Federal Practitioner

VIENNA – Prescription drugs designed to boost cognition in neurodevelopmental disorders do not increase overall cognitive performance in healthy individuals – and may even reduce productivity, new research suggests.

In a randomized controlled trial, 40 healthy adults were given the attention-deficit/hyperactivity disorder (ADHD) treatments methylphenidate or dexamphetamine or the wakefulness-promoting drug modafinil vs. placebo.

While receiving the so-called “smart drugs,” participants spent more time and made more moves more quickly while solving each problem on a complex cognitive task than when given the placebo. But with no significant improvement in overall performance, all drugs were associated with a significant reduction in efficiency.

The findings “reinforce the idea that, while the drugs administered were motivational, the resulting increase in effort came at a cost in the loss of productivity,” said study presenter David Coghill, MD, PhD, chair of developmental mental health, the University of Melbourne.

This was especially true for individuals who scored high when receiving placebo, “who ended up producing below average productivity when on the drugs,” he noted.

“Overall, these drugs don’t increase the performance. Instead, they cause a regression to the mean, and appear to have a more negative effect on those who performed best at baseline,” Dr. Coghill added.

He presented the findings at the 35th European College of Neuropsychopharmacology (ECNP) Congress.
 

Past evidence ambiguous

Dr. Coghill noted that prescription-only stimulant drugs are increasingly used by employees and students as “smart drugs” to enhance workplace or academic productivity.

He conducted the study with colleagues from the department of economics at his institution, because of “their interest in people using cognitive enhancers within the financial industry, in the hope that that would increase their productivity in what is a very competitive industry on the floor of the trading rooms.”

However, while “there’s a subjective belief” that these drugs are effective as cognitive enhancers, the evidence to actually demonstrate that in healthy individuals “is, at best, ambiguous,” he told meeting attendees.

Improvements in cognitive capacities, such as working memory and improved planning, are most evident in clinical populations such as those with ADHD, which could be due to a “ceiling effect” of the cognitive tasks in healthy individuals, Dr. Coghill noted.

To investigate further, the researchers conducted a randomized, double-blinded trial of standard adult doses of methylphenidate (30 mg), dexamphetamine (15 mg), and modafinil (200 mg) vs. placebo. The healthy participants (n = 40), all of whom were aged 18-35 years, crossed to each of the other treatment groups over the course of four intervention sessions.

All were asked to solve eight instances of the knapsack task, the aim of which is to place theoretical objects in a knapsack to achieve the maximum value within a certain weight limit.

“This looks very simple but as the number of items increases, it becomes incredibly complex to compute, and actually is not computable using standard approaches. You have to deal with trial and error,” Dr. Coghill said.

The participants also completed several CANTAB cognitive tasks.

‘Surprising’ findings

Results showed that, overall, the drugs did not have a significant effect on task performance (slope = –0.16; P = .011).

Moreover, the drugs, both individually and collectively, had a significant negative effect on the value attained during any one attempt at the knapsack task (slope = –0.003; P = .02), an effect that extended “across the whole range” of task complexity, Dr. Coghill reported.

He went on to show that “participants actually looked as if they were working harder” when they took the three active drugs than when they were given a placebo. They also “spent more time solving each problem,” he added.

When taking the active drugs, participants made more moves during each task than when taking placebo, and made their moves more quickly.

“So these medications increased motivation,” Dr. Coghill said. “If you were sitting [and] watching this person, you would think that they were working harder.”

Yet their productivity, defined as the average gain in value per move on the knapsack task, was lower. Regression analysis identified a “significant and sizable drop in productivity” vs. placebo, Dr. Coghill noted.

This was the case for methylphenidate (P < .001), dexamphetamine (P < .001), and modafinil (P < .05), “whether you looked at the mean or median performance,” he said.

“Breaking it down a little bit more, when you looked at the individual participant level, you find substantial heterogeneity across participants,” noted Dr. Coghill.

“More than that, we found a significant negative correlation between productivity under methylphenidate compared to productivity under placebo, and this suggests a regression to the mean,” with participants who performed better under placebo performing worse with methylphenidate, he explained.

While the relationship was “exactly the same with modafinil,” it was not found with dexamphetamine, with a strong negative correlation between the productivity effects between dexamphetamine and methylphenidate (slope = –0.29; P < .0001).

“This is surprising because we assume that methylphenidate and dexamphetamine are working in very similar ways,” Dr. Coghill said.
 

Time to rethink, rewind?

Commenting for this article, session chair John F. Cryan, PhD, department of anatomy and neuroscience, University College Cork, Ireland, said that, based on the current data, “we might need to rethink [how] ‘smart’ psychopharmacological agents are.”

Dr. Cryan, chair of the ECNP Scientific Program Committee, added that there may be a need to revisit the difficulty of different types of cognitive tasks used in studies assessing the abilities of cognitive enhancing drugs and to “rewind conventional wisdom” around them.

Also commenting, Andrew Westbrook, PhD, of the department of cognitive linguistics and psychological sciences, Brown University, Providence, R.I., said the results seem “reasonable” and are “consistent with my own perspective.”

However, he told this news organization, “some caveats are warranted,” not least that the context of the task can have an impact on the results it obtains.

“We have hypothesized that pharmacologically-enhanced striatal dopamine signaling can boost a kind of cognitive impulsivity, leading to errors and diminished performance, especially for people who already have high striatal dopamine functioning.”

He added that this impulsivity can also lead to errors “in situations where there are highly likely actions, thoughts, or behaviors” in a task, “which they would have to override to be successful” in performing it.

Dr. Westbrook gave the example of the “Stroop task where you are presented with words presented in some color ink and your job is to name the color of the ink but not read the word.”

If the word “green,” for example, was presented in green ink, “you may have no trouble naming the ink color,” but if it was presented in red ink “then you may impulsively read the word, because that is what we normally do with words. 

“Overriding this kind of habitual action can be particularly slippery business when striatal dopamine signaling is pharmacologically enhanced,” Dr. Westbrook said.

No funding for the study was reported. Dr. Coghill reported relationships with Medice, Novartis, Servier, Takeda/Shire Cambridge University Press, and Oxford University Press.

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

VIENNA – Prescription drugs designed to boost cognition in neurodevelopmental disorders do not increase overall cognitive performance in healthy individuals – and may even reduce productivity, new research suggests.

In a randomized controlled trial, 40 healthy adults were given the attention-deficit/hyperactivity disorder (ADHD) treatments methylphenidate or dexamphetamine or the wakefulness-promoting drug modafinil vs. placebo.

While receiving the so-called “smart drugs,” participants spent more time and made more moves more quickly while solving each problem on a complex cognitive task than when given the placebo. But with no significant improvement in overall performance, all drugs were associated with a significant reduction in efficiency.

The findings “reinforce the idea that, while the drugs administered were motivational, the resulting increase in effort came at a cost in the loss of productivity,” said study presenter David Coghill, MD, PhD, chair of developmental mental health, the University of Melbourne.

This was especially true for individuals who scored high when receiving placebo, “who ended up producing below average productivity when on the drugs,” he noted.

“Overall, these drugs don’t increase the performance. Instead, they cause a regression to the mean, and appear to have a more negative effect on those who performed best at baseline,” Dr. Coghill added.

He presented the findings at the 35th European College of Neuropsychopharmacology (ECNP) Congress.
 

Past evidence ambiguous

Dr. Coghill noted that prescription-only stimulant drugs are increasingly used by employees and students as “smart drugs” to enhance workplace or academic productivity.

He conducted the study with colleagues from the department of economics at his institution, because of “their interest in people using cognitive enhancers within the financial industry, in the hope that that would increase their productivity in what is a very competitive industry on the floor of the trading rooms.”

However, while “there’s a subjective belief” that these drugs are effective as cognitive enhancers, the evidence to actually demonstrate that in healthy individuals “is, at best, ambiguous,” he told meeting attendees.

Improvements in cognitive capacities, such as working memory and improved planning, are most evident in clinical populations such as those with ADHD, which could be due to a “ceiling effect” of the cognitive tasks in healthy individuals, Dr. Coghill noted.

To investigate further, the researchers conducted a randomized, double-blinded trial of standard adult doses of methylphenidate (30 mg), dexamphetamine (15 mg), and modafinil (200 mg) vs. placebo. The healthy participants (n = 40), all of whom were aged 18-35 years, crossed to each of the other treatment groups over the course of four intervention sessions.

All were asked to solve eight instances of the knapsack task, the aim of which is to place theoretical objects in a knapsack to achieve the maximum value within a certain weight limit.

“This looks very simple but as the number of items increases, it becomes incredibly complex to compute, and actually is not computable using standard approaches. You have to deal with trial and error,” Dr. Coghill said.

The participants also completed several CANTAB cognitive tasks.

‘Surprising’ findings

Results showed that, overall, the drugs did not have a significant effect on task performance (slope = –0.16; P = .011).

Moreover, the drugs, both individually and collectively, had a significant negative effect on the value attained during any one attempt at the knapsack task (slope = –0.003; P = .02), an effect that extended “across the whole range” of task complexity, Dr. Coghill reported.

He went on to show that “participants actually looked as if they were working harder” when they took the three active drugs than when they were given a placebo. They also “spent more time solving each problem,” he added.

When taking the active drugs, participants made more moves during each task than when taking placebo, and made their moves more quickly.

“So these medications increased motivation,” Dr. Coghill said. “If you were sitting [and] watching this person, you would think that they were working harder.”

Yet their productivity, defined as the average gain in value per move on the knapsack task, was lower. Regression analysis identified a “significant and sizable drop in productivity” vs. placebo, Dr. Coghill noted.

This was the case for methylphenidate (P < .001), dexamphetamine (P < .001), and modafinil (P < .05), “whether you looked at the mean or median performance,” he said.

“Breaking it down a little bit more, when you looked at the individual participant level, you find substantial heterogeneity across participants,” noted Dr. Coghill.

“More than that, we found a significant negative correlation between productivity under methylphenidate compared to productivity under placebo, and this suggests a regression to the mean,” with participants who performed better under placebo performing worse with methylphenidate, he explained.

While the relationship was “exactly the same with modafinil,” it was not found with dexamphetamine, with a strong negative correlation between the productivity effects between dexamphetamine and methylphenidate (slope = –0.29; P < .0001).

“This is surprising because we assume that methylphenidate and dexamphetamine are working in very similar ways,” Dr. Coghill said.
 

Time to rethink, rewind?

Commenting for this article, session chair John F. Cryan, PhD, department of anatomy and neuroscience, University College Cork, Ireland, said that, based on the current data, “we might need to rethink [how] ‘smart’ psychopharmacological agents are.”

Dr. Cryan, chair of the ECNP Scientific Program Committee, added that there may be a need to revisit the difficulty of different types of cognitive tasks used in studies assessing the abilities of cognitive enhancing drugs and to “rewind conventional wisdom” around them.

Also commenting, Andrew Westbrook, PhD, of the department of cognitive linguistics and psychological sciences, Brown University, Providence, R.I., said the results seem “reasonable” and are “consistent with my own perspective.”

However, he told this news organization, “some caveats are warranted,” not least that the context of the task can have an impact on the results it obtains.

“We have hypothesized that pharmacologically-enhanced striatal dopamine signaling can boost a kind of cognitive impulsivity, leading to errors and diminished performance, especially for people who already have high striatal dopamine functioning.”

He added that this impulsivity can also lead to errors “in situations where there are highly likely actions, thoughts, or behaviors” in a task, “which they would have to override to be successful” in performing it.

Dr. Westbrook gave the example of the “Stroop task where you are presented with words presented in some color ink and your job is to name the color of the ink but not read the word.”

If the word “green,” for example, was presented in green ink, “you may have no trouble naming the ink color,” but if it was presented in red ink “then you may impulsively read the word, because that is what we normally do with words. 

“Overriding this kind of habitual action can be particularly slippery business when striatal dopamine signaling is pharmacologically enhanced,” Dr. Westbrook said.

No funding for the study was reported. Dr. Coghill reported relationships with Medice, Novartis, Servier, Takeda/Shire Cambridge University Press, and Oxford University Press.

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

VIENNA – Prescription drugs designed to boost cognition in neurodevelopmental disorders do not increase overall cognitive performance in healthy individuals – and may even reduce productivity, new research suggests.

In a randomized controlled trial, 40 healthy adults were given the attention-deficit/hyperactivity disorder (ADHD) treatments methylphenidate or dexamphetamine or the wakefulness-promoting drug modafinil vs. placebo.

While receiving the so-called “smart drugs,” participants spent more time and made more moves more quickly while solving each problem on a complex cognitive task than when given the placebo. But with no significant improvement in overall performance, all drugs were associated with a significant reduction in efficiency.

The findings “reinforce the idea that, while the drugs administered were motivational, the resulting increase in effort came at a cost in the loss of productivity,” said study presenter David Coghill, MD, PhD, chair of developmental mental health, the University of Melbourne.

This was especially true for individuals who scored high when receiving placebo, “who ended up producing below average productivity when on the drugs,” he noted.

“Overall, these drugs don’t increase the performance. Instead, they cause a regression to the mean, and appear to have a more negative effect on those who performed best at baseline,” Dr. Coghill added.

He presented the findings at the 35th European College of Neuropsychopharmacology (ECNP) Congress.
 

Past evidence ambiguous

Dr. Coghill noted that prescription-only stimulant drugs are increasingly used by employees and students as “smart drugs” to enhance workplace or academic productivity.

He conducted the study with colleagues from the department of economics at his institution, because of “their interest in people using cognitive enhancers within the financial industry, in the hope that that would increase their productivity in what is a very competitive industry on the floor of the trading rooms.”

However, while “there’s a subjective belief” that these drugs are effective as cognitive enhancers, the evidence to actually demonstrate that in healthy individuals “is, at best, ambiguous,” he told meeting attendees.

