Federal Practitioner

The US Food and Drug Administration (FDA) has approved the first-in-class interleukin (IL)-15 superagonist nogapendekin alfa inbakicept-pmln (Anktiva), plus bacillus Calmette-Guérin (BCG), for the treatment of certain non–muscle-invasive bladder cancers that fail to respond to BCG alone.

Specifically, the agent is approved to treat patients with BCG-unresponsive non–muscle-invasive bladder cancer carcinoma in situ with or without Ta or T1 papillary disease. 

The FDA declined an initial approval for the combination in May 2023 because of deficiencies the agency observed during its prelicense inspection of third-party manufacturing organizations. In October 2023, ImmunityBio resubmitted the Biologics License Application, which was accepted.

The new therapy represents addresses “an unmet need” in this high-risk bladder cancer population, the company stated in a press release announcing the initial study findings. Typically, patients with intermediate or high-risk disease undergo bladder tumor resection followed by treatment with BCG, but the cancer recurs in up to 50% of patients, including those who experience a complete response, explained ImmunityBio, which acquired Altor BioScience. 

Approval was based on findings from the single arm, phase 2/3 open-label QUILT-3.032 study, which included 77 patients with BCG-unresponsive, high-risk disease following transurethral resection. All had Eastern Cooperative Oncology Group performance status of 0-2. 

Patients received nogapendekin alfa inbakicept-pmln induction via intravesical instillation with BCG followed by maintenance therapy for up to 37 months. 

According to the FDA’s press release, 62% of patients had a complete response, defined as a negative cystoscopy and urine cytology; 58% of those with a complete response had a duration of response lasting at least 12 months and 40% had a duration of response lasting 24 months or longer.

The safety of the combination was evaluated in a cohort of 88 patients. Serious adverse reactions occurred in 16% of patients. The most common treatment-emergent adverse effects included dysuria, pollakiuria, and hematuria, which are associated with intravesical BCG; 86% of these events were grade 1 or 2. Overall, 7% of patients discontinued the combination owing to adverse reactions.

The recommended dose is 400 mcg administered intravesically with BCG once a week for 6 weeks as induction therapy, with an option for a second induction course if patients don’t achieve a complete response at 3 months. The recommended maintenance therapy dose is 400 mcg with BCG once a week for 3 weeks at months 4, 7, 10, 13, and 19. Patients who achieve a complete response at 25 months and beyond may receive maintenance instillations with BCG once a week for 3 weeks at months 25, 31, and 37. The maximum treatment duration is 37 months.

The FDA recommends discontinuing treatment if disease persists after second induction or owing to disease recurrence, progression, or unacceptable toxicity. 
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the first-in-class interleukin (IL)-15 superagonist nogapendekin alfa inbakicept-pmln (Anktiva), plus bacillus Calmette-Guérin (BCG), for the treatment of certain non–muscle-invasive bladder cancers that fail to respond to BCG alone.

Specifically, the agent is approved to treat patients with BCG-unresponsive non–muscle-invasive bladder cancer carcinoma in situ with or without Ta or T1 papillary disease. 

The FDA declined an initial approval for the combination in May 2023 because of deficiencies the agency observed during its prelicense inspection of third-party manufacturing organizations. In October 2023, ImmunityBio resubmitted the Biologics License Application, which was accepted.

The new therapy represents addresses “an unmet need” in this high-risk bladder cancer population, the company stated in a press release announcing the initial study findings. Typically, patients with intermediate or high-risk disease undergo bladder tumor resection followed by treatment with BCG, but the cancer recurs in up to 50% of patients, including those who experience a complete response, explained ImmunityBio, which acquired Altor BioScience. 

Approval was based on findings from the single arm, phase 2/3 open-label QUILT-3.032 study, which included 77 patients with BCG-unresponsive, high-risk disease following transurethral resection. All had Eastern Cooperative Oncology Group performance status of 0-2. 

Patients received nogapendekin alfa inbakicept-pmln induction via intravesical instillation with BCG followed by maintenance therapy for up to 37 months. 

According to the FDA’s press release, 62% of patients had a complete response, defined as a negative cystoscopy and urine cytology; 58% of those with a complete response had a duration of response lasting at least 12 months and 40% had a duration of response lasting 24 months or longer.

The safety of the combination was evaluated in a cohort of 88 patients. Serious adverse reactions occurred in 16% of patients. The most common treatment-emergent adverse effects included dysuria, pollakiuria, and hematuria, which are associated with intravesical BCG; 86% of these events were grade 1 or 2. Overall, 7% of patients discontinued the combination owing to adverse reactions.

The recommended dose is 400 mcg administered intravesically with BCG once a week for 6 weeks as induction therapy, with an option for a second induction course if patients don’t achieve a complete response at 3 months. The recommended maintenance therapy dose is 400 mcg with BCG once a week for 3 weeks at months 4, 7, 10, 13, and 19. Patients who achieve a complete response at 25 months and beyond may receive maintenance instillations with BCG once a week for 3 weeks at months 25, 31, and 37. The maximum treatment duration is 37 months.

The FDA recommends discontinuing treatment if disease persists after second induction or owing to disease recurrence, progression, or unacceptable toxicity. 
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the first-in-class interleukin (IL)-15 superagonist nogapendekin alfa inbakicept-pmln (Anktiva), plus bacillus Calmette-Guérin (BCG), for the treatment of certain non–muscle-invasive bladder cancers that fail to respond to BCG alone.

Specifically, the agent is approved to treat patients with BCG-unresponsive non–muscle-invasive bladder cancer carcinoma in situ with or without Ta or T1 papillary disease. 

The FDA declined an initial approval for the combination in May 2023 because of deficiencies the agency observed during its prelicense inspection of third-party manufacturing organizations. In October 2023, ImmunityBio resubmitted the Biologics License Application, which was accepted.

The new therapy represents addresses “an unmet need” in this high-risk bladder cancer population, the company stated in a press release announcing the initial study findings. Typically, patients with intermediate or high-risk disease undergo bladder tumor resection followed by treatment with BCG, but the cancer recurs in up to 50% of patients, including those who experience a complete response, explained ImmunityBio, which acquired Altor BioScience. 

Approval was based on findings from the single arm, phase 2/3 open-label QUILT-3.032 study, which included 77 patients with BCG-unresponsive, high-risk disease following transurethral resection. All had Eastern Cooperative Oncology Group performance status of 0-2. 

Patients received nogapendekin alfa inbakicept-pmln induction via intravesical instillation with BCG followed by maintenance therapy for up to 37 months. 

According to the FDA’s press release, 62% of patients had a complete response, defined as a negative cystoscopy and urine cytology; 58% of those with a complete response had a duration of response lasting at least 12 months and 40% had a duration of response lasting 24 months or longer.

The safety of the combination was evaluated in a cohort of 88 patients. Serious adverse reactions occurred in 16% of patients. The most common treatment-emergent adverse effects included dysuria, pollakiuria, and hematuria, which are associated with intravesical BCG; 86% of these events were grade 1 or 2. Overall, 7% of patients discontinued the combination owing to adverse reactions.

The recommended dose is 400 mcg administered intravesically with BCG once a week for 6 weeks as induction therapy, with an option for a second induction course if patients don’t achieve a complete response at 3 months. The recommended maintenance therapy dose is 400 mcg with BCG once a week for 3 weeks at months 4, 7, 10, 13, and 19. Patients who achieve a complete response at 25 months and beyond may receive maintenance instillations with BCG once a week for 3 weeks at months 25, 31, and 37. The maximum treatment duration is 37 months.

The FDA recommends discontinuing treatment if disease persists after second induction or owing to disease recurrence, progression, or unacceptable toxicity. 
 

A version of this article appeared on Medscape.com.

Last year, I concluded a commentary for this news organization on colorectal cancer (CRC) screening guidelines by stating that between stool-based tests, flexible sigmoidoscopy, and colonoscopy, “the best screening test is the test that gets done.” But should that maxim apply to the new blood-based screening test, Guardant Health Shield? This proprietary test, which costs $895 and is not generally covered by insurance, identifies alterations in cell-free DNA that are characteristic of CRC.

Shield’s test characteristics were recently evaluated in a prospective study of more than 10,000 adults aged 45-84 at average risk for CRC. The test had an 87.5% sensitivity for stage I, II, or III colorectal cancer but only a 13% sensitivity for advanced precancerous lesions. Test specificity was 89.6%, meaning that about 1 in 10 participants without CRC or advanced precancerous lesions on colonoscopy had a false-positive result.

Although the Shield blood test has a higher rate of false positives than the traditional fecal immunochemical test (FIT) and lower sensitivity and specificity than a multitarget stool DNA (FIT-DNA) test designed to improve on Cologuard, it meets the previously established criteria set forth by the Centers for Medicare & Medicaid Services (CMS) to be covered for Medicare beneficiaries at 3-year intervals, pending FDA approval. If public and private payers start covering Shield alongside other CRC screening tests, it presents an opportunity for primary care physicians to reach the approximately 3 in 10 adults between ages 45 and 75 who are not being routinely screened.

A big concern, however, is that the availability of a blood test may cause patients who would have otherwise been screened with colonoscopy or stool tests to switch to the blood test. A cost-effectiveness analysis found that offering a blood test to patients who decline screening colonoscopy saves additional lives, but at the cost of more than $377,000 per life-year gained. Another study relying on three microsimulation models previously utilized by the US Preventive Services Task Force (USPSTF) found that annual FIT results in more life-years gained at substantially lower cost than blood-based screening every 3 years “even when uptake of blood-based screening was 20 percentage points higher than uptake of FIT.” As a result, a multidisciplinary expert panel concluded that blood-based screening should not substitute for established CRC screening tests, but instead be offered only to patients who decline those tests.

In practice, this will increase the complexity of the CRC screening conversations we have with patients. We will need to be clear that the blood test is not yet endorsed by the USPSTF or any major guideline group and is a second-line test that will miss most precancerous polyps. As with the stool tests, it is essential to emphasize that a positive result must be followed by diagnostic colonoscopy. To addend the cancer screening maxim I mentioned before, the blood test is not the best test for CRC, but it’s probably better than no test at all.

Dr. Lin is a family physician and associate director, Family Medicine Residency Program, Lancaster General Hospital, Lancaster, Pennsylvania. He blogs at Common Sense Family Doctor.

A version of this article appeared on Medscape.com.

Last year, I concluded a commentary for this news organization on colorectal cancer (CRC) screening guidelines by stating that between stool-based tests, flexible sigmoidoscopy, and colonoscopy, “the best screening test is the test that gets done.” But should that maxim apply to the new blood-based screening test, Guardant Health Shield? This proprietary test, which costs $895 and is not generally covered by insurance, identifies alterations in cell-free DNA that are characteristic of CRC.

Shield’s test characteristics were recently evaluated in a prospective study of more than 10,000 adults aged 45-84 at average risk for CRC. The test had an 87.5% sensitivity for stage I, II, or III colorectal cancer but only a 13% sensitivity for advanced precancerous lesions. Test specificity was 89.6%, meaning that about 1 in 10 participants without CRC or advanced precancerous lesions on colonoscopy had a false-positive result.

Although the Shield blood test has a higher rate of false positives than the traditional fecal immunochemical test (FIT) and lower sensitivity and specificity than a multitarget stool DNA (FIT-DNA) test designed to improve on Cologuard, it meets the previously established criteria set forth by the Centers for Medicare & Medicaid Services (CMS) to be covered for Medicare beneficiaries at 3-year intervals, pending FDA approval. If public and private payers start covering Shield alongside other CRC screening tests, it presents an opportunity for primary care physicians to reach the approximately 3 in 10 adults between ages 45 and 75 who are not being routinely screened.

A big concern, however, is that the availability of a blood test may cause patients who would have otherwise been screened with colonoscopy or stool tests to switch to the blood test. A cost-effectiveness analysis found that offering a blood test to patients who decline screening colonoscopy saves additional lives, but at the cost of more than $377,000 per life-year gained. Another study relying on three microsimulation models previously utilized by the US Preventive Services Task Force (USPSTF) found that annual FIT results in more life-years gained at substantially lower cost than blood-based screening every 3 years “even when uptake of blood-based screening was 20 percentage points higher than uptake of FIT.” As a result, a multidisciplinary expert panel concluded that blood-based screening should not substitute for established CRC screening tests, but instead be offered only to patients who decline those tests.

In practice, this will increase the complexity of the CRC screening conversations we have with patients. We will need to be clear that the blood test is not yet endorsed by the USPSTF or any major guideline group and is a second-line test that will miss most precancerous polyps. As with the stool tests, it is essential to emphasize that a positive result must be followed by diagnostic colonoscopy. To addend the cancer screening maxim I mentioned before, the blood test is not the best test for CRC, but it’s probably better than no test at all.

Dr. Lin is a family physician and associate director, Family Medicine Residency Program, Lancaster General Hospital, Lancaster, Pennsylvania. He blogs at Common Sense Family Doctor.

A version of this article appeared on Medscape.com.

Last year, I concluded a commentary for this news organization on colorectal cancer (CRC) screening guidelines by stating that between stool-based tests, flexible sigmoidoscopy, and colonoscopy, “the best screening test is the test that gets done.” But should that maxim apply to the new blood-based screening test, Guardant Health Shield? This proprietary test, which costs $895 and is not generally covered by insurance, identifies alterations in cell-free DNA that are characteristic of CRC.

Shield’s test characteristics were recently evaluated in a prospective study of more than 10,000 adults aged 45-84 at average risk for CRC. The test had an 87.5% sensitivity for stage I, II, or III colorectal cancer but only a 13% sensitivity for advanced precancerous lesions. Test specificity was 89.6%, meaning that about 1 in 10 participants without CRC or advanced precancerous lesions on colonoscopy had a false-positive result.

Although the Shield blood test has a higher rate of false positives than the traditional fecal immunochemical test (FIT) and lower sensitivity and specificity than a multitarget stool DNA (FIT-DNA) test designed to improve on Cologuard, it meets the previously established criteria set forth by the Centers for Medicare & Medicaid Services (CMS) to be covered for Medicare beneficiaries at 3-year intervals, pending FDA approval. If public and private payers start covering Shield alongside other CRC screening tests, it presents an opportunity for primary care physicians to reach the approximately 3 in 10 adults between ages 45 and 75 who are not being routinely screened.

A big concern, however, is that the availability of a blood test may cause patients who would have otherwise been screened with colonoscopy or stool tests to switch to the blood test. A cost-effectiveness analysis found that offering a blood test to patients who decline screening colonoscopy saves additional lives, but at the cost of more than $377,000 per life-year gained. Another study relying on three microsimulation models previously utilized by the US Preventive Services Task Force (USPSTF) found that annual FIT results in more life-years gained at substantially lower cost than blood-based screening every 3 years “even when uptake of blood-based screening was 20 percentage points higher than uptake of FIT.” As a result, a multidisciplinary expert panel concluded that blood-based screening should not substitute for established CRC screening tests, but instead be offered only to patients who decline those tests.

In practice, this will increase the complexity of the CRC screening conversations we have with patients. We will need to be clear that the blood test is not yet endorsed by the USPSTF or any major guideline group and is a second-line test that will miss most precancerous polyps. As with the stool tests, it is essential to emphasize that a positive result must be followed by diagnostic colonoscopy. To addend the cancer screening maxim I mentioned before, the blood test is not the best test for CRC, but it’s probably better than no test at all.

Dr. Lin is a family physician and associate director, Family Medicine Residency Program, Lancaster General Hospital, Lancaster, Pennsylvania. He blogs at Common Sense Family Doctor.

A version of this article appeared on Medscape.com.

