TOPLINE:

Individuals with fair or worse bowel preparation have lower adenoma detection rates and a higher risk for postcolonoscopy colorectal cancer (PCCRC) death, new data showed.

METHODOLOGY:

• Few large studies have investigated the degree of bowel preparation with long-term colorectal cancer (CRC) outcomes.
• Researchers analyzed data from 335,466 individuals aged 50 years and older who underwent screening colonoscopy in Austria over 10 years (2012-2022).
• Bowel preparation quality was assessed using the five-point Aronchick scale and categorized as excellent, good, fair, poor, or inadequate.
• Logistic regression and time-to-event analyses were used to assess the impact of bowel preparation quality on adenoma detection and PCCRC mortality.

TAKEAWAY:

• Bowel prep was excellent in 37% of procedures, good in 48%, fair in 11%, poor in 3%, and inadequate in 1%.
• With worsening degrees of bowel prep, the odds of detecting an adenoma, high-risk polyp, sessile serrated lesion (SSL), or traditional serrated adenoma (TSA) decreased significantly.
• For patients with inadequate bowel preparation, the odds ratio for detection was 0.44 for adenomas and 0.53 for SSL or TSA.
• The risk of dying from PCCRC was more than twofold higher with fair or poor bowel prep and more than fourfold higher with inadequate prep.
• Cumulative 10-year CRC mortality was 0.14% for excellent/good bowel preparation vs 0.41% for fair or worse preparation.

IN PRACTICE:

“Our findings further support the evidence that bowel preparation is a crucial element of high-quality colonoscopy that affects CRC outcomes in screening participants. Efforts should be made to increase bowel cleansing above fair scores,” the authors concluded.

SOURCE:

The study, led by Jasmin Zessner-Spitzenberg, MD, from the Division of Gastroenterology and Hepatology at the Medical University of Vienna, was published online in the American Journal of Gastroenterology.

LIMITATIONS:

The researchers lacked data on CRC risk factors and information on surveillance colonoscopies, which could bias the results. Bowel preparation solutions and preferences of endoscopists, or whether split dosing was applied, were unknown, which limits insights into variations in preparation effectiveness.

DISCLOSURES:

The study was supported by the Main Association of Statutory Insurance Institutions, the Austrian Society of Gastroenterology and Hepatology, and the Austrian Cancer Aid. Dr. Zessner-Spitzenberg had no relevant disclosures. Other participating authors disclosed competing interests in the form of advisory roles, grant/research support, and speaker fees received from industry and academic institutions.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Individuals with fair or worse bowel preparation have lower adenoma detection rates and a higher risk for postcolonoscopy colorectal cancer (PCCRC) death, new data showed.

METHODOLOGY:

• Few large studies have investigated the degree of bowel preparation with long-term colorectal cancer (CRC) outcomes.
• Researchers analyzed data from 335,466 individuals aged 50 years and older who underwent screening colonoscopy in Austria over 10 years (2012-2022).
• Bowel preparation quality was assessed using the five-point Aronchick scale and categorized as excellent, good, fair, poor, or inadequate.
• Logistic regression and time-to-event analyses were used to assess the impact of bowel preparation quality on adenoma detection and PCCRC mortality.

TAKEAWAY:

• Bowel prep was excellent in 37% of procedures, good in 48%, fair in 11%, poor in 3%, and inadequate in 1%.
• With worsening degrees of bowel prep, the odds of detecting an adenoma, high-risk polyp, sessile serrated lesion (SSL), or traditional serrated adenoma (TSA) decreased significantly.
• For patients with inadequate bowel preparation, the odds ratio for detection was 0.44 for adenomas and 0.53 for SSL or TSA.
• The risk of dying from PCCRC was more than twofold higher with fair or poor bowel prep and more than fourfold higher with inadequate prep.
• Cumulative 10-year CRC mortality was 0.14% for excellent/good bowel preparation vs 0.41% for fair or worse preparation.

IN PRACTICE:

“Our findings further support the evidence that bowel preparation is a crucial element of high-quality colonoscopy that affects CRC outcomes in screening participants. Efforts should be made to increase bowel cleansing above fair scores,” the authors concluded.

SOURCE:

The study, led by Jasmin Zessner-Spitzenberg, MD, from the Division of Gastroenterology and Hepatology at the Medical University of Vienna, was published online in the American Journal of Gastroenterology.

LIMITATIONS:

The researchers lacked data on CRC risk factors and information on surveillance colonoscopies, which could bias the results. Bowel preparation solutions and preferences of endoscopists, or whether split dosing was applied, were unknown, which limits insights into variations in preparation effectiveness.

DISCLOSURES:

The study was supported by the Main Association of Statutory Insurance Institutions, the Austrian Society of Gastroenterology and Hepatology, and the Austrian Cancer Aid. Dr. Zessner-Spitzenberg had no relevant disclosures. Other participating authors disclosed competing interests in the form of advisory roles, grant/research support, and speaker fees received from industry and academic institutions.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Individuals with fair or worse bowel preparation have lower adenoma detection rates and a higher risk for postcolonoscopy colorectal cancer (PCCRC) death, new data showed.

METHODOLOGY:

• Few large studies have investigated the degree of bowel preparation with long-term colorectal cancer (CRC) outcomes.
• Researchers analyzed data from 335,466 individuals aged 50 years and older who underwent screening colonoscopy in Austria over 10 years (2012-2022).
• Bowel preparation quality was assessed using the five-point Aronchick scale and categorized as excellent, good, fair, poor, or inadequate.
• Logistic regression and time-to-event analyses were used to assess the impact of bowel preparation quality on adenoma detection and PCCRC mortality.

TAKEAWAY:

• Bowel prep was excellent in 37% of procedures, good in 48%, fair in 11%, poor in 3%, and inadequate in 1%.
• With worsening degrees of bowel prep, the odds of detecting an adenoma, high-risk polyp, sessile serrated lesion (SSL), or traditional serrated adenoma (TSA) decreased significantly.
• For patients with inadequate bowel preparation, the odds ratio for detection was 0.44 for adenomas and 0.53 for SSL or TSA.
• The risk of dying from PCCRC was more than twofold higher with fair or poor bowel prep and more than fourfold higher with inadequate prep.
• Cumulative 10-year CRC mortality was 0.14% for excellent/good bowel preparation vs 0.41% for fair or worse preparation.

IN PRACTICE:

“Our findings further support the evidence that bowel preparation is a crucial element of high-quality colonoscopy that affects CRC outcomes in screening participants. Efforts should be made to increase bowel cleansing above fair scores,” the authors concluded.

SOURCE:

The study, led by Jasmin Zessner-Spitzenberg, MD, from the Division of Gastroenterology and Hepatology at the Medical University of Vienna, was published online in the American Journal of Gastroenterology.

LIMITATIONS:

The researchers lacked data on CRC risk factors and information on surveillance colonoscopies, which could bias the results. Bowel preparation solutions and preferences of endoscopists, or whether split dosing was applied, were unknown, which limits insights into variations in preparation effectiveness.

DISCLOSURES:

The study was supported by the Main Association of Statutory Insurance Institutions, the Austrian Society of Gastroenterology and Hepatology, and the Austrian Cancer Aid. Dr. Zessner-Spitzenberg had no relevant disclosures. Other participating authors disclosed competing interests in the form of advisory roles, grant/research support, and speaker fees received from industry and academic institutions.
 

A version of this article appeared on Medscape.com.

I recently encountered a study that reviewed return visits of pediatric patients after undergoing adenotonsillectomy. The investigators discovered that pain-related visits were higher for patients who had received prescriptions for opioids. After the Food and Drug Administration (FDA) issued a boxed warning about the use of codeine in postoperative pediatric tonsillectomy with adenoidectomy (T&A), patients pain-related return visits declined and steroid prescriptions increased.

On the surface, this inverse relationship between opioid prescriptions and pain-related visits seems counterintuitive. This is particularly true if you believe that opioids are effective pain medications. The relationship between pain-related visits, steroid use, and the boxed warning is a bit easier to understand and most likely points to the effectiveness of the steroids.

Keeping in mind this was a single-institution study that included more than 5000 patients and more than 700 return visits, we should be careful in reading too much into these results. However, I can’t resist the temptation to use it as a springboard from which to launch a short dissertation on pain management.

First, let’s consider whether there was something about the opioids that was causing more pain for the patients. I’m not aware of any studies that suggest pain as a side effect of codeine. Nausea and vomiting, yes. And, although the investigators were focusing on pain, it may have been that the general discomfort associated with the gastrointestinal effects of the drug were lowering the patients’ pain threshold. I certainly know of many adults who have said that they now avoid opioids postoperatively because of the general sense of unwellness they have experienced during previous surgical adventures.

However, my bias leads me to focus on this question: If the patients didn’t receive opioids postoperatively, were they receiving something else that was making them less likely to arrive at the hospital or clinic complaining of pain? I assume the researchers would have told us about some new alternative miracle painkiller that was being prescribed.

As a card-carrying nihilist in good standing, I am tempted to claim that this is another example of nothing is better than most well-intentioned somethings. However, I am going to posit that these patients were receiving something that lessened their need to seek help with their pain.

Most likely that something was a thoughtful preemptive dialogue postoperatively about what they (and in most cases their parents) might expect in the way of symptoms. And ... an easy-to-reach contact point preferably with a person with whom they were familiar. And ... were scheduled to receive follow up phone calls at intervals relevant to the details of their surgery.

I know many of you are going to say, “We are already doing those things.” And, if so, you are to be commended. And, I’m sure that every outpatient postoperative manual includes all of those common-sense ingredients of good follow-up care. However, you know as well as I do that not all postoperative instructions are delivered with same degree of thoroughness nor with sufficient pauses thoughtfully delivered to make it a real dialogue. Nor is the follow-up contact person as easy to reach as promised.

I’m not sure how much we can thank the FDA boxed warning about codeine for the decrease in postoperative pain-generated visits. However, it could be that when physicians were discouraged from prescribing postoperative opioids, they may have felt the need to lean more heavily on good old-fashioned postoperative follow-up care. Instructions presented more as a dialogue and preemptive follow-up calls made with an aura of caring are well known deterrents of middle-of-the-night calls for help.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

I recently encountered a study that reviewed return visits of pediatric patients after undergoing adenotonsillectomy. The investigators discovered that pain-related visits were higher for patients who had received prescriptions for opioids. After the Food and Drug Administration (FDA) issued a boxed warning about the use of codeine in postoperative pediatric tonsillectomy with adenoidectomy (T&A), patients pain-related return visits declined and steroid prescriptions increased.

On the surface, this inverse relationship between opioid prescriptions and pain-related visits seems counterintuitive. This is particularly true if you believe that opioids are effective pain medications. The relationship between pain-related visits, steroid use, and the boxed warning is a bit easier to understand and most likely points to the effectiveness of the steroids.

Keeping in mind this was a single-institution study that included more than 5000 patients and more than 700 return visits, we should be careful in reading too much into these results. However, I can’t resist the temptation to use it as a springboard from which to launch a short dissertation on pain management.

First, let’s consider whether there was something about the opioids that was causing more pain for the patients. I’m not aware of any studies that suggest pain as a side effect of codeine. Nausea and vomiting, yes. And, although the investigators were focusing on pain, it may have been that the general discomfort associated with the gastrointestinal effects of the drug were lowering the patients’ pain threshold. I certainly know of many adults who have said that they now avoid opioids postoperatively because of the general sense of unwellness they have experienced during previous surgical adventures.

However, my bias leads me to focus on this question: If the patients didn’t receive opioids postoperatively, were they receiving something else that was making them less likely to arrive at the hospital or clinic complaining of pain? I assume the researchers would have told us about some new alternative miracle painkiller that was being prescribed.

As a card-carrying nihilist in good standing, I am tempted to claim that this is another example of nothing is better than most well-intentioned somethings. However, I am going to posit that these patients were receiving something that lessened their need to seek help with their pain.

Most likely that something was a thoughtful preemptive dialogue postoperatively about what they (and in most cases their parents) might expect in the way of symptoms. And ... an easy-to-reach contact point preferably with a person with whom they were familiar. And ... were scheduled to receive follow up phone calls at intervals relevant to the details of their surgery.

I know many of you are going to say, “We are already doing those things.” And, if so, you are to be commended. And, I’m sure that every outpatient postoperative manual includes all of those common-sense ingredients of good follow-up care. However, you know as well as I do that not all postoperative instructions are delivered with same degree of thoroughness nor with sufficient pauses thoughtfully delivered to make it a real dialogue. Nor is the follow-up contact person as easy to reach as promised.

