Rheumatology News

If the initial success of the Pfizer-BioNTech rollout continues, and emergency use authorization (EAU) is granted to Moderna and Johnson & Johnson vaccines in development, Operation Warp Speed officials expect to have 300 million doses of COVID-19 vaccines to distribute across the United States between now and March 31.

The initial rollout remains on track, said Alex Azar, US Department of Health and Human Services (HHS) secretary, during a media briefing today. “We continue to have good news to report. As of today, shipments of vaccine will have been delivered to every delivery site identified by public health jurisdictions for our first wave of shipments.”

Anomalies in shipments to California and Alabama arose when temperature monitors showed the Pfizer vaccine dropped lower than the recommended -80 ºC (-112 °F). These vaccine trays remained on delivery trucks and were returned to Pfizer for prompt replacement, said Operation Warp Speed Chief Operating Officer Gen. Gustave F. Perna.

Azar estimated another 2 million doses of the Pfizer vaccine will be available next week. “And if the Moderna vaccine is authorized by the FDA in the coming days, we have allocated nearly 5.9 million doses of that product.”

The Moderna vaccine data released this week look promising, said Moncef Slaoui, PhD, Operation Warp Speed chief scientific adviser. “In the short term, I expect the protection to be quite significant.”

The findings in the first 2 weeks after the first dose show up to 65% protection, he said, and predicted the second-dose efficacy data will be coming in the next few weeks.

Enrollment in the phase 3 Johnson & Johnson trial with nearly 44,000 participants is expected to end December 17. Initial efficacy results are anticipated by early January, with more complete efficacy numbers by late January, Slaoui said.

The AstraZeneca COVID-19 vaccine trial also is underway with enrollment continuing. “We expect accruement to end in late December or early next year, with first results expected probably in February,” Slaoui said.
 

Antibody treatments underutilized

The media briefing also addressed COVID-19 therapeutics. Azar reported low uptake of available antibody therapies. “I want to remind Americans that there are two authorized antibody treatments that Operation Warp Speed has supported. They can help prevent hospitalization in those patients with the highest risk for severe disease.”

The higher-risk group includes those who are 65 and older and people with comorbid conditions that put them at increased risk for COVID-19 hospitalization.

The federal government allocated more than 330,000 doses of these treatments and many states have product available, Azar said.

Slaoui agreed, saying there is a “disappointing level of usage of monoclonal antibody therapy in hospitals. We look forward to that improving.”
 

Up to 3 billion vaccine doses possible

“We now have more than 900 million doses of the vaccine we have contracted delivery for,” Azar said. The government has options to increase that to a total of 3 billion doses.

In addition to the 100 million Pfizer vaccine doses and 100 million Moderna doses already ordered, the government just took an option for another 100 million Moderna doses for the second quarter of 2021. Operation Warp Speed officials are negotiating with Pfizer for additional product as well.

Azar added that there are 100 million doses of the Johnson & Johnson vaccine in active production and expects AstraZeneca can provide 300 million doses of their product.

With the possibility of three or more vaccine products and with 330 million Americans, minus the 70 million or so children under age 16, “we believe we will actually have surplus supplies,” Azar said. Plans are to take the US surplus vaccine and surplus manufacturing capacity “and use that for the benefit of the world community.”

This article first appeared on Medscape.com.

If the initial success of the Pfizer-BioNTech rollout continues, and emergency use authorization (EAU) is granted to Moderna and Johnson & Johnson vaccines in development, Operation Warp Speed officials expect to have 300 million doses of COVID-19 vaccines to distribute across the United States between now and March 31.

The initial rollout remains on track, said Alex Azar, US Department of Health and Human Services (HHS) secretary, during a media briefing today. “We continue to have good news to report. As of today, shipments of vaccine will have been delivered to every delivery site identified by public health jurisdictions for our first wave of shipments.”

Anomalies in shipments to California and Alabama arose when temperature monitors showed the Pfizer vaccine dropped lower than the recommended -80 ºC (-112 °F). These vaccine trays remained on delivery trucks and were returned to Pfizer for prompt replacement, said Operation Warp Speed Chief Operating Officer Gen. Gustave F. Perna.

Azar estimated another 2 million doses of the Pfizer vaccine will be available next week. “And if the Moderna vaccine is authorized by the FDA in the coming days, we have allocated nearly 5.9 million doses of that product.”

The Moderna vaccine data released this week look promising, said Moncef Slaoui, PhD, Operation Warp Speed chief scientific adviser. “In the short term, I expect the protection to be quite significant.”

The findings in the first 2 weeks after the first dose show up to 65% protection, he said, and predicted the second-dose efficacy data will be coming in the next few weeks.

Enrollment in the phase 3 Johnson & Johnson trial with nearly 44,000 participants is expected to end December 17. Initial efficacy results are anticipated by early January, with more complete efficacy numbers by late January, Slaoui said.

The AstraZeneca COVID-19 vaccine trial also is underway with enrollment continuing. “We expect accruement to end in late December or early next year, with first results expected probably in February,” Slaoui said.
 

Antibody treatments underutilized

The media briefing also addressed COVID-19 therapeutics. Azar reported low uptake of available antibody therapies. “I want to remind Americans that there are two authorized antibody treatments that Operation Warp Speed has supported. They can help prevent hospitalization in those patients with the highest risk for severe disease.”

The higher-risk group includes those who are 65 and older and people with comorbid conditions that put them at increased risk for COVID-19 hospitalization.

The federal government allocated more than 330,000 doses of these treatments and many states have product available, Azar said.

Slaoui agreed, saying there is a “disappointing level of usage of monoclonal antibody therapy in hospitals. We look forward to that improving.”
 

Up to 3 billion vaccine doses possible

“We now have more than 900 million doses of the vaccine we have contracted delivery for,” Azar said. The government has options to increase that to a total of 3 billion doses.

In addition to the 100 million Pfizer vaccine doses and 100 million Moderna doses already ordered, the government just took an option for another 100 million Moderna doses for the second quarter of 2021. Operation Warp Speed officials are negotiating with Pfizer for additional product as well.

Azar added that there are 100 million doses of the Johnson & Johnson vaccine in active production and expects AstraZeneca can provide 300 million doses of their product.

With the possibility of three or more vaccine products and with 330 million Americans, minus the 70 million or so children under age 16, “we believe we will actually have surplus supplies,” Azar said. Plans are to take the US surplus vaccine and surplus manufacturing capacity “and use that for the benefit of the world community.”

This article first appeared on Medscape.com.

If the initial success of the Pfizer-BioNTech rollout continues, and emergency use authorization (EAU) is granted to Moderna and Johnson & Johnson vaccines in development, Operation Warp Speed officials expect to have 300 million doses of COVID-19 vaccines to distribute across the United States between now and March 31.

The initial rollout remains on track, said Alex Azar, US Department of Health and Human Services (HHS) secretary, during a media briefing today. “We continue to have good news to report. As of today, shipments of vaccine will have been delivered to every delivery site identified by public health jurisdictions for our first wave of shipments.”

Anomalies in shipments to California and Alabama arose when temperature monitors showed the Pfizer vaccine dropped lower than the recommended -80 ºC (-112 °F). These vaccine trays remained on delivery trucks and were returned to Pfizer for prompt replacement, said Operation Warp Speed Chief Operating Officer Gen. Gustave F. Perna.

Azar estimated another 2 million doses of the Pfizer vaccine will be available next week. “And if the Moderna vaccine is authorized by the FDA in the coming days, we have allocated nearly 5.9 million doses of that product.”

The Moderna vaccine data released this week look promising, said Moncef Slaoui, PhD, Operation Warp Speed chief scientific adviser. “In the short term, I expect the protection to be quite significant.”

The findings in the first 2 weeks after the first dose show up to 65% protection, he said, and predicted the second-dose efficacy data will be coming in the next few weeks.

Enrollment in the phase 3 Johnson & Johnson trial with nearly 44,000 participants is expected to end December 17. Initial efficacy results are anticipated by early January, with more complete efficacy numbers by late January, Slaoui said.

The AstraZeneca COVID-19 vaccine trial also is underway with enrollment continuing. “We expect accruement to end in late December or early next year, with first results expected probably in February,” Slaoui said.
 

Antibody treatments underutilized

The media briefing also addressed COVID-19 therapeutics. Azar reported low uptake of available antibody therapies. “I want to remind Americans that there are two authorized antibody treatments that Operation Warp Speed has supported. They can help prevent hospitalization in those patients with the highest risk for severe disease.”

The higher-risk group includes those who are 65 and older and people with comorbid conditions that put them at increased risk for COVID-19 hospitalization.

The federal government allocated more than 330,000 doses of these treatments and many states have product available, Azar said.

Slaoui agreed, saying there is a “disappointing level of usage of monoclonal antibody therapy in hospitals. We look forward to that improving.”
 

Up to 3 billion vaccine doses possible

“We now have more than 900 million doses of the vaccine we have contracted delivery for,” Azar said. The government has options to increase that to a total of 3 billion doses.

In addition to the 100 million Pfizer vaccine doses and 100 million Moderna doses already ordered, the government just took an option for another 100 million Moderna doses for the second quarter of 2021. Operation Warp Speed officials are negotiating with Pfizer for additional product as well.

Azar added that there are 100 million doses of the Johnson & Johnson vaccine in active production and expects AstraZeneca can provide 300 million doses of their product.

With the possibility of three or more vaccine products and with 330 million Americans, minus the 70 million or so children under age 16, “we believe we will actually have surplus supplies,” Azar said. Plans are to take the US surplus vaccine and surplus manufacturing capacity “and use that for the benefit of the world community.”

This article first appeared on Medscape.com.

Adolescents who undergo sleeve gastrectomy have lower bone density and higher bone marrow fat at 1 year following surgery, new research shows.

“It’s almost paradoxical,” Miriam Bredella, MD, of Massachusetts General Hospital in Boston, told Medscape Medical News. “Despite marked loss of body fat, these children have more fat in their bones and decreased bone density.”

She explained that the dissected part of the stomach is filled with anabolic cells that are important for building bone mass. “When those cells are cut out, the body cannot produce the hormones for building up bone.” It’s a malabsorption problem, she added. “Cutting out parts of the stomach or gut leads to less absorption.”

It is well known that bariatric surgery in adults has long-term effects on bone, she said, but this is the first time it has been studied in children.

“Nobody thinks about bone loss in children, but it’s extremely important,” Bredella reports. “The adolescent years up to age 25 are when we accrue bone density, so if something happens during this critical time, it can lead to weak bones later in life.” In the case of these adolescents, peak bone mass is never reached.

To investigate the effects of sleeve gastrectomy on bone density and marrow adipose tissue in extremely obese teenagers, researchers at Massachusetts General Hospital and Harvard Medical School recruited 52 adolescents with a mean body mass index (BMI) of 45. They measured volumetric bone mineral density using quantitative computer tomography (QCT) of the lumbar spine.

“We used QCT instead of DEXA [dual energy x-ray absorptiometry] scan because it isn’t affected by changes in soft tissue; it’s less susceptible to extreme changes in body weight,” Bredella said. “With DEXA scan there are too many artifacts.”

Half of the group (n = 26) underwent surgery. At 1 year, those who underwent surgery lost an average of 34 kg (75 lb). Adolescents in the control group lost an average of 0.2 kg (0.5 lb) (P < .0001).

Both groups repeated the QCT scan at the 1-year follow-up. Researchers found a decrease in bone density in those who underwent sleeve gastrectomy vs. controls (P = .046).

In her presentation, Bredella showed the QCT of the L2 spine in a 17-year old female before surgery and 12 months later. Her volumetric bone mineral density decreased from 183 mg/cm³ to 146 mg/cm³.

“Sleeve gastrectomy in children is bad for bones,” Bradella said. “You have to take care of your bones. This is something people are not thinking about and it probably won’t be a problem when they’re young but will likely affect these patients with osteoporosis when they are older.”

Patients need to be aware of this, she warns, and take steps to combat the bone loss. “Drinking milk, taking vitamin D, and doing weight-bearing exercise may help increase the bone density,” she said.

The increased fat in the bone is also concerning, she said. “Increased fat in the bone is a phenomenon that we see in anorexic patients,” Bredella explained.

The body appears to store the fat in bone in case of need later on, she explained. “We know that in severe states of malnutrition the body has the ability to metabolize the fat in the bones.”

The obesity epidemic in America has given way to a 100-fold increase in sleeve gastrectomy procedures in teenagers between 2005 and 2014. “These patients need this surgery so they don›t die of cardiac arrest or diabetes,” she said. “But we need to make sure they get their bone mineral density checked frequently.”

“The results of this study are important,” Marc Michalsky, MD, Nationwide Children’s Hospital, Columbus, Ohio, told Medscape Medical News. “But they need to be put into context.”

“There is an impetus and argument to support bariatric surgery as it offers a significant reduction in BMI and an associated reversal and complete amelioration of obesity related diseases.”

What this study doesn’t address, he said, is whether this population will experience an increase in bone density-related fractures down the road.

“These results are a snapshot in time — a picture of one postoperative time point,” Michalsky pointed out. “Are we seeing a process that represents continued change in bone mineralization? It’s not unreasonable to assume that the radiological findings here may lead to real clinical impact, but we don’t know.”

Bredella and Michalsky have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Adolescents who undergo sleeve gastrectomy have lower bone density and higher bone marrow fat at 1 year following surgery, new research shows.

“It’s almost paradoxical,” Miriam Bredella, MD, of Massachusetts General Hospital in Boston, told Medscape Medical News. “Despite marked loss of body fat, these children have more fat in their bones and decreased bone density.”

She explained that the dissected part of the stomach is filled with anabolic cells that are important for building bone mass. “When those cells are cut out, the body cannot produce the hormones for building up bone.” It’s a malabsorption problem, she added. “Cutting out parts of the stomach or gut leads to less absorption.”

It is well known that bariatric surgery in adults has long-term effects on bone, she said, but this is the first time it has been studied in children.

“Nobody thinks about bone loss in children, but it’s extremely important,” Bredella reports. “The adolescent years up to age 25 are when we accrue bone density, so if something happens during this critical time, it can lead to weak bones later in life.” In the case of these adolescents, peak bone mass is never reached.

To investigate the effects of sleeve gastrectomy on bone density and marrow adipose tissue in extremely obese teenagers, researchers at Massachusetts General Hospital and Harvard Medical School recruited 52 adolescents with a mean body mass index (BMI) of 45. They measured volumetric bone mineral density using quantitative computer tomography (QCT) of the lumbar spine.

“We used QCT instead of DEXA [dual energy x-ray absorptiometry] scan because it isn’t affected by changes in soft tissue; it’s less susceptible to extreme changes in body weight,” Bredella said. “With DEXA scan there are too many artifacts.”

Half of the group (n = 26) underwent surgery. At 1 year, those who underwent surgery lost an average of 34 kg (75 lb). Adolescents in the control group lost an average of 0.2 kg (0.5 lb) (P < .0001).

