Guidelines

The American Gastroenterological Association recently published a clinical practice update concerning endoscopic evaluation and management of early complications after bariatric/metabolic surgery.

The seven best practice advice statements, based on available evidence and expert opinion, range from a general call for high familiarity with available interventions to specific approaches for managing postoperative leaks.

According to lead author Vivek Kumbhari, MD, PhD, director of advanced endoscopy, department of gastroenterology and hepatology, Mayo Clinic, Jacksonville, Fla., and colleagues, the update was written in consideration of increasing rates of bariatric/metabolic surgery.

“Bariatric/metabolic surgery is unmatched with respect to its weight loss and metabolic benefits,” the investigators wrote in Clinical Gastroenterology and Hepatology. “The selection criteria will continue to broaden, likely resulting in increasing numbers of less robust patients undergoing surgery (e.g., children, elderly, and those with significant cardiorespiratory comorbidities).”

Although the 90-day overall complication rate across all patients undergoing bariatric/metabolic surgery is only 4%, Dr. Kumbhari and colleagues noted that this rate is considerably higher, at 20.1%, among patients aged older than 65 years.

“As utilization escalates, so will the number of patients who suffer early complications,” they wrote.

The first three items of best practice advice describe who should be managing complications after bariatric/metabolic surgery, and how.

Foremost, Dr. Kumbhari and colleagues called for a multidisciplinary approach; they suggested that endoscopists should work closely with related specialists, such as bariatric/metabolic surgeons and interventional radiologists.

“Timely communication between the endoscopist, radiologist, surgeon, nutritionists, and inpatient medical team or primary care physician will result in efficient, effective care with prompt escalation and deescalation,” they wrote. “Daily communication is advised.”

The next two best practice advice statements encourage high familiarity with endoscopic treatments, postsurgical anatomy, interventional radiology, and surgical interventions, including risks and benefits of each approach.

“The endoscopist should ... have expertise in interventional endoscopy techniques, including but not limited to using concomitant fluoroscopy, stent deployment and retrieval, pneumatic balloon dilation, incisional therapies, endoscopic suturing, and managing percutaneous drains,” the investigators wrote. “Having the ability to perform a wide array of therapies will enhance the likelihood that the optimal endoscopic strategy will be employed, as opposed to simply performing a technique with which the endoscopist has experience.”

Following these best practices, Dr. Kumbhari and colleagues advised screening patients with postoperative complications for comorbidities, both medical in nature (such as infection) and psychological.

“Patients often have higher depression and anxiety scores, as well as a lower physical quality of life, and medical teams sometimes neglect the patient’s psychological state,” they wrote. “It is imperative that the multidisciplinary team recognize and acknowledge the patient’s psychological comorbidities and engage expertise to manage them.”

Next, the investigators advised that endoscopic intervention should be considered regardless of time interval since surgery, including the immediate postoperative period.

“Endoscopy is often indicated as the initial therapeutic modality, and it can safely be performed,” Dr. Kumbhari and colleagues wrote. “When endoscopy is performed, it is advised to use carbon dioxide for insufflation. Caution should be used when advancing the endoscope into the small bowel, as it is best to minimize pressure along the fresh staple lines. In cases in which the patient is critically ill or the interventional endoscopist does not have extensive experience with such a scenario, the endoscopy should be performed in the operating room with a surgeon present (preferably the surgeon who performed the operation).”

Dr. Kumbhari and colleagues discussed functional stenosis, which can precipitate and propagate leaks. They noted that “downstream stenosis is frequently seen at the level of the incisura angularis or in the proximal stomach when a sleeve gastrectomy is performed in a patient with a prior laparoscopic adjustable gastric band.”

To address stenosis, the update calls for “aggressive dilation” using a large pneumatic balloon, preferably with fluoroscopy to make sure the distal end of the balloon does not cross the pylorus. The investigators noted that endoscopic suturing may be needed if a tear involving the muscularis propria is encountered.

Lastly, the clinical practice update offers comprehensive guidance for managing staple-line leaks, which “most commonly occur along the staple line of the proximal stomach.”

As leaks are thought to stem from ischemia, “most leaks are not present upon completion of the operation, and they develop over the subsequent weeks, often in the setting of downstream stenosis,” the investigators wrote.

To guide management of staple-line leaks, the investigators presented a treatment algorithm that incorporates defect size, time since surgery, and presence or absence of stenosis.

For example, a defect smaller than 10 mm occurring within 6 weeks of surgery and lacking stenosis may be managed with a percutaneous drain and diversion. In contrast, a defect of similar size, also without stenosis, but occurring later than 6 weeks after the initial procedure, should be managed with endoscopic internal drainage or vacuum therapy.

“Clinicians should recognize that the goal for endoscopic management of staple-line leaks is often not necessarily initial closure of the leak site, but rather techniques to promote drainage of material from the perigastric collection into the gastric lumen such that the leak site closes by secondary intention,” wrote Dr. Kumbhari and colleagues.

The clinical practice update was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board. The investigators disclosed relationships with Boston Scientific, Medtronic, Apollo Endosurgery, and others.

The American Gastroenterological Association recently published a clinical practice update concerning endoscopic evaluation and management of early complications after bariatric/metabolic surgery.

The seven best practice advice statements, based on available evidence and expert opinion, range from a general call for high familiarity with available interventions to specific approaches for managing postoperative leaks.

According to lead author Vivek Kumbhari, MD, PhD, director of advanced endoscopy, department of gastroenterology and hepatology, Mayo Clinic, Jacksonville, Fla., and colleagues, the update was written in consideration of increasing rates of bariatric/metabolic surgery.

“Bariatric/metabolic surgery is unmatched with respect to its weight loss and metabolic benefits,” the investigators wrote in Clinical Gastroenterology and Hepatology. “The selection criteria will continue to broaden, likely resulting in increasing numbers of less robust patients undergoing surgery (e.g., children, elderly, and those with significant cardiorespiratory comorbidities).”

Although the 90-day overall complication rate across all patients undergoing bariatric/metabolic surgery is only 4%, Dr. Kumbhari and colleagues noted that this rate is considerably higher, at 20.1%, among patients aged older than 65 years.

“As utilization escalates, so will the number of patients who suffer early complications,” they wrote.

The first three items of best practice advice describe who should be managing complications after bariatric/metabolic surgery, and how.

Foremost, Dr. Kumbhari and colleagues called for a multidisciplinary approach; they suggested that endoscopists should work closely with related specialists, such as bariatric/metabolic surgeons and interventional radiologists.

“Timely communication between the endoscopist, radiologist, surgeon, nutritionists, and inpatient medical team or primary care physician will result in efficient, effective care with prompt escalation and deescalation,” they wrote. “Daily communication is advised.”

The next two best practice advice statements encourage high familiarity with endoscopic treatments, postsurgical anatomy, interventional radiology, and surgical interventions, including risks and benefits of each approach.

“The endoscopist should ... have expertise in interventional endoscopy techniques, including but not limited to using concomitant fluoroscopy, stent deployment and retrieval, pneumatic balloon dilation, incisional therapies, endoscopic suturing, and managing percutaneous drains,” the investigators wrote. “Having the ability to perform a wide array of therapies will enhance the likelihood that the optimal endoscopic strategy will be employed, as opposed to simply performing a technique with which the endoscopist has experience.”

Following these best practices, Dr. Kumbhari and colleagues advised screening patients with postoperative complications for comorbidities, both medical in nature (such as infection) and psychological.

“Patients often have higher depression and anxiety scores, as well as a lower physical quality of life, and medical teams sometimes neglect the patient’s psychological state,” they wrote. “It is imperative that the multidisciplinary team recognize and acknowledge the patient’s psychological comorbidities and engage expertise to manage them.”

Next, the investigators advised that endoscopic intervention should be considered regardless of time interval since surgery, including the immediate postoperative period.

“Endoscopy is often indicated as the initial therapeutic modality, and it can safely be performed,” Dr. Kumbhari and colleagues wrote. “When endoscopy is performed, it is advised to use carbon dioxide for insufflation. Caution should be used when advancing the endoscope into the small bowel, as it is best to minimize pressure along the fresh staple lines. In cases in which the patient is critically ill or the interventional endoscopist does not have extensive experience with such a scenario, the endoscopy should be performed in the operating room with a surgeon present (preferably the surgeon who performed the operation).”

Dr. Kumbhari and colleagues discussed functional stenosis, which can precipitate and propagate leaks. They noted that “downstream stenosis is frequently seen at the level of the incisura angularis or in the proximal stomach when a sleeve gastrectomy is performed in a patient with a prior laparoscopic adjustable gastric band.”

To address stenosis, the update calls for “aggressive dilation” using a large pneumatic balloon, preferably with fluoroscopy to make sure the distal end of the balloon does not cross the pylorus. The investigators noted that endoscopic suturing may be needed if a tear involving the muscularis propria is encountered.

Lastly, the clinical practice update offers comprehensive guidance for managing staple-line leaks, which “most commonly occur along the staple line of the proximal stomach.”

As leaks are thought to stem from ischemia, “most leaks are not present upon completion of the operation, and they develop over the subsequent weeks, often in the setting of downstream stenosis,” the investigators wrote.

To guide management of staple-line leaks, the investigators presented a treatment algorithm that incorporates defect size, time since surgery, and presence or absence of stenosis.

For example, a defect smaller than 10 mm occurring within 6 weeks of surgery and lacking stenosis may be managed with a percutaneous drain and diversion. In contrast, a defect of similar size, also without stenosis, but occurring later than 6 weeks after the initial procedure, should be managed with endoscopic internal drainage or vacuum therapy.

“Clinicians should recognize that the goal for endoscopic management of staple-line leaks is often not necessarily initial closure of the leak site, but rather techniques to promote drainage of material from the perigastric collection into the gastric lumen such that the leak site closes by secondary intention,” wrote Dr. Kumbhari and colleagues.

The clinical practice update was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board. The investigators disclosed relationships with Boston Scientific, Medtronic, Apollo Endosurgery, and others.

The American Gastroenterological Association recently published a clinical practice update concerning endoscopic evaluation and management of early complications after bariatric/metabolic surgery.

The seven best practice advice statements, based on available evidence and expert opinion, range from a general call for high familiarity with available interventions to specific approaches for managing postoperative leaks.

According to lead author Vivek Kumbhari, MD, PhD, director of advanced endoscopy, department of gastroenterology and hepatology, Mayo Clinic, Jacksonville, Fla., and colleagues, the update was written in consideration of increasing rates of bariatric/metabolic surgery.

“Bariatric/metabolic surgery is unmatched with respect to its weight loss and metabolic benefits,” the investigators wrote in Clinical Gastroenterology and Hepatology. “The selection criteria will continue to broaden, likely resulting in increasing numbers of less robust patients undergoing surgery (e.g., children, elderly, and those with significant cardiorespiratory comorbidities).”

Although the 90-day overall complication rate across all patients undergoing bariatric/metabolic surgery is only 4%, Dr. Kumbhari and colleagues noted that this rate is considerably higher, at 20.1%, among patients aged older than 65 years.

“As utilization escalates, so will the number of patients who suffer early complications,” they wrote.

The first three items of best practice advice describe who should be managing complications after bariatric/metabolic surgery, and how.

Foremost, Dr. Kumbhari and colleagues called for a multidisciplinary approach; they suggested that endoscopists should work closely with related specialists, such as bariatric/metabolic surgeons and interventional radiologists.

“Timely communication between the endoscopist, radiologist, surgeon, nutritionists, and inpatient medical team or primary care physician will result in efficient, effective care with prompt escalation and deescalation,” they wrote. “Daily communication is advised.”

The next two best practice advice statements encourage high familiarity with endoscopic treatments, postsurgical anatomy, interventional radiology, and surgical interventions, including risks and benefits of each approach.

“The endoscopist should ... have expertise in interventional endoscopy techniques, including but not limited to using concomitant fluoroscopy, stent deployment and retrieval, pneumatic balloon dilation, incisional therapies, endoscopic suturing, and managing percutaneous drains,” the investigators wrote. “Having the ability to perform a wide array of therapies will enhance the likelihood that the optimal endoscopic strategy will be employed, as opposed to simply performing a technique with which the endoscopist has experience.”

Following these best practices, Dr. Kumbhari and colleagues advised screening patients with postoperative complications for comorbidities, both medical in nature (such as infection) and psychological.

“Patients often have higher depression and anxiety scores, as well as a lower physical quality of life, and medical teams sometimes neglect the patient’s psychological state,” they wrote. “It is imperative that the multidisciplinary team recognize and acknowledge the patient’s psychological comorbidities and engage expertise to manage them.”

Next, the investigators advised that endoscopic intervention should be considered regardless of time interval since surgery, including the immediate postoperative period.

“Endoscopy is often indicated as the initial therapeutic modality, and it can safely be performed,” Dr. Kumbhari and colleagues wrote. “When endoscopy is performed, it is advised to use carbon dioxide for insufflation. Caution should be used when advancing the endoscope into the small bowel, as it is best to minimize pressure along the fresh staple lines. In cases in which the patient is critically ill or the interventional endoscopist does not have extensive experience with such a scenario, the endoscopy should be performed in the operating room with a surgeon present (preferably the surgeon who performed the operation).”

Dr. Kumbhari and colleagues discussed functional stenosis, which can precipitate and propagate leaks. They noted that “downstream stenosis is frequently seen at the level of the incisura angularis or in the proximal stomach when a sleeve gastrectomy is performed in a patient with a prior laparoscopic adjustable gastric band.”

To address stenosis, the update calls for “aggressive dilation” using a large pneumatic balloon, preferably with fluoroscopy to make sure the distal end of the balloon does not cross the pylorus. The investigators noted that endoscopic suturing may be needed if a tear involving the muscularis propria is encountered.

Lastly, the clinical practice update offers comprehensive guidance for managing staple-line leaks, which “most commonly occur along the staple line of the proximal stomach.”

As leaks are thought to stem from ischemia, “most leaks are not present upon completion of the operation, and they develop over the subsequent weeks, often in the setting of downstream stenosis,” the investigators wrote.

To guide management of staple-line leaks, the investigators presented a treatment algorithm that incorporates defect size, time since surgery, and presence or absence of stenosis.

For example, a defect smaller than 10 mm occurring within 6 weeks of surgery and lacking stenosis may be managed with a percutaneous drain and diversion. In contrast, a defect of similar size, also without stenosis, but occurring later than 6 weeks after the initial procedure, should be managed with endoscopic internal drainage or vacuum therapy.

“Clinicians should recognize that the goal for endoscopic management of staple-line leaks is often not necessarily initial closure of the leak site, but rather techniques to promote drainage of material from the perigastric collection into the gastric lumen such that the leak site closes by secondary intention,” wrote Dr. Kumbhari and colleagues.

The clinical practice update was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board. The investigators disclosed relationships with Boston Scientific, Medtronic, Apollo Endosurgery, and others.

Very-high-risk dyslipidemia patients unlikely to reach goal with a statin should be given combination statin–ezetimibe (Nustendi) therapy upfront, rather than wasting time and resources on trialing a statin alone, suggests a practical guidance document.

The document points out that, even with high-intensity statin therapy, patients achieve a reduction in low-density-lipoprotein (LDL) cholesterol levels of around 50%, which for many is not enough for them to achieve the stringent new guideline targets deemed necessary for risk reduction.

Instead, clinicians should determine at the first visit whether their patient, if they are not already on a statin, is likely to reach their goal with that drug alone, and if not, should immediately start them on the combination.

The guidance, which aims to offer a practical way to implement the 2019 European Society of Cardiology/EAS guidelines for the management of dyslipidemias, was published April 12 in Atherosclerosis .

Lead author Alberico L. Catapano, MD, PhD, discussed the new practical guidance at the recent European Atherosclerosis Society (EAS) 2021 Virtual Congress.

He explained that the motivation for creating the practical guidance was “very simple” and concerns something already embedded in the ESC/EAS guidelines; it’s just that “people didn’t notice” it.

Dr. Catapano, professor of pharmacology at the University of Milan and past president of the EAS, said the guidelines set out the average reduction in LDL-cholesterol levels “you can get by starting with high-intensity therapy and/or starting with a combination therapy.”

The guidelines, he said, suggest steps for achieving lipid control: Begin with a statin, add ezetimibe if the patient is still not at goal, and proceed to a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor if the patient is still not at target levels.

Dr. Catapano added that, “having said that, at the beginning, you can guess by knowing how far you are from the goal as to whether a statin by itself with help you get [there].”

If clinicians follow the new practical guidance of giving upfront combination statin–ezetimibe therapy in very-high-risk patients with high LDL-cholesterol levels, it will “save a lot of time, a lot of clinic visits, and will you get you to goal earlier.”

He gave the example of a patient who has an LDL-cholesterol level of 190 mg/dL, who would be classified as being at very high risk. With the target goal of 55 mg/dL, “you would never be able to get them to goal [with only] a high-intensity statin.”

The addition of ezetimibe to the regimen of this patient would have two advantages, Dr. Catapano said. The first is that “you get to goal more easily,” and the second is that, with the drugs available as a single-pill combination, it “makes it easier for the patient to be compliant.”

Consequently, there will be no “unnecessary back and forth,” he said. “Some of these are young people. They go to work; one less visit is less time lost at work.

“This is a practical issue,” he added. “It doesn’t contradict the guidelines,” it’s about “everyday clinical practice.”
 

Useful between updates

Responding to the guidance, Donald Lloyd-Jones, MD, president-elect of the American Heart Association (AHA), told this news organization that “this kind of document can be useful in periods between updates of the formal guidelines.”

New evidence comes out in between guidelines, and they “don’t often provide us with all of the practical solutions needed for everyday guidance when we’re dealing with individual patients with real-world problems.”