I’m not sure how much we can thank the FDA boxed warning about codeine for the decrease in postoperative pain-generated visits. However, it could be that when physicians were discouraged from prescribing postoperative opioids, they may have felt the need to lean more heavily on good old-fashioned postoperative follow-up care. Instructions presented more as a dialogue and preemptive follow-up calls made with an aura of caring are well known deterrents of middle-of-the-night calls for help.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

I recently encountered a study that reviewed return visits of pediatric patients after undergoing adenotonsillectomy. The investigators discovered that pain-related visits were higher for patients who had received prescriptions for opioids. After the Food and Drug Administration (FDA) issued a boxed warning about the use of codeine in postoperative pediatric tonsillectomy with adenoidectomy (T&A), patients pain-related return visits declined and steroid prescriptions increased.

On the surface, this inverse relationship between opioid prescriptions and pain-related visits seems counterintuitive. This is particularly true if you believe that opioids are effective pain medications. The relationship between pain-related visits, steroid use, and the boxed warning is a bit easier to understand and most likely points to the effectiveness of the steroids.

Keeping in mind this was a single-institution study that included more than 5000 patients and more than 700 return visits, we should be careful in reading too much into these results. However, I can’t resist the temptation to use it as a springboard from which to launch a short dissertation on pain management.

First, let’s consider whether there was something about the opioids that was causing more pain for the patients. I’m not aware of any studies that suggest pain as a side effect of codeine. Nausea and vomiting, yes. And, although the investigators were focusing on pain, it may have been that the general discomfort associated with the gastrointestinal effects of the drug were lowering the patients’ pain threshold. I certainly know of many adults who have said that they now avoid opioids postoperatively because of the general sense of unwellness they have experienced during previous surgical adventures.

However, my bias leads me to focus on this question: If the patients didn’t receive opioids postoperatively, were they receiving something else that was making them less likely to arrive at the hospital or clinic complaining of pain? I assume the researchers would have told us about some new alternative miracle painkiller that was being prescribed.

As a card-carrying nihilist in good standing, I am tempted to claim that this is another example of nothing is better than most well-intentioned somethings. However, I am going to posit that these patients were receiving something that lessened their need to seek help with their pain.

Most likely that something was a thoughtful preemptive dialogue postoperatively about what they (and in most cases their parents) might expect in the way of symptoms. And ... an easy-to-reach contact point preferably with a person with whom they were familiar. And ... were scheduled to receive follow up phone calls at intervals relevant to the details of their surgery.

I know many of you are going to say, “We are already doing those things.” And, if so, you are to be commended. And, I’m sure that every outpatient postoperative manual includes all of those common-sense ingredients of good follow-up care. However, you know as well as I do that not all postoperative instructions are delivered with same degree of thoroughness nor with sufficient pauses thoughtfully delivered to make it a real dialogue. Nor is the follow-up contact person as easy to reach as promised.

I’m not sure how much we can thank the FDA boxed warning about codeine for the decrease in postoperative pain-generated visits. However, it could be that when physicians were discouraged from prescribing postoperative opioids, they may have felt the need to lean more heavily on good old-fashioned postoperative follow-up care. Instructions presented more as a dialogue and preemptive follow-up calls made with an aura of caring are well known deterrents of middle-of-the-night calls for help.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

MILAN — Seladelpar, an investigational selective peroxisome proliferator-activated receptor delta agonist, achieves both biochemical and clinically meaningful improvements in pruritus and liver injury in patients with primary biliary cholangitis (PBC), both with and without compensated liver cirrhosis, according to two interim analyses of the ASSURE long-term extension study.

The first analysis of 337 patients with PBC, with and without cirrhosis, showed that treatment with seladelpar had a durable effect up to 2 years on cholestasis and markers of liver injury, as well as a sustained reduction in pruritus, Palak Trivedi, MD, associate professor at the National Institute for Health Research Birmingham Biomedical Research Centre, University of Birmingham, Birmingham, England, reported in a poster presented at the European Association for the Study of the Liver (EASL) Congress 2024.

The 2-year analysis also showed that seladelpar, a first-in-class, orally active agent, was safe and well tolerated in this patient population, he added.

These “results are consistent with the pivotal phase 3 RESPONSE study,” Dr. Trivedi noted. The RESPONSE study showed that seladelpar significantly improved liver biomarkers of disease activity and symptoms of pruritus at 12 months in patients with PBC who had an inadequate response or intolerance to ursodeoxycholic acid (UDCA), the standard of care, and had no history of hepatic decompensation. Patients with cirrhosis were allowed to enroll.

A total of 158 patients from the RESPONSE trial, both from the placebo and from the active treatment arm, were rolled over into the ASSURE trial. Another subset of 179 patients were drawn from prior seladelpar placebo-controlled studies (referred to as “legacy studies”), including the ENHANCE study. All participants in the current analysis received 10 mg of seladelpar, once daily, for up to 155 weeks.

Of the participants from the legacy studies, 99 completed 24 months of treatment with seladelpar, and 164 completed 12 months of treatment. In the 24-month treatment group, 70% met the composite response endpoint, which included alkaline phosphatase (ALP) levels below 1.67 times the upper limit of normal, a decrease in ALP levels of at least 15%, and total bilirubin levels at or below the upper limit of normal, according to a press release of the study findings. In addition, 42% of these participants achieved ALP normalization at 24 months, a marker of liver disease progression. In the 12-month treatment group, 73% achieved the clinically meaningful composite response endpoint, with 42% experiencing ALP normalization.

For patients rolled over from RESPONSE, 102 received 18 months of treatment with seladelpar, and 29 received 24 months of treatment. A total of 62% of patients in the 18-month group achieved the composite endpoint, and 33% achieved ALP normalization, while 72% of the 24-month group reached the composite endpoint, and 17% had ALP normalization.

Of patients who had received a placebo in the RESPONSE trial and went on to receive treatment with seladelpar, 75% achieved the composite endpoint, 27% had ALP normalization at 6 months, and 94% achieved the composite endpoint and 50% reached ALP normalization at 12 months.

Key secondary endpoints included ALP normalization and changes in liver enzymes (ALP, total bilirubin, gamma-glutamyl transferase [GGT], alanine transaminase [ALT], and aspartate aminotransferase [AST]).
 

Pruritus Relief Important for Quality of Life

Among study participants who reported a four or more at baseline on the numerical rating scale (NRS) for pruritus, legacy patients at 12 months and 24 months of treatment reported a mean reduction of 3.8 and 3.1, respectively. Participants from RESPONSE also reported a mean reduction of 3.8.

This level of reduction in NRS is “considered clinically significant” and takes patients from a level of moderate to severe itching down to mild, said Carrie Frenette, MD, executive director, Global Medical Affairs, Liver Diseases, Gilead Sciences, Foster City, California, and a former hepatologist of 20 years with a special interest in liver transplantation.

This “is a huge benefit in quality of life for these patients,” Dr. Frenette said in an interview.

Dr. Frenette also noted that UDCA, the current first-line treatment for PBC, is inadequate in up to 40% of patients, and second-line treatments, notably obeticholic acid, can cause itching.

European Society for Organ Transplantation

Eleonora De Martin, MD, transplant hepatologist at Centre Hépato-Biliaire, Paul Brousse Hospital, Paris, France, who comoderated the session, pointed out that PBC is a complex disease.

“We need both disease control and symptom control, and they’re not always compatible,” she said. “Sometimes you can control the disease but not the symptoms, and symptomatic control is so important,” especially with pruritus.
 

Patients With PBC and Cirrhosis

A separate analysis from ASSURE looked at a subset of 17 patients with PBC and cirrhosis who completed 24 months of treatment. The findings were presented by Stuart Gordon, MD, professor of medicine, Wayne State University School of Medicine, and hepatologist at Henry Ford Hospital, both in Detroit.

In this analysis, the mean patient age was 60.8 years, 91.4% were female, 88.6% were Child-Pugh A, and 22.9% had portal hypertension, while the mean baseline liver stiffness by FibroScan was 19.9 kPa.

Baseline biochemical measures were mean ALP of 245.4 U/L, mean total bilirubin of 0.995 mg/dL, mean GGT of 216.1 U/L, and mean ALT of 36.6 U/L.

A total of 11 participants (65%) met the composite endpoint at 24 months, with ALP normalization in 4 patients (24%). The overall mean percent change from baseline in ALP was approximately −30% and in total bilirubin was around −14%. Other changes in biochemical markers included reductions from baseline in GGT and ALT of approximately −30% and −10%, respectively. No change was observed in AST.

While 80% of patients with cirrhosis “had an adverse event of some form,” there were no treatment-related serious adverse events.

“It’s interesting to see results in these patients who have advanced disease and are cirrhotic because it might stabilize disease or even provide improvement,” Dr. De Martin commented. “However, the numbers in the study are very small, so it’s hard to draw firm conclusions yet, but it is a first step in showing that this drug is safe.”

Seladelpar is an “important step forward in PBC because we’ve been stuck with ursodeoxycholic acid for so many years,” Dr. De Martin added. “We’ve seen in liver disease with other etiologies that sometimes just one drug can make a difference, and you can change the natural history of the disease.”

Dr. Frenette is an employee and stockholder of Gilead Sciences. Dr. Gordon declared grants and support from AbbVie, Arbutus, CymaBay, Cour Pharmaceuticals, GlaxoSmithKline (GSK), Ipsen, and Mirum Pharmaceuticals; and advisory board activity from CymaBay, GSK, and Ipsen Pharmaceuticals. Dr. De Martin had no disclosures of relevance to seladelpar but has received speaker fees from other companies, including GSK, Ipsen, and Astellas. Dr. Trivedi reports institutional funding support from National Institute for Health Research Birmingham (UK); lecture fees from Advanz Pharma/Intercept Pharmaceuticals, Albireo/Ipsen, and Dr. Falk Pharma; advisory board/consulting fees from Advanz Pharma/Intercept Pharmaceuticals, Albireo/Ipsen, Chemomab Therapeutics, CymaBay, Dr. Falk Pharma, Gilead Sciences, Perspectum, and Pliant Therapeutics; and grant support from Advanz Pharma/Intercept Pharmaceuticals, Albireo/Ipsen, Bristol-Myers Squibb, Core (Guts UK), EASL, Gilead Sciences, GSK, LifeArc, NIHR, Mirum Pharma, PSC Support, The Wellcome Trust, The Medical Research Foundation (UK), and Regeneron.

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

MILAN — Seladelpar, an investigational selective peroxisome proliferator-activated receptor delta agonist, achieves both biochemical and clinically meaningful improvements in pruritus and liver injury in patients with primary biliary cholangitis (PBC), both with and without compensated liver cirrhosis, according to two interim analyses of the ASSURE long-term extension study.

The first analysis of 337 patients with PBC, with and without cirrhosis, showed that treatment with seladelpar had a durable effect up to 2 years on cholestasis and markers of liver injury, as well as a sustained reduction in pruritus, Palak Trivedi, MD, associate professor at the National Institute for Health Research Birmingham Biomedical Research Centre, University of Birmingham, Birmingham, England, reported in a poster presented at the European Association for the Study of the Liver (EASL) Congress 2024.

The 2-year analysis also showed that seladelpar, a first-in-class, orally active agent, was safe and well tolerated in this patient population, he added.

These “results are consistent with the pivotal phase 3 RESPONSE study,” Dr. Trivedi noted. The RESPONSE study showed that seladelpar significantly improved liver biomarkers of disease activity and symptoms of pruritus at 12 months in patients with PBC who had an inadequate response or intolerance to ursodeoxycholic acid (UDCA), the standard of care, and had no history of hepatic decompensation. Patients with cirrhosis were allowed to enroll.

A total of 158 patients from the RESPONSE trial, both from the placebo and from the active treatment arm, were rolled over into the ASSURE trial. Another subset of 179 patients were drawn from prior seladelpar placebo-controlled studies (referred to as “legacy studies”), including the ENHANCE study. All participants in the current analysis received 10 mg of seladelpar, once daily, for up to 155 weeks.

Of the participants from the legacy studies, 99 completed 24 months of treatment with seladelpar, and 164 completed 12 months of treatment. In the 24-month treatment group, 70% met the composite response endpoint, which included alkaline phosphatase (ALP) levels below 1.67 times the upper limit of normal, a decrease in ALP levels of at least 15%, and total bilirubin levels at or below the upper limit of normal, according to a press release of the study findings. In addition, 42% of these participants achieved ALP normalization at 24 months, a marker of liver disease progression. In the 12-month treatment group, 73% achieved the clinically meaningful composite response endpoint, with 42% experiencing ALP normalization.

