needed supplies, Mr. Slavitt said.

The administration has set up an array of Federal Emergency Management Agency–run community vaccination centers and mobile vaccination sites to complement state-led efforts, and it’s activated a federal health law called the Public Readiness and Emergency Preparedness Act, which provides immunity from liability for retired doctors and nurses, among others, who sign up to help give vaccinations. That’s helped get more people into the field giving shots. 

The administration also canceled a plan to allocate vaccines to states based on their pace of administration, which would have punished underperforming states. Instead, doses are allocated based on population. 

In a media call on April 7, when asked whether the administration would send additional vaccines to Michigan, a state that’s seeing a surge of COVID-19 cases with more transmissible variants, Mr. Slavitt said they weren’t managing vaccine supply “according to some formula.”

He said they were distributing based on population “because that’s fundamental,” but were also locating vaccines “surgically in places that have had the greatest disease and where people have the greatest exposure.”

He said sites like community health centers and retail pharmacies have the power to order vaccines directly from the federal government, which helps get more supply to harder-hit areas.

Mr. Slavitt said hitting 4.1 million daily vaccinations on April 3 was gratifying.

“I’ve seen photographs ... of people breaking down in tears when they get their vaccine, people who are giving standing ovations to active military for taking care of them,” he said, “and I think about people who have gone for a long time without hope, or who have been very scared.

“It’s incredibly encouraging to think about maybe a few million people taking a step back to normal life again,” he said.

A version of this article first appeared on Medscape.com.

Each afternoon, Cyrus Shahpar, MD, the data guru for the White House COVID-19 Response Team, sends an email to staffers with the daily count of COVID-19 vaccinations delivered in the United States.

The numbers, collected from states ahead of the final figures being posted on the Centers for Disease Control and Prevention website, act as a report card of sorts on the team’s efforts.

On Saturday, April 3, it was a new record: 4.1 million vaccinations delivered in a single day, more than the total population of some states.

While the United States has a long way to go before it is done with COVID-19, there’s finally some good news in the nation’s long and blundering slog through the pandemic.

After a rocky start in December 2020 and January 2021, vaccination is happening faster than nearly anyone thought possible. As more people see their friends and family roll up their sleeves, hesitancy is dropping, too.

In settings where large numbers of people are vaccinated, such as nursing homes, COVID-19 cases and deaths have plunged.

Those gains, however, haven’t been shared equally. According to CDC data, 69% of people who are fully vaccinated are White, while just 8% are Black and about 9% are Hispanic, a group that now represents most new COVID-19 cases. 

Officials say that’s partly because the vaccines were rolled out to the elderly first. The average life expectancy for Black people in the United States is now age 72, which means there were fewer people of color represented in the first groups to become eligible. Experts are hopeful that underrepresented groups will start to catch up as more states open up vaccinations to younger people.

Based on overall numbers of daily vaccine doses, the United States ranks third, behind China and India. America ranks fourth – behind Israel, the United Kingdom, and Chile – in the total share of the population that’s been vaccinated, according to the website Our World in Data.
 

A positive development

It’s a stunning turnaround for a country that failed for months to develop effective tests, and still struggles in some quarters to investigate new cases and quarantine their contacts.

The 7-day rolling average of vaccines administered in the United States is currently more than 3 million a day.

“We knew that we needed to get to 3 million a day at some point, if we were going to get most people vaccinated this year, but I don’t think that most people expected it to happen this early,” said Eric Toner, MD, a senior scholar with the Johns Hopkins Center for Health Security in Baltimore.

Before taking office, President Joe Biden pledged to get 100 million shots in arms within his first 100 days in office. After hitting that goal in late March, he doubled it, to 200 million vaccinations by April 30. After first saying all adults should be eligible to get in line for the vaccine by May 1, on April 6, he bumped up that date to April 19. 

Some media reports have seen this repeated moving of the goalposts as calculated – an unstated strategy of underpromising and overdelivering with the aim of rebuilding public trust.

But others pointed out that, even if that’s true, the goals being set aren’t easy, and hitting them has never been a given.

“I think the Biden administration really gets a lot of credit for pushing the companies to get more vaccine out faster than they had planned to,” Dr. Toner said. “And the states have really responded as well as the federal government in terms of getting vaccination sites going. So we’re not only getting the vaccines, we’re getting it into people’s arms faster than expected.”

Others agree.

“We’re doing an amazing job, and I think the U.S. is really beginning to bend the curve,” said Carlos del Rio, MD, an infectious disease specialist and distinguished professor of medicine at Emory University, Atlanta.

“I think overall it’s just that everybody’s putting in a ton of work to get it done,” he said.

On April 3, the day the United States hit its vaccination record, he was volunteering to give vaccinations.

“I mean, of all the bad things we do to people as clinicians, this is one thing that people are very happy about, right?” Dr. del Rio said.

He said he vaccinated a young woman who asked if she could video chat with her mom, who was feeling nervous about getting the shot. He answered her mom’s questions, and later that day, she came down to be vaccinated herself.