Dr. Lloyd-Jones, who is chair of the Department of Preventive Medicine at Northwestern University, Chicago, said the 2019 ESC/EAS guidelines set “quite aggressive targets, particularly for LDL cholesterol … but didn’t really provide much practical advice on how clinicians could get there for their patients.”

“While this document doesn’t completely address all patient groups, it does provide some good practical advice,” recognizing that “if you need to get to a certain LDL target, it’s unlikely you’re going to get there with just a statin in certain types of patients,” and “if you need a certain amount of LDL lowering, it’s certainly reasonable to start upfront with a statin and ezetimibe and see how you do.”

Crucially, Dr. Lloyd-Jones believes that the practical guidance does “flesh out some of the details the guidelines didn’t address.”

In terms of the aggressive LDL-cholesterol targets set out in the original guidelines, he said that “everyone agrees that lower is always better … and we’ve not get yet found a level that is too low.”

Further, “we’re certainly pushing patients lower and lower, especially with the use of PCSK9 inhibitors, so I think the general philosophy is consistent and correct,” although “it’s difficult to point to great evidence from clinical trials that specially says that 55 mg/dL or 40 mg/dL is the right target for a given group of patients.”

“There’s really very limited evidence for those specific numbers,” Dr. Lloyd-Jones added, “but I think everyone agrees, especially for patients at higher risk, the lower we can get them the better. What really matters, and what this document starts to address, is how we achieve as low as possible, and I think there are some important considerations that they take into account.”

Aside from how far patients need their LDL cholesterol lowered from baseline, there are issues like cost and patient preference for different types of medication, and these “weren’t particularly well addressed in the guidelines,” he added.

Scott D. Isaacs, MD, Secretary of the American Association of Clinical Endocrinologists (AACE), commented that the ESC/EAS recommendations echo the 2017 AACE/American College of Endocrinology guidelines for management of dyslipidemia and prevention of cardiovascular disease.

He said that both guidelines “call for the need to lower LDL cholesterol as much as possible to prevent cardiovascular disease.”

He agreed, however, that high- or very-high-risk patients “have aggressive LDL targets that are often lower than what can be accomplished with high-dose, high-intensity statin monotherapy. Therefore, starting with combination therapy … will get more patients to goal more quickly and will prevent more cardiovascular events.”

Isaacs added: “It just makes sense that if you know a drug will not be strong enough, then you should start with two drugs.”

He noted that this approach is commonly used for conditions such as diabetes and hypertension, “when monotherapy is not expected to achieve the desired results.”

Dr. Isaacs also underlined that the combination of a statin plus ezetimibe “is appealing because of the price and ease of use.”

Although PCSK9 inhibitors are more potent and achieve even lower LDL levels, “the higher price and need to take an injection has limited their use,” he noted.

“One would expect that as the prices of PCSK9 inhibitors come down, their place in care pathways will move up since they are more effective and have proven cardiovascular benefit, but for now, statin plus ezetimibe is a potent and cost-effective way to achieve LDL targets in high- and very-high-risk patients,” Dr. Isaacs concluded.

One issue Dr. Lloyd-Jones raised with the ESC/EAS guidelines is that they seem to have put a lot of weight Mendelian randomization analysis.

“Those are useful in understanding whether having low LDL-cholesterol levels or triglycerides naturally are better for you – of course they are – but they actually provide no evidence about treatment effects, so I think what we need from that is actual data from the clinical trials to understand the treatment effects, both positive and negative.”

He added that that “really then helps us to drive to how and in whom we want to achieve the lowest levels possible.”

Dr. Lloyd-Jones said that Mendelian randomization analyses “continue to crop in a lot of these ESC and EAS documents,” and although they are “elegant and interesting,” they “don’t really inform treatment at all.”

No funding declared. Catapano declares relationships with Pfizer, Sanofi, Regeneron, Merck, Mediolanum, SigmaTau, Menarini, Kowa, Recordati, Eli Lilly, AstraZeneca, Merck, Aegerion and Amgen.

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

Very-high-risk dyslipidemia patients unlikely to reach goal with a statin should be given combination statin–ezetimibe (Nustendi) therapy upfront, rather than wasting time and resources on trialing a statin alone, suggests a practical guidance document.

The document points out that, even with high-intensity statin therapy, patients achieve a reduction in low-density-lipoprotein (LDL) cholesterol levels of around 50%, which for many is not enough for them to achieve the stringent new guideline targets deemed necessary for risk reduction.

Instead, clinicians should determine at the first visit whether their patient, if they are not already on a statin, is likely to reach their goal with that drug alone, and if not, should immediately start them on the combination.

The guidance, which aims to offer a practical way to implement the 2019 European Society of Cardiology/EAS guidelines for the management of dyslipidemias, was published April 12 in Atherosclerosis .

Lead author Alberico L. Catapano, MD, PhD, discussed the new practical guidance at the recent European Atherosclerosis Society (EAS) 2021 Virtual Congress.

He explained that the motivation for creating the practical guidance was “very simple” and concerns something already embedded in the ESC/EAS guidelines; it’s just that “people didn’t notice” it.

Dr. Catapano, professor of pharmacology at the University of Milan and past president of the EAS, said the guidelines set out the average reduction in LDL-cholesterol levels “you can get by starting with high-intensity therapy and/or starting with a combination therapy.”

The guidelines, he said, suggest steps for achieving lipid control: Begin with a statin, add ezetimibe if the patient is still not at goal, and proceed to a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor if the patient is still not at target levels.

Dr. Catapano added that, “having said that, at the beginning, you can guess by knowing how far you are from the goal as to whether a statin by itself with help you get [there].”

If clinicians follow the new practical guidance of giving upfront combination statin–ezetimibe therapy in very-high-risk patients with high LDL-cholesterol levels, it will “save a lot of time, a lot of clinic visits, and will you get you to goal earlier.”

He gave the example of a patient who has an LDL-cholesterol level of 190 mg/dL, who would be classified as being at very high risk. With the target goal of 55 mg/dL, “you would never be able to get them to goal [with only] a high-intensity statin.”

The addition of ezetimibe to the regimen of this patient would have two advantages, Dr. Catapano said. The first is that “you get to goal more easily,” and the second is that, with the drugs available as a single-pill combination, it “makes it easier for the patient to be compliant.”

Consequently, there will be no “unnecessary back and forth,” he said. “Some of these are young people. They go to work; one less visit is less time lost at work.

“This is a practical issue,” he added. “It doesn’t contradict the guidelines,” it’s about “everyday clinical practice.”
 

Useful between updates

Responding to the guidance, Donald Lloyd-Jones, MD, president-elect of the American Heart Association (AHA), told this news organization that “this kind of document can be useful in periods between updates of the formal guidelines.”

New evidence comes out in between guidelines, and they “don’t often provide us with all of the practical solutions needed for everyday guidance when we’re dealing with individual patients with real-world problems.”

Dr. Lloyd-Jones, who is chair of the Department of Preventive Medicine at Northwestern University, Chicago, said the 2019 ESC/EAS guidelines set “quite aggressive targets, particularly for LDL cholesterol … but didn’t really provide much practical advice on how clinicians could get there for their patients.”

“While this document doesn’t completely address all patient groups, it does provide some good practical advice,” recognizing that “if you need to get to a certain LDL target, it’s unlikely you’re going to get there with just a statin in certain types of patients,” and “if you need a certain amount of LDL lowering, it’s certainly reasonable to start upfront with a statin and ezetimibe and see how you do.”

Crucially, Dr. Lloyd-Jones believes that the practical guidance does “flesh out some of the details the guidelines didn’t address.”

In terms of the aggressive LDL-cholesterol targets set out in the original guidelines, he said that “everyone agrees that lower is always better … and we’ve not get yet found a level that is too low.”

Further, “we’re certainly pushing patients lower and lower, especially with the use of PCSK9 inhibitors, so I think the general philosophy is consistent and correct,” although “it’s difficult to point to great evidence from clinical trials that specially says that 55 mg/dL or 40 mg/dL is the right target for a given group of patients.”

“There’s really very limited evidence for those specific numbers,” Dr. Lloyd-Jones added, “but I think everyone agrees, especially for patients at higher risk, the lower we can get them the better. What really matters, and what this document starts to address, is how we achieve as low as possible, and I think there are some important considerations that they take into account.”

Aside from how far patients need their LDL cholesterol lowered from baseline, there are issues like cost and patient preference for different types of medication, and these “weren’t particularly well addressed in the guidelines,” he added.

Scott D. Isaacs, MD, Secretary of the American Association of Clinical Endocrinologists (AACE), commented that the ESC/EAS recommendations echo the 2017 AACE/American College of Endocrinology guidelines for management of dyslipidemia and prevention of cardiovascular disease.

He said that both guidelines “call for the need to lower LDL cholesterol as much as possible to prevent cardiovascular disease.”

He agreed, however, that high- or very-high-risk patients “have aggressive LDL targets that are often lower than what can be accomplished with high-dose, high-intensity statin monotherapy. Therefore, starting with combination therapy … will get more patients to goal more quickly and will prevent more cardiovascular events.”

Isaacs added: “It just makes sense that if you know a drug will not be strong enough, then you should start with two drugs.”

He noted that this approach is commonly used for conditions such as diabetes and hypertension, “when monotherapy is not expected to achieve the desired results.”

Dr. Isaacs also underlined that the combination of a statin plus ezetimibe “is appealing because of the price and ease of use.”

Although PCSK9 inhibitors are more potent and achieve even lower LDL levels, “the higher price and need to take an injection has limited their use,” he noted.

“One would expect that as the prices of PCSK9 inhibitors come down, their place in care pathways will move up since they are more effective and have proven cardiovascular benefit, but for now, statin plus ezetimibe is a potent and cost-effective way to achieve LDL targets in high- and very-high-risk patients,” Dr. Isaacs concluded.

One issue Dr. Lloyd-Jones raised with the ESC/EAS guidelines is that they seem to have put a lot of weight Mendelian randomization analysis.

“Those are useful in understanding whether having low LDL-cholesterol levels or triglycerides naturally are better for you – of course they are – but they actually provide no evidence about treatment effects, so I think what we need from that is actual data from the clinical trials to understand the treatment effects, both positive and negative.”

He added that that “really then helps us to drive to how and in whom we want to achieve the lowest levels possible.”

Dr. Lloyd-Jones said that Mendelian randomization analyses “continue to crop in a lot of these ESC and EAS documents,” and although they are “elegant and interesting,” they “don’t really inform treatment at all.”

No funding declared. Catapano declares relationships with Pfizer, Sanofi, Regeneron, Merck, Mediolanum, SigmaTau, Menarini, Kowa, Recordati, Eli Lilly, AstraZeneca, Merck, Aegerion and Amgen.

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

Very-high-risk dyslipidemia patients unlikely to reach goal with a statin should be given combination statin–ezetimibe (Nustendi) therapy upfront, rather than wasting time and resources on trialing a statin alone, suggests a practical guidance document.

The document points out that, even with high-intensity statin therapy, patients achieve a reduction in low-density-lipoprotein (LDL) cholesterol levels of around 50%, which for many is not enough for them to achieve the stringent new guideline targets deemed necessary for risk reduction.

Instead, clinicians should determine at the first visit whether their patient, if they are not already on a statin, is likely to reach their goal with that drug alone, and if not, should immediately start them on the combination.

The guidance, which aims to offer a practical way to implement the 2019 European Society of Cardiology/EAS guidelines for the management of dyslipidemias, was published April 12 in Atherosclerosis .

Lead author Alberico L. Catapano, MD, PhD, discussed the new practical guidance at the recent European Atherosclerosis Society (EAS) 2021 Virtual Congress.

He explained that the motivation for creating the practical guidance was “very simple” and concerns something already embedded in the ESC/EAS guidelines; it’s just that “people didn’t notice” it.

Dr. Catapano, professor of pharmacology at the University of Milan and past president of the EAS, said the guidelines set out the average reduction in LDL-cholesterol levels “you can get by starting with high-intensity therapy and/or starting with a combination therapy.”

The guidelines, he said, suggest steps for achieving lipid control: Begin with a statin, add ezetimibe if the patient is still not at goal, and proceed to a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor if the patient is still not at target levels.

Dr. Catapano added that, “having said that, at the beginning, you can guess by knowing how far you are from the goal as to whether a statin by itself with help you get [there].”

If clinicians follow the new practical guidance of giving upfront combination statin–ezetimibe therapy in very-high-risk patients with high LDL-cholesterol levels, it will “save a lot of time, a lot of clinic visits, and will you get you to goal earlier.”

He gave the example of a patient who has an LDL-cholesterol level of 190 mg/dL, who would be classified as being at very high risk. With the target goal of 55 mg/dL, “you would never be able to get them to goal [with only] a high-intensity statin.”

The addition of ezetimibe to the regimen of this patient would have two advantages, Dr. Catapano said. The first is that “you get to goal more easily,” and the second is that, with the drugs available as a single-pill combination, it “makes it easier for the patient to be compliant.”

Consequently, there will be no “unnecessary back and forth,” he said. “Some of these are young people. They go to work; one less visit is less time lost at work.

“This is a practical issue,” he added. “It doesn’t contradict the guidelines,” it’s about “everyday clinical practice.”
 

Useful between updates

Responding to the guidance, Donald Lloyd-Jones, MD, president-elect of the American Heart Association (AHA), told this news organization that “this kind of document can be useful in periods between updates of the formal guidelines.”

New evidence comes out in between guidelines, and they “don’t often provide us with all of the practical solutions needed for everyday guidance when we’re dealing with individual patients with real-world problems.”

Dr. Lloyd-Jones, who is chair of the Department of Preventive Medicine at Northwestern University, Chicago, said the 2019 ESC/EAS guidelines set “quite aggressive targets, particularly for LDL cholesterol … but didn’t really provide much practical advice on how clinicians could get there for their patients.”

“While this document doesn’t completely address all patient groups, it does provide some good practical advice,” recognizing that “if you need to get to a certain LDL target, it’s unlikely you’re going to get there with just a statin in certain types of patients,” and “if you need a certain amount of LDL lowering, it’s certainly reasonable to start upfront with a statin and ezetimibe and see how you do.”

Crucially, Dr. Lloyd-Jones believes that the practical guidance does “flesh out some of the details the guidelines didn’t address.”

In terms of the aggressive LDL-cholesterol targets set out in the original guidelines, he said that “everyone agrees that lower is always better … and we’ve not get yet found a level that is too low.”

Further, “we’re certainly pushing patients lower and lower, especially with the use of PCSK9 inhibitors, so I think the general philosophy is consistent and correct,” although “it’s difficult to point to great evidence from clinical trials that specially says that 55 mg/dL or 40 mg/dL is the right target for a given group of patients.”

“There’s really very limited evidence for those specific numbers,” Dr. Lloyd-Jones added, “but I think everyone agrees, especially for patients at higher risk, the lower we can get them the better. What really matters, and what this document starts to address, is how we achieve as low as possible, and I think there are some important considerations that they take into account.”

Aside from how far patients need their LDL cholesterol lowered from baseline, there are issues like cost and patient preference for different types of medication, and these “weren’t particularly well addressed in the guidelines,” he added.

Scott D. Isaacs, MD, Secretary of the American Association of Clinical Endocrinologists (AACE), commented that the ESC/EAS recommendations echo the 2017 AACE/American College of Endocrinology guidelines for management of dyslipidemia and prevention of cardiovascular disease.

He said that both guidelines “call for the need to lower LDL cholesterol as much as possible to prevent cardiovascular disease.”

He agreed, however, that high- or very-high-risk patients “have aggressive LDL targets that are often lower than what can be accomplished with high-dose, high-intensity statin monotherapy. Therefore, starting with combination therapy … will get more patients to goal more quickly and will prevent more cardiovascular events.”

Isaacs added: “It just makes sense that if you know a drug will not be strong enough, then you should start with two drugs.”

He noted that this approach is commonly used for conditions such as diabetes and hypertension, “when monotherapy is not expected to achieve the desired results.”

Dr. Isaacs also underlined that the combination of a statin plus ezetimibe “is appealing because of the price and ease of use.”

Although PCSK9 inhibitors are more potent and achieve even lower LDL levels, “the higher price and need to take an injection has limited their use,” he noted.

“One would expect that as the prices of PCSK9 inhibitors come down, their place in care pathways will move up since they are more effective and have proven cardiovascular benefit, but for now, statin plus ezetimibe is a potent and cost-effective way to achieve LDL targets in high- and very-high-risk patients,” Dr. Isaacs concluded.

One issue Dr. Lloyd-Jones raised with the ESC/EAS guidelines is that they seem to have put a lot of weight Mendelian randomization analysis.

“Those are useful in understanding whether having low LDL-cholesterol levels or triglycerides naturally are better for you – of course they are – but they actually provide no evidence about treatment effects, so I think what we need from that is actual data from the clinical trials to understand the treatment effects, both positive and negative.”

He added that that “really then helps us to drive to how and in whom we want to achieve the lowest levels possible.”

Dr. Lloyd-Jones said that Mendelian randomization analyses “continue to crop in a lot of these ESC and EAS documents,” and although they are “elegant and interesting,” they “don’t really inform treatment at all.”

No funding declared. Catapano declares relationships with Pfizer, Sanofi, Regeneron, Merck, Mediolanum, SigmaTau, Menarini, Kowa, Recordati, Eli Lilly, AstraZeneca, Merck, Aegerion and Amgen.

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

The American College of Gastroenterology has issued new guidelines on management of Clostridioides difficile infection that now include roles for fecal microbial transplant (FMT), combination testing, and bezlotoxumab.

The ACG’s previous guidelines on the diagnosis, management, and treatment of what was then still called Clostridium difficile were published in 2013. Since then, the organism’s name changed to Clostridioides difficile, and that’s just the beginning of the changes reflected in the scientific literature, wrote lead author Colleen R. Kelly, MD, of Brown University, Providence, R.I., and colleagues.