For patients rolled over from RESPONSE, 102 received 18 months of treatment with seladelpar, and 29 received 24 months of treatment. A total of 62% of patients in the 18-month group achieved the composite endpoint, and 33% achieved ALP normalization, while 72% of the 24-month group reached the composite endpoint, and 17% had ALP normalization.

Of patients who had received a placebo in the RESPONSE trial and went on to receive treatment with seladelpar, 75% achieved the composite endpoint, 27% had ALP normalization at 6 months, and 94% achieved the composite endpoint and 50% reached ALP normalization at 12 months.

Key secondary endpoints included ALP normalization and changes in liver enzymes (ALP, total bilirubin, gamma-glutamyl transferase [GGT], alanine transaminase [ALT], and aspartate aminotransferase [AST]).
 

Pruritus Relief Important for Quality of Life

Among study participants who reported a four or more at baseline on the numerical rating scale (NRS) for pruritus, legacy patients at 12 months and 24 months of treatment reported a mean reduction of 3.8 and 3.1, respectively. Participants from RESPONSE also reported a mean reduction of 3.8.

This level of reduction in NRS is “considered clinically significant” and takes patients from a level of moderate to severe itching down to mild, said Carrie Frenette, MD, executive director, Global Medical Affairs, Liver Diseases, Gilead Sciences, Foster City, California, and a former hepatologist of 20 years with a special interest in liver transplantation.

This “is a huge benefit in quality of life for these patients,” Dr. Frenette said in an interview.

Dr. Frenette also noted that UDCA, the current first-line treatment for PBC, is inadequate in up to 40% of patients, and second-line treatments, notably obeticholic acid, can cause itching.

European Society for Organ Transplantation

Eleonora De Martin, MD, transplant hepatologist at Centre Hépato-Biliaire, Paul Brousse Hospital, Paris, France, who comoderated the session, pointed out that PBC is a complex disease.

“We need both disease control and symptom control, and they’re not always compatible,” she said. “Sometimes you can control the disease but not the symptoms, and symptomatic control is so important,” especially with pruritus.
 

Patients With PBC and Cirrhosis

A separate analysis from ASSURE looked at a subset of 17 patients with PBC and cirrhosis who completed 24 months of treatment. The findings were presented by Stuart Gordon, MD, professor of medicine, Wayne State University School of Medicine, and hepatologist at Henry Ford Hospital, both in Detroit.

In this analysis, the mean patient age was 60.8 years, 91.4% were female, 88.6% were Child-Pugh A, and 22.9% had portal hypertension, while the mean baseline liver stiffness by FibroScan was 19.9 kPa.

Baseline biochemical measures were mean ALP of 245.4 U/L, mean total bilirubin of 0.995 mg/dL, mean GGT of 216.1 U/L, and mean ALT of 36.6 U/L.

A total of 11 participants (65%) met the composite endpoint at 24 months, with ALP normalization in 4 patients (24%). The overall mean percent change from baseline in ALP was approximately −30% and in total bilirubin was around −14%. Other changes in biochemical markers included reductions from baseline in GGT and ALT of approximately −30% and −10%, respectively. No change was observed in AST.

While 80% of patients with cirrhosis “had an adverse event of some form,” there were no treatment-related serious adverse events.

“It’s interesting to see results in these patients who have advanced disease and are cirrhotic because it might stabilize disease or even provide improvement,” Dr. De Martin commented. “However, the numbers in the study are very small, so it’s hard to draw firm conclusions yet, but it is a first step in showing that this drug is safe.”

Seladelpar is an “important step forward in PBC because we’ve been stuck with ursodeoxycholic acid for so many years,” Dr. De Martin added. “We’ve seen in liver disease with other etiologies that sometimes just one drug can make a difference, and you can change the natural history of the disease.”

Dr. Frenette is an employee and stockholder of Gilead Sciences. Dr. Gordon declared grants and support from AbbVie, Arbutus, CymaBay, Cour Pharmaceuticals, GlaxoSmithKline (GSK), Ipsen, and Mirum Pharmaceuticals; and advisory board activity from CymaBay, GSK, and Ipsen Pharmaceuticals. Dr. De Martin had no disclosures of relevance to seladelpar but has received speaker fees from other companies, including GSK, Ipsen, and Astellas. Dr. Trivedi reports institutional funding support from National Institute for Health Research Birmingham (UK); lecture fees from Advanz Pharma/Intercept Pharmaceuticals, Albireo/Ipsen, and Dr. Falk Pharma; advisory board/consulting fees from Advanz Pharma/Intercept Pharmaceuticals, Albireo/Ipsen, Chemomab Therapeutics, CymaBay, Dr. Falk Pharma, Gilead Sciences, Perspectum, and Pliant Therapeutics; and grant support from Advanz Pharma/Intercept Pharmaceuticals, Albireo/Ipsen, Bristol-Myers Squibb, Core (Guts UK), EASL, Gilead Sciences, GSK, LifeArc, NIHR, Mirum Pharma, PSC Support, The Wellcome Trust, The Medical Research Foundation (UK), and Regeneron.

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

MILAN — Seladelpar, an investigational selective peroxisome proliferator-activated receptor delta agonist, achieves both biochemical and clinically meaningful improvements in pruritus and liver injury in patients with primary biliary cholangitis (PBC), both with and without compensated liver cirrhosis, according to two interim analyses of the ASSURE long-term extension study.

The first analysis of 337 patients with PBC, with and without cirrhosis, showed that treatment with seladelpar had a durable effect up to 2 years on cholestasis and markers of liver injury, as well as a sustained reduction in pruritus, Palak Trivedi, MD, associate professor at the National Institute for Health Research Birmingham Biomedical Research Centre, University of Birmingham, Birmingham, England, reported in a poster presented at the European Association for the Study of the Liver (EASL) Congress 2024.

The 2-year analysis also showed that seladelpar, a first-in-class, orally active agent, was safe and well tolerated in this patient population, he added.

These “results are consistent with the pivotal phase 3 RESPONSE study,” Dr. Trivedi noted. The RESPONSE study showed that seladelpar significantly improved liver biomarkers of disease activity and symptoms of pruritus at 12 months in patients with PBC who had an inadequate response or intolerance to ursodeoxycholic acid (UDCA), the standard of care, and had no history of hepatic decompensation. Patients with cirrhosis were allowed to enroll.

A total of 158 patients from the RESPONSE trial, both from the placebo and from the active treatment arm, were rolled over into the ASSURE trial. Another subset of 179 patients were drawn from prior seladelpar placebo-controlled studies (referred to as “legacy studies”), including the ENHANCE study. All participants in the current analysis received 10 mg of seladelpar, once daily, for up to 155 weeks.

Of the participants from the legacy studies, 99 completed 24 months of treatment with seladelpar, and 164 completed 12 months of treatment. In the 24-month treatment group, 70% met the composite response endpoint, which included alkaline phosphatase (ALP) levels below 1.67 times the upper limit of normal, a decrease in ALP levels of at least 15%, and total bilirubin levels at or below the upper limit of normal, according to a press release of the study findings. In addition, 42% of these participants achieved ALP normalization at 24 months, a marker of liver disease progression. In the 12-month treatment group, 73% achieved the clinically meaningful composite response endpoint, with 42% experiencing ALP normalization.

For patients rolled over from RESPONSE, 102 received 18 months of treatment with seladelpar, and 29 received 24 months of treatment. A total of 62% of patients in the 18-month group achieved the composite endpoint, and 33% achieved ALP normalization, while 72% of the 24-month group reached the composite endpoint, and 17% had ALP normalization.

Of patients who had received a placebo in the RESPONSE trial and went on to receive treatment with seladelpar, 75% achieved the composite endpoint, 27% had ALP normalization at 6 months, and 94% achieved the composite endpoint and 50% reached ALP normalization at 12 months.

Key secondary endpoints included ALP normalization and changes in liver enzymes (ALP, total bilirubin, gamma-glutamyl transferase [GGT], alanine transaminase [ALT], and aspartate aminotransferase [AST]).
 

Pruritus Relief Important for Quality of Life

Among study participants who reported a four or more at baseline on the numerical rating scale (NRS) for pruritus, legacy patients at 12 months and 24 months of treatment reported a mean reduction of 3.8 and 3.1, respectively. Participants from RESPONSE also reported a mean reduction of 3.8.

This level of reduction in NRS is “considered clinically significant” and takes patients from a level of moderate to severe itching down to mild, said Carrie Frenette, MD, executive director, Global Medical Affairs, Liver Diseases, Gilead Sciences, Foster City, California, and a former hepatologist of 20 years with a special interest in liver transplantation.

This “is a huge benefit in quality of life for these patients,” Dr. Frenette said in an interview.

Dr. Frenette also noted that UDCA, the current first-line treatment for PBC, is inadequate in up to 40% of patients, and second-line treatments, notably obeticholic acid, can cause itching.

European Society for Organ Transplantation

Eleonora De Martin, MD, transplant hepatologist at Centre Hépato-Biliaire, Paul Brousse Hospital, Paris, France, who comoderated the session, pointed out that PBC is a complex disease.

“We need both disease control and symptom control, and they’re not always compatible,” she said. “Sometimes you can control the disease but not the symptoms, and symptomatic control is so important,” especially with pruritus.
 

Patients With PBC and Cirrhosis

A separate analysis from ASSURE looked at a subset of 17 patients with PBC and cirrhosis who completed 24 months of treatment. The findings were presented by Stuart Gordon, MD, professor of medicine, Wayne State University School of Medicine, and hepatologist at Henry Ford Hospital, both in Detroit.

In this analysis, the mean patient age was 60.8 years, 91.4% were female, 88.6% were Child-Pugh A, and 22.9% had portal hypertension, while the mean baseline liver stiffness by FibroScan was 19.9 kPa.

Baseline biochemical measures were mean ALP of 245.4 U/L, mean total bilirubin of 0.995 mg/dL, mean GGT of 216.1 U/L, and mean ALT of 36.6 U/L.

A total of 11 participants (65%) met the composite endpoint at 24 months, with ALP normalization in 4 patients (24%). The overall mean percent change from baseline in ALP was approximately −30% and in total bilirubin was around −14%. Other changes in biochemical markers included reductions from baseline in GGT and ALT of approximately −30% and −10%, respectively. No change was observed in AST.

While 80% of patients with cirrhosis “had an adverse event of some form,” there were no treatment-related serious adverse events.

“It’s interesting to see results in these patients who have advanced disease and are cirrhotic because it might stabilize disease or even provide improvement,” Dr. De Martin commented. “However, the numbers in the study are very small, so it’s hard to draw firm conclusions yet, but it is a first step in showing that this drug is safe.”

Seladelpar is an “important step forward in PBC because we’ve been stuck with ursodeoxycholic acid for so many years,” Dr. De Martin added. “We’ve seen in liver disease with other etiologies that sometimes just one drug can make a difference, and you can change the natural history of the disease.”

Dr. Frenette is an employee and stockholder of Gilead Sciences. Dr. Gordon declared grants and support from AbbVie, Arbutus, CymaBay, Cour Pharmaceuticals, GlaxoSmithKline (GSK), Ipsen, and Mirum Pharmaceuticals; and advisory board activity from CymaBay, GSK, and Ipsen Pharmaceuticals. Dr. De Martin had no disclosures of relevance to seladelpar but has received speaker fees from other companies, including GSK, Ipsen, and Astellas. Dr. Trivedi reports institutional funding support from National Institute for Health Research Birmingham (UK); lecture fees from Advanz Pharma/Intercept Pharmaceuticals, Albireo/Ipsen, and Dr. Falk Pharma; advisory board/consulting fees from Advanz Pharma/Intercept Pharmaceuticals, Albireo/Ipsen, Chemomab Therapeutics, CymaBay, Dr. Falk Pharma, Gilead Sciences, Perspectum, and Pliant Therapeutics; and grant support from Advanz Pharma/Intercept Pharmaceuticals, Albireo/Ipsen, Bristol-Myers Squibb, Core (Guts UK), EASL, Gilead Sciences, GSK, LifeArc, NIHR, Mirum Pharma, PSC Support, The Wellcome Trust, The Medical Research Foundation (UK), and Regeneron.