Improvements in cognitive capacities, such as working memory and improved planning, are most evident in clinical populations such as those with ADHD, which could be due to a “ceiling effect” of the cognitive tasks in healthy individuals, Dr. Coghill noted.

To investigate further, the researchers conducted a randomized, double-blinded trial of standard adult doses of methylphenidate (30 mg), dexamphetamine (15 mg), and modafinil (200 mg) vs. placebo. The healthy participants (n = 40), all of whom were aged 18-35 years, crossed to each of the other treatment groups over the course of four intervention sessions.

All were asked to solve eight instances of the knapsack task, the aim of which is to place theoretical objects in a knapsack to achieve the maximum value within a certain weight limit.

“This looks very simple but as the number of items increases, it becomes incredibly complex to compute, and actually is not computable using standard approaches. You have to deal with trial and error,” Dr. Coghill said.

The participants also completed several CANTAB cognitive tasks.

‘Surprising’ findings

Results showed that, overall, the drugs did not have a significant effect on task performance (slope = –0.16; P = .011).

Moreover, the drugs, both individually and collectively, had a significant negative effect on the value attained during any one attempt at the knapsack task (slope = –0.003; P = .02), an effect that extended “across the whole range” of task complexity, Dr. Coghill reported.

He went on to show that “participants actually looked as if they were working harder” when they took the three active drugs than when they were given a placebo. They also “spent more time solving each problem,” he added.

When taking the active drugs, participants made more moves during each task than when taking placebo, and made their moves more quickly.

“So these medications increased motivation,” Dr. Coghill said. “If you were sitting [and] watching this person, you would think that they were working harder.”

Yet their productivity, defined as the average gain in value per move on the knapsack task, was lower. Regression analysis identified a “significant and sizable drop in productivity” vs. placebo, Dr. Coghill noted.

This was the case for methylphenidate (P < .001), dexamphetamine (P < .001), and modafinil (P < .05), “whether you looked at the mean or median performance,” he said.

“Breaking it down a little bit more, when you looked at the individual participant level, you find substantial heterogeneity across participants,” noted Dr. Coghill.

“More than that, we found a significant negative correlation between productivity under methylphenidate compared to productivity under placebo, and this suggests a regression to the mean,” with participants who performed better under placebo performing worse with methylphenidate, he explained.

While the relationship was “exactly the same with modafinil,” it was not found with dexamphetamine, with a strong negative correlation between the productivity effects between dexamphetamine and methylphenidate (slope = –0.29; P < .0001).

“This is surprising because we assume that methylphenidate and dexamphetamine are working in very similar ways,” Dr. Coghill said.
 

Time to rethink, rewind?

Commenting for this article, session chair John F. Cryan, PhD, department of anatomy and neuroscience, University College Cork, Ireland, said that, based on the current data, “we might need to rethink [how] ‘smart’ psychopharmacological agents are.”

Dr. Cryan, chair of the ECNP Scientific Program Committee, added that there may be a need to revisit the difficulty of different types of cognitive tasks used in studies assessing the abilities of cognitive enhancing drugs and to “rewind conventional wisdom” around them.

Also commenting, Andrew Westbrook, PhD, of the department of cognitive linguistics and psychological sciences, Brown University, Providence, R.I., said the results seem “reasonable” and are “consistent with my own perspective.”

However, he told this news organization, “some caveats are warranted,” not least that the context of the task can have an impact on the results it obtains.

“We have hypothesized that pharmacologically-enhanced striatal dopamine signaling can boost a kind of cognitive impulsivity, leading to errors and diminished performance, especially for people who already have high striatal dopamine functioning.”

He added that this impulsivity can also lead to errors “in situations where there are highly likely actions, thoughts, or behaviors” in a task, “which they would have to override to be successful” in performing it.

Dr. Westbrook gave the example of the “Stroop task where you are presented with words presented in some color ink and your job is to name the color of the ink but not read the word.”

If the word “green,” for example, was presented in green ink, “you may have no trouble naming the ink color,” but if it was presented in red ink “then you may impulsively read the word, because that is what we normally do with words. 

“Overriding this kind of habitual action can be particularly slippery business when striatal dopamine signaling is pharmacologically enhanced,” Dr. Westbrook said.

No funding for the study was reported. Dr. Coghill reported relationships with Medice, Novartis, Servier, Takeda/Shire Cambridge University Press, and Oxford University Press.

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

Florida is seeing a spike in deadly infections caused by the “flesh-eating” bacteria Vibrio vulnificus following Hurricane Ian. 

At least 4 people have died and 29 have been infected in Lee County after the hurricane, Florida health officials said in a news release. 

Vibrio vulnificus bacteria is found in warm, brackish seawater, according to the Florida Department of Health. Anyone with open wounds or cuts should avoid standing water, floodwater, or seawater in the area, health officials said. 

“Sewage spills in coastal waters, like those caused by Hurricane Ian, may increase bacteria levels,” the department advised in a news release. “People with open wounds, cuts, or scratches can be exposed to Vibrio vulnificus through direct contact with sea water or brackish water … Vibrio vulnificus can also cause disease in those who eat raw or undercooked oysters and shellfish.”

Infection can cause severe illness or death. Symptoms include fever, chills, decreased blood pressure, and blistering skin lesions. The bacteria does not spread person to person.

“If someone is concerned that they may have been exposed to Vibrio vulnificus and are experiencing the above symptoms, they should seek medical attention immediately,” officials said in the statement.  “Individuals with wound infections should also seek care promptly.”

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

Florida is seeing a spike in deadly infections caused by the “flesh-eating” bacteria Vibrio vulnificus following Hurricane Ian. 

At least 4 people have died and 29 have been infected in Lee County after the hurricane, Florida health officials said in a news release. 

Vibrio vulnificus bacteria is found in warm, brackish seawater, according to the Florida Department of Health. Anyone with open wounds or cuts should avoid standing water, floodwater, or seawater in the area, health officials said. 

“Sewage spills in coastal waters, like those caused by Hurricane Ian, may increase bacteria levels,” the department advised in a news release. “People with open wounds, cuts, or scratches can be exposed to Vibrio vulnificus through direct contact with sea water or brackish water … Vibrio vulnificus can also cause disease in those who eat raw or undercooked oysters and shellfish.”

Infection can cause severe illness or death. Symptoms include fever, chills, decreased blood pressure, and blistering skin lesions. The bacteria does not spread person to person.

“If someone is concerned that they may have been exposed to Vibrio vulnificus and are experiencing the above symptoms, they should seek medical attention immediately,” officials said in the statement.  “Individuals with wound infections should also seek care promptly.”

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

Florida is seeing a spike in deadly infections caused by the “flesh-eating” bacteria Vibrio vulnificus following Hurricane Ian. 

At least 4 people have died and 29 have been infected in Lee County after the hurricane, Florida health officials said in a news release. 

Vibrio vulnificus bacteria is found in warm, brackish seawater, according to the Florida Department of Health. Anyone with open wounds or cuts should avoid standing water, floodwater, or seawater in the area, health officials said. 

“Sewage spills in coastal waters, like those caused by Hurricane Ian, may increase bacteria levels,” the department advised in a news release. “People with open wounds, cuts, or scratches can be exposed to Vibrio vulnificus through direct contact with sea water or brackish water … Vibrio vulnificus can also cause disease in those who eat raw or undercooked oysters and shellfish.”

Infection can cause severe illness or death. Symptoms include fever, chills, decreased blood pressure, and blistering skin lesions. The bacteria does not spread person to person.

“If someone is concerned that they may have been exposed to Vibrio vulnificus and are experiencing the above symptoms, they should seek medical attention immediately,” officials said in the statement.  “Individuals with wound infections should also seek care promptly.”

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

MONTREAL – Amid common patient concerns about weight gain in the treatment of hyperthyroidism, findings from a large study suggest the therapy with the most favorable survival rate – radioiodine – is not associated with an increased risk of weight gain or obesity.

“EGRET is the first large study using population-based linked community and hospital data to elucidate the long-term consequences of treatment modalities for hyperthyroidism,” said co-author Kristien Boelaert, MD, PhD, while presenting the research at the American Thyroid Association annual meeting.

“The administration of [radioiodine] for hyperthyroidism is associated with a survival benefit for patients with hyperthyroidism and is not associated with increased risks of becoming obese,” Dr. Boelaert, a professor of endocrinology and consultant endocrinologist with the Institute of Applied Health Research, University of Birmingham, England, told this news organization.

However, “overall, there was a nearly 10% risk of major adverse cardiac events [MACE] in patients with hyperthyroidism regardless of the treatment modality used,” she noted.

Commenting on the findings, Jonathon O. Russell, MD, said the study offers surprising – but encouraging – results.

The discovery that radioiodine shows no increase in weight gain “contradicts numerous previous studies which have consistently demonstrated weight gain following definitive radioiodine,” Dr. Russell told this news organization.

Overall, however, “these findings reinforce our knowledge that definitive treatment of an overactive thyroid leads to a longer life – even if there is some weight gain,” added Dr. Russell, who is chief of the Division of Head and Neck Endocrine Surgery at Johns Hopkins, Baltimore.
 

Hyperthyroidism associated with serious long-term cardiometabolic issues

Hyperthyroidism is associated with serious long-term cardiovascular and metabolic morbidity and mortality, and treatment is therefore essential. However, the swing to hypothyroidism that often occurs afterward commonly results in regaining the weight lost due to the hyperthyroidism, if not more, potentially leading to obesity and its attendant health risks.

To investigate those risks in relation to the three key hyperthyroidism treatments, the authors conducted the EGRET trial. They identified 62,474 patients in the United Kingdom population-based electronic health record database who had newly diagnosed hyperthyroidism and were treated with antithyroid drugs (73.4%), radioiodine (19.5%), or thyroidectomy (7.1%) between April 1997 and December 2015.

Exclusion criteria included those with less than 6 months of antithyroid drugs as the only form of treatment, thyroid cancer, or pregnancy during the first episode.

With a median follow-up of about 8 years, those who were treated with thyroidectomy had a significantly increased risk of gaining weight, compared with the general population (P < .001), and of developing obesity (body mass index > 30 kg/m2; P = .003), while the corresponding increases with antithyroid drugs and radioiodine were not significantly different, compared with the general population over the same period.

In terms of survival, with an average follow-up of about 11 years per person, about 14% of the cohort died, with rates of 14.4% in the antithyroid drug group, 15.8% in the radioiodine group, and 9.2% in the thyroidectomy group.

Mortality rates were further assessed based on an average treatment effects analysis in which the average change was estimated, compared with the index of antithyroid drugs – for instance, if all were treated instead with radioiodine. In that extension of life analysis, those treated with radioiodine could be expected to die, on average, 1.2 years later than those taking antithyroid drugs (P < .001), while those treated with thyroidectomy would be expected to die 0.6 years later, which was not statistically significant.

Using the same average treatment effects analysis, Dr. Boelaert noted, “we found a slightly increased risk of major adverse cardiovascular events following radioiodine, compared with antithyroid drugs; [however], the risk was very small and may not be clinically relevant.”

“Previous data from our and other groups have shown reduced risks of mortality and cardiovascular death following radioiodine-induced hypothyroidism, although this is not confirmed in all studies.”
 

Weight gain after hyperthyroid treatment drives concerns

The findings are important because weight gain associated with hyperthyroidism treatment is no small matter for many patients, even prompting a lack of adherence to therapy for some, despite its importance, Dr. Boelaert noted.

“Since the majority of patients lose weight as a consequence of being hyperthyroid, it can be expected that they will at least regain the lost weight and possibly even have a weight overshoot,” she explained. “Indeed, many patients are reluctant to accept definitive treatment with surgery or radioiodine out of fear of weight gain.”

“This may cause difficulties to some patients who occasionally may even stop taking antithyroid drugs to prevent this weight regain. Such lack of adherence may have dire consequences and is likely a contributing factor to the increased mortality in these patients,” she observed.

In a previous study of 1,373 patients, Dr. Boelaert and colleagues found that men treated for hyperthyroidism gained an average of 8.0 kg (17.6 lb), and women gained an average of 5.5 kg (12.1 lb).

Compared with the background population, men were significantly more likely to gain weight over the study period (odds ratio, 1.7; P < .001) as were women (OR, 1.3; P < .001). Also in that study, radioiodine was associated with greater weight gain (0.6 kg; P < .001), compared with antithyroid drug treatment alone.

Dr. Russell added that even when weight gain does occur, the payoff of having treated the potentially serious state of hyperthyroidism is a highly beneficial trade-off.

Ultimately, “the goal of treating any patient with Graves’ should be to get them to become hypothyroid as quickly as possible,” he said. “Patients have options, and all of these options can be safe in the right situation.”

“It is unrealistic to think that going from a hyperthyroid state to a low thyroid state will not result in weight gain for many patients,” Dr. Russell added. “But the key point is that overall health is better despite this weight gain.”

Dr. Boelaert has disclosed consulting fees paid to the University of Birmingham by Lilly and Eisai. Dr. Russell has reported no relevant financial relationships.

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

MONTREAL – Amid common patient concerns about weight gain in the treatment of hyperthyroidism, findings from a large study suggest the therapy with the most favorable survival rate – radioiodine – is not associated with an increased risk of weight gain or obesity.

“EGRET is the first large study using population-based linked community and hospital data to elucidate the long-term consequences of treatment modalities for hyperthyroidism,” said co-author Kristien Boelaert, MD, PhD, while presenting the research at the American Thyroid Association annual meeting.

“The administration of [radioiodine] for hyperthyroidism is associated with a survival benefit for patients with hyperthyroidism and is not associated with increased risks of becoming obese,” Dr. Boelaert, a professor of endocrinology and consultant endocrinologist with the Institute of Applied Health Research, University of Birmingham, England, told this news organization.