“Other developments include the increased recognition of diagnostic challenges in the era of nucleic acid amplification–based testing, new therapeutic options for treatment and prevention of recurrence, and increasing evidence to support fecal microbiota transplantation (FMT) in recurrent and severe infection,” the authors said.

The guidelines, published in the American Journal of Gastroenterology, include 23 graded recommendations addressing issues of prevention, diagnosis, treatment, prevention of recurrence, and guidance for special populations in the management of C. difficile infection (CDI).
 

New faces among familiar ones

In terms of diagnosis, the new guidelines recommend using both a highly sensitive testing modality and a highly specific one to help distinguish colonization from active infection. Specifically, the authors recommend that stool is first tested using a highly sensitive test, either nucleic acid amplification testing or glutamate dehydrogenase, followed by an enzyme immunoassays for its high specificity.

Changes to treatment recommendations include the initial use of oral vancomycin or oral fidaxomicin for cases of nonsevere CDI. Oral metronidazole may be considered for initial nonsevere CDI in low-risk patients, the authors noted. The evidence is strong for the continued recommendations of vancomycin (125 mg four times daily for 10 days) and fidaxomicin (200 mg twice daily for 10 days) for patients with severe CDI. For patients with fulminant CDI, the recommendations call for medical therapy including volume resuscitation and oral vancomycin, although combination therapy with parenteral metronidazole may be considered despite the very low quality of evidence.

A notable update to the guidelines is the recommendation of fecal microbiota transplant (FMT) for both severe and fulminant CDI cases that are resistant to antibiotics and to prevent recurrence in at-risk patients. Although the quality of evidence is ranked as low, the recommendation is strong, the authors wrote. “Beyond improved cure rates, FMT may result in decreased rates of CDI-related colectomy and sepsis and may offer survival benefit in this critically ill patient population.” However, most patients in studies of FMT required multiple treatments in combination with anti-CDI antibiotics.

Other recommendations to prevent recurrence include oral vancomycin prophylaxis during the subsequent use of systemic antibiotics in patients with a history of CDI. The guidelines also recommend bezlotoxumab for prevention of CDI recurrence in high-risk patients, and advise against discontinuing antisecretory therapy in CDI patients if there is an appropriate indication for use.

Based on the lack of quality evidence, the guidelines recommend against the use of probiotics for preventing CDI in patients being treated with antibiotics and for prevention of recurrent infection.
 

Special populations

For patients with inflammatory bowel disease, the guidelines recommend C. difficile testing when these individuals present with acute flares and diarrhea, and the use of vancomycin for treatment. In addition, the authors strongly recommended FMT for recurrent CDI in these patients. For pregnant, postpartum, and breastfeeding patients with CDI, the guidelines recommend vancomycin, and either vancomycin or fidaxomicin may be used for treating CDI in immunocompromised patients, the authors noted.

The updated guidelines are designed to complement those issued by the Infections Disease Society of America and Society of Healthcare Epidemiologists of America, the researchers noted.
 

Reflecting the research

The previous guidelines for C. difficile were issued in 2013, and much has changed since then in terms of epidemiology, diagnosis, treatment, and infection control, Sahil Khanna, MBBS, MS, of the Mayo Clinic, Rochester, Minn., said in an interview.

Notably, diagnostic testing has “made leaps and bounds” and new treatments have become available that were not included in earlier guidelines, said Dr. Khanna. In particular, the new guidelines are recommending a two-step diagnostic assay; “the diagnostic algorithm has changed, and hopefully that will help us change practice” to identify active infection more quickly and efficiently.

Another important update is the recommendation of fidaxomicin as an option for initial nonfulminant CDI as an alternative to vancomycin, Dr. Khanna said, noting that metronidazole remains an option for low-risk patients. An additional change is the advice to use a different treatment for a second recurrent infection rather than repeating the initial treatment.  

The recommendation of bezlotoxumab for prevention of CDI recurrence in patients who are at high risk of recurrence is the first time this drug has appeared in major guidelines, Dr. Khanna observed.

The recommendation in support of fecal microbiota transplant is a key update to the management of CDI, including the guidance that the procedure can be repeated if necessary, he said.

Looking ahead, “Additional research is needed to fully understand the best testing algorithms for CDI,” Dr. Khanna explained. “More studies also are needed to show how FMT fully fits into the picture, and some current studies are looking at its potential earlier in the course of infection.”

The guidelines were developed in collaboration with the Practice Parameters Committee of the American College of Gastroenterology and received no outside funding. Dr. Kelly disclosed serving as a site investigator of a clinical trial for Finch Therapeutics and is an unpaid clinical advisory board member for OpenBiome. Dr. Khanna has coauthored previous guidelines on C. difficile. He disclosed consulting relationships with Finch, GlaxoSmithKline, Jetson, ProbioTech, and Shire/Takeda, as well as research support from Rebiotix, Seres, and Vedanta.

The American College of Gastroenterology has issued new guidelines on management of Clostridioides difficile infection that now include roles for fecal microbial transplant (FMT), combination testing, and bezlotoxumab.

The ACG’s previous guidelines on the diagnosis, management, and treatment of what was then still called Clostridium difficile were published in 2013. Since then, the organism’s name changed to Clostridioides difficile, and that’s just the beginning of the changes reflected in the scientific literature, wrote lead author Colleen R. Kelly, MD, of Brown University, Providence, R.I., and colleagues.

“Other developments include the increased recognition of diagnostic challenges in the era of nucleic acid amplification–based testing, new therapeutic options for treatment and prevention of recurrence, and increasing evidence to support fecal microbiota transplantation (FMT) in recurrent and severe infection,” the authors said.

The guidelines, published in the American Journal of Gastroenterology, include 23 graded recommendations addressing issues of prevention, diagnosis, treatment, prevention of recurrence, and guidance for special populations in the management of C. difficile infection (CDI).
 

New faces among familiar ones

In terms of diagnosis, the new guidelines recommend using both a highly sensitive testing modality and a highly specific one to help distinguish colonization from active infection. Specifically, the authors recommend that stool is first tested using a highly sensitive test, either nucleic acid amplification testing or glutamate dehydrogenase, followed by an enzyme immunoassays for its high specificity.

Changes to treatment recommendations include the initial use of oral vancomycin or oral fidaxomicin for cases of nonsevere CDI. Oral metronidazole may be considered for initial nonsevere CDI in low-risk patients, the authors noted. The evidence is strong for the continued recommendations of vancomycin (125 mg four times daily for 10 days) and fidaxomicin (200 mg twice daily for 10 days) for patients with severe CDI. For patients with fulminant CDI, the recommendations call for medical therapy including volume resuscitation and oral vancomycin, although combination therapy with parenteral metronidazole may be considered despite the very low quality of evidence.

A notable update to the guidelines is the recommendation of fecal microbiota transplant (FMT) for both severe and fulminant CDI cases that are resistant to antibiotics and to prevent recurrence in at-risk patients. Although the quality of evidence is ranked as low, the recommendation is strong, the authors wrote. “Beyond improved cure rates, FMT may result in decreased rates of CDI-related colectomy and sepsis and may offer survival benefit in this critically ill patient population.” However, most patients in studies of FMT required multiple treatments in combination with anti-CDI antibiotics.

Other recommendations to prevent recurrence include oral vancomycin prophylaxis during the subsequent use of systemic antibiotics in patients with a history of CDI. The guidelines also recommend bezlotoxumab for prevention of CDI recurrence in high-risk patients, and advise against discontinuing antisecretory therapy in CDI patients if there is an appropriate indication for use.

Based on the lack of quality evidence, the guidelines recommend against the use of probiotics for preventing CDI in patients being treated with antibiotics and for prevention of recurrent infection.
 

Special populations

For patients with inflammatory bowel disease, the guidelines recommend C. difficile testing when these individuals present with acute flares and diarrhea, and the use of vancomycin for treatment. In addition, the authors strongly recommended FMT for recurrent CDI in these patients. For pregnant, postpartum, and breastfeeding patients with CDI, the guidelines recommend vancomycin, and either vancomycin or fidaxomicin may be used for treating CDI in immunocompromised patients, the authors noted.

The updated guidelines are designed to complement those issued by the Infections Disease Society of America and Society of Healthcare Epidemiologists of America, the researchers noted.
 

Reflecting the research

The previous guidelines for C. difficile were issued in 2013, and much has changed since then in terms of epidemiology, diagnosis, treatment, and infection control, Sahil Khanna, MBBS, MS, of the Mayo Clinic, Rochester, Minn., said in an interview.

Notably, diagnostic testing has “made leaps and bounds” and new treatments have become available that were not included in earlier guidelines, said Dr. Khanna. In particular, the new guidelines are recommending a two-step diagnostic assay; “the diagnostic algorithm has changed, and hopefully that will help us change practice” to identify active infection more quickly and efficiently.

Another important update is the recommendation of fidaxomicin as an option for initial nonfulminant CDI as an alternative to vancomycin, Dr. Khanna said, noting that metronidazole remains an option for low-risk patients. An additional change is the advice to use a different treatment for a second recurrent infection rather than repeating the initial treatment.  

The recommendation of bezlotoxumab for prevention of CDI recurrence in patients who are at high risk of recurrence is the first time this drug has appeared in major guidelines, Dr. Khanna observed.

The recommendation in support of fecal microbiota transplant is a key update to the management of CDI, including the guidance that the procedure can be repeated if necessary, he said.

Looking ahead, “Additional research is needed to fully understand the best testing algorithms for CDI,” Dr. Khanna explained. “More studies also are needed to show how FMT fully fits into the picture, and some current studies are looking at its potential earlier in the course of infection.”

The guidelines were developed in collaboration with the Practice Parameters Committee of the American College of Gastroenterology and received no outside funding. Dr. Kelly disclosed serving as a site investigator of a clinical trial for Finch Therapeutics and is an unpaid clinical advisory board member for OpenBiome. Dr. Khanna has coauthored previous guidelines on C. difficile. He disclosed consulting relationships with Finch, GlaxoSmithKline, Jetson, ProbioTech, and Shire/Takeda, as well as research support from Rebiotix, Seres, and Vedanta.

The American College of Gastroenterology has issued new guidelines on management of Clostridioides difficile infection that now include roles for fecal microbial transplant (FMT), combination testing, and bezlotoxumab.

The ACG’s previous guidelines on the diagnosis, management, and treatment of what was then still called Clostridium difficile were published in 2013. Since then, the organism’s name changed to Clostridioides difficile, and that’s just the beginning of the changes reflected in the scientific literature, wrote lead author Colleen R. Kelly, MD, of Brown University, Providence, R.I., and colleagues.

“Other developments include the increased recognition of diagnostic challenges in the era of nucleic acid amplification–based testing, new therapeutic options for treatment and prevention of recurrence, and increasing evidence to support fecal microbiota transplantation (FMT) in recurrent and severe infection,” the authors said.

The guidelines, published in the American Journal of Gastroenterology, include 23 graded recommendations addressing issues of prevention, diagnosis, treatment, prevention of recurrence, and guidance for special populations in the management of C. difficile infection (CDI).
 

New faces among familiar ones

In terms of diagnosis, the new guidelines recommend using both a highly sensitive testing modality and a highly specific one to help distinguish colonization from active infection. Specifically, the authors recommend that stool is first tested using a highly sensitive test, either nucleic acid amplification testing or glutamate dehydrogenase, followed by an enzyme immunoassays for its high specificity.

Changes to treatment recommendations include the initial use of oral vancomycin or oral fidaxomicin for cases of nonsevere CDI. Oral metronidazole may be considered for initial nonsevere CDI in low-risk patients, the authors noted. The evidence is strong for the continued recommendations of vancomycin (125 mg four times daily for 10 days) and fidaxomicin (200 mg twice daily for 10 days) for patients with severe CDI. For patients with fulminant CDI, the recommendations call for medical therapy including volume resuscitation and oral vancomycin, although combination therapy with parenteral metronidazole may be considered despite the very low quality of evidence.

A notable update to the guidelines is the recommendation of fecal microbiota transplant (FMT) for both severe and fulminant CDI cases that are resistant to antibiotics and to prevent recurrence in at-risk patients. Although the quality of evidence is ranked as low, the recommendation is strong, the authors wrote. “Beyond improved cure rates, FMT may result in decreased rates of CDI-related colectomy and sepsis and may offer survival benefit in this critically ill patient population.” However, most patients in studies of FMT required multiple treatments in combination with anti-CDI antibiotics.

Other recommendations to prevent recurrence include oral vancomycin prophylaxis during the subsequent use of systemic antibiotics in patients with a history of CDI. The guidelines also recommend bezlotoxumab for prevention of CDI recurrence in high-risk patients, and advise against discontinuing antisecretory therapy in CDI patients if there is an appropriate indication for use.

Based on the lack of quality evidence, the guidelines recommend against the use of probiotics for preventing CDI in patients being treated with antibiotics and for prevention of recurrent infection.
 

Special populations

For patients with inflammatory bowel disease, the guidelines recommend C. difficile testing when these individuals present with acute flares and diarrhea, and the use of vancomycin for treatment. In addition, the authors strongly recommended FMT for recurrent CDI in these patients. For pregnant, postpartum, and breastfeeding patients with CDI, the guidelines recommend vancomycin, and either vancomycin or fidaxomicin may be used for treating CDI in immunocompromised patients, the authors noted.

The updated guidelines are designed to complement those issued by the Infections Disease Society of America and Society of Healthcare Epidemiologists of America, the researchers noted.
 

Reflecting the research

The previous guidelines for C. difficile were issued in 2013, and much has changed since then in terms of epidemiology, diagnosis, treatment, and infection control, Sahil Khanna, MBBS, MS, of the Mayo Clinic, Rochester, Minn., said in an interview.

Notably, diagnostic testing has “made leaps and bounds” and new treatments have become available that were not included in earlier guidelines, said Dr. Khanna. In particular, the new guidelines are recommending a two-step diagnostic assay; “the diagnostic algorithm has changed, and hopefully that will help us change practice” to identify active infection more quickly and efficiently.

Another important update is the recommendation of fidaxomicin as an option for initial nonfulminant CDI as an alternative to vancomycin, Dr. Khanna said, noting that metronidazole remains an option for low-risk patients. An additional change is the advice to use a different treatment for a second recurrent infection rather than repeating the initial treatment.  

The recommendation of bezlotoxumab for prevention of CDI recurrence in patients who are at high risk of recurrence is the first time this drug has appeared in major guidelines, Dr. Khanna observed.

The recommendation in support of fecal microbiota transplant is a key update to the management of CDI, including the guidance that the procedure can be repeated if necessary, he said.

Looking ahead, “Additional research is needed to fully understand the best testing algorithms for CDI,” Dr. Khanna explained. “More studies also are needed to show how FMT fully fits into the picture, and some current studies are looking at its potential earlier in the course of infection.”

The guidelines were developed in collaboration with the Practice Parameters Committee of the American College of Gastroenterology and received no outside funding. Dr. Kelly disclosed serving as a site investigator of a clinical trial for Finch Therapeutics and is an unpaid clinical advisory board member for OpenBiome. Dr. Khanna has coauthored previous guidelines on C. difficile. He disclosed consulting relationships with Finch, GlaxoSmithKline, Jetson, ProbioTech, and Shire/Takeda, as well as research support from Rebiotix, Seres, and Vedanta.

As pandemic restrictions ease and young athletes once again take to fields, courts, tracks, and rinks, doctors are sharing ways to help them get back to sports safely.

That means taking steps to prevent COVID-19.

It also means trying to avoid sports-related injuries, which may be more likely if young athletes didn’t move around so much during the pandemic.

For adolescents who are eligible, getting a COVID-19 vaccine may be the most important thing they can do, according to the American Academy of Pediatrics.

“The AAP encourages all people who are eligible to receive the COVID-19 vaccine as soon as it is available,” the organization wrote in updated guidance on returning to sports and physical activity.

“I don’t think it can be overemphasized how important these vaccines are, both for the individual and at the community level,” says Aaron L. Baggish, MD, an associate professor of medicine at Harvard Medical School, Boston, and director of the Cardiovascular Performance Program at Massachusetts General Hospital in Boston.

Dr. Baggish, team cardiologist for the New England Patriots, the Boston Bruins, the New England Revolution, U.S. Men’s and Women’s Soccer, and U.S. Rowing, as well as medical director for the Boston Marathon, has studied the effects of COVID-19 on the heart in college athletes and written return-to-play recommendations for athletes of high school age and older.

“Millions of people have received these vaccines from age 12 up,” Dr. Baggish says. “The efficacy continues to look very durable and near complete, and the risk associated with vaccination is incredibly low, to the point where the risk-benefit ratio across the age spectrum, whether you’re athletic or not, strongly favors getting vaccinated. There is really no reason to hold off at this point.”

While outdoor activities are lower-risk for spreading COVID-19 and many people have been vaccinated, masks still should be worn in certain settings, the AAP notes.

“Indoor spaces that are crowded are still high-risk for COVID-19 transmission. And we recognize that not everyone in these settings may be vaccinated,” says Susannah Briskin, MD, lead author of the AAP guidance.

“So for indoor sporting events with spectators, in locker rooms or other small spaces such as a training room, and during shared car rides or school transportation to and from events, individuals should continue to mask,” adds Dr. Briskin, a pediatrician in the Division of Sports Medicine and fellowship director for the Primary Care Sports Medicine program at University Hospitals Rainbow Babies & Children’s Hospital.

For outdoor sports, athletes who are not fully vaccinated should be encouraged to wear masks on the sidelines and during group training and competition when they are within 3 feet of others for sustained amounts of time, according to the AAP.
 

Get back into exercise gradually

In general, athletes who have not been active for more than a month should resume exercise gradually, Dr. Briskin says. Starting at 25% of normal volume and increasing slowly over time – with 10% increases each week – is one rule of thumb.

“Those who have taken a prolonged break from sports are at a higher risk of injury when they return,” she notes. “Families should also be aware of an increased risk for heat-related illness if they are not acclimated.”

