MDedge Rheumatology

Key clinical point: Complete treatment adherence has still not been achieved in rheumatoid arthritis (RA), and factors like having patient-physician agreement on the treatment and the type of treatment prescribed are significant predictors of adherence.

Major finding: The 6-month prevalence of adherence was 59.1% (95% CI 48.1%-71.8%), with treatment agreement between patient and physician (odds ratio [OR] 4.29; P = .01) and information adaptation (OR 1.54; P = .015) being significant predictors of adherence. Treatment adherence was higher with second-line conventional synthetic disease-modifying rheumatic drug (csDMARD; OR 4.72; P = .005) and biological DMARDs/targeted synthetic DMARDs (OR 3.50; P = .029) vs. first-line csDMARDs.

Study details: This was a 6-month observational longitudinal prospective cohort study involving 180 patients with RA.

Disclosures: The ADHIERA trial was supported by a grant from Roche España to the Spanish Foundation of Rheumatology. A Balsa reported receiving speaker fees from various sources including Roche. Two other authors did not receive fees or personal grants from any laboratory, although their institute works by contract for laboratories for various sources.

Source: Balsa A et al. Ann Rheum Dis. 2021 (Nov 29). Doi: 10.1136/annrheumdis-2021-221163.

Key clinical point: Complete treatment adherence has still not been achieved in rheumatoid arthritis (RA), and factors like having patient-physician agreement on the treatment and the type of treatment prescribed are significant predictors of adherence.

Major finding: The 6-month prevalence of adherence was 59.1% (95% CI 48.1%-71.8%), with treatment agreement between patient and physician (odds ratio [OR] 4.29; P = .01) and information adaptation (OR 1.54; P = .015) being significant predictors of adherence. Treatment adherence was higher with second-line conventional synthetic disease-modifying rheumatic drug (csDMARD; OR 4.72; P = .005) and biological DMARDs/targeted synthetic DMARDs (OR 3.50; P = .029) vs. first-line csDMARDs.

Study details: This was a 6-month observational longitudinal prospective cohort study involving 180 patients with RA.

Disclosures: The ADHIERA trial was supported by a grant from Roche España to the Spanish Foundation of Rheumatology. A Balsa reported receiving speaker fees from various sources including Roche. Two other authors did not receive fees or personal grants from any laboratory, although their institute works by contract for laboratories for various sources.

Source: Balsa A et al. Ann Rheum Dis. 2021 (Nov 29). Doi: 10.1136/annrheumdis-2021-221163.

Key clinical point: Complete treatment adherence has still not been achieved in rheumatoid arthritis (RA), and factors like having patient-physician agreement on the treatment and the type of treatment prescribed are significant predictors of adherence.

Major finding: The 6-month prevalence of adherence was 59.1% (95% CI 48.1%-71.8%), with treatment agreement between patient and physician (odds ratio [OR] 4.29; P = .01) and information adaptation (OR 1.54; P = .015) being significant predictors of adherence. Treatment adherence was higher with second-line conventional synthetic disease-modifying rheumatic drug (csDMARD; OR 4.72; P = .005) and biological DMARDs/targeted synthetic DMARDs (OR 3.50; P = .029) vs. first-line csDMARDs.

Study details: This was a 6-month observational longitudinal prospective cohort study involving 180 patients with RA.

Disclosures: The ADHIERA trial was supported by a grant from Roche España to the Spanish Foundation of Rheumatology. A Balsa reported receiving speaker fees from various sources including Roche. Two other authors did not receive fees or personal grants from any laboratory, although their institute works by contract for laboratories for various sources.

Source: Balsa A et al. Ann Rheum Dis. 2021 (Nov 29). Doi: 10.1136/annrheumdis-2021-221163.

Key clinical point: Compared with the general population, the risk for COVID-19 was significantly higher in patients with rheumatoid arthritis (RA) but not in those with osteoarthritis, supporting recommendations for booster vaccines and priority access to anti-SARS-CoV-2 monoclonal antibody treatment for patients with RA.

Major finding: Compared with the general population, the risk for suspected/confirmed COVID-19 was significantly higher in patients with RA (hazard ratio [HR] 1.19; 95% CI 1.04-1.36) but not in patients with osteoarthritis (HR 1.00; 95% CI 0.93-1.07).

Study details: This was a cohort analysis that compared the risk for COVID-19 among 17,268 patients with RA and 1,616,600 participants from the general population.

Disclosures: This work was supported by the National Natural Science Foundation of China, the Project Program of National Clinical Research Center for Geriatric Disorders (Xiangya Hospital), and others. No conflict of interests was reported.

Source: Wang Y et al. Arthritis Care Res (Hoboken). 2021 (Dec 7). Doi: 10.1002/acr.24831.

Key clinical point: Compared with the general population, the risk for COVID-19 was significantly higher in patients with rheumatoid arthritis (RA) but not in those with osteoarthritis, supporting recommendations for booster vaccines and priority access to anti-SARS-CoV-2 monoclonal antibody treatment for patients with RA.

Major finding: Compared with the general population, the risk for suspected/confirmed COVID-19 was significantly higher in patients with RA (hazard ratio [HR] 1.19; 95% CI 1.04-1.36) but not in patients with osteoarthritis (HR 1.00; 95% CI 0.93-1.07).

Study details: This was a cohort analysis that compared the risk for COVID-19 among 17,268 patients with RA and 1,616,600 participants from the general population.

Disclosures: This work was supported by the National Natural Science Foundation of China, the Project Program of National Clinical Research Center for Geriatric Disorders (Xiangya Hospital), and others. No conflict of interests was reported.

Source: Wang Y et al. Arthritis Care Res (Hoboken). 2021 (Dec 7). Doi: 10.1002/acr.24831.

Key clinical point: Compared with the general population, the risk for COVID-19 was significantly higher in patients with rheumatoid arthritis (RA) but not in those with osteoarthritis, supporting recommendations for booster vaccines and priority access to anti-SARS-CoV-2 monoclonal antibody treatment for patients with RA.

Major finding: Compared with the general population, the risk for suspected/confirmed COVID-19 was significantly higher in patients with RA (hazard ratio [HR] 1.19; 95% CI 1.04-1.36) but not in patients with osteoarthritis (HR 1.00; 95% CI 0.93-1.07).

Study details: This was a cohort analysis that compared the risk for COVID-19 among 17,268 patients with RA and 1,616,600 participants from the general population.

Disclosures: This work was supported by the National Natural Science Foundation of China, the Project Program of National Clinical Research Center for Geriatric Disorders (Xiangya Hospital), and others. No conflict of interests was reported.

Source: Wang Y et al. Arthritis Care Res (Hoboken). 2021 (Dec 7). Doi: 10.1002/acr.24831.

Key clinical point: The risk for preterm birth (PTB) and small for gestational age (SGA) is almost 2-fold higher in pregnant women with vs. without rheumatoid arthritis (RA), with high maternal RA disease activity during pregnancy being a significant risk factor.

Major finding: The risk for PTB (adjusted odds ratio [aOR] 1.92; 95% CI 1.56-2.35) and SGA (aOR 1.93; 95% CI 1.45-2.57) was significantly higher in RA pregnancies vs. control pregnancies, with the risk even higher with maternal Disease Activity Score in 28 joints-C-reactive protein of >4.1 vs. <3.2 during pregnancy (PTB: aOR 3.38; 95% CI 1.52-7.55; SGA: aOR 3.90; 95% CI 1.46-10.4).

Study details: This was a prospective cohort study of 1,739 RA-pregnancies matched with 17,390 control-pregnancies.

Disclosures: This study was supported by NordForsk and others. Some of the authors declared receiving consultancy fees, research grants, and serving on the steering committee for various sources.

Source: Hellgren K et al. Rheumatology (Oxford). 2021;keab894 (Dec 3). Doi:  10.1093/rheumatology/keab894.

Key clinical point: The risk for preterm birth (PTB) and small for gestational age (SGA) is almost 2-fold higher in pregnant women with vs. without rheumatoid arthritis (RA), with high maternal RA disease activity during pregnancy being a significant risk factor.

Major finding: The risk for PTB (adjusted odds ratio [aOR] 1.92; 95% CI 1.56-2.35) and SGA (aOR 1.93; 95% CI 1.45-2.57) was significantly higher in RA pregnancies vs. control pregnancies, with the risk even higher with maternal Disease Activity Score in 28 joints-C-reactive protein of >4.1 vs. <3.2 during pregnancy (PTB: aOR 3.38; 95% CI 1.52-7.55; SGA: aOR 3.90; 95% CI 1.46-10.4).

Study details: This was a prospective cohort study of 1,739 RA-pregnancies matched with 17,390 control-pregnancies.

Disclosures: This study was supported by NordForsk and others. Some of the authors declared receiving consultancy fees, research grants, and serving on the steering committee for various sources.

Source: Hellgren K et al. Rheumatology (Oxford). 2021;keab894 (Dec 3). Doi:  10.1093/rheumatology/keab894.

Key clinical point: The risk for preterm birth (PTB) and small for gestational age (SGA) is almost 2-fold higher in pregnant women with vs. without rheumatoid arthritis (RA), with high maternal RA disease activity during pregnancy being a significant risk factor.

Major finding: The risk for PTB (adjusted odds ratio [aOR] 1.92; 95% CI 1.56-2.35) and SGA (aOR 1.93; 95% CI 1.45-2.57) was significantly higher in RA pregnancies vs. control pregnancies, with the risk even higher with maternal Disease Activity Score in 28 joints-C-reactive protein of >4.1 vs. <3.2 during pregnancy (PTB: aOR 3.38; 95% CI 1.52-7.55; SGA: aOR 3.90; 95% CI 1.46-10.4).

Study details: This was a prospective cohort study of 1,739 RA-pregnancies matched with 17,390 control-pregnancies.

Disclosures: This study was supported by NordForsk and others. Some of the authors declared receiving consultancy fees, research grants, and serving on the steering committee for various sources.

Source: Hellgren K et al. Rheumatology (Oxford). 2021;keab894 (Dec 3). Doi:  10.1093/rheumatology/keab894.

Key clinical point: Patients with rheumatoid arthritis (RA) who are not obese, those who have high initial disease activity, and those with long disease duration are more responsive to tumor necrosis factor (TNF) inhibitors.