Both groups repeated the QCT scan at the 1-year follow-up. Researchers found a decrease in bone density in those who underwent sleeve gastrectomy vs. controls (P = .046).

In her presentation, Bredella showed the QCT of the L2 spine in a 17-year old female before surgery and 12 months later. Her volumetric bone mineral density decreased from 183 mg/cm³ to 146 mg/cm³.

“Sleeve gastrectomy in children is bad for bones,” Bradella said. “You have to take care of your bones. This is something people are not thinking about and it probably won’t be a problem when they’re young but will likely affect these patients with osteoporosis when they are older.”

Patients need to be aware of this, she warns, and take steps to combat the bone loss. “Drinking milk, taking vitamin D, and doing weight-bearing exercise may help increase the bone density,” she said.

The increased fat in the bone is also concerning, she said. “Increased fat in the bone is a phenomenon that we see in anorexic patients,” Bredella explained.

The body appears to store the fat in bone in case of need later on, she explained. “We know that in severe states of malnutrition the body has the ability to metabolize the fat in the bones.”

The obesity epidemic in America has given way to a 100-fold increase in sleeve gastrectomy procedures in teenagers between 2005 and 2014. “These patients need this surgery so they don›t die of cardiac arrest or diabetes,” she said. “But we need to make sure they get their bone mineral density checked frequently.”

“The results of this study are important,” Marc Michalsky, MD, Nationwide Children’s Hospital, Columbus, Ohio, told Medscape Medical News. “But they need to be put into context.”

“There is an impetus and argument to support bariatric surgery as it offers a significant reduction in BMI and an associated reversal and complete amelioration of obesity related diseases.”

What this study doesn’t address, he said, is whether this population will experience an increase in bone density-related fractures down the road.

“These results are a snapshot in time — a picture of one postoperative time point,” Michalsky pointed out. “Are we seeing a process that represents continued change in bone mineralization? It’s not unreasonable to assume that the radiological findings here may lead to real clinical impact, but we don’t know.”

Bredella and Michalsky have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Adolescents who undergo sleeve gastrectomy have lower bone density and higher bone marrow fat at 1 year following surgery, new research shows.

“It’s almost paradoxical,” Miriam Bredella, MD, of Massachusetts General Hospital in Boston, told Medscape Medical News. “Despite marked loss of body fat, these children have more fat in their bones and decreased bone density.”

She explained that the dissected part of the stomach is filled with anabolic cells that are important for building bone mass. “When those cells are cut out, the body cannot produce the hormones for building up bone.” It’s a malabsorption problem, she added. “Cutting out parts of the stomach or gut leads to less absorption.”

It is well known that bariatric surgery in adults has long-term effects on bone, she said, but this is the first time it has been studied in children.

“Nobody thinks about bone loss in children, but it’s extremely important,” Bredella reports. “The adolescent years up to age 25 are when we accrue bone density, so if something happens during this critical time, it can lead to weak bones later in life.” In the case of these adolescents, peak bone mass is never reached.

To investigate the effects of sleeve gastrectomy on bone density and marrow adipose tissue in extremely obese teenagers, researchers at Massachusetts General Hospital and Harvard Medical School recruited 52 adolescents with a mean body mass index (BMI) of 45. They measured volumetric bone mineral density using quantitative computer tomography (QCT) of the lumbar spine.

“We used QCT instead of DEXA [dual energy x-ray absorptiometry] scan because it isn’t affected by changes in soft tissue; it’s less susceptible to extreme changes in body weight,” Bredella said. “With DEXA scan there are too many artifacts.”

Half of the group (n = 26) underwent surgery. At 1 year, those who underwent surgery lost an average of 34 kg (75 lb). Adolescents in the control group lost an average of 0.2 kg (0.5 lb) (P < .0001).

Both groups repeated the QCT scan at the 1-year follow-up. Researchers found a decrease in bone density in those who underwent sleeve gastrectomy vs. controls (P = .046).

In her presentation, Bredella showed the QCT of the L2 spine in a 17-year old female before surgery and 12 months later. Her volumetric bone mineral density decreased from 183 mg/cm³ to 146 mg/cm³.

“Sleeve gastrectomy in children is bad for bones,” Bradella said. “You have to take care of your bones. This is something people are not thinking about and it probably won’t be a problem when they’re young but will likely affect these patients with osteoporosis when they are older.”

Patients need to be aware of this, she warns, and take steps to combat the bone loss. “Drinking milk, taking vitamin D, and doing weight-bearing exercise may help increase the bone density,” she said.

The increased fat in the bone is also concerning, she said. “Increased fat in the bone is a phenomenon that we see in anorexic patients,” Bredella explained.

The body appears to store the fat in bone in case of need later on, she explained. “We know that in severe states of malnutrition the body has the ability to metabolize the fat in the bones.”

The obesity epidemic in America has given way to a 100-fold increase in sleeve gastrectomy procedures in teenagers between 2005 and 2014. “These patients need this surgery so they don›t die of cardiac arrest or diabetes,” she said. “But we need to make sure they get their bone mineral density checked frequently.”

“The results of this study are important,” Marc Michalsky, MD, Nationwide Children’s Hospital, Columbus, Ohio, told Medscape Medical News. “But they need to be put into context.”

“There is an impetus and argument to support bariatric surgery as it offers a significant reduction in BMI and an associated reversal and complete amelioration of obesity related diseases.”

What this study doesn’t address, he said, is whether this population will experience an increase in bone density-related fractures down the road.

“These results are a snapshot in time — a picture of one postoperative time point,” Michalsky pointed out. “Are we seeing a process that represents continued change in bone mineralization? It’s not unreasonable to assume that the radiological findings here may lead to real clinical impact, but we don’t know.”

Bredella and Michalsky have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Rheumatoid arthritis patients who are on both oral glucocorticoids (CGs) and proton pump inhibitors (PPIs) have an increased risk of osteoporotic fractures, according to a retrospective study of RA patients in the United Kingdom.

“Considering the increasing life expectancies and high consumption of PPIs among elderly patients, fracture risk assessment could be considered when a patient with RA is co-prescribed oral GCs and PPIs,” wrote Shahab Abtahi, MD, of Maastricht (Netherlands) University Medical Centre and colleagues. The study was published in Annals of the Rheumatic Diseases.

To determine if concomitant use of the two medications – both already associated with osteoporotic fractures – would lead to a notable increase in fracture risk, the researchers conducted a population-based cohort study of RA patients aged 50 years or older who were diagnosed during 1997-2017. Patient data was gathered via the Clinical Practice Research Datalink, a primary care database of millions of U.K. medical records.

Patients with a recent history of GC/PPI use or those with a previous osteoporotic fracture were excluded from the study. Osteoporotic fractures were defined as fractures of the hip, vertebrae, humerus, forearm, pelvis, or rib. The study population included 12,351 patients, roughly two-thirds of whom were women, with a mean age of 68 years. Of the population, 4,254 patients were concomitant users of oral GCs and PPIs, compared with 3,138 patients who were not on either medication.

Among all patients, 1,411 osteoporotic fractures occurred, 264 of which occurred in the concomitant users group. After adjustments for age and sex, patients on both medications had a higher risk of fracture (adjusted hazard ratio, 1.93; 95% confidence interval, 1.65-2.27), compared to patients on oral GCs alone (aHR, 1.34; 95% CI, 1.12-1.59) or PPIs alone (aHR, 1.32; 95% CI, 1.14-1.54). After full adjustment, concomitant users again had a higher risk of fracture (aHR, 1.60; 95% CI, 1.35-1.89).

Regarding specific types of breaks, the concomitant users had a notably higher risk of hip (aHR, 1.45; 95% CI, 1.11-1.91), vertebrae (aHR, 2.84; 95% CI, 1.87-4.32), pelvis (aHR, 2.47; 95% CI, 1.41-4.34), and rib fractures (aHR, 4.03; 95% CI, 2.13-7.63). No increased risk was found for either humerus or forearm fractures. The risk of fracture did not rise for concomitant users who had either increasing daily doses of PPI or a longer duration of use.

The authors noted their study’s potential limitations, including having access to data on prescriptions only, not the actual use of medication, and a lack of information in the medical records regarding biologic therapies or certain indicators of RA disease activity. In addition, there was a likelihood that some patients who were improving might have stopped taking the drugs and lessened their risk of fracture, though the researchers attempted to account for this by “adjusting our analyses for six indicators of RA severity, including analgesics and csDMARDs.”

Two of the authors reported receiving research grants and speakers’ fees from various pharmaceutical companies. The others reported no conflicts of interest.

SOURCE: Abtahi S et al. Ann Rheum Dis. 2020 Dec 11. doi: 10.1136/annrheumdis-2020-218758.

Rheumatoid arthritis patients who are on both oral glucocorticoids (CGs) and proton pump inhibitors (PPIs) have an increased risk of osteoporotic fractures, according to a retrospective study of RA patients in the United Kingdom.

“Considering the increasing life expectancies and high consumption of PPIs among elderly patients, fracture risk assessment could be considered when a patient with RA is co-prescribed oral GCs and PPIs,” wrote Shahab Abtahi, MD, of Maastricht (Netherlands) University Medical Centre and colleagues. The study was published in Annals of the Rheumatic Diseases.

To determine if concomitant use of the two medications – both already associated with osteoporotic fractures – would lead to a notable increase in fracture risk, the researchers conducted a population-based cohort study of RA patients aged 50 years or older who were diagnosed during 1997-2017. Patient data was gathered via the Clinical Practice Research Datalink, a primary care database of millions of U.K. medical records.

Patients with a recent history of GC/PPI use or those with a previous osteoporotic fracture were excluded from the study. Osteoporotic fractures were defined as fractures of the hip, vertebrae, humerus, forearm, pelvis, or rib. The study population included 12,351 patients, roughly two-thirds of whom were women, with a mean age of 68 years. Of the population, 4,254 patients were concomitant users of oral GCs and PPIs, compared with 3,138 patients who were not on either medication.

Among all patients, 1,411 osteoporotic fractures occurred, 264 of which occurred in the concomitant users group. After adjustments for age and sex, patients on both medications had a higher risk of fracture (adjusted hazard ratio, 1.93; 95% confidence interval, 1.65-2.27), compared to patients on oral GCs alone (aHR, 1.34; 95% CI, 1.12-1.59) or PPIs alone (aHR, 1.32; 95% CI, 1.14-1.54). After full adjustment, concomitant users again had a higher risk of fracture (aHR, 1.60; 95% CI, 1.35-1.89).

Regarding specific types of breaks, the concomitant users had a notably higher risk of hip (aHR, 1.45; 95% CI, 1.11-1.91), vertebrae (aHR, 2.84; 95% CI, 1.87-4.32), pelvis (aHR, 2.47; 95% CI, 1.41-4.34), and rib fractures (aHR, 4.03; 95% CI, 2.13-7.63). No increased risk was found for either humerus or forearm fractures. The risk of fracture did not rise for concomitant users who had either increasing daily doses of PPI or a longer duration of use.

The authors noted their study’s potential limitations, including having access to data on prescriptions only, not the actual use of medication, and a lack of information in the medical records regarding biologic therapies or certain indicators of RA disease activity. In addition, there was a likelihood that some patients who were improving might have stopped taking the drugs and lessened their risk of fracture, though the researchers attempted to account for this by “adjusting our analyses for six indicators of RA severity, including analgesics and csDMARDs.”

Two of the authors reported receiving research grants and speakers’ fees from various pharmaceutical companies. The others reported no conflicts of interest.

SOURCE: Abtahi S et al. Ann Rheum Dis. 2020 Dec 11. doi: 10.1136/annrheumdis-2020-218758.

Rheumatoid arthritis patients who are on both oral glucocorticoids (CGs) and proton pump inhibitors (PPIs) have an increased risk of osteoporotic fractures, according to a retrospective study of RA patients in the United Kingdom.

“Considering the increasing life expectancies and high consumption of PPIs among elderly patients, fracture risk assessment could be considered when a patient with RA is co-prescribed oral GCs and PPIs,” wrote Shahab Abtahi, MD, of Maastricht (Netherlands) University Medical Centre and colleagues. The study was published in Annals of the Rheumatic Diseases.

To determine if concomitant use of the two medications – both already associated with osteoporotic fractures – would lead to a notable increase in fracture risk, the researchers conducted a population-based cohort study of RA patients aged 50 years or older who were diagnosed during 1997-2017. Patient data was gathered via the Clinical Practice Research Datalink, a primary care database of millions of U.K. medical records.

Patients with a recent history of GC/PPI use or those with a previous osteoporotic fracture were excluded from the study. Osteoporotic fractures were defined as fractures of the hip, vertebrae, humerus, forearm, pelvis, or rib. The study population included 12,351 patients, roughly two-thirds of whom were women, with a mean age of 68 years. Of the population, 4,254 patients were concomitant users of oral GCs and PPIs, compared with 3,138 patients who were not on either medication.

Among all patients, 1,411 osteoporotic fractures occurred, 264 of which occurred in the concomitant users group. After adjustments for age and sex, patients on both medications had a higher risk of fracture (adjusted hazard ratio, 1.93; 95% confidence interval, 1.65-2.27), compared to patients on oral GCs alone (aHR, 1.34; 95% CI, 1.12-1.59) or PPIs alone (aHR, 1.32; 95% CI, 1.14-1.54). After full adjustment, concomitant users again had a higher risk of fracture (aHR, 1.60; 95% CI, 1.35-1.89).

Regarding specific types of breaks, the concomitant users had a notably higher risk of hip (aHR, 1.45; 95% CI, 1.11-1.91), vertebrae (aHR, 2.84; 95% CI, 1.87-4.32), pelvis (aHR, 2.47; 95% CI, 1.41-4.34), and rib fractures (aHR, 4.03; 95% CI, 2.13-7.63). No increased risk was found for either humerus or forearm fractures. The risk of fracture did not rise for concomitant users who had either increasing daily doses of PPI or a longer duration of use.

The authors noted their study’s potential limitations, including having access to data on prescriptions only, not the actual use of medication, and a lack of information in the medical records regarding biologic therapies or certain indicators of RA disease activity. In addition, there was a likelihood that some patients who were improving might have stopped taking the drugs and lessened their risk of fracture, though the researchers attempted to account for this by “adjusting our analyses for six indicators of RA severity, including analgesics and csDMARDs.”

Two of the authors reported receiving research grants and speakers’ fees from various pharmaceutical companies. The others reported no conflicts of interest.

SOURCE: Abtahi S et al. Ann Rheum Dis. 2020 Dec 11. doi: 10.1136/annrheumdis-2020-218758.

A proposal to lower Medicare Part B reimbursements for 50 physician-administered drugs and biologics to what drug manufacturers receive for them in other wealthy nations seems unlikely to take effect as planned on January 1, 2021. The proposal has been strongly opposed by the pharmaceutical industry as well as oncologists and other physicians who use the products most often.

At least four lawsuits have been filed in US district courts to block the move, including from Regeneron, manufacturer of the ophthalmic biologic aflibercept, the first agent on the list; the Community Oncology Alliance; the Biotechnology Innovation Organization, California Life Sciences Association, and Biocom; and Pharmaceutical Research and Manufacturers of America, the Association of Community Cancer Centers, the Global Colon Cancer Association, and National Infusion Center Association.

