In patients with colorectal cancer bearing the KRAS G12C mutation, a combination of the Kirsten rat sarcoma viral oncogene homologue (KRAS) G12C inhibitor sotorasib and the epidermal growth factor receptor inhibitor panitumumab led to an improvement in quality of life (QoL) measures compared with standard therapy.

Dominik Modest, MD, presented these new results of the phase 3 CodeBreaK 300 trial at the 2024 ASCO Gastrointestinal Cancers Symposium.

The KRAS G12C mutation occurs in 3%-4% of metastatic colorectal cancer cases, according to Dr. Modest and the other authors of a paper published in the New England Journal of Medicine describing the primary outcome of the trial. The study included 160 patients who were randomized to once daily sotorasib (960 mg) plus panitumumab (Soto960), once daily sotorasib (240 mg) plus panitumumab (Soto240), or investigator’s choice of trifluridine–tipiracil or regorafenib.

The December 2023 paper described improvements in median progression-free survival, progression or death, and objective response (OR). The authors described statistically significant improvements in disease progression or death in the Soto960 group (hazard ratio [HR], 0.49; P = .006) and the Soto240 group (HR, 0.58; P = .03). The objective response rate was highest in the Soto960 group (26.4%; 95% CI, 15.3%-40.3%), followed by the Soto240 group (5.7%; 95% CI, 1.2%-15.7%), and the control group (0%; 95% CI, 0.0%-6.6%). Grade 3 or higher treatment-related adverse events were generally similar at 35.8% (Soto960), 30.2% (Soto240), and 43.1% (control) in each group. The most common adverse events associated with sotorasib-panitumumab were skin-related toxicity and hypomagnesemia.

The new analysis showed that both doses of sotorasib also improved patient-reported outcomes from baseline to week 8, Dr. Modest, professor of medicine at Charité University of Medicine in Berlin, said at the meeting.

Compared with the chemotherapy group, there were statistically significant differences in least square mean change from baseline to week 8 for: pain at its worst in the Soto240 group (Brief Pain Inventory [BPI], –1.18; 95% CI, –2.05 to –0.32) and the Soto960 group (BPI, –1.49; 95% CI, –2.36 to –0.61); and physical functioning, as measured by the European Organisation for Research and Treatment of Cancer Core 30-item Quality of Life questionnaire, in the Soto240 (7.95; 95% CI, 2.39-13.51) and Soto960 (6.73; 95% CI, 1.05-12.41) groups. Nearly all other measures trended toward favoring the sotorasib/panitumumab groups, but did not reach statistical significance. A similar pattern was seen in time to deterioration measures. Among adverse events, diarrhea trended toward being more frequent in the intervention arms.

At week 9, 63% of patients in Soto960 and 84% in Soto240 reported improvement in the Patient Global Impression of Change score (PGI-C), versus 37% in the chemotherapy arm. At week 17, the percentages were 77%, 59%, and 21%, respectively.

“The clinical benefits and the better quality of life outcomes associated with sotorasib at the high dose of 960 milligrams plus panitumumab establishes this combination as a potential new standard [therapy] for patients with chemorefractory KRAS G12C mutant colorectal cancer, and I think it’s quite reassuring that even if you compare two active drugs versus one active drug, this does not necessarily translate into impaired quality of life assessments by the patients,” Dr. Modest said during his presentation.

CodeBreaK 300 may point the way to other dual therapies involving kinase inhibitors, according to Rona Yaeger, MD, who wrote an accompanying editorial to the NEJM paper. Dr. Yaeger noted that clinical and preclinical studies had shown that targeted oncogenes like KRAS G12C and BRAF V600E alone would be insufficient in colorectal cancer.

When combined with KRAS G12C inhibitors, EGFR inhibitors prevent EGFR from participating in negative feedback loops that can otherwise lead to drug resistance. “Whether targeting [receptor tyrosine kinases like EGFR] in epithelial tumors other than those associated with colorectal cancers would improve the incidence of response to KRAS G12C inhibitors remains unknown,” wrote Dr. Yaeger, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York. There is an ongoing clinical trial evaluating KRAS G12C inhibitors combined with EGFR antibodies in both lung and pancreatic cancer.

She noted that colorectal tumors have high levels of receptor tyrosine kinases, and argued that this will require higher doses of KRAS G12C inhibitors or novel drugs with higher activity. This is supported by the higher frequency of response and longer PFS at the higher dose in CodeBreaK 300, but could present a challenge: “Lowering the drug dose to manage toxic effects may limit the efficacy of the drug against some cancers,” she wrote.

Dr. Yaeger highlighted the KRYSTAL-10 phase 3 randomized trial, which is assessing the KRAS G12C inhibitor adagrasib in combination with the EGFR antibody cetuximab versus chemotherapy in advanced solid tumors with the KRAS G12C mutation.

“The CodeBreaK 300 trial is an exciting first step for targeting KRAS in colorectal cancer,” Dr. Yaeger wrote.

Dr. Modest has financial relationships with Amgen, AstraZeneca/MedImmune, Bristol-Myers Squibb, Incyte, Lily, Merck Serono, Merck Sharp & Dohme, Onkowissen, Pierre Fabre, Roche, and SERVIER. Dr. Yaeger has financial relationships with Amgen, Boehringer Ingelheim, Daiichi Sankyo, Mirati, Pfizer, and Zai Lab.

In patients with colorectal cancer bearing the KRAS G12C mutation, a combination of the Kirsten rat sarcoma viral oncogene homologue (KRAS) G12C inhibitor sotorasib and the epidermal growth factor receptor inhibitor panitumumab led to an improvement in quality of life (QoL) measures compared with standard therapy.

Dominik Modest, MD, presented these new results of the phase 3 CodeBreaK 300 trial at the 2024 ASCO Gastrointestinal Cancers Symposium.

The KRAS G12C mutation occurs in 3%-4% of metastatic colorectal cancer cases, according to Dr. Modest and the other authors of a paper published in the New England Journal of Medicine describing the primary outcome of the trial. The study included 160 patients who were randomized to once daily sotorasib (960 mg) plus panitumumab (Soto960), once daily sotorasib (240 mg) plus panitumumab (Soto240), or investigator’s choice of trifluridine–tipiracil or regorafenib.

The December 2023 paper described improvements in median progression-free survival, progression or death, and objective response (OR). The authors described statistically significant improvements in disease progression or death in the Soto960 group (hazard ratio [HR], 0.49; P = .006) and the Soto240 group (HR, 0.58; P = .03). The objective response rate was highest in the Soto960 group (26.4%; 95% CI, 15.3%-40.3%), followed by the Soto240 group (5.7%; 95% CI, 1.2%-15.7%), and the control group (0%; 95% CI, 0.0%-6.6%). Grade 3 or higher treatment-related adverse events were generally similar at 35.8% (Soto960), 30.2% (Soto240), and 43.1% (control) in each group. The most common adverse events associated with sotorasib-panitumumab were skin-related toxicity and hypomagnesemia.

The new analysis showed that both doses of sotorasib also improved patient-reported outcomes from baseline to week 8, Dr. Modest, professor of medicine at Charité University of Medicine in Berlin, said at the meeting.

Compared with the chemotherapy group, there were statistically significant differences in least square mean change from baseline to week 8 for: pain at its worst in the Soto240 group (Brief Pain Inventory [BPI], –1.18; 95% CI, –2.05 to –0.32) and the Soto960 group (BPI, –1.49; 95% CI, –2.36 to –0.61); and physical functioning, as measured by the European Organisation for Research and Treatment of Cancer Core 30-item Quality of Life questionnaire, in the Soto240 (7.95; 95% CI, 2.39-13.51) and Soto960 (6.73; 95% CI, 1.05-12.41) groups. Nearly all other measures trended toward favoring the sotorasib/panitumumab groups, but did not reach statistical significance. A similar pattern was seen in time to deterioration measures. Among adverse events, diarrhea trended toward being more frequent in the intervention arms.

At week 9, 63% of patients in Soto960 and 84% in Soto240 reported improvement in the Patient Global Impression of Change score (PGI-C), versus 37% in the chemotherapy arm. At week 17, the percentages were 77%, 59%, and 21%, respectively.

“The clinical benefits and the better quality of life outcomes associated with sotorasib at the high dose of 960 milligrams plus panitumumab establishes this combination as a potential new standard [therapy] for patients with chemorefractory KRAS G12C mutant colorectal cancer, and I think it’s quite reassuring that even if you compare two active drugs versus one active drug, this does not necessarily translate into impaired quality of life assessments by the patients,” Dr. Modest said during his presentation.

CodeBreaK 300 may point the way to other dual therapies involving kinase inhibitors, according to Rona Yaeger, MD, who wrote an accompanying editorial to the NEJM paper. Dr. Yaeger noted that clinical and preclinical studies had shown that targeted oncogenes like KRAS G12C and BRAF V600E alone would be insufficient in colorectal cancer.

When combined with KRAS G12C inhibitors, EGFR inhibitors prevent EGFR from participating in negative feedback loops that can otherwise lead to drug resistance. “Whether targeting [receptor tyrosine kinases like EGFR] in epithelial tumors other than those associated with colorectal cancers would improve the incidence of response to KRAS G12C inhibitors remains unknown,” wrote Dr. Yaeger, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York. There is an ongoing clinical trial evaluating KRAS G12C inhibitors combined with EGFR antibodies in both lung and pancreatic cancer.

She noted that colorectal tumors have high levels of receptor tyrosine kinases, and argued that this will require higher doses of KRAS G12C inhibitors or novel drugs with higher activity. This is supported by the higher frequency of response and longer PFS at the higher dose in CodeBreaK 300, but could present a challenge: “Lowering the drug dose to manage toxic effects may limit the efficacy of the drug against some cancers,” she wrote.

Dr. Yaeger highlighted the KRYSTAL-10 phase 3 randomized trial, which is assessing the KRAS G12C inhibitor adagrasib in combination with the EGFR antibody cetuximab versus chemotherapy in advanced solid tumors with the KRAS G12C mutation.

“The CodeBreaK 300 trial is an exciting first step for targeting KRAS in colorectal cancer,” Dr. Yaeger wrote.

Dr. Modest has financial relationships with Amgen, AstraZeneca/MedImmune, Bristol-Myers Squibb, Incyte, Lily, Merck Serono, Merck Sharp & Dohme, Onkowissen, Pierre Fabre, Roche, and SERVIER. Dr. Yaeger has financial relationships with Amgen, Boehringer Ingelheim, Daiichi Sankyo, Mirati, Pfizer, and Zai Lab.

In patients with colorectal cancer bearing the KRAS G12C mutation, a combination of the Kirsten rat sarcoma viral oncogene homologue (KRAS) G12C inhibitor sotorasib and the epidermal growth factor receptor inhibitor panitumumab led to an improvement in quality of life (QoL) measures compared with standard therapy.

Dominik Modest, MD, presented these new results of the phase 3 CodeBreaK 300 trial at the 2024 ASCO Gastrointestinal Cancers Symposium.

The KRAS G12C mutation occurs in 3%-4% of metastatic colorectal cancer cases, according to Dr. Modest and the other authors of a paper published in the New England Journal of Medicine describing the primary outcome of the trial. The study included 160 patients who were randomized to once daily sotorasib (960 mg) plus panitumumab (Soto960), once daily sotorasib (240 mg) plus panitumumab (Soto240), or investigator’s choice of trifluridine–tipiracil or regorafenib.

The December 2023 paper described improvements in median progression-free survival, progression or death, and objective response (OR). The authors described statistically significant improvements in disease progression or death in the Soto960 group (hazard ratio [HR], 0.49; P = .006) and the Soto240 group (HR, 0.58; P = .03). The objective response rate was highest in the Soto960 group (26.4%; 95% CI, 15.3%-40.3%), followed by the Soto240 group (5.7%; 95% CI, 1.2%-15.7%), and the control group (0%; 95% CI, 0.0%-6.6%). Grade 3 or higher treatment-related adverse events were generally similar at 35.8% (Soto960), 30.2% (Soto240), and 43.1% (control) in each group. The most common adverse events associated with sotorasib-panitumumab were skin-related toxicity and hypomagnesemia.

The new analysis showed that both doses of sotorasib also improved patient-reported outcomes from baseline to week 8, Dr. Modest, professor of medicine at Charité University of Medicine in Berlin, said at the meeting.

Compared with the chemotherapy group, there were statistically significant differences in least square mean change from baseline to week 8 for: pain at its worst in the Soto240 group (Brief Pain Inventory [BPI], –1.18; 95% CI, –2.05 to –0.32) and the Soto960 group (BPI, –1.49; 95% CI, –2.36 to –0.61); and physical functioning, as measured by the European Organisation for Research and Treatment of Cancer Core 30-item Quality of Life questionnaire, in the Soto240 (7.95; 95% CI, 2.39-13.51) and Soto960 (6.73; 95% CI, 1.05-12.41) groups. Nearly all other measures trended toward favoring the sotorasib/panitumumab groups, but did not reach statistical significance. A similar pattern was seen in time to deterioration measures. Among adverse events, diarrhea trended toward being more frequent in the intervention arms.

At week 9, 63% of patients in Soto960 and 84% in Soto240 reported improvement in the Patient Global Impression of Change score (PGI-C), versus 37% in the chemotherapy arm. At week 17, the percentages were 77%, 59%, and 21%, respectively.

“The clinical benefits and the better quality of life outcomes associated with sotorasib at the high dose of 960 milligrams plus panitumumab establishes this combination as a potential new standard [therapy] for patients with chemorefractory KRAS G12C mutant colorectal cancer, and I think it’s quite reassuring that even if you compare two active drugs versus one active drug, this does not necessarily translate into impaired quality of life assessments by the patients,” Dr. Modest said during his presentation.

CodeBreaK 300 may point the way to other dual therapies involving kinase inhibitors, according to Rona Yaeger, MD, who wrote an accompanying editorial to the NEJM paper. Dr. Yaeger noted that clinical and preclinical studies had shown that targeted oncogenes like KRAS G12C and BRAF V600E alone would be insufficient in colorectal cancer.

When combined with KRAS G12C inhibitors, EGFR inhibitors prevent EGFR from participating in negative feedback loops that can otherwise lead to drug resistance. “Whether targeting [receptor tyrosine kinases like EGFR] in epithelial tumors other than those associated with colorectal cancers would improve the incidence of response to KRAS G12C inhibitors remains unknown,” wrote Dr. Yaeger, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York. There is an ongoing clinical trial evaluating KRAS G12C inhibitors combined with EGFR antibodies in both lung and pancreatic cancer.

She noted that colorectal tumors have high levels of receptor tyrosine kinases, and argued that this will require higher doses of KRAS G12C inhibitors or novel drugs with higher activity. This is supported by the higher frequency of response and longer PFS at the higher dose in CodeBreaK 300, but could present a challenge: “Lowering the drug dose to manage toxic effects may limit the efficacy of the drug against some cancers,” she wrote.

Dr. Yaeger highlighted the KRYSTAL-10 phase 3 randomized trial, which is assessing the KRAS G12C inhibitor adagrasib in combination with the EGFR antibody cetuximab versus chemotherapy in advanced solid tumors with the KRAS G12C mutation.

“The CodeBreaK 300 trial is an exciting first step for targeting KRAS in colorectal cancer,” Dr. Yaeger wrote.

Dr. Modest has financial relationships with Amgen, AstraZeneca/MedImmune, Bristol-Myers Squibb, Incyte, Lily, Merck Serono, Merck Sharp & Dohme, Onkowissen, Pierre Fabre, Roche, and SERVIER. Dr. Yaeger has financial relationships with Amgen, Boehringer Ingelheim, Daiichi Sankyo, Mirati, Pfizer, and Zai Lab.

SAN FRANCISCO — The immunotherapy combination nivolumab plus ipilimumab rivals chemotherapy as well as pembrolizumab monotherapy in the first-line treatment of metastatic colorectal cancer (CRC), new data indicated.

Findings from the CHECKMATE-8HW trial revealed that first-line nivolumab plus ipilimumab led to a significant improvement in progression-free survival (PFS) compared with chemotherapy among patients with metastatic CRC.

