Whipple's disease

The ultrasound features were highly suggestive of malabsorption, a hypothesis that was supported by the laboratory findings. Celiac disease, one of the most common causes of malabsorption, was excluded by serology tests. Esophagogastroduodenoscopy was therefore repeated: The mucosa of the distal first part and second part of the duodenum appeared completely covered with tiny white spots (Figure C). Histologic examination revealed that the mucosal architecture of the villi was altered by the presence of infiltrates of macrophages with wide cytoplasm filled with round periodic acid-Schiff (PAS)-positive inclusions, associated to aggregates of neutrophils attacking the epithelium (Figure D). These histologic findings are consistent with Whipple's disease.

In the literature, few case reports describe the ultrasound findings in patients with Whipple's disease. The most frequent sonographic features include small-bowel dilatation with wall thickening, the presence of peri-intestinal fluid effusion and mesenteric and retroperitoneal lymphadenopathy.2,3 

The final diagnosis relies on intestinal biopsy and the histologic finding of foamy macrophages containing large amounts of diastase-resistant PAS-positive particles in the lamina propria of the duodenum, jejunum, ileum, or gastric antral region.

The diagnosis, particularly in cases of extraintestinal involvement, can be confirmed by polymerase chain reaction positivity for T. whipplei in the examined tissue. 

Therapy consists of the administration of ceftriaxone (2 g IV once daily) for 2 weeks followed by oral therapy with trimethoprim-sulfamethoxazole for 1 year. 
 

References 

1. Schneider T et al. Whipple's disease: New aspects of pathogenesis and treatment. Lancet Infect Dis. 2008;8:179-90. 
2. Brindicci D et al. Ultrasonic findings in Whipple's disease. J Clin Ultrasound. 1984;12:286-8. 
3. Neye H et al. Der Morbus Whipple's Disease - A rare intestinal disease and its sonographic characteristics. Ultraschall Med. 2012;33(04):314-5.

Whipple's disease

The ultrasound features were highly suggestive of malabsorption, a hypothesis that was supported by the laboratory findings. Celiac disease, one of the most common causes of malabsorption, was excluded by serology tests. Esophagogastroduodenoscopy was therefore repeated: The mucosa of the distal first part and second part of the duodenum appeared completely covered with tiny white spots (Figure C). Histologic examination revealed that the mucosal architecture of the villi was altered by the presence of infiltrates of macrophages with wide cytoplasm filled with round periodic acid-Schiff (PAS)-positive inclusions, associated to aggregates of neutrophils attacking the epithelium (Figure D). These histologic findings are consistent with Whipple's disease.

In the literature, few case reports describe the ultrasound findings in patients with Whipple's disease. The most frequent sonographic features include small-bowel dilatation with wall thickening, the presence of peri-intestinal fluid effusion and mesenteric and retroperitoneal lymphadenopathy.2,3 

The final diagnosis relies on intestinal biopsy and the histologic finding of foamy macrophages containing large amounts of diastase-resistant PAS-positive particles in the lamina propria of the duodenum, jejunum, ileum, or gastric antral region.

The diagnosis, particularly in cases of extraintestinal involvement, can be confirmed by polymerase chain reaction positivity for T. whipplei in the examined tissue. 

Therapy consists of the administration of ceftriaxone (2 g IV once daily) for 2 weeks followed by oral therapy with trimethoprim-sulfamethoxazole for 1 year. 
 

References 

1. Schneider T et al. Whipple's disease: New aspects of pathogenesis and treatment. Lancet Infect Dis. 2008;8:179-90. 
2. Brindicci D et al. Ultrasonic findings in Whipple's disease. J Clin Ultrasound. 1984;12:286-8. 
3. Neye H et al. Der Morbus Whipple's Disease - A rare intestinal disease and its sonographic characteristics. Ultraschall Med. 2012;33(04):314-5.

Whipple's disease

The ultrasound features were highly suggestive of malabsorption, a hypothesis that was supported by the laboratory findings. Celiac disease, one of the most common causes of malabsorption, was excluded by serology tests. Esophagogastroduodenoscopy was therefore repeated: The mucosa of the distal first part and second part of the duodenum appeared completely covered with tiny white spots (Figure C). Histologic examination revealed that the mucosal architecture of the villi was altered by the presence of infiltrates of macrophages with wide cytoplasm filled with round periodic acid-Schiff (PAS)-positive inclusions, associated to aggregates of neutrophils attacking the epithelium (Figure D). These histologic findings are consistent with Whipple's disease.

In the literature, few case reports describe the ultrasound findings in patients with Whipple's disease. The most frequent sonographic features include small-bowel dilatation with wall thickening, the presence of peri-intestinal fluid effusion and mesenteric and retroperitoneal lymphadenopathy.2,3 

The final diagnosis relies on intestinal biopsy and the histologic finding of foamy macrophages containing large amounts of diastase-resistant PAS-positive particles in the lamina propria of the duodenum, jejunum, ileum, or gastric antral region.

The diagnosis, particularly in cases of extraintestinal involvement, can be confirmed by polymerase chain reaction positivity for T. whipplei in the examined tissue. 

Therapy consists of the administration of ceftriaxone (2 g IV once daily) for 2 weeks followed by oral therapy with trimethoprim-sulfamethoxazole for 1 year. 
 

References 

1. Schneider T et al. Whipple's disease: New aspects of pathogenesis and treatment. Lancet Infect Dis. 2008;8:179-90. 
2. Brindicci D et al. Ultrasonic findings in Whipple's disease. J Clin Ultrasound. 1984;12:286-8. 
3. Neye H et al. Der Morbus Whipple's Disease - A rare intestinal disease and its sonographic characteristics. Ultraschall Med. 2012;33(04):314-5.

In 2002, two landmark trials found that targeted temperature management (TTM) after out-of-hospital cardiac arrest led to improvements in neurologic outcomes. The larger of the two trials found a reduction in mortality. Such treatment benefits are hard to come by in critical care in general and in out-of-hospital cardiac arrest in particular. With the therapeutic overconfidence typical of our profession, my institution embraced TTM quickly and completely soon after these trials were published. Remember, this was “back in the day” when sepsis management included drotrecogin alfa, Cortrosyn stim tests, tight glucose control (90-120 mg/dL), and horrible over-resuscitation via the early goal-directed therapy paradigm.

If you’ve been practicing critical care medicine for more than a few years, you already know where I’m going. Most of the interventions in the preceding paragraph were adopted but discarded before 2010. Though TTM has managed to stand the test of time, our confidence in its benefit has waned since 2002. Hypothermia – temperature management with a goal of 32-36° C – has been struggling to stay relevant ever since the publication of the TTM randomized controlled trial (RCT) in 2013. Then came the HYPERION trial, which brought the 32-36° C target back from the dead (pun definitely intended) in 2019. This is critical care medicine: Today’s life-saving intervention proves harmful tomorrow, but withholding it may constitute malpractice a few months down the road.

So where are we now? Good question. I’ve had seasoned neurointensivists insist that 33° C remains the standard of care and others who’ve endorsed normothermia. So much for finding an answer via my more specialized colleagues.

Let’s go to the guidelines then. Prompted largely by HYPERION, a temperature target of 32-36° C was endorsed in 2020 and 2021. Then came publication of the TTM2 trial, the largest temperature management RCT to date, which found no benefit to targeting 33° C. A network meta-analysis published in 2021 reached a similar conclusion. A recently released update by the same international guideline group now recommends targeting normothermia (< 37.7° C) and avoiding fever, and it specifically says that there is insufficient evidence to support a 32-36° C target. Okay, everyone tracking all that?

Lest I sound overly catty and nihilistic, I see all this in a positive light. Huge credit goes to the critical care medicine academic community for putting together so many RCTs. The scientific reality is that it takes “a lotta” sample size to clarify the effects of an intervention. Throw in the inevitable bevy of confounders (in- vs. out-of-hospital cardiac arrest, resuscitation time, initial rhythm, and so on), and you get a feel for the work required to understand a treatment’s true effects.

Advances in guideline science and the hard, often unpaid work of panels are also important. The guideline panel I’ve been citing came out for aggressive temperature control (32-36° C) a few months before the TTM2 RCT was published. In the past, they updated their recommendations every 5 years, but this time, they were out with a new manuscript that incorporated TTM2 in less than a year. If you’ve been involved at any level with producing guidelines, you can appreciate this achievement. Assuming that aggressive hypothermia is truly harmful, waiting 5 years to incorporate TTM2 could have led to significant morbidity.