Major finding: The risk for European League Against Rheumatism nonresponse was significantly higher in patients with obesity vs. those with a body mass index of <30 kg/m² (odds ratio 0.52 vs. 0.36; P = .01). Among patients treated with TNF inhibitors, the final Disease Activity Score on 28 joints-C-reactive protein (DAS28-CRP) decreased by 0.02 each year of disease duration (P < .001), with a reduction of 0.21 in patients with a baseline DAS28-CRP of >5.1 (P = .05).

Study details: This was a pooled analysis of individual patient data of 11,617 patients with RA from 29 randomized controlled trials.

Disclosures: This work was partly supported by the French Higher Education and Research Ministry. P Goupille and D Mulleman declared serving as a consultant or speaker, participating in international congresses or clinical trials, and receiving grants from various sources.

Source: Law-Wan J et al. RMD Open. 2021;7(3):e001882 (Nov 17). Doi: 10.1136/rmdopen-2021-001882.

Key clinical point: Patients with rheumatoid arthritis (RA) who are not obese, those who have high initial disease activity, and those with long disease duration are more responsive to tumor necrosis factor (TNF) inhibitors.

Major finding: The risk for European League Against Rheumatism nonresponse was significantly higher in patients with obesity vs. those with a body mass index of <30 kg/m² (odds ratio 0.52 vs. 0.36; P = .01). Among patients treated with TNF inhibitors, the final Disease Activity Score on 28 joints-C-reactive protein (DAS28-CRP) decreased by 0.02 each year of disease duration (P < .001), with a reduction of 0.21 in patients with a baseline DAS28-CRP of >5.1 (P = .05).

Study details: This was a pooled analysis of individual patient data of 11,617 patients with RA from 29 randomized controlled trials.

Disclosures: This work was partly supported by the French Higher Education and Research Ministry. P Goupille and D Mulleman declared serving as a consultant or speaker, participating in international congresses or clinical trials, and receiving grants from various sources.

Source: Law-Wan J et al. RMD Open. 2021;7(3):e001882 (Nov 17). Doi: 10.1136/rmdopen-2021-001882.

Key clinical point: Patients with rheumatoid arthritis (RA) who are not obese, those who have high initial disease activity, and those with long disease duration are more responsive to tumor necrosis factor (TNF) inhibitors.

Major finding: The risk for European League Against Rheumatism nonresponse was significantly higher in patients with obesity vs. those with a body mass index of <30 kg/m² (odds ratio 0.52 vs. 0.36; P = .01). Among patients treated with TNF inhibitors, the final Disease Activity Score on 28 joints-C-reactive protein (DAS28-CRP) decreased by 0.02 each year of disease duration (P < .001), with a reduction of 0.21 in patients with a baseline DAS28-CRP of >5.1 (P = .05).

Study details: This was a pooled analysis of individual patient data of 11,617 patients with RA from 29 randomized controlled trials.

Disclosures: This work was partly supported by the French Higher Education and Research Ministry. P Goupille and D Mulleman declared serving as a consultant or speaker, participating in international congresses or clinical trials, and receiving grants from various sources.

Source: Law-Wan J et al. RMD Open. 2021;7(3):e001882 (Nov 17). Doi: 10.1136/rmdopen-2021-001882.

Key clinical point: Patients with rheumatoid arthritis (RA) who were treated with Janus kinase (JAK) inhibitor showed reduced humoral response following 2 doses of BNT162b2 COVID-19 vaccine compared with healthy individuals.

Major finding: Patients with RA treated with JAK inhibitors had significantly lower levels of anti-spike immunoglobulin G antibodies (P = .024) than healthy individuals.

Study details: This study involved 12 adult patients with RA treated with JAK inhibitors and 26 healthy individuals who received 2 doses of the BNT162b2 COVID-19 vaccine.

Disclosures: This work was funded by the ISF Corona grant. The authors declared no conflict of interests.

Source: Iancovici L et al. Rheumatology (Oxford). 2021:keab879 (Nov 25). Doi:  10.1093/rheumatology/keab879.

Key clinical point: Patients with rheumatoid arthritis (RA) who were treated with Janus kinase (JAK) inhibitor showed reduced humoral response following 2 doses of BNT162b2 COVID-19 vaccine compared with healthy individuals.

Major finding: Patients with RA treated with JAK inhibitors had significantly lower levels of anti-spike immunoglobulin G antibodies (P = .024) than healthy individuals.

Study details: This study involved 12 adult patients with RA treated with JAK inhibitors and 26 healthy individuals who received 2 doses of the BNT162b2 COVID-19 vaccine.

Disclosures: This work was funded by the ISF Corona grant. The authors declared no conflict of interests.

Source: Iancovici L et al. Rheumatology (Oxford). 2021:keab879 (Nov 25). Doi:  10.1093/rheumatology/keab879.

Key clinical point: Patients with rheumatoid arthritis (RA) who were treated with Janus kinase (JAK) inhibitor showed reduced humoral response following 2 doses of BNT162b2 COVID-19 vaccine compared with healthy individuals.

Major finding: Patients with RA treated with JAK inhibitors had significantly lower levels of anti-spike immunoglobulin G antibodies (P = .024) than healthy individuals.

Study details: This study involved 12 adult patients with RA treated with JAK inhibitors and 26 healthy individuals who received 2 doses of the BNT162b2 COVID-19 vaccine.

Disclosures: This work was funded by the ISF Corona grant. The authors declared no conflict of interests.

Source: Iancovici L et al. Rheumatology (Oxford). 2021:keab879 (Nov 25). Doi:  10.1093/rheumatology/keab879.

People who get COVID-19 infections caused by the Omicron variant are less likely to need hospital care, compared with those infected by the Delta variant, according to two large new studies from the U.K. and South Africa.

The findings, which were released ahead of peer review, add to previous glimmers of evidence suggesting that Omicron – while extremely contagious -– may result in less severe symptoms than its predecessors.

“This is helping us quantify how much less severe Omicron is than Delta, and it appears to be between 40 to 75% reduced risk of hospitalizations, adjusted for many factors, which is very good,” said Eric Topol, MD, the editor-in-chief of Medscape and a cardiologist at Scripps Research Translational Institute in La Jolla, CA.

The first analysis, which was done by the World Health Organization Collaborating Centre for Infectious Disease Modelling and Imperial College London, found that overall, people infected by Omicron had about a 20% reduced risk of needing any hospital care for their infections and a 40% lower risk of an overnight hospital stay, compared to those infected with Delta.

Meanwhile, people who were re-infected – meaning they caught Omicron after recovering from a previous COVID-19 infection – had a 50%-60% lower risk of needing hospital care, likely reflecting the benefits of having some prior immunity against the same family of viruses.

The study included everyone with polymerase chain reaction-confirmed COVID-19 in the U.K. during the first 2 weeks of December – roughly 56,000 Omicron cases and 269,000 Delta infections.

The second study, from researchers at the National Institute for Communicable Diseases in South Africa, included more than 29,000 COVID-19 cases that had lab results highly suggestive of Omicron infections. Compared to people infected with the Delta variant, those with presumed Omicron infections were about 70% less likely to have severe disease.

While the news is hopeful for individuals, on a population level, health care systems may still be stressed, the study authors warned.

“Given the high transmissibility of the Omicron virus, there remains the potential for health services to face increasing demand if Omicron cases continue to grow at the rate that has been seen in recent weeks,” said study author Neil Ferguson, PhD, who studies how infectious diseases spread at Imperial College London.

The study authors say their findings are specific to the U.K. and South Africa, where substantial portions of the population have some immune protection from past infection. In other words, they may not apply to countries where fewer people have been vaccinated or recovered from a bout with COVID-19.

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

People who get COVID-19 infections caused by the Omicron variant are less likely to need hospital care, compared with those infected by the Delta variant, according to two large new studies from the U.K. and South Africa.

The findings, which were released ahead of peer review, add to previous glimmers of evidence suggesting that Omicron – while extremely contagious -– may result in less severe symptoms than its predecessors.

“This is helping us quantify how much less severe Omicron is than Delta, and it appears to be between 40 to 75% reduced risk of hospitalizations, adjusted for many factors, which is very good,” said Eric Topol, MD, the editor-in-chief of Medscape and a cardiologist at Scripps Research Translational Institute in La Jolla, CA.

The first analysis, which was done by the World Health Organization Collaborating Centre for Infectious Disease Modelling and Imperial College London, found that overall, people infected by Omicron had about a 20% reduced risk of needing any hospital care for their infections and a 40% lower risk of an overnight hospital stay, compared to those infected with Delta.

Meanwhile, people who were re-infected – meaning they caught Omicron after recovering from a previous COVID-19 infection – had a 50%-60% lower risk of needing hospital care, likely reflecting the benefits of having some prior immunity against the same family of viruses.

The study included everyone with polymerase chain reaction-confirmed COVID-19 in the U.K. during the first 2 weeks of December – roughly 56,000 Omicron cases and 269,000 Delta infections.

The second study, from researchers at the National Institute for Communicable Diseases in South Africa, included more than 29,000 COVID-19 cases that had lab results highly suggestive of Omicron infections. Compared to people infected with the Delta variant, those with presumed Omicron infections were about 70% less likely to have severe disease.

While the news is hopeful for individuals, on a population level, health care systems may still be stressed, the study authors warned.

“Given the high transmissibility of the Omicron virus, there remains the potential for health services to face increasing demand if Omicron cases continue to grow at the rate that has been seen in recent weeks,” said study author Neil Ferguson, PhD, who studies how infectious diseases spread at Imperial College London.

The study authors say their findings are specific to the U.K. and South Africa, where substantial portions of the population have some immune protection from past infection. In other words, they may not apply to countries where fewer people have been vaccinated or recovered from a bout with COVID-19.

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

People who get COVID-19 infections caused by the Omicron variant are less likely to need hospital care, compared with those infected by the Delta variant, according to two large new studies from the U.K. and South Africa.

The findings, which were released ahead of peer review, add to previous glimmers of evidence suggesting that Omicron – while extremely contagious -– may result in less severe symptoms than its predecessors.

“This is helping us quantify how much less severe Omicron is than Delta, and it appears to be between 40 to 75% reduced risk of hospitalizations, adjusted for many factors, which is very good,” said Eric Topol, MD, the editor-in-chief of Medscape and a cardiologist at Scripps Research Translational Institute in La Jolla, CA.