More specifically, at 2 years, PFS was 72% among patients with microsatellite instability–high (MSI-H) or deficient mismatch repair (dMMR) randomized to the immunotherapy combination compared with just 14% among those randomized to chemotherapy with or without targeted therapy.

The magnitude of the benefit was unexpected, especially considering patients received only four cycles of the immunotherapy combination in the trial. “It’s a good surprise,” said lead investigator Thierry Andre, MD, who presented the findings at the 2024 ASCO Gastrointestinal Cancers Symposium.

The findings indicate that nivolumab plus ipilimumab should really be “a new standard,” said Andre, a medical oncologist at Sorbonne University, Paris.

The combination as well as nivolumab alone has received US Food and Drug Administration’s (FDA’s) approval to treat MSI-H or dMMR metastatic CRC in the second line, following chemotherapy failure.

The FDA also approved pembrolizumab as first-line monotherapy for this CRC indication in 2020. The KEYNOTE-177 trial, which led to the pembrolizumab approval, reported a 2-year PFS of 48% among patients receiving the monotherapy. Andre was the lead investigator on KEYNOTE-177.

To compare PFS results for pembrolizumab and nivolumab alone, the CHECKMATE-8HW trial included a nivolumab monotherapy arm, but these results are pending, as are the overall survival findings, Andre said.

Overall, CHECKMATE-8HW must be taken into context with KEYNOTE-177, and “we need a little bit more trial data” for oncologists to decide between the two options, said Neil Newman, MD, a radiation oncologist at the University of Texas Health Science Center, San Antonio, Texas, who co-moderated Dr. Andre’s presentation.

Andre noted, however, that if the nivolumab and pembrolizumab monotherapy results are similar, most patients will likely receive the nivolumab/ipilimumab combination, given the improved PFS outcomes.

In CHECKMATE-8HW, patients were randomized to three regimens. The 202 patients in the combination arm received nivolumab 240 mg plus ipilimumab 1 mg/kg every 3 weeks for four doses, followed by nivolumab 480 mg every 4 weeks. The 101 patients in the chemotherapy group received investigator’s choice of mFOLFOX6 or FOLFIRI with or without bevacizumab or cetuximab. And the nivolumab monotherapy arm received nivolumab 240 mg every 2 weeks for six doses, followed by nivolumab 480 mg every 4 weeks.

Treatment continued until disease progression or unacceptable toxicity over a maximum of 2 years. The median duration of treatment was 13.5 months in the nivolumab/ipilimumab arm vs 4 months in the chemotherapy arm.

PFS curves started to separate between nivolumab/ipilimumab and chemotherapy at about 3 months.

Patients receiving the combination exhibited a 79% reduction in the risk for disease progression or death at 2 years (72% vs 14%; hazard ratio, 0.21; P < .0001). The median PFS was not reached with the combination vs 5.9 months with chemotherapy. The PFS benefit of nivolumab/ipilimumab held across various subgroups, including patients with KRAS or NRAS mutations and baseline lung, liver, or peritoneal metastases.

The incidence of grade 3/4 treatment-related adverse events was 23% with nivolumab/ipilimumab vs 48% in the chemotherapy arm. The most common grade 3/4 events with nivolumab/ipilimumab were diarrhea/colitis (5%), adrenal insufficiency (4%), hepatitis (3%), and inflammation of the pituitary gland (3%).

Two treatment-related deaths occurred in the combination arm — one from pneumonitis and the second from myocarditis — and none occurred in the chemotherapy arm.

Mark A. Lewis, MD, a gastrointestinal oncologist at Intermountain Healthcare in Murray, Utah, was impressed with the CHECKMATE-8HW findings. The data are shaping up to make nivolumab/ipilimumab “the next great step in metastatic CRC management beyond KEYNOTE-177,” Dr. Lewis said.

Dr. Lewis noted that the new trial makes it “imperative” to standardize testing for immunotherapy candidacy upfront. “It is completely unacceptable for any patient with metastatic CRC to not have their MMR/MSI status assessed,” he said. “Much as no oncologist would dare treat breast cancer without testing ER, PR, HER2 status, biomarkers cannot be a later-line afterthought in stage IV CRC.”

Drugmaker Bristol-Myers Squibb told this news organization that the company will be seeking a first-line indication for the combination, and anticipates approval early next year or possibly sooner, if the FDA grants a priority review.

The work was funded by Bristol-Myers Squibb and the ONO Pharmaceutical Company. Dr. Andre had numerous industry ties, including being a consultant for both BMS and Merck. He also reported honoraria from both companies. Dr. Newman and Dr. Lewis didn’t have any disclosures.

A version of this article appeared on Medscape.com.

SAN FRANCISCO — The immunotherapy combination nivolumab plus ipilimumab rivals chemotherapy as well as pembrolizumab monotherapy in the first-line treatment of metastatic colorectal cancer (CRC), new data indicated.

Findings from the CHECKMATE-8HW trial revealed that first-line nivolumab plus ipilimumab led to a significant improvement in progression-free survival (PFS) compared with chemotherapy among patients with metastatic CRC.

More specifically, at 2 years, PFS was 72% among patients with microsatellite instability–high (MSI-H) or deficient mismatch repair (dMMR) randomized to the immunotherapy combination compared with just 14% among those randomized to chemotherapy with or without targeted therapy.

The magnitude of the benefit was unexpected, especially considering patients received only four cycles of the immunotherapy combination in the trial. “It’s a good surprise,” said lead investigator Thierry Andre, MD, who presented the findings at the 2024 ASCO Gastrointestinal Cancers Symposium.

The findings indicate that nivolumab plus ipilimumab should really be “a new standard,” said Andre, a medical oncologist at Sorbonne University, Paris.

The combination as well as nivolumab alone has received US Food and Drug Administration’s (FDA’s) approval to treat MSI-H or dMMR metastatic CRC in the second line, following chemotherapy failure.

The FDA also approved pembrolizumab as first-line monotherapy for this CRC indication in 2020. The KEYNOTE-177 trial, which led to the pembrolizumab approval, reported a 2-year PFS of 48% among patients receiving the monotherapy. Andre was the lead investigator on KEYNOTE-177.

To compare PFS results for pembrolizumab and nivolumab alone, the CHECKMATE-8HW trial included a nivolumab monotherapy arm, but these results are pending, as are the overall survival findings, Andre said.

Overall, CHECKMATE-8HW must be taken into context with KEYNOTE-177, and “we need a little bit more trial data” for oncologists to decide between the two options, said Neil Newman, MD, a radiation oncologist at the University of Texas Health Science Center, San Antonio, Texas, who co-moderated Dr. Andre’s presentation.

Andre noted, however, that if the nivolumab and pembrolizumab monotherapy results are similar, most patients will likely receive the nivolumab/ipilimumab combination, given the improved PFS outcomes.

In CHECKMATE-8HW, patients were randomized to three regimens. The 202 patients in the combination arm received nivolumab 240 mg plus ipilimumab 1 mg/kg every 3 weeks for four doses, followed by nivolumab 480 mg every 4 weeks. The 101 patients in the chemotherapy group received investigator’s choice of mFOLFOX6 or FOLFIRI with or without bevacizumab or cetuximab. And the nivolumab monotherapy arm received nivolumab 240 mg every 2 weeks for six doses, followed by nivolumab 480 mg every 4 weeks.

Treatment continued until disease progression or unacceptable toxicity over a maximum of 2 years. The median duration of treatment was 13.5 months in the nivolumab/ipilimumab arm vs 4 months in the chemotherapy arm.

PFS curves started to separate between nivolumab/ipilimumab and chemotherapy at about 3 months.

Patients receiving the combination exhibited a 79% reduction in the risk for disease progression or death at 2 years (72% vs 14%; hazard ratio, 0.21; P < .0001). The median PFS was not reached with the combination vs 5.9 months with chemotherapy. The PFS benefit of nivolumab/ipilimumab held across various subgroups, including patients with KRAS or NRAS mutations and baseline lung, liver, or peritoneal metastases.

The incidence of grade 3/4 treatment-related adverse events was 23% with nivolumab/ipilimumab vs 48% in the chemotherapy arm. The most common grade 3/4 events with nivolumab/ipilimumab were diarrhea/colitis (5%), adrenal insufficiency (4%), hepatitis (3%), and inflammation of the pituitary gland (3%).

Two treatment-related deaths occurred in the combination arm — one from pneumonitis and the second from myocarditis — and none occurred in the chemotherapy arm.

Mark A. Lewis, MD, a gastrointestinal oncologist at Intermountain Healthcare in Murray, Utah, was impressed with the CHECKMATE-8HW findings. The data are shaping up to make nivolumab/ipilimumab “the next great step in metastatic CRC management beyond KEYNOTE-177,” Dr. Lewis said.

Dr. Lewis noted that the new trial makes it “imperative” to standardize testing for immunotherapy candidacy upfront. “It is completely unacceptable for any patient with metastatic CRC to not have their MMR/MSI status assessed,” he said. “Much as no oncologist would dare treat breast cancer without testing ER, PR, HER2 status, biomarkers cannot be a later-line afterthought in stage IV CRC.”

Drugmaker Bristol-Myers Squibb told this news organization that the company will be seeking a first-line indication for the combination, and anticipates approval early next year or possibly sooner, if the FDA grants a priority review.

The work was funded by Bristol-Myers Squibb and the ONO Pharmaceutical Company. Dr. Andre had numerous industry ties, including being a consultant for both BMS and Merck. He also reported honoraria from both companies. Dr. Newman and Dr. Lewis didn’t have any disclosures.

A version of this article appeared on Medscape.com.

SAN FRANCISCO — The immunotherapy combination nivolumab plus ipilimumab rivals chemotherapy as well as pembrolizumab monotherapy in the first-line treatment of metastatic colorectal cancer (CRC), new data indicated.

Findings from the CHECKMATE-8HW trial revealed that first-line nivolumab plus ipilimumab led to a significant improvement in progression-free survival (PFS) compared with chemotherapy among patients with metastatic CRC.

More specifically, at 2 years, PFS was 72% among patients with microsatellite instability–high (MSI-H) or deficient mismatch repair (dMMR) randomized to the immunotherapy combination compared with just 14% among those randomized to chemotherapy with or without targeted therapy.

The magnitude of the benefit was unexpected, especially considering patients received only four cycles of the immunotherapy combination in the trial. “It’s a good surprise,” said lead investigator Thierry Andre, MD, who presented the findings at the 2024 ASCO Gastrointestinal Cancers Symposium.

The findings indicate that nivolumab plus ipilimumab should really be “a new standard,” said Andre, a medical oncologist at Sorbonne University, Paris.

The combination as well as nivolumab alone has received US Food and Drug Administration’s (FDA’s) approval to treat MSI-H or dMMR metastatic CRC in the second line, following chemotherapy failure.

The FDA also approved pembrolizumab as first-line monotherapy for this CRC indication in 2020. The KEYNOTE-177 trial, which led to the pembrolizumab approval, reported a 2-year PFS of 48% among patients receiving the monotherapy. Andre was the lead investigator on KEYNOTE-177.

To compare PFS results for pembrolizumab and nivolumab alone, the CHECKMATE-8HW trial included a nivolumab monotherapy arm, but these results are pending, as are the overall survival findings, Andre said.

Overall, CHECKMATE-8HW must be taken into context with KEYNOTE-177, and “we need a little bit more trial data” for oncologists to decide between the two options, said Neil Newman, MD, a radiation oncologist at the University of Texas Health Science Center, San Antonio, Texas, who co-moderated Dr. Andre’s presentation.

Andre noted, however, that if the nivolumab and pembrolizumab monotherapy results are similar, most patients will likely receive the nivolumab/ipilimumab combination, given the improved PFS outcomes.

In CHECKMATE-8HW, patients were randomized to three regimens. The 202 patients in the combination arm received nivolumab 240 mg plus ipilimumab 1 mg/kg every 3 weeks for four doses, followed by nivolumab 480 mg every 4 weeks. The 101 patients in the chemotherapy group received investigator’s choice of mFOLFOX6 or FOLFIRI with or without bevacizumab or cetuximab. And the nivolumab monotherapy arm received nivolumab 240 mg every 2 weeks for six doses, followed by nivolumab 480 mg every 4 weeks.

Treatment continued until disease progression or unacceptable toxicity over a maximum of 2 years. The median duration of treatment was 13.5 months in the nivolumab/ipilimumab arm vs 4 months in the chemotherapy arm.

PFS curves started to separate between nivolumab/ipilimumab and chemotherapy at about 3 months.

Patients receiving the combination exhibited a 79% reduction in the risk for disease progression or death at 2 years (72% vs 14%; hazard ratio, 0.21; P < .0001). The median PFS was not reached with the combination vs 5.9 months with chemotherapy. The PFS benefit of nivolumab/ipilimumab held across various subgroups, including patients with KRAS or NRAS mutations and baseline lung, liver, or peritoneal metastases.

The incidence of grade 3/4 treatment-related adverse events was 23% with nivolumab/ipilimumab vs 48% in the chemotherapy arm. The most common grade 3/4 events with nivolumab/ipilimumab were diarrhea/colitis (5%), adrenal insufficiency (4%), hepatitis (3%), and inflammation of the pituitary gland (3%).

Two treatment-related deaths occurred in the combination arm — one from pneumonitis and the second from myocarditis — and none occurred in the chemotherapy arm.

Mark A. Lewis, MD, a gastrointestinal oncologist at Intermountain Healthcare in Murray, Utah, was impressed with the CHECKMATE-8HW findings. The data are shaping up to make nivolumab/ipilimumab “the next great step in metastatic CRC management beyond KEYNOTE-177,” Dr. Lewis said.

Dr. Lewis noted that the new trial makes it “imperative” to standardize testing for immunotherapy candidacy upfront. “It is completely unacceptable for any patient with metastatic CRC to not have their MMR/MSI status assessed,” he said. “Much as no oncologist would dare treat breast cancer without testing ER, PR, HER2 status, biomarkers cannot be a later-line afterthought in stage IV CRC.”

Drugmaker Bristol-Myers Squibb told this news organization that the company will be seeking a first-line indication for the combination, and anticipates approval early next year or possibly sooner, if the FDA grants a priority review.

The work was funded by Bristol-Myers Squibb and the ONO Pharmaceutical Company. Dr. Andre had numerous industry ties, including being a consultant for both BMS and Merck. He also reported honoraria from both companies. Dr. Newman and Dr. Lewis didn’t have any disclosures.

A version of this article appeared on Medscape.com.

In treating young patients with T-cell acute lymphoblastic leukemia (T-ALL), prophylactic central nervous system (CNS)-directed cranial radiotherapy (CRT) can safely be omitted even for those with the greatest CNS involvement,i.e., CNS-3 disease. Doing so spares patients the treatment’s toxic effects without heightening the risk of relapse.

“Overall, comparison of these cohorts provides a strong indication that CRT provides minimal benefit to patients with CNS-3 disease at diagnosis,” first author Ajay Vora, MD, a consultant hematologist with Great Ormond Street Hospital, in London, and his colleagues report in a research letter published recently in Blood Advances.

“Given the high rates of neurocognitive impairment and secondary CNS malignancies, we believe strong consideration should be given to eliminating CRT in first-line treatment for all patients with T-ALL,” they wrote.

More aggressive than B-cell ALL, T-ALL is characterized by a higher likelihood of infiltration of the CNS at diagnosis, which increases the risk of relapse after treatment.

Until recently, treatment of T-ALL long entailed CNS-directed therapy using prophylactic CRT. Now, however, due to the risks of significant toxicity, including neurocognitive defects and secondary cancers, CRT is usually either omitted or limited to key subgroups, such as those with CNS-3 disease. As an alternative, intrathecal chemotherapy is used, the authors explain.

In a 2023 study evaluating the consecutive Children’s Oncology Group (COG) AALL0434 and AALL1231 phase 3 trials of 2,164 patients with T-ALL, patients with CNS-3 at diagnosis were found to have worse outcomes, compared with CNS-1 and 2.

Importantly, the outcomes in both of those two trials were similar, despite the use of CRT in more than 90% of patients in the AALL0434 trial--but in only 10% of patients AALL1231 trial (mainly those with CNS-3 and at high-risk). These outcomes suggested that CRT can safely be eliminated for CNS-1 and 2 patients.