Caitlyn Mooney, MD, a team doctor for the University of Texas, San Antonio, has heard reports of doctors seeing more injuries like stress fractures. Some cases may relate to people going from “months of doing nothing to all of a sudden going back to sports,” says Dr. Mooney, who is also a clinical assistant professor of pediatrics and orthopedics at UT Health San Antonio.

“The coaches, the parents, and the athletes themselves really need to keep in mind that it’s not like a regular season,” Dr. Mooney says. She suggests gradually ramping up activity and paying attention to any pain. “That’s a good indicator that maybe you’re going too fast,” she adds.

Athletes should be mindful of other symptoms too when restarting exercise, especially after illness.

It is “very important that any athlete with recent COVID-19 monitor for new symptoms when they return to exercise,” says Jonathan Drezner, MD, a professor of family medicine at the University of Washington, Seattle. “A little fatigue from detraining may be expected, but exertional chest pain deserves more evaluation.”

Dr. Drezner – editor-in-chief of the British Journal of Sports Medicine and team doctor for the Seattle Seahawks – along with Dr. Baggish and colleagues, found a low prevalence of cardiac involvement in a study of more than 3,000 college athletes with prior SARS-CoV-2 infection.

“Any athlete, despite their initial symptom course, who has cardiopulmonary symptoms on return to exercise, particularly chest pain, should see their physician for a comprehensive cardiac evaluation,” Dr. Drezner says. “Cardiac MRI should be reserved for athletes with abnormal testing or when clinical suspicion of myocardial involvement is high.”

If an athlete had COVID-19 with moderate symptoms (such as fever, chills, or a flu-like syndrome) or cardiopulmonary symptoms (such as chest pain or shortness of breath), cardiac testing should be considered, he notes.

These symptoms “were associated with a higher prevalence of cardiac involvement,” Dr. Drezner said in an email. “Testing may include an ECG, echocardiogram (ultrasound), and troponin (blood test).”

For kids who test positive for SARS-CoV-2 but do not have symptoms, or their symptoms last less than 4 days, a phone call or telemedicine visit with their doctor may be enough to clear them to play, says Dr. Briskin, who’s also an assistant professor of pediatrics at Case Western Reserve University, Cleveland.

“This will allow the physician an opportunity to screen for any concerning cardiac signs or symptoms, update the patient’s electronic medical record with the recent COVID-19 infection, and provide appropriate guidance back to exercise,” she adds.

Dr. Baggish, Dr. Briskin, Dr. Mooney, and Dr. Drezner had no relevant financial disclosures.

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

As pandemic restrictions ease and young athletes once again take to fields, courts, tracks, and rinks, doctors are sharing ways to help them get back to sports safely.

That means taking steps to prevent COVID-19.

It also means trying to avoid sports-related injuries, which may be more likely if young athletes didn’t move around so much during the pandemic.

For adolescents who are eligible, getting a COVID-19 vaccine may be the most important thing they can do, according to the American Academy of Pediatrics.

“The AAP encourages all people who are eligible to receive the COVID-19 vaccine as soon as it is available,” the organization wrote in updated guidance on returning to sports and physical activity.

“I don’t think it can be overemphasized how important these vaccines are, both for the individual and at the community level,” says Aaron L. Baggish, MD, an associate professor of medicine at Harvard Medical School, Boston, and director of the Cardiovascular Performance Program at Massachusetts General Hospital in Boston.

Dr. Baggish, team cardiologist for the New England Patriots, the Boston Bruins, the New England Revolution, U.S. Men’s and Women’s Soccer, and U.S. Rowing, as well as medical director for the Boston Marathon, has studied the effects of COVID-19 on the heart in college athletes and written return-to-play recommendations for athletes of high school age and older.

“Millions of people have received these vaccines from age 12 up,” Dr. Baggish says. “The efficacy continues to look very durable and near complete, and the risk associated with vaccination is incredibly low, to the point where the risk-benefit ratio across the age spectrum, whether you’re athletic or not, strongly favors getting vaccinated. There is really no reason to hold off at this point.”

While outdoor activities are lower-risk for spreading COVID-19 and many people have been vaccinated, masks still should be worn in certain settings, the AAP notes.

“Indoor spaces that are crowded are still high-risk for COVID-19 transmission. And we recognize that not everyone in these settings may be vaccinated,” says Susannah Briskin, MD, lead author of the AAP guidance.

“So for indoor sporting events with spectators, in locker rooms or other small spaces such as a training room, and during shared car rides or school transportation to and from events, individuals should continue to mask,” adds Dr. Briskin, a pediatrician in the Division of Sports Medicine and fellowship director for the Primary Care Sports Medicine program at University Hospitals Rainbow Babies & Children’s Hospital.

For outdoor sports, athletes who are not fully vaccinated should be encouraged to wear masks on the sidelines and during group training and competition when they are within 3 feet of others for sustained amounts of time, according to the AAP.
 

Get back into exercise gradually

In general, athletes who have not been active for more than a month should resume exercise gradually, Dr. Briskin says. Starting at 25% of normal volume and increasing slowly over time – with 10% increases each week – is one rule of thumb.

“Those who have taken a prolonged break from sports are at a higher risk of injury when they return,” she notes. “Families should also be aware of an increased risk for heat-related illness if they are not acclimated.”

Caitlyn Mooney, MD, a team doctor for the University of Texas, San Antonio, has heard reports of doctors seeing more injuries like stress fractures. Some cases may relate to people going from “months of doing nothing to all of a sudden going back to sports,” says Dr. Mooney, who is also a clinical assistant professor of pediatrics and orthopedics at UT Health San Antonio.

“The coaches, the parents, and the athletes themselves really need to keep in mind that it’s not like a regular season,” Dr. Mooney says. She suggests gradually ramping up activity and paying attention to any pain. “That’s a good indicator that maybe you’re going too fast,” she adds.

Athletes should be mindful of other symptoms too when restarting exercise, especially after illness.

It is “very important that any athlete with recent COVID-19 monitor for new symptoms when they return to exercise,” says Jonathan Drezner, MD, a professor of family medicine at the University of Washington, Seattle. “A little fatigue from detraining may be expected, but exertional chest pain deserves more evaluation.”

Dr. Drezner – editor-in-chief of the British Journal of Sports Medicine and team doctor for the Seattle Seahawks – along with Dr. Baggish and colleagues, found a low prevalence of cardiac involvement in a study of more than 3,000 college athletes with prior SARS-CoV-2 infection.

“Any athlete, despite their initial symptom course, who has cardiopulmonary symptoms on return to exercise, particularly chest pain, should see their physician for a comprehensive cardiac evaluation,” Dr. Drezner says. “Cardiac MRI should be reserved for athletes with abnormal testing or when clinical suspicion of myocardial involvement is high.”

If an athlete had COVID-19 with moderate symptoms (such as fever, chills, or a flu-like syndrome) or cardiopulmonary symptoms (such as chest pain or shortness of breath), cardiac testing should be considered, he notes.

These symptoms “were associated with a higher prevalence of cardiac involvement,” Dr. Drezner said in an email. “Testing may include an ECG, echocardiogram (ultrasound), and troponin (blood test).”

For kids who test positive for SARS-CoV-2 but do not have symptoms, or their symptoms last less than 4 days, a phone call or telemedicine visit with their doctor may be enough to clear them to play, says Dr. Briskin, who’s also an assistant professor of pediatrics at Case Western Reserve University, Cleveland.

“This will allow the physician an opportunity to screen for any concerning cardiac signs or symptoms, update the patient’s electronic medical record with the recent COVID-19 infection, and provide appropriate guidance back to exercise,” she adds.

Dr. Baggish, Dr. Briskin, Dr. Mooney, and Dr. Drezner had no relevant financial disclosures.

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

As pandemic restrictions ease and young athletes once again take to fields, courts, tracks, and rinks, doctors are sharing ways to help them get back to sports safely.

That means taking steps to prevent COVID-19.

It also means trying to avoid sports-related injuries, which may be more likely if young athletes didn’t move around so much during the pandemic.

For adolescents who are eligible, getting a COVID-19 vaccine may be the most important thing they can do, according to the American Academy of Pediatrics.

“The AAP encourages all people who are eligible to receive the COVID-19 vaccine as soon as it is available,” the organization wrote in updated guidance on returning to sports and physical activity.

“I don’t think it can be overemphasized how important these vaccines are, both for the individual and at the community level,” says Aaron L. Baggish, MD, an associate professor of medicine at Harvard Medical School, Boston, and director of the Cardiovascular Performance Program at Massachusetts General Hospital in Boston.

Dr. Baggish, team cardiologist for the New England Patriots, the Boston Bruins, the New England Revolution, U.S. Men’s and Women’s Soccer, and U.S. Rowing, as well as medical director for the Boston Marathon, has studied the effects of COVID-19 on the heart in college athletes and written return-to-play recommendations for athletes of high school age and older.

“Millions of people have received these vaccines from age 12 up,” Dr. Baggish says. “The efficacy continues to look very durable and near complete, and the risk associated with vaccination is incredibly low, to the point where the risk-benefit ratio across the age spectrum, whether you’re athletic or not, strongly favors getting vaccinated. There is really no reason to hold off at this point.”

While outdoor activities are lower-risk for spreading COVID-19 and many people have been vaccinated, masks still should be worn in certain settings, the AAP notes.

“Indoor spaces that are crowded are still high-risk for COVID-19 transmission. And we recognize that not everyone in these settings may be vaccinated,” says Susannah Briskin, MD, lead author of the AAP guidance.

“So for indoor sporting events with spectators, in locker rooms or other small spaces such as a training room, and during shared car rides or school transportation to and from events, individuals should continue to mask,” adds Dr. Briskin, a pediatrician in the Division of Sports Medicine and fellowship director for the Primary Care Sports Medicine program at University Hospitals Rainbow Babies & Children’s Hospital.

For outdoor sports, athletes who are not fully vaccinated should be encouraged to wear masks on the sidelines and during group training and competition when they are within 3 feet of others for sustained amounts of time, according to the AAP.
 

Get back into exercise gradually

In general, athletes who have not been active for more than a month should resume exercise gradually, Dr. Briskin says. Starting at 25% of normal volume and increasing slowly over time – with 10% increases each week – is one rule of thumb.

“Those who have taken a prolonged break from sports are at a higher risk of injury when they return,” she notes. “Families should also be aware of an increased risk for heat-related illness if they are not acclimated.”

Caitlyn Mooney, MD, a team doctor for the University of Texas, San Antonio, has heard reports of doctors seeing more injuries like stress fractures. Some cases may relate to people going from “months of doing nothing to all of a sudden going back to sports,” says Dr. Mooney, who is also a clinical assistant professor of pediatrics and orthopedics at UT Health San Antonio.

“The coaches, the parents, and the athletes themselves really need to keep in mind that it’s not like a regular season,” Dr. Mooney says. She suggests gradually ramping up activity and paying attention to any pain. “That’s a good indicator that maybe you’re going too fast,” she adds.

Athletes should be mindful of other symptoms too when restarting exercise, especially after illness.

It is “very important that any athlete with recent COVID-19 monitor for new symptoms when they return to exercise,” says Jonathan Drezner, MD, a professor of family medicine at the University of Washington, Seattle. “A little fatigue from detraining may be expected, but exertional chest pain deserves more evaluation.”

Dr. Drezner – editor-in-chief of the British Journal of Sports Medicine and team doctor for the Seattle Seahawks – along with Dr. Baggish and colleagues, found a low prevalence of cardiac involvement in a study of more than 3,000 college athletes with prior SARS-CoV-2 infection.

“Any athlete, despite their initial symptom course, who has cardiopulmonary symptoms on return to exercise, particularly chest pain, should see their physician for a comprehensive cardiac evaluation,” Dr. Drezner says. “Cardiac MRI should be reserved for athletes with abnormal testing or when clinical suspicion of myocardial involvement is high.”

If an athlete had COVID-19 with moderate symptoms (such as fever, chills, or a flu-like syndrome) or cardiopulmonary symptoms (such as chest pain or shortness of breath), cardiac testing should be considered, he notes.

These symptoms “were associated with a higher prevalence of cardiac involvement,” Dr. Drezner said in an email. “Testing may include an ECG, echocardiogram (ultrasound), and troponin (blood test).”

For kids who test positive for SARS-CoV-2 but do not have symptoms, or their symptoms last less than 4 days, a phone call or telemedicine visit with their doctor may be enough to clear them to play, says Dr. Briskin, who’s also an assistant professor of pediatrics at Case Western Reserve University, Cleveland.

“This will allow the physician an opportunity to screen for any concerning cardiac signs or symptoms, update the patient’s electronic medical record with the recent COVID-19 infection, and provide appropriate guidance back to exercise,” she adds.

Dr. Baggish, Dr. Briskin, Dr. Mooney, and Dr. Drezner had no relevant financial disclosures.

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

The American Society of Clinical Oncology (ASCO) now recommends offering 1 year of adjuvant olaparib therapy to patients with early-stage HER2-negative, BRCA-mutated breast cancer who have completed chemotherapy and local treatment.

The change in management of hereditary breast cancer is outlined in an update to 2020 guidelines, and it comes as a “rapid recommendation” on the heels of the phase 3 OlympiA trial results, which indicated a 42% improvement in invasive and distant disease-free survival with the PARP inhibitor olaparib (Lynparza) in comparison with placebo.

The OlympiA trial results, as reported by this news organization, were presented during the plenary session of the ASCO 2021 annual meeting and were published June 3 in The New England Journal of Medicine.

“These clear and positive data prompted ASCO to issue a provisional update of the guideline recommendation focused specifically on the role of olaparib in this setting,” states an ASCO press release.

The previous 2020 guidelines stated: “There are insufficient data ... to recommend a PARP inhibitor for patients with nonmetastatic breast cancer.” The OlympiA trial changed that. ASCO now recommends that patients with early-stage, HER2-negative, BRCA-mutated breast cancer at high risk for recurrence be offered olaparib after completion of chemotherapy and local treatment, including radiotherapy.

The update states: “For those who had surgery first, adjuvant olaparib is recommended for patients with TNBC [triple-negative breast cancer] and tumor size greater than 2 cm or any involved axillary nodes. For patients with hormone receptor–positive disease, adjuvant olaparib is recommended for those with at least four involved axillary lymph nodes. For patients who had neoadjuvant chemotherapy, adjuvant olaparib is recommended for patients with TNBC and any residual cancer. Adjuvant olaparib is recommended for patients with residual disease and an estrogen receptor status and tumor grade (CSP+EG) score greater than or equal to 3.”

“The findings from the OlympiA trial – presented just last week – mark a significant improvement in the care of these patients,” Julie Garlow, MD, ASCO’s executive vice president and chief medical officer, states in the ASCO press release.

“ASCO’s Expert Guideline Panel and Evidence-based Medicine Committee noted this and then quickly produced and provisionally approved this guideline update to enable patients to begin to benefit from this research advance as quickly as possible,” she said.

A formal assessment and submission for publication in the Journal of Clinical Oncology will follow the release notes.

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

The American Society of Clinical Oncology (ASCO) now recommends offering 1 year of adjuvant olaparib therapy to patients with early-stage HER2-negative, BRCA-mutated breast cancer who have completed chemotherapy and local treatment.

The change in management of hereditary breast cancer is outlined in an update to 2020 guidelines, and it comes as a “rapid recommendation” on the heels of the phase 3 OlympiA trial results, which indicated a 42% improvement in invasive and distant disease-free survival with the PARP inhibitor olaparib (Lynparza) in comparison with placebo.

The OlympiA trial results, as reported by this news organization, were presented during the plenary session of the ASCO 2021 annual meeting and were published June 3 in The New England Journal of Medicine.

“These clear and positive data prompted ASCO to issue a provisional update of the guideline recommendation focused specifically on the role of olaparib in this setting,” states an ASCO press release.

The previous 2020 guidelines stated: “There are insufficient data ... to recommend a PARP inhibitor for patients with nonmetastatic breast cancer.” The OlympiA trial changed that. ASCO now recommends that patients with early-stage, HER2-negative, BRCA-mutated breast cancer at high risk for recurrence be offered olaparib after completion of chemotherapy and local treatment, including radiotherapy.

The update states: “For those who had surgery first, adjuvant olaparib is recommended for patients with TNBC [triple-negative breast cancer] and tumor size greater than 2 cm or any involved axillary nodes. For patients with hormone receptor–positive disease, adjuvant olaparib is recommended for those with at least four involved axillary lymph nodes. For patients who had neoadjuvant chemotherapy, adjuvant olaparib is recommended for patients with TNBC and any residual cancer. Adjuvant olaparib is recommended for patients with residual disease and an estrogen receptor status and tumor grade (CSP+EG) score greater than or equal to 3.”

“The findings from the OlympiA trial – presented just last week – mark a significant improvement in the care of these patients,” Julie Garlow, MD, ASCO’s executive vice president and chief medical officer, states in the ASCO press release.

“ASCO’s Expert Guideline Panel and Evidence-based Medicine Committee noted this and then quickly produced and provisionally approved this guideline update to enable patients to begin to benefit from this research advance as quickly as possible,” she said.

A formal assessment and submission for publication in the Journal of Clinical Oncology will follow the release notes.

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

The American Society of Clinical Oncology (ASCO) now recommends offering 1 year of adjuvant olaparib therapy to patients with early-stage HER2-negative, BRCA-mutated breast cancer who have completed chemotherapy and local treatment.

The change in management of hereditary breast cancer is outlined in an update to 2020 guidelines, and it comes as a “rapid recommendation” on the heels of the phase 3 OlympiA trial results, which indicated a 42% improvement in invasive and distant disease-free survival with the PARP inhibitor olaparib (Lynparza) in comparison with placebo.

The OlympiA trial results, as reported by this news organization, were presented during the plenary session of the ASCO 2021 annual meeting and were published June 3 in The New England Journal of Medicine.