The first analysis, which was done by the World Health Organization Collaborating Centre for Infectious Disease Modelling and Imperial College London, found that overall, people infected by Omicron had about a 20% reduced risk of needing any hospital care for their infections and a 40% lower risk of an overnight hospital stay, compared to those infected with Delta.

Meanwhile, people who were re-infected – meaning they caught Omicron after recovering from a previous COVID-19 infection – had a 50%-60% lower risk of needing hospital care, likely reflecting the benefits of having some prior immunity against the same family of viruses.

The study included everyone with polymerase chain reaction-confirmed COVID-19 in the U.K. during the first 2 weeks of December – roughly 56,000 Omicron cases and 269,000 Delta infections.

The second study, from researchers at the National Institute for Communicable Diseases in South Africa, included more than 29,000 COVID-19 cases that had lab results highly suggestive of Omicron infections. Compared to people infected with the Delta variant, those with presumed Omicron infections were about 70% less likely to have severe disease.

While the news is hopeful for individuals, on a population level, health care systems may still be stressed, the study authors warned.

“Given the high transmissibility of the Omicron virus, there remains the potential for health services to face increasing demand if Omicron cases continue to grow at the rate that has been seen in recent weeks,” said study author Neil Ferguson, PhD, who studies how infectious diseases spread at Imperial College London.

The study authors say their findings are specific to the U.K. and South Africa, where substantial portions of the population have some immune protection from past infection. In other words, they may not apply to countries where fewer people have been vaccinated or recovered from a bout with COVID-19.

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

The Food and Drug Administration on Dec. 22, 2021, granted emergency use authorization (EUA) for a new antiviral pill to treat people with symptomatic COVID-19.

Pfizer’s ritonavir, name brand Paxlovid, can now be taken by patients ages 12 and up who weigh at least 88 pounds.

The antiviral is only for people who test positive for the coronavirus and who are at high risk for severe COVID-19, including hospitalization or death. It is available by prescription only and should be taken as soon as possible after diagnosis and within 5 days of the start of symptoms.

Paxlovid is taken as three tablets together orally twice a day for 5 days, for a total of 30 tablets.

Possible side effects include a reduced sense of taste, diarrhea, high blood pressure, and muscle aches.

The authorization arrives as U.S. cases of the Omicron variant are surging, some monoclonal antibody treatments are becoming less effective, and Americans struggle to maintain some sense of tradition and normalcy around the holidays.

Paxlovid joins remdesivir as an available antiviral to treat COVID-19. Remdesivir is fully approved by the FDA but is given only intravenously in a hospital.  

The COVID-19 antiviral pills come with some obvious advantages, including greater convenience for consumers – such as home use – and the potential to expand treatment for people in low- and middle-income countries.

‘An exciting step forward’

The EUA for Pfizer’s new drug has been highly anticipated, and news of its impending authorization circulated on social media on Tuesday. Eric Topol, MD, called the development an “exciting step forward.” Dr. Topol is editor in chief of Medscape, the parent company of MDedge.

He and many others also expected the FDA to grant emergency use authorization for an antiviral from Merck. But there was no immediate word Wednesday if that was still going to happen.

An accelerated authorization?

The FDA’s authorization for Pfizer’s antiviral comes about 5 weeks after the company submitted an application to the agency. In its submission, the company said a study showed the pill reduced by 89% the rate of hospitalization and death for people with mild to moderate COVID-19 illness.

In April 2021, Pfizer announced its antiviral pill for COVID-19 could be available by year’s end. In September, an official at the National Institutes of Allergy and Infectious Diseases seconded the prediction.

Merck filed its EUA application with the FDA in October. The company included results of its phase 3 study showing the treatment was linked to a 50% reduction in COVID-19 hospitalizations.

Interestingly, in September, Merck announced the findings of laboratory studies suggesting that molnupiravir would work against variants of the coronavirus because the agent does not target the virus’s spike protein. At the time, Delta was the dominant variant in the United States.

Faith-based purchasing

The U.S. government has already recognized the potential of these oral therapies, at least in terms of preorders.

Last month, it announced intentions to purchase $1 billion worth of Merck’s molnupiravir, adding to the $1.2 billion worth of the pills the U.S. ordered in June 2021. Also in November, the government announced it would purchase 10 million courses of the Pfizer pill at an estimated cost of $5.3 billion.

The government preorders of the antiviral pills for COVID-19 are separate from the orders for COVID-19 vaccines. Most recently, the Biden administration announced it will make 500 million tests for coronavirus infection available to Americans for free in early 2022.

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

The Food and Drug Administration on Dec. 22, 2021, granted emergency use authorization (EUA) for a new antiviral pill to treat people with symptomatic COVID-19.

Pfizer’s ritonavir, name brand Paxlovid, can now be taken by patients ages 12 and up who weigh at least 88 pounds.

The antiviral is only for people who test positive for the coronavirus and who are at high risk for severe COVID-19, including hospitalization or death. It is available by prescription only and should be taken as soon as possible after diagnosis and within 5 days of the start of symptoms.

Paxlovid is taken as three tablets together orally twice a day for 5 days, for a total of 30 tablets.

Possible side effects include a reduced sense of taste, diarrhea, high blood pressure, and muscle aches.

The authorization arrives as U.S. cases of the Omicron variant are surging, some monoclonal antibody treatments are becoming less effective, and Americans struggle to maintain some sense of tradition and normalcy around the holidays.

Paxlovid joins remdesivir as an available antiviral to treat COVID-19. Remdesivir is fully approved by the FDA but is given only intravenously in a hospital.  

The COVID-19 antiviral pills come with some obvious advantages, including greater convenience for consumers – such as home use – and the potential to expand treatment for people in low- and middle-income countries.

‘An exciting step forward’

The EUA for Pfizer’s new drug has been highly anticipated, and news of its impending authorization circulated on social media on Tuesday. Eric Topol, MD, called the development an “exciting step forward.” Dr. Topol is editor in chief of Medscape, the parent company of MDedge.

He and many others also expected the FDA to grant emergency use authorization for an antiviral from Merck. But there was no immediate word Wednesday if that was still going to happen.

An accelerated authorization?

The FDA’s authorization for Pfizer’s antiviral comes about 5 weeks after the company submitted an application to the agency. In its submission, the company said a study showed the pill reduced by 89% the rate of hospitalization and death for people with mild to moderate COVID-19 illness.

In April 2021, Pfizer announced its antiviral pill for COVID-19 could be available by year’s end. In September, an official at the National Institutes of Allergy and Infectious Diseases seconded the prediction.

Merck filed its EUA application with the FDA in October. The company included results of its phase 3 study showing the treatment was linked to a 50% reduction in COVID-19 hospitalizations.

Interestingly, in September, Merck announced the findings of laboratory studies suggesting that molnupiravir would work against variants of the coronavirus because the agent does not target the virus’s spike protein. At the time, Delta was the dominant variant in the United States.

Faith-based purchasing

The U.S. government has already recognized the potential of these oral therapies, at least in terms of preorders.

Last month, it announced intentions to purchase $1 billion worth of Merck’s molnupiravir, adding to the $1.2 billion worth of the pills the U.S. ordered in June 2021. Also in November, the government announced it would purchase 10 million courses of the Pfizer pill at an estimated cost of $5.3 billion.

The government preorders of the antiviral pills for COVID-19 are separate from the orders for COVID-19 vaccines. Most recently, the Biden administration announced it will make 500 million tests for coronavirus infection available to Americans for free in early 2022.

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

The Food and Drug Administration on Dec. 22, 2021, granted emergency use authorization (EUA) for a new antiviral pill to treat people with symptomatic COVID-19.

Pfizer’s ritonavir, name brand Paxlovid, can now be taken by patients ages 12 and up who weigh at least 88 pounds.

The antiviral is only for people who test positive for the coronavirus and who are at high risk for severe COVID-19, including hospitalization or death. It is available by prescription only and should be taken as soon as possible after diagnosis and within 5 days of the start of symptoms.

Paxlovid is taken as three tablets together orally twice a day for 5 days, for a total of 30 tablets.

Possible side effects include a reduced sense of taste, diarrhea, high blood pressure, and muscle aches.

The authorization arrives as U.S. cases of the Omicron variant are surging, some monoclonal antibody treatments are becoming less effective, and Americans struggle to maintain some sense of tradition and normalcy around the holidays.

Paxlovid joins remdesivir as an available antiviral to treat COVID-19. Remdesivir is fully approved by the FDA but is given only intravenously in a hospital.  

The COVID-19 antiviral pills come with some obvious advantages, including greater convenience for consumers – such as home use – and the potential to expand treatment for people in low- and middle-income countries.

‘An exciting step forward’

The EUA for Pfizer’s new drug has been highly anticipated, and news of its impending authorization circulated on social media on Tuesday. Eric Topol, MD, called the development an “exciting step forward.” Dr. Topol is editor in chief of Medscape, the parent company of MDedge.

He and many others also expected the FDA to grant emergency use authorization for an antiviral from Merck. But there was no immediate word Wednesday if that was still going to happen.

An accelerated authorization?

The FDA’s authorization for Pfizer’s antiviral comes about 5 weeks after the company submitted an application to the agency. In its submission, the company said a study showed the pill reduced by 89% the rate of hospitalization and death for people with mild to moderate COVID-19 illness.

In April 2021, Pfizer announced its antiviral pill for COVID-19 could be available by year’s end. In September, an official at the National Institutes of Allergy and Infectious Diseases seconded the prediction.

Merck filed its EUA application with the FDA in October. The company included results of its phase 3 study showing the treatment was linked to a 50% reduction in COVID-19 hospitalizations.

Interestingly, in September, Merck announced the findings of laboratory studies suggesting that molnupiravir would work against variants of the coronavirus because the agent does not target the virus’s spike protein. At the time, Delta was the dominant variant in the United States.

Faith-based purchasing

The U.S. government has already recognized the potential of these oral therapies, at least in terms of preorders.

Last month, it announced intentions to purchase $1 billion worth of Merck’s molnupiravir, adding to the $1.2 billion worth of the pills the U.S. ordered in June 2021. Also in November, the government announced it would purchase 10 million courses of the Pfizer pill at an estimated cost of $5.3 billion.

The government preorders of the antiviral pills for COVID-19 are separate from the orders for COVID-19 vaccines. Most recently, the Biden administration announced it will make 500 million tests for coronavirus infection available to Americans for free in early 2022.