However, “overall, there was a nearly 10% risk of major adverse cardiac events [MACE] in patients with hyperthyroidism regardless of the treatment modality used,” she noted.

Commenting on the findings, Jonathon O. Russell, MD, said the study offers surprising – but encouraging – results.

The discovery that radioiodine shows no increase in weight gain “contradicts numerous previous studies which have consistently demonstrated weight gain following definitive radioiodine,” Dr. Russell told this news organization.

Overall, however, “these findings reinforce our knowledge that definitive treatment of an overactive thyroid leads to a longer life – even if there is some weight gain,” added Dr. Russell, who is chief of the Division of Head and Neck Endocrine Surgery at Johns Hopkins, Baltimore.
 

Hyperthyroidism associated with serious long-term cardiometabolic issues

Hyperthyroidism is associated with serious long-term cardiovascular and metabolic morbidity and mortality, and treatment is therefore essential. However, the swing to hypothyroidism that often occurs afterward commonly results in regaining the weight lost due to the hyperthyroidism, if not more, potentially leading to obesity and its attendant health risks.

To investigate those risks in relation to the three key hyperthyroidism treatments, the authors conducted the EGRET trial. They identified 62,474 patients in the United Kingdom population-based electronic health record database who had newly diagnosed hyperthyroidism and were treated with antithyroid drugs (73.4%), radioiodine (19.5%), or thyroidectomy (7.1%) between April 1997 and December 2015.

Exclusion criteria included those with less than 6 months of antithyroid drugs as the only form of treatment, thyroid cancer, or pregnancy during the first episode.

With a median follow-up of about 8 years, those who were treated with thyroidectomy had a significantly increased risk of gaining weight, compared with the general population (P < .001), and of developing obesity (body mass index > 30 kg/m2; P = .003), while the corresponding increases with antithyroid drugs and radioiodine were not significantly different, compared with the general population over the same period.

In terms of survival, with an average follow-up of about 11 years per person, about 14% of the cohort died, with rates of 14.4% in the antithyroid drug group, 15.8% in the radioiodine group, and 9.2% in the thyroidectomy group.

Mortality rates were further assessed based on an average treatment effects analysis in which the average change was estimated, compared with the index of antithyroid drugs – for instance, if all were treated instead with radioiodine. In that extension of life analysis, those treated with radioiodine could be expected to die, on average, 1.2 years later than those taking antithyroid drugs (P < .001), while those treated with thyroidectomy would be expected to die 0.6 years later, which was not statistically significant.

Using the same average treatment effects analysis, Dr. Boelaert noted, “we found a slightly increased risk of major adverse cardiovascular events following radioiodine, compared with antithyroid drugs; [however], the risk was very small and may not be clinically relevant.”

“Previous data from our and other groups have shown reduced risks of mortality and cardiovascular death following radioiodine-induced hypothyroidism, although this is not confirmed in all studies.”
 

Weight gain after hyperthyroid treatment drives concerns

The findings are important because weight gain associated with hyperthyroidism treatment is no small matter for many patients, even prompting a lack of adherence to therapy for some, despite its importance, Dr. Boelaert noted.

“Since the majority of patients lose weight as a consequence of being hyperthyroid, it can be expected that they will at least regain the lost weight and possibly even have a weight overshoot,” she explained. “Indeed, many patients are reluctant to accept definitive treatment with surgery or radioiodine out of fear of weight gain.”

“This may cause difficulties to some patients who occasionally may even stop taking antithyroid drugs to prevent this weight regain. Such lack of adherence may have dire consequences and is likely a contributing factor to the increased mortality in these patients,” she observed.

In a previous study of 1,373 patients, Dr. Boelaert and colleagues found that men treated for hyperthyroidism gained an average of 8.0 kg (17.6 lb), and women gained an average of 5.5 kg (12.1 lb).

Compared with the background population, men were significantly more likely to gain weight over the study period (odds ratio, 1.7; P < .001) as were women (OR, 1.3; P < .001). Also in that study, radioiodine was associated with greater weight gain (0.6 kg; P < .001), compared with antithyroid drug treatment alone.

Dr. Russell added that even when weight gain does occur, the payoff of having treated the potentially serious state of hyperthyroidism is a highly beneficial trade-off.

Ultimately, “the goal of treating any patient with Graves’ should be to get them to become hypothyroid as quickly as possible,” he said. “Patients have options, and all of these options can be safe in the right situation.”

“It is unrealistic to think that going from a hyperthyroid state to a low thyroid state will not result in weight gain for many patients,” Dr. Russell added. “But the key point is that overall health is better despite this weight gain.”

Dr. Boelaert has disclosed consulting fees paid to the University of Birmingham by Lilly and Eisai. Dr. Russell has reported no relevant financial relationships.

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

MONTREAL – Amid common patient concerns about weight gain in the treatment of hyperthyroidism, findings from a large study suggest the therapy with the most favorable survival rate – radioiodine – is not associated with an increased risk of weight gain or obesity.

“EGRET is the first large study using population-based linked community and hospital data to elucidate the long-term consequences of treatment modalities for hyperthyroidism,” said co-author Kristien Boelaert, MD, PhD, while presenting the research at the American Thyroid Association annual meeting.

“The administration of [radioiodine] for hyperthyroidism is associated with a survival benefit for patients with hyperthyroidism and is not associated with increased risks of becoming obese,” Dr. Boelaert, a professor of endocrinology and consultant endocrinologist with the Institute of Applied Health Research, University of Birmingham, England, told this news organization.

However, “overall, there was a nearly 10% risk of major adverse cardiac events [MACE] in patients with hyperthyroidism regardless of the treatment modality used,” she noted.

Commenting on the findings, Jonathon O. Russell, MD, said the study offers surprising – but encouraging – results.

The discovery that radioiodine shows no increase in weight gain “contradicts numerous previous studies which have consistently demonstrated weight gain following definitive radioiodine,” Dr. Russell told this news organization.

Overall, however, “these findings reinforce our knowledge that definitive treatment of an overactive thyroid leads to a longer life – even if there is some weight gain,” added Dr. Russell, who is chief of the Division of Head and Neck Endocrine Surgery at Johns Hopkins, Baltimore.
 

Hyperthyroidism associated with serious long-term cardiometabolic issues

Hyperthyroidism is associated with serious long-term cardiovascular and metabolic morbidity and mortality, and treatment is therefore essential. However, the swing to hypothyroidism that often occurs afterward commonly results in regaining the weight lost due to the hyperthyroidism, if not more, potentially leading to obesity and its attendant health risks.

To investigate those risks in relation to the three key hyperthyroidism treatments, the authors conducted the EGRET trial. They identified 62,474 patients in the United Kingdom population-based electronic health record database who had newly diagnosed hyperthyroidism and were treated with antithyroid drugs (73.4%), radioiodine (19.5%), or thyroidectomy (7.1%) between April 1997 and December 2015.

Exclusion criteria included those with less than 6 months of antithyroid drugs as the only form of treatment, thyroid cancer, or pregnancy during the first episode.

With a median follow-up of about 8 years, those who were treated with thyroidectomy had a significantly increased risk of gaining weight, compared with the general population (P < .001), and of developing obesity (body mass index > 30 kg/m2; P = .003), while the corresponding increases with antithyroid drugs and radioiodine were not significantly different, compared with the general population over the same period.

In terms of survival, with an average follow-up of about 11 years per person, about 14% of the cohort died, with rates of 14.4% in the antithyroid drug group, 15.8% in the radioiodine group, and 9.2% in the thyroidectomy group.

Mortality rates were further assessed based on an average treatment effects analysis in which the average change was estimated, compared with the index of antithyroid drugs – for instance, if all were treated instead with radioiodine. In that extension of life analysis, those treated with radioiodine could be expected to die, on average, 1.2 years later than those taking antithyroid drugs (P < .001), while those treated with thyroidectomy would be expected to die 0.6 years later, which was not statistically significant.

Using the same average treatment effects analysis, Dr. Boelaert noted, “we found a slightly increased risk of major adverse cardiovascular events following radioiodine, compared with antithyroid drugs; [however], the risk was very small and may not be clinically relevant.”

“Previous data from our and other groups have shown reduced risks of mortality and cardiovascular death following radioiodine-induced hypothyroidism, although this is not confirmed in all studies.”
 

Weight gain after hyperthyroid treatment drives concerns

The findings are important because weight gain associated with hyperthyroidism treatment is no small matter for many patients, even prompting a lack of adherence to therapy for some, despite its importance, Dr. Boelaert noted.

“Since the majority of patients lose weight as a consequence of being hyperthyroid, it can be expected that they will at least regain the lost weight and possibly even have a weight overshoot,” she explained. “Indeed, many patients are reluctant to accept definitive treatment with surgery or radioiodine out of fear of weight gain.”

“This may cause difficulties to some patients who occasionally may even stop taking antithyroid drugs to prevent this weight regain. Such lack of adherence may have dire consequences and is likely a contributing factor to the increased mortality in these patients,” she observed.

In a previous study of 1,373 patients, Dr. Boelaert and colleagues found that men treated for hyperthyroidism gained an average of 8.0 kg (17.6 lb), and women gained an average of 5.5 kg (12.1 lb).

Compared with the background population, men were significantly more likely to gain weight over the study period (odds ratio, 1.7; P < .001) as were women (OR, 1.3; P < .001). Also in that study, radioiodine was associated with greater weight gain (0.6 kg; P < .001), compared with antithyroid drug treatment alone.

Dr. Russell added that even when weight gain does occur, the payoff of having treated the potentially serious state of hyperthyroidism is a highly beneficial trade-off.

Ultimately, “the goal of treating any patient with Graves’ should be to get them to become hypothyroid as quickly as possible,” he said. “Patients have options, and all of these options can be safe in the right situation.”

“It is unrealistic to think that going from a hyperthyroid state to a low thyroid state will not result in weight gain for many patients,” Dr. Russell added. “But the key point is that overall health is better despite this weight gain.”

Dr. Boelaert has disclosed consulting fees paid to the University of Birmingham by Lilly and Eisai. Dr. Russell has reported no relevant financial relationships.

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

WASHINGTON – In the 25 years since the United States first launched its universal vaccinations program to protect children against chickenpox (varicella), the program has seen dramatic results, a data analysis indicates.

Results from 1995 – when universal vaccinations began – through 2019 were presented an annual scientific meeting on infectious diseases by Mona Marin, MD, a medical epidemiologist at the Centers for Disease Control and Prevention. Researchers analyzed published data and surveillance data reported to the CDC.
 

Deaths in under-20 group all but eliminated

It’s now rare for children to be hospitalized with chickenpox, and deaths from the infection in people younger than 20 have largely been eliminated. But benefits extend even further.

Immunocompromised people or pregnant women and infants too young to be vaccinated also benefited from the children’s immunizations.

Each year, about 3.8 million cases, 10,500 hospitalizations, and 100 deaths from chickenpox are prevented in the United States thanks to the vaccination program, Dr. Marin said.

Over 25 years, 91 million cases, 238,000 hospitalizations, and 1,933 – 2,446 deaths have been prevented.

However, chickenpox is still widespread in most of the world.
 

U.S. first with universal program

The disease was thought to be of little consequence, Dr. Marin said, until the mid-1950s after the first cases of fatal varicella in immunocompromised children revealed the virus’ lethal potential.

The United States was the first country to introduce a universal vaccination program, Dr. Marin said. At the time, it was a one-dose vaccine. Within the first 10 years of the one-dose program, declines in chickenpox cases, hospitalization, and death rates went from 71% to 90% in comparison with previous years. But health care leaders wanted to close the remaining gap and target transmission in schools.

“It was a burden the United States considered unacceptable,” Dr. Marin said.

The leaders had seen the control of measles and polio and wanted the same for chickenpox.
 

Two-dose vaccines started in 2007

In 2007, the current two-dose policy was introduced. Administration of the first dose is recommended at age 12–15 months, and the second at age 4–6 years. Vaccination is required before the children enter kindergarten.

Coverage was high – at least 90% – the study authors reported; the two-dose program further reduced the number, size, and duration of outbreaks. Over the 25 years, the proportion of outbreaks with fewer than 10 cases increased from 28% to 73%.

By 2019, incidence had dropped by 97%, hospitalizations were down by 94%, and deaths had dropped by 97%.

The biggest decline was seen in those younger than 20, who were born during the vaccination program. That group saw declines of 97% to 99% in cases, hospitalizations, and incidence compared with rates before vaccinations.

Dr. Marin says one dose of the vaccine is moderately effective in preventing all varicella (82%) and is highly effective in preventing severe varicella (more than 97%).

“The second dose adds 10% or more improved protection against all varicella,” she said.

But there have been gains beyond medical advances.

Researchers calculated the economic benefit and found a net savings of $23 billion in medical costs (which also factored in lost wages from parents staying home to care for sick children).
 

Jaw-dropping results

Jeanne Marrazzo, MD, director of the division of infectious diseases at the University of Alabama at Birmingham, said in an interview that “as someone who is not a vaccinologist, the declines in deaths, let alone hospitalizations, were jaw-dropping. I hadn’t really seen a synthesis of the impact of one and two doses.”

She said the declines in zoster among young people were interesting. The big question, she said, is what impact this may have for shingles infections in middle-aged adults over time, since chickenpox and shingles are caused by the same virus.

Dr. Marrazzo also noted the economic savings calculations.

“It’s such a cheap intervention. It’s one of the best examples of how a simple vaccine can affect a cascade of events that are a result of chronic viral infection,” she said.

There are also messages for the current debates over COVID-19 vaccinations.

“For me, it is further evidence of the profound population-level effect safe vaccines can have,” Dr. Marrazzo said.

The authors and Dr. Marrazzo report no relevant financial relationships.

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

WASHINGTON – In the 25 years since the United States first launched its universal vaccinations program to protect children against chickenpox (varicella), the program has seen dramatic results, a data analysis indicates.