With CRT used in both trials among patients with CNS-3, conclusions about eliminating CRT among those patients could not be drawn. However, with other large groups (including the Dutch Childhood Oncology Group), eliminating CRT in the frontline treatment of all patients with T-ALL, including those with CNS-3, is what Dr. Vora and colleagues sought to further investigate.

For the current study, they evaluated outcomes in the UKALL2003 and UKALL2011 trials conducted by the UK National Cancer Research Institute, in which CRT was eliminated for all patients — including those with CNS-3 — and compared them with the COG AALL0434 and AALL1231 trials.

In the UK trials, involving 665 patients with T-ALL aged 1 to 24, treatment included a dexamethasone-based backbone chemotherapy consisting of a 4-drug induction, Berlin-Frankfurt-Münster (BFM) consolidation, interim maintenance, delayed intensification, and maintenance therapy, with the treatment stratified based on morphological early response and minimal residual disease at the end of induction.

While the UKALL2003 trial initially recommended CRT for patients with CNS-3, that practice ended in 2009, and CNS-directed therapy subsequently consisted of intrathecal methotrexate (MTX) at regular intervals throughout treatment. Additional weekly intrathecal MTX treatments were recommended throughout induction for patients with CNS-3.

In the UKALL2011 trial, the weekly intrathecal MTX treatments were recommended for patients with CNS-2, as well as CNS-3.

Overall, among those with CNS data available, 557 patients had CNS-1 (87.4%), 44 CNS-2 (6.9%), and 36 CNS-3 (5.7%).

For the outcomes of 4-year cumulative incidence of relapse (CIR), event-free survival (EFS) and overall survival (OS) in the combined cohort of the 2 UK trials, there were no significant differences between CNS-1, 2 or 3 groups.

Specifically, the mean rates of 4-year CIR in the CNS-1, 2, and 3 groups were 13.6%, 25.9% and 24.6%, respectively (P = .241); mean EFS rates were 82.9%, 74.1% and 77.8% (P = .623), and OS rates were 88.6%, 80.9% and 91.8%, (P = .453).

“Most importantly, outcomes are not significantly different for the patients with CNS-3, despite omission of CRT in the UK cohort,” the authors underscored.

Comparatively, in the cohort of the 2 COG trials, there were significant differences based on CNS status for 4-year CIR (P = .0002); EFS (P = .0004) and OS (P = .005).

The 4-year relapse rates among those with CNS-3 in the UK cohort were slightly higher compared with those in the COG cohort (24.6% UK vs 17.9%, COG). However, the difference did not translate to poorer long-term survival in the UK cohort (91.8% vs 82.7%, respectively).

Those findings are consistent with a previous meta-analysis that Dr. Vora and his colleagues conducted of more than 16,000 patients with mainly B-cell ALL, which showed that CRT reduced the risk of isolated and combined CNS relapse in patients with CNS-3. However, that risk had no impact on EFS and OS.

Of note, patients in the UK cohort with CNS-2 had worse outcomes compared with the COG group, with double the rate of relapse and lower EFS and OS. However, the authors speculate that factors including a lower proportion of patients with CNS-2 in the UK cohort and differences in methodologies may explain those different outcomes and may preclude their generalizability to other groups.

Overall, “these findings corroborate those of earlier studies that CRT has marginal, if any benefit, for any sub-group of ALL, especially as part of contemporary treatment,” Dr. Vora said in an interview.

In terms of therapies that do appear to make a difference in the treatment of CNS-3, Dr. Vora noted that the addition of nelarabine in the COG AALL0434 trial showed “remarkable benefit” in the CNS-3 group, with a 93.1% rate of disease-free survival in those patients versus 70.2% without nelarabine.

Importantly, those patients did also receive CRT. However, Dr. Vora and colleagues underscore that “the improvement is impressive and raises the question of whether nelarabine would have a similar beneficial effect in the absence of CRT.”

In an editorial published with the COG trials, Josep-Maria Ribera, MD, of the Josep Carreras Leukemia Research Institute, in Barcelona, Spain, agrees that “better approaches clearly are needed to treat CNS-3 T-ALL, especially if omission of CRT is a priority.”

Noting the improvements observed with nelarabine, as well as Capizzi escalating-dose methotrexate (C-MTX), and dexamethasone in reducing the risk of CNS relapse, he speculates that “it is possible that the additional use of C-MTX and induction dexamethasone could eliminate the need for CRT in these patients.”

The authors and Dr. Ribera had no disclosures to report.

In treating young patients with T-cell acute lymphoblastic leukemia (T-ALL), prophylactic central nervous system (CNS)-directed cranial radiotherapy (CRT) can safely be omitted even for those with the greatest CNS involvement,i.e., CNS-3 disease. Doing so spares patients the treatment’s toxic effects without heightening the risk of relapse.

“Overall, comparison of these cohorts provides a strong indication that CRT provides minimal benefit to patients with CNS-3 disease at diagnosis,” first author Ajay Vora, MD, a consultant hematologist with Great Ormond Street Hospital, in London, and his colleagues report in a research letter published recently in Blood Advances.

“Given the high rates of neurocognitive impairment and secondary CNS malignancies, we believe strong consideration should be given to eliminating CRT in first-line treatment for all patients with T-ALL,” they wrote.

More aggressive than B-cell ALL, T-ALL is characterized by a higher likelihood of infiltration of the CNS at diagnosis, which increases the risk of relapse after treatment.

Until recently, treatment of T-ALL long entailed CNS-directed therapy using prophylactic CRT. Now, however, due to the risks of significant toxicity, including neurocognitive defects and secondary cancers, CRT is usually either omitted or limited to key subgroups, such as those with CNS-3 disease. As an alternative, intrathecal chemotherapy is used, the authors explain.

In a 2023 study evaluating the consecutive Children’s Oncology Group (COG) AALL0434 and AALL1231 phase 3 trials of 2,164 patients with T-ALL, patients with CNS-3 at diagnosis were found to have worse outcomes, compared with CNS-1 and 2.

Importantly, the outcomes in both of those two trials were similar, despite the use of CRT in more than 90% of patients in the AALL0434 trial--but in only 10% of patients AALL1231 trial (mainly those with CNS-3 and at high-risk). These outcomes suggested that CRT can safely be eliminated for CNS-1 and 2 patients.

With CRT used in both trials among patients with CNS-3, conclusions about eliminating CRT among those patients could not be drawn. However, with other large groups (including the Dutch Childhood Oncology Group), eliminating CRT in the frontline treatment of all patients with T-ALL, including those with CNS-3, is what Dr. Vora and colleagues sought to further investigate.

For the current study, they evaluated outcomes in the UKALL2003 and UKALL2011 trials conducted by the UK National Cancer Research Institute, in which CRT was eliminated for all patients — including those with CNS-3 — and compared them with the COG AALL0434 and AALL1231 trials.

In the UK trials, involving 665 patients with T-ALL aged 1 to 24, treatment included a dexamethasone-based backbone chemotherapy consisting of a 4-drug induction, Berlin-Frankfurt-Münster (BFM) consolidation, interim maintenance, delayed intensification, and maintenance therapy, with the treatment stratified based on morphological early response and minimal residual disease at the end of induction.

While the UKALL2003 trial initially recommended CRT for patients with CNS-3, that practice ended in 2009, and CNS-directed therapy subsequently consisted of intrathecal methotrexate (MTX) at regular intervals throughout treatment. Additional weekly intrathecal MTX treatments were recommended throughout induction for patients with CNS-3.

In the UKALL2011 trial, the weekly intrathecal MTX treatments were recommended for patients with CNS-2, as well as CNS-3.

Overall, among those with CNS data available, 557 patients had CNS-1 (87.4%), 44 CNS-2 (6.9%), and 36 CNS-3 (5.7%).

For the outcomes of 4-year cumulative incidence of relapse (CIR), event-free survival (EFS) and overall survival (OS) in the combined cohort of the 2 UK trials, there were no significant differences between CNS-1, 2 or 3 groups.

Specifically, the mean rates of 4-year CIR in the CNS-1, 2, and 3 groups were 13.6%, 25.9% and 24.6%, respectively (P = .241); mean EFS rates were 82.9%, 74.1% and 77.8% (P = .623), and OS rates were 88.6%, 80.9% and 91.8%, (P = .453).

“Most importantly, outcomes are not significantly different for the patients with CNS-3, despite omission of CRT in the UK cohort,” the authors underscored.

Comparatively, in the cohort of the 2 COG trials, there were significant differences based on CNS status for 4-year CIR (P = .0002); EFS (P = .0004) and OS (P = .005).

The 4-year relapse rates among those with CNS-3 in the UK cohort were slightly higher compared with those in the COG cohort (24.6% UK vs 17.9%, COG). However, the difference did not translate to poorer long-term survival in the UK cohort (91.8% vs 82.7%, respectively).

Those findings are consistent with a previous meta-analysis that Dr. Vora and his colleagues conducted of more than 16,000 patients with mainly B-cell ALL, which showed that CRT reduced the risk of isolated and combined CNS relapse in patients with CNS-3. However, that risk had no impact on EFS and OS.

Of note, patients in the UK cohort with CNS-2 had worse outcomes compared with the COG group, with double the rate of relapse and lower EFS and OS. However, the authors speculate that factors including a lower proportion of patients with CNS-2 in the UK cohort and differences in methodologies may explain those different outcomes and may preclude their generalizability to other groups.

Overall, “these findings corroborate those of earlier studies that CRT has marginal, if any benefit, for any sub-group of ALL, especially as part of contemporary treatment,” Dr. Vora said in an interview.

In terms of therapies that do appear to make a difference in the treatment of CNS-3, Dr. Vora noted that the addition of nelarabine in the COG AALL0434 trial showed “remarkable benefit” in the CNS-3 group, with a 93.1% rate of disease-free survival in those patients versus 70.2% without nelarabine.

Importantly, those patients did also receive CRT. However, Dr. Vora and colleagues underscore that “the improvement is impressive and raises the question of whether nelarabine would have a similar beneficial effect in the absence of CRT.”

In an editorial published with the COG trials, Josep-Maria Ribera, MD, of the Josep Carreras Leukemia Research Institute, in Barcelona, Spain, agrees that “better approaches clearly are needed to treat CNS-3 T-ALL, especially if omission of CRT is a priority.”

Noting the improvements observed with nelarabine, as well as Capizzi escalating-dose methotrexate (C-MTX), and dexamethasone in reducing the risk of CNS relapse, he speculates that “it is possible that the additional use of C-MTX and induction dexamethasone could eliminate the need for CRT in these patients.”

The authors and Dr. Ribera had no disclosures to report.

In treating young patients with T-cell acute lymphoblastic leukemia (T-ALL), prophylactic central nervous system (CNS)-directed cranial radiotherapy (CRT) can safely be omitted even for those with the greatest CNS involvement,i.e., CNS-3 disease. Doing so spares patients the treatment’s toxic effects without heightening the risk of relapse.

“Overall, comparison of these cohorts provides a strong indication that CRT provides minimal benefit to patients with CNS-3 disease at diagnosis,” first author Ajay Vora, MD, a consultant hematologist with Great Ormond Street Hospital, in London, and his colleagues report in a research letter published recently in Blood Advances.

“Given the high rates of neurocognitive impairment and secondary CNS malignancies, we believe strong consideration should be given to eliminating CRT in first-line treatment for all patients with T-ALL,” they wrote.

More aggressive than B-cell ALL, T-ALL is characterized by a higher likelihood of infiltration of the CNS at diagnosis, which increases the risk of relapse after treatment.

Until recently, treatment of T-ALL long entailed CNS-directed therapy using prophylactic CRT. Now, however, due to the risks of significant toxicity, including neurocognitive defects and secondary cancers, CRT is usually either omitted or limited to key subgroups, such as those with CNS-3 disease. As an alternative, intrathecal chemotherapy is used, the authors explain.

In a 2023 study evaluating the consecutive Children’s Oncology Group (COG) AALL0434 and AALL1231 phase 3 trials of 2,164 patients with T-ALL, patients with CNS-3 at diagnosis were found to have worse outcomes, compared with CNS-1 and 2.

Importantly, the outcomes in both of those two trials were similar, despite the use of CRT in more than 90% of patients in the AALL0434 trial--but in only 10% of patients AALL1231 trial (mainly those with CNS-3 and at high-risk). These outcomes suggested that CRT can safely be eliminated for CNS-1 and 2 patients.

With CRT used in both trials among patients with CNS-3, conclusions about eliminating CRT among those patients could not be drawn. However, with other large groups (including the Dutch Childhood Oncology Group), eliminating CRT in the frontline treatment of all patients with T-ALL, including those with CNS-3, is what Dr. Vora and colleagues sought to further investigate.

For the current study, they evaluated outcomes in the UKALL2003 and UKALL2011 trials conducted by the UK National Cancer Research Institute, in which CRT was eliminated for all patients — including those with CNS-3 — and compared them with the COG AALL0434 and AALL1231 trials.

In the UK trials, involving 665 patients with T-ALL aged 1 to 24, treatment included a dexamethasone-based backbone chemotherapy consisting of a 4-drug induction, Berlin-Frankfurt-Münster (BFM) consolidation, interim maintenance, delayed intensification, and maintenance therapy, with the treatment stratified based on morphological early response and minimal residual disease at the end of induction.

While the UKALL2003 trial initially recommended CRT for patients with CNS-3, that practice ended in 2009, and CNS-directed therapy subsequently consisted of intrathecal methotrexate (MTX) at regular intervals throughout treatment. Additional weekly intrathecal MTX treatments were recommended throughout induction for patients with CNS-3.

In the UKALL2011 trial, the weekly intrathecal MTX treatments were recommended for patients with CNS-2, as well as CNS-3.

Overall, among those with CNS data available, 557 patients had CNS-1 (87.4%), 44 CNS-2 (6.9%), and 36 CNS-3 (5.7%).

For the outcomes of 4-year cumulative incidence of relapse (CIR), event-free survival (EFS) and overall survival (OS) in the combined cohort of the 2 UK trials, there were no significant differences between CNS-1, 2 or 3 groups.

Specifically, the mean rates of 4-year CIR in the CNS-1, 2, and 3 groups were 13.6%, 25.9% and 24.6%, respectively (P = .241); mean EFS rates were 82.9%, 74.1% and 77.8% (P = .623), and OS rates were 88.6%, 80.9% and 91.8%, (P = .453).

“Most importantly, outcomes are not significantly different for the patients with CNS-3, despite omission of CRT in the UK cohort,” the authors underscored.

Comparatively, in the cohort of the 2 COG trials, there were significant differences based on CNS status for 4-year CIR (P = .0002); EFS (P = .0004) and OS (P = .005).

The 4-year relapse rates among those with CNS-3 in the UK cohort were slightly higher compared with those in the COG cohort (24.6% UK vs 17.9%, COG). However, the difference did not translate to poorer long-term survival in the UK cohort (91.8% vs 82.7%, respectively).

Those findings are consistent with a previous meta-analysis that Dr. Vora and his colleagues conducted of more than 16,000 patients with mainly B-cell ALL, which showed that CRT reduced the risk of isolated and combined CNS relapse in patients with CNS-3. However, that risk had no impact on EFS and OS.

Of note, patients in the UK cohort with CNS-2 had worse outcomes compared with the COG group, with double the rate of relapse and lower EFS and OS. However, the authors speculate that factors including a lower proportion of patients with CNS-2 in the UK cohort and differences in methodologies may explain those different outcomes and may preclude their generalizability to other groups.

Overall, “these findings corroborate those of earlier studies that CRT has marginal, if any benefit, for any sub-group of ALL, especially as part of contemporary treatment,” Dr. Vora said in an interview.

In terms of therapies that do appear to make a difference in the treatment of CNS-3, Dr. Vora noted that the addition of nelarabine in the COG AALL0434 trial showed “remarkable benefit” in the CNS-3 group, with a 93.1% rate of disease-free survival in those patients versus 70.2% without nelarabine.

Importantly, those patients did also receive CRT. However, Dr. Vora and colleagues underscore that “the improvement is impressive and raises the question of whether nelarabine would have a similar beneficial effect in the absence of CRT.”