I do take issue with you early adopters, though. Given the litany of failed therapies that have shown initial promise, and the well-documented human tendency to underestimate the impact of sample size, your rapid implementation of major interventions is puzzling. One might think you’d learned your lessons after seeing drotrecogin alfa, Cortrosyn stim tests, tight glucose control, early goal-directed therapy, and aggressive TTM come and go. Your recent enthusiasm for vitamin C after publication of a single before-after study suggests that you haven’t.

Aaron B. Holley, MD, is an associate professor of medicine at Uniformed Services University and program director of pulmonary and critical care medicine at Walter Reed National Military Medical Center, Bethesda, Md. He has received a research grant from Fisher-Paykel.

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

In 2002, two landmark trials found that targeted temperature management (TTM) after out-of-hospital cardiac arrest led to improvements in neurologic outcomes. The larger of the two trials found a reduction in mortality. Such treatment benefits are hard to come by in critical care in general and in out-of-hospital cardiac arrest in particular. With the therapeutic overconfidence typical of our profession, my institution embraced TTM quickly and completely soon after these trials were published. Remember, this was “back in the day” when sepsis management included drotrecogin alfa, Cortrosyn stim tests, tight glucose control (90-120 mg/dL), and horrible over-resuscitation via the early goal-directed therapy paradigm.

If you’ve been practicing critical care medicine for more than a few years, you already know where I’m going. Most of the interventions in the preceding paragraph were adopted but discarded before 2010. Though TTM has managed to stand the test of time, our confidence in its benefit has waned since 2002. Hypothermia – temperature management with a goal of 32-36° C – has been struggling to stay relevant ever since the publication of the TTM randomized controlled trial (RCT) in 2013. Then came the HYPERION trial, which brought the 32-36° C target back from the dead (pun definitely intended) in 2019. This is critical care medicine: Today’s life-saving intervention proves harmful tomorrow, but withholding it may constitute malpractice a few months down the road.

So where are we now? Good question. I’ve had seasoned neurointensivists insist that 33° C remains the standard of care and others who’ve endorsed normothermia. So much for finding an answer via my more specialized colleagues.

Let’s go to the guidelines then. Prompted largely by HYPERION, a temperature target of 32-36° C was endorsed in 2020 and 2021. Then came publication of the TTM2 trial, the largest temperature management RCT to date, which found no benefit to targeting 33° C. A network meta-analysis published in 2021 reached a similar conclusion. A recently released update by the same international guideline group now recommends targeting normothermia (< 37.7° C) and avoiding fever, and it specifically says that there is insufficient evidence to support a 32-36° C target. Okay, everyone tracking all that?

Lest I sound overly catty and nihilistic, I see all this in a positive light. Huge credit goes to the critical care medicine academic community for putting together so many RCTs. The scientific reality is that it takes “a lotta” sample size to clarify the effects of an intervention. Throw in the inevitable bevy of confounders (in- vs. out-of-hospital cardiac arrest, resuscitation time, initial rhythm, and so on), and you get a feel for the work required to understand a treatment’s true effects.

Advances in guideline science and the hard, often unpaid work of panels are also important. The guideline panel I’ve been citing came out for aggressive temperature control (32-36° C) a few months before the TTM2 RCT was published. In the past, they updated their recommendations every 5 years, but this time, they were out with a new manuscript that incorporated TTM2 in less than a year. If you’ve been involved at any level with producing guidelines, you can appreciate this achievement. Assuming that aggressive hypothermia is truly harmful, waiting 5 years to incorporate TTM2 could have led to significant morbidity.

I do take issue with you early adopters, though. Given the litany of failed therapies that have shown initial promise, and the well-documented human tendency to underestimate the impact of sample size, your rapid implementation of major interventions is puzzling. One might think you’d learned your lessons after seeing drotrecogin alfa, Cortrosyn stim tests, tight glucose control, early goal-directed therapy, and aggressive TTM come and go. Your recent enthusiasm for vitamin C after publication of a single before-after study suggests that you haven’t.

Aaron B. Holley, MD, is an associate professor of medicine at Uniformed Services University and program director of pulmonary and critical care medicine at Walter Reed National Military Medical Center, Bethesda, Md. He has received a research grant from Fisher-Paykel.

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

In 2002, two landmark trials found that targeted temperature management (TTM) after out-of-hospital cardiac arrest led to improvements in neurologic outcomes. The larger of the two trials found a reduction in mortality. Such treatment benefits are hard to come by in critical care in general and in out-of-hospital cardiac arrest in particular. With the therapeutic overconfidence typical of our profession, my institution embraced TTM quickly and completely soon after these trials were published. Remember, this was “back in the day” when sepsis management included drotrecogin alfa, Cortrosyn stim tests, tight glucose control (90-120 mg/dL), and horrible over-resuscitation via the early goal-directed therapy paradigm.

If you’ve been practicing critical care medicine for more than a few years, you already know where I’m going. Most of the interventions in the preceding paragraph were adopted but discarded before 2010. Though TTM has managed to stand the test of time, our confidence in its benefit has waned since 2002. Hypothermia – temperature management with a goal of 32-36° C – has been struggling to stay relevant ever since the publication of the TTM randomized controlled trial (RCT) in 2013. Then came the HYPERION trial, which brought the 32-36° C target back from the dead (pun definitely intended) in 2019. This is critical care medicine: Today’s life-saving intervention proves harmful tomorrow, but withholding it may constitute malpractice a few months down the road.

So where are we now? Good question. I’ve had seasoned neurointensivists insist that 33° C remains the standard of care and others who’ve endorsed normothermia. So much for finding an answer via my more specialized colleagues.

Let’s go to the guidelines then. Prompted largely by HYPERION, a temperature target of 32-36° C was endorsed in 2020 and 2021. Then came publication of the TTM2 trial, the largest temperature management RCT to date, which found no benefit to targeting 33° C. A network meta-analysis published in 2021 reached a similar conclusion. A recently released update by the same international guideline group now recommends targeting normothermia (< 37.7° C) and avoiding fever, and it specifically says that there is insufficient evidence to support a 32-36° C target. Okay, everyone tracking all that?

Lest I sound overly catty and nihilistic, I see all this in a positive light. Huge credit goes to the critical care medicine academic community for putting together so many RCTs. The scientific reality is that it takes “a lotta” sample size to clarify the effects of an intervention. Throw in the inevitable bevy of confounders (in- vs. out-of-hospital cardiac arrest, resuscitation time, initial rhythm, and so on), and you get a feel for the work required to understand a treatment’s true effects.

Advances in guideline science and the hard, often unpaid work of panels are also important. The guideline panel I’ve been citing came out for aggressive temperature control (32-36° C) a few months before the TTM2 RCT was published. In the past, they updated their recommendations every 5 years, but this time, they were out with a new manuscript that incorporated TTM2 in less than a year. If you’ve been involved at any level with producing guidelines, you can appreciate this achievement. Assuming that aggressive hypothermia is truly harmful, waiting 5 years to incorporate TTM2 could have led to significant morbidity.

I do take issue with you early adopters, though. Given the litany of failed therapies that have shown initial promise, and the well-documented human tendency to underestimate the impact of sample size, your rapid implementation of major interventions is puzzling. One might think you’d learned your lessons after seeing drotrecogin alfa, Cortrosyn stim tests, tight glucose control, early goal-directed therapy, and aggressive TTM come and go. Your recent enthusiasm for vitamin C after publication of a single before-after study suggests that you haven’t.

Aaron B. Holley, MD, is an associate professor of medicine at Uniformed Services University and program director of pulmonary and critical care medicine at Walter Reed National Military Medical Center, Bethesda, Md. He has received a research grant from Fisher-Paykel.

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

Several new studies in noncolorectal GI cancers have launched in recent months. Could one of your patients benefit from participating?

Advanced hepatocellular cancer after at least two previous systemic therapies

Adult patients meeting this clinical scenario for whom there are no curative treatment options can join a randomized, blinded, phase 2 study testing the effectiveness of a radio wave device called TheraBionic. This home-administered device drenches the body in a nonthermal electromagnetic field via a spoon-shaped antenna held in the patient’s mouth. TheraBionic received Food and Drug Administration Breakthrough Device designation in 2019, and the device is still experimental.

In the trial, all participants will self-treat in three 1-hour sessions daily for up to 6 months. In the placebo arm, the device will not emit any therapeutic frequencies. Overall survival and quality of life over 6 months are the primary endpoints, and investigators are seeking to enroll 166 participants. Wake Forest Baptist Comprehensive Cancer Center in Winston-Salem, N.C., has begun recruitment, and centers in Phoenix and Chicago will begin recruiting soon. More details at clinicaltrials.gov.
 