“These clear and positive data prompted ASCO to issue a provisional update of the guideline recommendation focused specifically on the role of olaparib in this setting,” states an ASCO press release.

The previous 2020 guidelines stated: “There are insufficient data ... to recommend a PARP inhibitor for patients with nonmetastatic breast cancer.” The OlympiA trial changed that. ASCO now recommends that patients with early-stage, HER2-negative, BRCA-mutated breast cancer at high risk for recurrence be offered olaparib after completion of chemotherapy and local treatment, including radiotherapy.

The update states: “For those who had surgery first, adjuvant olaparib is recommended for patients with TNBC [triple-negative breast cancer] and tumor size greater than 2 cm or any involved axillary nodes. For patients with hormone receptor–positive disease, adjuvant olaparib is recommended for those with at least four involved axillary lymph nodes. For patients who had neoadjuvant chemotherapy, adjuvant olaparib is recommended for patients with TNBC and any residual cancer. Adjuvant olaparib is recommended for patients with residual disease and an estrogen receptor status and tumor grade (CSP+EG) score greater than or equal to 3.”

“The findings from the OlympiA trial – presented just last week – mark a significant improvement in the care of these patients,” Julie Garlow, MD, ASCO’s executive vice president and chief medical officer, states in the ASCO press release.

“ASCO’s Expert Guideline Panel and Evidence-based Medicine Committee noted this and then quickly produced and provisionally approved this guideline update to enable patients to begin to benefit from this research advance as quickly as possible,” she said.

A formal assessment and submission for publication in the Journal of Clinical Oncology will follow the release notes.

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

The optimal first step to address mild to moderately elevated blood pressure and cholesterol in otherwise healthy adults is a “prescription” to sit less and move more, the American Heart Association says in a new scientific statement.

“The current American Heart Association guidelines for diagnosing high blood pressure and cholesterol recognize that otherwise healthy individuals with mildly or moderately elevated levels of these cardiovascular risk factors should actively attempt to reduce these risks,” Bethany Barone Gibbs, PhD, chair of the statement writing group, said in an AHA news release.

“The first treatment strategy for many of these patients should be healthy lifestyle changes beginning with increasing physical activity,” said Dr. Gibbs, from the University of Pittsburgh.

The 12-page AHA scientific statement – Physical Activity as a Critical Component of First-Line Treatment for Elevated Blood Pressure or Cholesterol: Who, What, and How? – was published online June 2 in Hypertension.
 

Every little bit helps

According to the AHA, about 21% of American adults have systolic blood pressure between 120 and 139 mm Hg, or diastolic blood pressure between 80 and 89 mm Hg, which meets the criteria for lifestyle-only treatment for elevated BP outlined in the American College of Cardiology (ACC)/AHA high blood pressure guideline.

In addition, about 28% of American adults have LDL cholesterol above 70 mg/dL and otherwise meet the low-risk criteria for heart disease or stroke. These individuals would meet the criteria for lifestyle-only treatment outlined in the 2018 ACC/AHA cholesterol treatment guidelines, which include increased physical activity, weight loss, better diet, smoking cessation, and moderating alcohol intake.

“Of the recommended lifestyle changes, increasing physical activity has extensive benefits, including improving both blood pressure and blood cholesterol, that are comparable, superior, or complementary to other healthy lifestyle changes,” the writing group says.

“Physical activity assessment and prescription are an excellent lifestyle behavior treatment option for all patients, including for the large population of mild-moderate-risk patients with elevated blood pressure and blood cholesterol,” they note.

Research has shown that increasing physical activity can lead to clinically meaningful 3 or 4 mm Hg reductions in systolic and diastolic blood pressure, and 3 to 6 mg/dL decreases in LDL cholesterol, the authors point out.

Previous evidence also shows that physically active people have a 21% lower risk of developing cardiovascular disease and a 36% lower risk for death from cardiovascular diseases than those who are not physically active.

Physical activity also has benefits beyond heart health, including a lower risk for some cancers; improved bone, brain, and mental health; and better sleep, they note.

The U.S. Department of Health and Human Services 2018 physical activity guidelines advise Americans to log 150 minutes of moderate-intensity aerobic exercise or 75 minutes of vigorous aerobic activity each week and to participate in two or more weekly strength training sessions.

However, there is no minimum amount of time to receive benefits from physical activity.

“Every little bit of activity is better than none. Even small initial increases of 5 to 10 minutes a day can yield health benefits,” Dr. Gibbs said.
 

Translational advice for clinicians

The AHA statement encourages clinicians to ask patients about their physical activity at every interaction; provide ideas and resources to help patients improve and sustain regular life-long physical activity; and encourage and celebrate small increases in activity, such as walking more or taking the stairs, to help with motivation.

“In our world where physical activity is increasingly engineered out of our lives and the overwhelming default is to sit – and even more so now as the nation and the world is practicing quarantine and isolation to reduce the spread of coronavirus – the message that we must be relentless in our pursuit to ‘sit less and move more’ throughout the day is more important than ever,” said Dr. Gibbs.

The statement was prepared by a volunteer writing group on behalf of the AHA Council on Lifestyle and Cardiometabolic Health; the Council on Cardiovascular and Stroke Nursing; and the Council on Clinical Cardiology.

This research had no commercial funding. A list of disclosures for the writing group is available with the original article.

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

The optimal first step to address mild to moderately elevated blood pressure and cholesterol in otherwise healthy adults is a “prescription” to sit less and move more, the American Heart Association says in a new scientific statement.

“The current American Heart Association guidelines for diagnosing high blood pressure and cholesterol recognize that otherwise healthy individuals with mildly or moderately elevated levels of these cardiovascular risk factors should actively attempt to reduce these risks,” Bethany Barone Gibbs, PhD, chair of the statement writing group, said in an AHA news release.

“The first treatment strategy for many of these patients should be healthy lifestyle changes beginning with increasing physical activity,” said Dr. Gibbs, from the University of Pittsburgh.

The 12-page AHA scientific statement – Physical Activity as a Critical Component of First-Line Treatment for Elevated Blood Pressure or Cholesterol: Who, What, and How? – was published online June 2 in Hypertension.
 

Every little bit helps

According to the AHA, about 21% of American adults have systolic blood pressure between 120 and 139 mm Hg, or diastolic blood pressure between 80 and 89 mm Hg, which meets the criteria for lifestyle-only treatment for elevated BP outlined in the American College of Cardiology (ACC)/AHA high blood pressure guideline.

In addition, about 28% of American adults have LDL cholesterol above 70 mg/dL and otherwise meet the low-risk criteria for heart disease or stroke. These individuals would meet the criteria for lifestyle-only treatment outlined in the 2018 ACC/AHA cholesterol treatment guidelines, which include increased physical activity, weight loss, better diet, smoking cessation, and moderating alcohol intake.

“Of the recommended lifestyle changes, increasing physical activity has extensive benefits, including improving both blood pressure and blood cholesterol, that are comparable, superior, or complementary to other healthy lifestyle changes,” the writing group says.

“Physical activity assessment and prescription are an excellent lifestyle behavior treatment option for all patients, including for the large population of mild-moderate-risk patients with elevated blood pressure and blood cholesterol,” they note.

Research has shown that increasing physical activity can lead to clinically meaningful 3 or 4 mm Hg reductions in systolic and diastolic blood pressure, and 3 to 6 mg/dL decreases in LDL cholesterol, the authors point out.

Previous evidence also shows that physically active people have a 21% lower risk of developing cardiovascular disease and a 36% lower risk for death from cardiovascular diseases than those who are not physically active.

Physical activity also has benefits beyond heart health, including a lower risk for some cancers; improved bone, brain, and mental health; and better sleep, they note.

The U.S. Department of Health and Human Services 2018 physical activity guidelines advise Americans to log 150 minutes of moderate-intensity aerobic exercise or 75 minutes of vigorous aerobic activity each week and to participate in two or more weekly strength training sessions.

However, there is no minimum amount of time to receive benefits from physical activity.

“Every little bit of activity is better than none. Even small initial increases of 5 to 10 minutes a day can yield health benefits,” Dr. Gibbs said.
 

Translational advice for clinicians

The AHA statement encourages clinicians to ask patients about their physical activity at every interaction; provide ideas and resources to help patients improve and sustain regular life-long physical activity; and encourage and celebrate small increases in activity, such as walking more or taking the stairs, to help with motivation.

“In our world where physical activity is increasingly engineered out of our lives and the overwhelming default is to sit – and even more so now as the nation and the world is practicing quarantine and isolation to reduce the spread of coronavirus – the message that we must be relentless in our pursuit to ‘sit less and move more’ throughout the day is more important than ever,” said Dr. Gibbs.

The statement was prepared by a volunteer writing group on behalf of the AHA Council on Lifestyle and Cardiometabolic Health; the Council on Cardiovascular and Stroke Nursing; and the Council on Clinical Cardiology.

This research had no commercial funding. A list of disclosures for the writing group is available with the original article.

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

The optimal first step to address mild to moderately elevated blood pressure and cholesterol in otherwise healthy adults is a “prescription” to sit less and move more, the American Heart Association says in a new scientific statement.

“The current American Heart Association guidelines for diagnosing high blood pressure and cholesterol recognize that otherwise healthy individuals with mildly or moderately elevated levels of these cardiovascular risk factors should actively attempt to reduce these risks,” Bethany Barone Gibbs, PhD, chair of the statement writing group, said in an AHA news release.

“The first treatment strategy for many of these patients should be healthy lifestyle changes beginning with increasing physical activity,” said Dr. Gibbs, from the University of Pittsburgh.

The 12-page AHA scientific statement – Physical Activity as a Critical Component of First-Line Treatment for Elevated Blood Pressure or Cholesterol: Who, What, and How? – was published online June 2 in Hypertension.
 

Every little bit helps

According to the AHA, about 21% of American adults have systolic blood pressure between 120 and 139 mm Hg, or diastolic blood pressure between 80 and 89 mm Hg, which meets the criteria for lifestyle-only treatment for elevated BP outlined in the American College of Cardiology (ACC)/AHA high blood pressure guideline.

In addition, about 28% of American adults have LDL cholesterol above 70 mg/dL and otherwise meet the low-risk criteria for heart disease or stroke. These individuals would meet the criteria for lifestyle-only treatment outlined in the 2018 ACC/AHA cholesterol treatment guidelines, which include increased physical activity, weight loss, better diet, smoking cessation, and moderating alcohol intake.

“Of the recommended lifestyle changes, increasing physical activity has extensive benefits, including improving both blood pressure and blood cholesterol, that are comparable, superior, or complementary to other healthy lifestyle changes,” the writing group says.

“Physical activity assessment and prescription are an excellent lifestyle behavior treatment option for all patients, including for the large population of mild-moderate-risk patients with elevated blood pressure and blood cholesterol,” they note.

Research has shown that increasing physical activity can lead to clinically meaningful 3 or 4 mm Hg reductions in systolic and diastolic blood pressure, and 3 to 6 mg/dL decreases in LDL cholesterol, the authors point out.

Previous evidence also shows that physically active people have a 21% lower risk of developing cardiovascular disease and a 36% lower risk for death from cardiovascular diseases than those who are not physically active.

Physical activity also has benefits beyond heart health, including a lower risk for some cancers; improved bone, brain, and mental health; and better sleep, they note.

The U.S. Department of Health and Human Services 2018 physical activity guidelines advise Americans to log 150 minutes of moderate-intensity aerobic exercise or 75 minutes of vigorous aerobic activity each week and to participate in two or more weekly strength training sessions.

However, there is no minimum amount of time to receive benefits from physical activity.

“Every little bit of activity is better than none. Even small initial increases of 5 to 10 minutes a day can yield health benefits,” Dr. Gibbs said.
 

Translational advice for clinicians

The AHA statement encourages clinicians to ask patients about their physical activity at every interaction; provide ideas and resources to help patients improve and sustain regular life-long physical activity; and encourage and celebrate small increases in activity, such as walking more or taking the stairs, to help with motivation.

“In our world where physical activity is increasingly engineered out of our lives and the overwhelming default is to sit – and even more so now as the nation and the world is practicing quarantine and isolation to reduce the spread of coronavirus – the message that we must be relentless in our pursuit to ‘sit less and move more’ throughout the day is more important than ever,” said Dr. Gibbs.

The statement was prepared by a volunteer writing group on behalf of the AHA Council on Lifestyle and Cardiometabolic Health; the Council on Cardiovascular and Stroke Nursing; and the Council on Clinical Cardiology.

This research had no commercial funding. A list of disclosures for the writing group is available with the original article.

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

For adult outpatients with moderate to severe Crohn’s disease, new guidelines from the American Gastroenterological Association strongly recommend induction and maintenance therapy with anti–tumor necrosis factor–alpha agents or ustekinumab over no treatment.

“Although [related] evidence supporting infliximab and adalimumab was moderate certainty, the evidence for certolizumab pegol was low certainty,” wrote Joseph D. Feuerstein, MD, of Beth Israel Deaconess Medical Center in Boston and his associates, on behalf of the AGA Clinical Guidelines Committee in Gastroenterology. Vedolizumab received a conditional recommendation based on less robust evidence for induction in this setting.

Outcomes in Crohn’s disease have improved, likely “because of earlier diagnosis, increasing use of biologics, escalation or alteration of therapy based on disease severity, and endoscopic management of colorectal cancer,” Dr. Feuerstein and his associates wrote.

This update reflects these changes, strongly recommending biologic monotherapy over thiopurine monotherapy for induction. It also suggests “early induction with a biologic, with or without an immunomodulator, rather than delaying their use until after failure of 5-aminosalicylates and/or corticosteroids.” For the latter assessment, the guidelines noted that some studies were open label (which increases risk of bias) and that upfront combination therapy with a biologic and an immunomodulator could sometimes lead to overtreatment. Nonetheless, studies shown associations between the step-up approach and “a potential risk of harm from disease progression related to inadequate disease therapy.”

The guidelines also recommend that patients who have never received biologic drugs receive induction therapy with infliximab, adalimumab, or ustekinumab, rather than certolizumab pegol. This strong recommendation reflects the findings of a network meta-analysis conducted by the AGA in which certolizumab pegol was least effective, with no evidence for clear differences in efficacy among infliximab, adalimumab, and ustekinumab. A network meta-analysis is a type of study that enables experts to compare therapies indirectly when head-to-head trials are lacking.

For patients who are naive to both biologics and immunomodulators, the guidelines suggest combination treatment with infliximab or adalimumab plus a thiopurine rather than monotherapy with either biologic. Because of a lack of randomized controlled trials, no recommendation is made regarding combination therapy with ustekinumab or vedolizumab.

For patients who have received but never responded to anti-TNF-alpha therapy (so-called primary nonresponders), ustekinumab is strongly recommended, and vedolizumab is conditionally recommended. For patients who initially responded to infliximab and then lost their response (secondary nonresponders), adalimumab and ustekinumab are strongly recommended, while vedolizumab receives another conditional recommendation.

For patients with moderate to severe luminal disease, induction and maintenance with infliximab, adalimumab, certolizumab pegol, vedolizumab, or ustekinumab are recommended over no treatment. Thiopurine monotherapy is suggested over no treatment for maintenance of remission, but not for induction. For methotrexate, subcutaneous or intramuscular monotherapy is suggested over no treatment. The sole available trial on oral methotrexate (12.5 mg/week) was negative, and “it is not clear if a higher dose would have been more effective,” according to the guidelines. They strongly recommend against using 5-aminosalicytes or sulfasalazine because of lack of efficacy for maintaining remission and suggest not using natalizumab because of the risk of progressive multifocal leukoencephalopathy (PML). Corticosteroids are considered preferable to no treatment for induction but not for maintenance.

For patients with fistulizing disease, infliximab has “the most robust evidence” and receives a strong recommendation for induction and maintenance, while adalimumab, ustekinumab, and vedolizumab receive conditional recommendations. “In contrast, evidence suggests certolizumab pegol may not be effective for induction of fistula remission,” the guidelines state. For patients with perianal disease with an active fistula but no abscess, combining biologics with antibiotics is strongly recommended over biologic monotherapy.

The guidelines define moderate to severe Crohn’s disease as a Crohn’s Disease Activity Index (CDAI) score of 220 or higher, the typical cutoff used in clinical trials. The recommendations apply to outpatient management, but in most cases would also apply to inpatients.

An expert commentary accompanying the guidelines praises their “rigorous methods” based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. Edith Y. Ho, MD, of Stanford (Calif.) University and her associates also laud the “innovative methods” that were used to compare treatments and assess data quality. In addition to the network meta-analysis, the guidelines set an a priori minimal clinically important difference (MCID) score of 10% for risk of treatment failure versus placebo. This led to more clinically relevant guidance, such as the conditional recommendation for vedolizumab in luminal disease since this drug did not meet the MCID threshold. Finally, the commentators emphasized that the guidelines are meant to facilitate, not dictate, treatment decisions: “Choice of therapies and treatment strategies will continue to rely on clinical judgment as well, and will continue to be informed by patient-specific values and preferences.”

The AGA Institute was the sole source of funding. Four coauthors disclosed ties to Celgene, Takeda, Pendopharm, Merck Canada, Guardant Health, Ferring, and AbbVie. Dr. Feurstein and the other guidelines coauthors reported having no conflicts of interest. Some authors on the editorial disclosed relationships with AbbVie, Pfizer, and Janssen, but the remaining had no conflicts to disclose.

For adult outpatients with moderate to severe Crohn’s disease, new guidelines from the American Gastroenterological Association strongly recommend induction and maintenance therapy with anti–tumor necrosis factor–alpha agents or ustekinumab over no treatment.