In an editorial published with the COG trials, Josep-Maria Ribera, MD, of the Josep Carreras Leukemia Research Institute, in Barcelona, Spain, agrees that “better approaches clearly are needed to treat CNS-3 T-ALL, especially if omission of CRT is a priority.”

Noting the improvements observed with nelarabine, as well as Capizzi escalating-dose methotrexate (C-MTX), and dexamethasone in reducing the risk of CNS relapse, he speculates that “it is possible that the additional use of C-MTX and induction dexamethasone could eliminate the need for CRT in these patients.”

The authors and Dr. Ribera had no disclosures to report.

Xanomeline-trospium (KarXT) — a novel therapy that combines a muscarinic receptor agonist with an anticholinergic agent — led to statistically significant and clinically meaningful improvements in positive and negative symptoms of schizophrenia compared with placebo in the phase 3 EMERGENT-2 trial, a new study shows.

Xanomeline-trospium treatment was not associated with weight gain compared with placebo, and the incidences of extrapyramidal motor symptoms or akathisia were low and similar between treatment groups.

The EMERGENT-2 results “support the potential for KarXT to represent a new class of effective and well-tolerated antipsychotic medicines based on activating muscarinic receptors, not the D2 dopamine receptor-blocking mechanism of all current antipsychotic medications,” write the authors, led by Inder Kaul, MD, with Karuna Therapeutics, Boston, Massachusetts.

The US Food and Drug Administration has accepted the company’s new drug application for KarXT for the treatment of schizophrenia in adults. The Prescription Drug User Fee Act action date is September 26, 2024.

Results of the EMERGENT-2 trial were published online on December 14, 2023, in The Lancet.
 

Beyond the Dopamine System

Evidence suggests the muscarinic cholinergic system is involved in the pathophysiology of schizophrenia.

Xanomeline is an oral muscarinic cholinergic receptor agonist that does not have direct effects on the dopamine receptor. Combining it with trospium chloride, an oral pan-muscarinic receptor antagonist, is thought to reduce side effects associated with xanomeline’s activation of peripheral muscarinic receptors in peripheral tissues.

EMERGENT-2 was a multicenter, double-blind, placebo-controlled trial that enrolled 252 adults with schizophrenia who recently experienced a worsening of psychotic symptoms warranting hospitalization.

Patients were treated for 5 weeks, with xanomeline-trospium titrated from 50 mg/20 mg twice daily to 125 mg/30 mg twice daily. Efficacy and safety analyses were conducted in those who had received at least one dose of the study drug.

The primary endpoint was change in baseline to week 5 in Positive and Negative Syndrome Scale (PANSS) total score (range, 30-210, with higher scores indicating more severe symptoms).

At the end of the treatment period, xanomeline-trospium was associated with a significant 9.6-point reduction in PANSS total scores relative to placebo. PANSS total scores fell by 21.2 points with xanomeline-trospium vs 11.6 points with placebo (P < .0001; Cohen d effect size, 0.61).

All secondary endpoints were also met, with active treatment demonstrating statistically significant reductions compared with placebo at week 5 (P < .05).

These secondary endpoints included change in PANSS positive subscale, PANSS negative subscale, PANSS Marder negative factor, Clinical Global Impression-Severity score, and percentage of participants achieving at least a 30% reduction from baseline to week 5 in PANSS total score.

Rates of discontinuation related to side effects were similar with active treatment and placebo (7% and 6%, respectively). The most common side effects with xanomeline-trospium were constipation (21%), dyspepsia (19%), nausea (19%), vomiting (14%), headache (14%), hypertension (10%), dizziness (9%), and gastroesophageal reflux disease (6%).

Xanomeline-trospium demonstrated a “distinctive safety and tolerability profile and was not associated with many of the adverse events typically associated with current antipsychotic treatments, including extrapyramidal motor symptoms, weight gain, changes in lipid and glucose parameters, and somnolence,” the authors report.
 

Potential ‘Game-Changer’

Xanomeline-trospium is a potential “game-changer” for patients with schizophrenia, Ann Shinn, MD, MPH, director of clinical research, Schizophrenia and Bipolar Disorder Research Program, McLean Hospital, and assistant professor of psychiatry, Harvard Medical School, told this news organization.

There was a “clear separation between the people who were randomized to KarXT vs placebo. It’s not just a statistically significant but also a clinically significant difference in the reduction in symptoms of psychosis,” said Dr. Shinn, who wasn’t involved in the study.

“What’s really exciting” is that the drug did not cause weight gain or extrapyramidal symptoms compared with placebo. “Both from an efficacy and side-effect perspective, I think more patients with schizophrenia are going to be willing to take medication,” Dr. Shinn noted.

Also commenting on this research for this news organization, René Kahn, MD, PhD, professor and chair of psychiatry at the Icahn School of Medicine at Mount Sinai in New York, noted that current antipsychotic medications for schizophrenia work “directly on the dopamine system — either as dopamine antagonists or partial agonist.”

Xanomeline-trospium provides a “new mechanism of action, a new system that’s being targeted in the treatment of schizophrenia, and the effect size was rather large, so the drug didn’t just squeak by,” Dr. Kahn said.

Nonetheless, “we’ll have to wait and see whether it’s as effective or more effective than drugs currently on the market. The proof of the pudding will come when it’s marketed and used on thousands and thousands of patients,” Dr. Kahn added.

The coauthors of an accompanying commentary say the EMERGENT-2 findings “strongly support the possibility that agonism of muscarinic receptors provides the first viable antipsychotic alternative to blocking the dopamine D2 receptor for more than 70 years, and as such encourage further research.”

However, as a regulatory trial, EMERGENT-2 does not provide comparative data on the benefits and harms of KarXT with existing alternatives.

This represents a “missed opportunity to provide patients and clinicians with the information that is clinically needed — what is the treatment of choice for a patient?” writes Andrea Cipriani, MD, PhD, with the Department of Psychiatry, University of Oxford, United Kingdom, and co-authors.

The study was funded by Karuna Therapeutics. Several authors disclosed relationships with the company. Dr. Kahn disclosed various relationships with Boehringer Ingelheim International GmbH. Dr. Cipriani received research, educational, and consultancy fees from the Italian Network for Paediatric Trials, the CARIPLO Foundation, Lundbeck, and Angelini Pharma and was chief investigator of one trial about seltorexant in adolescent depression, sponsored by Janssen. Dr. Shinn had no relevant disclosures.

A version of this article appeared on Medscape.com.

Xanomeline-trospium (KarXT) — a novel therapy that combines a muscarinic receptor agonist with an anticholinergic agent — led to statistically significant and clinically meaningful improvements in positive and negative symptoms of schizophrenia compared with placebo in the phase 3 EMERGENT-2 trial, a new study shows.

Xanomeline-trospium treatment was not associated with weight gain compared with placebo, and the incidences of extrapyramidal motor symptoms or akathisia were low and similar between treatment groups.

The EMERGENT-2 results “support the potential for KarXT to represent a new class of effective and well-tolerated antipsychotic medicines based on activating muscarinic receptors, not the D2 dopamine receptor-blocking mechanism of all current antipsychotic medications,” write the authors, led by Inder Kaul, MD, with Karuna Therapeutics, Boston, Massachusetts.

The US Food and Drug Administration has accepted the company’s new drug application for KarXT for the treatment of schizophrenia in adults. The Prescription Drug User Fee Act action date is September 26, 2024.

Results of the EMERGENT-2 trial were published online on December 14, 2023, in The Lancet.
 

Beyond the Dopamine System

Evidence suggests the muscarinic cholinergic system is involved in the pathophysiology of schizophrenia.

Xanomeline is an oral muscarinic cholinergic receptor agonist that does not have direct effects on the dopamine receptor. Combining it with trospium chloride, an oral pan-muscarinic receptor antagonist, is thought to reduce side effects associated with xanomeline’s activation of peripheral muscarinic receptors in peripheral tissues.

EMERGENT-2 was a multicenter, double-blind, placebo-controlled trial that enrolled 252 adults with schizophrenia who recently experienced a worsening of psychotic symptoms warranting hospitalization.

Patients were treated for 5 weeks, with xanomeline-trospium titrated from 50 mg/20 mg twice daily to 125 mg/30 mg twice daily. Efficacy and safety analyses were conducted in those who had received at least one dose of the study drug.

The primary endpoint was change in baseline to week 5 in Positive and Negative Syndrome Scale (PANSS) total score (range, 30-210, with higher scores indicating more severe symptoms).

At the end of the treatment period, xanomeline-trospium was associated with a significant 9.6-point reduction in PANSS total scores relative to placebo. PANSS total scores fell by 21.2 points with xanomeline-trospium vs 11.6 points with placebo (P < .0001; Cohen d effect size, 0.61).

All secondary endpoints were also met, with active treatment demonstrating statistically significant reductions compared with placebo at week 5 (P < .05).

These secondary endpoints included change in PANSS positive subscale, PANSS negative subscale, PANSS Marder negative factor, Clinical Global Impression-Severity score, and percentage of participants achieving at least a 30% reduction from baseline to week 5 in PANSS total score.

Rates of discontinuation related to side effects were similar with active treatment and placebo (7% and 6%, respectively). The most common side effects with xanomeline-trospium were constipation (21%), dyspepsia (19%), nausea (19%), vomiting (14%), headache (14%), hypertension (10%), dizziness (9%), and gastroesophageal reflux disease (6%).

Xanomeline-trospium demonstrated a “distinctive safety and tolerability profile and was not associated with many of the adverse events typically associated with current antipsychotic treatments, including extrapyramidal motor symptoms, weight gain, changes in lipid and glucose parameters, and somnolence,” the authors report.
 

Potential ‘Game-Changer’

Xanomeline-trospium is a potential “game-changer” for patients with schizophrenia, Ann Shinn, MD, MPH, director of clinical research, Schizophrenia and Bipolar Disorder Research Program, McLean Hospital, and assistant professor of psychiatry, Harvard Medical School, told this news organization.

There was a “clear separation between the people who were randomized to KarXT vs placebo. It’s not just a statistically significant but also a clinically significant difference in the reduction in symptoms of psychosis,” said Dr. Shinn, who wasn’t involved in the study.

“What’s really exciting” is that the drug did not cause weight gain or extrapyramidal symptoms compared with placebo. “Both from an efficacy and side-effect perspective, I think more patients with schizophrenia are going to be willing to take medication,” Dr. Shinn noted.

Also commenting on this research for this news organization, René Kahn, MD, PhD, professor and chair of psychiatry at the Icahn School of Medicine at Mount Sinai in New York, noted that current antipsychotic medications for schizophrenia work “directly on the dopamine system — either as dopamine antagonists or partial agonist.”

Xanomeline-trospium provides a “new mechanism of action, a new system that’s being targeted in the treatment of schizophrenia, and the effect size was rather large, so the drug didn’t just squeak by,” Dr. Kahn said.

Nonetheless, “we’ll have to wait and see whether it’s as effective or more effective than drugs currently on the market. The proof of the pudding will come when it’s marketed and used on thousands and thousands of patients,” Dr. Kahn added.

The coauthors of an accompanying commentary say the EMERGENT-2 findings “strongly support the possibility that agonism of muscarinic receptors provides the first viable antipsychotic alternative to blocking the dopamine D2 receptor for more than 70 years, and as such encourage further research.”

However, as a regulatory trial, EMERGENT-2 does not provide comparative data on the benefits and harms of KarXT with existing alternatives.

This represents a “missed opportunity to provide patients and clinicians with the information that is clinically needed — what is the treatment of choice for a patient?” writes Andrea Cipriani, MD, PhD, with the Department of Psychiatry, University of Oxford, United Kingdom, and co-authors.

The study was funded by Karuna Therapeutics. Several authors disclosed relationships with the company. Dr. Kahn disclosed various relationships with Boehringer Ingelheim International GmbH. Dr. Cipriani received research, educational, and consultancy fees from the Italian Network for Paediatric Trials, the CARIPLO Foundation, Lundbeck, and Angelini Pharma and was chief investigator of one trial about seltorexant in adolescent depression, sponsored by Janssen. Dr. Shinn had no relevant disclosures.

A version of this article appeared on Medscape.com.

Xanomeline-trospium (KarXT) — a novel therapy that combines a muscarinic receptor agonist with an anticholinergic agent — led to statistically significant and clinically meaningful improvements in positive and negative symptoms of schizophrenia compared with placebo in the phase 3 EMERGENT-2 trial, a new study shows.

Xanomeline-trospium treatment was not associated with weight gain compared with placebo, and the incidences of extrapyramidal motor symptoms or akathisia were low and similar between treatment groups.

The EMERGENT-2 results “support the potential for KarXT to represent a new class of effective and well-tolerated antipsychotic medicines based on activating muscarinic receptors, not the D2 dopamine receptor-blocking mechanism of all current antipsychotic medications,” write the authors, led by Inder Kaul, MD, with Karuna Therapeutics, Boston, Massachusetts.

The US Food and Drug Administration has accepted the company’s new drug application for KarXT for the treatment of schizophrenia in adults. The Prescription Drug User Fee Act action date is September 26, 2024.

Results of the EMERGENT-2 trial were published online on December 14, 2023, in The Lancet.
 

Beyond the Dopamine System

Evidence suggests the muscarinic cholinergic system is involved in the pathophysiology of schizophrenia.

Xanomeline is an oral muscarinic cholinergic receptor agonist that does not have direct effects on the dopamine receptor. Combining it with trospium chloride, an oral pan-muscarinic receptor antagonist, is thought to reduce side effects associated with xanomeline’s activation of peripheral muscarinic receptors in peripheral tissues.

EMERGENT-2 was a multicenter, double-blind, placebo-controlled trial that enrolled 252 adults with schizophrenia who recently experienced a worsening of psychotic symptoms warranting hospitalization.

Patients were treated for 5 weeks, with xanomeline-trospium titrated from 50 mg/20 mg twice daily to 125 mg/30 mg twice daily. Efficacy and safety analyses were conducted in those who had received at least one dose of the study drug.

The primary endpoint was change in baseline to week 5 in Positive and Negative Syndrome Scale (PANSS) total score (range, 30-210, with higher scores indicating more severe symptoms).

At the end of the treatment period, xanomeline-trospium was associated with a significant 9.6-point reduction in PANSS total scores relative to placebo. PANSS total scores fell by 21.2 points with xanomeline-trospium vs 11.6 points with placebo (P < .0001; Cohen d effect size, 0.61).

All secondary endpoints were also met, with active treatment demonstrating statistically significant reductions compared with placebo at week 5 (P < .05).

These secondary endpoints included change in PANSS positive subscale, PANSS negative subscale, PANSS Marder negative factor, Clinical Global Impression-Severity score, and percentage of participants achieving at least a 30% reduction from baseline to week 5 in PANSS total score.

Rates of discontinuation related to side effects were similar with active treatment and placebo (7% and 6%, respectively). The most common side effects with xanomeline-trospium were constipation (21%), dyspepsia (19%), nausea (19%), vomiting (14%), headache (14%), hypertension (10%), dizziness (9%), and gastroesophageal reflux disease (6%).

Xanomeline-trospium demonstrated a “distinctive safety and tolerability profile and was not associated with many of the adverse events typically associated with current antipsychotic treatments, including extrapyramidal motor symptoms, weight gain, changes in lipid and glucose parameters, and somnolence,” the authors report.
 

Potential ‘Game-Changer’

Xanomeline-trospium is a potential “game-changer” for patients with schizophrenia, Ann Shinn, MD, MPH, director of clinical research, Schizophrenia and Bipolar Disorder Research Program, McLean Hospital, and assistant professor of psychiatry, Harvard Medical School, told this news organization.

There was a “clear separation between the people who were randomized to KarXT vs placebo. It’s not just a statistically significant but also a clinically significant difference in the reduction in symptoms of psychosis,” said Dr. Shinn, who wasn’t involved in the study.

“What’s really exciting” is that the drug did not cause weight gain or extrapyramidal symptoms compared with placebo. “Both from an efficacy and side-effect perspective, I think more patients with schizophrenia are going to be willing to take medication,” Dr. Shinn noted.