Unresectable nonmetastatic hepatocellular carcinoma

Individuals with this type of liver cancer who have not received any treatment are being recruited for a randomized, phase 2 study of a targeted radiation treatment called TheraSphere. The study will assess whether the effectiveness of TheraSphere can be boosted with immunotherapy.

TheraSphere was approved by the FDA in March 2021. It consists of yttrium-90 encased in millions of microscopic glass spheres that, after infusion, lodge exclusively in the tumor site.

All patients in the trial will receive a single dose of TheraSphere. People in the immunotherapy arm will also receive a single intravenous infusion of investigational tremelimumab plus durvalumab (Imfinzi), then monthly infusions of durvalumab for up to 18 months. The study, which opened in Illinois and New York in September, aims to enroll 150 participants. Objective response rate and duration of response are the primary outcomes; overall survival and quality of life are secondary endpoints. More details at clinicaltrials.gov.
 

Locally advanced or metastatic unresectable gastric or gastroesophageal-junction (GEJ) cancer

Adults with these types of cancer who have received two or three prior lines of standard treatment for metastatic disease are sought for a nonrandomized, phase 2 trial assessing whether disease progression can be slowed by navicixizumab in combination with paclitaxel (Taxol). Navicixizumab is an experimental antiangiogenic therapy that has been tested so far in a small phase 1 trial of patients with refractory gynecologic, breast, and GI cancers.

In this phase 2 trial, patients with gastric or GEJ cancer will receive navicixizumab infusions every other week for up to 1 year, as well as weekly paclitaxel infusions. The study opened in August in sites in Arkansas, Georgia, Louisiana, New York, Ohio, and Tennessee. It aims to enroll 180 participants who have a range of solid tumors. The primary outcomes are overall response rate and progression-free survival; overall survival is a secondary outcome. Quality of life will not be assessed. More details at clinicaltrials.gov.
 

Untreated metastatic pancreatic ductal adenocarcinoma

Adult patients with this disease can join a randomized, blinded, phase 2/3 study testing polyamine inhibitor SBP-101 (diethyl dihydroxyhomospermine) in combination with standard-of-care therapies gemcitabine (Gemzar) and nab-paclitaxel (Abraxane). Polyamine metabolism is central to cellular growth and proliferation.

SBP-101 inhibited pancreatic tumor growth in its phase 1 trial. In the phase 2/3 study, all participants will receive gemcitabine and nab-paclitaxel for up to 3 years; those in the experimental group will also receive SBP-101. The trial began recruiting an initial 150 participants in Arkansas, Texas, and Wisconsin in August, with the option to recruit additional patients on the basis of an interim analysis when 104 patients have either died or the disease has progressed. The primary outcome is overall survival, and the secondary outcome is quality of life. More details at clinicaltrials.gov.
 

Previously treated unresectable, locally advanced or metastatic liver cancer

People with this type of liver cancer are eligible for a randomized, phase 2 study to determine whether survival can be improved by combining the immunotherapy atezolizumab with a targeted therapy – carbozantinib or lenvatinib. All participants will take carbozantinib or lenvatinib capsules daily for up to 3 years. Half the group will also receive intravenous atezolizumab every 3 weeks. The University Medical Center New Orleans started recruiting 122 participants in May, and study sites are gearing up in eight more states. Overall survival and progression-free survival are primary endpoints; quality of life will not be tracked. More details at clinicaltrials.gov.

All trial information is from the National Institutes of Health U.S. National Library of Medicine (online at clinicaltrials.gov).

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

Several new studies in noncolorectal GI cancers have launched in recent months. Could one of your patients benefit from participating?

Advanced hepatocellular cancer after at least two previous systemic therapies

Adult patients meeting this clinical scenario for whom there are no curative treatment options can join a randomized, blinded, phase 2 study testing the effectiveness of a radio wave device called TheraBionic. This home-administered device drenches the body in a nonthermal electromagnetic field via a spoon-shaped antenna held in the patient’s mouth. TheraBionic received Food and Drug Administration Breakthrough Device designation in 2019, and the device is still experimental.

In the trial, all participants will self-treat in three 1-hour sessions daily for up to 6 months. In the placebo arm, the device will not emit any therapeutic frequencies. Overall survival and quality of life over 6 months are the primary endpoints, and investigators are seeking to enroll 166 participants. Wake Forest Baptist Comprehensive Cancer Center in Winston-Salem, N.C., has begun recruitment, and centers in Phoenix and Chicago will begin recruiting soon. More details at clinicaltrials.gov.
 

Unresectable nonmetastatic hepatocellular carcinoma

Individuals with this type of liver cancer who have not received any treatment are being recruited for a randomized, phase 2 study of a targeted radiation treatment called TheraSphere. The study will assess whether the effectiveness of TheraSphere can be boosted with immunotherapy.

TheraSphere was approved by the FDA in March 2021. It consists of yttrium-90 encased in millions of microscopic glass spheres that, after infusion, lodge exclusively in the tumor site.

All patients in the trial will receive a single dose of TheraSphere. People in the immunotherapy arm will also receive a single intravenous infusion of investigational tremelimumab plus durvalumab (Imfinzi), then monthly infusions of durvalumab for up to 18 months. The study, which opened in Illinois and New York in September, aims to enroll 150 participants. Objective response rate and duration of response are the primary outcomes; overall survival and quality of life are secondary endpoints. More details at clinicaltrials.gov.
 

Locally advanced or metastatic unresectable gastric or gastroesophageal-junction (GEJ) cancer

Adults with these types of cancer who have received two or three prior lines of standard treatment for metastatic disease are sought for a nonrandomized, phase 2 trial assessing whether disease progression can be slowed by navicixizumab in combination with paclitaxel (Taxol). Navicixizumab is an experimental antiangiogenic therapy that has been tested so far in a small phase 1 trial of patients with refractory gynecologic, breast, and GI cancers.

In this phase 2 trial, patients with gastric or GEJ cancer will receive navicixizumab infusions every other week for up to 1 year, as well as weekly paclitaxel infusions. The study opened in August in sites in Arkansas, Georgia, Louisiana, New York, Ohio, and Tennessee. It aims to enroll 180 participants who have a range of solid tumors. The primary outcomes are overall response rate and progression-free survival; overall survival is a secondary outcome. Quality of life will not be assessed. More details at clinicaltrials.gov.
 

Untreated metastatic pancreatic ductal adenocarcinoma

Adult patients with this disease can join a randomized, blinded, phase 2/3 study testing polyamine inhibitor SBP-101 (diethyl dihydroxyhomospermine) in combination with standard-of-care therapies gemcitabine (Gemzar) and nab-paclitaxel (Abraxane). Polyamine metabolism is central to cellular growth and proliferation.

SBP-101 inhibited pancreatic tumor growth in its phase 1 trial. In the phase 2/3 study, all participants will receive gemcitabine and nab-paclitaxel for up to 3 years; those in the experimental group will also receive SBP-101. The trial began recruiting an initial 150 participants in Arkansas, Texas, and Wisconsin in August, with the option to recruit additional patients on the basis of an interim analysis when 104 patients have either died or the disease has progressed. The primary outcome is overall survival, and the secondary outcome is quality of life. More details at clinicaltrials.gov.
 

Previously treated unresectable, locally advanced or metastatic liver cancer

People with this type of liver cancer are eligible for a randomized, phase 2 study to determine whether survival can be improved by combining the immunotherapy atezolizumab with a targeted therapy – carbozantinib or lenvatinib. All participants will take carbozantinib or lenvatinib capsules daily for up to 3 years. Half the group will also receive intravenous atezolizumab every 3 weeks. The University Medical Center New Orleans started recruiting 122 participants in May, and study sites are gearing up in eight more states. Overall survival and progression-free survival are primary endpoints; quality of life will not be tracked. More details at clinicaltrials.gov.

All trial information is from the National Institutes of Health U.S. National Library of Medicine (online at clinicaltrials.gov).

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

Several new studies in noncolorectal GI cancers have launched in recent months. Could one of your patients benefit from participating?

Advanced hepatocellular cancer after at least two previous systemic therapies

Adult patients meeting this clinical scenario for whom there are no curative treatment options can join a randomized, blinded, phase 2 study testing the effectiveness of a radio wave device called TheraBionic. This home-administered device drenches the body in a nonthermal electromagnetic field via a spoon-shaped antenna held in the patient’s mouth. TheraBionic received Food and Drug Administration Breakthrough Device designation in 2019, and the device is still experimental.