Results from 1995 – when universal vaccinations began – through 2019 were presented an annual scientific meeting on infectious diseases by Mona Marin, MD, a medical epidemiologist at the Centers for Disease Control and Prevention. Researchers analyzed published data and surveillance data reported to the CDC.
 

Deaths in under-20 group all but eliminated

It’s now rare for children to be hospitalized with chickenpox, and deaths from the infection in people younger than 20 have largely been eliminated. But benefits extend even further.

Immunocompromised people or pregnant women and infants too young to be vaccinated also benefited from the children’s immunizations.

Each year, about 3.8 million cases, 10,500 hospitalizations, and 100 deaths from chickenpox are prevented in the United States thanks to the vaccination program, Dr. Marin said.

Over 25 years, 91 million cases, 238,000 hospitalizations, and 1,933 – 2,446 deaths have been prevented.

However, chickenpox is still widespread in most of the world.
 

U.S. first with universal program

The disease was thought to be of little consequence, Dr. Marin said, until the mid-1950s after the first cases of fatal varicella in immunocompromised children revealed the virus’ lethal potential.

The United States was the first country to introduce a universal vaccination program, Dr. Marin said. At the time, it was a one-dose vaccine. Within the first 10 years of the one-dose program, declines in chickenpox cases, hospitalization, and death rates went from 71% to 90% in comparison with previous years. But health care leaders wanted to close the remaining gap and target transmission in schools.

“It was a burden the United States considered unacceptable,” Dr. Marin said.

The leaders had seen the control of measles and polio and wanted the same for chickenpox.
 

Two-dose vaccines started in 2007

In 2007, the current two-dose policy was introduced. Administration of the first dose is recommended at age 12–15 months, and the second at age 4–6 years. Vaccination is required before the children enter kindergarten.

Coverage was high – at least 90% – the study authors reported; the two-dose program further reduced the number, size, and duration of outbreaks. Over the 25 years, the proportion of outbreaks with fewer than 10 cases increased from 28% to 73%.

By 2019, incidence had dropped by 97%, hospitalizations were down by 94%, and deaths had dropped by 97%.

The biggest decline was seen in those younger than 20, who were born during the vaccination program. That group saw declines of 97% to 99% in cases, hospitalizations, and incidence compared with rates before vaccinations.

Dr. Marin says one dose of the vaccine is moderately effective in preventing all varicella (82%) and is highly effective in preventing severe varicella (more than 97%).

“The second dose adds 10% or more improved protection against all varicella,” she said.

But there have been gains beyond medical advances.

Researchers calculated the economic benefit and found a net savings of $23 billion in medical costs (which also factored in lost wages from parents staying home to care for sick children).
 

Jaw-dropping results

Jeanne Marrazzo, MD, director of the division of infectious diseases at the University of Alabama at Birmingham, said in an interview that “as someone who is not a vaccinologist, the declines in deaths, let alone hospitalizations, were jaw-dropping. I hadn’t really seen a synthesis of the impact of one and two doses.”

She said the declines in zoster among young people were interesting. The big question, she said, is what impact this may have for shingles infections in middle-aged adults over time, since chickenpox and shingles are caused by the same virus.

Dr. Marrazzo also noted the economic savings calculations.

“It’s such a cheap intervention. It’s one of the best examples of how a simple vaccine can affect a cascade of events that are a result of chronic viral infection,” she said.

There are also messages for the current debates over COVID-19 vaccinations.

“For me, it is further evidence of the profound population-level effect safe vaccines can have,” Dr. Marrazzo said.

The authors and Dr. Marrazzo report no relevant financial relationships.

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

WASHINGTON – In the 25 years since the United States first launched its universal vaccinations program to protect children against chickenpox (varicella), the program has seen dramatic results, a data analysis indicates.

Results from 1995 – when universal vaccinations began – through 2019 were presented an annual scientific meeting on infectious diseases by Mona Marin, MD, a medical epidemiologist at the Centers for Disease Control and Prevention. Researchers analyzed published data and surveillance data reported to the CDC.
 

Deaths in under-20 group all but eliminated

It’s now rare for children to be hospitalized with chickenpox, and deaths from the infection in people younger than 20 have largely been eliminated. But benefits extend even further.

Immunocompromised people or pregnant women and infants too young to be vaccinated also benefited from the children’s immunizations.

Each year, about 3.8 million cases, 10,500 hospitalizations, and 100 deaths from chickenpox are prevented in the United States thanks to the vaccination program, Dr. Marin said.

Over 25 years, 91 million cases, 238,000 hospitalizations, and 1,933 – 2,446 deaths have been prevented.

However, chickenpox is still widespread in most of the world.
 

U.S. first with universal program

The disease was thought to be of little consequence, Dr. Marin said, until the mid-1950s after the first cases of fatal varicella in immunocompromised children revealed the virus’ lethal potential.

The United States was the first country to introduce a universal vaccination program, Dr. Marin said. At the time, it was a one-dose vaccine. Within the first 10 years of the one-dose program, declines in chickenpox cases, hospitalization, and death rates went from 71% to 90% in comparison with previous years. But health care leaders wanted to close the remaining gap and target transmission in schools.

“It was a burden the United States considered unacceptable,” Dr. Marin said.

The leaders had seen the control of measles and polio and wanted the same for chickenpox.
 

Two-dose vaccines started in 2007

In 2007, the current two-dose policy was introduced. Administration of the first dose is recommended at age 12–15 months, and the second at age 4–6 years. Vaccination is required before the children enter kindergarten.

Coverage was high – at least 90% – the study authors reported; the two-dose program further reduced the number, size, and duration of outbreaks. Over the 25 years, the proportion of outbreaks with fewer than 10 cases increased from 28% to 73%.

By 2019, incidence had dropped by 97%, hospitalizations were down by 94%, and deaths had dropped by 97%.

The biggest decline was seen in those younger than 20, who were born during the vaccination program. That group saw declines of 97% to 99% in cases, hospitalizations, and incidence compared with rates before vaccinations.

Dr. Marin says one dose of the vaccine is moderately effective in preventing all varicella (82%) and is highly effective in preventing severe varicella (more than 97%).

“The second dose adds 10% or more improved protection against all varicella,” she said.

But there have been gains beyond medical advances.

Researchers calculated the economic benefit and found a net savings of $23 billion in medical costs (which also factored in lost wages from parents staying home to care for sick children).
 

Jaw-dropping results

Jeanne Marrazzo, MD, director of the division of infectious diseases at the University of Alabama at Birmingham, said in an interview that “as someone who is not a vaccinologist, the declines in deaths, let alone hospitalizations, were jaw-dropping. I hadn’t really seen a synthesis of the impact of one and two doses.”

She said the declines in zoster among young people were interesting. The big question, she said, is what impact this may have for shingles infections in middle-aged adults over time, since chickenpox and shingles are caused by the same virus.

Dr. Marrazzo also noted the economic savings calculations.

“It’s such a cheap intervention. It’s one of the best examples of how a simple vaccine can affect a cascade of events that are a result of chronic viral infection,” she said.

There are also messages for the current debates over COVID-19 vaccinations.

“For me, it is further evidence of the profound population-level effect safe vaccines can have,” Dr. Marrazzo said.

The authors and Dr. Marrazzo report no relevant financial relationships.

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

In the United States and around the globe, chronic obstructive pulmonary disease (COPD) remains one of the leading causes of death. In addition to new diagnostic guidelines, the Global Initiative for Chronic Obstructive Lung Disease 2022 Report, or GOLD report, sets forth recommendations for management and treatment. In 2022, a total of 160 new references were added to the previous year’s GOLD report.

According to the GOLD report, initial management of COPD should aim at reducing exposure to risk factors such as smoking or other chemical exposures. In addition to medications, stable COPD patients should be evaluated for inhaler technique, adherence to prescribed therapies, smoking status, and continued exposure to other risk factors. Also, physical activity should be advised and pulmonary rehabilitation should be considered. Spirometry should be performed annually.

These guidelines offer very practical advice but often are difficult to implement in clinical practice. Everyone knows smoking is harmful and quitting provides huge health benefits, not only regarding COPD. However, nicotine is very addictive, and most smokers cannot just quit. Many need smoking cessation aids and counseling. Additionally, some smokers just don’t want to quit. Regarding workplace exposures, it often is not easy for someone just to change their job. Many are afraid to speak because they are afraid of losing their jobs. Everyone, not just patients with COPD, can benefit from increased physical activity, and all doctors know how difficult it is to motivate patients to do this.

The decision to initiate medications should be based on an individual patient’s symptoms and risk of exacerbations. In general, long-acting bronchodilators, including long-acting beta agonists (LABA) and long-acting muscarinic antagonists (LAMA), are preferred except when immediate relief of dyspnea is needed, and then short-acting bronchodilators should be used. Either a single long-acting or dual long-acting bronchodilator can be initiated. If a patient continues to have dyspnea on a single long-acting bronchodilator, treatment should be switched to a dual therapy.

In general, inhaled corticosteroids (ICS) are not recommended for stable COPD patients. If a patient has exacerbations despite appropriate treatment with LABAs, an ICS may be added to the LABA, the GOLD guidelines say. Oral corticosteroids are not recommended for long-term use. PDE4 inhibitors should be considered in patents with severe to very severe airflow obstruction, chronic bronchitis, and exacerbations. Macrolide antibiotics, especially azithromycin, can be considered in acute exacerbations. There is no evidence to support the use of antitussives and mucolytics are advised in only certain patients. Inhaled bronchodilators are advised over oral ones and theophylline is recommended when long-acting bronchodilators are unavailable or unaffordable.

In clinical practice, I see many patients treated based on symptomatology with spirometry testing not being done. This may help control many symptoms, but unless my patient has an accurate diagnosis, I won’t know if my patient is receiving the correct treatment.

It is important to keep in mind that COPD is a progressive disease and without appropriate treatment and monitoring, it will just get worse, and this is most likely to be irreversible.

Medications and treatment goals for patients with COPD

Patients with alpha-1 antitrypsin deficiency may benefit from the addition of alpha-1 antitrypsin augmentation therapy, the new guidelines say. In patients with severe disease experiencing dyspnea, oral and parental opioids can be considered. Medications that are used to treat primary pulmonary hypertension are not advised to treat pulmonary hypertension secondary to COPD.

The treatment goals of COPD should be to decrease severity of symptoms, reduce the occurrence of exacerbations, and improve exercise tolerance. Peripheral eosinophil counts can be used to guide the use of ICS to prevent exacerbations. However, the best predictor of exacerbations is previous exacerbations. Frequent exacerbations are defined as two or more annually. Additionally, deteriorating airflow is correlated with increased risk of exacerbations, hospitalizations, and death. Forced expiratory volume in 1 second (FEV₁) alone lacks precision to predict exacerbations or death.

Vaccines and pulmonary rehabilitation recommended

The Centers for Disease Control and Prevention and World Health Organization recommend several vaccines for stable patients with COPD. Influenza vaccine was shown to reduce serious complications in COPD patients. Pneumococcal vaccines (PCV13 and PPSV23) reduced the likelihood of COPD exacerbations. The COVID-19 vaccine also has been effective at reducing hospitalizations, in particular ICU admissions, and death in patients with COPD. The CDC also recommends TdaP and Zoster vaccines.

An acute exacerbation of COPD occurs when a patient experiences worsening of respiratory symptoms that requires additional treatment, according to the updated GOLD guidelines. They are usually associated with increased airway inflammation, mucous productions, and trapping of gases. They are often triggered by viral infections, but bacterial and environment factors play a role as well. Less commonly, fungi such as Aspergillus can be observed as well. COPD exacerbations contribute to overall progression of the disease.

In patients with hypoxemia, supplemental oxygen should be titrated to a target O₂ saturation of 88%-92%. It is important to follow blood gases to be sure adequate oxygenation is taking place while at the same time avoiding carbon dioxide retention and/or worsening acidosis. In patients with severe exacerbations whose dyspnea does not respond to initial emergency therapy, ICU admission is warranted. Other factors indicating the need for ICU admission include mental status changes, persistent or worsening hypoxemia, severe or worsening respiratory acidosis, the need for mechanical ventilation, and hemodynamic instability. Following an acute exacerbation, steps to prevent further exacerbations should be initiated.

Systemic glucocorticoids are indicated during acute exacerbations. They have been shown to hasten recovery time and improve functioning of the lungs as well as oxygenation. It is recommended to give prednisone 40 mg per day for 5 days. Antibiotics should be used in exacerbations if patients have dyspnea, sputum production, and purulence of the sputum or require mechanical ventilation. The choice of which antibiotic to use should be based on local bacterial resistance.

Pulmonary rehabilitation is an important component of COPD management. It incorporates exercise, education, and self-management aimed to change behavior and improve conditioning. The benefits of rehab have been shown to be considerable. The optimal length is 6-8 weeks. Palliative and end-of-life care are also very important factors to consider when treating COPD patients, according to the GOLD guidelines.

COPD is a very common disease and cause of mortality seen by family physicians. The GOLD report is an extensive document providing very clear guidelines and evidence to support these guidelines in every level of the treatment of COPD patients. As primary care doctors, we are often the first to treat patients with COPD and it is important to know the latest guidelines.

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at fpnews@mdedge.com.

In the United States and around the globe, chronic obstructive pulmonary disease (COPD) remains one of the leading causes of death. In addition to new diagnostic guidelines, the Global Initiative for Chronic Obstructive Lung Disease 2022 Report, or GOLD report, sets forth recommendations for management and treatment. In 2022, a total of 160 new references were added to the previous year’s GOLD report.

According to the GOLD report, initial management of COPD should aim at reducing exposure to risk factors such as smoking or other chemical exposures. In addition to medications, stable COPD patients should be evaluated for inhaler technique, adherence to prescribed therapies, smoking status, and continued exposure to other risk factors. Also, physical activity should be advised and pulmonary rehabilitation should be considered. Spirometry should be performed annually.