VIENNA — The glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide (Wegovy) not only induced weight loss but also improved knee pain in people with knee osteoarthritis (OA) and obesity, according to results from the STEP 9 study reported at the Osteoarthritis Research Society International (OARSI) 2024  World Congress.

From baseline to week 68, the mean change in knee pain assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score was a reduction of 41.7 points for semaglutide and a decrease of 27.5 points for a matching placebo. The estimated treatment difference of 14.1 points between the groups was statistically significant (P < .001).

As for weight loss, this also fell by a significantly greater amount in the people treated with semaglutide vs those given placebo, with respective reductions of 13.7% and 3.2% from baseline, with an estimated 10.5% greater weight loss with semaglutide.

Sara Freeman/Medscape Medical News

“The interesting thing is whether there’s a specific action of GLP-1 receptor agonists on the joint, not through the weight loss but by itself,” principal study investigator Henning Bliddal, MD, DMSc, told this news organization ahead of reporting the results at OARSI 2024.

Weight loss is “obviously good” because “the knees suffer from the weight. But whether it’s good for the knee or just for the health or the well-being of the person is another matter,” said Dr. Bliddal, who is director of the Parker Institute at Bispebjerg Frederiksberg Hospital in Copenhagen, Denmark.
 

Not Approved in OA

Semaglutide and other potentially weight loss-inducing drugs are not currently indicated for use specifically in OA, Tonia Vincent, MBBS, PhD, told this news organization, and so “I think we have to be very cautious,” she said.

“Weight loss is one of the few things that has been shown to be successful in clinical trials,” said Dr. Vincent, who is a professor of musculoskeletal biology and an honorary rheumatologist at the Kennedy Institute of Rheumatology at Oxford University in Oxford, England.

“People always feel better too when they lose weight, so that helps manage pain. So, I’d be very surprised if there isn’t a benefit,” she added.

“I just think we need to know more about the long-term use of these drugs, whether the healthcare system can afford them, and how we would ration them.”
 

Previous Work

The STEP 9 study is not the first time that Dr. Bliddal has investigated the effects of a GLP-1 receptor agonist in people with knee OA, but it is the first to have shown a significant effect on knee pain.

Previously, results from the LOSEIT trial with liraglutide demonstrated that, after an 8-week dietary intervention run-in phase, people who were treated with the GLP-1 receptor agonist lost an average of 2.8 kg in body weight over a period of 1 year, vs a 1.2 kg gain in the placebo group. Knee injury and Osteoarthritis Outcome Scores, however, were largely unaffected.

“The study was more or less negative for knee pain because at that time we had to pretreat patients with some kind of weight loss before they were allowed to have the liraglutide,” Dr. Bliddal said.

“There’s so many different considerations with diets and the different ways that [dietary modification] is performed, that could be part of the explanation why some people didn’t find the pain relief,” Dr. Bliddal suggested.
 

STEP 9 Study Design

No pre-study dietary intervention was required in the STEP 9 trial, although a reduced-calorie diet and increased physical exercise were used alongside both semaglutide and placebo treatment.

STEP 9 was a multicenter, multinational phase 3 clinical trial that enrolled people if they had a body mass index (BMI) of > 30, had a clinical diagnosis of knee OA with moderate radiographic changes (Kellgren-Lawrence grade of 2-3), and were experiencing knee pain.

In addition to a baseline WOMAC pain score of at least 40 points (where 0 represents no and 100 the worst pain), the participants had to have a WOMAC numerical rating scale (NRS) score of ≥ 3.1.

A total of 407 participants were recruited and randomly allocated, 2:1, to receive once-weekly subcutaneous injections of either semaglutide 2.4 mg or placebo for a total of 68 weeks.

Dr. Bliddal presented demographic information only for the study population as a whole, showing that the mean was 56 years, 81.6% were women, 60.9% were White, 11.8% Native American, 7.6% Black, and 19.7% of other ethnic origin.

Moreover, the mean bodyweight at baseline was 108.6 kg, and the mean baseline BMI was 40.3, with 75% of participants having a BMI ≥ 35. The mean waist circumference was 118.7 cm. The mean baseline WOMAC pain score was 70.9.
 

Other Findings

In addition to the reductions seen in the coprimary endpoints of weight loss and knee pain, the WOMAC physical function score was also reduced from baseline to week 68 to a greater degree in the semaglutide than placebo arm, by a respective 41.5 vs 26.7 points, with a significant estimated treatment difference of -14.9 points.

“The use of pain medication went down as well; you can see the drop was faster in the semaglutide group than the placebo group, and it was maintained throughout the study,” Dr. Bliddal said during his presentation. He noted that patients had to temporarily stop taking pain relievers such as acetaminophen 3 days before their pain was assessed.

Additional findings reported in the abstract, but not presented at the meeting, were a significant estimated treatment difference of -1.0 in NRS pain intensity, more people treated with semaglutide than placebo achieving ≥ 5% (87.0% vs 29.2%) or ≥ 10% (70.4% vs 9.2%) weight loss.

“Safety and tolerability with semaglutide were consistent with the global STEP program and the GLP-1 receptor agonist class in general,” Dr. Bliddal reported.

Serious adverse events occurred in a respective 10.0% and 8.1% of participants, and adverse events leading to discontinuation were recorded in 6.7% and 3%. Around one third (2.2%) of those leading to discontinuation in the semaglutide arm were gastrointestinal adverse events.

The STEP 9 study was funded by Novo Nordisk. Henning is a principal investigator for the trial and acknowledged that research grants were received from Novo Nordisk to his institution, as well as consulting fees and honoraria. He has also received congress and travel support from Contura. Dr. Vincent was not involved in the study and had no relevant conflicts of interest to disclose.

A version of this article appeared on Medscape.com.

VIENNA — The glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide (Wegovy) not only induced weight loss but also improved knee pain in people with knee osteoarthritis (OA) and obesity, according to results from the STEP 9 study reported at the Osteoarthritis Research Society International (OARSI) 2024  World Congress.

From baseline to week 68, the mean change in knee pain assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score was a reduction of 41.7 points for semaglutide and a decrease of 27.5 points for a matching placebo. The estimated treatment difference of 14.1 points between the groups was statistically significant (P < .001).

As for weight loss, this also fell by a significantly greater amount in the people treated with semaglutide vs those given placebo, with respective reductions of 13.7% and 3.2% from baseline, with an estimated 10.5% greater weight loss with semaglutide.

Sara Freeman/Medscape Medical News

“The interesting thing is whether there’s a specific action of GLP-1 receptor agonists on the joint, not through the weight loss but by itself,” principal study investigator Henning Bliddal, MD, DMSc, told this news organization ahead of reporting the results at OARSI 2024.

Weight loss is “obviously good” because “the knees suffer from the weight. But whether it’s good for the knee or just for the health or the well-being of the person is another matter,” said Dr. Bliddal, who is director of the Parker Institute at Bispebjerg Frederiksberg Hospital in Copenhagen, Denmark.
 

Not Approved in OA

Semaglutide and other potentially weight loss-inducing drugs are not currently indicated for use specifically in OA, Tonia Vincent, MBBS, PhD, told this news organization, and so “I think we have to be very cautious,” she said.

“Weight loss is one of the few things that has been shown to be successful in clinical trials,” said Dr. Vincent, who is a professor of musculoskeletal biology and an honorary rheumatologist at the Kennedy Institute of Rheumatology at Oxford University in Oxford, England.

“People always feel better too when they lose weight, so that helps manage pain. So, I’d be very surprised if there isn’t a benefit,” she added.

“I just think we need to know more about the long-term use of these drugs, whether the healthcare system can afford them, and how we would ration them.”
 

Previous Work

The STEP 9 study is not the first time that Dr. Bliddal has investigated the effects of a GLP-1 receptor agonist in people with knee OA, but it is the first to have shown a significant effect on knee pain.

Previously, results from the LOSEIT trial with liraglutide demonstrated that, after an 8-week dietary intervention run-in phase, people who were treated with the GLP-1 receptor agonist lost an average of 2.8 kg in body weight over a period of 1 year, vs a 1.2 kg gain in the placebo group. Knee injury and Osteoarthritis Outcome Scores, however, were largely unaffected.

“The study was more or less negative for knee pain because at that time we had to pretreat patients with some kind of weight loss before they were allowed to have the liraglutide,” Dr. Bliddal said.

“There’s so many different considerations with diets and the different ways that [dietary modification] is performed, that could be part of the explanation why some people didn’t find the pain relief,” Dr. Bliddal suggested.
 

STEP 9 Study Design

No pre-study dietary intervention was required in the STEP 9 trial, although a reduced-calorie diet and increased physical exercise were used alongside both semaglutide and placebo treatment.

STEP 9 was a multicenter, multinational phase 3 clinical trial that enrolled people if they had a body mass index (BMI) of > 30, had a clinical diagnosis of knee OA with moderate radiographic changes (Kellgren-Lawrence grade of 2-3), and were experiencing knee pain.

In addition to a baseline WOMAC pain score of at least 40 points (where 0 represents no and 100 the worst pain), the participants had to have a WOMAC numerical rating scale (NRS) score of ≥ 3.1.

A total of 407 participants were recruited and randomly allocated, 2:1, to receive once-weekly subcutaneous injections of either semaglutide 2.4 mg or placebo for a total of 68 weeks.

Dr. Bliddal presented demographic information only for the study population as a whole, showing that the mean was 56 years, 81.6% were women, 60.9% were White, 11.8% Native American, 7.6% Black, and 19.7% of other ethnic origin.

Moreover, the mean bodyweight at baseline was 108.6 kg, and the mean baseline BMI was 40.3, with 75% of participants having a BMI ≥ 35. The mean waist circumference was 118.7 cm. The mean baseline WOMAC pain score was 70.9.
 

Other Findings

In addition to the reductions seen in the coprimary endpoints of weight loss and knee pain, the WOMAC physical function score was also reduced from baseline to week 68 to a greater degree in the semaglutide than placebo arm, by a respective 41.5 vs 26.7 points, with a significant estimated treatment difference of -14.9 points.

“The use of pain medication went down as well; you can see the drop was faster in the semaglutide group than the placebo group, and it was maintained throughout the study,” Dr. Bliddal said during his presentation. He noted that patients had to temporarily stop taking pain relievers such as acetaminophen 3 days before their pain was assessed.

Additional findings reported in the abstract, but not presented at the meeting, were a significant estimated treatment difference of -1.0 in NRS pain intensity, more people treated with semaglutide than placebo achieving ≥ 5% (87.0% vs 29.2%) or ≥ 10% (70.4% vs 9.2%) weight loss.

“Safety and tolerability with semaglutide were consistent with the global STEP program and the GLP-1 receptor agonist class in general,” Dr. Bliddal reported.

Serious adverse events occurred in a respective 10.0% and 8.1% of participants, and adverse events leading to discontinuation were recorded in 6.7% and 3%. Around one third (2.2%) of those leading to discontinuation in the semaglutide arm were gastrointestinal adverse events.

The STEP 9 study was funded by Novo Nordisk. Henning is a principal investigator for the trial and acknowledged that research grants were received from Novo Nordisk to his institution, as well as consulting fees and honoraria. He has also received congress and travel support from Contura. Dr. Vincent was not involved in the study and had no relevant conflicts of interest to disclose.

A version of this article appeared on Medscape.com.

VIENNA — The glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide (Wegovy) not only induced weight loss but also improved knee pain in people with knee osteoarthritis (OA) and obesity, according to results from the STEP 9 study reported at the Osteoarthritis Research Society International (OARSI) 2024  World Congress.

From baseline to week 68, the mean change in knee pain assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score was a reduction of 41.7 points for semaglutide and a decrease of 27.5 points for a matching placebo. The estimated treatment difference of 14.1 points between the groups was statistically significant (P < .001).

As for weight loss, this also fell by a significantly greater amount in the people treated with semaglutide vs those given placebo, with respective reductions of 13.7% and 3.2% from baseline, with an estimated 10.5% greater weight loss with semaglutide.

Sara Freeman/Medscape Medical News

“The interesting thing is whether there’s a specific action of GLP-1 receptor agonists on the joint, not through the weight loss but by itself,” principal study investigator Henning Bliddal, MD, DMSc, told this news organization ahead of reporting the results at OARSI 2024.

Weight loss is “obviously good” because “the knees suffer from the weight. But whether it’s good for the knee or just for the health or the well-being of the person is another matter,” said Dr. Bliddal, who is director of the Parker Institute at Bispebjerg Frederiksberg Hospital in Copenhagen, Denmark.
 

Not Approved in OA

Semaglutide and other potentially weight loss-inducing drugs are not currently indicated for use specifically in OA, Tonia Vincent, MBBS, PhD, told this news organization, and so “I think we have to be very cautious,” she said.

“Weight loss is one of the few things that has been shown to be successful in clinical trials,” said Dr. Vincent, who is a professor of musculoskeletal biology and an honorary rheumatologist at the Kennedy Institute of Rheumatology at Oxford University in Oxford, England.

“People always feel better too when they lose weight, so that helps manage pain. So, I’d be very surprised if there isn’t a benefit,” she added.

“I just think we need to know more about the long-term use of these drugs, whether the healthcare system can afford them, and how we would ration them.”
 

Previous Work

The STEP 9 study is not the first time that Dr. Bliddal has investigated the effects of a GLP-1 receptor agonist in people with knee OA, but it is the first to have shown a significant effect on knee pain.

Previously, results from the LOSEIT trial with liraglutide demonstrated that, after an 8-week dietary intervention run-in phase, people who were treated with the GLP-1 receptor agonist lost an average of 2.8 kg in body weight over a period of 1 year, vs a 1.2 kg gain in the placebo group. Knee injury and Osteoarthritis Outcome Scores, however, were largely unaffected.

“The study was more or less negative for knee pain because at that time we had to pretreat patients with some kind of weight loss before they were allowed to have the liraglutide,” Dr. Bliddal said.

“There’s so many different considerations with diets and the different ways that [dietary modification] is performed, that could be part of the explanation why some people didn’t find the pain relief,” Dr. Bliddal suggested.
 

STEP 9 Study Design

No pre-study dietary intervention was required in the STEP 9 trial, although a reduced-calorie diet and increased physical exercise were used alongside both semaglutide and placebo treatment.

STEP 9 was a multicenter, multinational phase 3 clinical trial that enrolled people if they had a body mass index (BMI) of > 30, had a clinical diagnosis of knee OA with moderate radiographic changes (Kellgren-Lawrence grade of 2-3), and were experiencing knee pain.

In addition to a baseline WOMAC pain score of at least 40 points (where 0 represents no and 100 the worst pain), the participants had to have a WOMAC numerical rating scale (NRS) score of ≥ 3.1.

A total of 407 participants were recruited and randomly allocated, 2:1, to receive once-weekly subcutaneous injections of either semaglutide 2.4 mg or placebo for a total of 68 weeks.

Dr. Bliddal presented demographic information only for the study population as a whole, showing that the mean was 56 years, 81.6% were women, 60.9% were White, 11.8% Native American, 7.6% Black, and 19.7% of other ethnic origin.

Moreover, the mean bodyweight at baseline was 108.6 kg, and the mean baseline BMI was 40.3, with 75% of participants having a BMI ≥ 35. The mean waist circumference was 118.7 cm. The mean baseline WOMAC pain score was 70.9.
 

Other Findings

In addition to the reductions seen in the coprimary endpoints of weight loss and knee pain, the WOMAC physical function score was also reduced from baseline to week 68 to a greater degree in the semaglutide than placebo arm, by a respective 41.5 vs 26.7 points, with a significant estimated treatment difference of -14.9 points.