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

Traction alopecia (TA) is a common type of alopecia that ultimately can result in permanent hair loss. It often is caused or worsened by repetitive and prolonged hairstyling practices such as tight ponytails, braids, or locs, or use of wigs or weaves.¹ Use of headwear, as in certain religious or ethnic groups, also can be contributory.² Individuals participating in or training for occupations involving military service or ballet are at risk for TA due to hairstyling-specific policies. Early stages of TA are reversible with proper treatment and avoidance of exacerbating factors, emphasizing the importance of prompt recognition.³

Epidemiology

Data on the true prevalence of TA are lacking. It can occur in individuals of any race or any hair type. However, it is most common in women of African descent, affecting approximately one-third of this population.⁴ Other commonly affected groups include ballerinas and active-duty service members due to tight ponytails and buns, as well as the Sikh population due to the use of turbans as a part of their religious practice.^2,5,6

Traction alopecia also impacts children, particularly those of African descent. A 2007 study of schoolchildren in South Africa determined that more than 17% of young African girls had evidence of TA—even some as young as 6 years of age.⁷

Traction alopecia can be caused or exacerbated by the use of hair clips and bobby pins that aid holding styles in place.⁸ Hair shaft morphology may contribute to the risk for TA, with more tightly coiled hair types being more susceptible.⁸ Variables such as use of chemical relaxers also increase the risk for disease, especially when combined with high-tension styling methods such as braids.⁹

Key clinical features

Patients with TA clinically present with hair loss and breakage in areas with tension, most commonly the marginal areas of the scalp as well as the frontal hairline and temporal scalp. Hair loss can result in a “fringe sign,” in which a patient may have preservation of a thin line of hairs at the frontal aspect of the hairline with a band of hair loss behind.¹⁰ This presentation may be used to differentiate TA from other forms of alopecia, including frontal fibrosing alopecia and female pattern hair loss. When the hair loss is not marginal, it may mimic other forms of patchy hair loss including alopecia areata and trichotillomania. Other clinical findings in TA may include broken hairs, pustules, and follicular papules.¹⁰ Patients also may describe symptoms such as scalp tenderness with specific hairstyles or headaches,¹¹ or they may be completely asymptomatic.

Trichoscopy can be helpful in guiding diagnosis and treatment. Patients with TA often have perifollicular erythema and hair casts (cylindrical structures that encircle the proximal hair shafts) in the earlier stages of the disease, with eventual loss of follicular ostia in the later stages.^10,12 Hair casts also may indicate ongoing traction.¹² The flambeau sign—white tracks seen on trichoscopy in the direction the hair is pulled—resembles a lit torch.¹³

Early-stage TA can be reversed by avoiding hair tension. However, patients may not be amenable to this due to personal hairstyling preferences, job duties, or religious practices. Treatment with topical or intralesional steroids or even oral antibiotics such as doxycycline for its anti-inflammatory ability may result in regrowth of lost hair if the follicles are not permanently lost and exacerbating factors are avoided.^3,14 Both topical and oral minoxidil have been used with success, with minoxidil thought to increase hair density by extending the anagen (growth) phase of hair follicles.^3,15 Culturally sensitive patient counseling on the condition and potential exacerbating factors is critical.¹⁶

At later stages of the disease—after loss of follicular ostia has occurred—surgical interventions should be considered,¹⁷ such as hair transplantation, which can be successful but remains a technical challenge due to variability in hair shaft curvature.¹⁸ Additionally, the cost of the procedure can limit use, and some patients may not be optimal candidates due to the extent of their hair loss. Traction alopecia may not be the only hair loss condition present. Examining the scalp is important even if the chief area of concern is the marginal scalp.

Health disparity highlight

Prevention, early identification, and treatment initiated in a timely fashion are crucial to prevent permanent hair loss. There are added societal and cultural pressures that impact hairstyle and hair care practices, especially for those with tightly coiled hair.¹⁹ Historically, tightly coiled hair has been unfairly viewed as “unprofessional,” “unkempt,” and a challenge to “manage” by some. Thus, heat, chemical relaxers, and tight hairstyles holding hair in one position have been used to straighten the hair permanently or temporarily or to keep it maintained in a style that did not necessitate excessive manipulation—often contributing to further tension on the hair.

Military service branches have evaluated and changed some hair-related policies to reflect the diverse hair types of military personnel.²⁰ The CROWN Act (www.thecrownact.com/about)—“Creating a Respectful and Open World for Natural Hair”—is a model law passed by 26 states that prohibits race-based hair discrimination, which is the denial of employment and educational opportunities because of hair texture. Although the law has not been passed in every state, it may help individuals with tightly coiled hair to embrace natural hairstyles. However, even hairstyles with one’s own natural curl pattern can contribute to tension and thus potential development of TA.

Traction alopecia (TA) is a common type of alopecia that ultimately can result in permanent hair loss. It often is caused or worsened by repetitive and prolonged hairstyling practices such as tight ponytails, braids, or locs, or use of wigs or weaves.¹ Use of headwear, as in certain religious or ethnic groups, also can be contributory.² Individuals participating in or training for occupations involving military service or ballet are at risk for TA due to hairstyling-specific policies. Early stages of TA are reversible with proper treatment and avoidance of exacerbating factors, emphasizing the importance of prompt recognition.³

Epidemiology

Data on the true prevalence of TA are lacking. It can occur in individuals of any race or any hair type. However, it is most common in women of African descent, affecting approximately one-third of this population.⁴ Other commonly affected groups include ballerinas and active-duty service members due to tight ponytails and buns, as well as the Sikh population due to the use of turbans as a part of their religious practice.^2,5,6

Traction alopecia also impacts children, particularly those of African descent. A 2007 study of schoolchildren in South Africa determined that more than 17% of young African girls had evidence of TA—even some as young as 6 years of age.⁷

Traction alopecia can be caused or exacerbated by the use of hair clips and bobby pins that aid holding styles in place.⁸ Hair shaft morphology may contribute to the risk for TA, with more tightly coiled hair types being more susceptible.⁸ Variables such as use of chemical relaxers also increase the risk for disease, especially when combined with high-tension styling methods such as braids.⁹

Key clinical features

Patients with TA clinically present with hair loss and breakage in areas with tension, most commonly the marginal areas of the scalp as well as the frontal hairline and temporal scalp. Hair loss can result in a “fringe sign,” in which a patient may have preservation of a thin line of hairs at the frontal aspect of the hairline with a band of hair loss behind.¹⁰ This presentation may be used to differentiate TA from other forms of alopecia, including frontal fibrosing alopecia and female pattern hair loss. When the hair loss is not marginal, it may mimic other forms of patchy hair loss including alopecia areata and trichotillomania. Other clinical findings in TA may include broken hairs, pustules, and follicular papules.¹⁰ Patients also may describe symptoms such as scalp tenderness with specific hairstyles or headaches,¹¹ or they may be completely asymptomatic.

Trichoscopy can be helpful in guiding diagnosis and treatment. Patients with TA often have perifollicular erythema and hair casts (cylindrical structures that encircle the proximal hair shafts) in the earlier stages of the disease, with eventual loss of follicular ostia in the later stages.^10,12 Hair casts also may indicate ongoing traction.¹² The flambeau sign—white tracks seen on trichoscopy in the direction the hair is pulled—resembles a lit torch.¹³

Early-stage TA can be reversed by avoiding hair tension. However, patients may not be amenable to this due to personal hairstyling preferences, job duties, or religious practices. Treatment with topical or intralesional steroids or even oral antibiotics such as doxycycline for its anti-inflammatory ability may result in regrowth of lost hair if the follicles are not permanently lost and exacerbating factors are avoided.^3,14 Both topical and oral minoxidil have been used with success, with minoxidil thought to increase hair density by extending the anagen (growth) phase of hair follicles.^3,15 Culturally sensitive patient counseling on the condition and potential exacerbating factors is critical.¹⁶

At later stages of the disease—after loss of follicular ostia has occurred—surgical interventions should be considered,¹⁷ such as hair transplantation, which can be successful but remains a technical challenge due to variability in hair shaft curvature.¹⁸ Additionally, the cost of the procedure can limit use, and some patients may not be optimal candidates due to the extent of their hair loss. Traction alopecia may not be the only hair loss condition present. Examining the scalp is important even if the chief area of concern is the marginal scalp.

Health disparity highlight

Prevention, early identification, and treatment initiated in a timely fashion are crucial to prevent permanent hair loss. There are added societal and cultural pressures that impact hairstyle and hair care practices, especially for those with tightly coiled hair.¹⁹ Historically, tightly coiled hair has been unfairly viewed as “unprofessional,” “unkempt,” and a challenge to “manage” by some. Thus, heat, chemical relaxers, and tight hairstyles holding hair in one position have been used to straighten the hair permanently or temporarily or to keep it maintained in a style that did not necessitate excessive manipulation—often contributing to further tension on the hair.

Military service branches have evaluated and changed some hair-related policies to reflect the diverse hair types of military personnel.²⁰ The CROWN Act (www.thecrownact.com/about)—“Creating a Respectful and Open World for Natural Hair”—is a model law passed by 26 states that prohibits race-based hair discrimination, which is the denial of employment and educational opportunities because of hair texture. Although the law has not been passed in every state, it may help individuals with tightly coiled hair to embrace natural hairstyles. However, even hairstyles with one’s own natural curl pattern can contribute to tension and thus potential development of TA.

Traction alopecia (TA) is a common type of alopecia that ultimately can result in permanent hair loss. It often is caused or worsened by repetitive and prolonged hairstyling practices such as tight ponytails, braids, or locs, or use of wigs or weaves.¹ Use of headwear, as in certain religious or ethnic groups, also can be contributory.² Individuals participating in or training for occupations involving military service or ballet are at risk for TA due to hairstyling-specific policies. Early stages of TA are reversible with proper treatment and avoidance of exacerbating factors, emphasizing the importance of prompt recognition.³

Epidemiology

Data on the true prevalence of TA are lacking. It can occur in individuals of any race or any hair type. However, it is most common in women of African descent, affecting approximately one-third of this population.⁴ Other commonly affected groups include ballerinas and active-duty service members due to tight ponytails and buns, as well as the Sikh population due to the use of turbans as a part of their religious practice.^2,5,6

Traction alopecia also impacts children, particularly those of African descent. A 2007 study of schoolchildren in South Africa determined that more than 17% of young African girls had evidence of TA—even some as young as 6 years of age.⁷

Traction alopecia can be caused or exacerbated by the use of hair clips and bobby pins that aid holding styles in place.⁸ Hair shaft morphology may contribute to the risk for TA, with more tightly coiled hair types being more susceptible.⁸ Variables such as use of chemical relaxers also increase the risk for disease, especially when combined with high-tension styling methods such as braids.⁹

Key clinical features

Patients with TA clinically present with hair loss and breakage in areas with tension, most commonly the marginal areas of the scalp as well as the frontal hairline and temporal scalp. Hair loss can result in a “fringe sign,” in which a patient may have preservation of a thin line of hairs at the frontal aspect of the hairline with a band of hair loss behind.¹⁰ This presentation may be used to differentiate TA from other forms of alopecia, including frontal fibrosing alopecia and female pattern hair loss. When the hair loss is not marginal, it may mimic other forms of patchy hair loss including alopecia areata and trichotillomania. Other clinical findings in TA may include broken hairs, pustules, and follicular papules.¹⁰ Patients also may describe symptoms such as scalp tenderness with specific hairstyles or headaches,¹¹ or they may be completely asymptomatic.

Trichoscopy can be helpful in guiding diagnosis and treatment. Patients with TA often have perifollicular erythema and hair casts (cylindrical structures that encircle the proximal hair shafts) in the earlier stages of the disease, with eventual loss of follicular ostia in the later stages.^10,12 Hair casts also may indicate ongoing traction.¹² The flambeau sign—white tracks seen on trichoscopy in the direction the hair is pulled—resembles a lit torch.¹³

Early-stage TA can be reversed by avoiding hair tension. However, patients may not be amenable to this due to personal hairstyling preferences, job duties, or religious practices. Treatment with topical or intralesional steroids or even oral antibiotics such as doxycycline for its anti-inflammatory ability may result in regrowth of lost hair if the follicles are not permanently lost and exacerbating factors are avoided.^3,14 Both topical and oral minoxidil have been used with success, with minoxidil thought to increase hair density by extending the anagen (growth) phase of hair follicles.^3,15 Culturally sensitive patient counseling on the condition and potential exacerbating factors is critical.¹⁶

At later stages of the disease—after loss of follicular ostia has occurred—surgical interventions should be considered,¹⁷ such as hair transplantation, which can be successful but remains a technical challenge due to variability in hair shaft curvature.¹⁸ Additionally, the cost of the procedure can limit use, and some patients may not be optimal candidates due to the extent of their hair loss. Traction alopecia may not be the only hair loss condition present. Examining the scalp is important even if the chief area of concern is the marginal scalp.