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

A “definitive study” from Johns Hopkins University researchers and others shows that convalescent plasma can cut hospital admissions for COVID-19 by 54% if therapy is administered within 8 days of symptom onset.

In the study of 1,181 adults randomly assigned to high-titer convalescent plasma or placebo, 2.9% of people receiving the therapy were hospitalized, compared with 6.3% who received placebo control plasma.

This translates to a 54% risk reduction for hospitalization with convalescent plasma.

“We have a clear difference,” principal investigator David Sullivan, MD, a professor at Johns Hopkins University, Baltimore, said during a Dec. 21 media briefing.

“This is very good news since we are in the midst of the Omicron surge, which has defeated [some of] our major monocular antibody therapies,” said Arturo Casadevall, MD, chair of the department of molecular microbiology and immunology at Johns Hopkins.

“So we have a new tool to keep people from progressing in their disease and to reduce progression or hospitalization,” Dr. Casadevall said.

The findings were published as a preprint study on Dec. 21, 2021, on medRxiv. The study has not yet been peer reviewed.

Whereas many convalescent plasma studies were done in hospitalized patients, this is one of only a handful performed in outpatients, the researchers noted.

There is a regulatory catch. The Food and Drug Administration restricted emergency use authorization (EUA) for convalescent plasma in February 2021 to include only high-dose titer plasma and to limit the therapy to hospitalized patients with early disease or for immunocompromised people who cannot mount an adequate antibody response.

Dr. Sullivan and colleagues hoped their findings will prompt the FDA to expand the EUA to include outpatients.

“We have shared this data with both the World Health Organization and the FDA,” study coauthor Kelly Gebo, MD, MPH, said during the media briefing.

“We do believe that this could be scaled up quickly,” added Dr. Gebo, professor of medicine at Johns Hopkins University. Convalescent plasma “could be used as a potential treatment as variants continue to evolve, such as we’ve seen with Omicron.”
 

Pre-Omicron results

The study was conducted at Johns Hopkins University and 23 other sites nationwide between June 2020 and October 2021. This means researchers enrolled symptomatic adults during circulation of the SARS-CoV-2 ancestral strain and the Alpha and Delta variants.

However, Dr. Sullivan said, “we think that ... plasma with high levels of antibodies can adapt faster to Omicron, although it will take us longer to get an Omicron-specific supply.”

Because of the timing of the study, 80% of participants were unvaccinated. Mean age was 44 years and 57% were women. Black and Hispanic participants each accounted for more than 12% of the study population.

On average, participants received a transfusion within 6 days of the start of symptoms.

In the study, 37 people out of 589 control group participants were hospitalized, compared with 17 of the 592 who received the convalescent plasma.

“We know antibodies work against SARS-CoV-2. The vaccines have been spectacular – producing antibodies that reduce hospitalizations and prevent transmission,” Dr. Sullivan said. “Convalescent plasma provides much of the same antibodies instantly.”
 

Convalescent and controversial

Convalescent plasma has been one of the controversial treatments for people with COVID-19 – with studies going back and forth on the potential benefits and efficacy. A National Institutes of Health–funded study published in August 2021, for example, showed no significant benefit.

“As you know, convalescent plasma has had a rocky ride,” Dr. Casadevall said.

“It was deployed with great excitement in the terrible, early days of the pandemic. Unfortunately, the early excitement and optimism was dampened with some of the randomized control trials appearing to show no benefit in reducing mortality and hospitalized patients,” he added.

In contrast, the current study shows “where convalescent plasma works using the latest, most rigorous clinical investigation tools available: a double-blinded, randomized, placebo-control trial,” Dr. Casadevall said.
 

Why a preprint, and why now?

The researchers decided to release their data in recognition of the lag time between reporting of COVID-19 cases and hospitalizations, Dr. Sullivan said. “That’s part of the reason we decided to act now with this knowledge – that it does take a couple of weeks – with cases of Omicron going up.”

Furthermore, “we thought this was actionable data for decision-makers,” he added.

A reporter asked why the Johns Hopkins researchers chose to hold a media briefing for a preprint study.

A preprint is “not so unusual given the SARS-CoV-2 pandemic,” said study senior author Daniel Hanley, MD, division director of brain injury outcomes at Johns Hopkins University.

“The data are the data,” Dr. Casadevall added. “This is not going to change from peer review.”

Peer review may change some of the wording of the manuscript, but not the numbers, he added.

“Now with the Omicron crisis and the fact that we have lost some more main monoclonal antibodies, it is essential to get this information out,” Dr. Casadevall said.
 

Plasma therapy nothing new

Donation and transfusion of convalescent plasma is highly regulated with strict criteria, said Evan Bloch, MBChB, associate director of the transfusion medicine division at Johns Hopkins University.

If the FDA opts to expand the EUA based on this or other evidence, administration of convalescent plasma could be rolled out fairly quickly, the researchers noted.

Plasma transfusion takes place in hospitals and at infusion centers every day. The infrastructure is in place in many countries, even low- and middle-resource nations, around the world to provide convalescent plasma therapy. The major difference between traditional plasma and SARS-CoV-2 convalescent plasma is the indication, Dr. Bloch added.

In addition, convalescent plasma has a polyclonal composition – a benefit compared with monoclonal antibodies, he added. “It’s more durable or adaptive [compared with] some of the targeted therapies, such as monoclonal antibodies, where we’ve witnessed this diminished efficacy with viral evolution.”

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

A “definitive study” from Johns Hopkins University researchers and others shows that convalescent plasma can cut hospital admissions for COVID-19 by 54% if therapy is administered within 8 days of symptom onset.

In the study of 1,181 adults randomly assigned to high-titer convalescent plasma or placebo, 2.9% of people receiving the therapy were hospitalized, compared with 6.3% who received placebo control plasma.

This translates to a 54% risk reduction for hospitalization with convalescent plasma.

“We have a clear difference,” principal investigator David Sullivan, MD, a professor at Johns Hopkins University, Baltimore, said during a Dec. 21 media briefing.

“This is very good news since we are in the midst of the Omicron surge, which has defeated [some of] our major monocular antibody therapies,” said Arturo Casadevall, MD, chair of the department of molecular microbiology and immunology at Johns Hopkins.

“So we have a new tool to keep people from progressing in their disease and to reduce progression or hospitalization,” Dr. Casadevall said.

The findings were published as a preprint study on Dec. 21, 2021, on medRxiv. The study has not yet been peer reviewed.

Whereas many convalescent plasma studies were done in hospitalized patients, this is one of only a handful performed in outpatients, the researchers noted.

There is a regulatory catch. The Food and Drug Administration restricted emergency use authorization (EUA) for convalescent plasma in February 2021 to include only high-dose titer plasma and to limit the therapy to hospitalized patients with early disease or for immunocompromised people who cannot mount an adequate antibody response.

Dr. Sullivan and colleagues hoped their findings will prompt the FDA to expand the EUA to include outpatients.

“We have shared this data with both the World Health Organization and the FDA,” study coauthor Kelly Gebo, MD, MPH, said during the media briefing.

“We do believe that this could be scaled up quickly,” added Dr. Gebo, professor of medicine at Johns Hopkins University. Convalescent plasma “could be used as a potential treatment as variants continue to evolve, such as we’ve seen with Omicron.”
 

Pre-Omicron results

The study was conducted at Johns Hopkins University and 23 other sites nationwide between June 2020 and October 2021. This means researchers enrolled symptomatic adults during circulation of the SARS-CoV-2 ancestral strain and the Alpha and Delta variants.

However, Dr. Sullivan said, “we think that ... plasma with high levels of antibodies can adapt faster to Omicron, although it will take us longer to get an Omicron-specific supply.”

Because of the timing of the study, 80% of participants were unvaccinated. Mean age was 44 years and 57% were women. Black and Hispanic participants each accounted for more than 12% of the study population.

On average, participants received a transfusion within 6 days of the start of symptoms.

In the study, 37 people out of 589 control group participants were hospitalized, compared with 17 of the 592 who received the convalescent plasma.

“We know antibodies work against SARS-CoV-2. The vaccines have been spectacular – producing antibodies that reduce hospitalizations and prevent transmission,” Dr. Sullivan said. “Convalescent plasma provides much of the same antibodies instantly.”
 

Convalescent and controversial

Convalescent plasma has been one of the controversial treatments for people with COVID-19 – with studies going back and forth on the potential benefits and efficacy. A National Institutes of Health–funded study published in August 2021, for example, showed no significant benefit.

“As you know, convalescent plasma has had a rocky ride,” Dr. Casadevall said.

“It was deployed with great excitement in the terrible, early days of the pandemic. Unfortunately, the early excitement and optimism was dampened with some of the randomized control trials appearing to show no benefit in reducing mortality and hospitalized patients,” he added.

In contrast, the current study shows “where convalescent plasma works using the latest, most rigorous clinical investigation tools available: a double-blinded, randomized, placebo-control trial,” Dr. Casadevall said.
 

Why a preprint, and why now?

The researchers decided to release their data in recognition of the lag time between reporting of COVID-19 cases and hospitalizations, Dr. Sullivan said. “That’s part of the reason we decided to act now with this knowledge – that it does take a couple of weeks – with cases of Omicron going up.”

Furthermore, “we thought this was actionable data for decision-makers,” he added.

A reporter asked why the Johns Hopkins researchers chose to hold a media briefing for a preprint study.

A preprint is “not so unusual given the SARS-CoV-2 pandemic,” said study senior author Daniel Hanley, MD, division director of brain injury outcomes at Johns Hopkins University.

“The data are the data,” Dr. Casadevall added. “This is not going to change from peer review.”

Peer review may change some of the wording of the manuscript, but not the numbers, he added.

“Now with the Omicron crisis and the fact that we have lost some more main monoclonal antibodies, it is essential to get this information out,” Dr. Casadevall said.
 

Plasma therapy nothing new

Donation and transfusion of convalescent plasma is highly regulated with strict criteria, said Evan Bloch, MBChB, associate director of the transfusion medicine division at Johns Hopkins University.

If the FDA opts to expand the EUA based on this or other evidence, administration of convalescent plasma could be rolled out fairly quickly, the researchers noted.

Plasma transfusion takes place in hospitals and at infusion centers every day. The infrastructure is in place in many countries, even low- and middle-resource nations, around the world to provide convalescent plasma therapy. The major difference between traditional plasma and SARS-CoV-2 convalescent plasma is the indication, Dr. Bloch added.