“The use of pain medication went down as well; you can see the drop was faster in the semaglutide group than the placebo group, and it was maintained throughout the study,” Dr. Bliddal said during his presentation. He noted that patients had to temporarily stop taking pain relievers such as acetaminophen 3 days before their pain was assessed.

Additional findings reported in the abstract, but not presented at the meeting, were a significant estimated treatment difference of -1.0 in NRS pain intensity, more people treated with semaglutide than placebo achieving ≥ 5% (87.0% vs 29.2%) or ≥ 10% (70.4% vs 9.2%) weight loss.

“Safety and tolerability with semaglutide were consistent with the global STEP program and the GLP-1 receptor agonist class in general,” Dr. Bliddal reported.

Serious adverse events occurred in a respective 10.0% and 8.1% of participants, and adverse events leading to discontinuation were recorded in 6.7% and 3%. Around one third (2.2%) of those leading to discontinuation in the semaglutide arm were gastrointestinal adverse events.

The STEP 9 study was funded by Novo Nordisk. Henning is a principal investigator for the trial and acknowledged that research grants were received from Novo Nordisk to his institution, as well as consulting fees and honoraria. He has also received congress and travel support from Contura. Dr. Vincent was not involved in the study and had no relevant conflicts of interest to disclose.

A version of this article appeared on Medscape.com.

Recent headlines scream that we have an obesity problem and that carbs are the culprit for the problem. That leads me to ask: How did we get to blaming carbs as the enemy in the war against obesity?

First, a quick review of the history of diet and macronutrient content.

A long time ago, prehistoric humans foraged and hunted for food. Protein and fat were procured from animal meat, which was very important for encephalization, or evolutionary increase in the complexity or relative size of the brain. Most of the requirements for protein and iron were satisfied by hunting and eating land animals as well as consuming marine life that washed up on shore.

Carbohydrates in the form of plant foods served as the only sources of energy available to prehistoric hunter-gatherers, which offset the high protein content of the rest of their diet. These were only available during spring and summer.

Then, about 10,000 years ago, plant and animal agriculture began, and humans saw a permanent shift in the macronutrient content of our daily intake so that it was more consistent and stable. Initially, the nutrient characteristic changes were subtle, going from wild food to cultivated food with the Agricultural Revolution in the mid-17th century. Then, it changed even more rapidly less than 200 years ago with the Industrial Revolution, resulting in semiprocessed and ultraprocessed foods.

This change in food intake altered human physiology, with major changes in our digestive, immune, and neural physiology and an increase in chronic disease prevalence. The last 50 years has seen an increase in obesity in the United States, along with increases in chronic disease such as type 2 diabetes, which leads cardiovascular disease and certain cancers. 
 

Back to Carbohydrates: Do We Need Them? How Much? What Kind?

The increase in the macronutrient content of the food we eat containing saturated fat and refined carbohydrates and sugars represents a major change and is arguably the smoking gun of the obesity epidemic. Unfortunately, ultraprocessed foods have become a staple of the standard American or Western diet. 

Ultraprocessed foods such as cakes, cookies, crackers, sugary breakfast cereals, pizza, potato chips, soft drinks, and ice cream are eons away from our prehistoric diet of wild game, nuts, fruits, and berries, at which time, our digestive immune and nervous systems evolved. The pace at which ultraprocessed foods have entered our diet outpaces the time necessary for adaptation of our digestive systems and genes to these foods. They are indeed pathogenic in this context. 

So when was the time when humans consumed an “optimal” diet? This is hard to say because during the time of brain evolution, we needed protein and iron and succumbed to infections and trauma. In the early 1900s, we continued to succumb to infection until the discovery of antibiotics. Soon thereafter, industrialization and processed foods led to weight gain and the chronic diseases of the cardiovascular system and type 2 diabetes. 

Carbohydrates provide calories and fiber and some micronutrients, which are needed for energy, metabolism, and bowel and immune health. But how much do we need? 

Currently in the United States, the percentage of total food energy derived from the three major macronutrients is: carbohydrates, 51.8%; fat, 32.8%; and protein, 15.4%. Current advice for a healthy diet to lower risk for cardiovascular disease is to limit fat intake to 30% of total energy, protein to 15%, and to increase complex carbohydrates to 55%-60% of total energy. But we also need to qualify this in terms of the quality of the macronutrient, particularly carbohydrates. 

In addition to the quality, the macronutrient content of the diet has varied considerably from our prehistoric times when dietary protein intakes were high at 19%-35% of energy at the expense of carbohydrate (22%-40% of energy). 

If our genes haven’t kept up with industrialization, then why do we need so many carbohydrates to equate to 55%-60% of energy? Is it possible that we are confusing what is available with what we actually need? What do I mean by this?

We certainly have changed the landscape of the world due to agriculture, which has allowed us to procreate and feed ourselves, and certainly, industrialization has increased the availability of accessible cheap food. Protein in the form of meat, fish, and fowl are harder to get in industrialized nations as are fruits and vegetables. These macronutrients were the foods of our ancestors. It may be that a healthy diet is considered the one that is available. 

For instance, the Mediterranean diet is somewhat higher in fat content, 40%-50% fat (mostly mono and unsaturated), and similar in protein content but lower in carbohydrate content than the typical Western diet. The Dietary Approaches to Stop Hypertension (DASH) diet is lower in fat at 25% total calories, is higher in carbohydrates at 55%, and is lower in protein, but this diet was generated in the United States, therefore it is more Western. 

We need high-quality protein for organ and muscle function, high-quality unsaturated and monounsaturated fats for brain function and cellular functions, and high-quality complex carbohydrates for energy and gut health as well as micronutrients for many cellular functions. A ketogenic diet is not sustainable in the long-term for these reasons: chiefly the need for some carbohydrates for gut health and micronutrients. 

How much carbohydrate content is needed should take into consideration energy expenditure as well as micronutrients and fiber intake. Protein and fat can contribute to energy production but not as readily as carbohydrates that can quickly restore glycogen in the muscle and liver. What’s interesting is that our ancestors were able to hunt and run away from danger with the small amounts of carbohydrates from plants and berries plus the protein and fat intake from animals and fish — but the Olympics weren’t a thing then!

It may be another 200,000 years before our genes catch up to ultraprocessed foods and the simple carbohydrates and sugars contained in these products. Evidence suggests that ultraprocessed foods cause inflammation in organs like the liver, adipose tissue, the heart, and even the brain. In the brain, this inflammation may be what’s causing us to defend a higher body weight set point in this environment of easily obtained highly palatable ultraprocessed foods. 

Let’s not wait until our genes catch up and our bodies tolerate junk food without disease progression. It could be like waiting for Godot!

Dr. Apovian is professor of medicine, Harvard Medical School, and codirector, Center for Weight Management and Wellness, Brigham and Women’s Hospital, Boston, Massachusetts. She disclosed ties to Altimmune, CinFina Pharma, Cowen and Company, EPG Communication Holdings, Form Health, Gelesis, and L-Nutra.

A version of this article appeared on Medscape.com.

Recent headlines scream that we have an obesity problem and that carbs are the culprit for the problem. That leads me to ask: How did we get to blaming carbs as the enemy in the war against obesity?

First, a quick review of the history of diet and macronutrient content.

A long time ago, prehistoric humans foraged and hunted for food. Protein and fat were procured from animal meat, which was very important for encephalization, or evolutionary increase in the complexity or relative size of the brain. Most of the requirements for protein and iron were satisfied by hunting and eating land animals as well as consuming marine life that washed up on shore.

Carbohydrates in the form of plant foods served as the only sources of energy available to prehistoric hunter-gatherers, which offset the high protein content of the rest of their diet. These were only available during spring and summer.

Then, about 10,000 years ago, plant and animal agriculture began, and humans saw a permanent shift in the macronutrient content of our daily intake so that it was more consistent and stable. Initially, the nutrient characteristic changes were subtle, going from wild food to cultivated food with the Agricultural Revolution in the mid-17th century. Then, it changed even more rapidly less than 200 years ago with the Industrial Revolution, resulting in semiprocessed and ultraprocessed foods.

This change in food intake altered human physiology, with major changes in our digestive, immune, and neural physiology and an increase in chronic disease prevalence. The last 50 years has seen an increase in obesity in the United States, along with increases in chronic disease such as type 2 diabetes, which leads cardiovascular disease and certain cancers. 
 

Back to Carbohydrates: Do We Need Them? How Much? What Kind?

The increase in the macronutrient content of the food we eat containing saturated fat and refined carbohydrates and sugars represents a major change and is arguably the smoking gun of the obesity epidemic. Unfortunately, ultraprocessed foods have become a staple of the standard American or Western diet. 

Ultraprocessed foods such as cakes, cookies, crackers, sugary breakfast cereals, pizza, potato chips, soft drinks, and ice cream are eons away from our prehistoric diet of wild game, nuts, fruits, and berries, at which time, our digestive immune and nervous systems evolved. The pace at which ultraprocessed foods have entered our diet outpaces the time necessary for adaptation of our digestive systems and genes to these foods. They are indeed pathogenic in this context. 

So when was the time when humans consumed an “optimal” diet? This is hard to say because during the time of brain evolution, we needed protein and iron and succumbed to infections and trauma. In the early 1900s, we continued to succumb to infection until the discovery of antibiotics. Soon thereafter, industrialization and processed foods led to weight gain and the chronic diseases of the cardiovascular system and type 2 diabetes. 

Carbohydrates provide calories and fiber and some micronutrients, which are needed for energy, metabolism, and bowel and immune health. But how much do we need? 

Currently in the United States, the percentage of total food energy derived from the three major macronutrients is: carbohydrates, 51.8%; fat, 32.8%; and protein, 15.4%. Current advice for a healthy diet to lower risk for cardiovascular disease is to limit fat intake to 30% of total energy, protein to 15%, and to increase complex carbohydrates to 55%-60% of total energy. But we also need to qualify this in terms of the quality of the macronutrient, particularly carbohydrates. 

In addition to the quality, the macronutrient content of the diet has varied considerably from our prehistoric times when dietary protein intakes were high at 19%-35% of energy at the expense of carbohydrate (22%-40% of energy). 

If our genes haven’t kept up with industrialization, then why do we need so many carbohydrates to equate to 55%-60% of energy? Is it possible that we are confusing what is available with what we actually need? What do I mean by this?

We certainly have changed the landscape of the world due to agriculture, which has allowed us to procreate and feed ourselves, and certainly, industrialization has increased the availability of accessible cheap food. Protein in the form of meat, fish, and fowl are harder to get in industrialized nations as are fruits and vegetables. These macronutrients were the foods of our ancestors. It may be that a healthy diet is considered the one that is available. 

For instance, the Mediterranean diet is somewhat higher in fat content, 40%-50% fat (mostly mono and unsaturated), and similar in protein content but lower in carbohydrate content than the typical Western diet. The Dietary Approaches to Stop Hypertension (DASH) diet is lower in fat at 25% total calories, is higher in carbohydrates at 55%, and is lower in protein, but this diet was generated in the United States, therefore it is more Western. 

We need high-quality protein for organ and muscle function, high-quality unsaturated and monounsaturated fats for brain function and cellular functions, and high-quality complex carbohydrates for energy and gut health as well as micronutrients for many cellular functions. A ketogenic diet is not sustainable in the long-term for these reasons: chiefly the need for some carbohydrates for gut health and micronutrients. 

How much carbohydrate content is needed should take into consideration energy expenditure as well as micronutrients and fiber intake. Protein and fat can contribute to energy production but not as readily as carbohydrates that can quickly restore glycogen in the muscle and liver. What’s interesting is that our ancestors were able to hunt and run away from danger with the small amounts of carbohydrates from plants and berries plus the protein and fat intake from animals and fish — but the Olympics weren’t a thing then!

It may be another 200,000 years before our genes catch up to ultraprocessed foods and the simple carbohydrates and sugars contained in these products. Evidence suggests that ultraprocessed foods cause inflammation in organs like the liver, adipose tissue, the heart, and even the brain. In the brain, this inflammation may be what’s causing us to defend a higher body weight set point in this environment of easily obtained highly palatable ultraprocessed foods. 

Let’s not wait until our genes catch up and our bodies tolerate junk food without disease progression. It could be like waiting for Godot!

Dr. Apovian is professor of medicine, Harvard Medical School, and codirector, Center for Weight Management and Wellness, Brigham and Women’s Hospital, Boston, Massachusetts. She disclosed ties to Altimmune, CinFina Pharma, Cowen and Company, EPG Communication Holdings, Form Health, Gelesis, and L-Nutra.

A version of this article appeared on Medscape.com.

Recent headlines scream that we have an obesity problem and that carbs are the culprit for the problem. That leads me to ask: How did we get to blaming carbs as the enemy in the war against obesity?

First, a quick review of the history of diet and macronutrient content.

A long time ago, prehistoric humans foraged and hunted for food. Protein and fat were procured from animal meat, which was very important for encephalization, or evolutionary increase in the complexity or relative size of the brain. Most of the requirements for protein and iron were satisfied by hunting and eating land animals as well as consuming marine life that washed up on shore.

Carbohydrates in the form of plant foods served as the only sources of energy available to prehistoric hunter-gatherers, which offset the high protein content of the rest of their diet. These were only available during spring and summer.

Then, about 10,000 years ago, plant and animal agriculture began, and humans saw a permanent shift in the macronutrient content of our daily intake so that it was more consistent and stable. Initially, the nutrient characteristic changes were subtle, going from wild food to cultivated food with the Agricultural Revolution in the mid-17th century. Then, it changed even more rapidly less than 200 years ago with the Industrial Revolution, resulting in semiprocessed and ultraprocessed foods.

This change in food intake altered human physiology, with major changes in our digestive, immune, and neural physiology and an increase in chronic disease prevalence. The last 50 years has seen an increase in obesity in the United States, along with increases in chronic disease such as type 2 diabetes, which leads cardiovascular disease and certain cancers. 
 

Back to Carbohydrates: Do We Need Them? How Much? What Kind?

The increase in the macronutrient content of the food we eat containing saturated fat and refined carbohydrates and sugars represents a major change and is arguably the smoking gun of the obesity epidemic. Unfortunately, ultraprocessed foods have become a staple of the standard American or Western diet. 

Ultraprocessed foods such as cakes, cookies, crackers, sugary breakfast cereals, pizza, potato chips, soft drinks, and ice cream are eons away from our prehistoric diet of wild game, nuts, fruits, and berries, at which time, our digestive immune and nervous systems evolved. The pace at which ultraprocessed foods have entered our diet outpaces the time necessary for adaptation of our digestive systems and genes to these foods. They are indeed pathogenic in this context. 

So when was the time when humans consumed an “optimal” diet? This is hard to say because during the time of brain evolution, we needed protein and iron and succumbed to infections and trauma. In the early 1900s, we continued to succumb to infection until the discovery of antibiotics. Soon thereafter, industrialization and processed foods led to weight gain and the chronic diseases of the cardiovascular system and type 2 diabetes. 

Carbohydrates provide calories and fiber and some micronutrients, which are needed for energy, metabolism, and bowel and immune health. But how much do we need? 

Currently in the United States, the percentage of total food energy derived from the three major macronutrients is: carbohydrates, 51.8%; fat, 32.8%; and protein, 15.4%. Current advice for a healthy diet to lower risk for cardiovascular disease is to limit fat intake to 30% of total energy, protein to 15%, and to increase complex carbohydrates to 55%-60% of total energy. But we also need to qualify this in terms of the quality of the macronutrient, particularly carbohydrates. 

In addition to the quality, the macronutrient content of the diet has varied considerably from our prehistoric times when dietary protein intakes were high at 19%-35% of energy at the expense of carbohydrate (22%-40% of energy). 