“Although [related] evidence supporting infliximab and adalimumab was moderate certainty, the evidence for certolizumab pegol was low certainty,” wrote Joseph D. Feuerstein, MD, of Beth Israel Deaconess Medical Center in Boston and his associates, on behalf of the AGA Clinical Guidelines Committee in Gastroenterology. Vedolizumab received a conditional recommendation based on less robust evidence for induction in this setting.

Outcomes in Crohn’s disease have improved, likely “because of earlier diagnosis, increasing use of biologics, escalation or alteration of therapy based on disease severity, and endoscopic management of colorectal cancer,” Dr. Feuerstein and his associates wrote.

This update reflects these changes, strongly recommending biologic monotherapy over thiopurine monotherapy for induction. It also suggests “early induction with a biologic, with or without an immunomodulator, rather than delaying their use until after failure of 5-aminosalicylates and/or corticosteroids.” For the latter assessment, the guidelines noted that some studies were open label (which increases risk of bias) and that upfront combination therapy with a biologic and an immunomodulator could sometimes lead to overtreatment. Nonetheless, studies shown associations between the step-up approach and “a potential risk of harm from disease progression related to inadequate disease therapy.”

The guidelines also recommend that patients who have never received biologic drugs receive induction therapy with infliximab, adalimumab, or ustekinumab, rather than certolizumab pegol. This strong recommendation reflects the findings of a network meta-analysis conducted by the AGA in which certolizumab pegol was least effective, with no evidence for clear differences in efficacy among infliximab, adalimumab, and ustekinumab. A network meta-analysis is a type of study that enables experts to compare therapies indirectly when head-to-head trials are lacking.

For patients who are naive to both biologics and immunomodulators, the guidelines suggest combination treatment with infliximab or adalimumab plus a thiopurine rather than monotherapy with either biologic. Because of a lack of randomized controlled trials, no recommendation is made regarding combination therapy with ustekinumab or vedolizumab.

For patients who have received but never responded to anti-TNF-alpha therapy (so-called primary nonresponders), ustekinumab is strongly recommended, and vedolizumab is conditionally recommended. For patients who initially responded to infliximab and then lost their response (secondary nonresponders), adalimumab and ustekinumab are strongly recommended, while vedolizumab receives another conditional recommendation.

For patients with moderate to severe luminal disease, induction and maintenance with infliximab, adalimumab, certolizumab pegol, vedolizumab, or ustekinumab are recommended over no treatment. Thiopurine monotherapy is suggested over no treatment for maintenance of remission, but not for induction. For methotrexate, subcutaneous or intramuscular monotherapy is suggested over no treatment. The sole available trial on oral methotrexate (12.5 mg/week) was negative, and “it is not clear if a higher dose would have been more effective,” according to the guidelines. They strongly recommend against using 5-aminosalicytes or sulfasalazine because of lack of efficacy for maintaining remission and suggest not using natalizumab because of the risk of progressive multifocal leukoencephalopathy (PML). Corticosteroids are considered preferable to no treatment for induction but not for maintenance.

For patients with fistulizing disease, infliximab has “the most robust evidence” and receives a strong recommendation for induction and maintenance, while adalimumab, ustekinumab, and vedolizumab receive conditional recommendations. “In contrast, evidence suggests certolizumab pegol may not be effective for induction of fistula remission,” the guidelines state. For patients with perianal disease with an active fistula but no abscess, combining biologics with antibiotics is strongly recommended over biologic monotherapy.

The guidelines define moderate to severe Crohn’s disease as a Crohn’s Disease Activity Index (CDAI) score of 220 or higher, the typical cutoff used in clinical trials. The recommendations apply to outpatient management, but in most cases would also apply to inpatients.

An expert commentary accompanying the guidelines praises their “rigorous methods” based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. Edith Y. Ho, MD, of Stanford (Calif.) University and her associates also laud the “innovative methods” that were used to compare treatments and assess data quality. In addition to the network meta-analysis, the guidelines set an a priori minimal clinically important difference (MCID) score of 10% for risk of treatment failure versus placebo. This led to more clinically relevant guidance, such as the conditional recommendation for vedolizumab in luminal disease since this drug did not meet the MCID threshold. Finally, the commentators emphasized that the guidelines are meant to facilitate, not dictate, treatment decisions: “Choice of therapies and treatment strategies will continue to rely on clinical judgment as well, and will continue to be informed by patient-specific values and preferences.”

The AGA Institute was the sole source of funding. Four coauthors disclosed ties to Celgene, Takeda, Pendopharm, Merck Canada, Guardant Health, Ferring, and AbbVie. Dr. Feurstein and the other guidelines coauthors reported having no conflicts of interest. Some authors on the editorial disclosed relationships with AbbVie, Pfizer, and Janssen, but the remaining had no conflicts to disclose.

For adult outpatients with moderate to severe Crohn’s disease, new guidelines from the American Gastroenterological Association strongly recommend induction and maintenance therapy with anti–tumor necrosis factor–alpha agents or ustekinumab over no treatment.

“Although [related] evidence supporting infliximab and adalimumab was moderate certainty, the evidence for certolizumab pegol was low certainty,” wrote Joseph D. Feuerstein, MD, of Beth Israel Deaconess Medical Center in Boston and his associates, on behalf of the AGA Clinical Guidelines Committee in Gastroenterology. Vedolizumab received a conditional recommendation based on less robust evidence for induction in this setting.

Outcomes in Crohn’s disease have improved, likely “because of earlier diagnosis, increasing use of biologics, escalation or alteration of therapy based on disease severity, and endoscopic management of colorectal cancer,” Dr. Feuerstein and his associates wrote.

This update reflects these changes, strongly recommending biologic monotherapy over thiopurine monotherapy for induction. It also suggests “early induction with a biologic, with or without an immunomodulator, rather than delaying their use until after failure of 5-aminosalicylates and/or corticosteroids.” For the latter assessment, the guidelines noted that some studies were open label (which increases risk of bias) and that upfront combination therapy with a biologic and an immunomodulator could sometimes lead to overtreatment. Nonetheless, studies shown associations between the step-up approach and “a potential risk of harm from disease progression related to inadequate disease therapy.”

The guidelines also recommend that patients who have never received biologic drugs receive induction therapy with infliximab, adalimumab, or ustekinumab, rather than certolizumab pegol. This strong recommendation reflects the findings of a network meta-analysis conducted by the AGA in which certolizumab pegol was least effective, with no evidence for clear differences in efficacy among infliximab, adalimumab, and ustekinumab. A network meta-analysis is a type of study that enables experts to compare therapies indirectly when head-to-head trials are lacking.

For patients who are naive to both biologics and immunomodulators, the guidelines suggest combination treatment with infliximab or adalimumab plus a thiopurine rather than monotherapy with either biologic. Because of a lack of randomized controlled trials, no recommendation is made regarding combination therapy with ustekinumab or vedolizumab.

For patients who have received but never responded to anti-TNF-alpha therapy (so-called primary nonresponders), ustekinumab is strongly recommended, and vedolizumab is conditionally recommended. For patients who initially responded to infliximab and then lost their response (secondary nonresponders), adalimumab and ustekinumab are strongly recommended, while vedolizumab receives another conditional recommendation.

For patients with moderate to severe luminal disease, induction and maintenance with infliximab, adalimumab, certolizumab pegol, vedolizumab, or ustekinumab are recommended over no treatment. Thiopurine monotherapy is suggested over no treatment for maintenance of remission, but not for induction. For methotrexate, subcutaneous or intramuscular monotherapy is suggested over no treatment. The sole available trial on oral methotrexate (12.5 mg/week) was negative, and “it is not clear if a higher dose would have been more effective,” according to the guidelines. They strongly recommend against using 5-aminosalicytes or sulfasalazine because of lack of efficacy for maintaining remission and suggest not using natalizumab because of the risk of progressive multifocal leukoencephalopathy (PML). Corticosteroids are considered preferable to no treatment for induction but not for maintenance.

For patients with fistulizing disease, infliximab has “the most robust evidence” and receives a strong recommendation for induction and maintenance, while adalimumab, ustekinumab, and vedolizumab receive conditional recommendations. “In contrast, evidence suggests certolizumab pegol may not be effective for induction of fistula remission,” the guidelines state. For patients with perianal disease with an active fistula but no abscess, combining biologics with antibiotics is strongly recommended over biologic monotherapy.

The guidelines define moderate to severe Crohn’s disease as a Crohn’s Disease Activity Index (CDAI) score of 220 or higher, the typical cutoff used in clinical trials. The recommendations apply to outpatient management, but in most cases would also apply to inpatients.

An expert commentary accompanying the guidelines praises their “rigorous methods” based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. Edith Y. Ho, MD, of Stanford (Calif.) University and her associates also laud the “innovative methods” that were used to compare treatments and assess data quality. In addition to the network meta-analysis, the guidelines set an a priori minimal clinically important difference (MCID) score of 10% for risk of treatment failure versus placebo. This led to more clinically relevant guidance, such as the conditional recommendation for vedolizumab in luminal disease since this drug did not meet the MCID threshold. Finally, the commentators emphasized that the guidelines are meant to facilitate, not dictate, treatment decisions: “Choice of therapies and treatment strategies will continue to rely on clinical judgment as well, and will continue to be informed by patient-specific values and preferences.”

The AGA Institute was the sole source of funding. Four coauthors disclosed ties to Celgene, Takeda, Pendopharm, Merck Canada, Guardant Health, Ferring, and AbbVie. Dr. Feurstein and the other guidelines coauthors reported having no conflicts of interest. Some authors on the editorial disclosed relationships with AbbVie, Pfizer, and Janssen, but the remaining had no conflicts to disclose.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has included more drugs and data and is moving toward a slightly more stepped approach to treating some forms of psoriatic disease in the latest iteration of their recommendations.

“There’s been an explosion over the last few years in terms of the number of medications,” available to treat psoriasis and psoriatic arthritis, Laura C. Coates, MBChB, PhD, said in an interview ahead of presenting the draft recommendations at the annual European Congress of Rheumatology.

“The good thing about having more drugs is you’ve got more choice, but actually it makes these recommendations even more important because it becomes more complicated to choose optimal treatment for individuals,” added Dr. Coates, a senior clinical research fellow at the University of Oxford (England).

“We’ve been waiting for a while now for the new GRAPPA recommendations,” Laure Gossec, MD, PhD, of Sorbonne University and Pitié-Salpêtrière Hospital in Paris, said in a separate interview.

New overarching principle and position statements

The goal of the recommendations hasn’t really changed since the first iteration of the guidelines in 2009, Dr. Coates noted in her presentation. They are intended to provide clinicians with recommendations “based on the best available evidence” for the management of patients with psoriatic disease.

To that end, a through process was followed, starting with the setting of PICO (Patient/population/problem; intervention; comparison; outcome) questions followed by systematic literature searches, data extraction, and review that assess the quality of evidence and then grade it accordingly before using it to inform the recommendation statements.

There is a new overarching principle that says: “These recommendations, which include the most current data concerning the optimal assessment of and therapeutic approached to psoriatic arthritis, present contextual considerations to empower shared decision making.”

The other overarching principles remain the same as in the 2015 version, with “minor wording changes particularly around the comorbidities overarching principle,” Dr. Coates said.

Also new are two position statements. “One of them is specifically around biosimilars, because that’s been a big shift since 2015,” Dr. Coates said. “It has basic rules about what evidence there should be, what we should consider when we’re using them, and patient involvement and decision making.”

The second statement covers “similar advice on tapering or discontinuing therapy – what we do when people are doing really well, how we should stop or taper, and which drugs we should choose to stop along with shared decision making with patients.”

GRAPPA intentionally gives clinicians more freedom

While there may be data to show differences in efficacy and side effects between the various drugs cited in the recommendations, “GRAPPA makes the choice to not prioritize one drug over another,” Dr. Gossec said. This decision gives “a lot of freedom then to the physician to make the decision.”

One important change according to Dr. Gossec is that oral “NSAIDs have clearly been put back as first-line treatment, before going on to disease-modifying drugs for most of the musculoskeletal manifestations. She added that for skin manifestations, topical NSAIDs were recommended, but that NSAIDs were more recommended for IBD and uveitis of course.

“I feel that’s a big step towards more of a step-up approach,” Dr. Gossec said. “The old recommendations were not clear that you would precede an NSAID before moving on to a disease-modifying drug. So, I think that makes it a little bit more similar to the 2019 EULAR recommendations.” The use of csDMARDs such as methotrexate has also been “pushed up a notch” in peripheral arthritis, she said.

What’s next?

There are a few fine tunings still to be made before the final recommendations are published. They also have to be discussed at the meeting of the GRAPPA task force, which consists of rheumatologists, dermatologists, and patient representatives.

Besides the recommendations manuscript, there will be individual papers detailing the evidence underpinning the recommendations in each of the eight domains, Dr. Coates noted. Those “will look at relative efficacy in detail,” she said. “There will be a lot more discussion/evidence summary included” to help with drug selection.

“We also plan to have some case studies to illustrate how the recommendations can be used, similar to that included in the 2015 recommendations,” she added.

Paul Studenic, MD, PhD, of the Karolinska Institute in Stockholm and Medical University of Vienna, tweeted that the GRAPPA recommendations showed treatment “needs to be tailored to the patient” taking “comorbidities as well as the heterogeneity of features of the clinical presentation into account.”

He said in an interview: “The third edition of the GRAPPA is a huge collaborative effort.” The new overarching principle put the recommendations in the context of shared decision making and, he added, they emphasize an “integrated management plan taking not only ‘classical’-related manifestations like uveitis into account but [also] a spectrum of comorbidities and reproductive health.”

GRAPPA is a not-for-profit organization and receives funding from multiple pharmaceutical companies. Currently this includes AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, Pfizer, UCB, and Sun Pharma with Galapagos and Nordic Bioscience as Innovation Partners. Dr. Coates acknowledged receiving research funding, honoraria, speaker fees or all of these from most of the aforementioned companies.

Dr. Gossec has received research funding or other support from numerous pharmaceutical companies and is a member of GRAPPA and the task force that developed the EULAR guidelines on the pharmacological management of psoriatic arthritis.

Dr. Studenic had nothing to disclose.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has included more drugs and data and is moving toward a slightly more stepped approach to treating some forms of psoriatic disease in the latest iteration of their recommendations.

“There’s been an explosion over the last few years in terms of the number of medications,” available to treat psoriasis and psoriatic arthritis, Laura C. Coates, MBChB, PhD, said in an interview ahead of presenting the draft recommendations at the annual European Congress of Rheumatology.

“The good thing about having more drugs is you’ve got more choice, but actually it makes these recommendations even more important because it becomes more complicated to choose optimal treatment for individuals,” added Dr. Coates, a senior clinical research fellow at the University of Oxford (England).

“We’ve been waiting for a while now for the new GRAPPA recommendations,” Laure Gossec, MD, PhD, of Sorbonne University and Pitié-Salpêtrière Hospital in Paris, said in a separate interview.

New overarching principle and position statements

The goal of the recommendations hasn’t really changed since the first iteration of the guidelines in 2009, Dr. Coates noted in her presentation. They are intended to provide clinicians with recommendations “based on the best available evidence” for the management of patients with psoriatic disease.

To that end, a through process was followed, starting with the setting of PICO (Patient/population/problem; intervention; comparison; outcome) questions followed by systematic literature searches, data extraction, and review that assess the quality of evidence and then grade it accordingly before using it to inform the recommendation statements.

There is a new overarching principle that says: “These recommendations, which include the most current data concerning the optimal assessment of and therapeutic approached to psoriatic arthritis, present contextual considerations to empower shared decision making.”

The other overarching principles remain the same as in the 2015 version, with “minor wording changes particularly around the comorbidities overarching principle,” Dr. Coates said.

Also new are two position statements. “One of them is specifically around biosimilars, because that’s been a big shift since 2015,” Dr. Coates said. “It has basic rules about what evidence there should be, what we should consider when we’re using them, and patient involvement and decision making.”

The second statement covers “similar advice on tapering or discontinuing therapy – what we do when people are doing really well, how we should stop or taper, and which drugs we should choose to stop along with shared decision making with patients.”

GRAPPA intentionally gives clinicians more freedom

While there may be data to show differences in efficacy and side effects between the various drugs cited in the recommendations, “GRAPPA makes the choice to not prioritize one drug over another,” Dr. Gossec said. This decision gives “a lot of freedom then to the physician to make the decision.”

One important change according to Dr. Gossec is that oral “NSAIDs have clearly been put back as first-line treatment, before going on to disease-modifying drugs for most of the musculoskeletal manifestations. She added that for skin manifestations, topical NSAIDs were recommended, but that NSAIDs were more recommended for IBD and uveitis of course.

“I feel that’s a big step towards more of a step-up approach,” Dr. Gossec said. “The old recommendations were not clear that you would precede an NSAID before moving on to a disease-modifying drug. So, I think that makes it a little bit more similar to the 2019 EULAR recommendations.” The use of csDMARDs such as methotrexate has also been “pushed up a notch” in peripheral arthritis, she said.

What’s next?

There are a few fine tunings still to be made before the final recommendations are published. They also have to be discussed at the meeting of the GRAPPA task force, which consists of rheumatologists, dermatologists, and patient representatives.

Besides the recommendations manuscript, there will be individual papers detailing the evidence underpinning the recommendations in each of the eight domains, Dr. Coates noted. Those “will look at relative efficacy in detail,” she said. “There will be a lot more discussion/evidence summary included” to help with drug selection.

“We also plan to have some case studies to illustrate how the recommendations can be used, similar to that included in the 2015 recommendations,” she added.

Paul Studenic, MD, PhD, of the Karolinska Institute in Stockholm and Medical University of Vienna, tweeted that the GRAPPA recommendations showed treatment “needs to be tailored to the patient” taking “comorbidities as well as the heterogeneity of features of the clinical presentation into account.”

He said in an interview: “The third edition of the GRAPPA is a huge collaborative effort.” The new overarching principle put the recommendations in the context of shared decision making and, he added, they emphasize an “integrated management plan taking not only ‘classical’-related manifestations like uveitis into account but [also] a spectrum of comorbidities and reproductive health.”