In addition, convalescent plasma has a polyclonal composition – a benefit compared with monoclonal antibodies, he added. “It’s more durable or adaptive [compared with] some of the targeted therapies, such as monoclonal antibodies, where we’ve witnessed this diminished efficacy with viral evolution.”

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

A “definitive study” from Johns Hopkins University researchers and others shows that convalescent plasma can cut hospital admissions for COVID-19 by 54% if therapy is administered within 8 days of symptom onset.

In the study of 1,181 adults randomly assigned to high-titer convalescent plasma or placebo, 2.9% of people receiving the therapy were hospitalized, compared with 6.3% who received placebo control plasma.

This translates to a 54% risk reduction for hospitalization with convalescent plasma.

“We have a clear difference,” principal investigator David Sullivan, MD, a professor at Johns Hopkins University, Baltimore, said during a Dec. 21 media briefing.

“This is very good news since we are in the midst of the Omicron surge, which has defeated [some of] our major monocular antibody therapies,” said Arturo Casadevall, MD, chair of the department of molecular microbiology and immunology at Johns Hopkins.

“So we have a new tool to keep people from progressing in their disease and to reduce progression or hospitalization,” Dr. Casadevall said.

The findings were published as a preprint study on Dec. 21, 2021, on medRxiv. The study has not yet been peer reviewed.

Whereas many convalescent plasma studies were done in hospitalized patients, this is one of only a handful performed in outpatients, the researchers noted.

There is a regulatory catch. The Food and Drug Administration restricted emergency use authorization (EUA) for convalescent plasma in February 2021 to include only high-dose titer plasma and to limit the therapy to hospitalized patients with early disease or for immunocompromised people who cannot mount an adequate antibody response.

Dr. Sullivan and colleagues hoped their findings will prompt the FDA to expand the EUA to include outpatients.

“We have shared this data with both the World Health Organization and the FDA,” study coauthor Kelly Gebo, MD, MPH, said during the media briefing.

“We do believe that this could be scaled up quickly,” added Dr. Gebo, professor of medicine at Johns Hopkins University. Convalescent plasma “could be used as a potential treatment as variants continue to evolve, such as we’ve seen with Omicron.”
 

Pre-Omicron results

The study was conducted at Johns Hopkins University and 23 other sites nationwide between June 2020 and October 2021. This means researchers enrolled symptomatic adults during circulation of the SARS-CoV-2 ancestral strain and the Alpha and Delta variants.

However, Dr. Sullivan said, “we think that ... plasma with high levels of antibodies can adapt faster to Omicron, although it will take us longer to get an Omicron-specific supply.”

Because of the timing of the study, 80% of participants were unvaccinated. Mean age was 44 years and 57% were women. Black and Hispanic participants each accounted for more than 12% of the study population.

On average, participants received a transfusion within 6 days of the start of symptoms.

In the study, 37 people out of 589 control group participants were hospitalized, compared with 17 of the 592 who received the convalescent plasma.

“We know antibodies work against SARS-CoV-2. The vaccines have been spectacular – producing antibodies that reduce hospitalizations and prevent transmission,” Dr. Sullivan said. “Convalescent plasma provides much of the same antibodies instantly.”
 

Convalescent and controversial

Convalescent plasma has been one of the controversial treatments for people with COVID-19 – with studies going back and forth on the potential benefits and efficacy. A National Institutes of Health–funded study published in August 2021, for example, showed no significant benefit.

“As you know, convalescent plasma has had a rocky ride,” Dr. Casadevall said.

“It was deployed with great excitement in the terrible, early days of the pandemic. Unfortunately, the early excitement and optimism was dampened with some of the randomized control trials appearing to show no benefit in reducing mortality and hospitalized patients,” he added.

In contrast, the current study shows “where convalescent plasma works using the latest, most rigorous clinical investigation tools available: a double-blinded, randomized, placebo-control trial,” Dr. Casadevall said.
 

Why a preprint, and why now?

The researchers decided to release their data in recognition of the lag time between reporting of COVID-19 cases and hospitalizations, Dr. Sullivan said. “That’s part of the reason we decided to act now with this knowledge – that it does take a couple of weeks – with cases of Omicron going up.”

Furthermore, “we thought this was actionable data for decision-makers,” he added.

A reporter asked why the Johns Hopkins researchers chose to hold a media briefing for a preprint study.

A preprint is “not so unusual given the SARS-CoV-2 pandemic,” said study senior author Daniel Hanley, MD, division director of brain injury outcomes at Johns Hopkins University.

“The data are the data,” Dr. Casadevall added. “This is not going to change from peer review.”

Peer review may change some of the wording of the manuscript, but not the numbers, he added.

“Now with the Omicron crisis and the fact that we have lost some more main monoclonal antibodies, it is essential to get this information out,” Dr. Casadevall said.
 

Plasma therapy nothing new

Donation and transfusion of convalescent plasma is highly regulated with strict criteria, said Evan Bloch, MBChB, associate director of the transfusion medicine division at Johns Hopkins University.

If the FDA opts to expand the EUA based on this or other evidence, administration of convalescent plasma could be rolled out fairly quickly, the researchers noted.

Plasma transfusion takes place in hospitals and at infusion centers every day. The infrastructure is in place in many countries, even low- and middle-resource nations, around the world to provide convalescent plasma therapy. The major difference between traditional plasma and SARS-CoV-2 convalescent plasma is the indication, Dr. Bloch added.

In addition, convalescent plasma has a polyclonal composition – a benefit compared with monoclonal antibodies, he added. “It’s more durable or adaptive [compared with] some of the targeted therapies, such as monoclonal antibodies, where we’ve witnessed this diminished efficacy with viral evolution.”

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

The clinical value of bamlanivimab for hospitalized COVID-19 patients depends on whether patients have endogenous neutralizing antibodies at the time of treatment, according to new research.

In the randomized controlled trial, in both the group who received bamlanivimab and the group who received placebo, higher antigen and viral RNA levels were associated with a lower proportion of patients achieving recovery.

Other studies have shown that the use of monoclonal antibodies reduces hospitalization risk in outpatients with early COVID-19, and appears to promote viral load decline in the nasopharynx, wrote Jens D. Lundgren, MD, of the University of Copenhagen and colleagues in their article published in the Annals of Internal Medicine. What had been missing prior to this new research was final results from hospitalized patients, the authors said.

In the new study, the researchers randomized 314 adults hospitalized with COVID-19 but without end-organ failure to receive 7,000 mg bamlanivimab (163 patients) or a placebo (151 patients). All patients received study-supplied remdesivir unless contraindicated. The researchers compared the efficacy of bamlanivimab versus placebo, but considered remdesivir the standard of care in this study.

At baseline, 50% of patients overall had antispike endogenous neutralizing antibodies (nAbs), and 50% had SARS-CoV-2 nucleocapsid plasma antigen levels of at least 1,000 ng/L.

The median time to sustained recovery, 19 days, was not significantly different between the bamlanivimab and placebo groups (subhazard ratio, 0.99).

“As hypothesized, among those who were negative for nAb, the difference between bamlanivimab and placebo was more evident if levels of plasma antigen or nasal-swab viral RNA were above the median entry levels,” with subhazard ratios of 1.48 and 1.89, respectively, the researchers explained.

However, the hazard ratio for death for bamlanivimab vs. placebo was 0.45 for patients negative for nAb vs. 3.53 for those positive for nAb. These differences with respect to nAb status were similar across all 90 elements of a composite safety outcome, the researchers said.

Potential benefits remain unclear

The use of neutralizing monoclonal antibodies has been extensively documented as an effective treatment for COVID-19 among ambulatory patients, corresponding author Dr. Lundgren said in an interview.

“Conversely, among admitted patients with COVID-19 pneumonia, the benefit has been questionable,” he said.

The researchers examined a hypothesis that the null finding in hospitalized patients may stem from differences in underlying mechanisms, “either from uncontrolled viral replication – which would be predicted to occur in particular among those not yet been able to mount an endogenous immune response – or from hyperinflammation among those that have mounted such a response,” Dr. Lundgren said.

 The study findings supported the stated hypothesis, said Dr. Lundgren. “However, it was surprising that not only was the neutralizing antibody without any benefit among those that had mounted an endogenous immune response, but it actually may have been harmful,” he said.

Bamlanivimab was effective against the viral strain that circulated at the time of enrollment in the study, but subsequent viral strains have appeared to be unaffected by the neutralizing activity of the antibody, said Dr. Lundgren.

From a practical standpoint, “the findings would suggest that use of neutralizing monoclonal antibodies for patients admitted to a hospital with COVID pneumonia should be restricted to those that have not yet mounted an endogenous immune response, as determined by lack of detectable neutralizing antibodies at the time of admission,” Dr. Lundgren said.

Looking ahead, studies are currently underway to examine how the findings translate to vaccinated patients, he added. Other questions to be addressed include whether the benefits and harms apply to some or all neutralizing antibody products, he said.

In addition, “our research consortium is currently doing field testing of several point-of-care test candidates to examine their reliability and functionality,” for how quickly they might identify an endogenous neutralizing antibody response in an admitted COVID pneumonia patient,” Dr. Lundgren noted.

Findings show bamlanivimab’s limits

“Based on the findings of the current study, no clear subgroup of patients could be identified who would benefit from bamlanivimab when hospitalized with COVID-19,” said Suman Pal, MD, of the University of New Mexico, Albuquerque, in an interview.

“The study findings also show possible harm of using bamlanivimab in hospitalized COVID-19 patients who were seropositive for neutralizing antibodies prior to receiving therapy,” Dr. Pal emphasized. “Moreover, the study did not include participants with COVID-19 from variant strains, such as delta and omicron, which currently account for a large number of cases.” “Therefore, the results of this study do not support the use of bamlanivimab in the clinical setting until further evidence is available to guide the selection of patients who may benefit from therapy,” he explained.

“The possible benefit of bamlanivimab does not outweigh the risks in patients hospitalized with COVID-19,” he concluded.

Dr. Pal emphasized the need for larger prospective studies to establish whether bamlanivimab may have benefits in a subgroup of patients, but “well-validated point-of-care tests to identify such patients need to be readily available before this therapy can be considered by clinicians at the bedside,” he concluded.