If our genes haven’t kept up with industrialization, then why do we need so many carbohydrates to equate to 55%-60% of energy? Is it possible that we are confusing what is available with what we actually need? What do I mean by this?

We certainly have changed the landscape of the world due to agriculture, which has allowed us to procreate and feed ourselves, and certainly, industrialization has increased the availability of accessible cheap food. Protein in the form of meat, fish, and fowl are harder to get in industrialized nations as are fruits and vegetables. These macronutrients were the foods of our ancestors. It may be that a healthy diet is considered the one that is available. 

For instance, the Mediterranean diet is somewhat higher in fat content, 40%-50% fat (mostly mono and unsaturated), and similar in protein content but lower in carbohydrate content than the typical Western diet. The Dietary Approaches to Stop Hypertension (DASH) diet is lower in fat at 25% total calories, is higher in carbohydrates at 55%, and is lower in protein, but this diet was generated in the United States, therefore it is more Western. 

We need high-quality protein for organ and muscle function, high-quality unsaturated and monounsaturated fats for brain function and cellular functions, and high-quality complex carbohydrates for energy and gut health as well as micronutrients for many cellular functions. A ketogenic diet is not sustainable in the long-term for these reasons: chiefly the need for some carbohydrates for gut health and micronutrients. 

How much carbohydrate content is needed should take into consideration energy expenditure as well as micronutrients and fiber intake. Protein and fat can contribute to energy production but not as readily as carbohydrates that can quickly restore glycogen in the muscle and liver. What’s interesting is that our ancestors were able to hunt and run away from danger with the small amounts of carbohydrates from plants and berries plus the protein and fat intake from animals and fish — but the Olympics weren’t a thing then!

It may be another 200,000 years before our genes catch up to ultraprocessed foods and the simple carbohydrates and sugars contained in these products. Evidence suggests that ultraprocessed foods cause inflammation in organs like the liver, adipose tissue, the heart, and even the brain. In the brain, this inflammation may be what’s causing us to defend a higher body weight set point in this environment of easily obtained highly palatable ultraprocessed foods. 

Let’s not wait until our genes catch up and our bodies tolerate junk food without disease progression. It could be like waiting for Godot!

Dr. Apovian is professor of medicine, Harvard Medical School, and codirector, Center for Weight Management and Wellness, Brigham and Women’s Hospital, Boston, Massachusetts. She disclosed ties to Altimmune, CinFina Pharma, Cowen and Company, EPG Communication Holdings, Form Health, Gelesis, and L-Nutra.

A version of this article appeared on Medscape.com.

TOPLINE:

A new three-phase screening protocol that incorporates a PSA test, a four-kallikrein panel, and an MRI scan appears to improve the prostate cancer detection rate among men invited to participate in a single screening compared with those not invited, according to preliminary findings from the Finnish ProScreen randomized clinical trial.

METHODOLOGY:

• Prostate-specific antigen (PSA) screening is currently recommended for men in the United States starting at age 55. However, the test is controversial, in large part because it often detects prostate cancer that is not clinically relevant and may lead to overtreatment of men with low-grade disease.
• The current ProScreen trial assessed a screening intervention that aims to reduce unnecessary diagnoses of prostate cancer but still catch relevant cancers and reduce prostate cancer mortality.
• The researchers randomized 60,745 eligible men aged 50-63 years to be invited to a three-phase screening intervention (n = 15,201) or to be part of a control group that was not invited to screen (n = 45,544).
• The screening group who agreed to participate (n = 7744) first underwent a PSA test. Those with a PSA of ≥ 3.0 ng/mL then underwent a four-kallikrein panel to identify high-grade prostate cancer. Those with a kallikrein panel risk score of 7.5% or higher underwent an MRI of the prostate gland.
• Targeted biopsies were performed in those with abnormal prostate gland findings on MRI. Most patients with a negative MRI were not recommended for systematic biopsy unless they had a PSA density of ≥ 0.15 ng/mL.

TAKEAWAY:

• Among the 7744 invited men who agreed to the three-phase screening protocol (51%), ultimately 209 (2.7% of all screened participants) had a targeted transrectal prostate biopsy. Overall, 136 of the biopsies (65%) detected cancer — 32 low-grade and 128 high-grade prostate cancers, for cumulative incidence rates of 0.41% and 1.65%, respectively.
• Over a 3.2-year median follow-up among the 7457 invited men who refused screening, seven low-grade and 44 high-grade prostate cancers were detected (cumulative incidence rates, 0.1% and 0.6%, respectively).
• Among the entire invited screening group, 39 low-grade (cumulative incidence, 0.26%) and 172 high-grade prostate cancers (cumulative incidence, 1.13%) were detected.
• Among men in the control group, 65 low-grade prostate cancers were ultimately identified and 282 high-grade. The risk difference between the invited screening group and control group was 0.11% for low-grade disease and 0.51% for high-grade disease. Compared with the control group, the intervention led to the detection of one additional low-grade prostate cancer per 909 men invited to screen and one additional high-grade prostate cancer per 196 men invited.

IN PRACTICE:

The three-phase screening approach used in this study detected additional cancers, compared with a control group not invited for screening, but “these results are descriptive and should be interpreted provisionally pending results from the trial on the primary outcomes of prostate cancer mortality,” the investigators said.

SOURCE:

This study was conducted by the ProScreen Trial Investigators, including first author Anssi Auvinen, MD, PhD, of Tampere University, Tampere, Finland, and was published online in JAMAalongside an accompanying editorial.

LIMITATIONS:

Absolute differences between the two randomized groups in this study were small and had unclear clinical importance. Prior screening was reported by several participants and may have reduced cancer detection. The results are based on a single invitation for screening, meaning some high-grade cancers were likely missed; subsequent screening invitations may identify missed cancers. No data were available on cancers missed at screening, and interval cancer incidence is needed to assess sensitivity of the screening protocol used in the study.

DISCLOSURES:

The ProScreen trial is funded by grants from the Academy of Finland, the Finnish Cancer Foundation, the Jane and Aatos Erkko Foundation, the Finland State Research Funding, Helsinki University Hospital, the Sigrid Jusélius Foundation, and the Päivikki and Sakari Sohlberg Foundation. Dr. Auvinen reported having no disclosures. Multiple co-authors reported associations outside the submitted work. The full list of author disclosures is included with the full text of the article.
 

A version of this article appeared on Medscape.com.

TOPLINE:

A new three-phase screening protocol that incorporates a PSA test, a four-kallikrein panel, and an MRI scan appears to improve the prostate cancer detection rate among men invited to participate in a single screening compared with those not invited, according to preliminary findings from the Finnish ProScreen randomized clinical trial.

METHODOLOGY:

• Prostate-specific antigen (PSA) screening is currently recommended for men in the United States starting at age 55. However, the test is controversial, in large part because it often detects prostate cancer that is not clinically relevant and may lead to overtreatment of men with low-grade disease.
• The current ProScreen trial assessed a screening intervention that aims to reduce unnecessary diagnoses of prostate cancer but still catch relevant cancers and reduce prostate cancer mortality.
• The researchers randomized 60,745 eligible men aged 50-63 years to be invited to a three-phase screening intervention (n = 15,201) or to be part of a control group that was not invited to screen (n = 45,544).
• The screening group who agreed to participate (n = 7744) first underwent a PSA test. Those with a PSA of ≥ 3.0 ng/mL then underwent a four-kallikrein panel to identify high-grade prostate cancer. Those with a kallikrein panel risk score of 7.5% or higher underwent an MRI of the prostate gland.
• Targeted biopsies were performed in those with abnormal prostate gland findings on MRI. Most patients with a negative MRI were not recommended for systematic biopsy unless they had a PSA density of ≥ 0.15 ng/mL.

TAKEAWAY:

• Among the 7744 invited men who agreed to the three-phase screening protocol (51%), ultimately 209 (2.7% of all screened participants) had a targeted transrectal prostate biopsy. Overall, 136 of the biopsies (65%) detected cancer — 32 low-grade and 128 high-grade prostate cancers, for cumulative incidence rates of 0.41% and 1.65%, respectively.
• Over a 3.2-year median follow-up among the 7457 invited men who refused screening, seven low-grade and 44 high-grade prostate cancers were detected (cumulative incidence rates, 0.1% and 0.6%, respectively).
• Among the entire invited screening group, 39 low-grade (cumulative incidence, 0.26%) and 172 high-grade prostate cancers (cumulative incidence, 1.13%) were detected.
• Among men in the control group, 65 low-grade prostate cancers were ultimately identified and 282 high-grade. The risk difference between the invited screening group and control group was 0.11% for low-grade disease and 0.51% for high-grade disease. Compared with the control group, the intervention led to the detection of one additional low-grade prostate cancer per 909 men invited to screen and one additional high-grade prostate cancer per 196 men invited.

IN PRACTICE:

The three-phase screening approach used in this study detected additional cancers, compared with a control group not invited for screening, but “these results are descriptive and should be interpreted provisionally pending results from the trial on the primary outcomes of prostate cancer mortality,” the investigators said.

SOURCE:

This study was conducted by the ProScreen Trial Investigators, including first author Anssi Auvinen, MD, PhD, of Tampere University, Tampere, Finland, and was published online in JAMAalongside an accompanying editorial.

LIMITATIONS:

Absolute differences between the two randomized groups in this study were small and had unclear clinical importance. Prior screening was reported by several participants and may have reduced cancer detection. The results are based on a single invitation for screening, meaning some high-grade cancers were likely missed; subsequent screening invitations may identify missed cancers. No data were available on cancers missed at screening, and interval cancer incidence is needed to assess sensitivity of the screening protocol used in the study.

DISCLOSURES:

The ProScreen trial is funded by grants from the Academy of Finland, the Finnish Cancer Foundation, the Jane and Aatos Erkko Foundation, the Finland State Research Funding, Helsinki University Hospital, the Sigrid Jusélius Foundation, and the Päivikki and Sakari Sohlberg Foundation. Dr. Auvinen reported having no disclosures. Multiple co-authors reported associations outside the submitted work. The full list of author disclosures is included with the full text of the article.
 

A version of this article appeared on Medscape.com.

TOPLINE:

A new three-phase screening protocol that incorporates a PSA test, a four-kallikrein panel, and an MRI scan appears to improve the prostate cancer detection rate among men invited to participate in a single screening compared with those not invited, according to preliminary findings from the Finnish ProScreen randomized clinical trial.

METHODOLOGY:

• Prostate-specific antigen (PSA) screening is currently recommended for men in the United States starting at age 55. However, the test is controversial, in large part because it often detects prostate cancer that is not clinically relevant and may lead to overtreatment of men with low-grade disease.
• The current ProScreen trial assessed a screening intervention that aims to reduce unnecessary diagnoses of prostate cancer but still catch relevant cancers and reduce prostate cancer mortality.
• The researchers randomized 60,745 eligible men aged 50-63 years to be invited to a three-phase screening intervention (n = 15,201) or to be part of a control group that was not invited to screen (n = 45,544).
• The screening group who agreed to participate (n = 7744) first underwent a PSA test. Those with a PSA of ≥ 3.0 ng/mL then underwent a four-kallikrein panel to identify high-grade prostate cancer. Those with a kallikrein panel risk score of 7.5% or higher underwent an MRI of the prostate gland.
• Targeted biopsies were performed in those with abnormal prostate gland findings on MRI. Most patients with a negative MRI were not recommended for systematic biopsy unless they had a PSA density of ≥ 0.15 ng/mL.

TAKEAWAY:

• Among the 7744 invited men who agreed to the three-phase screening protocol (51%), ultimately 209 (2.7% of all screened participants) had a targeted transrectal prostate biopsy. Overall, 136 of the biopsies (65%) detected cancer — 32 low-grade and 128 high-grade prostate cancers, for cumulative incidence rates of 0.41% and 1.65%, respectively.
• Over a 3.2-year median follow-up among the 7457 invited men who refused screening, seven low-grade and 44 high-grade prostate cancers were detected (cumulative incidence rates, 0.1% and 0.6%, respectively).
• Among the entire invited screening group, 39 low-grade (cumulative incidence, 0.26%) and 172 high-grade prostate cancers (cumulative incidence, 1.13%) were detected.
• Among men in the control group, 65 low-grade prostate cancers were ultimately identified and 282 high-grade. The risk difference between the invited screening group and control group was 0.11% for low-grade disease and 0.51% for high-grade disease. Compared with the control group, the intervention led to the detection of one additional low-grade prostate cancer per 909 men invited to screen and one additional high-grade prostate cancer per 196 men invited.

IN PRACTICE:

The three-phase screening approach used in this study detected additional cancers, compared with a control group not invited for screening, but “these results are descriptive and should be interpreted provisionally pending results from the trial on the primary outcomes of prostate cancer mortality,” the investigators said.

SOURCE:

This study was conducted by the ProScreen Trial Investigators, including first author Anssi Auvinen, MD, PhD, of Tampere University, Tampere, Finland, and was published online in JAMAalongside an accompanying editorial.

LIMITATIONS:

Absolute differences between the two randomized groups in this study were small and had unclear clinical importance. Prior screening was reported by several participants and may have reduced cancer detection. The results are based on a single invitation for screening, meaning some high-grade cancers were likely missed; subsequent screening invitations may identify missed cancers. No data were available on cancers missed at screening, and interval cancer incidence is needed to assess sensitivity of the screening protocol used in the study.

DISCLOSURES:

The ProScreen trial is funded by grants from the Academy of Finland, the Finnish Cancer Foundation, the Jane and Aatos Erkko Foundation, the Finland State Research Funding, Helsinki University Hospital, the Sigrid Jusélius Foundation, and the Päivikki and Sakari Sohlberg Foundation. Dr. Auvinen reported having no disclosures. Multiple co-authors reported associations outside the submitted work. The full list of author disclosures is included with the full text of the article.
 

A version of this article appeared on Medscape.com.

There have been many attempts to use immunotherapy to improve outcomes in pancreatic cancer, but they haven’t worked out.

The trials, however, have focused on adding immune checkpoint inhibitors to chemotherapy in metastatic disease, leaving open the question of whether immunotherapy might have a role in the neoadjuvant setting before surgery.

In the first study to test the hypothesis, Zev A. Wainberg, MD, a gastrointestinal medical oncologist at the University of California Los Angeles, reported promising results at the American Association for Cancer Research annual meeting.

The small, single arm pilot study included 28 patients with borderline resectable pancreatic cancer, meaning that tumors had some degree of vascular involvement. About 20% of pancreatic tumors are borderline resectable, Dr. Wainberg said.

Patients received 480 mg of nivolumab intravenously every 4 weeks plus mFOLFIRINOX chemotherapy (oxaliplatin, irinotecan, leucovorin, and 5-fluorouracil) on days 1 and 15 of the 28-day cycle.

Patients who downstaged to resectable disease after three cycles went on to surgery; if not, treatment continued for another 3 months. The median number of cycles was 5.5, and almost all patients completed at least 3.

Overall, 19 of the 22 patients who proceeded to surgery (86%) had a pathologic response to neoadjuvant treatment with nivolumab: 2 complete responses, 2 near-complete responses, and 15 partial responses.

Among patients receiving surgery, 21 had R0 resections, meaning negative surgical margins with no tumor left behind. This is key because R0 resections predict longer survival, and “every effort should be made to achieve” this outcome, Dr. Wainberg said. The remaining patient had an R1 resection.

Median progression-free survival was 21.9 months among all patients and 27.3 months among the 22 patients who had resections.

Median overall survival was 34.6 months across the entire group and 44 months among those who had surgery. Overall, 82% of patients were alive at 12 months, and 77% were alive at 18 months.