Health disparity highlight

Prevention, early identification, and treatment initiated in a timely fashion are crucial to prevent permanent hair loss. There are added societal and cultural pressures that impact hairstyle and hair care practices, especially for those with tightly coiled hair.¹⁹ Historically, tightly coiled hair has been unfairly viewed as “unprofessional,” “unkempt,” and a challenge to “manage” by some. Thus, heat, chemical relaxers, and tight hairstyles holding hair in one position have been used to straighten the hair permanently or temporarily or to keep it maintained in a style that did not necessitate excessive manipulation—often contributing to further tension on the hair.

Military service branches have evaluated and changed some hair-related policies to reflect the diverse hair types of military personnel.²⁰ The CROWN Act (www.thecrownact.com/about)—“Creating a Respectful and Open World for Natural Hair”—is a model law passed by 26 states that prohibits race-based hair discrimination, which is the denial of employment and educational opportunities because of hair texture. Although the law has not been passed in every state, it may help individuals with tightly coiled hair to embrace natural hairstyles. However, even hairstyles with one’s own natural curl pattern can contribute to tension and thus potential development of TA.

The newly updated US Department of Veterans Affairs (VA) prostate cancer clinical pathway looks like a set of guidelines, but it’s really something unique. As attendees learned at an Association of VA Hematology/Oncology (AVAHO) regional meeting in Detroit in June, the clinical pathways are designed to point the way toward a standard ideal treatment for the majority of cases, not just to suggest a number of possible options.

“Pathways will always offer one scenario. They try to get oncologists to practice in a similar fashion so things can be managed more uniformly,” Michael M. Goodman, MD, told Federal Practitioner prior to the AVAHO meeting that was focused on prostate cancer care. Goodman is an associate professor of medicine with Atrium Health Wake Forest Baptist Medical Center and helped develop the VA genitourinary oncology pathways.

“The overall goal is not just to standardize care as much as possible but also to synthesize the best and most cost-effective practices,” Goodman said. For example, “If you have 5 different therapies, and they all have about the same efficacy and safety, and 1 is less costly than the other 4, then it would make sense to choose that.”

The VA has offered pathways for multiple types of cancer since 2021, and the pathway for prostate cancer is among the most comprehensive. The VA system updated the pathway in March 2024, is available online both via SharePoint and externally.

“It goes through the entire gamut from screening, diagnosis, and management to end of life,” Goodman explained. Multiple disciplines, from primary care and surgery to genetics and imaging, can rely on the pathway to assist decision-making.

In terms of screening, the pathway offers a flow map guiding the screening choices. In patients aged ≤ 54 years, only certain high-risk groups, such as African Americans and those with a family history of prostate cancer, should be screened. From ages 54 to 69 years, patients should be consulted as part of a shared decision making process, while screening is not recommended for patients aged ≥ 70 years.

Pathway flow maps also provide information about diagnostic standards, evaluation of the newly diagnosed, risk stratification, molecular testing, and end-of-life care.

Goodman says the pathway is now integrated into the VA electronic health record system via a template so clinicians can easily document pathway use. This allows the VA to track the use of the pathways locally, regionally, and nationally track the use of the pathways.

Clinicians are not mandated to follow every step in the pathway, but Goodman said the goal is > 80% adherence. If clinicians follow the standards, he said, “you’re considering efficacy, safety, and cost for that veteran.”

Prospective data suggests that adherence to the pathway eliminates certain disparities. African American veterans, for example, are as well-represented or even better represented than White veterans in prostate cancer care when pathways are followed.

Why might clinicians veer from the pathway? “If you’re seeing a patient who was treated in the community with drug X, but drug Y is chosen by the pathway, you can carry on with the previous care.” Alternatively, in some cases, patients may not tolerate the pathway standard, Goodman noted.

Goodman reports that he consults the pathway every day. “It’s helped standardize the care I provide to ensure there’s no gaps in how I’m treating patients.”

The newly updated US Department of Veterans Affairs (VA) prostate cancer clinical pathway looks like a set of guidelines, but it’s really something unique. As attendees learned at an Association of VA Hematology/Oncology (AVAHO) regional meeting in Detroit in June, the clinical pathways are designed to point the way toward a standard ideal treatment for the majority of cases, not just to suggest a number of possible options.

“Pathways will always offer one scenario. They try to get oncologists to practice in a similar fashion so things can be managed more uniformly,” Michael M. Goodman, MD, told Federal Practitioner prior to the AVAHO meeting that was focused on prostate cancer care. Goodman is an associate professor of medicine with Atrium Health Wake Forest Baptist Medical Center and helped develop the VA genitourinary oncology pathways.

“The overall goal is not just to standardize care as much as possible but also to synthesize the best and most cost-effective practices,” Goodman said. For example, “If you have 5 different therapies, and they all have about the same efficacy and safety, and 1 is less costly than the other 4, then it would make sense to choose that.”

The VA has offered pathways for multiple types of cancer since 2021, and the pathway for prostate cancer is among the most comprehensive. The VA system updated the pathway in March 2024, is available online both via SharePoint and externally.

“It goes through the entire gamut from screening, diagnosis, and management to end of life,” Goodman explained. Multiple disciplines, from primary care and surgery to genetics and imaging, can rely on the pathway to assist decision-making.

In terms of screening, the pathway offers a flow map guiding the screening choices. In patients aged ≤ 54 years, only certain high-risk groups, such as African Americans and those with a family history of prostate cancer, should be screened. From ages 54 to 69 years, patients should be consulted as part of a shared decision making process, while screening is not recommended for patients aged ≥ 70 years.

Pathway flow maps also provide information about diagnostic standards, evaluation of the newly diagnosed, risk stratification, molecular testing, and end-of-life care.

Goodman says the pathway is now integrated into the VA electronic health record system via a template so clinicians can easily document pathway use. This allows the VA to track the use of the pathways locally, regionally, and nationally track the use of the pathways.

Clinicians are not mandated to follow every step in the pathway, but Goodman said the goal is > 80% adherence. If clinicians follow the standards, he said, “you’re considering efficacy, safety, and cost for that veteran.”

Prospective data suggests that adherence to the pathway eliminates certain disparities. African American veterans, for example, are as well-represented or even better represented than White veterans in prostate cancer care when pathways are followed.

Why might clinicians veer from the pathway? “If you’re seeing a patient who was treated in the community with drug X, but drug Y is chosen by the pathway, you can carry on with the previous care.” Alternatively, in some cases, patients may not tolerate the pathway standard, Goodman noted.

Goodman reports that he consults the pathway every day. “It’s helped standardize the care I provide to ensure there’s no gaps in how I’m treating patients.”

The newly updated US Department of Veterans Affairs (VA) prostate cancer clinical pathway looks like a set of guidelines, but it’s really something unique. As attendees learned at an Association of VA Hematology/Oncology (AVAHO) regional meeting in Detroit in June, the clinical pathways are designed to point the way toward a standard ideal treatment for the majority of cases, not just to suggest a number of possible options.

“Pathways will always offer one scenario. They try to get oncologists to practice in a similar fashion so things can be managed more uniformly,” Michael M. Goodman, MD, told Federal Practitioner prior to the AVAHO meeting that was focused on prostate cancer care. Goodman is an associate professor of medicine with Atrium Health Wake Forest Baptist Medical Center and helped develop the VA genitourinary oncology pathways.

“The overall goal is not just to standardize care as much as possible but also to synthesize the best and most cost-effective practices,” Goodman said. For example, “If you have 5 different therapies, and they all have about the same efficacy and safety, and 1 is less costly than the other 4, then it would make sense to choose that.”

The VA has offered pathways for multiple types of cancer since 2021, and the pathway for prostate cancer is among the most comprehensive. The VA system updated the pathway in March 2024, is available online both via SharePoint and externally.

“It goes through the entire gamut from screening, diagnosis, and management to end of life,” Goodman explained. Multiple disciplines, from primary care and surgery to genetics and imaging, can rely on the pathway to assist decision-making.

In terms of screening, the pathway offers a flow map guiding the screening choices. In patients aged ≤ 54 years, only certain high-risk groups, such as African Americans and those with a family history of prostate cancer, should be screened. From ages 54 to 69 years, patients should be consulted as part of a shared decision making process, while screening is not recommended for patients aged ≥ 70 years.

Pathway flow maps also provide information about diagnostic standards, evaluation of the newly diagnosed, risk stratification, molecular testing, and end-of-life care.

Goodman says the pathway is now integrated into the VA electronic health record system via a template so clinicians can easily document pathway use. This allows the VA to track the use of the pathways locally, regionally, and nationally track the use of the pathways.

Clinicians are not mandated to follow every step in the pathway, but Goodman said the goal is > 80% adherence. If clinicians follow the standards, he said, “you’re considering efficacy, safety, and cost for that veteran.”

Prospective data suggests that adherence to the pathway eliminates certain disparities. African American veterans, for example, are as well-represented or even better represented than White veterans in prostate cancer care when pathways are followed.

Why might clinicians veer from the pathway? “If you’re seeing a patient who was treated in the community with drug X, but drug Y is chosen by the pathway, you can carry on with the previous care.” Alternatively, in some cases, patients may not tolerate the pathway standard, Goodman noted.

Goodman reports that he consults the pathway every day. “It’s helped standardize the care I provide to ensure there’s no gaps in how I’m treating patients.”

Time was—recent time, that is—sailors had two chances to pass a physical fitness assessment (PFA). Failing the first meant no promotion. Failing the second: No career. They could neither be promoted nor reenlist.

That’s changed; as of this month, the Navy now allows the sailor’s commanding officer to decide whether the sailor gets to go on, even after failing a second test.

In an administrative letter, Vice Adm. Rick Cheeseman, chief of naval personnel, said, "Commanding officers can now evaluate a sailor's physical readiness progress or lack of progress in performance evaluations, giving them the ability to manage risk, recognize earnest effort, and best take care of their people.”

According to the new policy, sailors who fail any PFA no longer need to have it noted on their annual evaluation (although they still may not advance until they pass another test). Enlisted sailors who fail a second consecutive PFA are no longer required to receive the lowest possible score in the "Military Bearing/Professionalism" category and are not denied the ability to reenlist.

In assessing eligibility for enlisted members, the memo states that commanders should consider a sailor’s ability to perform the functions of their rate without physical or medical limitation at sea, shore or isolated duty; their overall ability to contribute to Navy missions; and the likelihood of improvement in meeting PFA standards within the next 12 months.

“Building the bodies of great people,” Cheeseman wrote, “is more than annual (or biannual) testing and includes ensuring healthy food, adequate sleep, opportunities to exercise (especially outside), and medical readiness.”  

According to a report by Military.com, “critics have argued that many of the changes were the Navy relaxing its standards in the face of a challenging recruiting environment and an increasingly overweight population of Americans.” However, Navy data provided in November indicate that the number of sailors failing PFAs has remained very low. In 2017, nearly 98% of sailors passed the PFA, and 95.1% passed the first post-pandemic PFA in 2022.

The PFA policy changes are part of the Navy’s Culture of Excellence 2.0, initiated earlier this year, Cheeseman says. This initiative “charges our leaders to build great people, great leaders, and great teams: their minds, bodies, and spirits, eliminating barriers wherever possible.  In response, we are modernizing our PFA policy to acknowledge our diverse population, increase sailor trust, and enhance quality of service.”

Time was—recent time, that is—sailors had two chances to pass a physical fitness assessment (PFA). Failing the first meant no promotion. Failing the second: No career. They could neither be promoted nor reenlist.

That’s changed; as of this month, the Navy now allows the sailor’s commanding officer to decide whether the sailor gets to go on, even after failing a second test.

In an administrative letter, Vice Adm. Rick Cheeseman, chief of naval personnel, said, "Commanding officers can now evaluate a sailor's physical readiness progress or lack of progress in performance evaluations, giving them the ability to manage risk, recognize earnest effort, and best take care of their people.”

According to the new policy, sailors who fail any PFA no longer need to have it noted on their annual evaluation (although they still may not advance until they pass another test). Enlisted sailors who fail a second consecutive PFA are no longer required to receive the lowest possible score in the "Military Bearing/Professionalism" category and are not denied the ability to reenlist.

In assessing eligibility for enlisted members, the memo states that commanders should consider a sailor’s ability to perform the functions of their rate without physical or medical limitation at sea, shore or isolated duty; their overall ability to contribute to Navy missions; and the likelihood of improvement in meeting PFA standards within the next 12 months.

“Building the bodies of great people,” Cheeseman wrote, “is more than annual (or biannual) testing and includes ensuring healthy food, adequate sleep, opportunities to exercise (especially outside), and medical readiness.”  