The proposal could hit oncologists/hematologists particularly hard because they are the primary prescribers of about 30 of the 50 agents on the list, including mainstay breast, lung, and prostate cancer treatments and newer immunotherapies. In its filing for injunctive relieve, the Community Oncology Alliance, a trade group for community oncologists, said the proposal exposes “the health and safety of cancer patients and other patients with potentially life-threatening diseases to real danger.”
 

Hearings are imminent

Hearings on the proposal, which was published by the Centers for Medicare & Medicaid Services (CMS) on November 27 following an executive order September 13, are scheduled for coming days. The first hearing is scheduled for December 18.

Given the looming implementation date, judges are likely to rule quickly on the motions for injunctive relief, said attorney Rachel Sachs, a health law expert and associate professor at the Washington University School of Law, St. Louis, Missouri. The odds are in plaintiffs’ favor based on procedural and Constitutional grounds. “It’s extremely unlikely to survive” the legal onslaught, she told Medscape Medical News.

Among the many issues raised in court filings, the proposal was released as an interim final rule (IFR), meaning it would take effect outside of the usual process of proposed rule, comment period, revision, then implementation. The law allows for bypassing normal rule-making requirements with an IFR, but they are meant for emergency situations — several have been issued in response to the COVID-19 pandemic — and the government must be able to show that delay would be “impracticable, unnecessary, or contrary to the public interest,” Sachs explained.

In contrast, some form of CMS’s new proposal, dubbed the “Most Favored Nation” (MFN) model for drug reimbursements, has been under consideration by the Trump administration since 2018.

“The way the [Trump] administration rolled this rule out at pretty much the last minute opens them up to greater legal challenges than if they pursued more normal regulatory pathways, which they had the opportunity to do. They are attempting to implement this on a time frame that is unprecedented for as large a change as this is,” said Juliette Cubanski, PhD, deputy director of Medicare policy at the Kaiser Family Foundation, San Francisco, California.
 

Reimbursement less than acquisition costs

In the proposal, CMS sought to offset the higher prices that pharmaceutical companies charge in the United States when compared with other developed nations — the prices are about double on average.

“One of the largest drivers of increasing Medicare spending is the growing prices for physician-administered separately payable Medicare Part B drugs, which have risen an average of 11.5% annually since 2015, with total spending of approximately $30 billion in 2019,” the agency said in a fact sheet. This is due in large part to “lack of competitive market forces on Medicare Part B drug costs,” it added.

The 50 agents covered by the new proposal are the ones Part B spends the most on, almost $3 billion in 2019 for aflibercept alone, followed closely by pembrolizumab, an immunotherapy used in many different cancer types.

A full list of the drugs and biologicals included in the proposal is on page 50 of the IFR.

CMS estimated that its move would cut reimbursements by approximately 65% once fully implemented in 4 years and save $87.8 billion over the 7 years of the proposed model, as well as reduce cost sharing for beneficiaries.

This model puts the onus on providers to negotiate down drug prices with companies to meet proposed reimbursement limits. However, if companies do not lower their prices, acquisition costs could be substantially lower than reimbursements.

Prescribers and their practices would either have to take the financial hit or stop offering the pharmaceuticals, in which case patients would have to do without, try a different option, or seek care elsewhere, including facilities excluded from the proposal: children’s hospitals, critical access hospitals, cancer hospitals, federally qualified health centers, rural health clinics, and extended neoplastic disease care hospitals.

CMS estimates that in the first year of MFN reimbursements, 9% of beneficiaries would forgo MFN therapies, growing to 19% by year 3, figures that were included in cost savings estimates.

The reimbursement cuts are meant to motivate manufactures to lower prices, but “we have not seen this occur with similar efforts in the past, and drug prices have continued to rise,” said American College of Rheumatology President David Karp, MD, PhD, in a press release. Many of the agents on the list are used by rheumatologists.

Under current policy, Medicare Part B prescribers are reimbursed manufactures’ average sales price plus a 6% add-on. Under the new proposal, reimbursements would be pegged to the lowest price charged among nations of the Organization for Economic Co-operation and Development with a gross domestic product per capita of at least 60% of the US price. In addition to the United States, there are 36 other member countries, including Canada, the United Kingdom, Japan, and Germany.

To remove incentives to prescribe more expensive drugs, the 6% add-on would be replaced with a flat add-on payment per dose, pegged at $148.73 for the first quarter of 2021. There is a hardship exemption for providers if the reimbursement cuts are too drastic, but that involves a lot of paperwork.

This article first appeared on Medscape.com.

A proposal to lower Medicare Part B reimbursements for 50 physician-administered drugs and biologics to what drug manufacturers receive for them in other wealthy nations seems unlikely to take effect as planned on January 1, 2021. The proposal has been strongly opposed by the pharmaceutical industry as well as oncologists and other physicians who use the products most often.

At least four lawsuits have been filed in US district courts to block the move, including from Regeneron, manufacturer of the ophthalmic biologic aflibercept, the first agent on the list; the Community Oncology Alliance; the Biotechnology Innovation Organization, California Life Sciences Association, and Biocom; and Pharmaceutical Research and Manufacturers of America, the Association of Community Cancer Centers, the Global Colon Cancer Association, and National Infusion Center Association.

The proposal could hit oncologists/hematologists particularly hard because they are the primary prescribers of about 30 of the 50 agents on the list, including mainstay breast, lung, and prostate cancer treatments and newer immunotherapies. In its filing for injunctive relieve, the Community Oncology Alliance, a trade group for community oncologists, said the proposal exposes “the health and safety of cancer patients and other patients with potentially life-threatening diseases to real danger.”
 

Hearings are imminent

Hearings on the proposal, which was published by the Centers for Medicare & Medicaid Services (CMS) on November 27 following an executive order September 13, are scheduled for coming days. The first hearing is scheduled for December 18.

Given the looming implementation date, judges are likely to rule quickly on the motions for injunctive relief, said attorney Rachel Sachs, a health law expert and associate professor at the Washington University School of Law, St. Louis, Missouri. The odds are in plaintiffs’ favor based on procedural and Constitutional grounds. “It’s extremely unlikely to survive” the legal onslaught, she told Medscape Medical News.

Among the many issues raised in court filings, the proposal was released as an interim final rule (IFR), meaning it would take effect outside of the usual process of proposed rule, comment period, revision, then implementation. The law allows for bypassing normal rule-making requirements with an IFR, but they are meant for emergency situations — several have been issued in response to the COVID-19 pandemic — and the government must be able to show that delay would be “impracticable, unnecessary, or contrary to the public interest,” Sachs explained.

In contrast, some form of CMS’s new proposal, dubbed the “Most Favored Nation” (MFN) model for drug reimbursements, has been under consideration by the Trump administration since 2018.

“The way the [Trump] administration rolled this rule out at pretty much the last minute opens them up to greater legal challenges than if they pursued more normal regulatory pathways, which they had the opportunity to do. They are attempting to implement this on a time frame that is unprecedented for as large a change as this is,” said Juliette Cubanski, PhD, deputy director of Medicare policy at the Kaiser Family Foundation, San Francisco, California.
 

Reimbursement less than acquisition costs

In the proposal, CMS sought to offset the higher prices that pharmaceutical companies charge in the United States when compared with other developed nations — the prices are about double on average.

“One of the largest drivers of increasing Medicare spending is the growing prices for physician-administered separately payable Medicare Part B drugs, which have risen an average of 11.5% annually since 2015, with total spending of approximately $30 billion in 2019,” the agency said in a fact sheet. This is due in large part to “lack of competitive market forces on Medicare Part B drug costs,” it added.

The 50 agents covered by the new proposal are the ones Part B spends the most on, almost $3 billion in 2019 for aflibercept alone, followed closely by pembrolizumab, an immunotherapy used in many different cancer types.

A full list of the drugs and biologicals included in the proposal is on page 50 of the IFR.

CMS estimated that its move would cut reimbursements by approximately 65% once fully implemented in 4 years and save $87.8 billion over the 7 years of the proposed model, as well as reduce cost sharing for beneficiaries.

This model puts the onus on providers to negotiate down drug prices with companies to meet proposed reimbursement limits. However, if companies do not lower their prices, acquisition costs could be substantially lower than reimbursements.

Prescribers and their practices would either have to take the financial hit or stop offering the pharmaceuticals, in which case patients would have to do without, try a different option, or seek care elsewhere, including facilities excluded from the proposal: children’s hospitals, critical access hospitals, cancer hospitals, federally qualified health centers, rural health clinics, and extended neoplastic disease care hospitals.

CMS estimates that in the first year of MFN reimbursements, 9% of beneficiaries would forgo MFN therapies, growing to 19% by year 3, figures that were included in cost savings estimates.

The reimbursement cuts are meant to motivate manufactures to lower prices, but “we have not seen this occur with similar efforts in the past, and drug prices have continued to rise,” said American College of Rheumatology President David Karp, MD, PhD, in a press release. Many of the agents on the list are used by rheumatologists.

Under current policy, Medicare Part B prescribers are reimbursed manufactures’ average sales price plus a 6% add-on. Under the new proposal, reimbursements would be pegged to the lowest price charged among nations of the Organization for Economic Co-operation and Development with a gross domestic product per capita of at least 60% of the US price. In addition to the United States, there are 36 other member countries, including Canada, the United Kingdom, Japan, and Germany.

To remove incentives to prescribe more expensive drugs, the 6% add-on would be replaced with a flat add-on payment per dose, pegged at $148.73 for the first quarter of 2021. There is a hardship exemption for providers if the reimbursement cuts are too drastic, but that involves a lot of paperwork.

This article first appeared on Medscape.com.

A proposal to lower Medicare Part B reimbursements for 50 physician-administered drugs and biologics to what drug manufacturers receive for them in other wealthy nations seems unlikely to take effect as planned on January 1, 2021. The proposal has been strongly opposed by the pharmaceutical industry as well as oncologists and other physicians who use the products most often.

At least four lawsuits have been filed in US district courts to block the move, including from Regeneron, manufacturer of the ophthalmic biologic aflibercept, the first agent on the list; the Community Oncology Alliance; the Biotechnology Innovation Organization, California Life Sciences Association, and Biocom; and Pharmaceutical Research and Manufacturers of America, the Association of Community Cancer Centers, the Global Colon Cancer Association, and National Infusion Center Association.

The proposal could hit oncologists/hematologists particularly hard because they are the primary prescribers of about 30 of the 50 agents on the list, including mainstay breast, lung, and prostate cancer treatments and newer immunotherapies. In its filing for injunctive relieve, the Community Oncology Alliance, a trade group for community oncologists, said the proposal exposes “the health and safety of cancer patients and other patients with potentially life-threatening diseases to real danger.”
 

Hearings are imminent

Hearings on the proposal, which was published by the Centers for Medicare & Medicaid Services (CMS) on November 27 following an executive order September 13, are scheduled for coming days. The first hearing is scheduled for December 18.

Given the looming implementation date, judges are likely to rule quickly on the motions for injunctive relief, said attorney Rachel Sachs, a health law expert and associate professor at the Washington University School of Law, St. Louis, Missouri. The odds are in plaintiffs’ favor based on procedural and Constitutional grounds. “It’s extremely unlikely to survive” the legal onslaught, she told Medscape Medical News.

Among the many issues raised in court filings, the proposal was released as an interim final rule (IFR), meaning it would take effect outside of the usual process of proposed rule, comment period, revision, then implementation. The law allows for bypassing normal rule-making requirements with an IFR, but they are meant for emergency situations — several have been issued in response to the COVID-19 pandemic — and the government must be able to show that delay would be “impracticable, unnecessary, or contrary to the public interest,” Sachs explained.

In contrast, some form of CMS’s new proposal, dubbed the “Most Favored Nation” (MFN) model for drug reimbursements, has been under consideration by the Trump administration since 2018.

“The way the [Trump] administration rolled this rule out at pretty much the last minute opens them up to greater legal challenges than if they pursued more normal regulatory pathways, which they had the opportunity to do. They are attempting to implement this on a time frame that is unprecedented for as large a change as this is,” said Juliette Cubanski, PhD, deputy director of Medicare policy at the Kaiser Family Foundation, San Francisco, California.
 

Reimbursement less than acquisition costs

In the proposal, CMS sought to offset the higher prices that pharmaceutical companies charge in the United States when compared with other developed nations — the prices are about double on average.

“One of the largest drivers of increasing Medicare spending is the growing prices for physician-administered separately payable Medicare Part B drugs, which have risen an average of 11.5% annually since 2015, with total spending of approximately $30 billion in 2019,” the agency said in a fact sheet. This is due in large part to “lack of competitive market forces on Medicare Part B drug costs,” it added.

The 50 agents covered by the new proposal are the ones Part B spends the most on, almost $3 billion in 2019 for aflibercept alone, followed closely by pembrolizumab, an immunotherapy used in many different cancer types.

A full list of the drugs and biologicals included in the proposal is on page 50 of the IFR.

CMS estimated that its move would cut reimbursements by approximately 65% once fully implemented in 4 years and save $87.8 billion over the 7 years of the proposed model, as well as reduce cost sharing for beneficiaries.

This model puts the onus on providers to negotiate down drug prices with companies to meet proposed reimbursement limits. However, if companies do not lower their prices, acquisition costs could be substantially lower than reimbursements.

Prescribers and their practices would either have to take the financial hit or stop offering the pharmaceuticals, in which case patients would have to do without, try a different option, or seek care elsewhere, including facilities excluded from the proposal: children’s hospitals, critical access hospitals, cancer hospitals, federally qualified health centers, rural health clinics, and extended neoplastic disease care hospitals.

CMS estimates that in the first year of MFN reimbursements, 9% of beneficiaries would forgo MFN therapies, growing to 19% by year 3, figures that were included in cost savings estimates.

The reimbursement cuts are meant to motivate manufactures to lower prices, but “we have not seen this occur with similar efforts in the past, and drug prices have continued to rise,” said American College of Rheumatology President David Karp, MD, PhD, in a press release. Many of the agents on the list are used by rheumatologists.

Under current policy, Medicare Part B prescribers are reimbursed manufactures’ average sales price plus a 6% add-on. Under the new proposal, reimbursements would be pegged to the lowest price charged among nations of the Organization for Economic Co-operation and Development with a gross domestic product per capita of at least 60% of the US price. In addition to the United States, there are 36 other member countries, including Canada, the United Kingdom, Japan, and Germany.

To remove incentives to prescribe more expensive drugs, the 6% add-on would be replaced with a flat add-on payment per dose, pegged at $148.73 for the first quarter of 2021. There is a hardship exemption for providers if the reimbursement cuts are too drastic, but that involves a lot of paperwork.

This article first appeared on Medscape.com.