The study outcomes, especially among the surgery cohort, stand in contrast to those observed in patients who receive the current standard neoadjuvant regimen for borderline resectable pancreatic cancer, mFOLFIRINOX alone, with studies finding a median overall survival of 29.8 months.

Adding nivolumab to neoadjuvant treatment also did not increase side effects. More than half of patients had grade 3 or worse adverse events, but they were all related to mFOLFIRINOX. There were no significant surgical complications, including no grade 2 or higher fistulas.

“We are very pleased” with the outcomes, Dr. Wainberg said. “We need to be studying [immune checkpoint inhibitors] earlier on in both borderline and locally advanced disease. Pancreatic cancer needs all the help it can get to engage immunity.”

Moderator Alice Ho, MD, a radiation oncologist at Duke University in Durham, North Carolina, called the R0 resection rate “stunning” in a “field that very much needs improvements and advancements.”

Dr. Ho also noted that the trial raises “a lot of interesting questions.”

For instance, why exactly is the addition of nivolumab seemingly improving outcomes?

The combination neoadjuvant therapy appeared to increase tertiary lymphoid structures, plasma cells, and CD4+ T cells — all indications that immunotherapy is having a positive impact — but the treatment also seemed to upregulate pathways for adenosine, an immunosuppressant associated with worse responses to checkpoint blockade.

A larger study is already in the works. In addition to a PD-1 blocker and mFOLFIRINOX, patients will receive a CD73 inhibitor to block adenosine production, Dr. Wainberg said.

Bristol Myers Squibb (BMS) provided the nivolumab used in the study. Dr. Wainberg is a consultant for and reported research funding from BMS and other companies. Dr. Ho had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

There have been many attempts to use immunotherapy to improve outcomes in pancreatic cancer, but they haven’t worked out.

The trials, however, have focused on adding immune checkpoint inhibitors to chemotherapy in metastatic disease, leaving open the question of whether immunotherapy might have a role in the neoadjuvant setting before surgery.

In the first study to test the hypothesis, Zev A. Wainberg, MD, a gastrointestinal medical oncologist at the University of California Los Angeles, reported promising results at the American Association for Cancer Research annual meeting.

The small, single arm pilot study included 28 patients with borderline resectable pancreatic cancer, meaning that tumors had some degree of vascular involvement. About 20% of pancreatic tumors are borderline resectable, Dr. Wainberg said.

Patients received 480 mg of nivolumab intravenously every 4 weeks plus mFOLFIRINOX chemotherapy (oxaliplatin, irinotecan, leucovorin, and 5-fluorouracil) on days 1 and 15 of the 28-day cycle.

Patients who downstaged to resectable disease after three cycles went on to surgery; if not, treatment continued for another 3 months. The median number of cycles was 5.5, and almost all patients completed at least 3.

Overall, 19 of the 22 patients who proceeded to surgery (86%) had a pathologic response to neoadjuvant treatment with nivolumab: 2 complete responses, 2 near-complete responses, and 15 partial responses.

Among patients receiving surgery, 21 had R0 resections, meaning negative surgical margins with no tumor left behind. This is key because R0 resections predict longer survival, and “every effort should be made to achieve” this outcome, Dr. Wainberg said. The remaining patient had an R1 resection.

Median progression-free survival was 21.9 months among all patients and 27.3 months among the 22 patients who had resections.

Median overall survival was 34.6 months across the entire group and 44 months among those who had surgery. Overall, 82% of patients were alive at 12 months, and 77% were alive at 18 months.

The study outcomes, especially among the surgery cohort, stand in contrast to those observed in patients who receive the current standard neoadjuvant regimen for borderline resectable pancreatic cancer, mFOLFIRINOX alone, with studies finding a median overall survival of 29.8 months.

Adding nivolumab to neoadjuvant treatment also did not increase side effects. More than half of patients had grade 3 or worse adverse events, but they were all related to mFOLFIRINOX. There were no significant surgical complications, including no grade 2 or higher fistulas.

“We are very pleased” with the outcomes, Dr. Wainberg said. “We need to be studying [immune checkpoint inhibitors] earlier on in both borderline and locally advanced disease. Pancreatic cancer needs all the help it can get to engage immunity.”

Moderator Alice Ho, MD, a radiation oncologist at Duke University in Durham, North Carolina, called the R0 resection rate “stunning” in a “field that very much needs improvements and advancements.”

Dr. Ho also noted that the trial raises “a lot of interesting questions.”

For instance, why exactly is the addition of nivolumab seemingly improving outcomes?

The combination neoadjuvant therapy appeared to increase tertiary lymphoid structures, plasma cells, and CD4+ T cells — all indications that immunotherapy is having a positive impact — but the treatment also seemed to upregulate pathways for adenosine, an immunosuppressant associated with worse responses to checkpoint blockade.

A larger study is already in the works. In addition to a PD-1 blocker and mFOLFIRINOX, patients will receive a CD73 inhibitor to block adenosine production, Dr. Wainberg said.

Bristol Myers Squibb (BMS) provided the nivolumab used in the study. Dr. Wainberg is a consultant for and reported research funding from BMS and other companies. Dr. Ho had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

There have been many attempts to use immunotherapy to improve outcomes in pancreatic cancer, but they haven’t worked out.

The trials, however, have focused on adding immune checkpoint inhibitors to chemotherapy in metastatic disease, leaving open the question of whether immunotherapy might have a role in the neoadjuvant setting before surgery.

In the first study to test the hypothesis, Zev A. Wainberg, MD, a gastrointestinal medical oncologist at the University of California Los Angeles, reported promising results at the American Association for Cancer Research annual meeting.

The small, single arm pilot study included 28 patients with borderline resectable pancreatic cancer, meaning that tumors had some degree of vascular involvement. About 20% of pancreatic tumors are borderline resectable, Dr. Wainberg said.

Patients received 480 mg of nivolumab intravenously every 4 weeks plus mFOLFIRINOX chemotherapy (oxaliplatin, irinotecan, leucovorin, and 5-fluorouracil) on days 1 and 15 of the 28-day cycle.

Patients who downstaged to resectable disease after three cycles went on to surgery; if not, treatment continued for another 3 months. The median number of cycles was 5.5, and almost all patients completed at least 3.

Overall, 19 of the 22 patients who proceeded to surgery (86%) had a pathologic response to neoadjuvant treatment with nivolumab: 2 complete responses, 2 near-complete responses, and 15 partial responses.

Among patients receiving surgery, 21 had R0 resections, meaning negative surgical margins with no tumor left behind. This is key because R0 resections predict longer survival, and “every effort should be made to achieve” this outcome, Dr. Wainberg said. The remaining patient had an R1 resection.

Median progression-free survival was 21.9 months among all patients and 27.3 months among the 22 patients who had resections.

Median overall survival was 34.6 months across the entire group and 44 months among those who had surgery. Overall, 82% of patients were alive at 12 months, and 77% were alive at 18 months.

The study outcomes, especially among the surgery cohort, stand in contrast to those observed in patients who receive the current standard neoadjuvant regimen for borderline resectable pancreatic cancer, mFOLFIRINOX alone, with studies finding a median overall survival of 29.8 months.

Adding nivolumab to neoadjuvant treatment also did not increase side effects. More than half of patients had grade 3 or worse adverse events, but they were all related to mFOLFIRINOX. There were no significant surgical complications, including no grade 2 or higher fistulas.

“We are very pleased” with the outcomes, Dr. Wainberg said. “We need to be studying [immune checkpoint inhibitors] earlier on in both borderline and locally advanced disease. Pancreatic cancer needs all the help it can get to engage immunity.”

Moderator Alice Ho, MD, a radiation oncologist at Duke University in Durham, North Carolina, called the R0 resection rate “stunning” in a “field that very much needs improvements and advancements.”

Dr. Ho also noted that the trial raises “a lot of interesting questions.”

For instance, why exactly is the addition of nivolumab seemingly improving outcomes?

The combination neoadjuvant therapy appeared to increase tertiary lymphoid structures, plasma cells, and CD4+ T cells — all indications that immunotherapy is having a positive impact — but the treatment also seemed to upregulate pathways for adenosine, an immunosuppressant associated with worse responses to checkpoint blockade.

A larger study is already in the works. In addition to a PD-1 blocker and mFOLFIRINOX, patients will receive a CD73 inhibitor to block adenosine production, Dr. Wainberg said.

Bristol Myers Squibb (BMS) provided the nivolumab used in the study. Dr. Wainberg is a consultant for and reported research funding from BMS and other companies. Dr. Ho had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

The latest research supports immune checkpoint inhibitor therapy for clear cell and non–clear cell renal cell carcinoma, but patient selection is key to optimize outcomes, according to a medical oncologist from the Dana-Farber Cancer Institute, Boston.

Michael Serzan, MD, who works in the Lank Center for Genitourinary Oncology at the institute, stated this at the 2024 National Comprehensive Cancer Network Annual Conference, during a presentation.

A systematic review and meta-analysis published in 2022 in European Urology Open Science summarized six randomized controlled trials with a total of 5121 adult patients. In the review, the researchers found that immune checkpoint inhibitors plus vascular endothelial growth factor tyrosine kinase inhibitors (VEGF TKI) were associated with consistent improvements across all risk groups for metastatic renal cell carcinoma.

Additional newer research supports the use of immunotherapy combinations or other immunotherapy plus tyrosine kinase inhibitors as first-line or adjuvant treatments for renal cell carcinoma, Dr. Serzan said during an interview. However, more genomic and histology-directed therapies are needed, he noted.
 

Tips for Evaluating Risk When Treating Renal Cell Carcinoma?

For patients with localized clear cell renal cell carcinoma who have undergone partial or radical nephrectomy, there are several models that estimate the risk of recurrence based on pathologic tumor stage, grade, histology, invasion, and the extent of necrosis, Dr. Serzan said. These models can help guide selection of patients who may be at high risk of recurrence and, therefore, may benefit from adjuvant therapy.

For patients with metastatic clear cell renal cell carcinoma, the IMDC and MSKCC prognostic models stratify patients to favorable, intermediate, and poor risk groups based on clinical and lab factors. The IMDC risk stratification model is used as a prognostic model to stratify patients diagnosed with metastatic kidney cancer, Dr. Serzan said.
 

What Research Supports Treatments for Clear Cell and Non–Clear Cell Renal Cell Carcinoma?

The US Food and Drug Administration (FDA) approved pembrolizumab in 2021 for the adjuvant treatment of renal cell carcinoma (RCC) in patients with intermediate-risk or high-risk of recurrence after nephrectomy or after nephrectomy and resection of metastatic lesions.

Pembrolizumab is the first adjuvant therapy shown to significantly improve overall survival in these patients, Dr. Serzan said. In the KEYNOTE-564 study, published in 2024 in the Journal of Clinical Oncology, pembrolizumab demonstrated an improvement in disease free survival as well as overall survival when compared with placebo.

Several similar studies of adjuvant immune checkpoint inhibitors for renal cell carcinoma involving atezolizumab vs. placebo, nivolumab plus ipilimumab vs. placebo, and nivolumab vs. observation have not shown significant benefits in terms of disease-free survival, Dr. Serzan noted.

The current NCCN Clinical Practice Guidelines in Oncology for Kidney Cancer (Version: 3.2024), which were updated this year, support the use of adjuvant pembrolizumab for patients with stage II, III, or IV clear cell renal cell carcinoma after partial or radical nephrectomy, he said.

Looking ahead, biomarkers are needed to understand the risk of recurrence, and which patients benefit from adjuvant pembrolizumab, Dr. Serzan added.
 

Where Do VEGF-TKIs Fit In?

VEGF is a treatment target for renal cancer, and angiogenesis inhibition with VEGF TKIs continues to be a subject for study, Dr. Serzan said. In the CABOSUN study, published in the Journal of Clinical Oncology in 2017, patients were randomized to cabozantinib or sunitinib. Progression-free survival was significantly greater in the cabozantinib group, but overall survival was similar between the groups.

In another randomized trial, the CheckMate 214 study, patients received either sunitinib or a combination of nivolumab plus ipilimumab in four doses given every 3 weeks, followed by nivolumab alone every 2 weeks, and these patients were stratified by risk, Dr. Serzan noted.

The median progression-free survival was 12.4 months in the combination group vs. 8.5 months in the sunitinib group for patients at intermediate or poor risk of recurrence. The median progression-free survival was significantly greater in sunitinib patients with favorable risk vs. combination patients with favorable risk (28.9 months vs. 12.4 months).

Overall survival was higher for all patients with combination therapy vs. sunitinib regardless of risk stratification.

Dr. Serzan reviewed the pros of VEGF/PD1 (programmed death-ligand 1) combinations as including a high response rate (generally 52%-72%) and a low rate of primary progressive disease (5%-12%), as well as favorable progression-free and overall survival and low rates of immune-related adverse events.

However, cons of this treatment include lack of data on treatment-free survival as well as the decrease in progression-free survival and overall survival hazard ratios over time and potential chronic VEGF/TKI toxicities, he said.
 

What Treatments Are Recommended for Metastatic Clear Cell Renal Cell Carcinoma Now?

Clear cell renal cell carcinoma (ccRCC) is the most prevalent histological subtype of kidney cancer, accounting for 70%-75% of cases, and these patients are prone to metastasis, recurrence, and resistance to radiotherapy and chemotherapy, according to authors of a recent review published in Frontiers in Oncology.

Dr. Serzan shared his preferred protocol for treatment-naive metastatic ccRCC patients, based on the NCCN guidelines for Kidney Cancer (Version: 3.2024) that had been updated in 2024.

For those with sarcomatoid features, he favors the use of nivolumab/ipilimumab combination, while those without sarcomatoid features, if highly symptomatic, may be treated with any of several combinations: nivolumab/ipilimumab, axitinib/pembrolizumab, cabozantinib/nivolumab, or lenvatinib/pembrolizumab.

For asymptomatic patients without sarcomatoid features, treatment depends on eligibility for immune checkpoint inhibitors or ipilimumab, Dr. Serzan said. His first choice for those eligible is nivolumab/ipilimumab; those not eligible for ipilimumab could receive nivolumab, pembrolizumab, axitinib/pembrolizumab, cabozantinib/nivolumab, or lenvatinib/pembrolizumab.

For patients not eligible for ICIs because of uncontrolled autoimmune disease, or high-dose glucocorticoids, Dr. Serzan recommended treatment with cabozantinib, lenvatinib/everolimus, pazopanib, or sunitinib.
 

What are Some Takeaway Points About Immunotherapy and Renal Cell Carcinoma?

“Immunotherapy has revolutionized treatment for renal cell carcinoma, with significant increases in overall survival, and a small but consistent cure fraction that was unimaginable 10 years ago,” Eric Jonasch, MD, of The University of Texas MD Anderson Cancer Center and vice-chair of the NCCN Guidelines Panel for Kidney Cancer, said in an interview.

However, challenges to implementing new treatments in clinical practice are ongoing, he said. The major challenges facing clinicians, patients, and their families include the cost of therapy, logistics of treatment administration, and managing toxicities, Dr. Jonasch said.  

Patient selection is key to optimize outcomes with immunotherapy, and shared decision-making is essential to ensure that choice of therapy matches patient expectations and needs — and to maintain clear and open channels of communication while patients are on therapy, Dr. Jonasch said. “In my clinic, we empower patients to take treatment breaks to manage side effects, thereby optimizing quality of life while maintaining treatment efficacy,” he said.

Although significant progress has been made in managing renal cell carcinoma, more research is needed to increase the proportion of patients cured, said Dr. Jonasch. “A clearer understanding of the determinants of response and resistance, which will be driven by information rich clinical trials, will help move us in that direction,” he said.