Diligent screening required before use

Monoclonal antibody treatment has been administered to individuals with diagnosis of COVID-19 infection as outpatients as well as for hospitalized inpatients, said Noel Deep, MD, an internist in Antigo, Wisc., in an interview. “This study is important because it helps physicians and health care institutions to evaluate whether continued use of the monoclonal antibodies would be beneficial and, if so, in what patient populations,” he said.

The findings present interesting implications for the care of COVID-19 patients, said Dr. Deep. “This study indicates that bamlanivimab does not provide the benefit that was initially envisioned when the monoclonal antibody infusions were initially initiated in the treatment of COVID-19 infections. “Serological screening of the patients would help to identify that subgroup of individuals who could benefit from this monoclonal antibody rather than administering it to every COVID-19–positive individual,” he explained.

However, “it is important to note that the emergency use authorization (EUA) for single-agent bamlanivimab has been revoked,” Dr. Deep said.

“The potential benefits of bamlanivimab can be realized only if adequate attention is paid to identifying the appropriate candidates based on serological screening, and administering bamlanivimab to those who are already producing endogenous antibodies could lead to increased risk to those individuals,” he said. Dr. Deep added that he would favor administration of bamlanivimab “in those appropriately screened and eligible candidates, and it is my opinion that the benefits outweigh the risks in those individuals.”

Although the EUA for single-agent bamlanivimab has been revoked, “alternative monoclonal antibody therapies remain available under EUA, including REGEN-COV (casirivimab and imdevimab, administered together), and bamlanivimab and etesevimab administered together, for the same uses as previously authorized for bamlanivimab alone,” Dr. Deep said. “The FDA believes that these alternative monoclonal antibody therapies remain appropriate to treat patients with COVID-19, and I would like to see some data about the benefits and risks of these agents,” he noted.

Limitations, funding, and disclosures

The main limitation of the study was the small size and the fact that it was a subgroup analysis of a trial that ended early because of futility, the researchers wrote. However, the Therapeutics for Inpatients With COVID-19 (TICO) platform will proceed with clinical evaluation of additional COVID-19 treatments, they said.

The study was supported primarily by the U.S. government Operation Warp Speed and the National Institute of Allergy and Infectious Diseases. Other funding sources included the Division of Clinical Research and Leidos Biomedical Research for the INSIGHT (International Network for Strategic Initiatives in Global HIV Trials) Network, as well as an agreement between the National Heart, Lung, and Blood Institute and the Research Triangle Institute for the PETAL (Prevention & Early Treatment of Acute Lung Injury) Network and CTSN (Cardiothoracic Surgical Trials Network). Other support came from the U.S. Department of Veterans Affairs and the governments of Denmark (National Research Foundation), Australia (National Health and Medical Research Council), and the United Kingdom (Medical Research Council).

The medications used in the study were donated by Gilead Sciences and Eli Lilly.

The researchers had no financial conflicts do disclose. Dr. Deep and Dr. Pal had no relevant financial conflicts to disclose.

The clinical value of bamlanivimab for hospitalized COVID-19 patients depends on whether patients have endogenous neutralizing antibodies at the time of treatment, according to new research.

In the randomized controlled trial, in both the group who received bamlanivimab and the group who received placebo, higher antigen and viral RNA levels were associated with a lower proportion of patients achieving recovery.

Other studies have shown that the use of monoclonal antibodies reduces hospitalization risk in outpatients with early COVID-19, and appears to promote viral load decline in the nasopharynx, wrote Jens D. Lundgren, MD, of the University of Copenhagen and colleagues in their article published in the Annals of Internal Medicine. What had been missing prior to this new research was final results from hospitalized patients, the authors said.

In the new study, the researchers randomized 314 adults hospitalized with COVID-19 but without end-organ failure to receive 7,000 mg bamlanivimab (163 patients) or a placebo (151 patients). All patients received study-supplied remdesivir unless contraindicated. The researchers compared the efficacy of bamlanivimab versus placebo, but considered remdesivir the standard of care in this study.

At baseline, 50% of patients overall had antispike endogenous neutralizing antibodies (nAbs), and 50% had SARS-CoV-2 nucleocapsid plasma antigen levels of at least 1,000 ng/L.

The median time to sustained recovery, 19 days, was not significantly different between the bamlanivimab and placebo groups (subhazard ratio, 0.99).

“As hypothesized, among those who were negative for nAb, the difference between bamlanivimab and placebo was more evident if levels of plasma antigen or nasal-swab viral RNA were above the median entry levels,” with subhazard ratios of 1.48 and 1.89, respectively, the researchers explained.

However, the hazard ratio for death for bamlanivimab vs. placebo was 0.45 for patients negative for nAb vs. 3.53 for those positive for nAb. These differences with respect to nAb status were similar across all 90 elements of a composite safety outcome, the researchers said.

Potential benefits remain unclear

The use of neutralizing monoclonal antibodies has been extensively documented as an effective treatment for COVID-19 among ambulatory patients, corresponding author Dr. Lundgren said in an interview.

“Conversely, among admitted patients with COVID-19 pneumonia, the benefit has been questionable,” he said.

The researchers examined a hypothesis that the null finding in hospitalized patients may stem from differences in underlying mechanisms, “either from uncontrolled viral replication – which would be predicted to occur in particular among those not yet been able to mount an endogenous immune response – or from hyperinflammation among those that have mounted such a response,” Dr. Lundgren said.

 The study findings supported the stated hypothesis, said Dr. Lundgren. “However, it was surprising that not only was the neutralizing antibody without any benefit among those that had mounted an endogenous immune response, but it actually may have been harmful,” he said.

Bamlanivimab was effective against the viral strain that circulated at the time of enrollment in the study, but subsequent viral strains have appeared to be unaffected by the neutralizing activity of the antibody, said Dr. Lundgren.

From a practical standpoint, “the findings would suggest that use of neutralizing monoclonal antibodies for patients admitted to a hospital with COVID pneumonia should be restricted to those that have not yet mounted an endogenous immune response, as determined by lack of detectable neutralizing antibodies at the time of admission,” Dr. Lundgren said.

Looking ahead, studies are currently underway to examine how the findings translate to vaccinated patients, he added. Other questions to be addressed include whether the benefits and harms apply to some or all neutralizing antibody products, he said.

In addition, “our research consortium is currently doing field testing of several point-of-care test candidates to examine their reliability and functionality,” for how quickly they might identify an endogenous neutralizing antibody response in an admitted COVID pneumonia patient,” Dr. Lundgren noted.

Findings show bamlanivimab’s limits

“Based on the findings of the current study, no clear subgroup of patients could be identified who would benefit from bamlanivimab when hospitalized with COVID-19,” said Suman Pal, MD, of the University of New Mexico, Albuquerque, in an interview.

“The study findings also show possible harm of using bamlanivimab in hospitalized COVID-19 patients who were seropositive for neutralizing antibodies prior to receiving therapy,” Dr. Pal emphasized. “Moreover, the study did not include participants with COVID-19 from variant strains, such as delta and omicron, which currently account for a large number of cases.” “Therefore, the results of this study do not support the use of bamlanivimab in the clinical setting until further evidence is available to guide the selection of patients who may benefit from therapy,” he explained.

“The possible benefit of bamlanivimab does not outweigh the risks in patients hospitalized with COVID-19,” he concluded.

Dr. Pal emphasized the need for larger prospective studies to establish whether bamlanivimab may have benefits in a subgroup of patients, but “well-validated point-of-care tests to identify such patients need to be readily available before this therapy can be considered by clinicians at the bedside,” he concluded.

Diligent screening required before use

Monoclonal antibody treatment has been administered to individuals with diagnosis of COVID-19 infection as outpatients as well as for hospitalized inpatients, said Noel Deep, MD, an internist in Antigo, Wisc., in an interview. “This study is important because it helps physicians and health care institutions to evaluate whether continued use of the monoclonal antibodies would be beneficial and, if so, in what patient populations,” he said.

The findings present interesting implications for the care of COVID-19 patients, said Dr. Deep. “This study indicates that bamlanivimab does not provide the benefit that was initially envisioned when the monoclonal antibody infusions were initially initiated in the treatment of COVID-19 infections. “Serological screening of the patients would help to identify that subgroup of individuals who could benefit from this monoclonal antibody rather than administering it to every COVID-19–positive individual,” he explained.

However, “it is important to note that the emergency use authorization (EUA) for single-agent bamlanivimab has been revoked,” Dr. Deep said.

“The potential benefits of bamlanivimab can be realized only if adequate attention is paid to identifying the appropriate candidates based on serological screening, and administering bamlanivimab to those who are already producing endogenous antibodies could lead to increased risk to those individuals,” he said. Dr. Deep added that he would favor administration of bamlanivimab “in those appropriately screened and eligible candidates, and it is my opinion that the benefits outweigh the risks in those individuals.”

Although the EUA for single-agent bamlanivimab has been revoked, “alternative monoclonal antibody therapies remain available under EUA, including REGEN-COV (casirivimab and imdevimab, administered together), and bamlanivimab and etesevimab administered together, for the same uses as previously authorized for bamlanivimab alone,” Dr. Deep said. “The FDA believes that these alternative monoclonal antibody therapies remain appropriate to treat patients with COVID-19, and I would like to see some data about the benefits and risks of these agents,” he noted.

Limitations, funding, and disclosures

The main limitation of the study was the small size and the fact that it was a subgroup analysis of a trial that ended early because of futility, the researchers wrote. However, the Therapeutics for Inpatients With COVID-19 (TICO) platform will proceed with clinical evaluation of additional COVID-19 treatments, they said.

The study was supported primarily by the U.S. government Operation Warp Speed and the National Institute of Allergy and Infectious Diseases. Other funding sources included the Division of Clinical Research and Leidos Biomedical Research for the INSIGHT (International Network for Strategic Initiatives in Global HIV Trials) Network, as well as an agreement between the National Heart, Lung, and Blood Institute and the Research Triangle Institute for the PETAL (Prevention & Early Treatment of Acute Lung Injury) Network and CTSN (Cardiothoracic Surgical Trials Network). Other support came from the U.S. Department of Veterans Affairs and the governments of Denmark (National Research Foundation), Australia (National Health and Medical Research Council), and the United Kingdom (Medical Research Council).

The medications used in the study were donated by Gilead Sciences and Eli Lilly.

The researchers had no financial conflicts do disclose. Dr. Deep and Dr. Pal had no relevant financial conflicts to disclose.

The clinical value of bamlanivimab for hospitalized COVID-19 patients depends on whether patients have endogenous neutralizing antibodies at the time of treatment, according to new research.