Also commenting on this research for this news organization, René Kahn, MD, PhD, professor and chair of psychiatry at the Icahn School of Medicine at Mount Sinai in New York, noted that current antipsychotic medications for schizophrenia work “directly on the dopamine system — either as dopamine antagonists or partial agonist.”

Xanomeline-trospium provides a “new mechanism of action, a new system that’s being targeted in the treatment of schizophrenia, and the effect size was rather large, so the drug didn’t just squeak by,” Dr. Kahn said.

Nonetheless, “we’ll have to wait and see whether it’s as effective or more effective than drugs currently on the market. The proof of the pudding will come when it’s marketed and used on thousands and thousands of patients,” Dr. Kahn added.

The coauthors of an accompanying commentary say the EMERGENT-2 findings “strongly support the possibility that agonism of muscarinic receptors provides the first viable antipsychotic alternative to blocking the dopamine D2 receptor for more than 70 years, and as such encourage further research.”

However, as a regulatory trial, EMERGENT-2 does not provide comparative data on the benefits and harms of KarXT with existing alternatives.

This represents a “missed opportunity to provide patients and clinicians with the information that is clinically needed — what is the treatment of choice for a patient?” writes Andrea Cipriani, MD, PhD, with the Department of Psychiatry, University of Oxford, United Kingdom, and co-authors.

The study was funded by Karuna Therapeutics. Several authors disclosed relationships with the company. Dr. Kahn disclosed various relationships with Boehringer Ingelheim International GmbH. Dr. Cipriani received research, educational, and consultancy fees from the Italian Network for Paediatric Trials, the CARIPLO Foundation, Lundbeck, and Angelini Pharma and was chief investigator of one trial about seltorexant in adolescent depression, sponsored by Janssen. Dr. Shinn had no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Deaths caused by both substance use (SU) and cardiovascular disease (CVD) increased substantially in the United States between 1999 and 2019, with the most pronounced rise among women, American Indians, younger people, rural residents, and users of cannabis and psychostimulants, results of new research suggest.

METHODOLOGY:

• From the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database and using International Classification of Diseases (ICD) codes, researchers collected data on deaths within the United States where both SU and CVD (SU+CVD) were a contributing or an underlying cause and gathered information on location of death (medical facility, home, hospice, nursing home/long-term care facility), demographics (sex, race/ethnicity, age), and region (urban-rural, state).
• Researchers determined crude and age-adjusted mortality rates (AAMRs) per 100,000 population, identified trends in AAMR using annual percent change (APC) and calculated the weighted average of APCs (AAPCs).
• Between 1999 and 2019, there were 636,572 deaths related to CVD+SU, 75.6% of which were among men and 70.6% among non-Hispanic White individuals, with 65% related to alcohol, and where location of death was available, 47.7% occurred in medical facilities.

TAKEAWAY:

• The overall SU+CVD-related AAMR from 1999 to 2019 was 14.3 (95% CI, 14.3-14.3) per 100,000 individuals, with the rate being higher in men (22.5) than in women (6.8) and highest in American Indians or Alaska Natives (37.7) compared with other races/ethnicities.
• Rural areas had higher SU+CVD-related AAMR (15.2; 95% CI, 15.1-15.3) than urban areas, with the District of Columbia having the highest AAMR geographically (25.4), individuals aged 55-69 years having the highest rate agewise (25.1), and alcohol accounting for the highest rate (9.09) among substance types.
• Temporal trends show that the overall SU+CVD-related AAMR increased from 9.9 in 1999 to 21.4 in 2019, a rate that started accelerating in 2012, with an AAPC of 4.0% (95% CI, 3.7-4.3); increases were across all ethnicities and age groups and were particularly pronounced among women (4.8%; 95% CI, 4.5-5.1).
• Cannabis had the highest AAPC of all substances (12.7%), but stimulants had an APC of 21.4 (95% CI, 20.0-22.8) from 2009 to 2019, a period during which stimulants were the fastest-growing substance abuse category.

IN PRACTICE:

These new results identify high-risk groups, which “is crucial for prioritizing preventive measures aiming to reduce substance use and cardiovascular disease-related mortality in these populations,” the researchers wrote.

SOURCE:

Abdul Mannan Khan Minhas, MD, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, and Jakrin Kewcharoen, MD, Division of Cardiology, Loma Linda University Medical Center, Loma Linda, California, were co-first authors of the study, which was published online in the Journal of the American Heart Association.

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

TOPLINE:

Deaths caused by both substance use (SU) and cardiovascular disease (CVD) increased substantially in the United States between 1999 and 2019, with the most pronounced rise among women, American Indians, younger people, rural residents, and users of cannabis and psychostimulants, results of new research suggest.

METHODOLOGY:

• From the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database and using International Classification of Diseases (ICD) codes, researchers collected data on deaths within the United States where both SU and CVD (SU+CVD) were a contributing or an underlying cause and gathered information on location of death (medical facility, home, hospice, nursing home/long-term care facility), demographics (sex, race/ethnicity, age), and region (urban-rural, state).
• Researchers determined crude and age-adjusted mortality rates (AAMRs) per 100,000 population, identified trends in AAMR using annual percent change (APC) and calculated the weighted average of APCs (AAPCs).
• Between 1999 and 2019, there were 636,572 deaths related to CVD+SU, 75.6% of which were among men and 70.6% among non-Hispanic White individuals, with 65% related to alcohol, and where location of death was available, 47.7% occurred in medical facilities.

TAKEAWAY:

• The overall SU+CVD-related AAMR from 1999 to 2019 was 14.3 (95% CI, 14.3-14.3) per 100,000 individuals, with the rate being higher in men (22.5) than in women (6.8) and highest in American Indians or Alaska Natives (37.7) compared with other races/ethnicities.
• Rural areas had higher SU+CVD-related AAMR (15.2; 95% CI, 15.1-15.3) than urban areas, with the District of Columbia having the highest AAMR geographically (25.4), individuals aged 55-69 years having the highest rate agewise (25.1), and alcohol accounting for the highest rate (9.09) among substance types.
• Temporal trends show that the overall SU+CVD-related AAMR increased from 9.9 in 1999 to 21.4 in 2019, a rate that started accelerating in 2012, with an AAPC of 4.0% (95% CI, 3.7-4.3); increases were across all ethnicities and age groups and were particularly pronounced among women (4.8%; 95% CI, 4.5-5.1).
• Cannabis had the highest AAPC of all substances (12.7%), but stimulants had an APC of 21.4 (95% CI, 20.0-22.8) from 2009 to 2019, a period during which stimulants were the fastest-growing substance abuse category.

IN PRACTICE:

These new results identify high-risk groups, which “is crucial for prioritizing preventive measures aiming to reduce substance use and cardiovascular disease-related mortality in these populations,” the researchers wrote.

SOURCE:

Abdul Mannan Khan Minhas, MD, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, and Jakrin Kewcharoen, MD, Division of Cardiology, Loma Linda University Medical Center, Loma Linda, California, were co-first authors of the study, which was published online in the Journal of the American Heart Association.

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

TOPLINE:

Deaths caused by both substance use (SU) and cardiovascular disease (CVD) increased substantially in the United States between 1999 and 2019, with the most pronounced rise among women, American Indians, younger people, rural residents, and users of cannabis and psychostimulants, results of new research suggest.

METHODOLOGY:

• From the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database and using International Classification of Diseases (ICD) codes, researchers collected data on deaths within the United States where both SU and CVD (SU+CVD) were a contributing or an underlying cause and gathered information on location of death (medical facility, home, hospice, nursing home/long-term care facility), demographics (sex, race/ethnicity, age), and region (urban-rural, state).
• Researchers determined crude and age-adjusted mortality rates (AAMRs) per 100,000 population, identified trends in AAMR using annual percent change (APC) and calculated the weighted average of APCs (AAPCs).
• Between 1999 and 2019, there were 636,572 deaths related to CVD+SU, 75.6% of which were among men and 70.6% among non-Hispanic White individuals, with 65% related to alcohol, and where location of death was available, 47.7% occurred in medical facilities.

TAKEAWAY:

• The overall SU+CVD-related AAMR from 1999 to 2019 was 14.3 (95% CI, 14.3-14.3) per 100,000 individuals, with the rate being higher in men (22.5) than in women (6.8) and highest in American Indians or Alaska Natives (37.7) compared with other races/ethnicities.
• Rural areas had higher SU+CVD-related AAMR (15.2; 95% CI, 15.1-15.3) than urban areas, with the District of Columbia having the highest AAMR geographically (25.4), individuals aged 55-69 years having the highest rate agewise (25.1), and alcohol accounting for the highest rate (9.09) among substance types.
• Temporal trends show that the overall SU+CVD-related AAMR increased from 9.9 in 1999 to 21.4 in 2019, a rate that started accelerating in 2012, with an AAPC of 4.0% (95% CI, 3.7-4.3); increases were across all ethnicities and age groups and were particularly pronounced among women (4.8%; 95% CI, 4.5-5.1).
• Cannabis had the highest AAPC of all substances (12.7%), but stimulants had an APC of 21.4 (95% CI, 20.0-22.8) from 2009 to 2019, a period during which stimulants were the fastest-growing substance abuse category.

IN PRACTICE:

These new results identify high-risk groups, which “is crucial for prioritizing preventive measures aiming to reduce substance use and cardiovascular disease-related mortality in these populations,” the researchers wrote.

SOURCE:

Abdul Mannan Khan Minhas, MD, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, and Jakrin Kewcharoen, MD, Division of Cardiology, Loma Linda University Medical Center, Loma Linda, California, were co-first authors of the study, which was published online in the Journal of the American Heart Association.

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

Gastroenterology

October 2023

El-Salhy M et al. Efficacy of Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome at 3 Years After Transplantation. Gastroenterology. 2022 Oct;163(4):982-994.e14. doi: 10.1053/j.gastro.2022.06.020. Epub 2022 Jun 14. PMID: 35709830.



Bajaj JS and Nagy LE. Natural History of Alcohol-Associated Liver Disease: Understanding the Changing Landscape of Pathophysiology and Patient Care. Gastroenterology. 2022 Oct;163(4):840-851. doi: 10.1053/j.gastro.2022.05.031. Epub 2022 May 19. PMID: 35598629; PMCID: PMC9509416.



Lo CH et al. Association of Proton Pump Inhibitor Use With All-Cause and Cause-Specific Mortality. Gastroenterology. 2022 Oct;163(4):852-861.e2. doi: 10.1053/j.gastro.2022.06.067. Epub 2022 Jul 1. PMID: 35788344; PMCID: PMC9509450.



November 2023

Khoshiwal AM et al. The Tissue Systems Pathology Test Outperforms Pathology Review in Risk Stratifying Patients With Low-Grade Dysplasia. Gastroenterology. 2023 Nov;165(5):1168-1179.e6. doi: 10.1053/j.gastro.2023.07.029. Epub 2023 Aug 30. PMID: 37657759.



Chen YI et al. Endoscopic Ultrasound-Guided Biliary Drainage of First Intent With a Lumen-Apposing Metal Stent vs Endoscopic Retrograde Cholangiopancreatography in Malignant Distal Biliary Obstruction: A Multicenter Randomized Controlled Study (ELEMENT Trial). Gastroenterology. 2023 Nov;165(5):1249-1261.e5. doi: 10.1053/j.gastro.2023.07.024. Epub 2023 Aug 6. PMID: 37549753.



December 2023

Almario CV et al. Prevalence and Burden of Illness of Rome IV Irritable Bowel Syndrome in the United States: Results From a Nationwide Cross-Sectional Study. Gastroenterology. 2023 Dec;165(6):1475-1487. doi: 10.1053/j.gastro.2023.08.010. Epub 2023 Aug 16. PMID: 37595647.



Koopmann BDM et al. The Natural Disease Course of Pancreatic Cyst-Associated Neoplasia, Dysplasia, and Ductal Adenocarcinoma: Results of a Microsimulation Model. Gastroenterology. 2023 Dec;165(6):1522-1532. doi: 10.1053/j.gastro.2023.08.027. Epub 2023 Aug 24. PMID: 37633497.


 

Clinical Gastroenterology and Hepatology

October 2023

Jung DH et al. Comparison of a Polysaccharide Hemostatic Powder and Conventional Therapy for Peptic Ulcer Bleeding. Clin Gastroenterol Hepatol. 2023 Oct;21(11):2844-2253.e5. doi: 10.1016/j.cgh.2023.02.031. Epub 2023 Mar 10. PMID: 36906081.



Liang PS et al. Blood Test Increases Colorectal Cancer Screening in Persons Who Declined Colonoscopy and Fecal Immunochemical Test: A Randomized Controlled Trial. Clin Gastroenterol Hepatol. 2023 Oct;21(11):2951-2957.e2. doi: 10.1016/j.cgh.2023.03.036. Epub 2023 Apr 8. PMID: 37037262; PMCID: PMC10523873.



November 2023

Li YK et al. Risk of Postcolonoscopy Thromboembolic Events: A Real-World Cohort Study. Clin Gastroenterol Hepatol. 2023 Nov;21(12):3051-3059.e4. doi: 10.1016/j.cgh.2022.09.021. Epub 2022 Sep 24. PMID: 36167228.



Tome J et al. Bile Acid Sequestrants in Microscopic Colitis: Clinical Outcomes and Utility of Bile Acid Testing. Clin Gastroenterol Hepatol. 2023 Nov;21(12):3125-3131.e2. doi: 10.1016/j.cgh.2023.04.031. Epub 2023 May 10. PMID: 37172800.



Berry SK et al. A Randomized Parallel-group Study of Digital Gut-directed Hypnotherapy vs Muscle Relaxation for Irritable Bowel Syndrome. Clin Gastroenterol Hepatol. 2023 Nov;21(12):3152-3159.e2. doi: 10.1016/j.cgh.2023.06.015. Epub 2023 Jun 28. PMID: 37391055.



December 2023

Kanwal F et al. Risk Stratification Model for Hepatocellular Cancer in Patients With Cirrhosis. Clin Gastroenterol Hepatol. 2023 Dec;21(13):3296-3304.e3. doi: 10.1016/j.cgh.2023.04.019. Epub 2023 Apr 30. PMID: 37390101; PMCID: PMC10661677.



Forss A et al. Patients With Microscopic Colitis Are at Higher Risk of Major Adverse Cardiovascular Events: A Matched Cohort Study. Clin Gastroenterol Hepatol. 2023 Dec;21(13):3356-3364.e9. doi: 10.1016/j.cgh.2023.05.014. Epub 2023 May 26. PMID: 37245713.



Zheng T et al. A Randomized, Controlled Trial of Efficacy and Safety of Cannabidiol in Idiopathic and Diabetic Gastroparesis. Clin Gastroenterol Hepatol. 2023 Dec;21(13):3405-3414.e4. doi: 10.1016/j.cgh.2023.07.008. Epub 2023 Jul 22. PMID: 37482172.


 

Techniques and Innovations in Gastrointestinal Endoscopy

Rengarajan A and Aadam A. Peroral Endoscopic Myotomy (POEM) and Its Use in Esophageal Dysmotility. Tech Innov Gastrointest Endosc. 2023 Dec 16. doi: 10.1016/j.tige.2023.12.004.



Wang D et al. Sphincterotomy vs Sham Procedure for Pain Relief in Sphincter of Oddi Dysfunction: Systematic Review and Meta-analysis. Tech Innov Gastrointest Endosc. 2023 Nov 7. doi: 10.1016/j.tige.2023.10.003


 

Gastro Hep Advances

Gregory MH et al. Short Bowel Syndrome: Transition of Pediatric Patients to Adult Gastroenterology Care. Gastro Hep Advances. 2023 Sep 8. doi: 10.1016/j.gastha.2023.09.006.



Viser AC et al. Inflammatory Bowel Disease Patients in the Ambulatory Setting Commonly Screen Positive for Malnutrition. Gastro Hep Advances. 2023 Nov 16. doi: 10.1016/j.gastha.2023.11.007.

Gastroenterology

October 2023

El-Salhy M et al. Efficacy of Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome at 3 Years After Transplantation. Gastroenterology. 2022 Oct;163(4):982-994.e14. doi: 10.1053/j.gastro.2022.06.020. Epub 2022 Jun 14. PMID: 35709830.