In the trial, all participants will self-treat in three 1-hour sessions daily for up to 6 months. In the placebo arm, the device will not emit any therapeutic frequencies. Overall survival and quality of life over 6 months are the primary endpoints, and investigators are seeking to enroll 166 participants. Wake Forest Baptist Comprehensive Cancer Center in Winston-Salem, N.C., has begun recruitment, and centers in Phoenix and Chicago will begin recruiting soon. More details at clinicaltrials.gov.
 

Unresectable nonmetastatic hepatocellular carcinoma

Individuals with this type of liver cancer who have not received any treatment are being recruited for a randomized, phase 2 study of a targeted radiation treatment called TheraSphere. The study will assess whether the effectiveness of TheraSphere can be boosted with immunotherapy.

TheraSphere was approved by the FDA in March 2021. It consists of yttrium-90 encased in millions of microscopic glass spheres that, after infusion, lodge exclusively in the tumor site.

All patients in the trial will receive a single dose of TheraSphere. People in the immunotherapy arm will also receive a single intravenous infusion of investigational tremelimumab plus durvalumab (Imfinzi), then monthly infusions of durvalumab for up to 18 months. The study, which opened in Illinois and New York in September, aims to enroll 150 participants. Objective response rate and duration of response are the primary outcomes; overall survival and quality of life are secondary endpoints. More details at clinicaltrials.gov.
 

Locally advanced or metastatic unresectable gastric or gastroesophageal-junction (GEJ) cancer

Adults with these types of cancer who have received two or three prior lines of standard treatment for metastatic disease are sought for a nonrandomized, phase 2 trial assessing whether disease progression can be slowed by navicixizumab in combination with paclitaxel (Taxol). Navicixizumab is an experimental antiangiogenic therapy that has been tested so far in a small phase 1 trial of patients with refractory gynecologic, breast, and GI cancers.

In this phase 2 trial, patients with gastric or GEJ cancer will receive navicixizumab infusions every other week for up to 1 year, as well as weekly paclitaxel infusions. The study opened in August in sites in Arkansas, Georgia, Louisiana, New York, Ohio, and Tennessee. It aims to enroll 180 participants who have a range of solid tumors. The primary outcomes are overall response rate and progression-free survival; overall survival is a secondary outcome. Quality of life will not be assessed. More details at clinicaltrials.gov.
 

Untreated metastatic pancreatic ductal adenocarcinoma

Adult patients with this disease can join a randomized, blinded, phase 2/3 study testing polyamine inhibitor SBP-101 (diethyl dihydroxyhomospermine) in combination with standard-of-care therapies gemcitabine (Gemzar) and nab-paclitaxel (Abraxane). Polyamine metabolism is central to cellular growth and proliferation.

SBP-101 inhibited pancreatic tumor growth in its phase 1 trial. In the phase 2/3 study, all participants will receive gemcitabine and nab-paclitaxel for up to 3 years; those in the experimental group will also receive SBP-101. The trial began recruiting an initial 150 participants in Arkansas, Texas, and Wisconsin in August, with the option to recruit additional patients on the basis of an interim analysis when 104 patients have either died or the disease has progressed. The primary outcome is overall survival, and the secondary outcome is quality of life. More details at clinicaltrials.gov.
 

Previously treated unresectable, locally advanced or metastatic liver cancer

People with this type of liver cancer are eligible for a randomized, phase 2 study to determine whether survival can be improved by combining the immunotherapy atezolizumab with a targeted therapy – carbozantinib or lenvatinib. All participants will take carbozantinib or lenvatinib capsules daily for up to 3 years. Half the group will also receive intravenous atezolizumab every 3 weeks. The University Medical Center New Orleans started recruiting 122 participants in May, and study sites are gearing up in eight more states. Overall survival and progression-free survival are primary endpoints; quality of life will not be tracked. More details at clinicaltrials.gov.

All trial information is from the National Institutes of Health U.S. National Library of Medicine (online at clinicaltrials.gov).

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

Shortly after osimertinib was approved for patients with non–small cell lung cancer in 2020 by the Food and Drug Administration, a patient came to me with increasing shortness of breath. He had been on erlotinib (Tarceva) for about 2 years and had done well. Nearly all of his pulmonary lesions had resolved and he was feeling well. He enjoyed boating in the summer and visiting grandkids in California in the winter. However, on this day, it was different. He was losing weight; he was tired and didn’t feel strong enough to put his boat in the water that spring. Long story short: We ordered a CT scan and all of his lesions were progressing. Since osimertinib had just been approved, we got a second biopsy, hoping that his insurance would pay for it. It did and sure enough, a new T790M mutation was present. He was on osimertinib for another 2 years before progressing and starting chemotherapy.

Second biopsies increasingly routine

The practice of ordering a second biopsy for patients with non–small cell lung carcinoma (NSCLC) was not common practice until after 2015 when the Food and Drug Administration approved gefitinib, a tyrosine kinase inhibitor (TKI) for patients whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations.

Up until then, second biopsies were not routinely done for lung cancers. But with the advent of targeted therapy and new drugs designed specifically to tackle first- and second-line treatment resistance mutations, rebiopsies have become a necessity for patients with progressive disease.

Epidermal growth factors, including HER2, ErbB2, and MET, are receptors of tyrosine kinases that control cell growth, but when in overdrive, they can lead to the development of cancers, including lung adenocarcinoma, conventional glioblastoma multiforme, glioblastoma, colon adenocarcinoma, and NSCLC.

EGFRs date back to 1962 with their discovery by Stanley Cohen. The discovery was so important that in 1986, Mr. Cohen was awarded the Nobel Prize in physiology or medicine for the discovery along with Rita Levi-Montalcini.

Now, many years later, we finally have a string of new approvals for mutations in the EGF family of receptors and several under study.

Sensitizing mutations

The more commonly used strategy for blocking EGFR signaling in lung cancer is the use of tyrosine kinase inhibitors, which compete with adenosine triphosphate (ATP) for binding to the tyrosine kinase portion of the receptor. They are located at chromosome 7p11.2. The most frequent mutations that sensitize patients to EGFR inhibitors include exon 19 deletions and L858R point mutation in exon 21, although multiple other driver mutations also exist.

The first-generation of EGFR TKIs include gefitinib and erlotinib, which bind reversibly to the EGF receptor. Second-generation inhibitors afatinib and dacomitinib bind irreversibly. Osimertinib, a third-generation EGFR TKI, which also binds irreversibly, was approved in 2020 for adjuvant therapy, and first- and second-line treatment in patients with NSCLC who have EGFR mutation–positive disease.
 

First-generation EGFR tyrosine kinase inhibitors

Four randomized, first-line, placebo-controlled phase 3 trials conducted with EGFR TKIs in combination with platinum-based doublet chemotherapy in an EGFR nonselected patient population failed to show a survival benefit with erlotinib or gefitinib (TRIBUTE, Tarceva Lung Cancer Investigation Trial, INTACT 1, INTACT 2).

However, a first-line study randomized patients to gefitinib or chemotherapy with carboplatin-paclitaxel, and included patients with or without an EGFR mutations. In the subgroup of patients with an EGFR mutation, progression-free survival (PFS) was significantly longer among those who received gefitinib than among those who received carboplatin–paclitaxel (hazard ratio for progression or death, 0.48), whereas in the subgroup of patients who were negative for the mutation, PFS was significantly longer among those who received chemotherapy (HR for progression or death with gefitinib, 2.85).

Numerous studies have shown that EGFR TKIs used in the first-line setting improved progression free survival, response rates, and quality of life while reducing toxicity. A recent meta-analysis of randomized clinical trials involving EGFR TKIs showed that EGFR TKI improved PFS with a HR of 0.40, compared with standard chemotherapy with fewer serious adverse events, although no benefit on overall survival was observed (HR, 0.96; 95% confidence interval, 0.83-1.10; P = .556).
 

T790M: The most common resistance mutation

T790M is the most common resistance mechanism to develop in patients with EGFR mutations being treated with EGFR TKIs. A randomized phase 3 trial of osimertinib vs. chemotherapy in patients with T790M-positive advanced NSCLC who had disease progression after first-line EGFR-TKI therapy, reported a median duration of progression-free survival that was significantly longer with osimertinib than with platinum therapy plus pemetrexed (10.1 months vs. 4.4 months; HR, 0.30). In addition, among 144 patients with metastases to the central nervous system, the median duration of PFS was longer among patients receiving osimertinib than among those receiving platinum therapy plus pemetrexed (8.5 months vs. 4.2 months; HR, 0.32). However, now that osimertinib has moved into the front-line setting, it has left a void for the treatment of patients with advanced disease who have failed osimertinib.