These guidelines offer very practical advice but often are difficult to implement in clinical practice. Everyone knows smoking is harmful and quitting provides huge health benefits, not only regarding COPD. However, nicotine is very addictive, and most smokers cannot just quit. Many need smoking cessation aids and counseling. Additionally, some smokers just don’t want to quit. Regarding workplace exposures, it often is not easy for someone just to change their job. Many are afraid to speak because they are afraid of losing their jobs. Everyone, not just patients with COPD, can benefit from increased physical activity, and all doctors know how difficult it is to motivate patients to do this.

The decision to initiate medications should be based on an individual patient’s symptoms and risk of exacerbations. In general, long-acting bronchodilators, including long-acting beta agonists (LABA) and long-acting muscarinic antagonists (LAMA), are preferred except when immediate relief of dyspnea is needed, and then short-acting bronchodilators should be used. Either a single long-acting or dual long-acting bronchodilator can be initiated. If a patient continues to have dyspnea on a single long-acting bronchodilator, treatment should be switched to a dual therapy.

In general, inhaled corticosteroids (ICS) are not recommended for stable COPD patients. If a patient has exacerbations despite appropriate treatment with LABAs, an ICS may be added to the LABA, the GOLD guidelines say. Oral corticosteroids are not recommended for long-term use. PDE4 inhibitors should be considered in patents with severe to very severe airflow obstruction, chronic bronchitis, and exacerbations. Macrolide antibiotics, especially azithromycin, can be considered in acute exacerbations. There is no evidence to support the use of antitussives and mucolytics are advised in only certain patients. Inhaled bronchodilators are advised over oral ones and theophylline is recommended when long-acting bronchodilators are unavailable or unaffordable.

In clinical practice, I see many patients treated based on symptomatology with spirometry testing not being done. This may help control many symptoms, but unless my patient has an accurate diagnosis, I won’t know if my patient is receiving the correct treatment.

It is important to keep in mind that COPD is a progressive disease and without appropriate treatment and monitoring, it will just get worse, and this is most likely to be irreversible.

Medications and treatment goals for patients with COPD

Patients with alpha-1 antitrypsin deficiency may benefit from the addition of alpha-1 antitrypsin augmentation therapy, the new guidelines say. In patients with severe disease experiencing dyspnea, oral and parental opioids can be considered. Medications that are used to treat primary pulmonary hypertension are not advised to treat pulmonary hypertension secondary to COPD.

The treatment goals of COPD should be to decrease severity of symptoms, reduce the occurrence of exacerbations, and improve exercise tolerance. Peripheral eosinophil counts can be used to guide the use of ICS to prevent exacerbations. However, the best predictor of exacerbations is previous exacerbations. Frequent exacerbations are defined as two or more annually. Additionally, deteriorating airflow is correlated with increased risk of exacerbations, hospitalizations, and death. Forced expiratory volume in 1 second (FEV₁) alone lacks precision to predict exacerbations or death.

Vaccines and pulmonary rehabilitation recommended

The Centers for Disease Control and Prevention and World Health Organization recommend several vaccines for stable patients with COPD. Influenza vaccine was shown to reduce serious complications in COPD patients. Pneumococcal vaccines (PCV13 and PPSV23) reduced the likelihood of COPD exacerbations. The COVID-19 vaccine also has been effective at reducing hospitalizations, in particular ICU admissions, and death in patients with COPD. The CDC also recommends TdaP and Zoster vaccines.

An acute exacerbation of COPD occurs when a patient experiences worsening of respiratory symptoms that requires additional treatment, according to the updated GOLD guidelines. They are usually associated with increased airway inflammation, mucous productions, and trapping of gases. They are often triggered by viral infections, but bacterial and environment factors play a role as well. Less commonly, fungi such as Aspergillus can be observed as well. COPD exacerbations contribute to overall progression of the disease.

In patients with hypoxemia, supplemental oxygen should be titrated to a target O₂ saturation of 88%-92%. It is important to follow blood gases to be sure adequate oxygenation is taking place while at the same time avoiding carbon dioxide retention and/or worsening acidosis. In patients with severe exacerbations whose dyspnea does not respond to initial emergency therapy, ICU admission is warranted. Other factors indicating the need for ICU admission include mental status changes, persistent or worsening hypoxemia, severe or worsening respiratory acidosis, the need for mechanical ventilation, and hemodynamic instability. Following an acute exacerbation, steps to prevent further exacerbations should be initiated.

Systemic glucocorticoids are indicated during acute exacerbations. They have been shown to hasten recovery time and improve functioning of the lungs as well as oxygenation. It is recommended to give prednisone 40 mg per day for 5 days. Antibiotics should be used in exacerbations if patients have dyspnea, sputum production, and purulence of the sputum or require mechanical ventilation. The choice of which antibiotic to use should be based on local bacterial resistance.

Pulmonary rehabilitation is an important component of COPD management. It incorporates exercise, education, and self-management aimed to change behavior and improve conditioning. The benefits of rehab have been shown to be considerable. The optimal length is 6-8 weeks. Palliative and end-of-life care are also very important factors to consider when treating COPD patients, according to the GOLD guidelines.

COPD is a very common disease and cause of mortality seen by family physicians. The GOLD report is an extensive document providing very clear guidelines and evidence to support these guidelines in every level of the treatment of COPD patients. As primary care doctors, we are often the first to treat patients with COPD and it is important to know the latest guidelines.

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at fpnews@mdedge.com.

In the United States and around the globe, chronic obstructive pulmonary disease (COPD) remains one of the leading causes of death. In addition to new diagnostic guidelines, the Global Initiative for Chronic Obstructive Lung Disease 2022 Report, or GOLD report, sets forth recommendations for management and treatment. In 2022, a total of 160 new references were added to the previous year’s GOLD report.

According to the GOLD report, initial management of COPD should aim at reducing exposure to risk factors such as smoking or other chemical exposures. In addition to medications, stable COPD patients should be evaluated for inhaler technique, adherence to prescribed therapies, smoking status, and continued exposure to other risk factors. Also, physical activity should be advised and pulmonary rehabilitation should be considered. Spirometry should be performed annually.

These guidelines offer very practical advice but often are difficult to implement in clinical practice. Everyone knows smoking is harmful and quitting provides huge health benefits, not only regarding COPD. However, nicotine is very addictive, and most smokers cannot just quit. Many need smoking cessation aids and counseling. Additionally, some smokers just don’t want to quit. Regarding workplace exposures, it often is not easy for someone just to change their job. Many are afraid to speak because they are afraid of losing their jobs. Everyone, not just patients with COPD, can benefit from increased physical activity, and all doctors know how difficult it is to motivate patients to do this.

The decision to initiate medications should be based on an individual patient’s symptoms and risk of exacerbations. In general, long-acting bronchodilators, including long-acting beta agonists (LABA) and long-acting muscarinic antagonists (LAMA), are preferred except when immediate relief of dyspnea is needed, and then short-acting bronchodilators should be used. Either a single long-acting or dual long-acting bronchodilator can be initiated. If a patient continues to have dyspnea on a single long-acting bronchodilator, treatment should be switched to a dual therapy.

In general, inhaled corticosteroids (ICS) are not recommended for stable COPD patients. If a patient has exacerbations despite appropriate treatment with LABAs, an ICS may be added to the LABA, the GOLD guidelines say. Oral corticosteroids are not recommended for long-term use. PDE4 inhibitors should be considered in patents with severe to very severe airflow obstruction, chronic bronchitis, and exacerbations. Macrolide antibiotics, especially azithromycin, can be considered in acute exacerbations. There is no evidence to support the use of antitussives and mucolytics are advised in only certain patients. Inhaled bronchodilators are advised over oral ones and theophylline is recommended when long-acting bronchodilators are unavailable or unaffordable.

In clinical practice, I see many patients treated based on symptomatology with spirometry testing not being done. This may help control many symptoms, but unless my patient has an accurate diagnosis, I won’t know if my patient is receiving the correct treatment.

It is important to keep in mind that COPD is a progressive disease and without appropriate treatment and monitoring, it will just get worse, and this is most likely to be irreversible.

Medications and treatment goals for patients with COPD

Patients with alpha-1 antitrypsin deficiency may benefit from the addition of alpha-1 antitrypsin augmentation therapy, the new guidelines say. In patients with severe disease experiencing dyspnea, oral and parental opioids can be considered. Medications that are used to treat primary pulmonary hypertension are not advised to treat pulmonary hypertension secondary to COPD.

The treatment goals of COPD should be to decrease severity of symptoms, reduce the occurrence of exacerbations, and improve exercise tolerance. Peripheral eosinophil counts can be used to guide the use of ICS to prevent exacerbations. However, the best predictor of exacerbations is previous exacerbations. Frequent exacerbations are defined as two or more annually. Additionally, deteriorating airflow is correlated with increased risk of exacerbations, hospitalizations, and death. Forced expiratory volume in 1 second (FEV₁) alone lacks precision to predict exacerbations or death.

Vaccines and pulmonary rehabilitation recommended

The Centers for Disease Control and Prevention and World Health Organization recommend several vaccines for stable patients with COPD. Influenza vaccine was shown to reduce serious complications in COPD patients. Pneumococcal vaccines (PCV13 and PPSV23) reduced the likelihood of COPD exacerbations. The COVID-19 vaccine also has been effective at reducing hospitalizations, in particular ICU admissions, and death in patients with COPD. The CDC also recommends TdaP and Zoster vaccines.

An acute exacerbation of COPD occurs when a patient experiences worsening of respiratory symptoms that requires additional treatment, according to the updated GOLD guidelines. They are usually associated with increased airway inflammation, mucous productions, and trapping of gases. They are often triggered by viral infections, but bacterial and environment factors play a role as well. Less commonly, fungi such as Aspergillus can be observed as well. COPD exacerbations contribute to overall progression of the disease.

In patients with hypoxemia, supplemental oxygen should be titrated to a target O₂ saturation of 88%-92%. It is important to follow blood gases to be sure adequate oxygenation is taking place while at the same time avoiding carbon dioxide retention and/or worsening acidosis. In patients with severe exacerbations whose dyspnea does not respond to initial emergency therapy, ICU admission is warranted. Other factors indicating the need for ICU admission include mental status changes, persistent or worsening hypoxemia, severe or worsening respiratory acidosis, the need for mechanical ventilation, and hemodynamic instability. Following an acute exacerbation, steps to prevent further exacerbations should be initiated.

Systemic glucocorticoids are indicated during acute exacerbations. They have been shown to hasten recovery time and improve functioning of the lungs as well as oxygenation. It is recommended to give prednisone 40 mg per day for 5 days. Antibiotics should be used in exacerbations if patients have dyspnea, sputum production, and purulence of the sputum or require mechanical ventilation. The choice of which antibiotic to use should be based on local bacterial resistance.

Pulmonary rehabilitation is an important component of COPD management. It incorporates exercise, education, and self-management aimed to change behavior and improve conditioning. The benefits of rehab have been shown to be considerable. The optimal length is 6-8 weeks. Palliative and end-of-life care are also very important factors to consider when treating COPD patients, according to the GOLD guidelines.

COPD is a very common disease and cause of mortality seen by family physicians. The GOLD report is an extensive document providing very clear guidelines and evidence to support these guidelines in every level of the treatment of COPD patients. As primary care doctors, we are often the first to treat patients with COPD and it is important to know the latest guidelines.

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at fpnews@mdedge.com.

People taking methotrexate for immunomodulatory diseases can skip one or two scheduled doses after they get an mRNA-based vaccine booster for COVID-19 and achieve a level of immunity against Omicron variants that’s comparable to people who aren’t immunosuppressed, a small observational cohort study from Germany reported.

Kmatta/Moment/Getty Images

“In general, the data suggest that pausing methotrexate is feasible, and it’s sufficient if the last dose occurs 1-3 days before the vaccination,” study coauthor Gerd Burmester, MD, a senior professor of rheumatology and immunology at the University of Medicine Berlin, told this news organization. “In pragmatic terms: pausing the methotrexate injection just twice after the vaccine is finished and, interestingly, not prior to the vaccination.”

Study results

The study found that serum neutralizing activity against the Omicron BA.1 variant, measured as geometric mean 50% inhibitory serum dilution (ID50s), wasn’t significantly different between the methotrexate and the nonimmunosuppressed groups before getting their mRNA booster (P = .657). However, 4 weeks after getting the booster, the nonimmunosuppressed group had a 68-fold increase in antibody activity versus a 20-fold increase in the methotrexate patients. After 12 weeks, ID50s in both groups decreased by about half (P = .001).

The methotrexate patients who continued therapy after the booster had significantly lower neutralization against Omicron BA.1 at both 4 weeks and 12 weeks than did their counterparts who paused therapy, as well as control patients.

The results were very similar in the same group comparisons of the serum neutralizing activity against the Omicron BA.2 variant at 4 and 12 weeks after booster vaccination.
 

Expert commentary

This study is noteworthy because it used SARS-CoV-2 pseudovirus neutralization assays to evaluate antibody levels, Kevin Winthrop, MD, MPH, professor of infectious disease and public health at Oregon Health & Science University, Portland, who was not involved in the study, said. “A lot of studies don’t look at neutralizing antibody titers, and that’s really what we care about,” Dr. Winthrop said. “What we want are functional antibodies that are doing something, and the only way to do that is to test them.”

The study is “confirmatory” of other studies that call for pausing methotrexate after vaccination, Dr. Winthrop said, including a study he coauthored, and which the German researchers cited, that found pausing methotrexate for a week or so after the influenza vaccination in RA patients improved vaccine immunogenicity. He added that the findings with the early Omicron variants are important because the newest boosters target the later Omicron variants, BA.4 and BA.5.