Bajaj JS and Nagy LE. Natural History of Alcohol-Associated Liver Disease: Understanding the Changing Landscape of Pathophysiology and Patient Care. Gastroenterology. 2022 Oct;163(4):840-851. doi: 10.1053/j.gastro.2022.05.031. Epub 2022 May 19. PMID: 35598629; PMCID: PMC9509416.



Lo CH et al. Association of Proton Pump Inhibitor Use With All-Cause and Cause-Specific Mortality. Gastroenterology. 2022 Oct;163(4):852-861.e2. doi: 10.1053/j.gastro.2022.06.067. Epub 2022 Jul 1. PMID: 35788344; PMCID: PMC9509450.



November 2023

Khoshiwal AM et al. The Tissue Systems Pathology Test Outperforms Pathology Review in Risk Stratifying Patients With Low-Grade Dysplasia. Gastroenterology. 2023 Nov;165(5):1168-1179.e6. doi: 10.1053/j.gastro.2023.07.029. Epub 2023 Aug 30. PMID: 37657759.



Chen YI et al. Endoscopic Ultrasound-Guided Biliary Drainage of First Intent With a Lumen-Apposing Metal Stent vs Endoscopic Retrograde Cholangiopancreatography in Malignant Distal Biliary Obstruction: A Multicenter Randomized Controlled Study (ELEMENT Trial). Gastroenterology. 2023 Nov;165(5):1249-1261.e5. doi: 10.1053/j.gastro.2023.07.024. Epub 2023 Aug 6. PMID: 37549753.



December 2023

Almario CV et al. Prevalence and Burden of Illness of Rome IV Irritable Bowel Syndrome in the United States: Results From a Nationwide Cross-Sectional Study. Gastroenterology. 2023 Dec;165(6):1475-1487. doi: 10.1053/j.gastro.2023.08.010. Epub 2023 Aug 16. PMID: 37595647.



Koopmann BDM et al. The Natural Disease Course of Pancreatic Cyst-Associated Neoplasia, Dysplasia, and Ductal Adenocarcinoma: Results of a Microsimulation Model. Gastroenterology. 2023 Dec;165(6):1522-1532. doi: 10.1053/j.gastro.2023.08.027. Epub 2023 Aug 24. PMID: 37633497.


 

Clinical Gastroenterology and Hepatology

October 2023

Jung DH et al. Comparison of a Polysaccharide Hemostatic Powder and Conventional Therapy for Peptic Ulcer Bleeding. Clin Gastroenterol Hepatol. 2023 Oct;21(11):2844-2253.e5. doi: 10.1016/j.cgh.2023.02.031. Epub 2023 Mar 10. PMID: 36906081.



Liang PS et al. Blood Test Increases Colorectal Cancer Screening in Persons Who Declined Colonoscopy and Fecal Immunochemical Test: A Randomized Controlled Trial. Clin Gastroenterol Hepatol. 2023 Oct;21(11):2951-2957.e2. doi: 10.1016/j.cgh.2023.03.036. Epub 2023 Apr 8. PMID: 37037262; PMCID: PMC10523873.



November 2023

Li YK et al. Risk of Postcolonoscopy Thromboembolic Events: A Real-World Cohort Study. Clin Gastroenterol Hepatol. 2023 Nov;21(12):3051-3059.e4. doi: 10.1016/j.cgh.2022.09.021. Epub 2022 Sep 24. PMID: 36167228.



Tome J et al. Bile Acid Sequestrants in Microscopic Colitis: Clinical Outcomes and Utility of Bile Acid Testing. Clin Gastroenterol Hepatol. 2023 Nov;21(12):3125-3131.e2. doi: 10.1016/j.cgh.2023.04.031. Epub 2023 May 10. PMID: 37172800.



Berry SK et al. A Randomized Parallel-group Study of Digital Gut-directed Hypnotherapy vs Muscle Relaxation for Irritable Bowel Syndrome. Clin Gastroenterol Hepatol. 2023 Nov;21(12):3152-3159.e2. doi: 10.1016/j.cgh.2023.06.015. Epub 2023 Jun 28. PMID: 37391055.



December 2023

Kanwal F et al. Risk Stratification Model for Hepatocellular Cancer in Patients With Cirrhosis. Clin Gastroenterol Hepatol. 2023 Dec;21(13):3296-3304.e3. doi: 10.1016/j.cgh.2023.04.019. Epub 2023 Apr 30. PMID: 37390101; PMCID: PMC10661677.



Forss A et al. Patients With Microscopic Colitis Are at Higher Risk of Major Adverse Cardiovascular Events: A Matched Cohort Study. Clin Gastroenterol Hepatol. 2023 Dec;21(13):3356-3364.e9. doi: 10.1016/j.cgh.2023.05.014. Epub 2023 May 26. PMID: 37245713.



Zheng T et al. A Randomized, Controlled Trial of Efficacy and Safety of Cannabidiol in Idiopathic and Diabetic Gastroparesis. Clin Gastroenterol Hepatol. 2023 Dec;21(13):3405-3414.e4. doi: 10.1016/j.cgh.2023.07.008. Epub 2023 Jul 22. PMID: 37482172.


 

Techniques and Innovations in Gastrointestinal Endoscopy

Rengarajan A and Aadam A. Peroral Endoscopic Myotomy (POEM) and Its Use in Esophageal Dysmotility. Tech Innov Gastrointest Endosc. 2023 Dec 16. doi: 10.1016/j.tige.2023.12.004.



Wang D et al. Sphincterotomy vs Sham Procedure for Pain Relief in Sphincter of Oddi Dysfunction: Systematic Review and Meta-analysis. Tech Innov Gastrointest Endosc. 2023 Nov 7. doi: 10.1016/j.tige.2023.10.003


 

Gastro Hep Advances

Gregory MH et al. Short Bowel Syndrome: Transition of Pediatric Patients to Adult Gastroenterology Care. Gastro Hep Advances. 2023 Sep 8. doi: 10.1016/j.gastha.2023.09.006.



Viser AC et al. Inflammatory Bowel Disease Patients in the Ambulatory Setting Commonly Screen Positive for Malnutrition. Gastro Hep Advances. 2023 Nov 16. doi: 10.1016/j.gastha.2023.11.007.

Gastroenterology

October 2023

El-Salhy M et al. Efficacy of Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome at 3 Years After Transplantation. Gastroenterology. 2022 Oct;163(4):982-994.e14. doi: 10.1053/j.gastro.2022.06.020. Epub 2022 Jun 14. PMID: 35709830.



Bajaj JS and Nagy LE. Natural History of Alcohol-Associated Liver Disease: Understanding the Changing Landscape of Pathophysiology and Patient Care. Gastroenterology. 2022 Oct;163(4):840-851. doi: 10.1053/j.gastro.2022.05.031. Epub 2022 May 19. PMID: 35598629; PMCID: PMC9509416.



Lo CH et al. Association of Proton Pump Inhibitor Use With All-Cause and Cause-Specific Mortality. Gastroenterology. 2022 Oct;163(4):852-861.e2. doi: 10.1053/j.gastro.2022.06.067. Epub 2022 Jul 1. PMID: 35788344; PMCID: PMC9509450.



November 2023

Khoshiwal AM et al. The Tissue Systems Pathology Test Outperforms Pathology Review in Risk Stratifying Patients With Low-Grade Dysplasia. Gastroenterology. 2023 Nov;165(5):1168-1179.e6. doi: 10.1053/j.gastro.2023.07.029. Epub 2023 Aug 30. PMID: 37657759.



Chen YI et al. Endoscopic Ultrasound-Guided Biliary Drainage of First Intent With a Lumen-Apposing Metal Stent vs Endoscopic Retrograde Cholangiopancreatography in Malignant Distal Biliary Obstruction: A Multicenter Randomized Controlled Study (ELEMENT Trial). Gastroenterology. 2023 Nov;165(5):1249-1261.e5. doi: 10.1053/j.gastro.2023.07.024. Epub 2023 Aug 6. PMID: 37549753.



December 2023

Almario CV et al. Prevalence and Burden of Illness of Rome IV Irritable Bowel Syndrome in the United States: Results From a Nationwide Cross-Sectional Study. Gastroenterology. 2023 Dec;165(6):1475-1487. doi: 10.1053/j.gastro.2023.08.010. Epub 2023 Aug 16. PMID: 37595647.



Koopmann BDM et al. The Natural Disease Course of Pancreatic Cyst-Associated Neoplasia, Dysplasia, and Ductal Adenocarcinoma: Results of a Microsimulation Model. Gastroenterology. 2023 Dec;165(6):1522-1532. doi: 10.1053/j.gastro.2023.08.027. Epub 2023 Aug 24. PMID: 37633497.


 

Clinical Gastroenterology and Hepatology

October 2023

Jung DH et al. Comparison of a Polysaccharide Hemostatic Powder and Conventional Therapy for Peptic Ulcer Bleeding. Clin Gastroenterol Hepatol. 2023 Oct;21(11):2844-2253.e5. doi: 10.1016/j.cgh.2023.02.031. Epub 2023 Mar 10. PMID: 36906081.



Liang PS et al. Blood Test Increases Colorectal Cancer Screening in Persons Who Declined Colonoscopy and Fecal Immunochemical Test: A Randomized Controlled Trial. Clin Gastroenterol Hepatol. 2023 Oct;21(11):2951-2957.e2. doi: 10.1016/j.cgh.2023.03.036. Epub 2023 Apr 8. PMID: 37037262; PMCID: PMC10523873.



November 2023

Li YK et al. Risk of Postcolonoscopy Thromboembolic Events: A Real-World Cohort Study. Clin Gastroenterol Hepatol. 2023 Nov;21(12):3051-3059.e4. doi: 10.1016/j.cgh.2022.09.021. Epub 2022 Sep 24. PMID: 36167228.



Tome J et al. Bile Acid Sequestrants in Microscopic Colitis: Clinical Outcomes and Utility of Bile Acid Testing. Clin Gastroenterol Hepatol. 2023 Nov;21(12):3125-3131.e2. doi: 10.1016/j.cgh.2023.04.031. Epub 2023 May 10. PMID: 37172800.



Berry SK et al. A Randomized Parallel-group Study of Digital Gut-directed Hypnotherapy vs Muscle Relaxation for Irritable Bowel Syndrome. Clin Gastroenterol Hepatol. 2023 Nov;21(12):3152-3159.e2. doi: 10.1016/j.cgh.2023.06.015. Epub 2023 Jun 28. PMID: 37391055.



December 2023

Kanwal F et al. Risk Stratification Model for Hepatocellular Cancer in Patients With Cirrhosis. Clin Gastroenterol Hepatol. 2023 Dec;21(13):3296-3304.e3. doi: 10.1016/j.cgh.2023.04.019. Epub 2023 Apr 30. PMID: 37390101; PMCID: PMC10661677.



Forss A et al. Patients With Microscopic Colitis Are at Higher Risk of Major Adverse Cardiovascular Events: A Matched Cohort Study. Clin Gastroenterol Hepatol. 2023 Dec;21(13):3356-3364.e9. doi: 10.1016/j.cgh.2023.05.014. Epub 2023 May 26. PMID: 37245713.



Zheng T et al. A Randomized, Controlled Trial of Efficacy and Safety of Cannabidiol in Idiopathic and Diabetic Gastroparesis. Clin Gastroenterol Hepatol. 2023 Dec;21(13):3405-3414.e4. doi: 10.1016/j.cgh.2023.07.008. Epub 2023 Jul 22. PMID: 37482172.


 

Techniques and Innovations in Gastrointestinal Endoscopy

Rengarajan A and Aadam A. Peroral Endoscopic Myotomy (POEM) and Its Use in Esophageal Dysmotility. Tech Innov Gastrointest Endosc. 2023 Dec 16. doi: 10.1016/j.tige.2023.12.004.



Wang D et al. Sphincterotomy vs Sham Procedure for Pain Relief in Sphincter of Oddi Dysfunction: Systematic Review and Meta-analysis. Tech Innov Gastrointest Endosc. 2023 Nov 7. doi: 10.1016/j.tige.2023.10.003


 

Gastro Hep Advances

Gregory MH et al. Short Bowel Syndrome: Transition of Pediatric Patients to Adult Gastroenterology Care. Gastro Hep Advances. 2023 Sep 8. doi: 10.1016/j.gastha.2023.09.006.



Viser AC et al. Inflammatory Bowel Disease Patients in the Ambulatory Setting Commonly Screen Positive for Malnutrition. Gastro Hep Advances. 2023 Nov 16. doi: 10.1016/j.gastha.2023.11.007.

When clinicians suspect lung fibrosis and particularly its most devastating form, idiopathic pulmonary fibrosis (IPF), a noninvasive artificial intelligence (AI)-driven digital diagnostic tool may identify subtype classifications facilitating proper treatment at earlier disease stages. On January 16, 2024, the tool, Fibresolve, developed and produced by the digital biomarker company IMVARIA Inc., received the first-ever US Food and Drug Administration (FDA) marketing authorization of a Breakthrough Designated AI diagnostic tool. Simultaneously, the American Medical Association adopted relevant CPT [Current Procedural Terminology] billing codes, according to an IMVARIA Inc. press release.

Diagnosis and treatment of the lung inflammation and fibrosis that drive IPF lung function decline are often long delayed, Joshua Reicher, MD, CEO of IMVARIA Inc. and an adjunct clinical professor at Stanford (California) University said in an interview for CHEST Physician.

“There are multiple challenges with this somewhat uncommon condition. Part of the frequent delays in diagnosis is the lack of access to local experts. Another part is vague presenting symptoms like general fatigue, for example, which can have an overlap with a lot of other conditions. The published median average delay in diagnosis after first presenting symptoms is about 2.2 years. But it’s often longer.”
 

Determining Type of Lung Fibrosis

Conventional diagnosis based on lab tests for inflammatory biomarkers and extensive clinical history is “fairly straightforward,” Dr. Reicher continued, for determining that a patient has some form of lung fibrosis. “The critical element is to find out what type of lung fibrosis and then begin appropriate therapy. The literature lists about 200 different subtypes, but the top 5 make up the majority of cases. The focus with Fibresolve is on improving noninvasive sensitivity, especially for the cases that are less straightforward, but rather indeterminate and therefore particularly challenging,” Dr. Reicher stated.

Will adjunctive diagnostic use of Fibresolve obviate the need for invasive confirmatory tests? Dr. Reicher was cautious. “We like to be thoughtful about our positioning of artificial intelligence and prefer to say that it puts complementary information in the hands of the physician. It’s really up to the clinicians to decide if they have sufficient information to avoid that biopsy.” The uniqueness of Fibresolve, Dr. Reicher pointed out, is that it is widely accessible and does not require hyper-specialized providers. “You can use it at any center that has standard CT scans.”
 

Reducing Burden on Physicians

An essential feature of Fibresolve use is that its software analysis is conducted centrally. “Part of our goal is to reduce the burden on the clinicians as much as possible, and we try to offload as much of the technical work from them as we can.”

The clinicians send images to IMVARIA Inc. (typically electronically) where they are processed rapidly, and a report is generated with outputs identifying the specific classification, perhaps with one indicating that the findings are suggestive of IPF. Dr. Reicher observed that the Fibresolve’s deep learning algorithm was trained on thousands of cases. “We’re very confident in the results that it puts out,” he said.

“We’re very excited. This is the first FDA-authorized diagnostic tool of any type in lung fibrosis. We really think this supports doctors and patients in areas where there’s a high unmet need,” Dr. Reicher said.

IMVARIA is next developing, in collaboration with the Mayo Clinic, a Fibresolve application for use in lung cancer, he said.

When clinicians suspect lung fibrosis and particularly its most devastating form, idiopathic pulmonary fibrosis (IPF), a noninvasive artificial intelligence (AI)-driven digital diagnostic tool may identify subtype classifications facilitating proper treatment at earlier disease stages. On January 16, 2024, the tool, Fibresolve, developed and produced by the digital biomarker company IMVARIA Inc., received the first-ever US Food and Drug Administration (FDA) marketing authorization of a Breakthrough Designated AI diagnostic tool. Simultaneously, the American Medical Association adopted relevant CPT [Current Procedural Terminology] billing codes, according to an IMVARIA Inc. press release.