Dr. Serzan had no financial conflicts to disclose. Dr. Jonasch disclosed research support from AbbVie, Arrowhead, Aveo, BMS, Corvus, Merck, NiKang, ProfoundBio, and Telix, as well as honoraria from Aveo, Eisai, Exelixis, GlaxoSmithKline, Ipsen, Merck, Novartis, NiKang, and Takeda.

The latest research supports immune checkpoint inhibitor therapy for clear cell and non–clear cell renal cell carcinoma, but patient selection is key to optimize outcomes, according to a medical oncologist from the Dana-Farber Cancer Institute, Boston.

Michael Serzan, MD, who works in the Lank Center for Genitourinary Oncology at the institute, stated this at the 2024 National Comprehensive Cancer Network Annual Conference, during a presentation.

A systematic review and meta-analysis published in 2022 in European Urology Open Science summarized six randomized controlled trials with a total of 5121 adult patients. In the review, the researchers found that immune checkpoint inhibitors plus vascular endothelial growth factor tyrosine kinase inhibitors (VEGF TKI) were associated with consistent improvements across all risk groups for metastatic renal cell carcinoma.

Additional newer research supports the use of immunotherapy combinations or other immunotherapy plus tyrosine kinase inhibitors as first-line or adjuvant treatments for renal cell carcinoma, Dr. Serzan said during an interview. However, more genomic and histology-directed therapies are needed, he noted.
 

Tips for Evaluating Risk When Treating Renal Cell Carcinoma?

For patients with localized clear cell renal cell carcinoma who have undergone partial or radical nephrectomy, there are several models that estimate the risk of recurrence based on pathologic tumor stage, grade, histology, invasion, and the extent of necrosis, Dr. Serzan said. These models can help guide selection of patients who may be at high risk of recurrence and, therefore, may benefit from adjuvant therapy.

For patients with metastatic clear cell renal cell carcinoma, the IMDC and MSKCC prognostic models stratify patients to favorable, intermediate, and poor risk groups based on clinical and lab factors. The IMDC risk stratification model is used as a prognostic model to stratify patients diagnosed with metastatic kidney cancer, Dr. Serzan said.
 

What Research Supports Treatments for Clear Cell and Non–Clear Cell Renal Cell Carcinoma?

The US Food and Drug Administration (FDA) approved pembrolizumab in 2021 for the adjuvant treatment of renal cell carcinoma (RCC) in patients with intermediate-risk or high-risk of recurrence after nephrectomy or after nephrectomy and resection of metastatic lesions.

Pembrolizumab is the first adjuvant therapy shown to significantly improve overall survival in these patients, Dr. Serzan said. In the KEYNOTE-564 study, published in 2024 in the Journal of Clinical Oncology, pembrolizumab demonstrated an improvement in disease free survival as well as overall survival when compared with placebo.

Several similar studies of adjuvant immune checkpoint inhibitors for renal cell carcinoma involving atezolizumab vs. placebo, nivolumab plus ipilimumab vs. placebo, and nivolumab vs. observation have not shown significant benefits in terms of disease-free survival, Dr. Serzan noted.

The current NCCN Clinical Practice Guidelines in Oncology for Kidney Cancer (Version: 3.2024), which were updated this year, support the use of adjuvant pembrolizumab for patients with stage II, III, or IV clear cell renal cell carcinoma after partial or radical nephrectomy, he said.

Looking ahead, biomarkers are needed to understand the risk of recurrence, and which patients benefit from adjuvant pembrolizumab, Dr. Serzan added.
 

Where Do VEGF-TKIs Fit In?

VEGF is a treatment target for renal cancer, and angiogenesis inhibition with VEGF TKIs continues to be a subject for study, Dr. Serzan said. In the CABOSUN study, published in the Journal of Clinical Oncology in 2017, patients were randomized to cabozantinib or sunitinib. Progression-free survival was significantly greater in the cabozantinib group, but overall survival was similar between the groups.

In another randomized trial, the CheckMate 214 study, patients received either sunitinib or a combination of nivolumab plus ipilimumab in four doses given every 3 weeks, followed by nivolumab alone every 2 weeks, and these patients were stratified by risk, Dr. Serzan noted.

The median progression-free survival was 12.4 months in the combination group vs. 8.5 months in the sunitinib group for patients at intermediate or poor risk of recurrence. The median progression-free survival was significantly greater in sunitinib patients with favorable risk vs. combination patients with favorable risk (28.9 months vs. 12.4 months).

Overall survival was higher for all patients with combination therapy vs. sunitinib regardless of risk stratification.

Dr. Serzan reviewed the pros of VEGF/PD1 (programmed death-ligand 1) combinations as including a high response rate (generally 52%-72%) and a low rate of primary progressive disease (5%-12%), as well as favorable progression-free and overall survival and low rates of immune-related adverse events.

However, cons of this treatment include lack of data on treatment-free survival as well as the decrease in progression-free survival and overall survival hazard ratios over time and potential chronic VEGF/TKI toxicities, he said.
 

What Treatments Are Recommended for Metastatic Clear Cell Renal Cell Carcinoma Now?

Clear cell renal cell carcinoma (ccRCC) is the most prevalent histological subtype of kidney cancer, accounting for 70%-75% of cases, and these patients are prone to metastasis, recurrence, and resistance to radiotherapy and chemotherapy, according to authors of a recent review published in Frontiers in Oncology.

Dr. Serzan shared his preferred protocol for treatment-naive metastatic ccRCC patients, based on the NCCN guidelines for Kidney Cancer (Version: 3.2024) that had been updated in 2024.

For those with sarcomatoid features, he favors the use of nivolumab/ipilimumab combination, while those without sarcomatoid features, if highly symptomatic, may be treated with any of several combinations: nivolumab/ipilimumab, axitinib/pembrolizumab, cabozantinib/nivolumab, or lenvatinib/pembrolizumab.

For asymptomatic patients without sarcomatoid features, treatment depends on eligibility for immune checkpoint inhibitors or ipilimumab, Dr. Serzan said. His first choice for those eligible is nivolumab/ipilimumab; those not eligible for ipilimumab could receive nivolumab, pembrolizumab, axitinib/pembrolizumab, cabozantinib/nivolumab, or lenvatinib/pembrolizumab.

For patients not eligible for ICIs because of uncontrolled autoimmune disease, or high-dose glucocorticoids, Dr. Serzan recommended treatment with cabozantinib, lenvatinib/everolimus, pazopanib, or sunitinib.
 

What are Some Takeaway Points About Immunotherapy and Renal Cell Carcinoma?

“Immunotherapy has revolutionized treatment for renal cell carcinoma, with significant increases in overall survival, and a small but consistent cure fraction that was unimaginable 10 years ago,” Eric Jonasch, MD, of The University of Texas MD Anderson Cancer Center and vice-chair of the NCCN Guidelines Panel for Kidney Cancer, said in an interview.

However, challenges to implementing new treatments in clinical practice are ongoing, he said. The major challenges facing clinicians, patients, and their families include the cost of therapy, logistics of treatment administration, and managing toxicities, Dr. Jonasch said.  

Patient selection is key to optimize outcomes with immunotherapy, and shared decision-making is essential to ensure that choice of therapy matches patient expectations and needs — and to maintain clear and open channels of communication while patients are on therapy, Dr. Jonasch said. “In my clinic, we empower patients to take treatment breaks to manage side effects, thereby optimizing quality of life while maintaining treatment efficacy,” he said.

Although significant progress has been made in managing renal cell carcinoma, more research is needed to increase the proportion of patients cured, said Dr. Jonasch. “A clearer understanding of the determinants of response and resistance, which will be driven by information rich clinical trials, will help move us in that direction,” he said.

Dr. Serzan had no financial conflicts to disclose. Dr. Jonasch disclosed research support from AbbVie, Arrowhead, Aveo, BMS, Corvus, Merck, NiKang, ProfoundBio, and Telix, as well as honoraria from Aveo, Eisai, Exelixis, GlaxoSmithKline, Ipsen, Merck, Novartis, NiKang, and Takeda.

The latest research supports immune checkpoint inhibitor therapy for clear cell and non–clear cell renal cell carcinoma, but patient selection is key to optimize outcomes, according to a medical oncologist from the Dana-Farber Cancer Institute, Boston.

Michael Serzan, MD, who works in the Lank Center for Genitourinary Oncology at the institute, stated this at the 2024 National Comprehensive Cancer Network Annual Conference, during a presentation.

A systematic review and meta-analysis published in 2022 in European Urology Open Science summarized six randomized controlled trials with a total of 5121 adult patients. In the review, the researchers found that immune checkpoint inhibitors plus vascular endothelial growth factor tyrosine kinase inhibitors (VEGF TKI) were associated with consistent improvements across all risk groups for metastatic renal cell carcinoma.

Additional newer research supports the use of immunotherapy combinations or other immunotherapy plus tyrosine kinase inhibitors as first-line or adjuvant treatments for renal cell carcinoma, Dr. Serzan said during an interview. However, more genomic and histology-directed therapies are needed, he noted.
 

Tips for Evaluating Risk When Treating Renal Cell Carcinoma?

For patients with localized clear cell renal cell carcinoma who have undergone partial or radical nephrectomy, there are several models that estimate the risk of recurrence based on pathologic tumor stage, grade, histology, invasion, and the extent of necrosis, Dr. Serzan said. These models can help guide selection of patients who may be at high risk of recurrence and, therefore, may benefit from adjuvant therapy.

For patients with metastatic clear cell renal cell carcinoma, the IMDC and MSKCC prognostic models stratify patients to favorable, intermediate, and poor risk groups based on clinical and lab factors. The IMDC risk stratification model is used as a prognostic model to stratify patients diagnosed with metastatic kidney cancer, Dr. Serzan said.
 

What Research Supports Treatments for Clear Cell and Non–Clear Cell Renal Cell Carcinoma?

The US Food and Drug Administration (FDA) approved pembrolizumab in 2021 for the adjuvant treatment of renal cell carcinoma (RCC) in patients with intermediate-risk or high-risk of recurrence after nephrectomy or after nephrectomy and resection of metastatic lesions.

Pembrolizumab is the first adjuvant therapy shown to significantly improve overall survival in these patients, Dr. Serzan said. In the KEYNOTE-564 study, published in 2024 in the Journal of Clinical Oncology, pembrolizumab demonstrated an improvement in disease free survival as well as overall survival when compared with placebo.

Several similar studies of adjuvant immune checkpoint inhibitors for renal cell carcinoma involving atezolizumab vs. placebo, nivolumab plus ipilimumab vs. placebo, and nivolumab vs. observation have not shown significant benefits in terms of disease-free survival, Dr. Serzan noted.

The current NCCN Clinical Practice Guidelines in Oncology for Kidney Cancer (Version: 3.2024), which were updated this year, support the use of adjuvant pembrolizumab for patients with stage II, III, or IV clear cell renal cell carcinoma after partial or radical nephrectomy, he said.

Looking ahead, biomarkers are needed to understand the risk of recurrence, and which patients benefit from adjuvant pembrolizumab, Dr. Serzan added.
 

Where Do VEGF-TKIs Fit In?

VEGF is a treatment target for renal cancer, and angiogenesis inhibition with VEGF TKIs continues to be a subject for study, Dr. Serzan said. In the CABOSUN study, published in the Journal of Clinical Oncology in 2017, patients were randomized to cabozantinib or sunitinib. Progression-free survival was significantly greater in the cabozantinib group, but overall survival was similar between the groups.

In another randomized trial, the CheckMate 214 study, patients received either sunitinib or a combination of nivolumab plus ipilimumab in four doses given every 3 weeks, followed by nivolumab alone every 2 weeks, and these patients were stratified by risk, Dr. Serzan noted.

The median progression-free survival was 12.4 months in the combination group vs. 8.5 months in the sunitinib group for patients at intermediate or poor risk of recurrence. The median progression-free survival was significantly greater in sunitinib patients with favorable risk vs. combination patients with favorable risk (28.9 months vs. 12.4 months).

Overall survival was higher for all patients with combination therapy vs. sunitinib regardless of risk stratification.

Dr. Serzan reviewed the pros of VEGF/PD1 (programmed death-ligand 1) combinations as including a high response rate (generally 52%-72%) and a low rate of primary progressive disease (5%-12%), as well as favorable progression-free and overall survival and low rates of immune-related adverse events.

However, cons of this treatment include lack of data on treatment-free survival as well as the decrease in progression-free survival and overall survival hazard ratios over time and potential chronic VEGF/TKI toxicities, he said.
 

What Treatments Are Recommended for Metastatic Clear Cell Renal Cell Carcinoma Now?

Clear cell renal cell carcinoma (ccRCC) is the most prevalent histological subtype of kidney cancer, accounting for 70%-75% of cases, and these patients are prone to metastasis, recurrence, and resistance to radiotherapy and chemotherapy, according to authors of a recent review published in Frontiers in Oncology.

Dr. Serzan shared his preferred protocol for treatment-naive metastatic ccRCC patients, based on the NCCN guidelines for Kidney Cancer (Version: 3.2024) that had been updated in 2024.

For those with sarcomatoid features, he favors the use of nivolumab/ipilimumab combination, while those without sarcomatoid features, if highly symptomatic, may be treated with any of several combinations: nivolumab/ipilimumab, axitinib/pembrolizumab, cabozantinib/nivolumab, or lenvatinib/pembrolizumab.

For asymptomatic patients without sarcomatoid features, treatment depends on eligibility for immune checkpoint inhibitors or ipilimumab, Dr. Serzan said. His first choice for those eligible is nivolumab/ipilimumab; those not eligible for ipilimumab could receive nivolumab, pembrolizumab, axitinib/pembrolizumab, cabozantinib/nivolumab, or lenvatinib/pembrolizumab.

For patients not eligible for ICIs because of uncontrolled autoimmune disease, or high-dose glucocorticoids, Dr. Serzan recommended treatment with cabozantinib, lenvatinib/everolimus, pazopanib, or sunitinib.
 

What are Some Takeaway Points About Immunotherapy and Renal Cell Carcinoma?

“Immunotherapy has revolutionized treatment for renal cell carcinoma, with significant increases in overall survival, and a small but consistent cure fraction that was unimaginable 10 years ago,” Eric Jonasch, MD, of The University of Texas MD Anderson Cancer Center and vice-chair of the NCCN Guidelines Panel for Kidney Cancer, said in an interview.

However, challenges to implementing new treatments in clinical practice are ongoing, he said. The major challenges facing clinicians, patients, and their families include the cost of therapy, logistics of treatment administration, and managing toxicities, Dr. Jonasch said.  

Patient selection is key to optimize outcomes with immunotherapy, and shared decision-making is essential to ensure that choice of therapy matches patient expectations and needs — and to maintain clear and open channels of communication while patients are on therapy, Dr. Jonasch said. “In my clinic, we empower patients to take treatment breaks to manage side effects, thereby optimizing quality of life while maintaining treatment efficacy,” he said.

Although significant progress has been made in managing renal cell carcinoma, more research is needed to increase the proportion of patients cured, said Dr. Jonasch. “A clearer understanding of the determinants of response and resistance, which will be driven by information rich clinical trials, will help move us in that direction,” he said.

Dr. Serzan had no financial conflicts to disclose. Dr. Jonasch disclosed research support from AbbVie, Arrowhead, Aveo, BMS, Corvus, Merck, NiKang, ProfoundBio, and Telix, as well as honoraria from Aveo, Eisai, Exelixis, GlaxoSmithKline, Ipsen, Merck, Novartis, NiKang, and Takeda.