“The bottom line is that when someone comes in for a COVID-19 vaccination, tell them to be off of methotrexate for 7-10 days,” Dr. Winthrop said. “This is for the booster, but it raises the question: If you go out to three, four, or five vaccinations, does this matter anymore? With the flu vaccine, most people are out to 10 or 15 boosters, and we haven’t seen any significant increase in disease flares.”

The study received funding from Medac, Gilead/Galapagos, and Friends and Sponsors of Berlin Charity. Dr. Burmester reported no relevant disclosures. Dr. Winthrop is a research consultant to Pfizer.

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

People taking methotrexate for immunomodulatory diseases can skip one or two scheduled doses after they get an mRNA-based vaccine booster for COVID-19 and achieve a level of immunity against Omicron variants that’s comparable to people who aren’t immunosuppressed, a small observational cohort study from Germany reported.

Kmatta/Moment/Getty Images

“In general, the data suggest that pausing methotrexate is feasible, and it’s sufficient if the last dose occurs 1-3 days before the vaccination,” study coauthor Gerd Burmester, MD, a senior professor of rheumatology and immunology at the University of Medicine Berlin, told this news organization. “In pragmatic terms: pausing the methotrexate injection just twice after the vaccine is finished and, interestingly, not prior to the vaccination.”

Study results

The study found that serum neutralizing activity against the Omicron BA.1 variant, measured as geometric mean 50% inhibitory serum dilution (ID50s), wasn’t significantly different between the methotrexate and the nonimmunosuppressed groups before getting their mRNA booster (P = .657). However, 4 weeks after getting the booster, the nonimmunosuppressed group had a 68-fold increase in antibody activity versus a 20-fold increase in the methotrexate patients. After 12 weeks, ID50s in both groups decreased by about half (P = .001).

The methotrexate patients who continued therapy after the booster had significantly lower neutralization against Omicron BA.1 at both 4 weeks and 12 weeks than did their counterparts who paused therapy, as well as control patients.

The results were very similar in the same group comparisons of the serum neutralizing activity against the Omicron BA.2 variant at 4 and 12 weeks after booster vaccination.
 

Expert commentary

This study is noteworthy because it used SARS-CoV-2 pseudovirus neutralization assays to evaluate antibody levels, Kevin Winthrop, MD, MPH, professor of infectious disease and public health at Oregon Health & Science University, Portland, who was not involved in the study, said. “A lot of studies don’t look at neutralizing antibody titers, and that’s really what we care about,” Dr. Winthrop said. “What we want are functional antibodies that are doing something, and the only way to do that is to test them.”

The study is “confirmatory” of other studies that call for pausing methotrexate after vaccination, Dr. Winthrop said, including a study he coauthored, and which the German researchers cited, that found pausing methotrexate for a week or so after the influenza vaccination in RA patients improved vaccine immunogenicity. He added that the findings with the early Omicron variants are important because the newest boosters target the later Omicron variants, BA.4 and BA.5.

“The bottom line is that when someone comes in for a COVID-19 vaccination, tell them to be off of methotrexate for 7-10 days,” Dr. Winthrop said. “This is for the booster, but it raises the question: If you go out to three, four, or five vaccinations, does this matter anymore? With the flu vaccine, most people are out to 10 or 15 boosters, and we haven’t seen any significant increase in disease flares.”

The study received funding from Medac, Gilead/Galapagos, and Friends and Sponsors of Berlin Charity. Dr. Burmester reported no relevant disclosures. Dr. Winthrop is a research consultant to Pfizer.

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

People taking methotrexate for immunomodulatory diseases can skip one or two scheduled doses after they get an mRNA-based vaccine booster for COVID-19 and achieve a level of immunity against Omicron variants that’s comparable to people who aren’t immunosuppressed, a small observational cohort study from Germany reported.

Kmatta/Moment/Getty Images

“In general, the data suggest that pausing methotrexate is feasible, and it’s sufficient if the last dose occurs 1-3 days before the vaccination,” study coauthor Gerd Burmester, MD, a senior professor of rheumatology and immunology at the University of Medicine Berlin, told this news organization. “In pragmatic terms: pausing the methotrexate injection just twice after the vaccine is finished and, interestingly, not prior to the vaccination.”

Study results

The study found that serum neutralizing activity against the Omicron BA.1 variant, measured as geometric mean 50% inhibitory serum dilution (ID50s), wasn’t significantly different between the methotrexate and the nonimmunosuppressed groups before getting their mRNA booster (P = .657). However, 4 weeks after getting the booster, the nonimmunosuppressed group had a 68-fold increase in antibody activity versus a 20-fold increase in the methotrexate patients. After 12 weeks, ID50s in both groups decreased by about half (P = .001).

The methotrexate patients who continued therapy after the booster had significantly lower neutralization against Omicron BA.1 at both 4 weeks and 12 weeks than did their counterparts who paused therapy, as well as control patients.

The results were very similar in the same group comparisons of the serum neutralizing activity against the Omicron BA.2 variant at 4 and 12 weeks after booster vaccination.
 

Expert commentary

This study is noteworthy because it used SARS-CoV-2 pseudovirus neutralization assays to evaluate antibody levels, Kevin Winthrop, MD, MPH, professor of infectious disease and public health at Oregon Health & Science University, Portland, who was not involved in the study, said. “A lot of studies don’t look at neutralizing antibody titers, and that’s really what we care about,” Dr. Winthrop said. “What we want are functional antibodies that are doing something, and the only way to do that is to test them.”

The study is “confirmatory” of other studies that call for pausing methotrexate after vaccination, Dr. Winthrop said, including a study he coauthored, and which the German researchers cited, that found pausing methotrexate for a week or so after the influenza vaccination in RA patients improved vaccine immunogenicity. He added that the findings with the early Omicron variants are important because the newest boosters target the later Omicron variants, BA.4 and BA.5.

“The bottom line is that when someone comes in for a COVID-19 vaccination, tell them to be off of methotrexate for 7-10 days,” Dr. Winthrop said. “This is for the booster, but it raises the question: If you go out to three, four, or five vaccinations, does this matter anymore? With the flu vaccine, most people are out to 10 or 15 boosters, and we haven’t seen any significant increase in disease flares.”

The study received funding from Medac, Gilead/Galapagos, and Friends and Sponsors of Berlin Charity. Dr. Burmester reported no relevant disclosures. Dr. Winthrop is a research consultant to Pfizer.

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

“I’m not getting the vaccine. Nobody knows the long-term effects, and I heard that people are getting clots.”

We were screening patients at a low-cost clinic in Philadelphia for concerns surrounding social determinants of health. During one patient visit, in addition to concerns including housing, medication affordability, and transportation, we found that she had not received the COVID-19 vaccine, and we asked if she was interested in being immunized.

News reports have endlessly covered antivaccine sentiment, but this personal encounter hit home. From simple face masks to groundbreaking vaccines, we failed as physicians to encourage widespread uptake of health-protective measures despite strong scientific backing.

Large swaths of the public deny these tools’ importance or question their safety. This is ultimately rooted in the inability of community leaders and health care professionals to communicate with the public.

Science communication is inherently difficult. Scientists use complex language, and it is hard to evaluate the lay public’s baseline knowledge. Moreover, we are trained to speak with qualifications, encourage doubt, and accept change and evolution of fact. These qualities contrast the definitive messaging necessary in public settings. COVID-19 highlighted these gaps, where regardless of novel scientific solutions, poor communication led to a resistance to accept the tested scientific solution, which ultimately was the rate-limiting factor for overcoming the virus.

As directors of Physician Executive Leadership, an organization that trains future physicians at Thomas Jefferson University to tackle emerging health care issues, we hosted Paul Offit, MD, a national media figure and vaccine advocate. Dr. Offit shared his personal growth during the pandemic, from being abruptly thrown into the spotlight to eventually honing his communication skills. Dr. Offit discussed the challenges of sharing medical knowledge with laypeople and adaptations that are necessary. We found this transformative, realizing the importance of science communication training early in medical education.

Emphasizing the humanities and building soft skills will improve outcomes and benefit broader society by producing physician-leaders in public health and policy. We hope to improve our own communication skills and work in medical education to incorporate similar training into education paradigms for future students.

As seen in our patient interaction, strong science alone will not drive patient adherence; instead, we must work at personal and system levels to induce change. Physicians have a unique opportunity to generate trust and guide evidence-based policy. We must communicate, whether one-on-one with patients, or to millions of viewers via media or policymaker settings. We hope to not only be doctors, but to be advocates, leaders, and trusted advisers for the public.

Mr. Kieran and Mr. Shah are second-year medical students at Sidney Kimmel Medical College, Philadelphia. Neither disclosed any relevant conflicts of interest. A version of this article first appeared on Medscape.com.

“I’m not getting the vaccine. Nobody knows the long-term effects, and I heard that people are getting clots.”

We were screening patients at a low-cost clinic in Philadelphia for concerns surrounding social determinants of health. During one patient visit, in addition to concerns including housing, medication affordability, and transportation, we found that she had not received the COVID-19 vaccine, and we asked if she was interested in being immunized.

News reports have endlessly covered antivaccine sentiment, but this personal encounter hit home. From simple face masks to groundbreaking vaccines, we failed as physicians to encourage widespread uptake of health-protective measures despite strong scientific backing.

Large swaths of the public deny these tools’ importance or question their safety. This is ultimately rooted in the inability of community leaders and health care professionals to communicate with the public.

Science communication is inherently difficult. Scientists use complex language, and it is hard to evaluate the lay public’s baseline knowledge. Moreover, we are trained to speak with qualifications, encourage doubt, and accept change and evolution of fact. These qualities contrast the definitive messaging necessary in public settings. COVID-19 highlighted these gaps, where regardless of novel scientific solutions, poor communication led to a resistance to accept the tested scientific solution, which ultimately was the rate-limiting factor for overcoming the virus.

As directors of Physician Executive Leadership, an organization that trains future physicians at Thomas Jefferson University to tackle emerging health care issues, we hosted Paul Offit, MD, a national media figure and vaccine advocate. Dr. Offit shared his personal growth during the pandemic, from being abruptly thrown into the spotlight to eventually honing his communication skills. Dr. Offit discussed the challenges of sharing medical knowledge with laypeople and adaptations that are necessary. We found this transformative, realizing the importance of science communication training early in medical education.

Emphasizing the humanities and building soft skills will improve outcomes and benefit broader society by producing physician-leaders in public health and policy. We hope to improve our own communication skills and work in medical education to incorporate similar training into education paradigms for future students.

As seen in our patient interaction, strong science alone will not drive patient adherence; instead, we must work at personal and system levels to induce change. Physicians have a unique opportunity to generate trust and guide evidence-based policy. We must communicate, whether one-on-one with patients, or to millions of viewers via media or policymaker settings. We hope to not only be doctors, but to be advocates, leaders, and trusted advisers for the public.

Mr. Kieran and Mr. Shah are second-year medical students at Sidney Kimmel Medical College, Philadelphia. Neither disclosed any relevant conflicts of interest. A version of this article first appeared on Medscape.com.

“I’m not getting the vaccine. Nobody knows the long-term effects, and I heard that people are getting clots.”

We were screening patients at a low-cost clinic in Philadelphia for concerns surrounding social determinants of health. During one patient visit, in addition to concerns including housing, medication affordability, and transportation, we found that she had not received the COVID-19 vaccine, and we asked if she was interested in being immunized.

News reports have endlessly covered antivaccine sentiment, but this personal encounter hit home. From simple face masks to groundbreaking vaccines, we failed as physicians to encourage widespread uptake of health-protective measures despite strong scientific backing.

Large swaths of the public deny these tools’ importance or question their safety. This is ultimately rooted in the inability of community leaders and health care professionals to communicate with the public.

Science communication is inherently difficult. Scientists use complex language, and it is hard to evaluate the lay public’s baseline knowledge. Moreover, we are trained to speak with qualifications, encourage doubt, and accept change and evolution of fact. These qualities contrast the definitive messaging necessary in public settings. COVID-19 highlighted these gaps, where regardless of novel scientific solutions, poor communication led to a resistance to accept the tested scientific solution, which ultimately was the rate-limiting factor for overcoming the virus.

As directors of Physician Executive Leadership, an organization that trains future physicians at Thomas Jefferson University to tackle emerging health care issues, we hosted Paul Offit, MD, a national media figure and vaccine advocate. Dr. Offit shared his personal growth during the pandemic, from being abruptly thrown into the spotlight to eventually honing his communication skills. Dr. Offit discussed the challenges of sharing medical knowledge with laypeople and adaptations that are necessary. We found this transformative, realizing the importance of science communication training early in medical education.

Emphasizing the humanities and building soft skills will improve outcomes and benefit broader society by producing physician-leaders in public health and policy. We hope to improve our own communication skills and work in medical education to incorporate similar training into education paradigms for future students.

As seen in our patient interaction, strong science alone will not drive patient adherence; instead, we must work at personal and system levels to induce change. Physicians have a unique opportunity to generate trust and guide evidence-based policy. We must communicate, whether one-on-one with patients, or to millions of viewers via media or policymaker settings. We hope to not only be doctors, but to be advocates, leaders, and trusted advisers for the public.

Mr. Kieran and Mr. Shah are second-year medical students at Sidney Kimmel Medical College, Philadelphia. Neither disclosed any relevant conflicts of interest. A version of this article first appeared on Medscape.com.

Researchers have developed a computer program to identify drugs for other diseases that might be repurposed to treat type 2 diabetes and/or obesity by targeting genetic pathways for these two conditions.

The scientists identified four pathways with known drug targets for type 2 diabetes and five with known drug targets for obesity.