Diagnosis and treatment of the lung inflammation and fibrosis that drive IPF lung function decline are often long delayed, Joshua Reicher, MD, CEO of IMVARIA Inc. and an adjunct clinical professor at Stanford (California) University said in an interview for CHEST Physician.

“There are multiple challenges with this somewhat uncommon condition. Part of the frequent delays in diagnosis is the lack of access to local experts. Another part is vague presenting symptoms like general fatigue, for example, which can have an overlap with a lot of other conditions. The published median average delay in diagnosis after first presenting symptoms is about 2.2 years. But it’s often longer.”
 

Determining Type of Lung Fibrosis

Conventional diagnosis based on lab tests for inflammatory biomarkers and extensive clinical history is “fairly straightforward,” Dr. Reicher continued, for determining that a patient has some form of lung fibrosis. “The critical element is to find out what type of lung fibrosis and then begin appropriate therapy. The literature lists about 200 different subtypes, but the top 5 make up the majority of cases. The focus with Fibresolve is on improving noninvasive sensitivity, especially for the cases that are less straightforward, but rather indeterminate and therefore particularly challenging,” Dr. Reicher stated.

Will adjunctive diagnostic use of Fibresolve obviate the need for invasive confirmatory tests? Dr. Reicher was cautious. “We like to be thoughtful about our positioning of artificial intelligence and prefer to say that it puts complementary information in the hands of the physician. It’s really up to the clinicians to decide if they have sufficient information to avoid that biopsy.” The uniqueness of Fibresolve, Dr. Reicher pointed out, is that it is widely accessible and does not require hyper-specialized providers. “You can use it at any center that has standard CT scans.”
 

Reducing Burden on Physicians

An essential feature of Fibresolve use is that its software analysis is conducted centrally. “Part of our goal is to reduce the burden on the clinicians as much as possible, and we try to offload as much of the technical work from them as we can.”

The clinicians send images to IMVARIA Inc. (typically electronically) where they are processed rapidly, and a report is generated with outputs identifying the specific classification, perhaps with one indicating that the findings are suggestive of IPF. Dr. Reicher observed that the Fibresolve’s deep learning algorithm was trained on thousands of cases. “We’re very confident in the results that it puts out,” he said.

“We’re very excited. This is the first FDA-authorized diagnostic tool of any type in lung fibrosis. We really think this supports doctors and patients in areas where there’s a high unmet need,” Dr. Reicher said.

IMVARIA is next developing, in collaboration with the Mayo Clinic, a Fibresolve application for use in lung cancer, he said.

When clinicians suspect lung fibrosis and particularly its most devastating form, idiopathic pulmonary fibrosis (IPF), a noninvasive artificial intelligence (AI)-driven digital diagnostic tool may identify subtype classifications facilitating proper treatment at earlier disease stages. On January 16, 2024, the tool, Fibresolve, developed and produced by the digital biomarker company IMVARIA Inc., received the first-ever US Food and Drug Administration (FDA) marketing authorization of a Breakthrough Designated AI diagnostic tool. Simultaneously, the American Medical Association adopted relevant CPT [Current Procedural Terminology] billing codes, according to an IMVARIA Inc. press release.

Diagnosis and treatment of the lung inflammation and fibrosis that drive IPF lung function decline are often long delayed, Joshua Reicher, MD, CEO of IMVARIA Inc. and an adjunct clinical professor at Stanford (California) University said in an interview for CHEST Physician.

“There are multiple challenges with this somewhat uncommon condition. Part of the frequent delays in diagnosis is the lack of access to local experts. Another part is vague presenting symptoms like general fatigue, for example, which can have an overlap with a lot of other conditions. The published median average delay in diagnosis after first presenting symptoms is about 2.2 years. But it’s often longer.”
 

Determining Type of Lung Fibrosis

Conventional diagnosis based on lab tests for inflammatory biomarkers and extensive clinical history is “fairly straightforward,” Dr. Reicher continued, for determining that a patient has some form of lung fibrosis. “The critical element is to find out what type of lung fibrosis and then begin appropriate therapy. The literature lists about 200 different subtypes, but the top 5 make up the majority of cases. The focus with Fibresolve is on improving noninvasive sensitivity, especially for the cases that are less straightforward, but rather indeterminate and therefore particularly challenging,” Dr. Reicher stated.

Will adjunctive diagnostic use of Fibresolve obviate the need for invasive confirmatory tests? Dr. Reicher was cautious. “We like to be thoughtful about our positioning of artificial intelligence and prefer to say that it puts complementary information in the hands of the physician. It’s really up to the clinicians to decide if they have sufficient information to avoid that biopsy.” The uniqueness of Fibresolve, Dr. Reicher pointed out, is that it is widely accessible and does not require hyper-specialized providers. “You can use it at any center that has standard CT scans.”
 

Reducing Burden on Physicians

An essential feature of Fibresolve use is that its software analysis is conducted centrally. “Part of our goal is to reduce the burden on the clinicians as much as possible, and we try to offload as much of the technical work from them as we can.”

The clinicians send images to IMVARIA Inc. (typically electronically) where they are processed rapidly, and a report is generated with outputs identifying the specific classification, perhaps with one indicating that the findings are suggestive of IPF. Dr. Reicher observed that the Fibresolve’s deep learning algorithm was trained on thousands of cases. “We’re very confident in the results that it puts out,” he said.

“We’re very excited. This is the first FDA-authorized diagnostic tool of any type in lung fibrosis. We really think this supports doctors and patients in areas where there’s a high unmet need,” Dr. Reicher said.

IMVARIA is next developing, in collaboration with the Mayo Clinic, a Fibresolve application for use in lung cancer, he said.

A post hoc analysis of three clinical trials of tenapanor (Ibsrela, Ardelyx) shows the drug works within weeks to improve bowel function and abdominal symptoms in people with irritable bowel syndrome with constipation (IBS-C).

“Although onset of action occurs within the first week, continued therapy allows for a greater percentage of patients to achieve a meaningful response,” wrote Brian Lacy, MD, PhD, of the Mayo Clinic in Jacksonville, Florida, and co-authors in an abstract.

Dr. Lacy presented the results of this work at the annual scientific meeting of the American College of Gastroenterology (ACG) in Vancouver, Canada.

Tenapanor acts as an inhibitor of the sodium-hydrogen exchanger 3 (NHE3) and works to reduce dietary sodium absorption, which, in turn, leads to retention of fluid in the intestinal lumen, resulting in softer stool and accelerated intestinal transit, he explained.

Tenapanor is approved by the US Food and Drug Administration for adults with IBS-C.

The major goal of the analysis presented at ACG was to identify times to responses for individual symptoms, said Dr. Lacy in an email exchange with GI & Hepatology News.

Prior studies focused on global improvement in IBS-C symptoms using the FDA-approved definition of a responder: A patient who experienced at least a 30% reduction in the weekly average abdominal pain score and an increase of at least one complete spontaneous bowel movement (CSBM) in the same week for at least 6 of the first 12 treatment weeks.

“Thus, we thought it important to pool all of the data together for this post-hoc analysis, as clinicians and patients often wonder when an individual symptom will respond,” Dr. Lacy wrote in an email.

Dr. Lacy and colleagues conducted a post hoc analysis of pooled data from the phase 2b (NCT01923428) and phase 3 T3MPO-1 (NCT02621892) and T3MPO-2 (NCT02686138) studies to evaluate time to onset of tenapanor effect on bowel function and on individual and global abdominal symptoms in patients with IBS-C.

This resulted in a pooled population of 1372 intent-to-treat patients (688 placebo, 684 on the study drug), with demographics generally similar across the studies, they said.

They found that the median time to CSBM was 2 weeks, with an estimated response probability of 52.3% by week 2, 72.5% by week 8, and 76.7% by week 12.

The median time to abdominal pain response was 4 weeks; the estimated response probability was 54.6% by week 4, 67.9% by week 8, and 72.3% by week 12.

The median time to abdominal bloating response was 5 weeks; the estimated response probability was 48.1% by week 4, 61.9% by week 8, and 67.7% by week 12.

“The teaching message to patients and providers is not to give up too early; staying on this medication allowed 25% more people to improve symptoms,” Dr. Lacy wrote.

In separate interviews, two other researchers Anthony Lembo, MD, AGAF, director of research for Cleveland Clinic’s Digestive Disease & Surgery Institute, and Brooks D. Cash, MD, AGAF, chief for gastroenterology, hepatology, and nutrition at the University of Texas Health Science Center at Houston, agreed with Dr. Lacy’s message.

The study will help in counseling patients who may need to wait a bit to see a response from tenapanor, Dr. Lembo said.

“You wish patients would get better right away of course,” he said, but there can be some delay, even in cases where a drug will ultimately work for a patient.

Patients want to know if they should continue and if it is worth getting another prescription for another month if they haven’t had a significant improvement response, Dr. Lembo said.

Both Dr. Lembo and Dr. Cash said that it takes time for many drugs, not just these medications, to produce a noticeable effect for patients.

Still, “disorders of the gut-brain interaction likely do require a longer runway time to really assess their effects on multiple symptoms,” Dr. Cash said.

The tenapanor research presented at ACG will help in conveying that message to patients, Dr. Cash said.

“It also reinforces for clinicians not to be impatient,” he said.

Dr. Lacy and co-authors directed the development of the poster, and medical writing support was provided by Ashfield MedComms, an Inizio company, and funded by Ardelyx. Dr. Lacy has financial and consulting relationships with AbbVie, Ardelyx, Gernelli, Ironwood Pharmaceuticals, Salix, and Sanofi, Co-authors are employees of Ardelyx. Dr. Lembo and Dr. Cash have financial relationships with Ardelyx and other makers of IBS drugs.

A post hoc analysis of three clinical trials of tenapanor (Ibsrela, Ardelyx) shows the drug works within weeks to improve bowel function and abdominal symptoms in people with irritable bowel syndrome with constipation (IBS-C).

“Although onset of action occurs within the first week, continued therapy allows for a greater percentage of patients to achieve a meaningful response,” wrote Brian Lacy, MD, PhD, of the Mayo Clinic in Jacksonville, Florida, and co-authors in an abstract.

Dr. Lacy presented the results of this work at the annual scientific meeting of the American College of Gastroenterology (ACG) in Vancouver, Canada.

Tenapanor acts as an inhibitor of the sodium-hydrogen exchanger 3 (NHE3) and works to reduce dietary sodium absorption, which, in turn, leads to retention of fluid in the intestinal lumen, resulting in softer stool and accelerated intestinal transit, he explained.

Tenapanor is approved by the US Food and Drug Administration for adults with IBS-C.

The major goal of the analysis presented at ACG was to identify times to responses for individual symptoms, said Dr. Lacy in an email exchange with GI & Hepatology News.

Prior studies focused on global improvement in IBS-C symptoms using the FDA-approved definition of a responder: A patient who experienced at least a 30% reduction in the weekly average abdominal pain score and an increase of at least one complete spontaneous bowel movement (CSBM) in the same week for at least 6 of the first 12 treatment weeks.

“Thus, we thought it important to pool all of the data together for this post-hoc analysis, as clinicians and patients often wonder when an individual symptom will respond,” Dr. Lacy wrote in an email.

Dr. Lacy and colleagues conducted a post hoc analysis of pooled data from the phase 2b (NCT01923428) and phase 3 T3MPO-1 (NCT02621892) and T3MPO-2 (NCT02686138) studies to evaluate time to onset of tenapanor effect on bowel function and on individual and global abdominal symptoms in patients with IBS-C.

This resulted in a pooled population of 1372 intent-to-treat patients (688 placebo, 684 on the study drug), with demographics generally similar across the studies, they said.

They found that the median time to CSBM was 2 weeks, with an estimated response probability of 52.3% by week 2, 72.5% by week 8, and 76.7% by week 12.

The median time to abdominal pain response was 4 weeks; the estimated response probability was 54.6% by week 4, 67.9% by week 8, and 72.3% by week 12.

The median time to abdominal bloating response was 5 weeks; the estimated response probability was 48.1% by week 4, 61.9% by week 8, and 67.7% by week 12.

“The teaching message to patients and providers is not to give up too early; staying on this medication allowed 25% more people to improve symptoms,” Dr. Lacy wrote.

In separate interviews, two other researchers Anthony Lembo, MD, AGAF, director of research for Cleveland Clinic’s Digestive Disease & Surgery Institute, and Brooks D. Cash, MD, AGAF, chief for gastroenterology, hepatology, and nutrition at the University of Texas Health Science Center at Houston, agreed with Dr. Lacy’s message.

The study will help in counseling patients who may need to wait a bit to see a response from tenapanor, Dr. Lembo said.

“You wish patients would get better right away of course,” he said, but there can be some delay, even in cases where a drug will ultimately work for a patient.

Patients want to know if they should continue and if it is worth getting another prescription for another month if they haven’t had a significant improvement response, Dr. Lembo said.

Both Dr. Lembo and Dr. Cash said that it takes time for many drugs, not just these medications, to produce a noticeable effect for patients.

Still, “disorders of the gut-brain interaction likely do require a longer runway time to really assess their effects on multiple symptoms,” Dr. Cash said.

The tenapanor research presented at ACG will help in conveying that message to patients, Dr. Cash said.

“It also reinforces for clinicians not to be impatient,” he said.

Dr. Lacy and co-authors directed the development of the poster, and medical writing support was provided by Ashfield MedComms, an Inizio company, and funded by Ardelyx. Dr. Lacy has financial and consulting relationships with AbbVie, Ardelyx, Gernelli, Ironwood Pharmaceuticals, Salix, and Sanofi, Co-authors are employees of Ardelyx. Dr. Lembo and Dr. Cash have financial relationships with Ardelyx and other makers of IBS drugs.

A post hoc analysis of three clinical trials of tenapanor (Ibsrela, Ardelyx) shows the drug works within weeks to improve bowel function and abdominal symptoms in people with irritable bowel syndrome with constipation (IBS-C).

“Although onset of action occurs within the first week, continued therapy allows for a greater percentage of patients to achieve a meaningful response,” wrote Brian Lacy, MD, PhD, of the Mayo Clinic in Jacksonville, Florida, and co-authors in an abstract.

Dr. Lacy presented the results of this work at the annual scientific meeting of the American College of Gastroenterology (ACG) in Vancouver, Canada.

Tenapanor acts as an inhibitor of the sodium-hydrogen exchanger 3 (NHE3) and works to reduce dietary sodium absorption, which, in turn, leads to retention of fluid in the intestinal lumen, resulting in softer stool and accelerated intestinal transit, he explained.

Tenapanor is approved by the US Food and Drug Administration for adults with IBS-C.

The major goal of the analysis presented at ACG was to identify times to responses for individual symptoms, said Dr. Lacy in an email exchange with GI & Hepatology News.

Prior studies focused on global improvement in IBS-C symptoms using the FDA-approved definition of a responder: A patient who experienced at least a 30% reduction in the weekly average abdominal pain score and an increase of at least one complete spontaneous bowel movement (CSBM) in the same week for at least 6 of the first 12 treatment weeks.

“Thus, we thought it important to pool all of the data together for this post-hoc analysis, as clinicians and patients often wonder when an individual symptom will respond,” Dr. Lacy wrote in an email.

Dr. Lacy and colleagues conducted a post hoc analysis of pooled data from the phase 2b (NCT01923428) and phase 3 T3MPO-1 (NCT02621892) and T3MPO-2 (NCT02686138) studies to evaluate time to onset of tenapanor effect on bowel function and on individual and global abdominal symptoms in patients with IBS-C.

This resulted in a pooled population of 1372 intent-to-treat patients (688 placebo, 684 on the study drug), with demographics generally similar across the studies, they said.

They found that the median time to CSBM was 2 weeks, with an estimated response probability of 52.3% by week 2, 72.5% by week 8, and 76.7% by week 12.

The median time to abdominal pain response was 4 weeks; the estimated response probability was 54.6% by week 4, 67.9% by week 8, and 72.3% by week 12.