Picture a healthcare system where physicians aren’t bogged down by excessive charting but are instead fully present with their patients, offering undivided attention and personalized care. In a recent X post, Stuart Blitz, COO and co-founder of Hone Health, sparked a thought-provoking conversation. “The problem with US healthcare is physicians are burned out since they spend way too much time charting, not enough with patients,” he wrote. “If you created a health system that did zero charting, you’d attract the best physicians and all patients would go there. Who is working on this?” 

This resonates with many in the medical community, myself included, because the strain of extensive documentation detracts from patient care. Having worked in both large and small healthcare systems, I know the burden of extensive charting is a palpable challenge, often detracting from the time we can devote to our patients.

The first part of this two-part series examines the overarching benefits of artificial intelligence (AI)–based clinical documentation in modern healthcare, a field witnessing a paradigm shift thanks to advancements in AI.
 

Transformative Evolution of Clinical Documentation

The transition from manual documentation to AI-driven solutions marks a significant shift in the field, with a number of products in development including Nuance, Abridge, Ambience, ScribeAmerica, 3M, and DeepScribe. These tools use ambient clinical intelligence (ACI) to automate documentation, capturing patient conversations and translating them into structured clinical summaries. This innovation aligns with the vision of reducing charting burdens and enhancing patient-physician interactions.

How does it work? ACI refers to a sophisticated form of AI applied in healthcare settings, particularly focusing on enhancing the clinical documentation process without disrupting the natural flow of the consultation. Here’s a technical yet practical breakdown of ACI and the algorithms it typically employs:

Data capture and processing: ACI systems employ various sensors and processing units, typically integrated into clinical settings. These sensors, like microphones and cameras, gather diverse data such as audio from patient-doctor dialogues and visual cues. This information is then processed in real-time or near–real-time.

Natural language processing (NLP): A core component of ACI is advanced NLP algorithms. These algorithms analyze the captured audio data, transcribing spoken words into text. NLP goes beyond mere transcription; it involves understanding context, extracting relevant medical information (like symptoms, diagnoses, and treatment plans), and interpreting the nuances of human language.

Deep learning: Machine learning, particularly deep-learning techniques, are employed to improve the accuracy of ACI systems continually. These algorithms can learn from vast datasets of clinical interactions, enhancing their ability to transcribe and interpret future conversations accurately. As they learn, they become better at understanding different accents, complex medical terms, and variations in speech patterns.

Integration with electronic health records (EHRs): ACI systems are often designed to integrate seamlessly with existing EHR systems. They can automatically populate patient records with information from patient-clinician interactions, reducing manual entry and potential errors.

Customization and personalization: Many ACI systems offer customizable templates or allow clinicians to tailor documentation workflows. This flexibility ensures that the output aligns with the specific needs and preferences of healthcare providers.

Ethical and privacy considerations: ACI systems must navigate significant ethical and privacy concerns, especially related to patient consent and data security. These systems need to comply with healthcare privacy regulations such as HIPAA. They need to securely manage sensitive patient data and restrict access to authorized personnel only.
 

Broad-Spectrum Benefits of AI in Documentation

• Reducing clinician burnout: By automating the documentation process, AI tools like DAX Copilot alleviate a significant contributor to physician burnout, enabling clinicians to focus more on patient care.
• Enhanced patient care: With AI handling documentation, clinicians can engage more with their patients, leading to improved care quality and patient satisfaction.
• Data accuracy and quality: AI-driven documentation captures detailed patient encounters accurately, ensuring high-quality and comprehensive medical records.
• Response to the growing need for efficient healthcare: AI-based documentation is a direct response to the growing call for more efficient healthcare practices, where clinicians spend less time on paperwork and more with patients.

The shift toward AI-based clinical documentation represents a critical step in addressing the inefficiencies in healthcare systems. It’s a move towards a more patient-centered approach, where clinicians can focus more on patient care by reducing the time spent on excessive charting. Hopefully, we can integrate these solutions into our clinics at a large enough scale to make such an impact.

In the next column, we will explore in-depth insights from Kenneth Harper at Nuance on the technical implementation of these tools, with DAX as an example.

I would love to read your comments on AI in clinical trials as well as other AI-related topics. Write me at Arturo.ai.medtech@gmail.com or find me on X @DrBonillaOnc.

Dr. Loaiza-Bonilla is the co-founder and chief medical officer at Massive Bio, a company connecting patients to clinical trials using artificial intelligence. His research and professional interests focus on precision medicine, clinical trial design, digital health, entrepreneurship, and patient advocacy. Dr Loaiza-Bonilla serves as medical director of oncology research at Capital Health in New Jersey, where he maintains a connection to patient care by attending to patients 2 days a week. He has served as a consultant for Verify, PSI CRO, Bayer, AstraZeneca, Cardinal Health, BrightInsight, The Lynx Group, Fresenius, Pfizer, Ipsen, and Guardant; served as a speaker or a member of a speakers bureau for Amgen, Guardant, Eisai, Ipsen, Natera, Merck, Bristol-Myers Squibb, and AstraZeneca. He holds a 5% or greater equity interest in Massive Bio.

A version of this article appeared on Medscape.com.

Picture a healthcare system where physicians aren’t bogged down by excessive charting but are instead fully present with their patients, offering undivided attention and personalized care. In a recent X post, Stuart Blitz, COO and co-founder of Hone Health, sparked a thought-provoking conversation. “The problem with US healthcare is physicians are burned out since they spend way too much time charting, not enough with patients,” he wrote. “If you created a health system that did zero charting, you’d attract the best physicians and all patients would go there. Who is working on this?” 

This resonates with many in the medical community, myself included, because the strain of extensive documentation detracts from patient care. Having worked in both large and small healthcare systems, I know the burden of extensive charting is a palpable challenge, often detracting from the time we can devote to our patients.

The first part of this two-part series examines the overarching benefits of artificial intelligence (AI)–based clinical documentation in modern healthcare, a field witnessing a paradigm shift thanks to advancements in AI.
 

Transformative Evolution of Clinical Documentation

The transition from manual documentation to AI-driven solutions marks a significant shift in the field, with a number of products in development including Nuance, Abridge, Ambience, ScribeAmerica, 3M, and DeepScribe. These tools use ambient clinical intelligence (ACI) to automate documentation, capturing patient conversations and translating them into structured clinical summaries. This innovation aligns with the vision of reducing charting burdens and enhancing patient-physician interactions.

How does it work? ACI refers to a sophisticated form of AI applied in healthcare settings, particularly focusing on enhancing the clinical documentation process without disrupting the natural flow of the consultation. Here’s a technical yet practical breakdown of ACI and the algorithms it typically employs:

Data capture and processing: ACI systems employ various sensors and processing units, typically integrated into clinical settings. These sensors, like microphones and cameras, gather diverse data such as audio from patient-doctor dialogues and visual cues. This information is then processed in real-time or near–real-time.

Natural language processing (NLP): A core component of ACI is advanced NLP algorithms. These algorithms analyze the captured audio data, transcribing spoken words into text. NLP goes beyond mere transcription; it involves understanding context, extracting relevant medical information (like symptoms, diagnoses, and treatment plans), and interpreting the nuances of human language.

Deep learning: Machine learning, particularly deep-learning techniques, are employed to improve the accuracy of ACI systems continually. These algorithms can learn from vast datasets of clinical interactions, enhancing their ability to transcribe and interpret future conversations accurately. As they learn, they become better at understanding different accents, complex medical terms, and variations in speech patterns.

Integration with electronic health records (EHRs): ACI systems are often designed to integrate seamlessly with existing EHR systems. They can automatically populate patient records with information from patient-clinician interactions, reducing manual entry and potential errors.

Customization and personalization: Many ACI systems offer customizable templates or allow clinicians to tailor documentation workflows. This flexibility ensures that the output aligns with the specific needs and preferences of healthcare providers.

Ethical and privacy considerations: ACI systems must navigate significant ethical and privacy concerns, especially related to patient consent and data security. These systems need to comply with healthcare privacy regulations such as HIPAA. They need to securely manage sensitive patient data and restrict access to authorized personnel only.
 

Broad-Spectrum Benefits of AI in Documentation

• Reducing clinician burnout: By automating the documentation process, AI tools like DAX Copilot alleviate a significant contributor to physician burnout, enabling clinicians to focus more on patient care.
• Enhanced patient care: With AI handling documentation, clinicians can engage more with their patients, leading to improved care quality and patient satisfaction.
• Data accuracy and quality: AI-driven documentation captures detailed patient encounters accurately, ensuring high-quality and comprehensive medical records.
• Response to the growing need for efficient healthcare: AI-based documentation is a direct response to the growing call for more efficient healthcare practices, where clinicians spend less time on paperwork and more with patients.

The shift toward AI-based clinical documentation represents a critical step in addressing the inefficiencies in healthcare systems. It’s a move towards a more patient-centered approach, where clinicians can focus more on patient care by reducing the time spent on excessive charting. Hopefully, we can integrate these solutions into our clinics at a large enough scale to make such an impact.

In the next column, we will explore in-depth insights from Kenneth Harper at Nuance on the technical implementation of these tools, with DAX as an example.

I would love to read your comments on AI in clinical trials as well as other AI-related topics. Write me at Arturo.ai.medtech@gmail.com or find me on X @DrBonillaOnc.

Dr. Loaiza-Bonilla is the co-founder and chief medical officer at Massive Bio, a company connecting patients to clinical trials using artificial intelligence. His research and professional interests focus on precision medicine, clinical trial design, digital health, entrepreneurship, and patient advocacy. Dr Loaiza-Bonilla serves as medical director of oncology research at Capital Health in New Jersey, where he maintains a connection to patient care by attending to patients 2 days a week. He has served as a consultant for Verify, PSI CRO, Bayer, AstraZeneca, Cardinal Health, BrightInsight, The Lynx Group, Fresenius, Pfizer, Ipsen, and Guardant; served as a speaker or a member of a speakers bureau for Amgen, Guardant, Eisai, Ipsen, Natera, Merck, Bristol-Myers Squibb, and AstraZeneca. He holds a 5% or greater equity interest in Massive Bio.

A version of this article appeared on Medscape.com.

Picture a healthcare system where physicians aren’t bogged down by excessive charting but are instead fully present with their patients, offering undivided attention and personalized care. In a recent X post, Stuart Blitz, COO and co-founder of Hone Health, sparked a thought-provoking conversation. “The problem with US healthcare is physicians are burned out since they spend way too much time charting, not enough with patients,” he wrote. “If you created a health system that did zero charting, you’d attract the best physicians and all patients would go there. Who is working on this?” 

This resonates with many in the medical community, myself included, because the strain of extensive documentation detracts from patient care. Having worked in both large and small healthcare systems, I know the burden of extensive charting is a palpable challenge, often detracting from the time we can devote to our patients.

The first part of this two-part series examines the overarching benefits of artificial intelligence (AI)–based clinical documentation in modern healthcare, a field witnessing a paradigm shift thanks to advancements in AI.
 

Transformative Evolution of Clinical Documentation

The transition from manual documentation to AI-driven solutions marks a significant shift in the field, with a number of products in development including Nuance, Abridge, Ambience, ScribeAmerica, 3M, and DeepScribe. These tools use ambient clinical intelligence (ACI) to automate documentation, capturing patient conversations and translating them into structured clinical summaries. This innovation aligns with the vision of reducing charting burdens and enhancing patient-physician interactions.

How does it work? ACI refers to a sophisticated form of AI applied in healthcare settings, particularly focusing on enhancing the clinical documentation process without disrupting the natural flow of the consultation. Here’s a technical yet practical breakdown of ACI and the algorithms it typically employs:

Data capture and processing: ACI systems employ various sensors and processing units, typically integrated into clinical settings. These sensors, like microphones and cameras, gather diverse data such as audio from patient-doctor dialogues and visual cues. This information is then processed in real-time or near–real-time.

Natural language processing (NLP): A core component of ACI is advanced NLP algorithms. These algorithms analyze the captured audio data, transcribing spoken words into text. NLP goes beyond mere transcription; it involves understanding context, extracting relevant medical information (like symptoms, diagnoses, and treatment plans), and interpreting the nuances of human language.

Deep learning: Machine learning, particularly deep-learning techniques, are employed to improve the accuracy of ACI systems continually. These algorithms can learn from vast datasets of clinical interactions, enhancing their ability to transcribe and interpret future conversations accurately. As they learn, they become better at understanding different accents, complex medical terms, and variations in speech patterns.

Integration with electronic health records (EHRs): ACI systems are often designed to integrate seamlessly with existing EHR systems. They can automatically populate patient records with information from patient-clinician interactions, reducing manual entry and potential errors.

Customization and personalization: Many ACI systems offer customizable templates or allow clinicians to tailor documentation workflows. This flexibility ensures that the output aligns with the specific needs and preferences of healthcare providers.

Ethical and privacy considerations: ACI systems must navigate significant ethical and privacy concerns, especially related to patient consent and data security. These systems need to comply with healthcare privacy regulations such as HIPAA. They need to securely manage sensitive patient data and restrict access to authorized personnel only.
 

Broad-Spectrum Benefits of AI in Documentation

• Reducing clinician burnout: By automating the documentation process, AI tools like DAX Copilot alleviate a significant contributor to physician burnout, enabling clinicians to focus more on patient care.
• Enhanced patient care: With AI handling documentation, clinicians can engage more with their patients, leading to improved care quality and patient satisfaction.
• Data accuracy and quality: AI-driven documentation captures detailed patient encounters accurately, ensuring high-quality and comprehensive medical records.
• Response to the growing need for efficient healthcare: AI-based documentation is a direct response to the growing call for more efficient healthcare practices, where clinicians spend less time on paperwork and more with patients.

The shift toward AI-based clinical documentation represents a critical step in addressing the inefficiencies in healthcare systems. It’s a move towards a more patient-centered approach, where clinicians can focus more on patient care by reducing the time spent on excessive charting. Hopefully, we can integrate these solutions into our clinics at a large enough scale to make such an impact.

In the next column, we will explore in-depth insights from Kenneth Harper at Nuance on the technical implementation of these tools, with DAX as an example.

I would love to read your comments on AI in clinical trials as well as other AI-related topics. Write me at Arturo.ai.medtech@gmail.com or find me on X @DrBonillaOnc.

Dr. Loaiza-Bonilla is the co-founder and chief medical officer at Massive Bio, a company connecting patients to clinical trials using artificial intelligence. His research and professional interests focus on precision medicine, clinical trial design, digital health, entrepreneurship, and patient advocacy. Dr Loaiza-Bonilla serves as medical director of oncology research at Capital Health in New Jersey, where he maintains a connection to patient care by attending to patients 2 days a week. He has served as a consultant for Verify, PSI CRO, Bayer, AstraZeneca, Cardinal Health, BrightInsight, The Lynx Group, Fresenius, Pfizer, Ipsen, and Guardant; served as a speaker or a member of a speakers bureau for Amgen, Guardant, Eisai, Ipsen, Natera, Merck, Bristol-Myers Squibb, and AstraZeneca. He holds a 5% or greater equity interest in Massive Bio.

A version of this article appeared on Medscape.com.

PARIS — Irritable bowel syndrome (IBS) is a common brain-gut axis disorder, and patients are often dissatisfied with conventional treatments.

The role of the microbiota in IBS is now well established, and patients frequently take probiotics on their own initiative or on the advice of a physician or pharmacist. However, not all probiotics have equal efficacy, so which ones should be recommended?

Jean-Marc Sabaté, MD, PhD, a gastroenterologist at Avicenne Hospital in Bobigny, France, shared insights about probiotics at the Francophone Days of Hepatology, Gastroenterology, and Digestive Oncology.