GRAPPA is a not-for-profit organization and receives funding from multiple pharmaceutical companies. Currently this includes AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, Pfizer, UCB, and Sun Pharma with Galapagos and Nordic Bioscience as Innovation Partners. Dr. Coates acknowledged receiving research funding, honoraria, speaker fees or all of these from most of the aforementioned companies.

Dr. Gossec has received research funding or other support from numerous pharmaceutical companies and is a member of GRAPPA and the task force that developed the EULAR guidelines on the pharmacological management of psoriatic arthritis.

Dr. Studenic had nothing to disclose.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has included more drugs and data and is moving toward a slightly more stepped approach to treating some forms of psoriatic disease in the latest iteration of their recommendations.

“There’s been an explosion over the last few years in terms of the number of medications,” available to treat psoriasis and psoriatic arthritis, Laura C. Coates, MBChB, PhD, said in an interview ahead of presenting the draft recommendations at the annual European Congress of Rheumatology.

“The good thing about having more drugs is you’ve got more choice, but actually it makes these recommendations even more important because it becomes more complicated to choose optimal treatment for individuals,” added Dr. Coates, a senior clinical research fellow at the University of Oxford (England).

“We’ve been waiting for a while now for the new GRAPPA recommendations,” Laure Gossec, MD, PhD, of Sorbonne University and Pitié-Salpêtrière Hospital in Paris, said in a separate interview.

New overarching principle and position statements

The goal of the recommendations hasn’t really changed since the first iteration of the guidelines in 2009, Dr. Coates noted in her presentation. They are intended to provide clinicians with recommendations “based on the best available evidence” for the management of patients with psoriatic disease.

To that end, a through process was followed, starting with the setting of PICO (Patient/population/problem; intervention; comparison; outcome) questions followed by systematic literature searches, data extraction, and review that assess the quality of evidence and then grade it accordingly before using it to inform the recommendation statements.

There is a new overarching principle that says: “These recommendations, which include the most current data concerning the optimal assessment of and therapeutic approached to psoriatic arthritis, present contextual considerations to empower shared decision making.”

The other overarching principles remain the same as in the 2015 version, with “minor wording changes particularly around the comorbidities overarching principle,” Dr. Coates said.

Also new are two position statements. “One of them is specifically around biosimilars, because that’s been a big shift since 2015,” Dr. Coates said. “It has basic rules about what evidence there should be, what we should consider when we’re using them, and patient involvement and decision making.”

The second statement covers “similar advice on tapering or discontinuing therapy – what we do when people are doing really well, how we should stop or taper, and which drugs we should choose to stop along with shared decision making with patients.”

GRAPPA intentionally gives clinicians more freedom

While there may be data to show differences in efficacy and side effects between the various drugs cited in the recommendations, “GRAPPA makes the choice to not prioritize one drug over another,” Dr. Gossec said. This decision gives “a lot of freedom then to the physician to make the decision.”

One important change according to Dr. Gossec is that oral “NSAIDs have clearly been put back as first-line treatment, before going on to disease-modifying drugs for most of the musculoskeletal manifestations. She added that for skin manifestations, topical NSAIDs were recommended, but that NSAIDs were more recommended for IBD and uveitis of course.

“I feel that’s a big step towards more of a step-up approach,” Dr. Gossec said. “The old recommendations were not clear that you would precede an NSAID before moving on to a disease-modifying drug. So, I think that makes it a little bit more similar to the 2019 EULAR recommendations.” The use of csDMARDs such as methotrexate has also been “pushed up a notch” in peripheral arthritis, she said.

What’s next?

There are a few fine tunings still to be made before the final recommendations are published. They also have to be discussed at the meeting of the GRAPPA task force, which consists of rheumatologists, dermatologists, and patient representatives.

Besides the recommendations manuscript, there will be individual papers detailing the evidence underpinning the recommendations in each of the eight domains, Dr. Coates noted. Those “will look at relative efficacy in detail,” she said. “There will be a lot more discussion/evidence summary included” to help with drug selection.

“We also plan to have some case studies to illustrate how the recommendations can be used, similar to that included in the 2015 recommendations,” she added.

Paul Studenic, MD, PhD, of the Karolinska Institute in Stockholm and Medical University of Vienna, tweeted that the GRAPPA recommendations showed treatment “needs to be tailored to the patient” taking “comorbidities as well as the heterogeneity of features of the clinical presentation into account.”

He said in an interview: “The third edition of the GRAPPA is a huge collaborative effort.” The new overarching principle put the recommendations in the context of shared decision making and, he added, they emphasize an “integrated management plan taking not only ‘classical’-related manifestations like uveitis into account but [also] a spectrum of comorbidities and reproductive health.”

GRAPPA is a not-for-profit organization and receives funding from multiple pharmaceutical companies. Currently this includes AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, Pfizer, UCB, and Sun Pharma with Galapagos and Nordic Bioscience as Innovation Partners. Dr. Coates acknowledged receiving research funding, honoraria, speaker fees or all of these from most of the aforementioned companies.

Dr. Gossec has received research funding or other support from numerous pharmaceutical companies and is a member of GRAPPA and the task force that developed the EULAR guidelines on the pharmacological management of psoriatic arthritis.

Dr. Studenic had nothing to disclose.

As researchers learn more about the genetic etiology of immunopathology, they have been able to more clearly understand rare but debilitating autoinflammatory conditions in ways that have improved identification and management of these diseases. At this year’s European Congress of Rheumatology, two researchers outlined new recommendations from the European Alliance of Associations for Rheumatology (EULAR) and the American College of Rheumatology (ACR) for the management of two groups of such autoinflammatory diseases: interleukin-1-mediated and Type-I interferonopathies, and suspected macrophage activation syndrome and hemophagocytic lymphohistiocytosis.

These are the first recommendations from EULAR for these diseases, according to Loreto Carmona, MD, PhD, chair of the EULAR scientific program committee and scientific director of the Institute for Musculoskeletal Health in Madrid.

“They are rare diseases and there is a great need to standardize diagnosis and care for the safety and outcome of the patients,” Dr. Carmona said in an interview. “These diseases need deep expertise and so the experts are trying, they are still preliminary, to add clarity to their management.” Dr. Carmona was not involved with the development of the guidelines and moderated the session during which they were presented.

“The rapidly emerging knowledge of the genetic causes of novel systemic autoinflammatory diseases, which present typically in early childhood with severe and chronic systemic and organ-specific inflammation, linked the disease pathogenesis to the pathologic production of major proinflammatory cytokines,” presenter Raphaela Goldbach-Mansky, MD, a senior investigator and chief of the translational autoinflammatory disease studies unit of the U.S. National Institute of Allergy and Infectious Diseases, told congress attendees. This greater understanding led to the “targeted and anticytokine treatments that have changed patients’ lives,” she said.

The guidelines relied on the products of three working groups for each disease type. After meeting to come up with clinical questions, the groups each conducted systematic literature reviews through EMBASE, PubMed, and the Cochrane Library for publications dated from 1970 to August 2020 that excluded non-English-language studies, case reports, and animal model or basic science studies. They then met again to develop final consensus statements.

The interferonopathy and interleukin (IL)-1-mediated systemic autoinflammatory diseases (SAIDs) working groups met throughout 2020, and the hemophagocytic lymphohistiocytosis (HLH)/ macrophage activation syndrome (MAS) working group met in March and April of 2021.

“One needs a lot of experience with these diseases to even think about them,” Dr. Carmona said. “We haven’t been presented yet with all the details of the recommendations, but we hope they are clear because they are much needed.”

She noted that these preliminary recommendations are based on the best available evidence to date along with expertise from multidisciplinary panels.

“We need to be acquainted with these recommendations, as the majority of us, either if we are pediatric or adult rheumatologists, will face some problem with these diseases at some point,” Dr. Carmona said.

IL-1-mediated SAIDs

Recommendations for IL-1-mediated SAIDs focused on mevalonate kinase deficiency (MKD), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), cryopyrinopathies (CAPS), and deficiency of the IL-1 receptor antagonist (DIRA). Presentation of these conditions involves chronic or intermittent flares of systemic and organ inflammation that can cause progressive organ damage, morbidity, and increased mortality if not treated. Diagnosis requires a multidisciplinary team whose evaluation should include disease-related complications and long-term care plans.

Diagnostic workup should include genetic testing using next-generation sequencing as this “facilitates initiation of targeted treatments, genetic counseling, and informs prognosis” for patients with CAPS, TRAPS, MKD, and DIRA, Erkan Demirkaya, MD, a scientist at the Children’s Health Research Institute and professor of pediatric rheumatology at the University of Western Ontario in London, Canada, told attendees. Evaluation should also include clinical workup that focuses on the extent of inflammatory organ involvement, and screening for disease- and treatment-related comorbidities.

“The goal of therapy is to control clinical signs and symptoms and normalize laboratory biomarkers of systemic inflammation,” Dr. Demirkaya said. Long-term monitoring goals should focus on the following:

• “Adequate treatment adjusted to the needs of the growing child and prevention of systemic and organ-specific inflammatory manifestations;
• Fostering of self-management skills and medical decision-making;
• Initiating a transition program to adult specialist care in adolescent patients.”

Type-1 interferonopathies

The recommendations for this disease group focused on chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures (CANDLE)/proteasome-associated autoinflammatory syndromes (PRAAS), STING-associated vasculopathy with onset in infancy (SAVI), and Aicardi-Goutières syndrome (AGS).

These patients similarly present with chronic and organ-specific inflammation that leads to progressive organ damage, morbidity, and higher mortality risk when not managed. Each of these diseases requires a confirmed genetic diagnosis so that treatments can be targeted and the patient receives appropriate genetic counseling, screening for complications, and information on prognosis, Dr. Goldbach-Mansky said.

Treatment goals for type-1 interferonopathies are to “reduce systematic and organ inflammation to prevent or limit the development of progression of organ injury or damage and to improve quality of life,” Dr. Goldbach-Mansky told attendees.

Each patient requires a multidisciplinary care provider team that conducts long-term monitoring of disease activity, damage to specific organs, and any treatment-related complications.
 

Management of HLH/MAS

Early recognition and management of HLH and MAS can be challenging because systemic hyperinflammation exists along an immunopathologic continuum with typically nonspecific clinical and laboratory findings, Dr. Goldbach-Mansky said, but holistic, longitudinal consideration of these findings “are recognizable and warrant prompt diagnostic evaluation.” Even if the patient does not meet all specific diagnostic criteria for HLH/MAS, it may be necessary to begin therapies, she said.

One important point to consider is that “systemic hyperinflammation can be associated with hyperferritinemia and can progress to life-threatening HLH/MAS,” Dr. Goldbach-Mansky said. Further, although “systemic hyperinflammation and HLH/MAS can occur in nearly any inflammatory state,” certain common triggers and predisposing conditions can indicate the need to consider these conditions and begin appropriate treatment if needed. Part of effective management of systemic hyperinflammation and HLH/MAS is determining any modifiable factors contributing to the disease and mitigating or treating those.

HLH/MAS requires urgent intervention based on the patient’s degree of inflammation and extent of organ dysfunction, the recommendations state. Treatment goals include preventing or limiting immunopathology, preserving the integrity of the diagnostic workup, and minimizing therapy-related toxicity.

Dr. Carmona, Dr. Goldbach-Mansky, and Dr. Demirkaya have reported no relevant financial relationships.


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

As researchers learn more about the genetic etiology of immunopathology, they have been able to more clearly understand rare but debilitating autoinflammatory conditions in ways that have improved identification and management of these diseases. At this year’s European Congress of Rheumatology, two researchers outlined new recommendations from the European Alliance of Associations for Rheumatology (EULAR) and the American College of Rheumatology (ACR) for the management of two groups of such autoinflammatory diseases: interleukin-1-mediated and Type-I interferonopathies, and suspected macrophage activation syndrome and hemophagocytic lymphohistiocytosis.

These are the first recommendations from EULAR for these diseases, according to Loreto Carmona, MD, PhD, chair of the EULAR scientific program committee and scientific director of the Institute for Musculoskeletal Health in Madrid.

“They are rare diseases and there is a great need to standardize diagnosis and care for the safety and outcome of the patients,” Dr. Carmona said in an interview. “These diseases need deep expertise and so the experts are trying, they are still preliminary, to add clarity to their management.” Dr. Carmona was not involved with the development of the guidelines and moderated the session during which they were presented.

“The rapidly emerging knowledge of the genetic causes of novel systemic autoinflammatory diseases, which present typically in early childhood with severe and chronic systemic and organ-specific inflammation, linked the disease pathogenesis to the pathologic production of major proinflammatory cytokines,” presenter Raphaela Goldbach-Mansky, MD, a senior investigator and chief of the translational autoinflammatory disease studies unit of the U.S. National Institute of Allergy and Infectious Diseases, told congress attendees. This greater understanding led to the “targeted and anticytokine treatments that have changed patients’ lives,” she said.

The guidelines relied on the products of three working groups for each disease type. After meeting to come up with clinical questions, the groups each conducted systematic literature reviews through EMBASE, PubMed, and the Cochrane Library for publications dated from 1970 to August 2020 that excluded non-English-language studies, case reports, and animal model or basic science studies. They then met again to develop final consensus statements.

The interferonopathy and interleukin (IL)-1-mediated systemic autoinflammatory diseases (SAIDs) working groups met throughout 2020, and the hemophagocytic lymphohistiocytosis (HLH)/ macrophage activation syndrome (MAS) working group met in March and April of 2021.

“One needs a lot of experience with these diseases to even think about them,” Dr. Carmona said. “We haven’t been presented yet with all the details of the recommendations, but we hope they are clear because they are much needed.”

She noted that these preliminary recommendations are based on the best available evidence to date along with expertise from multidisciplinary panels.

“We need to be acquainted with these recommendations, as the majority of us, either if we are pediatric or adult rheumatologists, will face some problem with these diseases at some point,” Dr. Carmona said.

IL-1-mediated SAIDs

Recommendations for IL-1-mediated SAIDs focused on mevalonate kinase deficiency (MKD), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), cryopyrinopathies (CAPS), and deficiency of the IL-1 receptor antagonist (DIRA). Presentation of these conditions involves chronic or intermittent flares of systemic and organ inflammation that can cause progressive organ damage, morbidity, and increased mortality if not treated. Diagnosis requires a multidisciplinary team whose evaluation should include disease-related complications and long-term care plans.

Diagnostic workup should include genetic testing using next-generation sequencing as this “facilitates initiation of targeted treatments, genetic counseling, and informs prognosis” for patients with CAPS, TRAPS, MKD, and DIRA, Erkan Demirkaya, MD, a scientist at the Children’s Health Research Institute and professor of pediatric rheumatology at the University of Western Ontario in London, Canada, told attendees. Evaluation should also include clinical workup that focuses on the extent of inflammatory organ involvement, and screening for disease- and treatment-related comorbidities.

“The goal of therapy is to control clinical signs and symptoms and normalize laboratory biomarkers of systemic inflammation,” Dr. Demirkaya said. Long-term monitoring goals should focus on the following:

• “Adequate treatment adjusted to the needs of the growing child and prevention of systemic and organ-specific inflammatory manifestations;
• Fostering of self-management skills and medical decision-making;
• Initiating a transition program to adult specialist care in adolescent patients.”

Type-1 interferonopathies

The recommendations for this disease group focused on chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures (CANDLE)/proteasome-associated autoinflammatory syndromes (PRAAS), STING-associated vasculopathy with onset in infancy (SAVI), and Aicardi-Goutières syndrome (AGS).

These patients similarly present with chronic and organ-specific inflammation that leads to progressive organ damage, morbidity, and higher mortality risk when not managed. Each of these diseases requires a confirmed genetic diagnosis so that treatments can be targeted and the patient receives appropriate genetic counseling, screening for complications, and information on prognosis, Dr. Goldbach-Mansky said.

Treatment goals for type-1 interferonopathies are to “reduce systematic and organ inflammation to prevent or limit the development of progression of organ injury or damage and to improve quality of life,” Dr. Goldbach-Mansky told attendees.

Each patient requires a multidisciplinary care provider team that conducts long-term monitoring of disease activity, damage to specific organs, and any treatment-related complications.
 

Management of HLH/MAS

Early recognition and management of HLH and MAS can be challenging because systemic hyperinflammation exists along an immunopathologic continuum with typically nonspecific clinical and laboratory findings, Dr. Goldbach-Mansky said, but holistic, longitudinal consideration of these findings “are recognizable and warrant prompt diagnostic evaluation.” Even if the patient does not meet all specific diagnostic criteria for HLH/MAS, it may be necessary to begin therapies, she said.

One important point to consider is that “systemic hyperinflammation can be associated with hyperferritinemia and can progress to life-threatening HLH/MAS,” Dr. Goldbach-Mansky said. Further, although “systemic hyperinflammation and HLH/MAS can occur in nearly any inflammatory state,” certain common triggers and predisposing conditions can indicate the need to consider these conditions and begin appropriate treatment if needed. Part of effective management of systemic hyperinflammation and HLH/MAS is determining any modifiable factors contributing to the disease and mitigating or treating those.

HLH/MAS requires urgent intervention based on the patient’s degree of inflammation and extent of organ dysfunction, the recommendations state. Treatment goals include preventing or limiting immunopathology, preserving the integrity of the diagnostic workup, and minimizing therapy-related toxicity.

Dr. Carmona, Dr. Goldbach-Mansky, and Dr. Demirkaya have reported no relevant financial relationships.


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

As researchers learn more about the genetic etiology of immunopathology, they have been able to more clearly understand rare but debilitating autoinflammatory conditions in ways that have improved identification and management of these diseases. At this year’s European Congress of Rheumatology, two researchers outlined new recommendations from the European Alliance of Associations for Rheumatology (EULAR) and the American College of Rheumatology (ACR) for the management of two groups of such autoinflammatory diseases: interleukin-1-mediated and Type-I interferonopathies, and suspected macrophage activation syndrome and hemophagocytic lymphohistiocytosis.