New resistance mechanisms continue to be identified

One of the most common sets of resistance mutations are insertions in exon 20 of the EGF receptor gene. These are a heterogenous group of mutations, many of which do not respond to first-, second-, or third-generation TKIs. Some, such as EGFR-A763_Y764insFQEA, may be sensitive to first- and third-generation EGFR TKIs. Other drugs targeting exon 20 insertion mutations are under development.

Newly approved by the FDA within the last year are mobocertinib and CLN-081 for adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations.

Savolitinib is a receptor tyrosine kinase (MET) inhibitor currently under development for NSCLC and other cancers. Amivantamab-vmjw was approved by the FDA last year for metastatic NSCLC. It targets EGF and MET receptors in patients with EGFR exon 20 insertion mutations.

We finally have approved drugs for exon 20 insertions and c-Met amplification, even though their approvals are based on small, single arm studies with no definitive claims of improved efficacy over older therapies. Taking a second biopsy will help determine which resistance mechanisms are active to better identify subsequent treatment as in my patient described in this article.

Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.

Shortly after osimertinib was approved for patients with non–small cell lung cancer in 2020 by the Food and Drug Administration, a patient came to me with increasing shortness of breath. He had been on erlotinib (Tarceva) for about 2 years and had done well. Nearly all of his pulmonary lesions had resolved and he was feeling well. He enjoyed boating in the summer and visiting grandkids in California in the winter. However, on this day, it was different. He was losing weight; he was tired and didn’t feel strong enough to put his boat in the water that spring. Long story short: We ordered a CT scan and all of his lesions were progressing. Since osimertinib had just been approved, we got a second biopsy, hoping that his insurance would pay for it. It did and sure enough, a new T790M mutation was present. He was on osimertinib for another 2 years before progressing and starting chemotherapy.

Second biopsies increasingly routine

The practice of ordering a second biopsy for patients with non–small cell lung carcinoma (NSCLC) was not common practice until after 2015 when the Food and Drug Administration approved gefitinib, a tyrosine kinase inhibitor (TKI) for patients whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations.

Up until then, second biopsies were not routinely done for lung cancers. But with the advent of targeted therapy and new drugs designed specifically to tackle first- and second-line treatment resistance mutations, rebiopsies have become a necessity for patients with progressive disease.

Epidermal growth factors, including HER2, ErbB2, and MET, are receptors of tyrosine kinases that control cell growth, but when in overdrive, they can lead to the development of cancers, including lung adenocarcinoma, conventional glioblastoma multiforme, glioblastoma, colon adenocarcinoma, and NSCLC.

EGFRs date back to 1962 with their discovery by Stanley Cohen. The discovery was so important that in 1986, Mr. Cohen was awarded the Nobel Prize in physiology or medicine for the discovery along with Rita Levi-Montalcini.

Now, many years later, we finally have a string of new approvals for mutations in the EGF family of receptors and several under study.

Sensitizing mutations

The more commonly used strategy for blocking EGFR signaling in lung cancer is the use of tyrosine kinase inhibitors, which compete with adenosine triphosphate (ATP) for binding to the tyrosine kinase portion of the receptor. They are located at chromosome 7p11.2. The most frequent mutations that sensitize patients to EGFR inhibitors include exon 19 deletions and L858R point mutation in exon 21, although multiple other driver mutations also exist.

The first-generation of EGFR TKIs include gefitinib and erlotinib, which bind reversibly to the EGF receptor. Second-generation inhibitors afatinib and dacomitinib bind irreversibly. Osimertinib, a third-generation EGFR TKI, which also binds irreversibly, was approved in 2020 for adjuvant therapy, and first- and second-line treatment in patients with NSCLC who have EGFR mutation–positive disease.
 

First-generation EGFR tyrosine kinase inhibitors

Four randomized, first-line, placebo-controlled phase 3 trials conducted with EGFR TKIs in combination with platinum-based doublet chemotherapy in an EGFR nonselected patient population failed to show a survival benefit with erlotinib or gefitinib (TRIBUTE, Tarceva Lung Cancer Investigation Trial, INTACT 1, INTACT 2).

However, a first-line study randomized patients to gefitinib or chemotherapy with carboplatin-paclitaxel, and included patients with or without an EGFR mutations. In the subgroup of patients with an EGFR mutation, progression-free survival (PFS) was significantly longer among those who received gefitinib than among those who received carboplatin–paclitaxel (hazard ratio for progression or death, 0.48), whereas in the subgroup of patients who were negative for the mutation, PFS was significantly longer among those who received chemotherapy (HR for progression or death with gefitinib, 2.85).

Numerous studies have shown that EGFR TKIs used in the first-line setting improved progression free survival, response rates, and quality of life while reducing toxicity. A recent meta-analysis of randomized clinical trials involving EGFR TKIs showed that EGFR TKI improved PFS with a HR of 0.40, compared with standard chemotherapy with fewer serious adverse events, although no benefit on overall survival was observed (HR, 0.96; 95% confidence interval, 0.83-1.10; P = .556).
 

T790M: The most common resistance mutation

T790M is the most common resistance mechanism to develop in patients with EGFR mutations being treated with EGFR TKIs. A randomized phase 3 trial of osimertinib vs. chemotherapy in patients with T790M-positive advanced NSCLC who had disease progression after first-line EGFR-TKI therapy, reported a median duration of progression-free survival that was significantly longer with osimertinib than with platinum therapy plus pemetrexed (10.1 months vs. 4.4 months; HR, 0.30). In addition, among 144 patients with metastases to the central nervous system, the median duration of PFS was longer among patients receiving osimertinib than among those receiving platinum therapy plus pemetrexed (8.5 months vs. 4.2 months; HR, 0.32). However, now that osimertinib has moved into the front-line setting, it has left a void for the treatment of patients with advanced disease who have failed osimertinib.

New resistance mechanisms continue to be identified

One of the most common sets of resistance mutations are insertions in exon 20 of the EGF receptor gene. These are a heterogenous group of mutations, many of which do not respond to first-, second-, or third-generation TKIs. Some, such as EGFR-A763_Y764insFQEA, may be sensitive to first- and third-generation EGFR TKIs. Other drugs targeting exon 20 insertion mutations are under development.

Newly approved by the FDA within the last year are mobocertinib and CLN-081 for adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations.

Savolitinib is a receptor tyrosine kinase (MET) inhibitor currently under development for NSCLC and other cancers. Amivantamab-vmjw was approved by the FDA last year for metastatic NSCLC. It targets EGF and MET receptors in patients with EGFR exon 20 insertion mutations.

We finally have approved drugs for exon 20 insertions and c-Met amplification, even though their approvals are based on small, single arm studies with no definitive claims of improved efficacy over older therapies. Taking a second biopsy will help determine which resistance mechanisms are active to better identify subsequent treatment as in my patient described in this article.

Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.

Shortly after osimertinib was approved for patients with non–small cell lung cancer in 2020 by the Food and Drug Administration, a patient came to me with increasing shortness of breath. He had been on erlotinib (Tarceva) for about 2 years and had done well. Nearly all of his pulmonary lesions had resolved and he was feeling well. He enjoyed boating in the summer and visiting grandkids in California in the winter. However, on this day, it was different. He was losing weight; he was tired and didn’t feel strong enough to put his boat in the water that spring. Long story short: We ordered a CT scan and all of his lesions were progressing. Since osimertinib had just been approved, we got a second biopsy, hoping that his insurance would pay for it. It did and sure enough, a new T790M mutation was present. He was on osimertinib for another 2 years before progressing and starting chemotherapy.

Second biopsies increasingly routine

The practice of ordering a second biopsy for patients with non–small cell lung carcinoma (NSCLC) was not common practice until after 2015 when the Food and Drug Administration approved gefitinib, a tyrosine kinase inhibitor (TKI) for patients whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations.

Up until then, second biopsies were not routinely done for lung cancers. But with the advent of targeted therapy and new drugs designed specifically to tackle first- and second-line treatment resistance mutations, rebiopsies have become a necessity for patients with progressive disease.

Epidermal growth factors, including HER2, ErbB2, and MET, are receptors of tyrosine kinases that control cell growth, but when in overdrive, they can lead to the development of cancers, including lung adenocarcinoma, conventional glioblastoma multiforme, glioblastoma, colon adenocarcinoma, and NSCLC.

EGFRs date back to 1962 with their discovery by Stanley Cohen. The discovery was so important that in 1986, Mr. Cohen was awarded the Nobel Prize in physiology or medicine for the discovery along with Rita Levi-Montalcini.