According to a report by Military.com, “critics have argued that many of the changes were the Navy relaxing its standards in the face of a challenging recruiting environment and an increasingly overweight population of Americans.” However, Navy data provided in November indicate that the number of sailors failing PFAs has remained very low. In 2017, nearly 98% of sailors passed the PFA, and 95.1% passed the first post-pandemic PFA in 2022.

The PFA policy changes are part of the Navy’s Culture of Excellence 2.0, initiated earlier this year, Cheeseman says. This initiative “charges our leaders to build great people, great leaders, and great teams: their minds, bodies, and spirits, eliminating barriers wherever possible.  In response, we are modernizing our PFA policy to acknowledge our diverse population, increase sailor trust, and enhance quality of service.”

Time was—recent time, that is—sailors had two chances to pass a physical fitness assessment (PFA). Failing the first meant no promotion. Failing the second: No career. They could neither be promoted nor reenlist.

That’s changed; as of this month, the Navy now allows the sailor’s commanding officer to decide whether the sailor gets to go on, even after failing a second test.

In an administrative letter, Vice Adm. Rick Cheeseman, chief of naval personnel, said, "Commanding officers can now evaluate a sailor's physical readiness progress or lack of progress in performance evaluations, giving them the ability to manage risk, recognize earnest effort, and best take care of their people.”

According to the new policy, sailors who fail any PFA no longer need to have it noted on their annual evaluation (although they still may not advance until they pass another test). Enlisted sailors who fail a second consecutive PFA are no longer required to receive the lowest possible score in the "Military Bearing/Professionalism" category and are not denied the ability to reenlist.

In assessing eligibility for enlisted members, the memo states that commanders should consider a sailor’s ability to perform the functions of their rate without physical or medical limitation at sea, shore or isolated duty; their overall ability to contribute to Navy missions; and the likelihood of improvement in meeting PFA standards within the next 12 months.

“Building the bodies of great people,” Cheeseman wrote, “is more than annual (or biannual) testing and includes ensuring healthy food, adequate sleep, opportunities to exercise (especially outside), and medical readiness.”  

According to a report by Military.com, “critics have argued that many of the changes were the Navy relaxing its standards in the face of a challenging recruiting environment and an increasingly overweight population of Americans.” However, Navy data provided in November indicate that the number of sailors failing PFAs has remained very low. In 2017, nearly 98% of sailors passed the PFA, and 95.1% passed the first post-pandemic PFA in 2022.

The PFA policy changes are part of the Navy’s Culture of Excellence 2.0, initiated earlier this year, Cheeseman says. This initiative “charges our leaders to build great people, great leaders, and great teams: their minds, bodies, and spirits, eliminating barriers wherever possible.  In response, we are modernizing our PFA policy to acknowledge our diverse population, increase sailor trust, and enhance quality of service.”

MILAN — Tirzepatide, a glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) receptor agonist, was more effective than was placebo in the resolution of metabolic dysfunction–associated steatohepatitis (MASH) and in the improvement of fibrosis, according to the results of the phase 2 SYNERGY-NASH trial.

Specifically, 44%-62% of participants with MASH and moderate or severe fibrosis treated with 5-15 mg of tirzepatide achieved MASH resolution without worsening of fibrosis compared with 10% on placebo; 51%-55% of those on tirzepatide achieved at least one stage of fibrosis improvement without worsening of MASH compared with 30% on placebo. Tirzepatide also led to weight loss.

The study (Abstract LBO-001) was presented at the European Association for the Study of the Liver (EASL) Congress 2024 by Rohit Loomba, MD, professor of medicine, NAFLD Research Center, University of California at San Diego in La Jolla, and published simultaneously in The New England Journal of Medicine. 

“The results are clinically meaningful,” Dr. Loomba said in an interview. 

University of California, San Diego

Both of the endpoints — improvements in MASH resolution and fibrosis — are considered approvable endpoints for MASH therapeutic development, and therefore, increase the likelihood of success of using such a strategy in a phase 3 setting, Dr. Loomba said.
 

MASH Resolution, No Worsening of Fibrosis

The dose-finding, multicenter, double-blind, placebo-controlled trial randomly assigned a total of 190 participants to receive once-weekly subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 52 weeks. Participants had biopsy-confirmed MASH and stage F2 or F3 (moderate or severe) fibrosis. 

Overall, approximately 42% of participants had F2 fibrosis and over 57% had F3 fibrosis. The proportion of F3 fibrosis was numerically higher in the placebo (64.6%) and 5-mg tirzepatide (63.8%) groups. 

The mean age of the study cohort was 54 years; 57% were female, 86% were White, and 36% were Hispanic; the mean body mass index was 36; 58% had type 2 diabetes; and A1c was 6.5. NAFLD activity score (NAS) was 5.3. Baseline noninvasive test results were consistent with the study population of MASH with F2/F3 fibrosis and NAS ≥ 4. 

The primary endpoint was resolution of MASH without worsening of fibrosis at 52 weeks, and the key secondary endpoint was an improvement (decrease) of at least one fibrosis stage without worsening of MASH. Other secondary endpoints included a ≥ 2-point decrease in NAS with ≤ 1-point decrease in two or more NAS components.

A total of 157 participants (83%) underwent liver biopsies at week 52, providing results for the current analysis. 

Among tirzepatide-treated patients, 43.6% in the 5-mg group, 55.5% in the 10-mg group, and 62.4% in the 15-mg group met the criteria for resolution of MASH without worsening of fibrosis compared with  10% in the placebo group (P < .001 for all three comparisons). 

Fibrosis improved by at least one stage without worsening of MASH in 54.9% of participants in the 5-mg tirzepatide group, 51.3% in the 10-mg tirzepatide group, and 51.0% in the 15-mg tirzepatide group compared with 29.7% in the placebo group (P < .001 for all risk differences with placebo). 

Changes in NAS and subscores for the individual components of NAS, including steatosis, lobular inflammation, and hepatocellular ballooning, were also seen in participants on tirzepatide. 

The researchers used a composite endpoint of a ≥ 2-point decrease in NAS with a ≥ 1-point decrease in at least two NAS components. Of the tirzepatide-treated groups, 71.7%,78.3%, and 76.6% in the 5-mg, 10-mg, and 15-mg groups, respectively, met this endpoint compared with 36.7% in placebo. 

Imaging of liver fat with MRI-based proton density fat fraction (MRI-PDFF) showed reductions from baseline of -45.7, -41.3, -57.0 in participants on 5-mg, 10-mg, and 15-mg tirzepatide, respectively. Differences from placebo were all statistically significant. 

Percentage of body weight change from baseline was -10.7%, -13.3%, and -15.6% in the 5-mg, 10-mg, and 15-mg tirzepatide groups, respectively, compared with weight loss of -0.8% in the placebo group. 

“Tirzepatide led to significant weight loss in both patients with diabetes and those without diabetes,” reported Dr. Loomba. 

There were more adverse events in patients on tirzepatide (92.3%) compared with patients on placebo (83.3%). 

“The most common adverse events were gastrointestinal in nature, with 96% of them mild to moderate in severity,” said Dr. Loomba. “Discontinuations occurred in 4.2% of participants, which was similar between patients on tirzepatide and those on placebo.”

He pointed out that the safety profile of tirzepatide in a MASH population “was generally similar to that observed in the phase 3 trials of type 2 diabetes and obesity.”

Incidence of serious adverse events was also similar at 6.3% for participants on tirzepatide vs 6.2% for those on placebo; 2.8% on tirzepatide and 4.2% on placebo progressed to cirrhosis. There was no evidence of drug-induced liver injury. 
 

‘Convincing Results’

Commenting on the study, co-moderator Sven Francque, MD, hepatologist and head of department at the University Hospital of Antwerp, Belgium, said that the study was in a relatively “severe” patient population, which was one of its strengths. 

“These are convincing results in terms of MASH resolution, showing a strong response and dose-dependence,” he said. 

Dr. Francque

MILAN — Tirzepatide, a glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) receptor agonist, was more effective than was placebo in the resolution of metabolic dysfunction–associated steatohepatitis (MASH) and in the improvement of fibrosis, according to the results of the phase 2 SYNERGY-NASH trial.

Specifically, 44%-62% of participants with MASH and moderate or severe fibrosis treated with 5-15 mg of tirzepatide achieved MASH resolution without worsening of fibrosis compared with 10% on placebo; 51%-55% of those on tirzepatide achieved at least one stage of fibrosis improvement without worsening of MASH compared with 30% on placebo. Tirzepatide also led to weight loss.

The study (Abstract LBO-001) was presented at the European Association for the Study of the Liver (EASL) Congress 2024 by Rohit Loomba, MD, professor of medicine, NAFLD Research Center, University of California at San Diego in La Jolla, and published simultaneously in The New England Journal of Medicine. 

“The results are clinically meaningful,” Dr. Loomba said in an interview. 

University of California, San Diego

Both of the endpoints — improvements in MASH resolution and fibrosis — are considered approvable endpoints for MASH therapeutic development, and therefore, increase the likelihood of success of using such a strategy in a phase 3 setting, Dr. Loomba said.
 

MASH Resolution, No Worsening of Fibrosis

The dose-finding, multicenter, double-blind, placebo-controlled trial randomly assigned a total of 190 participants to receive once-weekly subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 52 weeks. Participants had biopsy-confirmed MASH and stage F2 or F3 (moderate or severe) fibrosis. 

Overall, approximately 42% of participants had F2 fibrosis and over 57% had F3 fibrosis. The proportion of F3 fibrosis was numerically higher in the placebo (64.6%) and 5-mg tirzepatide (63.8%) groups. 

The mean age of the study cohort was 54 years; 57% were female, 86% were White, and 36% were Hispanic; the mean body mass index was 36; 58% had type 2 diabetes; and A1c was 6.5. NAFLD activity score (NAS) was 5.3. Baseline noninvasive test results were consistent with the study population of MASH with F2/F3 fibrosis and NAS ≥ 4. 

The primary endpoint was resolution of MASH without worsening of fibrosis at 52 weeks, and the key secondary endpoint was an improvement (decrease) of at least one fibrosis stage without worsening of MASH. Other secondary endpoints included a ≥ 2-point decrease in NAS with ≤ 1-point decrease in two or more NAS components.

A total of 157 participants (83%) underwent liver biopsies at week 52, providing results for the current analysis. 

Among tirzepatide-treated patients, 43.6% in the 5-mg group, 55.5% in the 10-mg group, and 62.4% in the 15-mg group met the criteria for resolution of MASH without worsening of fibrosis compared with  10% in the placebo group (P < .001 for all three comparisons). 

Fibrosis improved by at least one stage without worsening of MASH in 54.9% of participants in the 5-mg tirzepatide group, 51.3% in the 10-mg tirzepatide group, and 51.0% in the 15-mg tirzepatide group compared with 29.7% in the placebo group (P < .001 for all risk differences with placebo). 

Changes in NAS and subscores for the individual components of NAS, including steatosis, lobular inflammation, and hepatocellular ballooning, were also seen in participants on tirzepatide. 

The researchers used a composite endpoint of a ≥ 2-point decrease in NAS with a ≥ 1-point decrease in at least two NAS components. Of the tirzepatide-treated groups, 71.7%,78.3%, and 76.6% in the 5-mg, 10-mg, and 15-mg groups, respectively, met this endpoint compared with 36.7% in placebo. 

Imaging of liver fat with MRI-based proton density fat fraction (MRI-PDFF) showed reductions from baseline of -45.7, -41.3, -57.0 in participants on 5-mg, 10-mg, and 15-mg tirzepatide, respectively. Differences from placebo were all statistically significant. 

Percentage of body weight change from baseline was -10.7%, -13.3%, and -15.6% in the 5-mg, 10-mg, and 15-mg tirzepatide groups, respectively, compared with weight loss of -0.8% in the placebo group. 

“Tirzepatide led to significant weight loss in both patients with diabetes and those without diabetes,” reported Dr. Loomba. 

There were more adverse events in patients on tirzepatide (92.3%) compared with patients on placebo (83.3%). 

“The most common adverse events were gastrointestinal in nature, with 96% of them mild to moderate in severity,” said Dr. Loomba. “Discontinuations occurred in 4.2% of participants, which was similar between patients on tirzepatide and those on placebo.”

He pointed out that the safety profile of tirzepatide in a MASH population “was generally similar to that observed in the phase 3 trials of type 2 diabetes and obesity.”

Incidence of serious adverse events was also similar at 6.3% for participants on tirzepatide vs 6.2% for those on placebo; 2.8% on tirzepatide and 4.2% on placebo progressed to cirrhosis. There was no evidence of drug-induced liver injury. 
 