IBS, according to the Rome IV symptom-based classification, is a “disorder of brain-gut axis interactions” with a prevalence of about 4% in the adult population. In France, during an average care pathway of about 8 years, patients try an average of five therapeutic strategies (and as many as 11), including antispasmodics (85%), diets (78%), and probiotics. In addition, 66.4% of patients had either taken or were taking probiotics at the time of a recent survey.

While the 2022 recommendations from the American College of Gastroenterology on the diagnosis and management of IBS do not support the use of probiotics for overall symptom relief — a recommendation for which they cite a low level of evidence — “there is nevertheless a rationale for prescribing probiotics in IBS due to the significant role of the microbiota (or dysbiosis) in this condition,” said Dr. Sabaté.
 

Microbiota in IBS 

Evidence indicating that antibiotics exacerbate IBS symptoms and revealing chronic bacterial overgrowth in the small intestine of patients with IBS supports the role of the microbiota. Studies using a molecular approach (16s rRNA) have settled the debate, confirming differences in the intestinal flora between patients with IBS and healthy subjects. Data also indicate differences in flora between patient subtypes, such as an increased Firmicutes to Bacteroidetes ratio. However, one subgroup, which can represent as much as a third of patients, seems to harbor a “normal” microbiota. 

Nonetheless, the microbiota plays a significant role in IBS. A Swedish study highlighted the influence of bacterial enterotypes on transit type associated with IBS and symptom severity, independent of diet composition or medication use. 

This dysbiosis could play a significant role as it interacts with other mechanisms involved in IBS, including changes in intestinal motility related to diet (related to fermentable carbohydrates, for example). Moreover, the microbiota seems to induce a low level of immune activation in patients with IBS, leading to microinflammation and increased intestinal permeability, especially after an infection.

Furthermore, alterations in the regulation of bile acid deconjugation by the microbiota partly explain the frequency and consistency of stools in diarrhea-predominant IBS patients.

In addition, colonic gas production is higher in these patients. Those complaining of flatulence have poor tolerance to intestinal gases after a flatulent meal, associated with microbiota instability.

Data regarding the interaction between the microbiota and central mechanisms mainly come from animal studies. In rodents, microbiota constituents seem to affect brain development, function, and morphology. Emotional and physical traumas during childhood appear to be risk factors. Moreover, even brief exposure to broad-spectrum antibiotics in neonates could cause subsequent visceral hypersensitivity.

Lastly, the role of the microbiota in changes in medullary pain control after visceral stimulation (eg, rectal distension) has still not been demonstrated in humans.
 

Recent Guideline 

In its February 2023 Global Guideline “Probiotics and Prebiotics” for IBS, the World Gastroenterology Organization looked at the level of evidence for probiotics.

Three strains, as well as a combination of several strains, were supported by level 2 evidence, meaning at least two randomized studies with converging results. These are Bifidobacterium bifidum MIMBb75, which improves overall symptoms and quality of life; Lactobacillus plantarum 299v (DSM 9843), which acts on the severity of abdominal pain and bloating; and B infantis 35624 (new name: B longum 35624), which improves the overall assessment of IBS symptoms, as does the multistrain product containing L rhamnosus GG, L rhamnosus LC705, Propionibacterium freudenreichii ssp shermanii JS DSM 7067, and B animalis ssp lactis B012 DSM 15954.
 

Efficacy and Availability 

Probiotics belonging to the category of dietary supplements or medical devices are not required to provide evidence for a mechanism of action or even efficacy to be marketed. Thus, for most probiotics sold, there are no human or even animal studies available.

Dr. Sabaté proposed a choice of probiotics based on the literature and the presence of at least one randomized placebo-controlled trial conducted in patients with IBS showing positive results.

“Probiotic efficacy largely depends on the bacterial species, strain, and clinical situation treated. Only probiotics with demonstrated clinical efficacy in randomized placebo-controlled trials should be recommended,” he emphasized. The parameters that can be improved include symptom severity, quality of life, abdominal pain, and bloating.
 

Effective Probiotics 

B longum 35624, which was developed with researchers from University College Cork in Ireland, is probably the most studied in animals and humans. Research has encompassed the mechanistic, clinical, and safety aspects of the probiotic. It has shown good results on the IBS-Symptom Severity Score (SSS), quality of life, abdominal pain, bowel disturbances, and bloating. The treatment duration in studies is 4-8 weeks.

L plantarum 299v (DSM 9843) affects the frequency of abdominal pain and pain score. The treatment duration in studies is 4 weeks.

The multistrain product that includes L plantarum CECT 7484/L plantarum CECT 7485/ Pediococcus acidilactici CECT 7483 allows for an improvement in quality of life and anxiety related to digestive symptoms. No positive effect has been described on digestive symptoms, especially diarrhea. The treatment duration is 6 weeks.

B bifidum MIMBb75 (both normal and heat-inactivated forms) is beneficial for pain, the composite IBS-SSS score, and quality of life. The treatment duration is 4-8 weeks.

“Except for the multistrain combination, which is more suited to patients with diarrhea-predominant IBS, the other three probiotics can be prescribed regardless of the IBS subtype,” said Dr. Sabaté. “Treatment durations are typically 4 weeks, but it is possible to continue up to 8 weeks, which is the maximum duration of these studies. In practice, there are no tolerance issues with probiotics prescribed for IBS based on the literature. These should be tested under the conditions and for the duration of the published studies and should only be continued if there is individual benefit on symptoms or quality of life.”

Note that microbiota analyses conducted for individual purposes are of no help in choosing probiotics.
 

Mechanisms of Action 

In a murine model, but not in humans, some strains, especially L acidophilus NCFM, have shown an antinociceptive effect by inducing opioid and cannabinoid receptors.

Only in animals to date, L farciminis and B lactis CNCM I-2494 have shown prevention of induced hypersensitivity (ie, inhibition of the cytoskeleton contraction of colon epithelial cells and subsequent opening of tight junctions).

B infantis 35624 has an anti-inflammatory action by modifying the IL-10 and IL-12 cytokine ratio in animals and humans. It has an immunomodulatory action by increasing dendritic cells in the mucosa and decreasing Th1 and Th7 helper T cells.

B infantis 35624 and L farciminis are two strains that decrease visceral sensitivity in mice.

Escherichia coli Nissle 1917 acts on lipopeptide production with an antinociceptive effect, as observed in mice, by decreasing visceral sensitivity through calcium nociceptor flux blockade (action on GABA type B receptor).

Acting on dysbiosis by modifying fecal microbiota during probiotic intake is possible but depends on the probiotics, like B infantis 35624. In humans, B longum NCC 3001 could modify brain activations.

Dr. Sabaté disclosed financial relationships with Mayoly Spindler, Kyowa Kirin, Tillotts, Servier, Norgine, Biocodex, Merck, Viatris, Abivax, and Inventiva.

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

PARIS — Irritable bowel syndrome (IBS) is a common brain-gut axis disorder, and patients are often dissatisfied with conventional treatments.

The role of the microbiota in IBS is now well established, and patients frequently take probiotics on their own initiative or on the advice of a physician or pharmacist. However, not all probiotics have equal efficacy, so which ones should be recommended?

Jean-Marc Sabaté, MD, PhD, a gastroenterologist at Avicenne Hospital in Bobigny, France, shared insights about probiotics at the Francophone Days of Hepatology, Gastroenterology, and Digestive Oncology.

IBS, according to the Rome IV symptom-based classification, is a “disorder of brain-gut axis interactions” with a prevalence of about 4% in the adult population. In France, during an average care pathway of about 8 years, patients try an average of five therapeutic strategies (and as many as 11), including antispasmodics (85%), diets (78%), and probiotics. In addition, 66.4% of patients had either taken or were taking probiotics at the time of a recent survey.

While the 2022 recommendations from the American College of Gastroenterology on the diagnosis and management of IBS do not support the use of probiotics for overall symptom relief — a recommendation for which they cite a low level of evidence — “there is nevertheless a rationale for prescribing probiotics in IBS due to the significant role of the microbiota (or dysbiosis) in this condition,” said Dr. Sabaté.
 

Microbiota in IBS 

Evidence indicating that antibiotics exacerbate IBS symptoms and revealing chronic bacterial overgrowth in the small intestine of patients with IBS supports the role of the microbiota. Studies using a molecular approach (16s rRNA) have settled the debate, confirming differences in the intestinal flora between patients with IBS and healthy subjects. Data also indicate differences in flora between patient subtypes, such as an increased Firmicutes to Bacteroidetes ratio. However, one subgroup, which can represent as much as a third of patients, seems to harbor a “normal” microbiota. 

Nonetheless, the microbiota plays a significant role in IBS. A Swedish study highlighted the influence of bacterial enterotypes on transit type associated with IBS and symptom severity, independent of diet composition or medication use. 

This dysbiosis could play a significant role as it interacts with other mechanisms involved in IBS, including changes in intestinal motility related to diet (related to fermentable carbohydrates, for example). Moreover, the microbiota seems to induce a low level of immune activation in patients with IBS, leading to microinflammation and increased intestinal permeability, especially after an infection.

Furthermore, alterations in the regulation of bile acid deconjugation by the microbiota partly explain the frequency and consistency of stools in diarrhea-predominant IBS patients.

In addition, colonic gas production is higher in these patients. Those complaining of flatulence have poor tolerance to intestinal gases after a flatulent meal, associated with microbiota instability.

Data regarding the interaction between the microbiota and central mechanisms mainly come from animal studies. In rodents, microbiota constituents seem to affect brain development, function, and morphology. Emotional and physical traumas during childhood appear to be risk factors. Moreover, even brief exposure to broad-spectrum antibiotics in neonates could cause subsequent visceral hypersensitivity.

Lastly, the role of the microbiota in changes in medullary pain control after visceral stimulation (eg, rectal distension) has still not been demonstrated in humans.
 

Recent Guideline 

In its February 2023 Global Guideline “Probiotics and Prebiotics” for IBS, the World Gastroenterology Organization looked at the level of evidence for probiotics.

Three strains, as well as a combination of several strains, were supported by level 2 evidence, meaning at least two randomized studies with converging results. These are Bifidobacterium bifidum MIMBb75, which improves overall symptoms and quality of life; Lactobacillus plantarum 299v (DSM 9843), which acts on the severity of abdominal pain and bloating; and B infantis 35624 (new name: B longum 35624), which improves the overall assessment of IBS symptoms, as does the multistrain product containing L rhamnosus GG, L rhamnosus LC705, Propionibacterium freudenreichii ssp shermanii JS DSM 7067, and B animalis ssp lactis B012 DSM 15954.
 

Efficacy and Availability 

Probiotics belonging to the category of dietary supplements or medical devices are not required to provide evidence for a mechanism of action or even efficacy to be marketed. Thus, for most probiotics sold, there are no human or even animal studies available.

Dr. Sabaté proposed a choice of probiotics based on the literature and the presence of at least one randomized placebo-controlled trial conducted in patients with IBS showing positive results.

“Probiotic efficacy largely depends on the bacterial species, strain, and clinical situation treated. Only probiotics with demonstrated clinical efficacy in randomized placebo-controlled trials should be recommended,” he emphasized. The parameters that can be improved include symptom severity, quality of life, abdominal pain, and bloating.
 

Effective Probiotics 

B longum 35624, which was developed with researchers from University College Cork in Ireland, is probably the most studied in animals and humans. Research has encompassed the mechanistic, clinical, and safety aspects of the probiotic. It has shown good results on the IBS-Symptom Severity Score (SSS), quality of life, abdominal pain, bowel disturbances, and bloating. The treatment duration in studies is 4-8 weeks.

L plantarum 299v (DSM 9843) affects the frequency of abdominal pain and pain score. The treatment duration in studies is 4 weeks.

The multistrain product that includes L plantarum CECT 7484/L plantarum CECT 7485/ Pediococcus acidilactici CECT 7483 allows for an improvement in quality of life and anxiety related to digestive symptoms. No positive effect has been described on digestive symptoms, especially diarrhea. The treatment duration is 6 weeks.

B bifidum MIMBb75 (both normal and heat-inactivated forms) is beneficial for pain, the composite IBS-SSS score, and quality of life. The treatment duration is 4-8 weeks.

“Except for the multistrain combination, which is more suited to patients with diarrhea-predominant IBS, the other three probiotics can be prescribed regardless of the IBS subtype,” said Dr. Sabaté. “Treatment durations are typically 4 weeks, but it is possible to continue up to 8 weeks, which is the maximum duration of these studies. In practice, there are no tolerance issues with probiotics prescribed for IBS based on the literature. These should be tested under the conditions and for the duration of the published studies and should only be continued if there is individual benefit on symptoms or quality of life.”

Note that microbiota analyses conducted for individual purposes are of no help in choosing probiotics.
 

Mechanisms of Action 

In a murine model, but not in humans, some strains, especially L acidophilus NCFM, have shown an antinociceptive effect by inducing opioid and cannabinoid receptors.

Only in animals to date, L farciminis and B lactis CNCM I-2494 have shown prevention of induced hypersensitivity (ie, inhibition of the cytoskeleton contraction of colon epithelial cells and subsequent opening of tight junctions).

B infantis 35624 has an anti-inflammatory action by modifying the IL-10 and IL-12 cytokine ratio in animals and humans. It has an immunomodulatory action by increasing dendritic cells in the mucosa and decreasing Th1 and Th7 helper T cells.

B infantis 35624 and L farciminis are two strains that decrease visceral sensitivity in mice.

Escherichia coli Nissle 1917 acts on lipopeptide production with an antinociceptive effect, as observed in mice, by decreasing visceral sensitivity through calcium nociceptor flux blockade (action on GABA type B receptor).

Acting on dysbiosis by modifying fecal microbiota during probiotic intake is possible but depends on the probiotics, like B infantis 35624. In humans, B longum NCC 3001 could modify brain activations.

Dr. Sabaté disclosed financial relationships with Mayoly Spindler, Kyowa Kirin, Tillotts, Servier, Norgine, Biocodex, Merck, Viatris, Abivax, and Inventiva.

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

PARIS — Irritable bowel syndrome (IBS) is a common brain-gut axis disorder, and patients are often dissatisfied with conventional treatments.

The role of the microbiota in IBS is now well established, and patients frequently take probiotics on their own initiative or on the advice of a physician or pharmacist. However, not all probiotics have equal efficacy, so which ones should be recommended?

Jean-Marc Sabaté, MD, PhD, a gastroenterologist at Avicenne Hospital in Bobigny, France, shared insights about probiotics at the Francophone Days of Hepatology, Gastroenterology, and Digestive Oncology.

IBS, according to the Rome IV symptom-based classification, is a “disorder of brain-gut axis interactions” with a prevalence of about 4% in the adult population. In France, during an average care pathway of about 8 years, patients try an average of five therapeutic strategies (and as many as 11), including antispasmodics (85%), diets (78%), and probiotics. In addition, 66.4% of patients had either taken or were taking probiotics at the time of a recent survey.

While the 2022 recommendations from the American College of Gastroenterology on the diagnosis and management of IBS do not support the use of probiotics for overall symptom relief — a recommendation for which they cite a low level of evidence — “there is nevertheless a rationale for prescribing probiotics in IBS due to the significant role of the microbiota (or dysbiosis) in this condition,” said Dr. Sabaté.
 

Microbiota in IBS 

Evidence indicating that antibiotics exacerbate IBS symptoms and revealing chronic bacterial overgrowth in the small intestine of patients with IBS supports the role of the microbiota. Studies using a molecular approach (16s rRNA) have settled the debate, confirming differences in the intestinal flora between patients with IBS and healthy subjects. Data also indicate differences in flora between patient subtypes, such as an increased Firmicutes to Bacteroidetes ratio. However, one subgroup, which can represent as much as a third of patients, seems to harbor a “normal” microbiota.