The median time to abdominal bloating response was 5 weeks; the estimated response probability was 48.1% by week 4, 61.9% by week 8, and 67.7% by week 12.

“The teaching message to patients and providers is not to give up too early; staying on this medication allowed 25% more people to improve symptoms,” Dr. Lacy wrote.

In separate interviews, two other researchers Anthony Lembo, MD, AGAF, director of research for Cleveland Clinic’s Digestive Disease & Surgery Institute, and Brooks D. Cash, MD, AGAF, chief for gastroenterology, hepatology, and nutrition at the University of Texas Health Science Center at Houston, agreed with Dr. Lacy’s message.

The study will help in counseling patients who may need to wait a bit to see a response from tenapanor, Dr. Lembo said.

“You wish patients would get better right away of course,” he said, but there can be some delay, even in cases where a drug will ultimately work for a patient.

Patients want to know if they should continue and if it is worth getting another prescription for another month if they haven’t had a significant improvement response, Dr. Lembo said.

Both Dr. Lembo and Dr. Cash said that it takes time for many drugs, not just these medications, to produce a noticeable effect for patients.

Still, “disorders of the gut-brain interaction likely do require a longer runway time to really assess their effects on multiple symptoms,” Dr. Cash said.

The tenapanor research presented at ACG will help in conveying that message to patients, Dr. Cash said.

“It also reinforces for clinicians not to be impatient,” he said.

Dr. Lacy and co-authors directed the development of the poster, and medical writing support was provided by Ashfield MedComms, an Inizio company, and funded by Ardelyx. Dr. Lacy has financial and consulting relationships with AbbVie, Ardelyx, Gernelli, Ironwood Pharmaceuticals, Salix, and Sanofi, Co-authors are employees of Ardelyx. Dr. Lembo and Dr. Cash have financial relationships with Ardelyx and other makers of IBS drugs.

TOPLINE:

Intra-articular corticosteroid (IACS) injections pose a minimal risk of accelerating diabetes for most people, despite temporarily elevating blood glucose levels, according to a study published in Clinical Diabetes.

METHODOLOGY:

• Almost half of Americans with diabetes have arthritis, so glycemic control is a concern for many receiving IACS injections.
• IACS injections are known to cause short-term hyperglycemia, but their long-term effects on glycemic control are not well studied.
• For the retrospective cohort study, researchers at Mayo Clinic in Rochester, Minnesota, used electronic health records from 1169 adults who had received an IACS injection in one large joint between 2012 and 2018.
• They analyzed data on A1C levels for study participants from 18 months before and after the injections.
• Researchers assessed if participants had a greater-than-expected (defined as an increase of more than 0.5% above expected) concentration of A1C after the injection, and examined rates of diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome in the 30 days following an injection.

TAKEAWAY:

• Nearly 16% of people experienced a greater-than-expected A1C level after receiving an injection.
• A1C levels rose by an average of 1.2% in the greater-than-expected group, but decreased by an average of 0.2% in the average group.
• One patient had an episode of severe hyperglycemia that was linked to the injection.
• A baseline level of A1C above 8% was the only factor associated with a greater-than-expected increase in the marker after an IACS injection.

IN PRACTICE:

“Although most patients do not experience an increase in A1C after IACS, clinicians should counsel patients with suboptimally controlled diabetes about risks of further hyperglycemia after IACS administration,” the researchers wrote. 

SOURCE: 

The study was led by Terin T. Sytsma, MD, of Mayo Clinic in Rochester, Minnesota.

LIMITATIONS: 

The study was retrospective and could not establish causation. In addition, the population was of residents from one county in Minnesota, and was not racially or ethnically diverse. Details about the injection, such as location and total dose, were not available. The study also did not include a control group. 

DISCLOSURES:

The study was funded by Mayo Clinic and the National Center for Advancing Translational Sciences. The authors reported no relevant disclosures.

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

TOPLINE:

Intra-articular corticosteroid (IACS) injections pose a minimal risk of accelerating diabetes for most people, despite temporarily elevating blood glucose levels, according to a study published in Clinical Diabetes.

METHODOLOGY:

• Almost half of Americans with diabetes have arthritis, so glycemic control is a concern for many receiving IACS injections.
• IACS injections are known to cause short-term hyperglycemia, but their long-term effects on glycemic control are not well studied.
• For the retrospective cohort study, researchers at Mayo Clinic in Rochester, Minnesota, used electronic health records from 1169 adults who had received an IACS injection in one large joint between 2012 and 2018.
• They analyzed data on A1C levels for study participants from 18 months before and after the injections.
• Researchers assessed if participants had a greater-than-expected (defined as an increase of more than 0.5% above expected) concentration of A1C after the injection, and examined rates of diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome in the 30 days following an injection.

TAKEAWAY:

• Nearly 16% of people experienced a greater-than-expected A1C level after receiving an injection.
• A1C levels rose by an average of 1.2% in the greater-than-expected group, but decreased by an average of 0.2% in the average group.
• One patient had an episode of severe hyperglycemia that was linked to the injection.
• A baseline level of A1C above 8% was the only factor associated with a greater-than-expected increase in the marker after an IACS injection.

IN PRACTICE:

“Although most patients do not experience an increase in A1C after IACS, clinicians should counsel patients with suboptimally controlled diabetes about risks of further hyperglycemia after IACS administration,” the researchers wrote. 

SOURCE: 

The study was led by Terin T. Sytsma, MD, of Mayo Clinic in Rochester, Minnesota.

LIMITATIONS: 

The study was retrospective and could not establish causation. In addition, the population was of residents from one county in Minnesota, and was not racially or ethnically diverse. Details about the injection, such as location and total dose, were not available. The study also did not include a control group. 

DISCLOSURES:

The study was funded by Mayo Clinic and the National Center for Advancing Translational Sciences. The authors reported no relevant disclosures.

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

TOPLINE:

Intra-articular corticosteroid (IACS) injections pose a minimal risk of accelerating diabetes for most people, despite temporarily elevating blood glucose levels, according to a study published in Clinical Diabetes.

METHODOLOGY:

• Almost half of Americans with diabetes have arthritis, so glycemic control is a concern for many receiving IACS injections.
• IACS injections are known to cause short-term hyperglycemia, but their long-term effects on glycemic control are not well studied.
• For the retrospective cohort study, researchers at Mayo Clinic in Rochester, Minnesota, used electronic health records from 1169 adults who had received an IACS injection in one large joint between 2012 and 2018.
• They analyzed data on A1C levels for study participants from 18 months before and after the injections.
• Researchers assessed if participants had a greater-than-expected (defined as an increase of more than 0.5% above expected) concentration of A1C after the injection, and examined rates of diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome in the 30 days following an injection.

TAKEAWAY:

• Nearly 16% of people experienced a greater-than-expected A1C level after receiving an injection.
• A1C levels rose by an average of 1.2% in the greater-than-expected group, but decreased by an average of 0.2% in the average group.
• One patient had an episode of severe hyperglycemia that was linked to the injection.
• A baseline level of A1C above 8% was the only factor associated with a greater-than-expected increase in the marker after an IACS injection.

IN PRACTICE:

“Although most patients do not experience an increase in A1C after IACS, clinicians should counsel patients with suboptimally controlled diabetes about risks of further hyperglycemia after IACS administration,” the researchers wrote. 

SOURCE: 

The study was led by Terin T. Sytsma, MD, of Mayo Clinic in Rochester, Minnesota.

LIMITATIONS: 

The study was retrospective and could not establish causation. In addition, the population was of residents from one county in Minnesota, and was not racially or ethnically diverse. Details about the injection, such as location and total dose, were not available. The study also did not include a control group. 

DISCLOSURES:

The study was funded by Mayo Clinic and the National Center for Advancing Translational Sciences. The authors reported no relevant disclosures.

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

TOPLINE: 

Among patients hospitalized with a first ischemic stroke, 80% were rehospitalized, primarily because of subsequent primary cardiovascular and cerebrovascular diagnoses.

METHODOLOGY:

• To gather information on post-stroke hospital admission, investigators followed 1412 participants (mean age, 72.4 years; 52.1% women, 35.3% Black individuals) from the Atherosclerosis Risk in Communities (ARIC) study who were living in Maryland, Minnesota, North Carolina, and Mississippi.
• Participants were recruited between 1987 and 1989 when they were 45-64 years old and were followed on an annual and then semiannual basis from the index discharge until discharge after their second hospitalization, death, or end of the study in December 2019.
• Specific diagnoses for each hospitalization were based on hospital records, discharge diagnoses, and annual and semiannual phone interviews.

TAKEAWAY: 

• During the study period, 1143 hospitalizations occurred over 41,849 person-months.
• 81% of participants were hospitalized over a maximum of 26.6 years of follow-up. Primary cardiovascular and cerebrovascular diagnoses were reported for half of readmissions.
• Over the follow-up period, compared with cardioembolic stroke, readmission risk was lower for thrombotic/lacunar stroke (adjusted hazard ratio [aHR], 0.82; 95% CI, 0.71-0.95) and hemorrhagic stroke (aHR, 0.74; 95% CI, 0.58-0.93). However, when adjusting for atrial fibrillation and competing risk for death, there were no significant differences between stroke subtypes.
• Compared with cardioembolic stroke, thrombotic/lacunar stroke was associated with lower readmission risk within 1 month (aHR, 0.66; 95% CI, 0.46-0.93) and from 1 month to 1 year (aHR, 0.78; 95% CI, 0.62-0.97), and hemorrhagic stroke was associated with lower risk from 1 month to 1 year (aHR, 0.60; 95% CI, 0.41-0.87).

IN PRACTICE:

“These results suggest that prevention strategies focused on cardiovascular and cerebrovascular health warrant further investigation, especially within the first year after incident stroke and perhaps particularly among individuals with an incident cardioembolic stroke,” the authors wrote.

SOURCE:

Kelly Sloane, MD, of the University of Pennsylvania Perelman School of Medicine in Philadelphia, led the study along with colleagues at the National Institute of Neurological Disorders and Stroke, Johns Hopkins University in Baltimore, and the University of North Carolina, Chapel Hill. The article was published online on January 5 in Neurology.

LIMITATIONS:

The ARIC study classification of stroke subtype grouped embolic strokes of undetermined source as thrombotic strokes, and investigators were unable to distinguish between the groups. In addition, there was no way to measure stroke severity, which could have played a role in readmission risk.

DISCLOSURES:

The study was funded by the National Heart, Lung, and Blood Institute, the National Institute of Neurological Disorders and Stroke, and the National Institutes of Health.

A version of this article appeared on Medscape.com.

TOPLINE: 

Among patients hospitalized with a first ischemic stroke, 80% were rehospitalized, primarily because of subsequent primary cardiovascular and cerebrovascular diagnoses.

METHODOLOGY:

• To gather information on post-stroke hospital admission, investigators followed 1412 participants (mean age, 72.4 years; 52.1% women, 35.3% Black individuals) from the Atherosclerosis Risk in Communities (ARIC) study who were living in Maryland, Minnesota, North Carolina, and Mississippi.
• Participants were recruited between 1987 and 1989 when they were 45-64 years old and were followed on an annual and then semiannual basis from the index discharge until discharge after their second hospitalization, death, or end of the study in December 2019.
• Specific diagnoses for each hospitalization were based on hospital records, discharge diagnoses, and annual and semiannual phone interviews.

TAKEAWAY: 

• During the study period, 1143 hospitalizations occurred over 41,849 person-months.
• 81% of participants were hospitalized over a maximum of 26.6 years of follow-up. Primary cardiovascular and cerebrovascular diagnoses were reported for half of readmissions.
• Over the follow-up period, compared with cardioembolic stroke, readmission risk was lower for thrombotic/lacunar stroke (adjusted hazard ratio [aHR], 0.82; 95% CI, 0.71-0.95) and hemorrhagic stroke (aHR, 0.74; 95% CI, 0.58-0.93). However, when adjusting for atrial fibrillation and competing risk for death, there were no significant differences between stroke subtypes.
• Compared with cardioembolic stroke, thrombotic/lacunar stroke was associated with lower readmission risk within 1 month (aHR, 0.66; 95% CI, 0.46-0.93) and from 1 month to 1 year (aHR, 0.78; 95% CI, 0.62-0.97), and hemorrhagic stroke was associated with lower risk from 1 month to 1 year (aHR, 0.60; 95% CI, 0.41-0.87).

IN PRACTICE:

“These results suggest that prevention strategies focused on cardiovascular and cerebrovascular health warrant further investigation, especially within the first year after incident stroke and perhaps particularly among individuals with an incident cardioembolic stroke,” the authors wrote.

SOURCE:

Kelly Sloane, MD, of the University of Pennsylvania Perelman School of Medicine in Philadelphia, led the study along with colleagues at the National Institute of Neurological Disorders and Stroke, Johns Hopkins University in Baltimore, and the University of North Carolina, Chapel Hill. The article was published online on January 5 in Neurology.

LIMITATIONS:

The ARIC study classification of stroke subtype grouped embolic strokes of undetermined source as thrombotic strokes, and investigators were unable to distinguish between the groups. In addition, there was no way to measure stroke severity, which could have played a role in readmission risk.

DISCLOSURES:

The study was funded by the National Heart, Lung, and Blood Institute, the National Institute of Neurological Disorders and Stroke, and the National Institutes of Health.

A version of this article appeared on Medscape.com.

TOPLINE: 

Among patients hospitalized with a first ischemic stroke, 80% were rehospitalized, primarily because of subsequent primary cardiovascular and cerebrovascular diagnoses.

METHODOLOGY:

• To gather information on post-stroke hospital admission, investigators followed 1412 participants (mean age, 72.4 years; 52.1% women, 35.3% Black individuals) from the Atherosclerosis Risk in Communities (ARIC) study who were living in Maryland, Minnesota, North Carolina, and Mississippi.
• Participants were recruited between 1987 and 1989 when they were 45-64 years old and were followed on an annual and then semiannual basis from the index discharge until discharge after their second hospitalization, death, or end of the study in December 2019.
• Specific diagnoses for each hospitalization were based on hospital records, discharge diagnoses, and annual and semiannual phone interviews.

TAKEAWAY: 

• During the study period, 1143 hospitalizations occurred over 41,849 person-months.
• 81% of participants were hospitalized over a maximum of 26.6 years of follow-up. Primary cardiovascular and cerebrovascular diagnoses were reported for half of readmissions.
• Over the follow-up period, compared with cardioembolic stroke, readmission risk was lower for thrombotic/lacunar stroke (adjusted hazard ratio [aHR], 0.82; 95% CI, 0.71-0.95) and hemorrhagic stroke (aHR, 0.74; 95% CI, 0.58-0.93). However, when adjusting for atrial fibrillation and competing risk for death, there were no significant differences between stroke subtypes.
• Compared with cardioembolic stroke, thrombotic/lacunar stroke was associated with lower readmission risk within 1 month (aHR, 0.66; 95% CI, 0.46-0.93) and from 1 month to 1 year (aHR, 0.78; 95% CI, 0.62-0.97), and hemorrhagic stroke was associated with lower risk from 1 month to 1 year (aHR, 0.60; 95% CI, 0.41-0.87).

IN PRACTICE:

“These results suggest that prevention strategies focused on cardiovascular and cerebrovascular health warrant further investigation, especially within the first year after incident stroke and perhaps particularly among individuals with an incident cardioembolic stroke,” the authors wrote.

SOURCE:

Kelly Sloane, MD, of the University of Pennsylvania Perelman School of Medicine in Philadelphia, led the study along with colleagues at the National Institute of Neurological Disorders and Stroke, Johns Hopkins University in Baltimore, and the University of North Carolina, Chapel Hill. The article was published online on January 5 in Neurology.

LIMITATIONS:

The ARIC study classification of stroke subtype grouped embolic strokes of undetermined source as thrombotic strokes, and investigators were unable to distinguish between the groups. In addition, there was no way to measure stroke severity, which could have played a role in readmission risk.

DISCLOSURES:

The study was funded by the National Heart, Lung, and Blood Institute, the National Institute of Neurological Disorders and Stroke, and the National Institutes of Health.

A version of this article appeared on Medscape.com.