Coronavirus vaccines have become a reality, as they are now being approved and authorized for use in a growing number of countries including the United States. The U.S. Food and Drug Administration has just issued emergency authorization for the use of the COVID-19 vaccine produced by Pfizer and BioNTech. Close behind is the vaccine developed by Moderna, which has also applied to the FDA for emergency authorization.

scyther5/thinkstock

The efficacy of a two-dose administration of the vaccine has been pegged at 95.0%, and the FDA has said that the 95% credible interval for the vaccine efficacy was 90.3%-97.6%. But as with many initial clinical trials, whether for drugs or vaccines, not all populations were represented in the trial cohort, including individuals who are immunocompromised. At the current time, it is largely unknown how safe or effective the vaccine may be in this large population, many of whom are at high risk for serious COVID-19 complications.

At a special session held during the recent annual meeting of the American Society of Hematology, Anthony Fauci, MD, the nation’s leading infectious disease expert, said that individuals with compromised immune systems, whether because of chemotherapy or a bone marrow transplant, should plan to be vaccinated when the opportunity arises.

In response to a question from ASH President Stephanie J. Lee, MD, of the Fred Hutchinson Cancer Center, Seattle, Dr. Fauci emphasized that, despite being excluded from clinical trials, this population should get vaccinated. “I think we should recommend that they get vaccinated,” he said. “I mean, it is clear that, if you are on immunosuppressive agents, history tells us that you’re not going to have as robust a response as if you had an intact immune system that was not being compromised. But some degree of immunity is better than no degree of immunity.”

That does seem to be the consensus among experts who spoke in interviews: that as long as these are not live attenuated vaccines, they hold no specific risk to an immunocompromised patient, other than any factors specific to the individual that could be a contraindication.

“Patients, family members, friends, and work contacts should be encouraged to receive the vaccine,” said William Stohl, MD, PhD, chief of the division of rheumatology at the University of Southern California, Los Angeles. “Clinicians should advise patients to obtain the vaccine sooner rather than later.”
 

Kevin C. Wang, MD, PhD, of the department of dermatology at Stanford (Calif.) University, agreed. “I am 100% with Dr. Fauci. Everyone should get the vaccine, even if it may not be as effective,” he said. “I would treat it exactly like the flu vaccines that we recommend folks get every year.”

Dr. Wang noted that he couldn’t think of any contraindications unless the immunosuppressed patients have a history of severe allergic reactions to prior vaccinations. “But I would even say patients with history of cancer, upon recommendation of their oncologists, are likely to be suitable candidates for the vaccine,” he added. “I would say clinicians should approach counseling the same way they counsel patients for the flu vaccine, and as far as I know, there are no concerns for systemic drugs commonly used in dermatology patients.”

However, guidance has not yet been issued from either the FDA or the Centers for Disease Control and Prevention regarding the use of the vaccine in immunocompromised individuals. Given the lack of data, the FDA has said that “it will be something that providers will need to consider on an individual basis,” and that individuals should consult with physicians to weigh the potential benefits and potential risks.

The CDC’s Advisory Committee on Immunization Practices has said that clinicians need more guidance on whether to use the vaccine in pregnant or breastfeeding women, the immunocompromised, or those who have a history of allergies. The CDC itself has not yet released its formal guidance on vaccine use.


 

COVID-19 vaccines

Vaccines typically require years of research and testing before reaching the clinic, but this year researchers embarked on a global effort to develop safe and effective coronavirus vaccines in record time. Both the Pfizer/BioNTech and Moderna vaccines have only a few months of phase 3 clinical trial data, so much remains unknown about them, including their duration of effect and any long-term safety signals. In addition to excluding immunocompromised individuals, the clinical trials did not include children or pregnant women, so data are lacking for several population subgroups.

But these will not be the only vaccines available, as the pipeline is already becoming crowded. U.S. clinical trial data from a vaccine jointly being developed by Oxford-AstraZeneca, could potentially be ready, along with a request for FDA emergency use authorization, by late January 2021.

In addition, China and Russia have released vaccines, and there are currently 61 vaccines being investigated in clinical trials and at least 85 preclinical products under active investigation.

The vaccine candidates are using both conventional and novel mechanisms of action to elicit an immune response in patients. Conventional methods include attenuated inactivated (killed) virus and recombinant viral protein vaccines to develop immunity. Novel approaches include replication-deficient, adenovirus vector-based vaccines that contain the viral protein, and mRNA-based vaccines, such as the Pfizer and Moderna vaccines, that encode for a SARS-CoV-2 spike protein.

“The special vaccine concern for immunocompromised individuals is introduction of a live virus,” Dr. Stohl said. “Neither the Moderna nor Pfizer vaccines are live viruses, so there should be no special contraindication for such individuals.”

Live vaccine should be avoided in immunocompromised patients, and currently, live SARS-CoV-2 vaccines are only being developed in India and Turkey.

It is not unusual for vaccine trials to begin with cohorts that exclude participants with various health conditions, including those who are immunocompromised. These groups are generally then evaluated in phase 4 trials, or postmarketing surveillance. While the precise number of immunosuppressed adults in the United States is not known, the numbers are believed to be rising because of increased life expectancy among immunosuppressed adults as a result of advances in treatment and new and wider indications for therapies that can affect the immune system.

According to data from the 2013 National Health Interview Survey, an estimated 2.7% of U.S. adults are immunosuppressed. This population covers a broad array of health conditions and medical specialties; people living with inflammatory or autoimmune conditions, such as inflammatory rheumatic diseases (rheumatoid arthritis, axial spondyloarthritis, lupus); inflammatory bowel disease (Crohn’s disease and ulcerative colitis); psoriasis; multiple sclerosis; organ transplant recipients; patients undergoing chemotherapy; and life-long immunosuppression attributable to HIV infection.

As the vaccines begin to roll out and become available, how should clinicians advise their patients, in the absence of any clinical trial data?


 

Risk vs. benefit

Gilaad Kaplan, MD, MPH, a gastroenterologist and professor of medicine at the University of Calgary (Alta.), noted that the inflammatory bowel disease (IBD) community has dealt with tremendous anxiety during the pandemic because many are immunocompromised because of the medications they use to treat their disease.

“For example, many patients with IBD are on biologics like anti-TNF [tumor necrosis factor] therapies, which are also used in other immune-mediated inflammatory diseases such as rheumatoid arthritis,” he said. “Understandably, individuals with IBD on immunosuppressive medications are concerned about the risk of severe complications due to COVID-19.”

The entire IBD community, along with the world, celebrated the announcement that multiple vaccines are protective against SARS-CoV-2, he noted. “Vaccines offer the potential to reduce the spread of COVID-19, allowing society to revert back to normalcy,” Dr. Kaplan said. “Moreover, for vulnerable populations, including those who are immunocompromised, vaccines offer the potential to directly protect them from the morbidity and mortality associated with COVID-19.”

That said, even though the news of vaccines are extremely promising, some cautions must be raised regarding their use in immunocompromised populations, such as persons with IBD. “The current trials, to my knowledge, did not include immunocompromised individuals and thus, we can only extrapolate from what we know from other trials of different vaccines,” he explained. “We know from prior vaccines studies that the immune response following vaccination is less robust in those who are immunocompromised as compared to a healthy control population.”

Dr. Kaplan also pointed to recent reports of allergic reactions that have been reported in healthy individuals. “We don’t know whether side effects, like allergic reactions, may be different in unstudied populations,” he said. “Thus, the medical and scientific community should prioritize clinical studies of safety and effectiveness of COVID-19 vaccines in immunocompromised populations.”

So, what does this mean for an individual with an immune-mediated inflammatory disease like Crohn’s disease or ulcerative colitis who is immunocompromised? Dr. Kaplan explained that it is a balance between the potential harm of being infected with COVID-19 and the uncertainty of receiving a vaccine in an understudied population. For those who are highly susceptible to dying from COVID-19, such as an older adult with IBD, or someone who faces high exposure, such as a health care worker, the potential protection of the vaccine greatly outweighs the uncertainty.

“However, for individuals who are at otherwise lower risk – for example, young and able to work from home – then waiting a few extra months for postmarketing surveillance studies in immunocompromised populations may be a reasonable approach, as long as these individuals are taking great care to avoid infection,” he said.
 

No waiting needed

Joel M. Gelfand, MD, MSCE, professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia, feels that the newly approved vaccine should be safe for most of his patients.

“Patients with psoriatic disease should get the mRNA-based COVID-19 vaccine as soon as possible based on eligibility as determined by the CDC and local public health officials,” he said. “It is not a live vaccine, and therefore patients on biologics or other immune-modulating or immune-suppressing treatment can receive it.”

However, the impact of psoriasis treatment on immune response to the mRNA-based vaccines is not known. Dr. Gelfand noted that, extrapolating from the vaccine literature, there is some evidence that methotrexate reduces response to the influenza vaccine. “However, the clinical significance of this finding is not clear,” he said. “Since the mRNA vaccine needs to be taken twice, a few weeks apart, I do not recommend interrupting or delaying treatment for psoriatic disease while undergoing vaccination for COVID-19.”

Given the reports of allergic reactions, he added that it is advisable for patients with a history of life-threatening allergic reactions such as anaphylaxis or who have been advised to carry an epinephrine autoinjector, to talk with their health care provider to determine if COVID-19 vaccination is medically appropriate.

The National Psoriasis Foundation has issued guidance on COVID-19, explained Steven R. Feldman, MD, PhD, professor of dermatology, pathology, and social sciences & health policy at Wake Forest University, Winston-Salem, N.C., who is also a member of the committee that is working on those guidelines and keeping them up to date. “We are in the process of updating the guidelines with information on COVID vaccines,” he said.

He agreed that there are no contraindications for psoriasis patients to receive the vaccine, regardless of whether they are on immunosuppressive treatment, even though definitive data are lacking. “Fortunately, there’s a lot of good data coming out of Italy that patients with psoriasis on biologics do not appear to be at increased risk of getting COVID or of having worse outcomes from COVID,” he said.

Patients are going to ask about the vaccines, and when counseling them, clinicians should discuss the available data, the residual uncertainty, and patients’ concerns should be considered, Dr. Feldman explained. “There may be some concern that steroids and cyclosporine would reduce the effectiveness of vaccines, but there is no concern that any of the drugs would cause increased risk from nonlive vaccines.”

He added that there is evidence that “patients on biologics who receive nonlive vaccines do develop antibody responses and are immunized.”


 

Boosting efficacy

Even prior to making their announcement, the American College of Rheumatology had said that they would endorse the vaccine for all patients, explained rheumatologist Brett Smith, DO, from Blount Memorial Physicians Group and East Tennessee Children’s Hospital, Alcoa. “The vaccine is safe for all patients, but the problem may be that it’s not as effective,” he said. “But we don’t know that because it hasn’t been tested.”

With other vaccines, biologic medicines are held for 2 weeks before and afterwards, to get the best response. “But some patients don’t want to stop the medication,” Dr. Smith said. “They are afraid that their symptoms will return.”

As for counseling patients as to whether they should receive this vaccine, he explained that he typically doesn’t try to sway patients one way or another until they are really high risk. “When I counsel, it really depends on the individual situation. And for this vaccine, we have to be open to the fact that many people have already made up their mind.”

There are a lot of questions regarding the vaccine. One is the short time frame of development. “Vaccines typically take 6-10 years to come on the market, and this one is now available after a 3-month study,” Dr. Smith said. “Some have already decided that it’s too new for them.”

The process is also new, and patients need to understand that it doesn’t contain an active virus and “you can’t catch coronavirus from it.”

Dr. Smith also explained that, because the vaccine may be less effective in a person using biologic therapies, there is currently no information available on repeat vaccination. “These are all unanswered questions,” he said. “If the antibodies wane in a short time, can we be revaccinated and in what time frame? We just don’t know that yet.”

Marcelo Bonomi, MD, a medical oncologist from The Ohio State University Comprehensive Cancer Center, Columbus, explained that one way to ensure a more optimal response to the vaccine would be to wait until the patient has finished chemotherapy.* “The vaccine can be offered at that time, and in the meantime, they can take other steps to avoid infection,” he said. “If they are very immunosuppressed, it isn’t worth trying to give the vaccine.”

Cancer patients should be encouraged to stay as healthy as possible, and to wear masks and social distance. “It’s a comprehensive approach. Eat healthy, avoid alcohol and tobacco, and exercise. [These things] will help boost the immune system,” Dr. Bonomi said. “Family members should be encouraged to get vaccinated, which will help them avoid infection and exposing the patient.”

Jim Boonyaratanakornkit, MD, PhD, an infectious disease specialist who cares for cancer patients at the Fred Hutchinson Cancer Research Center, agreed. “Giving a vaccine right after a transplant is a futile endeavor,” he said. “We need to wait 6 months to have an immune response.”

He pointed out there may be a continuing higher number of cases, with high levels peaking in Washington in February and March. “Close friends and family should be vaccinated if possible,” he said, “which will help interrupt transmission.”

The vaccines are using new platforms that are totally different, and there is no clear data as to how long the antibodies will persist. “We know that they last for at least 4 months,” said Dr. Boonyaratanakornkit. “We don’t know what level of antibody will protect them from COVID-19 infection. Current studies are being conducted, but we don’t have that information for anyone yet.”
 

*Correction, 1/7/21: An earlier version of this article misattributed quotes from Dr. Marcelo Bonomi.

Coronavirus vaccines have become a reality, as they are now being approved and authorized for use in a growing number of countries including the United States. The U.S. Food and Drug Administration has just issued emergency authorization for the use of the COVID-19 vaccine produced by Pfizer and BioNTech. Close behind is the vaccine developed by Moderna, which has also applied to the FDA for emergency authorization.

scyther5/thinkstock

The efficacy of a two-dose administration of the vaccine has been pegged at 95.0%, and the FDA has said that the 95% credible interval for the vaccine efficacy was 90.3%-97.6%. But as with many initial clinical trials, whether for drugs or vaccines, not all populations were represented in the trial cohort, including individuals who are immunocompromised. At the current time, it is largely unknown how safe or effective the vaccine may be in this large population, many of whom are at high risk for serious COVID-19 complications.

At a special session held during the recent annual meeting of the American Society of Hematology, Anthony Fauci, MD, the nation’s leading infectious disease expert, said that individuals with compromised immune systems, whether because of chemotherapy or a bone marrow transplant, should plan to be vaccinated when the opportunity arises.

In response to a question from ASH President Stephanie J. Lee, MD, of the Fred Hutchinson Cancer Center, Seattle, Dr. Fauci emphasized that, despite being excluded from clinical trials, this population should get vaccinated. “I think we should recommend that they get vaccinated,” he said. “I mean, it is clear that, if you are on immunosuppressive agents, history tells us that you’re not going to have as robust a response as if you had an intact immune system that was not being compromised. But some degree of immunity is better than no degree of immunity.”

That does seem to be the consensus among experts who spoke in interviews: that as long as these are not live attenuated vaccines, they hold no specific risk to an immunocompromised patient, other than any factors specific to the individual that could be a contraindication.