These are the first recommendations from EULAR for these diseases, according to Loreto Carmona, MD, PhD, chair of the EULAR scientific program committee and scientific director of the Institute for Musculoskeletal Health in Madrid.

“They are rare diseases and there is a great need to standardize diagnosis and care for the safety and outcome of the patients,” Dr. Carmona said in an interview. “These diseases need deep expertise and so the experts are trying, they are still preliminary, to add clarity to their management.” Dr. Carmona was not involved with the development of the guidelines and moderated the session during which they were presented.

“The rapidly emerging knowledge of the genetic causes of novel systemic autoinflammatory diseases, which present typically in early childhood with severe and chronic systemic and organ-specific inflammation, linked the disease pathogenesis to the pathologic production of major proinflammatory cytokines,” presenter Raphaela Goldbach-Mansky, MD, a senior investigator and chief of the translational autoinflammatory disease studies unit of the U.S. National Institute of Allergy and Infectious Diseases, told congress attendees. This greater understanding led to the “targeted and anticytokine treatments that have changed patients’ lives,” she said.

The guidelines relied on the products of three working groups for each disease type. After meeting to come up with clinical questions, the groups each conducted systematic literature reviews through EMBASE, PubMed, and the Cochrane Library for publications dated from 1970 to August 2020 that excluded non-English-language studies, case reports, and animal model or basic science studies. They then met again to develop final consensus statements.

The interferonopathy and interleukin (IL)-1-mediated systemic autoinflammatory diseases (SAIDs) working groups met throughout 2020, and the hemophagocytic lymphohistiocytosis (HLH)/ macrophage activation syndrome (MAS) working group met in March and April of 2021.

“One needs a lot of experience with these diseases to even think about them,” Dr. Carmona said. “We haven’t been presented yet with all the details of the recommendations, but we hope they are clear because they are much needed.”

She noted that these preliminary recommendations are based on the best available evidence to date along with expertise from multidisciplinary panels.

“We need to be acquainted with these recommendations, as the majority of us, either if we are pediatric or adult rheumatologists, will face some problem with these diseases at some point,” Dr. Carmona said.

IL-1-mediated SAIDs

Recommendations for IL-1-mediated SAIDs focused on mevalonate kinase deficiency (MKD), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), cryopyrinopathies (CAPS), and deficiency of the IL-1 receptor antagonist (DIRA). Presentation of these conditions involves chronic or intermittent flares of systemic and organ inflammation that can cause progressive organ damage, morbidity, and increased mortality if not treated. Diagnosis requires a multidisciplinary team whose evaluation should include disease-related complications and long-term care plans.

Diagnostic workup should include genetic testing using next-generation sequencing as this “facilitates initiation of targeted treatments, genetic counseling, and informs prognosis” for patients with CAPS, TRAPS, MKD, and DIRA, Erkan Demirkaya, MD, a scientist at the Children’s Health Research Institute and professor of pediatric rheumatology at the University of Western Ontario in London, Canada, told attendees. Evaluation should also include clinical workup that focuses on the extent of inflammatory organ involvement, and screening for disease- and treatment-related comorbidities.

“The goal of therapy is to control clinical signs and symptoms and normalize laboratory biomarkers of systemic inflammation,” Dr. Demirkaya said. Long-term monitoring goals should focus on the following:

• “Adequate treatment adjusted to the needs of the growing child and prevention of systemic and organ-specific inflammatory manifestations;
• Fostering of self-management skills and medical decision-making;
• Initiating a transition program to adult specialist care in adolescent patients.”

Type-1 interferonopathies

The recommendations for this disease group focused on chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures (CANDLE)/proteasome-associated autoinflammatory syndromes (PRAAS), STING-associated vasculopathy with onset in infancy (SAVI), and Aicardi-Goutières syndrome (AGS).

These patients similarly present with chronic and organ-specific inflammation that leads to progressive organ damage, morbidity, and higher mortality risk when not managed. Each of these diseases requires a confirmed genetic diagnosis so that treatments can be targeted and the patient receives appropriate genetic counseling, screening for complications, and information on prognosis, Dr. Goldbach-Mansky said.

Treatment goals for type-1 interferonopathies are to “reduce systematic and organ inflammation to prevent or limit the development of progression of organ injury or damage and to improve quality of life,” Dr. Goldbach-Mansky told attendees.

Each patient requires a multidisciplinary care provider team that conducts long-term monitoring of disease activity, damage to specific organs, and any treatment-related complications.
 

Management of HLH/MAS

Early recognition and management of HLH and MAS can be challenging because systemic hyperinflammation exists along an immunopathologic continuum with typically nonspecific clinical and laboratory findings, Dr. Goldbach-Mansky said, but holistic, longitudinal consideration of these findings “are recognizable and warrant prompt diagnostic evaluation.” Even if the patient does not meet all specific diagnostic criteria for HLH/MAS, it may be necessary to begin therapies, she said.

One important point to consider is that “systemic hyperinflammation can be associated with hyperferritinemia and can progress to life-threatening HLH/MAS,” Dr. Goldbach-Mansky said. Further, although “systemic hyperinflammation and HLH/MAS can occur in nearly any inflammatory state,” certain common triggers and predisposing conditions can indicate the need to consider these conditions and begin appropriate treatment if needed. Part of effective management of systemic hyperinflammation and HLH/MAS is determining any modifiable factors contributing to the disease and mitigating or treating those.

HLH/MAS requires urgent intervention based on the patient’s degree of inflammation and extent of organ dysfunction, the recommendations state. Treatment goals include preventing or limiting immunopathology, preserving the integrity of the diagnostic workup, and minimizing therapy-related toxicity.

Dr. Carmona, Dr. Goldbach-Mansky, and Dr. Demirkaya have reported no relevant financial relationships.


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

New guidelines from the American College of Gastroenterology on idiosyncratic drug-induced liver injury (DILI) emphasize that idiosyncratic DILI is increasingly driven by the burgeoning popularity of herbal and dietary supplements, as well as tyrosine kinase inhibitors and immune checkpoint inhibitors used to treat cancer.

Sebastian Kaulitzki/Science Photo Library

The guidelines, which represent an update from 2014, are published in The American Journal of Gastroenterology.

DILI is commonly seen by gastroenterologists and hepatologists, but it is challenging to diagnose because there are many potential causes, and no objective diagnostic tests. Its incidence in the general population is low, but it must be considered when facing unexplained liver injury. Its potential presence should also be considered when prescribing gastrointestinal medications like azathioprine, anti–tumor necrosis factor agents, and sulfonamides.

DILI can be characterized as intrinsic or idiosyncratic. Intrinsic DILI is somewhat predictable, based on human or animal studies that have revealed the potential for liver toxicity at higher doses. The best-known example is acetaminophen. Idiosyncratic DILI is rarer and shows up in individuals with a preexisting susceptibility. Clinical signs of idiosyncratic DILI are more diverse than intrinsic DILI. The ACG guideline focuses on idiosyncratic DILI, since guidelines are already available for intrinsic DILI.

Idiosyncratic DILI diagnosis can have a wide range of presentations, including asymptomatic liver biochemistry, jaundice, liver failure, and chronic hepatitis. Diagnosis is made by eliminating other potential causes.

In the presence of hepatocellular jaundice, mortality can reach 10%. DILI patients who develop progressive jaundice, regardless of concomitant coagulopathy, should be sent to a tertiary center and may be a candidate for liver transplantation.

Corticosteroids may be considered when there is uncertainty if a liver injury is from DILI or autoimmune hepatitis, but this remains controversial because some studies have shown benefit, while others have not, according to Bubu Banini, MD, PhD, assistant professor of medicine and research director of the metabolic health and weight management program at Yale University, New Haven, Conn. “Large-scale randomized controlled trials are needed for further elucidation of the role of steroids in DILI. For now, the guideline recommends consideration of steroid therapy, particularly in patients with features of autoimmune hepatitis,” she added.

An important factor driving DILI is the increasing popularity of herbal supplements, as well as increased use of some cancer therapies. “With the advent of immune checkpoint inhibitors as effective therapies for a variety of malignancies, physicians need to be aware of the potential side effects of these agents and the possibility of immune checkpoint inhibitor–related drug induced liver injury,” Dr. Banini said. The updated ACG guideline summarizes current FDA-approved immune checkpoint inhibitors and their potential to cause DILI. The drugs can also lead to reactivation of hepatitis B infection. Studies have shown liver enzyme elevation occurs in about 30% of patients treated with immune checkpoint inhibitors.

The guidelines recommend assessing DILI patients for hepatitis B and C, and treating patients prior to, or in combination with, immune checkpoint inhibitors or other chemotherapy drugs. The recommendations are in line with preliminary data from the ICI field, according to Dr. Banini.

Dr. Banini also noted there has been an increase in the use of herbal and dietary supplements in the United States over the past decade, and these now account for about one-fifth of DILI cases. The guidelines recommend that severe cholestatic disease from these agents should be managed similarly to cases caused by prescription drugs, and patients should be considered for liver transplant if necessary.

A web-based 6-month mortality calculator for suspected DILI is available. It uses Model for End-Stage Liver Disease, Charlson comorbidity Index, and serum albumin data. Those variables predict mortality in liver disease, and an independent analysis showed they predict 6-month mortality in DILI.

DILI is difficult to diagnose, but physicians should keep it in mind when faced with a case of liver enzyme abnormality, where other possibilities have been excluded. “With over a thousand medications potentially causing DILI, physicians should be familiar with LiverTox as a very useful and practical resource. The DILI mortality calculator can serve as a clinical tool to predict 6-month mortality in patients with suspected DILI,” Dr. Banini said.

Some authors disclosed relationships with several pharmaceutical companies. Dr. Banini reports having nothing to disclose.

New guidelines from the American College of Gastroenterology on idiosyncratic drug-induced liver injury (DILI) emphasize that idiosyncratic DILI is increasingly driven by the burgeoning popularity of herbal and dietary supplements, as well as tyrosine kinase inhibitors and immune checkpoint inhibitors used to treat cancer.

Sebastian Kaulitzki/Science Photo Library

The guidelines, which represent an update from 2014, are published in The American Journal of Gastroenterology.

DILI is commonly seen by gastroenterologists and hepatologists, but it is challenging to diagnose because there are many potential causes, and no objective diagnostic tests. Its incidence in the general population is low, but it must be considered when facing unexplained liver injury. Its potential presence should also be considered when prescribing gastrointestinal medications like azathioprine, anti–tumor necrosis factor agents, and sulfonamides.

DILI can be characterized as intrinsic or idiosyncratic. Intrinsic DILI is somewhat predictable, based on human or animal studies that have revealed the potential for liver toxicity at higher doses. The best-known example is acetaminophen. Idiosyncratic DILI is rarer and shows up in individuals with a preexisting susceptibility. Clinical signs of idiosyncratic DILI are more diverse than intrinsic DILI. The ACG guideline focuses on idiosyncratic DILI, since guidelines are already available for intrinsic DILI.

Idiosyncratic DILI diagnosis can have a wide range of presentations, including asymptomatic liver biochemistry, jaundice, liver failure, and chronic hepatitis. Diagnosis is made by eliminating other potential causes.

In the presence of hepatocellular jaundice, mortality can reach 10%. DILI patients who develop progressive jaundice, regardless of concomitant coagulopathy, should be sent to a tertiary center and may be a candidate for liver transplantation.

Corticosteroids may be considered when there is uncertainty if a liver injury is from DILI or autoimmune hepatitis, but this remains controversial because some studies have shown benefit, while others have not, according to Bubu Banini, MD, PhD, assistant professor of medicine and research director of the metabolic health and weight management program at Yale University, New Haven, Conn. “Large-scale randomized controlled trials are needed for further elucidation of the role of steroids in DILI. For now, the guideline recommends consideration of steroid therapy, particularly in patients with features of autoimmune hepatitis,” she added.

An important factor driving DILI is the increasing popularity of herbal supplements, as well as increased use of some cancer therapies. “With the advent of immune checkpoint inhibitors as effective therapies for a variety of malignancies, physicians need to be aware of the potential side effects of these agents and the possibility of immune checkpoint inhibitor–related drug induced liver injury,” Dr. Banini said. The updated ACG guideline summarizes current FDA-approved immune checkpoint inhibitors and their potential to cause DILI. The drugs can also lead to reactivation of hepatitis B infection. Studies have shown liver enzyme elevation occurs in about 30% of patients treated with immune checkpoint inhibitors.

The guidelines recommend assessing DILI patients for hepatitis B and C, and treating patients prior to, or in combination with, immune checkpoint inhibitors or other chemotherapy drugs. The recommendations are in line with preliminary data from the ICI field, according to Dr. Banini.

Dr. Banini also noted there has been an increase in the use of herbal and dietary supplements in the United States over the past decade, and these now account for about one-fifth of DILI cases. The guidelines recommend that severe cholestatic disease from these agents should be managed similarly to cases caused by prescription drugs, and patients should be considered for liver transplant if necessary.

A web-based 6-month mortality calculator for suspected DILI is available. It uses Model for End-Stage Liver Disease, Charlson comorbidity Index, and serum albumin data. Those variables predict mortality in liver disease, and an independent analysis showed they predict 6-month mortality in DILI.

DILI is difficult to diagnose, but physicians should keep it in mind when faced with a case of liver enzyme abnormality, where other possibilities have been excluded. “With over a thousand medications potentially causing DILI, physicians should be familiar with LiverTox as a very useful and practical resource. The DILI mortality calculator can serve as a clinical tool to predict 6-month mortality in patients with suspected DILI,” Dr. Banini said.

Some authors disclosed relationships with several pharmaceutical companies. Dr. Banini reports having nothing to disclose.

New guidelines from the American College of Gastroenterology on idiosyncratic drug-induced liver injury (DILI) emphasize that idiosyncratic DILI is increasingly driven by the burgeoning popularity of herbal and dietary supplements, as well as tyrosine kinase inhibitors and immune checkpoint inhibitors used to treat cancer.

Sebastian Kaulitzki/Science Photo Library

The guidelines, which represent an update from 2014, are published in The American Journal of Gastroenterology.

DILI is commonly seen by gastroenterologists and hepatologists, but it is challenging to diagnose because there are many potential causes, and no objective diagnostic tests. Its incidence in the general population is low, but it must be considered when facing unexplained liver injury. Its potential presence should also be considered when prescribing gastrointestinal medications like azathioprine, anti–tumor necrosis factor agents, and sulfonamides.

DILI can be characterized as intrinsic or idiosyncratic. Intrinsic DILI is somewhat predictable, based on human or animal studies that have revealed the potential for liver toxicity at higher doses. The best-known example is acetaminophen. Idiosyncratic DILI is rarer and shows up in individuals with a preexisting susceptibility. Clinical signs of idiosyncratic DILI are more diverse than intrinsic DILI. The ACG guideline focuses on idiosyncratic DILI, since guidelines are already available for intrinsic DILI.

Idiosyncratic DILI diagnosis can have a wide range of presentations, including asymptomatic liver biochemistry, jaundice, liver failure, and chronic hepatitis. Diagnosis is made by eliminating other potential causes.

In the presence of hepatocellular jaundice, mortality can reach 10%. DILI patients who develop progressive jaundice, regardless of concomitant coagulopathy, should be sent to a tertiary center and may be a candidate for liver transplantation.

Corticosteroids may be considered when there is uncertainty if a liver injury is from DILI or autoimmune hepatitis, but this remains controversial because some studies have shown benefit, while others have not, according to Bubu Banini, MD, PhD, assistant professor of medicine and research director of the metabolic health and weight management program at Yale University, New Haven, Conn. “Large-scale randomized controlled trials are needed for further elucidation of the role of steroids in DILI. For now, the guideline recommends consideration of steroid therapy, particularly in patients with features of autoimmune hepatitis,” she added.

An important factor driving DILI is the increasing popularity of herbal supplements, as well as increased use of some cancer therapies. “With the advent of immune checkpoint inhibitors as effective therapies for a variety of malignancies, physicians need to be aware of the potential side effects of these agents and the possibility of immune checkpoint inhibitor–related drug induced liver injury,” Dr. Banini said. The updated ACG guideline summarizes current FDA-approved immune checkpoint inhibitors and their potential to cause DILI. The drugs can also lead to reactivation of hepatitis B infection. Studies have shown liver enzyme elevation occurs in about 30% of patients treated with immune checkpoint inhibitors.

The guidelines recommend assessing DILI patients for hepatitis B and C, and treating patients prior to, or in combination with, immune checkpoint inhibitors or other chemotherapy drugs. The recommendations are in line with preliminary data from the ICI field, according to Dr. Banini.

Dr. Banini also noted there has been an increase in the use of herbal and dietary supplements in the United States over the past decade, and these now account for about one-fifth of DILI cases. The guidelines recommend that severe cholestatic disease from these agents should be managed similarly to cases caused by prescription drugs, and patients should be considered for liver transplant if necessary.

A web-based 6-month mortality calculator for suspected DILI is available. It uses Model for End-Stage Liver Disease, Charlson comorbidity Index, and serum albumin data. Those variables predict mortality in liver disease, and an independent analysis showed they predict 6-month mortality in DILI.

DILI is difficult to diagnose, but physicians should keep it in mind when faced with a case of liver enzyme abnormality, where other possibilities have been excluded. “With over a thousand medications potentially causing DILI, physicians should be familiar with LiverTox as a very useful and practical resource. The DILI mortality calculator can serve as a clinical tool to predict 6-month mortality in patients with suspected DILI,” Dr. Banini said.

Some authors disclosed relationships with several pharmaceutical companies. Dr. Banini reports having nothing to disclose.