Now, many years later, we finally have a string of new approvals for mutations in the EGF family of receptors and several under study.

Sensitizing mutations

The more commonly used strategy for blocking EGFR signaling in lung cancer is the use of tyrosine kinase inhibitors, which compete with adenosine triphosphate (ATP) for binding to the tyrosine kinase portion of the receptor. They are located at chromosome 7p11.2. The most frequent mutations that sensitize patients to EGFR inhibitors include exon 19 deletions and L858R point mutation in exon 21, although multiple other driver mutations also exist.

The first-generation of EGFR TKIs include gefitinib and erlotinib, which bind reversibly to the EGF receptor. Second-generation inhibitors afatinib and dacomitinib bind irreversibly. Osimertinib, a third-generation EGFR TKI, which also binds irreversibly, was approved in 2020 for adjuvant therapy, and first- and second-line treatment in patients with NSCLC who have EGFR mutation–positive disease.
 

First-generation EGFR tyrosine kinase inhibitors

Four randomized, first-line, placebo-controlled phase 3 trials conducted with EGFR TKIs in combination with platinum-based doublet chemotherapy in an EGFR nonselected patient population failed to show a survival benefit with erlotinib or gefitinib (TRIBUTE, Tarceva Lung Cancer Investigation Trial, INTACT 1, INTACT 2).

However, a first-line study randomized patients to gefitinib or chemotherapy with carboplatin-paclitaxel, and included patients with or without an EGFR mutations. In the subgroup of patients with an EGFR mutation, progression-free survival (PFS) was significantly longer among those who received gefitinib than among those who received carboplatin–paclitaxel (hazard ratio for progression or death, 0.48), whereas in the subgroup of patients who were negative for the mutation, PFS was significantly longer among those who received chemotherapy (HR for progression or death with gefitinib, 2.85).

Numerous studies have shown that EGFR TKIs used in the first-line setting improved progression free survival, response rates, and quality of life while reducing toxicity. A recent meta-analysis of randomized clinical trials involving EGFR TKIs showed that EGFR TKI improved PFS with a HR of 0.40, compared with standard chemotherapy with fewer serious adverse events, although no benefit on overall survival was observed (HR, 0.96; 95% confidence interval, 0.83-1.10; P = .556).
 

T790M: The most common resistance mutation

T790M is the most common resistance mechanism to develop in patients with EGFR mutations being treated with EGFR TKIs. A randomized phase 3 trial of osimertinib vs. chemotherapy in patients with T790M-positive advanced NSCLC who had disease progression after first-line EGFR-TKI therapy, reported a median duration of progression-free survival that was significantly longer with osimertinib than with platinum therapy plus pemetrexed (10.1 months vs. 4.4 months; HR, 0.30). In addition, among 144 patients with metastases to the central nervous system, the median duration of PFS was longer among patients receiving osimertinib than among those receiving platinum therapy plus pemetrexed (8.5 months vs. 4.2 months; HR, 0.32). However, now that osimertinib has moved into the front-line setting, it has left a void for the treatment of patients with advanced disease who have failed osimertinib.

New resistance mechanisms continue to be identified

One of the most common sets of resistance mutations are insertions in exon 20 of the EGF receptor gene. These are a heterogenous group of mutations, many of which do not respond to first-, second-, or third-generation TKIs. Some, such as EGFR-A763_Y764insFQEA, may be sensitive to first- and third-generation EGFR TKIs. Other drugs targeting exon 20 insertion mutations are under development.

Newly approved by the FDA within the last year are mobocertinib and CLN-081 for adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations.

Savolitinib is a receptor tyrosine kinase (MET) inhibitor currently under development for NSCLC and other cancers. Amivantamab-vmjw was approved by the FDA last year for metastatic NSCLC. It targets EGF and MET receptors in patients with EGFR exon 20 insertion mutations.

We finally have approved drugs for exon 20 insertions and c-Met amplification, even though their approvals are based on small, single arm studies with no definitive claims of improved efficacy over older therapies. Taking a second biopsy will help determine which resistance mechanisms are active to better identify subsequent treatment as in my patient described in this article.

Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.

STOCKHOLM – The investigational once-weekly insulin icodec (Novo Nordisk) significantly reduces A1c without increasing hypoglycemia in people with type 2 diabetes, the first phase 3 data of such an insulin formulation suggest. The data are from one of six trials in the company’s ONWARDS program.

“Once-weekly insulin may redefine diabetes management,” enthused Athena Philis-Tsimikas, MD, who presented the findings at a session during the European Association for the Study of Diabetes (EASD) 2022 Annual Meeting, which also included a summary of previously reported top-line data from other ONWARDS trials as well as phase 2 data for Lilly›s investigational once-weekly Basal Insulin Fc (BIF).

Phase 2 data for icodec were published in 2020 in the New England Journal of Medicine and in 2021 in Diabetes Care, as reported by this news organization.

The capacity for reducing the number of basal insulin injections from at least 365 to just 52 per year means that once-weekly insulin “has the potential to facilitate insulin initiation and improve treatment adherence and persistence in diabetes,” noted Dr. Philis-Tsimikas, corporate vice president of Scripps Whittier Diabetes Institute, San Diego.

Asked to comment, independent diabetes industry consultant Charles Alexander, MD, told this news organization that the new data from ONWARDS 2 of patients switching from daily to once-weekly basal insulin were reassuring with regard to hypoglycemia, at least for people with type 2 diabetes.

“For type 2, I think there’s enough data now to feel comfortable that it’s going to be good, especially for people who are on once-weekly [glucagon-like peptide-1 (GLP-1) agonists].”

However, for type 1 diabetes, the company reported top-line ONWARDS 6 data earlier this year, in which icodec was associated with significantly increased rates of hypoglycemia compared with daily degludec. “In type 1, even the basal needs are [often] changing. That kind of person would want to stay away from once-weekly insulin,” Dr. Alexander said.

And he noted, for any patient who adjusts their insulin dose frequently, “obviously, you’re not going to be able to do that with a once-weekly.”
 

Similar A1c reduction as daily basal without increased hypoglycemia

In ONWARDS 2, 526 adults with type 2 diabetes were randomized to switch from their current once- or twice-daily basal insulin to either once-weekly icodec or once-daily insulin degludec (Tresiba) for 26 weeks. The study was open-label, with a treat-to-glucose target of 80-130 mg/dL design.

Participants had A1c levels of 7.0%-10.0% and were also taking stable doses of other noninsulin glucose-lowering medications. Over 80% were taking metformin, a third were taking an SGLT2 inhibitor, and about a quarter each were taking a GLP-1 agonist or DPP-4 inhibitor. Those medications were continued, but sulfonylureas were discontinued in the 22% taking those at baseline.

The basal insulin used at baseline was glargine U100 for 42%, degludec for 28%, and glargine U300 for 16%, “so, a very typical presentation of patients we see in our practices today,” Dr. Philis-Tsimikas noted.

The primary endpoint, change in A1c from baseline to week 26, dropped from 8.17% to 7.20% with icodec and from 8.10% to 7.42% with degludec. The estimated treatment difference of –0.22 percentage points met the margins for both noninferiority (P < .0001) and superiority (P = .0028). Those taking icodec were significantly more likely to achieve an A1c under 7% compared with degludec, at 40.3% versus 26.5% (P = .0019).

Continuous glucose monitoring parameters during weeks 22-26 showed time in glucose range of 70-180 mg/dL (3.9-10.0 mmol/L) was 63.1% for icodec and 59.5% for degludec, which was not significantly different, Dr. Philis-Tsimikas reported.

Body weight increased by 1.4 kg (3 lb) with icodec but dropped slightly by 0.30 kg with degludec, which was significantly different (P < .001).

When asked about the body weight results, Dr. Alexander said: “It’s really hard to say. We know that insulin generally causes weight gain. A 1.4-kg weight gain over 6 months isn’t really surprising. Why there wasn’t with degludec, I don’t know.”

There was just one episode of severe hypoglycemia (requiring assistance) in the trial in the degludec group. Rates of combined severe or clinically significant hypoglycemic events (glucose < 54 mg/dL / < 3.0 mmol/L) per patient-year exposed were 0.73 for icodec versus 0.27 for degludec, which was not significantly different (P = .0782). Similar findings were seen for nocturnal hypoglycemia.

Significantly more patients achieved an A1c under 7% without significant hypoglycemia with icodec than degludec, at 36.7% versus 26.8% (P = .0223). Other adverse events were equivalent between the two groups, Dr. Philis-Tsimikas reported.