Their findings suggest that:

• Palbociclib (used to treat breast cancer) and cardiac glycosides (used to treat heart failure and heart rhythm disorders) might be repurposed to treat type 2 diabetes.
• Baclofen (a muscle relaxant) and carfilzomib (a chemotherapy) could potentially be used to treat obesity.
• Fostamatinib (used to treat thrombocytopenia), sucralfate (used to treat stomach ulcers), and regorafenib (used to treat cancer) might be used to treat type 2 diabetes and obesity.
• Baclofen and sucralfate would have favorable safety profiles as repurposed treatments.

Sahar El Shair, a PhD student at the Faculty of Health and Medicine, University of Newcastle, New South Wales, Australia, presented the research during an oral session at the International Congress on Obesity, the biennial congress of the World Obesity Federation, in Melbourne.

“New treatments with higher activity and specificity are urgently needed to tackle a pandemic of chronic illness associated with type 2 diabetes and obesity,” senior coauthor Murray Cairns, PhD, said in a press release from the ICO.   

“Our technology harnesses genetically informed precision medicine to identify and target new treatments for these complex disorders,” said Dr. Cairns, from the school of biomedical sciences and pharmacy at the University of Newcastle.

Matchmaking between individual, their genetic traits, and drugs

Dr. Cairns and senior coauthor William Reay, PhD, also from the school of biomedical sciences and pharmacy, have cofounded a company called PolygenRx.

The company website explains that they have developed a propriety platform termed the pharmagenic enrichment score (PES), which is “essentially a matchmaking service between patients and drugs, allowing treatment to be optimized for each individual using their unique combination of genetic risk factors.”

It is important to note the genetic risk from complex traits, such as type 2 diabetes and obesity, “are quite different [from] the rare genetic disorders caused mostly by a devastating mutation in a single gene,” Dr. Cairns explained in an email.

“Complex traits,” he noted, “are associated with thousands of [genetic] variants that are common in people and have a cumulative effect.”

For this specific research, the investigators obtained genetic data from genome-wide association studies of obesity and type 2 diabetes.

“By using very large cohorts (hundreds of thousands of individuals) and comparing the frequency of millions of genetic variants in subjects with these conditions with controls, these studies have revealed regions of the genome and genes associated with the condition,” Dr. Cairns noted.

The pharmagenic enrichment score integrates a person’s genetics with drug pharmacology to determine if a person would respond more readily to a certain drug.

“We are investigating the potential of thousands of drugs across a broad spectrum of complex traits (the list is almost endless),” Dr. Cairns explained.

From the PES score, “we have an estimate of each individual’s likelihood of a positive response to said drug,” he noted. “We all have variants that increase (and decrease) the risk of these conditions to various degrees as they are common (high frequency) genetic variants.”

With this research, “we can implement this precision medicine strategy to match the right [repurposed] drugs for individuals based on their specific burden of genetic risk” for obesity and type 2 diabetes.

“Drug repurposing can be a fast track to new medicines because there is existing knowledge about their safety and activity in humans,” he said.

Next steps: Raising funds for clinical trials

“We would like to progress some of these compounds to preclinical and clinical trials,” Dr. Cairns said, “but need to raise the funds for this expensive research. With limited government research funding opportunities, we have recently spun out a startup company to attract commercial investment in our platform and the development of new drug candidates.”

The authors have reported no relevant financial relationships. Dr. Reay and Dr. Cairns are cofounders of PolygenRx.

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

Researchers have developed a computer program to identify drugs for other diseases that might be repurposed to treat type 2 diabetes and/or obesity by targeting genetic pathways for these two conditions.

The scientists identified four pathways with known drug targets for type 2 diabetes and five with known drug targets for obesity.

Their findings suggest that:

• Palbociclib (used to treat breast cancer) and cardiac glycosides (used to treat heart failure and heart rhythm disorders) might be repurposed to treat type 2 diabetes.
• Baclofen (a muscle relaxant) and carfilzomib (a chemotherapy) could potentially be used to treat obesity.
• Fostamatinib (used to treat thrombocytopenia), sucralfate (used to treat stomach ulcers), and regorafenib (used to treat cancer) might be used to treat type 2 diabetes and obesity.
• Baclofen and sucralfate would have favorable safety profiles as repurposed treatments.

Sahar El Shair, a PhD student at the Faculty of Health and Medicine, University of Newcastle, New South Wales, Australia, presented the research during an oral session at the International Congress on Obesity, the biennial congress of the World Obesity Federation, in Melbourne.

“New treatments with higher activity and specificity are urgently needed to tackle a pandemic of chronic illness associated with type 2 diabetes and obesity,” senior coauthor Murray Cairns, PhD, said in a press release from the ICO.   

“Our technology harnesses genetically informed precision medicine to identify and target new treatments for these complex disorders,” said Dr. Cairns, from the school of biomedical sciences and pharmacy at the University of Newcastle.

Matchmaking between individual, their genetic traits, and drugs

Dr. Cairns and senior coauthor William Reay, PhD, also from the school of biomedical sciences and pharmacy, have cofounded a company called PolygenRx.

The company website explains that they have developed a propriety platform termed the pharmagenic enrichment score (PES), which is “essentially a matchmaking service between patients and drugs, allowing treatment to be optimized for each individual using their unique combination of genetic risk factors.”

It is important to note the genetic risk from complex traits, such as type 2 diabetes and obesity, “are quite different [from] the rare genetic disorders caused mostly by a devastating mutation in a single gene,” Dr. Cairns explained in an email.

“Complex traits,” he noted, “are associated with thousands of [genetic] variants that are common in people and have a cumulative effect.”

For this specific research, the investigators obtained genetic data from genome-wide association studies of obesity and type 2 diabetes.

“By using very large cohorts (hundreds of thousands of individuals) and comparing the frequency of millions of genetic variants in subjects with these conditions with controls, these studies have revealed regions of the genome and genes associated with the condition,” Dr. Cairns noted.

The pharmagenic enrichment score integrates a person’s genetics with drug pharmacology to determine if a person would respond more readily to a certain drug.

“We are investigating the potential of thousands of drugs across a broad spectrum of complex traits (the list is almost endless),” Dr. Cairns explained.

From the PES score, “we have an estimate of each individual’s likelihood of a positive response to said drug,” he noted. “We all have variants that increase (and decrease) the risk of these conditions to various degrees as they are common (high frequency) genetic variants.”

With this research, “we can implement this precision medicine strategy to match the right [repurposed] drugs for individuals based on their specific burden of genetic risk” for obesity and type 2 diabetes.

“Drug repurposing can be a fast track to new medicines because there is existing knowledge about their safety and activity in humans,” he said.

Next steps: Raising funds for clinical trials

“We would like to progress some of these compounds to preclinical and clinical trials,” Dr. Cairns said, “but need to raise the funds for this expensive research. With limited government research funding opportunities, we have recently spun out a startup company to attract commercial investment in our platform and the development of new drug candidates.”

The authors have reported no relevant financial relationships. Dr. Reay and Dr. Cairns are cofounders of PolygenRx.

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

Researchers have developed a computer program to identify drugs for other diseases that might be repurposed to treat type 2 diabetes and/or obesity by targeting genetic pathways for these two conditions.

The scientists identified four pathways with known drug targets for type 2 diabetes and five with known drug targets for obesity.

Their findings suggest that:

• Palbociclib (used to treat breast cancer) and cardiac glycosides (used to treat heart failure and heart rhythm disorders) might be repurposed to treat type 2 diabetes.
• Baclofen (a muscle relaxant) and carfilzomib (a chemotherapy) could potentially be used to treat obesity.
• Fostamatinib (used to treat thrombocytopenia), sucralfate (used to treat stomach ulcers), and regorafenib (used to treat cancer) might be used to treat type 2 diabetes and obesity.
• Baclofen and sucralfate would have favorable safety profiles as repurposed treatments.

Sahar El Shair, a PhD student at the Faculty of Health and Medicine, University of Newcastle, New South Wales, Australia, presented the research during an oral session at the International Congress on Obesity, the biennial congress of the World Obesity Federation, in Melbourne.

“New treatments with higher activity and specificity are urgently needed to tackle a pandemic of chronic illness associated with type 2 diabetes and obesity,” senior coauthor Murray Cairns, PhD, said in a press release from the ICO.   

“Our technology harnesses genetically informed precision medicine to identify and target new treatments for these complex disorders,” said Dr. Cairns, from the school of biomedical sciences and pharmacy at the University of Newcastle.

Matchmaking between individual, their genetic traits, and drugs

Dr. Cairns and senior coauthor William Reay, PhD, also from the school of biomedical sciences and pharmacy, have cofounded a company called PolygenRx.

The company website explains that they have developed a propriety platform termed the pharmagenic enrichment score (PES), which is “essentially a matchmaking service between patients and drugs, allowing treatment to be optimized for each individual using their unique combination of genetic risk factors.”

It is important to note the genetic risk from complex traits, such as type 2 diabetes and obesity, “are quite different [from] the rare genetic disorders caused mostly by a devastating mutation in a single gene,” Dr. Cairns explained in an email.

“Complex traits,” he noted, “are associated with thousands of [genetic] variants that are common in people and have a cumulative effect.”

For this specific research, the investigators obtained genetic data from genome-wide association studies of obesity and type 2 diabetes.

“By using very large cohorts (hundreds of thousands of individuals) and comparing the frequency of millions of genetic variants in subjects with these conditions with controls, these studies have revealed regions of the genome and genes associated with the condition,” Dr. Cairns noted.

The pharmagenic enrichment score integrates a person’s genetics with drug pharmacology to determine if a person would respond more readily to a certain drug.

“We are investigating the potential of thousands of drugs across a broad spectrum of complex traits (the list is almost endless),” Dr. Cairns explained.

From the PES score, “we have an estimate of each individual’s likelihood of a positive response to said drug,” he noted. “We all have variants that increase (and decrease) the risk of these conditions to various degrees as they are common (high frequency) genetic variants.”

With this research, “we can implement this precision medicine strategy to match the right [repurposed] drugs for individuals based on their specific burden of genetic risk” for obesity and type 2 diabetes.

“Drug repurposing can be a fast track to new medicines because there is existing knowledge about their safety and activity in humans,” he said.

Next steps: Raising funds for clinical trials

“We would like to progress some of these compounds to preclinical and clinical trials,” Dr. Cairns said, “but need to raise the funds for this expensive research. With limited government research funding opportunities, we have recently spun out a startup company to attract commercial investment in our platform and the development of new drug candidates.”

The authors have reported no relevant financial relationships. Dr. Reay and Dr. Cairns are cofounders of PolygenRx.

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

Janus kinase inhibitors tofacitinib (Xeljanz) and baricitinib (Olumiant) may pose no greater risk than does adalimumab (Humira and biosimilars) for major adverse cardiovascular events (MACEs) or venous thromboembolism (VTE) on the basis of a nationwide cohort study.

The French data, which included almost 16,000 patients with rheumatoid arthritis, revealed similar safety across subgroups, including older patients with at least one preexisting cardiovascular risk factor, reported lead author Léa Hoisnard, MD, of Henri Mondor Hospital, Paris, and colleagues.

These findings arrive 1 year after the U.S. Food and Drug Administration imposed class-wide boxed warnings on three Janus kinase (JAK) inhibitors, citing increased risks for both cancer and serious cardiac events detected by the open-label, randomized ORAL Surveillance postmarketing trial, which compared tofacitinib against adalimumab and etanercept.

More recently, the observational STAR-RA study, relying upon private insurance and Medicare claims in the United States, found no significant increase in cardiovascular events among patients taking tofacitinib, adding some uncertainty to the conversation.

“In this context, observational studies of unselected populations outside of North America are still needed to assess other JAK inhibitor agents,” Dr. Hoisnard and colleagues write in Annals of the Rheumatic Diseases.

Their retrospective study included 8,481 patients who received baricitinib or tofacitinib, and 7,354 patients who received adalimumab. Almost all patients in the tofacitinib group received 5 mg twice daily instead of 10 mg twice daily (99.4% vs. 0.6%), so cardiovascular safety was assessed only for the 5-mg dose. Baricitinib was prescribed at 4-mg and 2-mg doses (79.5% vs. 20.5%), allowing inclusion of both dose levels. The investigators accounted for a range of covariates, including concurrent therapy, comorbidities, and other patient characteristics.

Median follow-up durations were 440 days in the JAK inhibitor group and 344 days in the adalimumab group. The JAK inhibitor group had numerically more MACEs than did the adalimumab group, but the difference in risk was not statistically significant (54 vs. 35 MACEs; weighted hazard ratio, 1.0; 95% confidence interval, 0.7-1.5; P = .99). Similarly, more patients taking JAK inhibitors had VTEs, but relative risk was, again, not significant (75 vs. 32 VTEs; HRw, 1.1; 95% CI, 0.7-1.6; P = .63).

These findings were consistent for all subgroups, including patients aged 50 years or older and patients aged 65 years or older, although the investigators noted that statistical power was lacking for subgroup analyses.
 

Findings from Echo ORAL Surveillance

“I think the baricitinib data are important,” Kevin Winthrop, MD, MPH, professor of infectious diseases and epidemiology at Oregon Health & Science University, Portland, told this news organization. “There’s no difference between 2 mg and 4 mg [dose levels] in this analysis. And there doesn’t really seem to be a difference between baricitinib and tofacitinib. Most of the results are pretty consistent with ORAL Surveillance, which was a randomized, controlled trial.”

Dr. Winthrop, who has been active in JAK inhibitor clinical trials, recently coauthored an article in Nature Reviews Rheumatology encouraging clinicians to remember that the cardiovascular risks of JAK inhibitors are relative to adalimumab, and safety should be framed within the context of risk-to-benefit ratios.

He and his coauthor also called into question the FDA’s “better to be safe than sorry” approach, which resulted in boxed warnings across all JAK inhibitors, despite differences in target specificity.