In the randomized controlled trial, in both the group who received bamlanivimab and the group who received placebo, higher antigen and viral RNA levels were associated with a lower proportion of patients achieving recovery.

Other studies have shown that the use of monoclonal antibodies reduces hospitalization risk in outpatients with early COVID-19, and appears to promote viral load decline in the nasopharynx, wrote Jens D. Lundgren, MD, of the University of Copenhagen and colleagues in their article published in the Annals of Internal Medicine. What had been missing prior to this new research was final results from hospitalized patients, the authors said.

In the new study, the researchers randomized 314 adults hospitalized with COVID-19 but without end-organ failure to receive 7,000 mg bamlanivimab (163 patients) or a placebo (151 patients). All patients received study-supplied remdesivir unless contraindicated. The researchers compared the efficacy of bamlanivimab versus placebo, but considered remdesivir the standard of care in this study.

At baseline, 50% of patients overall had antispike endogenous neutralizing antibodies (nAbs), and 50% had SARS-CoV-2 nucleocapsid plasma antigen levels of at least 1,000 ng/L.

The median time to sustained recovery, 19 days, was not significantly different between the bamlanivimab and placebo groups (subhazard ratio, 0.99).

“As hypothesized, among those who were negative for nAb, the difference between bamlanivimab and placebo was more evident if levels of plasma antigen or nasal-swab viral RNA were above the median entry levels,” with subhazard ratios of 1.48 and 1.89, respectively, the researchers explained.

However, the hazard ratio for death for bamlanivimab vs. placebo was 0.45 for patients negative for nAb vs. 3.53 for those positive for nAb. These differences with respect to nAb status were similar across all 90 elements of a composite safety outcome, the researchers said.

Potential benefits remain unclear

The use of neutralizing monoclonal antibodies has been extensively documented as an effective treatment for COVID-19 among ambulatory patients, corresponding author Dr. Lundgren said in an interview.

“Conversely, among admitted patients with COVID-19 pneumonia, the benefit has been questionable,” he said.

The researchers examined a hypothesis that the null finding in hospitalized patients may stem from differences in underlying mechanisms, “either from uncontrolled viral replication – which would be predicted to occur in particular among those not yet been able to mount an endogenous immune response – or from hyperinflammation among those that have mounted such a response,” Dr. Lundgren said.

 The study findings supported the stated hypothesis, said Dr. Lundgren. “However, it was surprising that not only was the neutralizing antibody without any benefit among those that had mounted an endogenous immune response, but it actually may have been harmful,” he said.

Bamlanivimab was effective against the viral strain that circulated at the time of enrollment in the study, but subsequent viral strains have appeared to be unaffected by the neutralizing activity of the antibody, said Dr. Lundgren.

From a practical standpoint, “the findings would suggest that use of neutralizing monoclonal antibodies for patients admitted to a hospital with COVID pneumonia should be restricted to those that have not yet mounted an endogenous immune response, as determined by lack of detectable neutralizing antibodies at the time of admission,” Dr. Lundgren said.

Looking ahead, studies are currently underway to examine how the findings translate to vaccinated patients, he added. Other questions to be addressed include whether the benefits and harms apply to some or all neutralizing antibody products, he said.

In addition, “our research consortium is currently doing field testing of several point-of-care test candidates to examine their reliability and functionality,” for how quickly they might identify an endogenous neutralizing antibody response in an admitted COVID pneumonia patient,” Dr. Lundgren noted.

Findings show bamlanivimab’s limits

“Based on the findings of the current study, no clear subgroup of patients could be identified who would benefit from bamlanivimab when hospitalized with COVID-19,” said Suman Pal, MD, of the University of New Mexico, Albuquerque, in an interview.

“The study findings also show possible harm of using bamlanivimab in hospitalized COVID-19 patients who were seropositive for neutralizing antibodies prior to receiving therapy,” Dr. Pal emphasized. “Moreover, the study did not include participants with COVID-19 from variant strains, such as delta and omicron, which currently account for a large number of cases.” “Therefore, the results of this study do not support the use of bamlanivimab in the clinical setting until further evidence is available to guide the selection of patients who may benefit from therapy,” he explained.

“The possible benefit of bamlanivimab does not outweigh the risks in patients hospitalized with COVID-19,” he concluded.

Dr. Pal emphasized the need for larger prospective studies to establish whether bamlanivimab may have benefits in a subgroup of patients, but “well-validated point-of-care tests to identify such patients need to be readily available before this therapy can be considered by clinicians at the bedside,” he concluded.

Diligent screening required before use

Monoclonal antibody treatment has been administered to individuals with diagnosis of COVID-19 infection as outpatients as well as for hospitalized inpatients, said Noel Deep, MD, an internist in Antigo, Wisc., in an interview. “This study is important because it helps physicians and health care institutions to evaluate whether continued use of the monoclonal antibodies would be beneficial and, if so, in what patient populations,” he said.

The findings present interesting implications for the care of COVID-19 patients, said Dr. Deep. “This study indicates that bamlanivimab does not provide the benefit that was initially envisioned when the monoclonal antibody infusions were initially initiated in the treatment of COVID-19 infections. “Serological screening of the patients would help to identify that subgroup of individuals who could benefit from this monoclonal antibody rather than administering it to every COVID-19–positive individual,” he explained.

However, “it is important to note that the emergency use authorization (EUA) for single-agent bamlanivimab has been revoked,” Dr. Deep said.

“The potential benefits of bamlanivimab can be realized only if adequate attention is paid to identifying the appropriate candidates based on serological screening, and administering bamlanivimab to those who are already producing endogenous antibodies could lead to increased risk to those individuals,” he said. Dr. Deep added that he would favor administration of bamlanivimab “in those appropriately screened and eligible candidates, and it is my opinion that the benefits outweigh the risks in those individuals.”

Although the EUA for single-agent bamlanivimab has been revoked, “alternative monoclonal antibody therapies remain available under EUA, including REGEN-COV (casirivimab and imdevimab, administered together), and bamlanivimab and etesevimab administered together, for the same uses as previously authorized for bamlanivimab alone,” Dr. Deep said. “The FDA believes that these alternative monoclonal antibody therapies remain appropriate to treat patients with COVID-19, and I would like to see some data about the benefits and risks of these agents,” he noted.

Limitations, funding, and disclosures

The main limitation of the study was the small size and the fact that it was a subgroup analysis of a trial that ended early because of futility, the researchers wrote. However, the Therapeutics for Inpatients With COVID-19 (TICO) platform will proceed with clinical evaluation of additional COVID-19 treatments, they said.

The study was supported primarily by the U.S. government Operation Warp Speed and the National Institute of Allergy and Infectious Diseases. Other funding sources included the Division of Clinical Research and Leidos Biomedical Research for the INSIGHT (International Network for Strategic Initiatives in Global HIV Trials) Network, as well as an agreement between the National Heart, Lung, and Blood Institute and the Research Triangle Institute for the PETAL (Prevention & Early Treatment of Acute Lung Injury) Network and CTSN (Cardiothoracic Surgical Trials Network). Other support came from the U.S. Department of Veterans Affairs and the governments of Denmark (National Research Foundation), Australia (National Health and Medical Research Council), and the United Kingdom (Medical Research Council).

The medications used in the study were donated by Gilead Sciences and Eli Lilly.

The researchers had no financial conflicts do disclose. Dr. Deep and Dr. Pal had no relevant financial conflicts to disclose.

Editors at the BMJ have released an urgent request to Facebook’s Mark Zuckerberg and parent company Meta regarding a recent “fact-check” on the medical trade journal’s article about questionable Pfizer vaccine trial practices.

According to an open letter written by outgoing BMJ editor-in-chief Fiona Godlee, MD, and incoming editor-in-chief Kamran Abbasi, MD, Facebook hired a third-party contractor to evaluate the article’s findings. This resulted in “inaccurate, incompetent, and irresponsible” conclusions that “should be of concern to anyone who values and relies on sources such as the BMJ for reliable medical information.”

The article in question investigated data integrity concerns at Pfizer vaccine clinical trial sites. In September 2020, the letter states, a former employee of the research group involved in Pfizer’s main vaccine trials, Ventavia, reached out to the BMJ and “began providing ... dozens of internal company documents, photos, audio recordings, and emails.” According to the company’s website, Ventavia “played a significant part in [COVID-19 clinical trial] recruitment” and “has received recognition by Pfizer for their contribution to vaccine trials.”

It was previously reported that the whistle-blower is a former regional director who was involved in Pfizer’s vaccine trials in Texas during the fall of 2020. She alleges “the company falsified data, unblinded patients, employed inadequately trained vaccinators, and was slow to follow up on adverse events reported in Pfizer’s pivotal phase 3 trial.”

The images provided to the BMJ “showed needles discarded in a plastic biohazard bag instead of a sharps container box” and another displayed “vaccine packaging materials with trial participants’ identification numbers written on them left out in the open, potentially unblinding participants.”

Despite informing Ventavia, the director’s concerns went unaddressed. She then filed a complaint with the Food and Drug Administration and was subsequently fired the same day. The FDA did not investigate the director’s allegations, said Dr. Godlee and Dr. Abbasi, even though the evidence “revealed a host of poor clinical trial research practices occurring at Ventavia that could impact data integrity and patient safety.”
 

Article labeled as ‘hoax,’ without pointing out errors

The BMJ hired an investigative reporter to follow up on the clinical trial claims. The findings were published in an article on Nov. 2, 2021, after the article “went through ... the usual high-level legal and editorial oversight and peer review,” according to the journal.

However, by Nov. 10, the journal began receiving complaints from readers unable to share the article on social media. Others had their posts flagged with warnings, such as “missing context ... independent fact-checkers say this information could mislead people.” Administrators of various Facebook groups were notified that posts containing the article were “partly false.”

Readers were informed that Facebook contractor Lead Stories performed the article’s “fact check.” Lead Stories is “an award-winning innovative fact checking and debunking website” and “an active part of Facebook’s partnership with third-party fact checkers” – with the latter granting them “access to listings of content that has been flagged as potentially false by Facebook’s systems or its users.” The company said they “decide independently if we want to fact check it or not.”

Lead Stories stated that they “can enter our fact checks into a tool provided by Facebook and Facebook then uses our data to help slow down the spread of false information on its platform.” Although the contractor is compensated, Lead Stories claims they have “no say or influence over what we fact check or what our conclusions are.”