“Patients, family members, friends, and work contacts should be encouraged to receive the vaccine,” said William Stohl, MD, PhD, chief of the division of rheumatology at the University of Southern California, Los Angeles. “Clinicians should advise patients to obtain the vaccine sooner rather than later.”
 

Kevin C. Wang, MD, PhD, of the department of dermatology at Stanford (Calif.) University, agreed. “I am 100% with Dr. Fauci. Everyone should get the vaccine, even if it may not be as effective,” he said. “I would treat it exactly like the flu vaccines that we recommend folks get every year.”

Dr. Wang noted that he couldn’t think of any contraindications unless the immunosuppressed patients have a history of severe allergic reactions to prior vaccinations. “But I would even say patients with history of cancer, upon recommendation of their oncologists, are likely to be suitable candidates for the vaccine,” he added. “I would say clinicians should approach counseling the same way they counsel patients for the flu vaccine, and as far as I know, there are no concerns for systemic drugs commonly used in dermatology patients.”

However, guidance has not yet been issued from either the FDA or the Centers for Disease Control and Prevention regarding the use of the vaccine in immunocompromised individuals. Given the lack of data, the FDA has said that “it will be something that providers will need to consider on an individual basis,” and that individuals should consult with physicians to weigh the potential benefits and potential risks.

The CDC’s Advisory Committee on Immunization Practices has said that clinicians need more guidance on whether to use the vaccine in pregnant or breastfeeding women, the immunocompromised, or those who have a history of allergies. The CDC itself has not yet released its formal guidance on vaccine use.


 

COVID-19 vaccines

Vaccines typically require years of research and testing before reaching the clinic, but this year researchers embarked on a global effort to develop safe and effective coronavirus vaccines in record time. Both the Pfizer/BioNTech and Moderna vaccines have only a few months of phase 3 clinical trial data, so much remains unknown about them, including their duration of effect and any long-term safety signals. In addition to excluding immunocompromised individuals, the clinical trials did not include children or pregnant women, so data are lacking for several population subgroups.

But these will not be the only vaccines available, as the pipeline is already becoming crowded. U.S. clinical trial data from a vaccine jointly being developed by Oxford-AstraZeneca, could potentially be ready, along with a request for FDA emergency use authorization, by late January 2021.

In addition, China and Russia have released vaccines, and there are currently 61 vaccines being investigated in clinical trials and at least 85 preclinical products under active investigation.

The vaccine candidates are using both conventional and novel mechanisms of action to elicit an immune response in patients. Conventional methods include attenuated inactivated (killed) virus and recombinant viral protein vaccines to develop immunity. Novel approaches include replication-deficient, adenovirus vector-based vaccines that contain the viral protein, and mRNA-based vaccines, such as the Pfizer and Moderna vaccines, that encode for a SARS-CoV-2 spike protein.

“The special vaccine concern for immunocompromised individuals is introduction of a live virus,” Dr. Stohl said. “Neither the Moderna nor Pfizer vaccines are live viruses, so there should be no special contraindication for such individuals.”

Live vaccine should be avoided in immunocompromised patients, and currently, live SARS-CoV-2 vaccines are only being developed in India and Turkey.

It is not unusual for vaccine trials to begin with cohorts that exclude participants with various health conditions, including those who are immunocompromised. These groups are generally then evaluated in phase 4 trials, or postmarketing surveillance. While the precise number of immunosuppressed adults in the United States is not known, the numbers are believed to be rising because of increased life expectancy among immunosuppressed adults as a result of advances in treatment and new and wider indications for therapies that can affect the immune system.

According to data from the 2013 National Health Interview Survey, an estimated 2.7% of U.S. adults are immunosuppressed. This population covers a broad array of health conditions and medical specialties; people living with inflammatory or autoimmune conditions, such as inflammatory rheumatic diseases (rheumatoid arthritis, axial spondyloarthritis, lupus); inflammatory bowel disease (Crohn’s disease and ulcerative colitis); psoriasis; multiple sclerosis; organ transplant recipients; patients undergoing chemotherapy; and life-long immunosuppression attributable to HIV infection.

As the vaccines begin to roll out and become available, how should clinicians advise their patients, in the absence of any clinical trial data?


 

Risk vs. benefit

Gilaad Kaplan, MD, MPH, a gastroenterologist and professor of medicine at the University of Calgary (Alta.), noted that the inflammatory bowel disease (IBD) community has dealt with tremendous anxiety during the pandemic because many are immunocompromised because of the medications they use to treat their disease.

“For example, many patients with IBD are on biologics like anti-TNF [tumor necrosis factor] therapies, which are also used in other immune-mediated inflammatory diseases such as rheumatoid arthritis,” he said. “Understandably, individuals with IBD on immunosuppressive medications are concerned about the risk of severe complications due to COVID-19.”

The entire IBD community, along with the world, celebrated the announcement that multiple vaccines are protective against SARS-CoV-2, he noted. “Vaccines offer the potential to reduce the spread of COVID-19, allowing society to revert back to normalcy,” Dr. Kaplan said. “Moreover, for vulnerable populations, including those who are immunocompromised, vaccines offer the potential to directly protect them from the morbidity and mortality associated with COVID-19.”

That said, even though the news of vaccines are extremely promising, some cautions must be raised regarding their use in immunocompromised populations, such as persons with IBD. “The current trials, to my knowledge, did not include immunocompromised individuals and thus, we can only extrapolate from what we know from other trials of different vaccines,” he explained. “We know from prior vaccines studies that the immune response following vaccination is less robust in those who are immunocompromised as compared to a healthy control population.”

Dr. Kaplan also pointed to recent reports of allergic reactions that have been reported in healthy individuals. “We don’t know whether side effects, like allergic reactions, may be different in unstudied populations,” he said. “Thus, the medical and scientific community should prioritize clinical studies of safety and effectiveness of COVID-19 vaccines in immunocompromised populations.”

So, what does this mean for an individual with an immune-mediated inflammatory disease like Crohn’s disease or ulcerative colitis who is immunocompromised? Dr. Kaplan explained that it is a balance between the potential harm of being infected with COVID-19 and the uncertainty of receiving a vaccine in an understudied population. For those who are highly susceptible to dying from COVID-19, such as an older adult with IBD, or someone who faces high exposure, such as a health care worker, the potential protection of the vaccine greatly outweighs the uncertainty.

“However, for individuals who are at otherwise lower risk – for example, young and able to work from home – then waiting a few extra months for postmarketing surveillance studies in immunocompromised populations may be a reasonable approach, as long as these individuals are taking great care to avoid infection,” he said.
 

No waiting needed

Joel M. Gelfand, MD, MSCE, professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia, feels that the newly approved vaccine should be safe for most of his patients.

“Patients with psoriatic disease should get the mRNA-based COVID-19 vaccine as soon as possible based on eligibility as determined by the CDC and local public health officials,” he said. “It is not a live vaccine, and therefore patients on biologics or other immune-modulating or immune-suppressing treatment can receive it.”

However, the impact of psoriasis treatment on immune response to the mRNA-based vaccines is not known. Dr. Gelfand noted that, extrapolating from the vaccine literature, there is some evidence that methotrexate reduces response to the influenza vaccine. “However, the clinical significance of this finding is not clear,” he said. “Since the mRNA vaccine needs to be taken twice, a few weeks apart, I do not recommend interrupting or delaying treatment for psoriatic disease while undergoing vaccination for COVID-19.”

Given the reports of allergic reactions, he added that it is advisable for patients with a history of life-threatening allergic reactions such as anaphylaxis or who have been advised to carry an epinephrine autoinjector, to talk with their health care provider to determine if COVID-19 vaccination is medically appropriate.

The National Psoriasis Foundation has issued guidance on COVID-19, explained Steven R. Feldman, MD, PhD, professor of dermatology, pathology, and social sciences & health policy at Wake Forest University, Winston-Salem, N.C., who is also a member of the committee that is working on those guidelines and keeping them up to date. “We are in the process of updating the guidelines with information on COVID vaccines,” he said.

He agreed that there are no contraindications for psoriasis patients to receive the vaccine, regardless of whether they are on immunosuppressive treatment, even though definitive data are lacking. “Fortunately, there’s a lot of good data coming out of Italy that patients with psoriasis on biologics do not appear to be at increased risk of getting COVID or of having worse outcomes from COVID,” he said.

Patients are going to ask about the vaccines, and when counseling them, clinicians should discuss the available data, the residual uncertainty, and patients’ concerns should be considered, Dr. Feldman explained. “There may be some concern that steroids and cyclosporine would reduce the effectiveness of vaccines, but there is no concern that any of the drugs would cause increased risk from nonlive vaccines.”

He added that there is evidence that “patients on biologics who receive nonlive vaccines do develop antibody responses and are immunized.”


 

Boosting efficacy

Even prior to making their announcement, the American College of Rheumatology had said that they would endorse the vaccine for all patients, explained rheumatologist Brett Smith, DO, from Blount Memorial Physicians Group and East Tennessee Children’s Hospital, Alcoa. “The vaccine is safe for all patients, but the problem may be that it’s not as effective,” he said. “But we don’t know that because it hasn’t been tested.”

With other vaccines, biologic medicines are held for 2 weeks before and afterwards, to get the best response. “But some patients don’t want to stop the medication,” Dr. Smith said. “They are afraid that their symptoms will return.”

As for counseling patients as to whether they should receive this vaccine, he explained that he typically doesn’t try to sway patients one way or another until they are really high risk. “When I counsel, it really depends on the individual situation. And for this vaccine, we have to be open to the fact that many people have already made up their mind.”

There are a lot of questions regarding the vaccine. One is the short time frame of development. “Vaccines typically take 6-10 years to come on the market, and this one is now available after a 3-month study,” Dr. Smith said. “Some have already decided that it’s too new for them.”

The process is also new, and patients need to understand that it doesn’t contain an active virus and “you can’t catch coronavirus from it.”

Dr. Smith also explained that, because the vaccine may be less effective in a person using biologic therapies, there is currently no information available on repeat vaccination. “These are all unanswered questions,” he said. “If the antibodies wane in a short time, can we be revaccinated and in what time frame? We just don’t know that yet.”

Marcelo Bonomi, MD, a medical oncologist from The Ohio State University Comprehensive Cancer Center, Columbus, explained that one way to ensure a more optimal response to the vaccine would be to wait until the patient has finished chemotherapy.* “The vaccine can be offered at that time, and in the meantime, they can take other steps to avoid infection,” he said. “If they are very immunosuppressed, it isn’t worth trying to give the vaccine.”

Cancer patients should be encouraged to stay as healthy as possible, and to wear masks and social distance. “It’s a comprehensive approach. Eat healthy, avoid alcohol and tobacco, and exercise. [These things] will help boost the immune system,” Dr. Bonomi said. “Family members should be encouraged to get vaccinated, which will help them avoid infection and exposing the patient.”

Jim Boonyaratanakornkit, MD, PhD, an infectious disease specialist who cares for cancer patients at the Fred Hutchinson Cancer Research Center, agreed. “Giving a vaccine right after a transplant is a futile endeavor,” he said. “We need to wait 6 months to have an immune response.”

He pointed out there may be a continuing higher number of cases, with high levels peaking in Washington in February and March. “Close friends and family should be vaccinated if possible,” he said, “which will help interrupt transmission.”

The vaccines are using new platforms that are totally different, and there is no clear data as to how long the antibodies will persist. “We know that they last for at least 4 months,” said Dr. Boonyaratanakornkit. “We don’t know what level of antibody will protect them from COVID-19 infection. Current studies are being conducted, but we don’t have that information for anyone yet.”
 

*Correction, 1/7/21: An earlier version of this article misattributed quotes from Dr. Marcelo Bonomi.

Coronavirus vaccines have become a reality, as they are now being approved and authorized for use in a growing number of countries including the United States. The U.S. Food and Drug Administration has just issued emergency authorization for the use of the COVID-19 vaccine produced by Pfizer and BioNTech. Close behind is the vaccine developed by Moderna, which has also applied to the FDA for emergency authorization.

scyther5/thinkstock

The efficacy of a two-dose administration of the vaccine has been pegged at 95.0%, and the FDA has said that the 95% credible interval for the vaccine efficacy was 90.3%-97.6%. But as with many initial clinical trials, whether for drugs or vaccines, not all populations were represented in the trial cohort, including individuals who are immunocompromised. At the current time, it is largely unknown how safe or effective the vaccine may be in this large population, many of whom are at high risk for serious COVID-19 complications.

At a special session held during the recent annual meeting of the American Society of Hematology, Anthony Fauci, MD, the nation’s leading infectious disease expert, said that individuals with compromised immune systems, whether because of chemotherapy or a bone marrow transplant, should plan to be vaccinated when the opportunity arises.

In response to a question from ASH President Stephanie J. Lee, MD, of the Fred Hutchinson Cancer Center, Seattle, Dr. Fauci emphasized that, despite being excluded from clinical trials, this population should get vaccinated. “I think we should recommend that they get vaccinated,” he said. “I mean, it is clear that, if you are on immunosuppressive agents, history tells us that you’re not going to have as robust a response as if you had an intact immune system that was not being compromised. But some degree of immunity is better than no degree of immunity.”

That does seem to be the consensus among experts who spoke in interviews: that as long as these are not live attenuated vaccines, they hold no specific risk to an immunocompromised patient, other than any factors specific to the individual that could be a contraindication.

“Patients, family members, friends, and work contacts should be encouraged to receive the vaccine,” said William Stohl, MD, PhD, chief of the division of rheumatology at the University of Southern California, Los Angeles. “Clinicians should advise patients to obtain the vaccine sooner rather than later.”
 

Kevin C. Wang, MD, PhD, of the department of dermatology at Stanford (Calif.) University, agreed. “I am 100% with Dr. Fauci. Everyone should get the vaccine, even if it may not be as effective,” he said. “I would treat it exactly like the flu vaccines that we recommend folks get every year.”

Dr. Wang noted that he couldn’t think of any contraindications unless the immunosuppressed patients have a history of severe allergic reactions to prior vaccinations. “But I would even say patients with history of cancer, upon recommendation of their oncologists, are likely to be suitable candidates for the vaccine,” he added. “I would say clinicians should approach counseling the same way they counsel patients for the flu vaccine, and as far as I know, there are no concerns for systemic drugs commonly used in dermatology patients.”

However, guidance has not yet been issued from either the FDA or the Centers for Disease Control and Prevention regarding the use of the vaccine in immunocompromised individuals. Given the lack of data, the FDA has said that “it will be something that providers will need to consider on an individual basis,” and that individuals should consult with physicians to weigh the potential benefits and potential risks.

The CDC’s Advisory Committee on Immunization Practices has said that clinicians need more guidance on whether to use the vaccine in pregnant or breastfeeding women, the immunocompromised, or those who have a history of allergies. The CDC itself has not yet released its formal guidance on vaccine use.


 

COVID-19 vaccines

Vaccines typically require years of research and testing before reaching the clinic, but this year researchers embarked on a global effort to develop safe and effective coronavirus vaccines in record time. Both the Pfizer/BioNTech and Moderna vaccines have only a few months of phase 3 clinical trial data, so much remains unknown about them, including their duration of effect and any long-term safety signals. In addition to excluding immunocompromised individuals, the clinical trials did not include children or pregnant women, so data are lacking for several population subgroups.