“There are pros and cons of taking that approach,” Dr. Winthrop said in an interview. “The FDA might ultimately be right. Certainly, these drugs appear similar for some types of events, like herpes zoster, for example. But whether they’re similar with regard to malignancy or cardiovascular events, I don’t think we know.”

Dr. Winthrop noted that deucravacitinib was recently approved for psoriasis sans boxed warning, suggesting inconsistency in the FDA’s approach. The agent headlines as a “TYK2 inhibitor,” but TYK2 is a member of the JAK family.

“I don’t know why the FDA decided to treat them differently,” Dr. Winthrop said.

Boxed warnings encourage caution, lock treatment sequence

Michael Thakor, MD, of Arthritis & Rheumatology Clinic of Northern Colorado, Fort Collins, supports the boxed warnings because they encourage caution and transparency.

“It forces you to have that discussion with your patient, which may take some time, but it’s actually a very good thing,” Dr. Thakor said in an interview. “Some patients will say, ‘Oh my gosh, I don’t want to take that drug.’ But most patients, considering the level of risk that you’re talking about, are actually okay going ahead with the medication.”

If these risks aren’t discussed, he noted, patient trust may falter.

“They’re going to go online, and they’re going to be reading about it,” Dr. Thakor said. “And then they tend to get more spooked. They also may question your advice from then on, if you’re not telling them the possible risk.”

Reflecting on the present study, Dr. Thakor said that the findings initially appeared reassuring, but he became concerned about the lack of power and how adverse events trended higher in the JAK inhibitor group, particularly for VTEs, most of which occurred with baricitinib. This latter finding is challenging to interpret, however, because the 4-mg dose is not used in the United States, he added.

Dr. Thakor described how JAK inhibitors once seemed poised to assume a frontline role in RA until the boxed warnings came out. These safety concerns don’t take JAK inhibitors off the table, he said, but they do keep the class further down the treatment sequence, and the present data don’t alter this picture in daily practice.

“If I had a patient who was over the age of 50 with at least one cardiovascular risk factor, I might have a little bit of concern, but if they need their RA treated, I would definitely discuss the possibility of using a JAK inhibitor,” Dr. Thakor said. “If the patient is comfortable with it, then I would feel comfortable going ahead.”

The investigators disclosed no outside funding or conflicts of interest. Dr. Winthrop disclosed relationships with AbbVie, AstraZeneca, Bristol-Myers Squibb, and others. Dr. Thakor disclosed no conflicts of interest.

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

Janus kinase inhibitors tofacitinib (Xeljanz) and baricitinib (Olumiant) may pose no greater risk than does adalimumab (Humira and biosimilars) for major adverse cardiovascular events (MACEs) or venous thromboembolism (VTE) on the basis of a nationwide cohort study.

The French data, which included almost 16,000 patients with rheumatoid arthritis, revealed similar safety across subgroups, including older patients with at least one preexisting cardiovascular risk factor, reported lead author Léa Hoisnard, MD, of Henri Mondor Hospital, Paris, and colleagues.

These findings arrive 1 year after the U.S. Food and Drug Administration imposed class-wide boxed warnings on three Janus kinase (JAK) inhibitors, citing increased risks for both cancer and serious cardiac events detected by the open-label, randomized ORAL Surveillance postmarketing trial, which compared tofacitinib against adalimumab and etanercept.

More recently, the observational STAR-RA study, relying upon private insurance and Medicare claims in the United States, found no significant increase in cardiovascular events among patients taking tofacitinib, adding some uncertainty to the conversation.

“In this context, observational studies of unselected populations outside of North America are still needed to assess other JAK inhibitor agents,” Dr. Hoisnard and colleagues write in Annals of the Rheumatic Diseases.

Their retrospective study included 8,481 patients who received baricitinib or tofacitinib, and 7,354 patients who received adalimumab. Almost all patients in the tofacitinib group received 5 mg twice daily instead of 10 mg twice daily (99.4% vs. 0.6%), so cardiovascular safety was assessed only for the 5-mg dose. Baricitinib was prescribed at 4-mg and 2-mg doses (79.5% vs. 20.5%), allowing inclusion of both dose levels. The investigators accounted for a range of covariates, including concurrent therapy, comorbidities, and other patient characteristics.

Median follow-up durations were 440 days in the JAK inhibitor group and 344 days in the adalimumab group. The JAK inhibitor group had numerically more MACEs than did the adalimumab group, but the difference in risk was not statistically significant (54 vs. 35 MACEs; weighted hazard ratio, 1.0; 95% confidence interval, 0.7-1.5; P = .99). Similarly, more patients taking JAK inhibitors had VTEs, but relative risk was, again, not significant (75 vs. 32 VTEs; HRw, 1.1; 95% CI, 0.7-1.6; P = .63).

These findings were consistent for all subgroups, including patients aged 50 years or older and patients aged 65 years or older, although the investigators noted that statistical power was lacking for subgroup analyses.
 

Findings from Echo ORAL Surveillance

“I think the baricitinib data are important,” Kevin Winthrop, MD, MPH, professor of infectious diseases and epidemiology at Oregon Health & Science University, Portland, told this news organization. “There’s no difference between 2 mg and 4 mg [dose levels] in this analysis. And there doesn’t really seem to be a difference between baricitinib and tofacitinib. Most of the results are pretty consistent with ORAL Surveillance, which was a randomized, controlled trial.”

Dr. Winthrop, who has been active in JAK inhibitor clinical trials, recently coauthored an article in Nature Reviews Rheumatology encouraging clinicians to remember that the cardiovascular risks of JAK inhibitors are relative to adalimumab, and safety should be framed within the context of risk-to-benefit ratios.

He and his coauthor also called into question the FDA’s “better to be safe than sorry” approach, which resulted in boxed warnings across all JAK inhibitors, despite differences in target specificity.

“There are pros and cons of taking that approach,” Dr. Winthrop said in an interview. “The FDA might ultimately be right. Certainly, these drugs appear similar for some types of events, like herpes zoster, for example. But whether they’re similar with regard to malignancy or cardiovascular events, I don’t think we know.”

Dr. Winthrop noted that deucravacitinib was recently approved for psoriasis sans boxed warning, suggesting inconsistency in the FDA’s approach. The agent headlines as a “TYK2 inhibitor,” but TYK2 is a member of the JAK family.

“I don’t know why the FDA decided to treat them differently,” Dr. Winthrop said.

Boxed warnings encourage caution, lock treatment sequence

Michael Thakor, MD, of Arthritis & Rheumatology Clinic of Northern Colorado, Fort Collins, supports the boxed warnings because they encourage caution and transparency.

“It forces you to have that discussion with your patient, which may take some time, but it’s actually a very good thing,” Dr. Thakor said in an interview. “Some patients will say, ‘Oh my gosh, I don’t want to take that drug.’ But most patients, considering the level of risk that you’re talking about, are actually okay going ahead with the medication.”

If these risks aren’t discussed, he noted, patient trust may falter.

“They’re going to go online, and they’re going to be reading about it,” Dr. Thakor said. “And then they tend to get more spooked. They also may question your advice from then on, if you’re not telling them the possible risk.”

Reflecting on the present study, Dr. Thakor said that the findings initially appeared reassuring, but he became concerned about the lack of power and how adverse events trended higher in the JAK inhibitor group, particularly for VTEs, most of which occurred with baricitinib. This latter finding is challenging to interpret, however, because the 4-mg dose is not used in the United States, he added.

Dr. Thakor described how JAK inhibitors once seemed poised to assume a frontline role in RA until the boxed warnings came out. These safety concerns don’t take JAK inhibitors off the table, he said, but they do keep the class further down the treatment sequence, and the present data don’t alter this picture in daily practice.

“If I had a patient who was over the age of 50 with at least one cardiovascular risk factor, I might have a little bit of concern, but if they need their RA treated, I would definitely discuss the possibility of using a JAK inhibitor,” Dr. Thakor said. “If the patient is comfortable with it, then I would feel comfortable going ahead.”

The investigators disclosed no outside funding or conflicts of interest. Dr. Winthrop disclosed relationships with AbbVie, AstraZeneca, Bristol-Myers Squibb, and others. Dr. Thakor disclosed no conflicts of interest.

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

Janus kinase inhibitors tofacitinib (Xeljanz) and baricitinib (Olumiant) may pose no greater risk than does adalimumab (Humira and biosimilars) for major adverse cardiovascular events (MACEs) or venous thromboembolism (VTE) on the basis of a nationwide cohort study.

The French data, which included almost 16,000 patients with rheumatoid arthritis, revealed similar safety across subgroups, including older patients with at least one preexisting cardiovascular risk factor, reported lead author Léa Hoisnard, MD, of Henri Mondor Hospital, Paris, and colleagues.

These findings arrive 1 year after the U.S. Food and Drug Administration imposed class-wide boxed warnings on three Janus kinase (JAK) inhibitors, citing increased risks for both cancer and serious cardiac events detected by the open-label, randomized ORAL Surveillance postmarketing trial, which compared tofacitinib against adalimumab and etanercept.

More recently, the observational STAR-RA study, relying upon private insurance and Medicare claims in the United States, found no significant increase in cardiovascular events among patients taking tofacitinib, adding some uncertainty to the conversation.

“In this context, observational studies of unselected populations outside of North America are still needed to assess other JAK inhibitor agents,” Dr. Hoisnard and colleagues write in Annals of the Rheumatic Diseases.

Their retrospective study included 8,481 patients who received baricitinib or tofacitinib, and 7,354 patients who received adalimumab. Almost all patients in the tofacitinib group received 5 mg twice daily instead of 10 mg twice daily (99.4% vs. 0.6%), so cardiovascular safety was assessed only for the 5-mg dose. Baricitinib was prescribed at 4-mg and 2-mg doses (79.5% vs. 20.5%), allowing inclusion of both dose levels. The investigators accounted for a range of covariates, including concurrent therapy, comorbidities, and other patient characteristics.

Median follow-up durations were 440 days in the JAK inhibitor group and 344 days in the adalimumab group. The JAK inhibitor group had numerically more MACEs than did the adalimumab group, but the difference in risk was not statistically significant (54 vs. 35 MACEs; weighted hazard ratio, 1.0; 95% confidence interval, 0.7-1.5; P = .99). Similarly, more patients taking JAK inhibitors had VTEs, but relative risk was, again, not significant (75 vs. 32 VTEs; HRw, 1.1; 95% CI, 0.7-1.6; P = .63).

These findings were consistent for all subgroups, including patients aged 50 years or older and patients aged 65 years or older, although the investigators noted that statistical power was lacking for subgroup analyses.
 

Findings from Echo ORAL Surveillance

“I think the baricitinib data are important,” Kevin Winthrop, MD, MPH, professor of infectious diseases and epidemiology at Oregon Health & Science University, Portland, told this news organization. “There’s no difference between 2 mg and 4 mg [dose levels] in this analysis. And there doesn’t really seem to be a difference between baricitinib and tofacitinib. Most of the results are pretty consistent with ORAL Surveillance, which was a randomized, controlled trial.”

Dr. Winthrop, who has been active in JAK inhibitor clinical trials, recently coauthored an article in Nature Reviews Rheumatology encouraging clinicians to remember that the cardiovascular risks of JAK inhibitors are relative to adalimumab, and safety should be framed within the context of risk-to-benefit ratios.

He and his coauthor also called into question the FDA’s “better to be safe than sorry” approach, which resulted in boxed warnings across all JAK inhibitors, despite differences in target specificity.

“There are pros and cons of taking that approach,” Dr. Winthrop said in an interview. “The FDA might ultimately be right. Certainly, these drugs appear similar for some types of events, like herpes zoster, for example. But whether they’re similar with regard to malignancy or cardiovascular events, I don’t think we know.”

Dr. Winthrop noted that deucravacitinib was recently approved for psoriasis sans boxed warning, suggesting inconsistency in the FDA’s approach. The agent headlines as a “TYK2 inhibitor,” but TYK2 is a member of the JAK family.

“I don’t know why the FDA decided to treat them differently,” Dr. Winthrop said.

Boxed warnings encourage caution, lock treatment sequence

Michael Thakor, MD, of Arthritis & Rheumatology Clinic of Northern Colorado, Fort Collins, supports the boxed warnings because they encourage caution and transparency.

“It forces you to have that discussion with your patient, which may take some time, but it’s actually a very good thing,” Dr. Thakor said in an interview. “Some patients will say, ‘Oh my gosh, I don’t want to take that drug.’ But most patients, considering the level of risk that you’re talking about, are actually okay going ahead with the medication.”

If these risks aren’t discussed, he noted, patient trust may falter.

“They’re going to go online, and they’re going to be reading about it,” Dr. Thakor said. “And then they tend to get more spooked. They also may question your advice from then on, if you’re not telling them the possible risk.”

Reflecting on the present study, Dr. Thakor said that the findings initially appeared reassuring, but he became concerned about the lack of power and how adverse events trended higher in the JAK inhibitor group, particularly for VTEs, most of which occurred with baricitinib. This latter finding is challenging to interpret, however, because the 4-mg dose is not used in the United States, he added.

Dr. Thakor described how JAK inhibitors once seemed poised to assume a frontline role in RA until the boxed warnings came out. These safety concerns don’t take JAK inhibitors off the table, he said, but they do keep the class further down the treatment sequence, and the present data don’t alter this picture in daily practice.

“If I had a patient who was over the age of 50 with at least one cardiovascular risk factor, I might have a little bit of concern, but if they need their RA treated, I would definitely discuss the possibility of using a JAK inhibitor,” Dr. Thakor said. “If the patient is comfortable with it, then I would feel comfortable going ahead.”

The investigators disclosed no outside funding or conflicts of interest. Dr. Winthrop disclosed relationships with AbbVie, AstraZeneca, Bristol-Myers Squibb, and others. Dr. Thakor disclosed no conflicts of interest.

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