Scores on the diabetes treatment satisfaction questionnaire, which addresses convenience, flexibility, satisfaction, and willingness to recommend treatment to others, were significantly higher for icodec than degludec, at 4.22 versus 2.96 (P = .0036).

“For me, this is one of the most important outcomes,” she commented.  
 

Benefit in type 2 diabetes, potential concern in type 1 diabetes

Top-line results from ONWARDS 1, a phase 3a 78-week trial in 984 drug-naive people with type 2 diabetes and ONWARDS 6, a 52-week trial in 583 people with type 1 diabetes, were presented earlier this year at the American Diabetes Association 81st Scientific Sessions.

In ONWARDS 1, icodec achieved noninferiority to daily insulin glargine, reducing A1c by 1.55 versus 1.35 percentage points, with superior time in range and no significant differences in hypoglycemia rates.

However, in ONWARDS 6, while noninferiority in A1c lowering compared with daily degludec was achieved, with reductions of 0.47 versus 0.51 percentage points from a baseline A1c of 7.6%, there was a significantly greater rate of severe or clinically significant hypoglycemia with icodec, at 19.93 versus 10.37 events per patient-year with degludec.

Dr. Philis-Tsimikas has reported performing research and serving as an advisor on behalf of her employer for Abbott, Bayer, Dexcom, Eli Lilly, Medtronic, Merck, Novo Nordisk, and Sanofi. All reimbursements go to her employer. Dr. Alexander has reported being a nonpaid advisor for diaTribe and a consultant for Kinexum.

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

STOCKHOLM – The investigational once-weekly insulin icodec (Novo Nordisk) significantly reduces A1c without increasing hypoglycemia in people with type 2 diabetes, the first phase 3 data of such an insulin formulation suggest. The data are from one of six trials in the company’s ONWARDS program.

“Once-weekly insulin may redefine diabetes management,” enthused Athena Philis-Tsimikas, MD, who presented the findings at a session during the European Association for the Study of Diabetes (EASD) 2022 Annual Meeting, which also included a summary of previously reported top-line data from other ONWARDS trials as well as phase 2 data for Lilly›s investigational once-weekly Basal Insulin Fc (BIF).

Phase 2 data for icodec were published in 2020 in the New England Journal of Medicine and in 2021 in Diabetes Care, as reported by this news organization.

The capacity for reducing the number of basal insulin injections from at least 365 to just 52 per year means that once-weekly insulin “has the potential to facilitate insulin initiation and improve treatment adherence and persistence in diabetes,” noted Dr. Philis-Tsimikas, corporate vice president of Scripps Whittier Diabetes Institute, San Diego.

Asked to comment, independent diabetes industry consultant Charles Alexander, MD, told this news organization that the new data from ONWARDS 2 of patients switching from daily to once-weekly basal insulin were reassuring with regard to hypoglycemia, at least for people with type 2 diabetes.

“For type 2, I think there’s enough data now to feel comfortable that it’s going to be good, especially for people who are on once-weekly [glucagon-like peptide-1 (GLP-1) agonists].”

However, for type 1 diabetes, the company reported top-line ONWARDS 6 data earlier this year, in which icodec was associated with significantly increased rates of hypoglycemia compared with daily degludec. “In type 1, even the basal needs are [often] changing. That kind of person would want to stay away from once-weekly insulin,” Dr. Alexander said.

And he noted, for any patient who adjusts their insulin dose frequently, “obviously, you’re not going to be able to do that with a once-weekly.”
 

Similar A1c reduction as daily basal without increased hypoglycemia

In ONWARDS 2, 526 adults with type 2 diabetes were randomized to switch from their current once- or twice-daily basal insulin to either once-weekly icodec or once-daily insulin degludec (Tresiba) for 26 weeks. The study was open-label, with a treat-to-glucose target of 80-130 mg/dL design.

Participants had A1c levels of 7.0%-10.0% and were also taking stable doses of other noninsulin glucose-lowering medications. Over 80% were taking metformin, a third were taking an SGLT2 inhibitor, and about a quarter each were taking a GLP-1 agonist or DPP-4 inhibitor. Those medications were continued, but sulfonylureas were discontinued in the 22% taking those at baseline.

The basal insulin used at baseline was glargine U100 for 42%, degludec for 28%, and glargine U300 for 16%, “so, a very typical presentation of patients we see in our practices today,” Dr. Philis-Tsimikas noted.

The primary endpoint, change in A1c from baseline to week 26, dropped from 8.17% to 7.20% with icodec and from 8.10% to 7.42% with degludec. The estimated treatment difference of –0.22 percentage points met the margins for both noninferiority (P < .0001) and superiority (P = .0028). Those taking icodec were significantly more likely to achieve an A1c under 7% compared with degludec, at 40.3% versus 26.5% (P = .0019).

Continuous glucose monitoring parameters during weeks 22-26 showed time in glucose range of 70-180 mg/dL (3.9-10.0 mmol/L) was 63.1% for icodec and 59.5% for degludec, which was not significantly different, Dr. Philis-Tsimikas reported.

Body weight increased by 1.4 kg (3 lb) with icodec but dropped slightly by 0.30 kg with degludec, which was significantly different (P < .001).

When asked about the body weight results, Dr. Alexander said: “It’s really hard to say. We know that insulin generally causes weight gain. A 1.4-kg weight gain over 6 months isn’t really surprising. Why there wasn’t with degludec, I don’t know.”

There was just one episode of severe hypoglycemia (requiring assistance) in the trial in the degludec group. Rates of combined severe or clinically significant hypoglycemic events (glucose < 54 mg/dL / < 3.0 mmol/L) per patient-year exposed were 0.73 for icodec versus 0.27 for degludec, which was not significantly different (P = .0782). Similar findings were seen for nocturnal hypoglycemia.

Significantly more patients achieved an A1c under 7% without significant hypoglycemia with icodec than degludec, at 36.7% versus 26.8% (P = .0223). Other adverse events were equivalent between the two groups, Dr. Philis-Tsimikas reported.

Scores on the diabetes treatment satisfaction questionnaire, which addresses convenience, flexibility, satisfaction, and willingness to recommend treatment to others, were significantly higher for icodec than degludec, at 4.22 versus 2.96 (P = .0036).

“For me, this is one of the most important outcomes,” she commented.  
 

Benefit in type 2 diabetes, potential concern in type 1 diabetes

Top-line results from ONWARDS 1, a phase 3a 78-week trial in 984 drug-naive people with type 2 diabetes and ONWARDS 6, a 52-week trial in 583 people with type 1 diabetes, were presented earlier this year at the American Diabetes Association 81st Scientific Sessions.

In ONWARDS 1, icodec achieved noninferiority to daily insulin glargine, reducing A1c by 1.55 versus 1.35 percentage points, with superior time in range and no significant differences in hypoglycemia rates.

However, in ONWARDS 6, while noninferiority in A1c lowering compared with daily degludec was achieved, with reductions of 0.47 versus 0.51 percentage points from a baseline A1c of 7.6%, there was a significantly greater rate of severe or clinically significant hypoglycemia with icodec, at 19.93 versus 10.37 events per patient-year with degludec.

Dr. Philis-Tsimikas has reported performing research and serving as an advisor on behalf of her employer for Abbott, Bayer, Dexcom, Eli Lilly, Medtronic, Merck, Novo Nordisk, and Sanofi. All reimbursements go to her employer. Dr. Alexander has reported being a nonpaid advisor for diaTribe and a consultant for Kinexum.

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

STOCKHOLM – The investigational once-weekly insulin icodec (Novo Nordisk) significantly reduces A1c without increasing hypoglycemia in people with type 2 diabetes, the first phase 3 data of such an insulin formulation suggest. The data are from one of six trials in the company’s ONWARDS program.

“Once-weekly insulin may redefine diabetes management,” enthused Athena Philis-Tsimikas, MD, who presented the findings at a session during the European Association for the Study of Diabetes (EASD) 2022 Annual Meeting, which also included a summary of previously reported top-line data from other ONWARDS trials as well as phase 2 data for Lilly›s investigational once-weekly Basal Insulin Fc (BIF).

Phase 2 data for icodec were published in 2020 in the New England Journal of Medicine and in 2021 in Diabetes Care, as reported by this news organization.

The capacity for reducing the number of basal insulin injections from at least 365 to just 52 per year means that once-weekly insulin “has the potential to facilitate insulin initiation and improve treatment adherence and persistence in diabetes,” noted Dr. Philis-Tsimikas, corporate vice president of Scripps Whittier Diabetes Institute, San Diego.