But these will not be the only vaccines available, as the pipeline is already becoming crowded. U.S. clinical trial data from a vaccine jointly being developed by Oxford-AstraZeneca, could potentially be ready, along with a request for FDA emergency use authorization, by late January 2021.

In addition, China and Russia have released vaccines, and there are currently 61 vaccines being investigated in clinical trials and at least 85 preclinical products under active investigation.

The vaccine candidates are using both conventional and novel mechanisms of action to elicit an immune response in patients. Conventional methods include attenuated inactivated (killed) virus and recombinant viral protein vaccines to develop immunity. Novel approaches include replication-deficient, adenovirus vector-based vaccines that contain the viral protein, and mRNA-based vaccines, such as the Pfizer and Moderna vaccines, that encode for a SARS-CoV-2 spike protein.

“The special vaccine concern for immunocompromised individuals is introduction of a live virus,” Dr. Stohl said. “Neither the Moderna nor Pfizer vaccines are live viruses, so there should be no special contraindication for such individuals.”

Live vaccine should be avoided in immunocompromised patients, and currently, live SARS-CoV-2 vaccines are only being developed in India and Turkey.

It is not unusual for vaccine trials to begin with cohorts that exclude participants with various health conditions, including those who are immunocompromised. These groups are generally then evaluated in phase 4 trials, or postmarketing surveillance. While the precise number of immunosuppressed adults in the United States is not known, the numbers are believed to be rising because of increased life expectancy among immunosuppressed adults as a result of advances in treatment and new and wider indications for therapies that can affect the immune system.

According to data from the 2013 National Health Interview Survey, an estimated 2.7% of U.S. adults are immunosuppressed. This population covers a broad array of health conditions and medical specialties; people living with inflammatory or autoimmune conditions, such as inflammatory rheumatic diseases (rheumatoid arthritis, axial spondyloarthritis, lupus); inflammatory bowel disease (Crohn’s disease and ulcerative colitis); psoriasis; multiple sclerosis; organ transplant recipients; patients undergoing chemotherapy; and life-long immunosuppression attributable to HIV infection.

As the vaccines begin to roll out and become available, how should clinicians advise their patients, in the absence of any clinical trial data?


 

Risk vs. benefit

Gilaad Kaplan, MD, MPH, a gastroenterologist and professor of medicine at the University of Calgary (Alta.), noted that the inflammatory bowel disease (IBD) community has dealt with tremendous anxiety during the pandemic because many are immunocompromised because of the medications they use to treat their disease.

“For example, many patients with IBD are on biologics like anti-TNF [tumor necrosis factor] therapies, which are also used in other immune-mediated inflammatory diseases such as rheumatoid arthritis,” he said. “Understandably, individuals with IBD on immunosuppressive medications are concerned about the risk of severe complications due to COVID-19.”

The entire IBD community, along with the world, celebrated the announcement that multiple vaccines are protective against SARS-CoV-2, he noted. “Vaccines offer the potential to reduce the spread of COVID-19, allowing society to revert back to normalcy,” Dr. Kaplan said. “Moreover, for vulnerable populations, including those who are immunocompromised, vaccines offer the potential to directly protect them from the morbidity and mortality associated with COVID-19.”

That said, even though the news of vaccines are extremely promising, some cautions must be raised regarding their use in immunocompromised populations, such as persons with IBD. “The current trials, to my knowledge, did not include immunocompromised individuals and thus, we can only extrapolate from what we know from other trials of different vaccines,” he explained. “We know from prior vaccines studies that the immune response following vaccination is less robust in those who are immunocompromised as compared to a healthy control population.”

Dr. Kaplan also pointed to recent reports of allergic reactions that have been reported in healthy individuals. “We don’t know whether side effects, like allergic reactions, may be different in unstudied populations,” he said. “Thus, the medical and scientific community should prioritize clinical studies of safety and effectiveness of COVID-19 vaccines in immunocompromised populations.”

So, what does this mean for an individual with an immune-mediated inflammatory disease like Crohn’s disease or ulcerative colitis who is immunocompromised? Dr. Kaplan explained that it is a balance between the potential harm of being infected with COVID-19 and the uncertainty of receiving a vaccine in an understudied population. For those who are highly susceptible to dying from COVID-19, such as an older adult with IBD, or someone who faces high exposure, such as a health care worker, the potential protection of the vaccine greatly outweighs the uncertainty.

“However, for individuals who are at otherwise lower risk – for example, young and able to work from home – then waiting a few extra months for postmarketing surveillance studies in immunocompromised populations may be a reasonable approach, as long as these individuals are taking great care to avoid infection,” he said.
 

No waiting needed

Joel M. Gelfand, MD, MSCE, professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia, feels that the newly approved vaccine should be safe for most of his patients.

“Patients with psoriatic disease should get the mRNA-based COVID-19 vaccine as soon as possible based on eligibility as determined by the CDC and local public health officials,” he said. “It is not a live vaccine, and therefore patients on biologics or other immune-modulating or immune-suppressing treatment can receive it.”

However, the impact of psoriasis treatment on immune response to the mRNA-based vaccines is not known. Dr. Gelfand noted that, extrapolating from the vaccine literature, there is some evidence that methotrexate reduces response to the influenza vaccine. “However, the clinical significance of this finding is not clear,” he said. “Since the mRNA vaccine needs to be taken twice, a few weeks apart, I do not recommend interrupting or delaying treatment for psoriatic disease while undergoing vaccination for COVID-19.”

Given the reports of allergic reactions, he added that it is advisable for patients with a history of life-threatening allergic reactions such as anaphylaxis or who have been advised to carry an epinephrine autoinjector, to talk with their health care provider to determine if COVID-19 vaccination is medically appropriate.

The National Psoriasis Foundation has issued guidance on COVID-19, explained Steven R. Feldman, MD, PhD, professor of dermatology, pathology, and social sciences & health policy at Wake Forest University, Winston-Salem, N.C., who is also a member of the committee that is working on those guidelines and keeping them up to date. “We are in the process of updating the guidelines with information on COVID vaccines,” he said.

He agreed that there are no contraindications for psoriasis patients to receive the vaccine, regardless of whether they are on immunosuppressive treatment, even though definitive data are lacking. “Fortunately, there’s a lot of good data coming out of Italy that patients with psoriasis on biologics do not appear to be at increased risk of getting COVID or of having worse outcomes from COVID,” he said.

Patients are going to ask about the vaccines, and when counseling them, clinicians should discuss the available data, the residual uncertainty, and patients’ concerns should be considered, Dr. Feldman explained. “There may be some concern that steroids and cyclosporine would reduce the effectiveness of vaccines, but there is no concern that any of the drugs would cause increased risk from nonlive vaccines.”

He added that there is evidence that “patients on biologics who receive nonlive vaccines do develop antibody responses and are immunized.”


 

Boosting efficacy

Even prior to making their announcement, the American College of Rheumatology had said that they would endorse the vaccine for all patients, explained rheumatologist Brett Smith, DO, from Blount Memorial Physicians Group and East Tennessee Children’s Hospital, Alcoa. “The vaccine is safe for all patients, but the problem may be that it’s not as effective,” he said. “But we don’t know that because it hasn’t been tested.”

With other vaccines, biologic medicines are held for 2 weeks before and afterwards, to get the best response. “But some patients don’t want to stop the medication,” Dr. Smith said. “They are afraid that their symptoms will return.”

As for counseling patients as to whether they should receive this vaccine, he explained that he typically doesn’t try to sway patients one way or another until they are really high risk. “When I counsel, it really depends on the individual situation. And for this vaccine, we have to be open to the fact that many people have already made up their mind.”

There are a lot of questions regarding the vaccine. One is the short time frame of development. “Vaccines typically take 6-10 years to come on the market, and this one is now available after a 3-month study,” Dr. Smith said. “Some have already decided that it’s too new for them.”

The process is also new, and patients need to understand that it doesn’t contain an active virus and “you can’t catch coronavirus from it.”

Dr. Smith also explained that, because the vaccine may be less effective in a person using biologic therapies, there is currently no information available on repeat vaccination. “These are all unanswered questions,” he said. “If the antibodies wane in a short time, can we be revaccinated and in what time frame? We just don’t know that yet.”

Marcelo Bonomi, MD, a medical oncologist from The Ohio State University Comprehensive Cancer Center, Columbus, explained that one way to ensure a more optimal response to the vaccine would be to wait until the patient has finished chemotherapy.* “The vaccine can be offered at that time, and in the meantime, they can take other steps to avoid infection,” he said. “If they are very immunosuppressed, it isn’t worth trying to give the vaccine.”

Cancer patients should be encouraged to stay as healthy as possible, and to wear masks and social distance. “It’s a comprehensive approach. Eat healthy, avoid alcohol and tobacco, and exercise. [These things] will help boost the immune system,” Dr. Bonomi said. “Family members should be encouraged to get vaccinated, which will help them avoid infection and exposing the patient.”

Jim Boonyaratanakornkit, MD, PhD, an infectious disease specialist who cares for cancer patients at the Fred Hutchinson Cancer Research Center, agreed. “Giving a vaccine right after a transplant is a futile endeavor,” he said. “We need to wait 6 months to have an immune response.”

He pointed out there may be a continuing higher number of cases, with high levels peaking in Washington in February and March. “Close friends and family should be vaccinated if possible,” he said, “which will help interrupt transmission.”

The vaccines are using new platforms that are totally different, and there is no clear data as to how long the antibodies will persist. “We know that they last for at least 4 months,” said Dr. Boonyaratanakornkit. “We don’t know what level of antibody will protect them from COVID-19 infection. Current studies are being conducted, but we don’t have that information for anyone yet.”
 

*Correction, 1/7/21: An earlier version of this article misattributed quotes from Dr. Marcelo Bonomi.

You can now buy vegan eggnog, made from almond milk. The fact that someone created this wasn’t a surprise – plant milks are taking over. That it gave me such pleasure was. It’s rich, and if you love eggnog, like all normal people, it’s amazingly satisfying when mixed in a Nespresso latte swirled creamy white and brown. It seems some things, like Netflix’s The Crown, my Peloton spin classes, long Sunday walks on the beach, and the best mushroom risotto I ever made were still pleasurable this year, despite all. I’d daresay, there was joy even in the time of COVID.

But, before we get to that, it might be useful to distinguish between joy and pleasure.

Pleasure is pretty constant. It pops up even in the worst times. It seems, there’s plenty to be found even now. Unless, perhaps it’s just me. The label my mother pinned on me as a boy has remained into adulthood: “Easy to please.” There’s hardly a movie I’ve seen that I didn’t like. I’m quite comfortable in the middle seat. I thought the EPIC updates this year were nice. I’ve liked the vast majority of pizzas I’ve ever eaten – even those contaminated with Truffle salt. Easy to please is a gift, not something I’ve acquired through hours of meditation or aesthetic fasts. But surely pleasure isn’t the same as joy. No one has tears of pleasure. (Not to mention, pleasure as a verb has obvious NSFW connotations; not true of joy).

No, joy is waaay bigger. Joy is shared. Joy is to the whole world. Joy is what happens when you have a baby. Pleasure is what happens when you remembered to put a burp cloth in the car. Pleasure is when three patients in a row take merely 5 minutes each. Joy is when an itchy patient is cured.

2020 was one of the most miserable years in the last century. We didn’t expect it, but we ought to have. I mean really, how many plagues have we endured? How many times has inequality led to social unrest? Many times. We, by luck and dint of hard work, have always managed to get through. Although suffering would surely have been greater during those times of sickness and loss, I don’t believe joy would have been less. Indeed, maybe it is those difficulties and that suffering that allows us to feel joy in the first place. It is only once you summit that you experience joy. The run-up is just pain.

It is no coincidence that it is now during this cold, dark, difficult part of the year that we wish joy. We’ve made it. We light the darkness with candles to joyously celebrate Mawlid, Diwali, then Hanukkah and Christmas. Had malls been open now, you’d hear amongst the din of ringing bells Rejoice! Rejoice! O Emmanuel! You’d sing along, “Joy to the world, now we sing, let the Angel voices ring.” Joy: A pleasure so great and so deserved, it is shared by all. It is good news, hope, gratitude.

A joy shared amongst us all is also coming. Through the wrenching pain of watching patients suffocate, fogged shields, and bleached masks, through canceled Thanksgivings, through weekends spent in the OR on the backlog of patients, after months spent sitting in empty clinics, though the long, orange-cone-winding lines of testing, at last, at last a vaccine is here to light the darkness.

Let the sea resound, and everything in it,
the world, and all who live in it.
Let the rivers clap their hands,
let the mountains sing together for joy.
Joy to the world.
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

You can now buy vegan eggnog, made from almond milk. The fact that someone created this wasn’t a surprise – plant milks are taking over. That it gave me such pleasure was. It’s rich, and if you love eggnog, like all normal people, it’s amazingly satisfying when mixed in a Nespresso latte swirled creamy white and brown. It seems some things, like Netflix’s The Crown, my Peloton spin classes, long Sunday walks on the beach, and the best mushroom risotto I ever made were still pleasurable this year, despite all. I’d daresay, there was joy even in the time of COVID.

But, before we get to that, it might be useful to distinguish between joy and pleasure.

Pleasure is pretty constant. It pops up even in the worst times. It seems, there’s plenty to be found even now. Unless, perhaps it’s just me. The label my mother pinned on me as a boy has remained into adulthood: “Easy to please.” There’s hardly a movie I’ve seen that I didn’t like. I’m quite comfortable in the middle seat. I thought the EPIC updates this year were nice. I’ve liked the vast majority of pizzas I’ve ever eaten – even those contaminated with Truffle salt. Easy to please is a gift, not something I’ve acquired through hours of meditation or aesthetic fasts. But surely pleasure isn’t the same as joy. No one has tears of pleasure. (Not to mention, pleasure as a verb has obvious NSFW connotations; not true of joy).

No, joy is waaay bigger. Joy is shared. Joy is to the whole world. Joy is what happens when you have a baby. Pleasure is what happens when you remembered to put a burp cloth in the car. Pleasure is when three patients in a row take merely 5 minutes each. Joy is when an itchy patient is cured.

2020 was one of the most miserable years in the last century. We didn’t expect it, but we ought to have. I mean really, how many plagues have we endured? How many times has inequality led to social unrest? Many times. We, by luck and dint of hard work, have always managed to get through. Although suffering would surely have been greater during those times of sickness and loss, I don’t believe joy would have been less. Indeed, maybe it is those difficulties and that suffering that allows us to feel joy in the first place. It is only once you summit that you experience joy. The run-up is just pain.

It is no coincidence that it is now during this cold, dark, difficult part of the year that we wish joy. We’ve made it. We light the darkness with candles to joyously celebrate Mawlid, Diwali, then Hanukkah and Christmas. Had malls been open now, you’d hear amongst the din of ringing bells Rejoice! Rejoice! O Emmanuel! You’d sing along, “Joy to the world, now we sing, let the Angel voices ring.” Joy: A pleasure so great and so deserved, it is shared by all. It is good news, hope, gratitude.