Both editors question the validity of the fact check performed by Lead Stories, as it failed to provide any “assertions of fact” as to what the BMJ got wrong. Moreover, the editors take issue with Lead Stories referring to the journal as a “news blog” and using the phrase “hoax-alert” in the URL when publishing the story on its site.

The BMJ has reached out to Lead Stories and Facebook, said the letter, but Lead Stories refuses to “change anything about their article or actions that have led to Facebook flagging our article.” Requests for Facebook to remove the “fact-checking” label and allow “readers to freely share the article on [Facebook’s] platform” have been unfruitful.

Dr. Godlee and Dr. Abbasi expressed concern that other “high quality information provider[s] have been affected by the incompetence of Meta’s fact checking regime.” In November, Instagram censored Cochrane, an international provider of independent systematic medical reviews. Instagram, also owned by Meta, prohibited users from tagging Cochrane because the organization “repeatedly posted ... false content about COVID-19 or vaccines.” Cochrane refuted the allegations.

While “fact checking has been a staple of good journalism for decades,” said the editors, Meta has “apparently delegated responsibility to people incompetent in carrying out this crucial task.” They urged the company to reconsider its fact-checking strategy and review the issues that contributed to the error.

This news organization reached out to Meta for comment but did not receive a response at press time.

Lead Stories has posted a reply (Lead Stories’ Response To BMJ Open Letter Objecting To A Lead Stories Fact Check) to the BMJ’s complaint on its website.

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

Editors at the BMJ have released an urgent request to Facebook’s Mark Zuckerberg and parent company Meta regarding a recent “fact-check” on the medical trade journal’s article about questionable Pfizer vaccine trial practices.

According to an open letter written by outgoing BMJ editor-in-chief Fiona Godlee, MD, and incoming editor-in-chief Kamran Abbasi, MD, Facebook hired a third-party contractor to evaluate the article’s findings. This resulted in “inaccurate, incompetent, and irresponsible” conclusions that “should be of concern to anyone who values and relies on sources such as the BMJ for reliable medical information.”

The article in question investigated data integrity concerns at Pfizer vaccine clinical trial sites. In September 2020, the letter states, a former employee of the research group involved in Pfizer’s main vaccine trials, Ventavia, reached out to the BMJ and “began providing ... dozens of internal company documents, photos, audio recordings, and emails.” According to the company’s website, Ventavia “played a significant part in [COVID-19 clinical trial] recruitment” and “has received recognition by Pfizer for their contribution to vaccine trials.”

It was previously reported that the whistle-blower is a former regional director who was involved in Pfizer’s vaccine trials in Texas during the fall of 2020. She alleges “the company falsified data, unblinded patients, employed inadequately trained vaccinators, and was slow to follow up on adverse events reported in Pfizer’s pivotal phase 3 trial.”

The images provided to the BMJ “showed needles discarded in a plastic biohazard bag instead of a sharps container box” and another displayed “vaccine packaging materials with trial participants’ identification numbers written on them left out in the open, potentially unblinding participants.”

Despite informing Ventavia, the director’s concerns went unaddressed. She then filed a complaint with the Food and Drug Administration and was subsequently fired the same day. The FDA did not investigate the director’s allegations, said Dr. Godlee and Dr. Abbasi, even though the evidence “revealed a host of poor clinical trial research practices occurring at Ventavia that could impact data integrity and patient safety.”
 

Article labeled as ‘hoax,’ without pointing out errors

The BMJ hired an investigative reporter to follow up on the clinical trial claims. The findings were published in an article on Nov. 2, 2021, after the article “went through ... the usual high-level legal and editorial oversight and peer review,” according to the journal.

However, by Nov. 10, the journal began receiving complaints from readers unable to share the article on social media. Others had their posts flagged with warnings, such as “missing context ... independent fact-checkers say this information could mislead people.” Administrators of various Facebook groups were notified that posts containing the article were “partly false.”

Readers were informed that Facebook contractor Lead Stories performed the article’s “fact check.” Lead Stories is “an award-winning innovative fact checking and debunking website” and “an active part of Facebook’s partnership with third-party fact checkers” – with the latter granting them “access to listings of content that has been flagged as potentially false by Facebook’s systems or its users.” The company said they “decide independently if we want to fact check it or not.”

Lead Stories stated that they “can enter our fact checks into a tool provided by Facebook and Facebook then uses our data to help slow down the spread of false information on its platform.” Although the contractor is compensated, Lead Stories claims they have “no say or influence over what we fact check or what our conclusions are.”

Both editors question the validity of the fact check performed by Lead Stories, as it failed to provide any “assertions of fact” as to what the BMJ got wrong. Moreover, the editors take issue with Lead Stories referring to the journal as a “news blog” and using the phrase “hoax-alert” in the URL when publishing the story on its site.

The BMJ has reached out to Lead Stories and Facebook, said the letter, but Lead Stories refuses to “change anything about their article or actions that have led to Facebook flagging our article.” Requests for Facebook to remove the “fact-checking” label and allow “readers to freely share the article on [Facebook’s] platform” have been unfruitful.

Dr. Godlee and Dr. Abbasi expressed concern that other “high quality information provider[s] have been affected by the incompetence of Meta’s fact checking regime.” In November, Instagram censored Cochrane, an international provider of independent systematic medical reviews. Instagram, also owned by Meta, prohibited users from tagging Cochrane because the organization “repeatedly posted ... false content about COVID-19 or vaccines.” Cochrane refuted the allegations.

While “fact checking has been a staple of good journalism for decades,” said the editors, Meta has “apparently delegated responsibility to people incompetent in carrying out this crucial task.” They urged the company to reconsider its fact-checking strategy and review the issues that contributed to the error.

This news organization reached out to Meta for comment but did not receive a response at press time.

Lead Stories has posted a reply (Lead Stories’ Response To BMJ Open Letter Objecting To A Lead Stories Fact Check) to the BMJ’s complaint on its website.

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

Editors at the BMJ have released an urgent request to Facebook’s Mark Zuckerberg and parent company Meta regarding a recent “fact-check” on the medical trade journal’s article about questionable Pfizer vaccine trial practices.

According to an open letter written by outgoing BMJ editor-in-chief Fiona Godlee, MD, and incoming editor-in-chief Kamran Abbasi, MD, Facebook hired a third-party contractor to evaluate the article’s findings. This resulted in “inaccurate, incompetent, and irresponsible” conclusions that “should be of concern to anyone who values and relies on sources such as the BMJ for reliable medical information.”

The article in question investigated data integrity concerns at Pfizer vaccine clinical trial sites. In September 2020, the letter states, a former employee of the research group involved in Pfizer’s main vaccine trials, Ventavia, reached out to the BMJ and “began providing ... dozens of internal company documents, photos, audio recordings, and emails.” According to the company’s website, Ventavia “played a significant part in [COVID-19 clinical trial] recruitment” and “has received recognition by Pfizer for their contribution to vaccine trials.”

It was previously reported that the whistle-blower is a former regional director who was involved in Pfizer’s vaccine trials in Texas during the fall of 2020. She alleges “the company falsified data, unblinded patients, employed inadequately trained vaccinators, and was slow to follow up on adverse events reported in Pfizer’s pivotal phase 3 trial.”

The images provided to the BMJ “showed needles discarded in a plastic biohazard bag instead of a sharps container box” and another displayed “vaccine packaging materials with trial participants’ identification numbers written on them left out in the open, potentially unblinding participants.”

Despite informing Ventavia, the director’s concerns went unaddressed. She then filed a complaint with the Food and Drug Administration and was subsequently fired the same day. The FDA did not investigate the director’s allegations, said Dr. Godlee and Dr. Abbasi, even though the evidence “revealed a host of poor clinical trial research practices occurring at Ventavia that could impact data integrity and patient safety.”
 

Article labeled as ‘hoax,’ without pointing out errors

The BMJ hired an investigative reporter to follow up on the clinical trial claims. The findings were published in an article on Nov. 2, 2021, after the article “went through ... the usual high-level legal and editorial oversight and peer review,” according to the journal.

However, by Nov. 10, the journal began receiving complaints from readers unable to share the article on social media. Others had their posts flagged with warnings, such as “missing context ... independent fact-checkers say this information could mislead people.” Administrators of various Facebook groups were notified that posts containing the article were “partly false.”

Readers were informed that Facebook contractor Lead Stories performed the article’s “fact check.” Lead Stories is “an award-winning innovative fact checking and debunking website” and “an active part of Facebook’s partnership with third-party fact checkers” – with the latter granting them “access to listings of content that has been flagged as potentially false by Facebook’s systems or its users.” The company said they “decide independently if we want to fact check it or not.”

Lead Stories stated that they “can enter our fact checks into a tool provided by Facebook and Facebook then uses our data to help slow down the spread of false information on its platform.” Although the contractor is compensated, Lead Stories claims they have “no say or influence over what we fact check or what our conclusions are.”

Both editors question the validity of the fact check performed by Lead Stories, as it failed to provide any “assertions of fact” as to what the BMJ got wrong. Moreover, the editors take issue with Lead Stories referring to the journal as a “news blog” and using the phrase “hoax-alert” in the URL when publishing the story on its site.

The BMJ has reached out to Lead Stories and Facebook, said the letter, but Lead Stories refuses to “change anything about their article or actions that have led to Facebook flagging our article.” Requests for Facebook to remove the “fact-checking” label and allow “readers to freely share the article on [Facebook’s] platform” have been unfruitful.

Dr. Godlee and Dr. Abbasi expressed concern that other “high quality information provider[s] have been affected by the incompetence of Meta’s fact checking regime.” In November, Instagram censored Cochrane, an international provider of independent systematic medical reviews. Instagram, also owned by Meta, prohibited users from tagging Cochrane because the organization “repeatedly posted ... false content about COVID-19 or vaccines.” Cochrane refuted the allegations.

While “fact checking has been a staple of good journalism for decades,” said the editors, Meta has “apparently delegated responsibility to people incompetent in carrying out this crucial task.” They urged the company to reconsider its fact-checking strategy and review the issues that contributed to the error.

This news organization reached out to Meta for comment but did not receive a response at press time.

Lead Stories has posted a reply (Lead Stories’ Response To BMJ Open Letter Objecting To A Lead Stories Fact Check) to the BMJ’s complaint on its website.

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