‘Convincing Results’

Commenting on the study, co-moderator Sven Francque, MD, hepatologist and head of department at the University Hospital of Antwerp, Belgium, said that the study was in a relatively “severe” patient population, which was one of its strengths. 

“These are convincing results in terms of MASH resolution, showing a strong response and dose-dependence,” he said. 

Dr. Francque

MILAN — Tirzepatide, a glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) receptor agonist, was more effective than was placebo in the resolution of metabolic dysfunction–associated steatohepatitis (MASH) and in the improvement of fibrosis, according to the results of the phase 2 SYNERGY-NASH trial.

Specifically, 44%-62% of participants with MASH and moderate or severe fibrosis treated with 5-15 mg of tirzepatide achieved MASH resolution without worsening of fibrosis compared with 10% on placebo; 51%-55% of those on tirzepatide achieved at least one stage of fibrosis improvement without worsening of MASH compared with 30% on placebo. Tirzepatide also led to weight loss.

The study (Abstract LBO-001) was presented at the European Association for the Study of the Liver (EASL) Congress 2024 by Rohit Loomba, MD, professor of medicine, NAFLD Research Center, University of California at San Diego in La Jolla, and published simultaneously in The New England Journal of Medicine. 

“The results are clinically meaningful,” Dr. Loomba said in an interview. 

University of California, San Diego

Both of the endpoints — improvements in MASH resolution and fibrosis — are considered approvable endpoints for MASH therapeutic development, and therefore, increase the likelihood of success of using such a strategy in a phase 3 setting, Dr. Loomba said.
 

MASH Resolution, No Worsening of Fibrosis

The dose-finding, multicenter, double-blind, placebo-controlled trial randomly assigned a total of 190 participants to receive once-weekly subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 52 weeks. Participants had biopsy-confirmed MASH and stage F2 or F3 (moderate or severe) fibrosis. 

Overall, approximately 42% of participants had F2 fibrosis and over 57% had F3 fibrosis. The proportion of F3 fibrosis was numerically higher in the placebo (64.6%) and 5-mg tirzepatide (63.8%) groups. 

The mean age of the study cohort was 54 years; 57% were female, 86% were White, and 36% were Hispanic; the mean body mass index was 36; 58% had type 2 diabetes; and A1c was 6.5. NAFLD activity score (NAS) was 5.3. Baseline noninvasive test results were consistent with the study population of MASH with F2/F3 fibrosis and NAS ≥ 4. 

The primary endpoint was resolution of MASH without worsening of fibrosis at 52 weeks, and the key secondary endpoint was an improvement (decrease) of at least one fibrosis stage without worsening of MASH. Other secondary endpoints included a ≥ 2-point decrease in NAS with ≤ 1-point decrease in two or more NAS components.

A total of 157 participants (83%) underwent liver biopsies at week 52, providing results for the current analysis. 

Among tirzepatide-treated patients, 43.6% in the 5-mg group, 55.5% in the 10-mg group, and 62.4% in the 15-mg group met the criteria for resolution of MASH without worsening of fibrosis compared with  10% in the placebo group (P < .001 for all three comparisons). 

Fibrosis improved by at least one stage without worsening of MASH in 54.9% of participants in the 5-mg tirzepatide group, 51.3% in the 10-mg tirzepatide group, and 51.0% in the 15-mg tirzepatide group compared with 29.7% in the placebo group (P < .001 for all risk differences with placebo). 

Changes in NAS and subscores for the individual components of NAS, including steatosis, lobular inflammation, and hepatocellular ballooning, were also seen in participants on tirzepatide. 

The researchers used a composite endpoint of a ≥ 2-point decrease in NAS with a ≥ 1-point decrease in at least two NAS components. Of the tirzepatide-treated groups, 71.7%,78.3%, and 76.6% in the 5-mg, 10-mg, and 15-mg groups, respectively, met this endpoint compared with 36.7% in placebo. 

Imaging of liver fat with MRI-based proton density fat fraction (MRI-PDFF) showed reductions from baseline of -45.7, -41.3, -57.0 in participants on 5-mg, 10-mg, and 15-mg tirzepatide, respectively. Differences from placebo were all statistically significant. 

Percentage of body weight change from baseline was -10.7%, -13.3%, and -15.6% in the 5-mg, 10-mg, and 15-mg tirzepatide groups, respectively, compared with weight loss of -0.8% in the placebo group. 

“Tirzepatide led to significant weight loss in both patients with diabetes and those without diabetes,” reported Dr. Loomba. 

There were more adverse events in patients on tirzepatide (92.3%) compared with patients on placebo (83.3%). 

“The most common adverse events were gastrointestinal in nature, with 96% of them mild to moderate in severity,” said Dr. Loomba. “Discontinuations occurred in 4.2% of participants, which was similar between patients on tirzepatide and those on placebo.”

He pointed out that the safety profile of tirzepatide in a MASH population “was generally similar to that observed in the phase 3 trials of type 2 diabetes and obesity.”

Incidence of serious adverse events was also similar at 6.3% for participants on tirzepatide vs 6.2% for those on placebo; 2.8% on tirzepatide and 4.2% on placebo progressed to cirrhosis. There was no evidence of drug-induced liver injury. 
 

‘Convincing Results’

Commenting on the study, co-moderator Sven Francque, MD, hepatologist and head of department at the University Hospital of Antwerp, Belgium, said that the study was in a relatively “severe” patient population, which was one of its strengths. 

“These are convincing results in terms of MASH resolution, showing a strong response and dose-dependence,” he said. 

Dr. Francque

The AGA Research Foundation plays an important role in medical research by providing grants to talented scientists at a critical time in their career. AGA’s flagship award is the Research Scholar Award (RSA), which provides career development support for young investigators in gastroenterology and hepatology research.

“The AGA Research Scholar Award will have a significant impact on my career,” said Dr. Jason (Yanjia) Zhang, 2024 AGA Research Scholar Award grant recipient, and a gastroenterologist at Boston Children’s Hospital. “I aspire to lead a laboratory studying the impact of the microbiome on human gastroenterological diseases. Our lab will focus on the molecular mechanisms underlying how microbes activate gut signaling. The AGA Research Foundation grant will support my transition to independence and build key capacities that will be the foundation of my future lab.”

Boston Children&#039;s Hospital

Funded by the generosity of donors, the AGA Research Foundation’s research award program ensures that AGA is building a community of researchers whose work serves the greater community and benefits all our patients.

By joining other AGA members in supporting the AGA Research Foundation, you will ensure that young researchers have opportunities to continue their life-saving work. Your tax-deductible contribution supports the foundation’s research award program, including the RSA, which ensures that studies are funded, discoveries are made and patients are treated.

Learn more or make a contribution at www.foundation.gastro.org.

The AGA Research Foundation plays an important role in medical research by providing grants to talented scientists at a critical time in their career. AGA’s flagship award is the Research Scholar Award (RSA), which provides career development support for young investigators in gastroenterology and hepatology research.

“The AGA Research Scholar Award will have a significant impact on my career,” said Dr. Jason (Yanjia) Zhang, 2024 AGA Research Scholar Award grant recipient, and a gastroenterologist at Boston Children’s Hospital. “I aspire to lead a laboratory studying the impact of the microbiome on human gastroenterological diseases. Our lab will focus on the molecular mechanisms underlying how microbes activate gut signaling. The AGA Research Foundation grant will support my transition to independence and build key capacities that will be the foundation of my future lab.”

Boston Children&#039;s Hospital

Funded by the generosity of donors, the AGA Research Foundation’s research award program ensures that AGA is building a community of researchers whose work serves the greater community and benefits all our patients.

By joining other AGA members in supporting the AGA Research Foundation, you will ensure that young researchers have opportunities to continue their life-saving work. Your tax-deductible contribution supports the foundation’s research award program, including the RSA, which ensures that studies are funded, discoveries are made and patients are treated.

Learn more or make a contribution at www.foundation.gastro.org.

The AGA Research Foundation plays an important role in medical research by providing grants to talented scientists at a critical time in their career. AGA’s flagship award is the Research Scholar Award (RSA), which provides career development support for young investigators in gastroenterology and hepatology research.

“The AGA Research Scholar Award will have a significant impact on my career,” said Dr. Jason (Yanjia) Zhang, 2024 AGA Research Scholar Award grant recipient, and a gastroenterologist at Boston Children’s Hospital. “I aspire to lead a laboratory studying the impact of the microbiome on human gastroenterological diseases. Our lab will focus on the molecular mechanisms underlying how microbes activate gut signaling. The AGA Research Foundation grant will support my transition to independence and build key capacities that will be the foundation of my future lab.”

Boston Children&#039;s Hospital

Funded by the generosity of donors, the AGA Research Foundation’s research award program ensures that AGA is building a community of researchers whose work serves the greater community and benefits all our patients.

By joining other AGA members in supporting the AGA Research Foundation, you will ensure that young researchers have opportunities to continue their life-saving work. Your tax-deductible contribution supports the foundation’s research award program, including the RSA, which ensures that studies are funded, discoveries are made and patients are treated.

Learn more or make a contribution at www.foundation.gastro.org.

The recent Food and Drug Administration (FDA) approval of ensifentrine marks the first new treatment for patients with persistent chronic obstructive pulmonary disease (COPD) in more than a decade, according to manufacturer Verona Pharma.

Ensifentrine offers a new medication and a new delivery method, according to a company press release. Ensifentrine is the first-in-class selective dual inhibitor of both phosphodiesterase 3 (PDE 3) and PDE 4, combining both bronchodilator and nonsteroidal anti-inflammatory effects in a single molecule. The drug is delivered through a standard jet nebulizer.
 

Disease Management Made Easier

Although currently approved therapies for COPD, such as bronchodilators and inhaled corticosteroids (ICS), have benefited many patients, additional treatment options are still needed to help those who remain symptomatic and suffer from frequent exacerbations, said Diego J. Maselli, MD, of the University of Texas Health Science Center, San Antonio.

“Ensifentrine is a new class of medication that inhibits both PDE 3 and PDE 4; this results in both bronchodilation and suppression of the inflammatory response in COPD,” said Dr. Maselli, who was not involved in studies of ensifentrine.

“Large phase III, double-blind, randomized, placebo-controlled studies have demonstrated that ensifentrine improved lung function and reduced the risk of exacerbations in patients with symptomatic moderate to severe COPD,” he said. The study participants were on no long-acting maintenance therapy, or they were receiving long-acting beta agonist (LABA) or long-acting muscarinic antagonist (LAMA) with or without inhaled corticosteroids, he noted.

The FDA approval was supported by data from the phase 3 ENHANCE 1 and 2 trials, which included 760 and 789 adults aged 40-80 years with moderate to severe symptomatic COPD, respectively. Participants were randomized to 3 mg ensifentrine delivered via nebulizer or a placebo twice daily.

In the studies, ensifentrine significantly improved lung function based on the primary outcome of average forced expiratory volume per second within 0-12 hours of administration compared with placebo in both studies. In ENHANCE 1, ensifentrine significantly improved symptoms and quality of life compared with placebo at 24 weeks. The ENHANCE 2 results showed similar trends in favor of ensifentrine, although the differences were not significant at 24 weeks. However, the effects of ensifentrine vs placebo were consistent overall across all symptom and quality of life endpoints at all assessments during the study period, the researchers wrote.

In addition, the inhaled drug was well tolerated, with similar proportions of ensifentrine and placebo patients reporting treatment-emergent adverse events (38.4% and 36.4%, respectively, in ENHANCE 1 and 35.3% and 35.4%, respectively, in ENHANCE 2). The most common treatment-emergent adverse events were nasopharyngitis, hypertension, and back pain, reported in < 3% of the ensifentrine group.

The safety profile of ensifentrine is a plus for patients, said Dr. Maselli. “Ensifentrine was well tolerated in these studies, and the side effect profile was similar to placebo,” he said. The “ensifentrine is delivered via nebulizer and dosed every 12 hours. Some patients may still prefer the use of inhalers, while others may feel more comfortable with this mode of delivery,” he said. 

In clinical practice, “ensifentrine is a welcome addition to the current armamentarium of therapies for COPD as an option for patients who are symptomatic or who have frequent exacerbations,” Dr. Maselli emphasized.

Looking ahead, more studies are needed to evaluate ensifentrine in broader populations of COPD patients, Dr. Maselli said. For example, ensifentrine could be used as an add-on therapy for patients receiving triple therapy (ICS/LABA/LAMA) and for patients with other obstructive inflammatory diseases such as asthma, bronchiectasis, and cystic fibrosis, he noted.

Dr. Maselli disclosed serving as a consultant for GlaxoSmithKline, AstraZeneca, Amgen, and Sanofi/Regeneron; he also serves on the Editorial Board of CHEST Physician.
 