A joy shared amongst us all is also coming. Through the wrenching pain of watching patients suffocate, fogged shields, and bleached masks, through canceled Thanksgivings, through weekends spent in the OR on the backlog of patients, after months spent sitting in empty clinics, though the long, orange-cone-winding lines of testing, at last, at last a vaccine is here to light the darkness.

Let the sea resound, and everything in it,
the world, and all who live in it.
Let the rivers clap their hands,
let the mountains sing together for joy.
Joy to the world.
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

You can now buy vegan eggnog, made from almond milk. The fact that someone created this wasn’t a surprise – plant milks are taking over. That it gave me such pleasure was. It’s rich, and if you love eggnog, like all normal people, it’s amazingly satisfying when mixed in a Nespresso latte swirled creamy white and brown. It seems some things, like Netflix’s The Crown, my Peloton spin classes, long Sunday walks on the beach, and the best mushroom risotto I ever made were still pleasurable this year, despite all. I’d daresay, there was joy even in the time of COVID.

But, before we get to that, it might be useful to distinguish between joy and pleasure.

Pleasure is pretty constant. It pops up even in the worst times. It seems, there’s plenty to be found even now. Unless, perhaps it’s just me. The label my mother pinned on me as a boy has remained into adulthood: “Easy to please.” There’s hardly a movie I’ve seen that I didn’t like. I’m quite comfortable in the middle seat. I thought the EPIC updates this year were nice. I’ve liked the vast majority of pizzas I’ve ever eaten – even those contaminated with Truffle salt. Easy to please is a gift, not something I’ve acquired through hours of meditation or aesthetic fasts. But surely pleasure isn’t the same as joy. No one has tears of pleasure. (Not to mention, pleasure as a verb has obvious NSFW connotations; not true of joy).

No, joy is waaay bigger. Joy is shared. Joy is to the whole world. Joy is what happens when you have a baby. Pleasure is what happens when you remembered to put a burp cloth in the car. Pleasure is when three patients in a row take merely 5 minutes each. Joy is when an itchy patient is cured.

2020 was one of the most miserable years in the last century. We didn’t expect it, but we ought to have. I mean really, how many plagues have we endured? How many times has inequality led to social unrest? Many times. We, by luck and dint of hard work, have always managed to get through. Although suffering would surely have been greater during those times of sickness and loss, I don’t believe joy would have been less. Indeed, maybe it is those difficulties and that suffering that allows us to feel joy in the first place. It is only once you summit that you experience joy. The run-up is just pain.

It is no coincidence that it is now during this cold, dark, difficult part of the year that we wish joy. We’ve made it. We light the darkness with candles to joyously celebrate Mawlid, Diwali, then Hanukkah and Christmas. Had malls been open now, you’d hear amongst the din of ringing bells Rejoice! Rejoice! O Emmanuel! You’d sing along, “Joy to the world, now we sing, let the Angel voices ring.” Joy: A pleasure so great and so deserved, it is shared by all. It is good news, hope, gratitude.

A joy shared amongst us all is also coming. Through the wrenching pain of watching patients suffocate, fogged shields, and bleached masks, through canceled Thanksgivings, through weekends spent in the OR on the backlog of patients, after months spent sitting in empty clinics, though the long, orange-cone-winding lines of testing, at last, at last a vaccine is here to light the darkness.

Let the sea resound, and everything in it,
the world, and all who live in it.
Let the rivers clap their hands,
let the mountains sing together for joy.
Joy to the world.
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

Treatment with etanercept does not appear to achieve significant clinical improvement in patients suspected of having nonradiographic axial spondyloarthritis (nr-axSpA) but without positive MRI signs of sacroiliitis and/or elevated C-reactive protein (CRP) levels, research suggests.

A paper published in Arthritis & Rheumatology presents the outcomes of a randomized, double-blind, placebo-controlled trial of a 16-week course of etanercept at 25 mg twice weekly in 80 tumor necrosis factor inhibitor (TNFi)–naive patients with suspected nr-axSpA. Patients all had chronic inflammatory back pain, at least two spondyloarthritis features – such as HLA-B27 positivity, asymmetrical arthritis, or family history of ankylosing spondylitis – as well as high disease activity and insufficient response to at least two NSAIDs. These patients meet the “clinical arm” of Assessment of SpondyloArthritis international Society (ASAS) criteria for classifying axSpA at an early stage of disease but not “imaging-arm” requirements for the presence of active inflammatory lesions of the sacroiliac joints (SIJ) on MRI and one additional SpA feature.

Whether these imaging criteria and objective evidence of elevated inflammation are necessary to fulfill when considering TNFi treatment for patients with suspected nr-axSpA in daily practice is an important question to address, the authors pointed out, because “in many studies, the presence of a positive MRI-SIJ is one of the prerequisites to start a TNF inhibitor treatment in patients with nr-axSpA.” In addition, starting a TNFi is dependent on failure of at least two NSAIDs and an elevated CRP level when the MRI is negative, which is problematic since in some studies raised CRP levels were found in only 30% of the nr-axSpA patients and 59%-64% of nr-axSpA patients with high disease activity do not have active inflammatory SIJ lesions on MRI. On top of these concerns is the fact that many people who do not have axSpA show false-positive results of bone marrow edema on MRI of the SIJ, such as postpartum women, recreational runners, professional athletes, and army recruits undergoing physical training, they added.

In the current study at the end of the 16-week course of treatment, researchers found no statistically significant difference between the treatment and placebo group in the number of patients who achieved a 20% improvement in ASAS response criteria (16.7% vs. 11.1%; P = .5), nor in those who had at least 40% improvement (8.3% in both groups). This was regardless of sex, age, NSAID or disease-modifying antirheumatic drug use, HLA-B27 status, or other clinical factors.

Similarly, there was no statistically significant difference between the two groups in the number of patients who met response criteria for the Ankylosing Spondylitis Disease Activity Score based on CRP for either clinical improvement or major improvement.

Participants underwent MRI at baseline and at 16 and 24 weeks, which revealed similar numbers of active inflammatory SIJ lesions in each group. The two groups also had similar Spondyloarthritis Research Consortium of Canada scores at baseline and 16 weeks, but a slightly – yet statistically significant – higher score in the etanercept group at 24 weeks.

However, during the first 16 weeks of the study, patients in the etanercept group showed greater improvements in pain and erythrocyte sedimentation rate (ESR), compared with those in the placebo group.

After the 16-week treatment course, participants were followed for another 8 weeks. During this time, participants in the etanercept group showed a worsening in their mean Bath Ankylosing Spondylitis Metrology Index score, CRP level, and ESR, compared with the placebo group.

While the number of participants who experienced an adverse event by 16 weeks was similar in both groups, more patients in the etanercept group experienced an adverse effect likely related to the study drug.

Study results in the context of previous findings

Commenting on their findings, first author Tamara Rusman, of the Amsterdam University Medical Center, and coauthors wrote that the results suggested early treatment with etanercept in patients without a positive MRI and raised CRP levels was not effective.

However, they acknowledged that two previous placebo-controlled studies had specifically included patients with nr-axSpA and found a significantly better treatment response to TNF inhibitors than to placebo. One of these studies included a significant number of patients with MRI-detected active inflammatory SIJ lesions at baseline, which is a known predictor of treatment response.

“The relatively low number of patients with either a positive MRI-SIJ (23%) and/or elevated CRP level (13%) at baseline in our study could be an explanation for the absence of a treatment effect in favor of etanercept,” they wrote.

They also raised the possibility that their choice of study population didn’t truly capture patients with nr-axSpA, and that it was not powered to compare patients with or without a positive MRI or raised CRP level at baseline.

“It would be interesting to know whether our study results will be replicated by others in comparable study populations with equal numbers of patients with and without a positive MRI-SIJ and raised CRP in the future,” they wrote.

The study was supported by an unrestricted financial grant from Pfizer and ReumaNederland. No conflicts of interest were declared.

SOURCE: Rusman T et al. Arthritis Rheumatol. 2020 Dec 5. doi: 10.1002/art.41607.

Treatment with etanercept does not appear to achieve significant clinical improvement in patients suspected of having nonradiographic axial spondyloarthritis (nr-axSpA) but without positive MRI signs of sacroiliitis and/or elevated C-reactive protein (CRP) levels, research suggests.

A paper published in Arthritis & Rheumatology presents the outcomes of a randomized, double-blind, placebo-controlled trial of a 16-week course of etanercept at 25 mg twice weekly in 80 tumor necrosis factor inhibitor (TNFi)–naive patients with suspected nr-axSpA. Patients all had chronic inflammatory back pain, at least two spondyloarthritis features – such as HLA-B27 positivity, asymmetrical arthritis, or family history of ankylosing spondylitis – as well as high disease activity and insufficient response to at least two NSAIDs. These patients meet the “clinical arm” of Assessment of SpondyloArthritis international Society (ASAS) criteria for classifying axSpA at an early stage of disease but not “imaging-arm” requirements for the presence of active inflammatory lesions of the sacroiliac joints (SIJ) on MRI and one additional SpA feature.

Whether these imaging criteria and objective evidence of elevated inflammation are necessary to fulfill when considering TNFi treatment for patients with suspected nr-axSpA in daily practice is an important question to address, the authors pointed out, because “in many studies, the presence of a positive MRI-SIJ is one of the prerequisites to start a TNF inhibitor treatment in patients with nr-axSpA.” In addition, starting a TNFi is dependent on failure of at least two NSAIDs and an elevated CRP level when the MRI is negative, which is problematic since in some studies raised CRP levels were found in only 30% of the nr-axSpA patients and 59%-64% of nr-axSpA patients with high disease activity do not have active inflammatory SIJ lesions on MRI. On top of these concerns is the fact that many people who do not have axSpA show false-positive results of bone marrow edema on MRI of the SIJ, such as postpartum women, recreational runners, professional athletes, and army recruits undergoing physical training, they added.

In the current study at the end of the 16-week course of treatment, researchers found no statistically significant difference between the treatment and placebo group in the number of patients who achieved a 20% improvement in ASAS response criteria (16.7% vs. 11.1%; P = .5), nor in those who had at least 40% improvement (8.3% in both groups). This was regardless of sex, age, NSAID or disease-modifying antirheumatic drug use, HLA-B27 status, or other clinical factors.

Similarly, there was no statistically significant difference between the two groups in the number of patients who met response criteria for the Ankylosing Spondylitis Disease Activity Score based on CRP for either clinical improvement or major improvement.

Participants underwent MRI at baseline and at 16 and 24 weeks, which revealed similar numbers of active inflammatory SIJ lesions in each group. The two groups also had similar Spondyloarthritis Research Consortium of Canada scores at baseline and 16 weeks, but a slightly – yet statistically significant – higher score in the etanercept group at 24 weeks.

However, during the first 16 weeks of the study, patients in the etanercept group showed greater improvements in pain and erythrocyte sedimentation rate (ESR), compared with those in the placebo group.

After the 16-week treatment course, participants were followed for another 8 weeks. During this time, participants in the etanercept group showed a worsening in their mean Bath Ankylosing Spondylitis Metrology Index score, CRP level, and ESR, compared with the placebo group.

While the number of participants who experienced an adverse event by 16 weeks was similar in both groups, more patients in the etanercept group experienced an adverse effect likely related to the study drug.

Study results in the context of previous findings

Commenting on their findings, first author Tamara Rusman, of the Amsterdam University Medical Center, and coauthors wrote that the results suggested early treatment with etanercept in patients without a positive MRI and raised CRP levels was not effective.

However, they acknowledged that two previous placebo-controlled studies had specifically included patients with nr-axSpA and found a significantly better treatment response to TNF inhibitors than to placebo. One of these studies included a significant number of patients with MRI-detected active inflammatory SIJ lesions at baseline, which is a known predictor of treatment response.

“The relatively low number of patients with either a positive MRI-SIJ (23%) and/or elevated CRP level (13%) at baseline in our study could be an explanation for the absence of a treatment effect in favor of etanercept,” they wrote.

They also raised the possibility that their choice of study population didn’t truly capture patients with nr-axSpA, and that it was not powered to compare patients with or without a positive MRI or raised CRP level at baseline.

“It would be interesting to know whether our study results will be replicated by others in comparable study populations with equal numbers of patients with and without a positive MRI-SIJ and raised CRP in the future,” they wrote.

The study was supported by an unrestricted financial grant from Pfizer and ReumaNederland. No conflicts of interest were declared.

SOURCE: Rusman T et al. Arthritis Rheumatol. 2020 Dec 5. doi: 10.1002/art.41607.

Treatment with etanercept does not appear to achieve significant clinical improvement in patients suspected of having nonradiographic axial spondyloarthritis (nr-axSpA) but without positive MRI signs of sacroiliitis and/or elevated C-reactive protein (CRP) levels, research suggests.

A paper published in Arthritis & Rheumatology presents the outcomes of a randomized, double-blind, placebo-controlled trial of a 16-week course of etanercept at 25 mg twice weekly in 80 tumor necrosis factor inhibitor (TNFi)–naive patients with suspected nr-axSpA. Patients all had chronic inflammatory back pain, at least two spondyloarthritis features – such as HLA-B27 positivity, asymmetrical arthritis, or family history of ankylosing spondylitis – as well as high disease activity and insufficient response to at least two NSAIDs. These patients meet the “clinical arm” of Assessment of SpondyloArthritis international Society (ASAS) criteria for classifying axSpA at an early stage of disease but not “imaging-arm” requirements for the presence of active inflammatory lesions of the sacroiliac joints (SIJ) on MRI and one additional SpA feature.

Whether these imaging criteria and objective evidence of elevated inflammation are necessary to fulfill when considering TNFi treatment for patients with suspected nr-axSpA in daily practice is an important question to address, the authors pointed out, because “in many studies, the presence of a positive MRI-SIJ is one of the prerequisites to start a TNF inhibitor treatment in patients with nr-axSpA.” In addition, starting a TNFi is dependent on failure of at least two NSAIDs and an elevated CRP level when the MRI is negative, which is problematic since in some studies raised CRP levels were found in only 30% of the nr-axSpA patients and 59%-64% of nr-axSpA patients with high disease activity do not have active inflammatory SIJ lesions on MRI. On top of these concerns is the fact that many people who do not have axSpA show false-positive results of bone marrow edema on MRI of the SIJ, such as postpartum women, recreational runners, professional athletes, and army recruits undergoing physical training, they added.

In the current study at the end of the 16-week course of treatment, researchers found no statistically significant difference between the treatment and placebo group in the number of patients who achieved a 20% improvement in ASAS response criteria (16.7% vs. 11.1%; P = .5), nor in those who had at least 40% improvement (8.3% in both groups). This was regardless of sex, age, NSAID or disease-modifying antirheumatic drug use, HLA-B27 status, or other clinical factors.

Similarly, there was no statistically significant difference between the two groups in the number of patients who met response criteria for the Ankylosing Spondylitis Disease Activity Score based on CRP for either clinical improvement or major improvement.

Participants underwent MRI at baseline and at 16 and 24 weeks, which revealed similar numbers of active inflammatory SIJ lesions in each group. The two groups also had similar Spondyloarthritis Research Consortium of Canada scores at baseline and 16 weeks, but a slightly – yet statistically significant – higher score in the etanercept group at 24 weeks.

However, during the first 16 weeks of the study, patients in the etanercept group showed greater improvements in pain and erythrocyte sedimentation rate (ESR), compared with those in the placebo group.

After the 16-week treatment course, participants were followed for another 8 weeks. During this time, participants in the etanercept group showed a worsening in their mean Bath Ankylosing Spondylitis Metrology Index score, CRP level, and ESR, compared with the placebo group.

While the number of participants who experienced an adverse event by 16 weeks was similar in both groups, more patients in the etanercept group experienced an adverse effect likely related to the study drug.

Study results in the context of previous findings

Commenting on their findings, first author Tamara Rusman, of the Amsterdam University Medical Center, and coauthors wrote that the results suggested early treatment with etanercept in patients without a positive MRI and raised CRP levels was not effective.

However, they acknowledged that two previous placebo-controlled studies had specifically included patients with nr-axSpA and found a significantly better treatment response to TNF inhibitors than to placebo. One of these studies included a significant number of patients with MRI-detected active inflammatory SIJ lesions at baseline, which is a known predictor of treatment response.

“The relatively low number of patients with either a positive MRI-SIJ (23%) and/or elevated CRP level (13%) at baseline in our study could be an explanation for the absence of a treatment effect in favor of etanercept,” they wrote.

They also raised the possibility that their choice of study population didn’t truly capture patients with nr-axSpA, and that it was not powered to compare patients with or without a positive MRI or raised CRP level at baseline.

“It would be interesting to know whether our study results will be replicated by others in comparable study populations with equal numbers of patients with and without a positive MRI-SIJ and raised CRP in the future,” they wrote.

The study was supported by an unrestricted financial grant from Pfizer and ReumaNederland. No conflicts of interest were declared.

SOURCE: Rusman T et al. Arthritis Rheumatol. 2020 Dec 5. doi: 10.1002/art.41607.

The Food and Drug Administration has issued an emergency-use authorization (EUA) for the first COVID-19 diagnostic test that can be completed at home without a prescription.

Authorization of the Ellume COVID-19 Home Test is “a major milestone in diagnostic testing for COVID-19,” FDA Commissioner Stephen M. Hahn, MD, said in a news release.

“By authorizing a test for over-the-counter use, the FDA allows it to be sold in places like drug stores, where a patient can buy it, swab their nose, run the test, and find out their results in as little as 20 minutes,” said Dr. Hahn.

The Ellume COVID-19 Home Test is a rapid antigen test that detects fragments of the SARS-CoV-2 virus from a nasal swab sample taken from anyone aged 2 years and older, including those not showing any symptoms.

In testing, the Ellume COVID-19 Home Test correctly identified 96% of positive samples and 100% of negative samples in individuals with symptoms.

In people without symptoms, the test correctly identified 91% of positive samples and 96% of negative samples, the FDA said.

The test includes a sterile nasal swab, a dropper, processing fluid, and a Bluetooth-connected analyzer for use with an app on the user’s smartphone. The sample is analyzed and results are automatically transmitted to the user’s smartphone.

“The Ellume COVID-19 home test’s core technology combines ultra-sensitive optics, electronics, and proprietary software to leverage best-in-class digital immunoassay technology with next-generation multi-quantum dot fluorescence technology,” the company said in a news release.

The mobile app requires individuals to input their ZIP code and date of birth, with optional fields including name and email address. The app automatically reports the results as appropriate to public health authorities to monitor disease prevalence.

Ellume expects to produce more than 3 million tests in January 2021. The company said the test will cost around $30.

FDA authorization of this first fully at-home nonprescription COVID-19 diagnostic test follows last month’s EUA for the first prescription COVID-19 test for home use, as reported this news organization.

Since the start of the pandemic, the FDA has authorized more than 225 diagnostic tests for COVID-19, including more than 25 tests that allow for home collection of samples, which are then sent to a lab for testing.

“As we continue to authorize additional tests for home use, we are helping expand Americans’ access to testing, reducing the burden on laboratories and test supplies, and giving Americans more testing options from the comfort and safety of their own homes,” Dr. Hahn said.

“This test, like other antigen tests, is less sensitive and less specific than typical molecular tests run in a lab,” said Jeffrey Shuren, MD, JD, director of FDA’s Center for Devices and Radiological Health, in the release. “However, the fact that it can be used completely at home and return results quickly means that it can play an important role in response to the pandemic.”

As with other antigen tests, a small percentage of positive and negative results from the Ellume test may be false. In patients without symptoms, positive results should be treated as presumptively positive until confirmed by another test as soon as possible, the FDA advised.

This is especially true if there are fewer infections in a particular community, as false-positive results can be more common when antigen tests are used in populations where there is a low prevalence of COVID-19, the agency said.

Because all tests can give false-negative and false-positive results, individuals with positive results should self-isolate and seek additional care from their health care provider.

Individuals who test negative and have symptoms of COVID-19 should follow up with their health care provider, as negative results don’t preclude an individual from SARS-CoV-2 infection.

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

The Food and Drug Administration has issued an emergency-use authorization (EUA) for the first COVID-19 diagnostic test that can be completed at home without a prescription.

Authorization of the Ellume COVID-19 Home Test is “a major milestone in diagnostic testing for COVID-19,” FDA Commissioner Stephen M. Hahn, MD, said in a news release.

“By authorizing a test for over-the-counter use, the FDA allows it to be sold in places like drug stores, where a patient can buy it, swab their nose, run the test, and find out their results in as little as 20 minutes,” said Dr. Hahn.

The Ellume COVID-19 Home Test is a rapid antigen test that detects fragments of the SARS-CoV-2 virus from a nasal swab sample taken from anyone aged 2 years and older, including those not showing any symptoms.

In testing, the Ellume COVID-19 Home Test correctly identified 96% of positive samples and 100% of negative samples in individuals with symptoms.

In people without symptoms, the test correctly identified 91% of positive samples and 96% of negative samples, the FDA said.

The test includes a sterile nasal swab, a dropper, processing fluid, and a Bluetooth-connected analyzer for use with an app on the user’s smartphone. The sample is analyzed and results are automatically transmitted to the user’s smartphone.

“The Ellume COVID-19 home test’s core technology combines ultra-sensitive optics, electronics, and proprietary software to leverage best-in-class digital immunoassay technology with next-generation multi-quantum dot fluorescence technology,” the company said in a news release.

The mobile app requires individuals to input their ZIP code and date of birth, with optional fields including name and email address. The app automatically reports the results as appropriate to public health authorities to monitor disease prevalence.

Ellume expects to produce more than 3 million tests in January 2021. The company said the test will cost around $30.

FDA authorization of this first fully at-home nonprescription COVID-19 diagnostic test follows last month’s EUA for the first prescription COVID-19 test for home use, as reported this news organization.

Since the start of the pandemic, the FDA has authorized more than 225 diagnostic tests for COVID-19, including more than 25 tests that allow for home collection of samples, which are then sent to a lab for testing.

“As we continue to authorize additional tests for home use, we are helping expand Americans’ access to testing, reducing the burden on laboratories and test supplies, and giving Americans more testing options from the comfort and safety of their own homes,” Dr. Hahn said.

“This test, like other antigen tests, is less sensitive and less specific than typical molecular tests run in a lab,” said Jeffrey Shuren, MD, JD, director of FDA’s Center for Devices and Radiological Health, in the release. “However, the fact that it can be used completely at home and return results quickly means that it can play an important role in response to the pandemic.”

As with other antigen tests, a small percentage of positive and negative results from the Ellume test may be false. In patients without symptoms, positive results should be treated as presumptively positive until confirmed by another test as soon as possible, the FDA advised.

This is especially true if there are fewer infections in a particular community, as false-positive results can be more common when antigen tests are used in populations where there is a low prevalence of COVID-19, the agency said.

Because all tests can give false-negative and false-positive results, individuals with positive results should self-isolate and seek additional care from their health care provider.

Individuals who test negative and have symptoms of COVID-19 should follow up with their health care provider, as negative results don’t preclude an individual from SARS-CoV-2 infection.

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

The Food and Drug Administration has issued an emergency-use authorization (EUA) for the first COVID-19 diagnostic test that can be completed at home without a prescription.

Authorization of the Ellume COVID-19 Home Test is “a major milestone in diagnostic testing for COVID-19,” FDA Commissioner Stephen M. Hahn, MD, said in a news release.

“By authorizing a test for over-the-counter use, the FDA allows it to be sold in places like drug stores, where a patient can buy it, swab their nose, run the test, and find out their results in as little as 20 minutes,” said Dr. Hahn.

The Ellume COVID-19 Home Test is a rapid antigen test that detects fragments of the SARS-CoV-2 virus from a nasal swab sample taken from anyone aged 2 years and older, including those not showing any symptoms.

In testing, the Ellume COVID-19 Home Test correctly identified 96% of positive samples and 100% of negative samples in individuals with symptoms.

In people without symptoms, the test correctly identified 91% of positive samples and 96% of negative samples, the FDA said.

The test includes a sterile nasal swab, a dropper, processing fluid, and a Bluetooth-connected analyzer for use with an app on the user’s smartphone. The sample is analyzed and results are automatically transmitted to the user’s smartphone.

“The Ellume COVID-19 home test’s core technology combines ultra-sensitive optics, electronics, and proprietary software to leverage best-in-class digital immunoassay technology with next-generation multi-quantum dot fluorescence technology,” the company said in a news release.

The mobile app requires individuals to input their ZIP code and date of birth, with optional fields including name and email address. The app automatically reports the results as appropriate to public health authorities to monitor disease prevalence.

Ellume expects to produce more than 3 million tests in January 2021. The company said the test will cost around $30.

FDA authorization of this first fully at-home nonprescription COVID-19 diagnostic test follows last month’s EUA for the first prescription COVID-19 test for home use, as reported this news organization.

Since the start of the pandemic, the FDA has authorized more than 225 diagnostic tests for COVID-19, including more than 25 tests that allow for home collection of samples, which are then sent to a lab for testing.

“As we continue to authorize additional tests for home use, we are helping expand Americans’ access to testing, reducing the burden on laboratories and test supplies, and giving Americans more testing options from the comfort and safety of their own homes,” Dr. Hahn said.

“This test, like other antigen tests, is less sensitive and less specific than typical molecular tests run in a lab,” said Jeffrey Shuren, MD, JD, director of FDA’s Center for Devices and Radiological Health, in the release. “However, the fact that it can be used completely at home and return results quickly means that it can play an important role in response to the pandemic.”

As with other antigen tests, a small percentage of positive and negative results from the Ellume test may be false. In patients without symptoms, positive results should be treated as presumptively positive until confirmed by another test as soon as possible, the FDA advised.

This is especially true if there are fewer infections in a particular community, as false-positive results can be more common when antigen tests are used in populations where there is a low prevalence of COVID-19, the agency said.

Because all tests can give false-negative and false-positive results, individuals with positive results should self-isolate and seek additional care from their health care provider.

Individuals who test negative and have symptoms of COVID-19 should follow up with their health care provider, as negative results don’t preclude an individual from SARS-CoV-2 infection.

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

Recently I posted a simple question on several social media pages and internet blogs populated exclusively by board-certified dermatologists and dermatologic surgeons: How would you respond to a patient asking (or demanding) to record all or part of their office visit? (Or, if you have encountered such a situation, how did you respond?)

The question was simple, but the answers were somewhat complicated.

First, I noticed a fundamental misunderstanding of applicable laws: Many practitioners apparently believe that taping or recording a private conversation is per se illegal. Perhaps they are conflating with wiretapping laws, which don’t apply in this situation. HIPAA laws don’t apply either, because the patient, by definition, is waiving the right to privacy by initiating the recording in the first place.

In fact, every U.S. jurisdiction permits the taping or recording of doctor-patient conversations; and only 11 states (California, Florida, Illinois, Maryland, Massachusetts, Michigan, Montana, New Hampshire, Oregon, Pennsylvania, and Washington) require the consent of both parties. All other states and territories actually allow it even if one party has not given consent. And some patients don’t ask permission at all; they just do it.

Another misconception was the perceived frequency of such situations. Recordings of conversations in the doctor’s office are by no means rare. A 2014 survey in the United Kingdom revealed that 15% of the public had secretly recorded a clinic visit, and a further 11% were aware of someone else doing the same, a topic discussed by a Dartmouth group in the Aug. 8, 2017, issue of JAMA.

In general, younger respondents to my (admittedly unscientific) informal survey tended to be less receptive to being recorded. “I do not allow recordings by patients because I can’t control how they may be used later and it’s just creepy,” wrote one. “It just seems a strange way to begin a trusting, transparent patient/doctor relationship … this is not Instagram.”

“I will sometimes let them take a photo of a specimen or a defect but I don’t allow recording,” wrote another. “Same reasons; creepy and out of my control. I worry about it happening surreptitiously, but what can you do?”

You can proactively prohibit all office recordings by posting a “no recording” sign in your waiting room in the name of confidentiality and privacy. Should a patient initiate a covert recording anyway, you have the option of terminating the visit with a warning that a repeat attempt will result in discharge. If you practice in one of the 39 one-party states, the recording would still be admissible, but your notice gives your attorney an argument – specifically, that the patient made the recording after being expressly directed not to do so – if anyone ever tries to use the recording against you, or without your permission.

Older, more experienced practitioners in the survey tended to be more sanguine about recordings. “I have allowed patients to record all or parts of the visit,” wrote one. “I even allowed a patient to film a [liposuction] procedure. My decision … was that the patient might think I had something to hide, which I [did not].”

Another reported, “I have no problem with patients or family recording office visits or procedures. When someone is recording a procedure, I have no problem ignoring them.”

“We don’t have anything to hide, after all,” affirmed another. “In the era of telemedicine, many things can be recorded, even without permission.”

Several other veteran practitioners summarized my own philosophy on the subject: Patients have a right to record visits in my state (New Jersey), whether I like it or not, so I simply assume I’m being recorded during every visit, and conduct myself accordingly.

Risk managers and malpractice carriers are divided on recordings. At one neurology clinic in Arizona, patients are routinely offered videos of their visits, and clinicians who participate in these recordings receive a 10% reduction in the cost of their medical defense and extra liability coverage. There are clear advantages to having a permanent record of a doctor’s professional opinion. Other carriers are not as supportive, discouraging their insureds from allowing recordings to be made.

In the end, like it or not, recordings are here to stay, and the omnipresence of modern communications devices such as smartphones, tablets, etc., will only increase their prevalence. My advice: Familiarize yourself with the laws in your state, and never say anything during an office visit that you would not stand behind, if it ever turns out to have been recorded.