A version of this article appeared on Medscape.com.

The recent Food and Drug Administration (FDA) approval of ensifentrine marks the first new treatment for patients with persistent chronic obstructive pulmonary disease (COPD) in more than a decade, according to manufacturer Verona Pharma.

Ensifentrine offers a new medication and a new delivery method, according to a company press release. Ensifentrine is the first-in-class selective dual inhibitor of both phosphodiesterase 3 (PDE 3) and PDE 4, combining both bronchodilator and nonsteroidal anti-inflammatory effects in a single molecule. The drug is delivered through a standard jet nebulizer.
 

Disease Management Made Easier

Although currently approved therapies for COPD, such as bronchodilators and inhaled corticosteroids (ICS), have benefited many patients, additional treatment options are still needed to help those who remain symptomatic and suffer from frequent exacerbations, said Diego J. Maselli, MD, of the University of Texas Health Science Center, San Antonio.

“Ensifentrine is a new class of medication that inhibits both PDE 3 and PDE 4; this results in both bronchodilation and suppression of the inflammatory response in COPD,” said Dr. Maselli, who was not involved in studies of ensifentrine.

“Large phase III, double-blind, randomized, placebo-controlled studies have demonstrated that ensifentrine improved lung function and reduced the risk of exacerbations in patients with symptomatic moderate to severe COPD,” he said. The study participants were on no long-acting maintenance therapy, or they were receiving long-acting beta agonist (LABA) or long-acting muscarinic antagonist (LAMA) with or without inhaled corticosteroids, he noted.

The FDA approval was supported by data from the phase 3 ENHANCE 1 and 2 trials, which included 760 and 789 adults aged 40-80 years with moderate to severe symptomatic COPD, respectively. Participants were randomized to 3 mg ensifentrine delivered via nebulizer or a placebo twice daily.

In the studies, ensifentrine significantly improved lung function based on the primary outcome of average forced expiratory volume per second within 0-12 hours of administration compared with placebo in both studies. In ENHANCE 1, ensifentrine significantly improved symptoms and quality of life compared with placebo at 24 weeks. The ENHANCE 2 results showed similar trends in favor of ensifentrine, although the differences were not significant at 24 weeks. However, the effects of ensifentrine vs placebo were consistent overall across all symptom and quality of life endpoints at all assessments during the study period, the researchers wrote.

In addition, the inhaled drug was well tolerated, with similar proportions of ensifentrine and placebo patients reporting treatment-emergent adverse events (38.4% and 36.4%, respectively, in ENHANCE 1 and 35.3% and 35.4%, respectively, in ENHANCE 2). The most common treatment-emergent adverse events were nasopharyngitis, hypertension, and back pain, reported in < 3% of the ensifentrine group.

The safety profile of ensifentrine is a plus for patients, said Dr. Maselli. “Ensifentrine was well tolerated in these studies, and the side effect profile was similar to placebo,” he said. The “ensifentrine is delivered via nebulizer and dosed every 12 hours. Some patients may still prefer the use of inhalers, while others may feel more comfortable with this mode of delivery,” he said. 

In clinical practice, “ensifentrine is a welcome addition to the current armamentarium of therapies for COPD as an option for patients who are symptomatic or who have frequent exacerbations,” Dr. Maselli emphasized.

Looking ahead, more studies are needed to evaluate ensifentrine in broader populations of COPD patients, Dr. Maselli said. For example, ensifentrine could be used as an add-on therapy for patients receiving triple therapy (ICS/LABA/LAMA) and for patients with other obstructive inflammatory diseases such as asthma, bronchiectasis, and cystic fibrosis, he noted.

Dr. Maselli disclosed serving as a consultant for GlaxoSmithKline, AstraZeneca, Amgen, and Sanofi/Regeneron; he also serves on the Editorial Board of CHEST Physician.
 

A version of this article appeared on Medscape.com.

The recent Food and Drug Administration (FDA) approval of ensifentrine marks the first new treatment for patients with persistent chronic obstructive pulmonary disease (COPD) in more than a decade, according to manufacturer Verona Pharma.

Ensifentrine offers a new medication and a new delivery method, according to a company press release. Ensifentrine is the first-in-class selective dual inhibitor of both phosphodiesterase 3 (PDE 3) and PDE 4, combining both bronchodilator and nonsteroidal anti-inflammatory effects in a single molecule. The drug is delivered through a standard jet nebulizer.
 

Disease Management Made Easier

Although currently approved therapies for COPD, such as bronchodilators and inhaled corticosteroids (ICS), have benefited many patients, additional treatment options are still needed to help those who remain symptomatic and suffer from frequent exacerbations, said Diego J. Maselli, MD, of the University of Texas Health Science Center, San Antonio.

“Ensifentrine is a new class of medication that inhibits both PDE 3 and PDE 4; this results in both bronchodilation and suppression of the inflammatory response in COPD,” said Dr. Maselli, who was not involved in studies of ensifentrine.

“Large phase III, double-blind, randomized, placebo-controlled studies have demonstrated that ensifentrine improved lung function and reduced the risk of exacerbations in patients with symptomatic moderate to severe COPD,” he said. The study participants were on no long-acting maintenance therapy, or they were receiving long-acting beta agonist (LABA) or long-acting muscarinic antagonist (LAMA) with or without inhaled corticosteroids, he noted.

The FDA approval was supported by data from the phase 3 ENHANCE 1 and 2 trials, which included 760 and 789 adults aged 40-80 years with moderate to severe symptomatic COPD, respectively. Participants were randomized to 3 mg ensifentrine delivered via nebulizer or a placebo twice daily.

In the studies, ensifentrine significantly improved lung function based on the primary outcome of average forced expiratory volume per second within 0-12 hours of administration compared with placebo in both studies. In ENHANCE 1, ensifentrine significantly improved symptoms and quality of life compared with placebo at 24 weeks. The ENHANCE 2 results showed similar trends in favor of ensifentrine, although the differences were not significant at 24 weeks. However, the effects of ensifentrine vs placebo were consistent overall across all symptom and quality of life endpoints at all assessments during the study period, the researchers wrote.

In addition, the inhaled drug was well tolerated, with similar proportions of ensifentrine and placebo patients reporting treatment-emergent adverse events (38.4% and 36.4%, respectively, in ENHANCE 1 and 35.3% and 35.4%, respectively, in ENHANCE 2). The most common treatment-emergent adverse events were nasopharyngitis, hypertension, and back pain, reported in < 3% of the ensifentrine group.

The safety profile of ensifentrine is a plus for patients, said Dr. Maselli. “Ensifentrine was well tolerated in these studies, and the side effect profile was similar to placebo,” he said. The “ensifentrine is delivered via nebulizer and dosed every 12 hours. Some patients may still prefer the use of inhalers, while others may feel more comfortable with this mode of delivery,” he said. 

In clinical practice, “ensifentrine is a welcome addition to the current armamentarium of therapies for COPD as an option for patients who are symptomatic or who have frequent exacerbations,” Dr. Maselli emphasized.

Looking ahead, more studies are needed to evaluate ensifentrine in broader populations of COPD patients, Dr. Maselli said. For example, ensifentrine could be used as an add-on therapy for patients receiving triple therapy (ICS/LABA/LAMA) and for patients with other obstructive inflammatory diseases such as asthma, bronchiectasis, and cystic fibrosis, he noted.

Dr. Maselli disclosed serving as a consultant for GlaxoSmithKline, AstraZeneca, Amgen, and Sanofi/Regeneron; he also serves on the Editorial Board of CHEST Physician.
 

A version of this article appeared on Medscape.com.

Philips Respironics Inc. has issued updated instructions for the use of its OmniLab Advanced+ (OLA+) Ventilator because of its demonstrated failure in the ventilator inoperative alarm that can cause an interruption or loss of therapy, according to a recall statement from the US Food and Drug Administration (FDA).

The OLA+ Ventilator is designed for use by individuals with obstructive sleep apnea, breathing problems, and mixed apnea and is approved for children aged 7 years and older, as well as adults.

The recall does not involve removal of the devices from where they are used or sold but does update the instructions for use, and its use without following the updated instructions could result in serious injury or death, according to the statement.

Following an alarm failure, the device may fail in one of two ways: By entering a ventilator inoperative state after three reboots within 24 hours (with no therapy and audible and visual alarms present) or by entering a ventilator inoperative state without rebooting first.

According to the statement, the alarm issue may be corrected with a software patch, available from Philips, or the company will offer a replacement device for patients until the affected devices are repaired. The statement updates an April 1, 2024, urgent recall from Philips urging the immediate removal of a patient from an OLA+ Ventilator and connecting them to alternative ventilation if possible if the ventilator’s inoperative alarm occurs.

The device failures may cause interruption or loss of therapy with effects including anxiety, confusion/disorientation, changes in respiratory rate, dyspnea, tachycardia, respiratory failure, and even death in especially vulnerable individuals. One death and 15 injuries have been reported as a result of the alarm failure, according to the FDA.

US customers can contact Philips Respironics Inc. at 1-800-345-6443 or [email protected] with questions, according to the FDA, and clinicians and patients may report adverse reactions or other problems with the devices to MedWatch: The FDA Safety Information and Adverse Event Reporting Program.

A version of this article appeared on Medscape.com.

Philips Respironics Inc. has issued updated instructions for the use of its OmniLab Advanced+ (OLA+) Ventilator because of its demonstrated failure in the ventilator inoperative alarm that can cause an interruption or loss of therapy, according to a recall statement from the US Food and Drug Administration (FDA).

The OLA+ Ventilator is designed for use by individuals with obstructive sleep apnea, breathing problems, and mixed apnea and is approved for children aged 7 years and older, as well as adults.

The recall does not involve removal of the devices from where they are used or sold but does update the instructions for use, and its use without following the updated instructions could result in serious injury or death, according to the statement.

Following an alarm failure, the device may fail in one of two ways: By entering a ventilator inoperative state after three reboots within 24 hours (with no therapy and audible and visual alarms present) or by entering a ventilator inoperative state without rebooting first.

According to the statement, the alarm issue may be corrected with a software patch, available from Philips, or the company will offer a replacement device for patients until the affected devices are repaired. The statement updates an April 1, 2024, urgent recall from Philips urging the immediate removal of a patient from an OLA+ Ventilator and connecting them to alternative ventilation if possible if the ventilator’s inoperative alarm occurs.

The device failures may cause interruption or loss of therapy with effects including anxiety, confusion/disorientation, changes in respiratory rate, dyspnea, tachycardia, respiratory failure, and even death in especially vulnerable individuals. One death and 15 injuries have been reported as a result of the alarm failure, according to the FDA.

US customers can contact Philips Respironics Inc. at 1-800-345-6443 or [email protected] with questions, according to the FDA, and clinicians and patients may report adverse reactions or other problems with the devices to MedWatch: The FDA Safety Information and Adverse Event Reporting Program.

A version of this article appeared on Medscape.com.

Philips Respironics Inc. has issued updated instructions for the use of its OmniLab Advanced+ (OLA+) Ventilator because of its demonstrated failure in the ventilator inoperative alarm that can cause an interruption or loss of therapy, according to a recall statement from the US Food and Drug Administration (FDA).

The OLA+ Ventilator is designed for use by individuals with obstructive sleep apnea, breathing problems, and mixed apnea and is approved for children aged 7 years and older, as well as adults.

The recall does not involve removal of the devices from where they are used or sold but does update the instructions for use, and its use without following the updated instructions could result in serious injury or death, according to the statement.

Following an alarm failure, the device may fail in one of two ways: By entering a ventilator inoperative state after three reboots within 24 hours (with no therapy and audible and visual alarms present) or by entering a ventilator inoperative state without rebooting first.

According to the statement, the alarm issue may be corrected with a software patch, available from Philips, or the company will offer a replacement device for patients until the affected devices are repaired. The statement updates an April 1, 2024, urgent recall from Philips urging the immediate removal of a patient from an OLA+ Ventilator and connecting them to alternative ventilation if possible if the ventilator’s inoperative alarm occurs.

The device failures may cause interruption or loss of therapy with effects including anxiety, confusion/disorientation, changes in respiratory rate, dyspnea, tachycardia, respiratory failure, and even death in especially vulnerable individuals. One death and 15 injuries have been reported as a result of the alarm failure, according to the FDA.

US customers can contact Philips Respironics Inc. at 1-800-345-6443 or [email protected] with questions, according to the FDA, and clinicians and patients may report adverse reactions or other problems with the devices to MedWatch: The FDA Safety Information and Adverse Event Reporting Program.

A version of this article appeared on Medscape.com.