Asked to comment, independent diabetes industry consultant Charles Alexander, MD, told this news organization that the new data from ONWARDS 2 of patients switching from daily to once-weekly basal insulin were reassuring with regard to hypoglycemia, at least for people with type 2 diabetes.

“For type 2, I think there’s enough data now to feel comfortable that it’s going to be good, especially for people who are on once-weekly [glucagon-like peptide-1 (GLP-1) agonists].”

However, for type 1 diabetes, the company reported top-line ONWARDS 6 data earlier this year, in which icodec was associated with significantly increased rates of hypoglycemia compared with daily degludec. “In type 1, even the basal needs are [often] changing. That kind of person would want to stay away from once-weekly insulin,” Dr. Alexander said.

And he noted, for any patient who adjusts their insulin dose frequently, “obviously, you’re not going to be able to do that with a once-weekly.”
 

Similar A1c reduction as daily basal without increased hypoglycemia

In ONWARDS 2, 526 adults with type 2 diabetes were randomized to switch from their current once- or twice-daily basal insulin to either once-weekly icodec or once-daily insulin degludec (Tresiba) for 26 weeks. The study was open-label, with a treat-to-glucose target of 80-130 mg/dL design.

Participants had A1c levels of 7.0%-10.0% and were also taking stable doses of other noninsulin glucose-lowering medications. Over 80% were taking metformin, a third were taking an SGLT2 inhibitor, and about a quarter each were taking a GLP-1 agonist or DPP-4 inhibitor. Those medications were continued, but sulfonylureas were discontinued in the 22% taking those at baseline.

The basal insulin used at baseline was glargine U100 for 42%, degludec for 28%, and glargine U300 for 16%, “so, a very typical presentation of patients we see in our practices today,” Dr. Philis-Tsimikas noted.

The primary endpoint, change in A1c from baseline to week 26, dropped from 8.17% to 7.20% with icodec and from 8.10% to 7.42% with degludec. The estimated treatment difference of –0.22 percentage points met the margins for both noninferiority (P < .0001) and superiority (P = .0028). Those taking icodec were significantly more likely to achieve an A1c under 7% compared with degludec, at 40.3% versus 26.5% (P = .0019).

Continuous glucose monitoring parameters during weeks 22-26 showed time in glucose range of 70-180 mg/dL (3.9-10.0 mmol/L) was 63.1% for icodec and 59.5% for degludec, which was not significantly different, Dr. Philis-Tsimikas reported.

Body weight increased by 1.4 kg (3 lb) with icodec but dropped slightly by 0.30 kg with degludec, which was significantly different (P < .001).

When asked about the body weight results, Dr. Alexander said: “It’s really hard to say. We know that insulin generally causes weight gain. A 1.4-kg weight gain over 6 months isn’t really surprising. Why there wasn’t with degludec, I don’t know.”

There was just one episode of severe hypoglycemia (requiring assistance) in the trial in the degludec group. Rates of combined severe or clinically significant hypoglycemic events (glucose < 54 mg/dL / < 3.0 mmol/L) per patient-year exposed were 0.73 for icodec versus 0.27 for degludec, which was not significantly different (P = .0782). Similar findings were seen for nocturnal hypoglycemia.

Significantly more patients achieved an A1c under 7% without significant hypoglycemia with icodec than degludec, at 36.7% versus 26.8% (P = .0223). Other adverse events were equivalent between the two groups, Dr. Philis-Tsimikas reported.

Scores on the diabetes treatment satisfaction questionnaire, which addresses convenience, flexibility, satisfaction, and willingness to recommend treatment to others, were significantly higher for icodec than degludec, at 4.22 versus 2.96 (P = .0036).

“For me, this is one of the most important outcomes,” she commented.  
 

Benefit in type 2 diabetes, potential concern in type 1 diabetes

Top-line results from ONWARDS 1, a phase 3a 78-week trial in 984 drug-naive people with type 2 diabetes and ONWARDS 6, a 52-week trial in 583 people with type 1 diabetes, were presented earlier this year at the American Diabetes Association 81st Scientific Sessions.

In ONWARDS 1, icodec achieved noninferiority to daily insulin glargine, reducing A1c by 1.55 versus 1.35 percentage points, with superior time in range and no significant differences in hypoglycemia rates.

However, in ONWARDS 6, while noninferiority in A1c lowering compared with daily degludec was achieved, with reductions of 0.47 versus 0.51 percentage points from a baseline A1c of 7.6%, there was a significantly greater rate of severe or clinically significant hypoglycemia with icodec, at 19.93 versus 10.37 events per patient-year with degludec.

Dr. Philis-Tsimikas has reported performing research and serving as an advisor on behalf of her employer for Abbott, Bayer, Dexcom, Eli Lilly, Medtronic, Merck, Novo Nordisk, and Sanofi. All reimbursements go to her employer. Dr. Alexander has reported being a nonpaid advisor for diaTribe and a consultant for Kinexum.

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

Women with inflammatory arthritis (IA) are more likely to use healthcare services than men, a Canadian study found. The results suggest there are biological differences in disease course and sociocultural differences in health care access and patient behavior among the sexes, Sanjana Tarannum said in a presentation at the Lancet Summit on Sex and Gender in Rheumatology.

Ms. Tarannum and colleagues also recently published the study in Annals of the Rheumatic Diseases.

Effectively managing IA patients calls for timely access to and appropriate use of health care resources, said Ms. Tarannum, of the Women’s College Research Institute in Toronto.

Sex and gender are often used interchangeably but they refer to different things. “Sex is the biological characteristic of being male or female. It relates to disease inheritance patterns, pain processing mechanisms, and immune dysregulation in the context of inflammatory arthritis,” Ms. Tarannum said during her presentation.

Gender is a sociocultural construct associated with masculine or feminine traits. In the context of IA, gender relates to coping strategies, pain perception and reporting, and health care–seeking behavior of patients and interaction with care providers.

A patient’s sex relates to healthcare encounters, time to diagnosis, and prescription patterns. These all affect disease outcomes. Previous studies have yielded inconsistent results and mainly focused on rheumatoid arthritis rather than other IA types such as ankylosing spondylitis (AS).

Ms. Tarannum and colleagues sought to compare health care usage between male and female patients for musculoskeletal-related issues before and after IA diagnosis. They used Ontario administrative health data to create three cohorts of patients with RA, AS, and psoriatic arthritis (PsA), the three most common types of IA. The patients were diagnosed during 2010-2017, and outcomes were assessed in each year for 3 years before and after diagnosis.

Health care use indicators included visits to physicians, musculoskeletal imaging, laboratory tests, and dispensation of drugs. Regression models adjusting for sociodemographic factors and comorbidities were used to compare male and female patients.

Sex-related differences emerge in all IA groups

The investigators assessed 41,277 patients with RA (69% female), 8,150 patients with AS (51% female), and 6,446 patients with PsA (54% female). Male patients had more cardiovascular disease, whereas female patients had higher incidences of depression and osteoporosis.

Similar trends of sex-related differences emerged in all three cohorts. Before diagnosis, female patients were more likely to visit rheumatologists or family physicians for musculoskeletal reasons or use musculoskeletal imaging and laboratory tests. Women were also more likely to remain in rheumatology care after diagnosis.

Men were more likely to visit the ED for musculoskeletal reasons immediately before diagnosis.

No sex- or gender-related differences were observed in medication use, although older females with RA or AS were more likely to get prescriptions for NSAIDs and opioids and conventional disease-modifying antirheumatic drugs, respectively.

The findings show that overall musculoskeletal health care use was higher in female patients with IA. “Sex differences were more pronounced the earlier the encounter was from the time of diagnosis and tended to diminish with time,” Ms. Tarannum observed. Sex differences were also more prominent in the RA and AS cohorts.
 

Women seek out care, do repeat visits

Several reasons may explain why utilization was higher in females. Women with IA have a higher overall risk of musculoskeletal conditions such as osteoarthritis, which could have driven the health care encounters. Numerous studies have also reported that female patients have a lower threshold for pain as well as a greater tendency to seek out health care.

Additionally, female patients often present with pain and fatigue, which are often misdiagnosed as fibromyalgia or depression. Therefore, they often require repeated health care encounters to arrive at an IA diagnosis, Ms. Tarannum said.

An early prodromal phase in females could have triggered a health care encounter as well.

Men, by comparison, are more likely to have acute-onset or severe disease. Objective signs and radiologic features can facilitate diagnosis in men, she said. Male patients also show more reluctance in seeking care, have a higher threshold for pain, and are less likely to have a usual source of care such as a family physician.

Higher confidence in hospital-based emergency services also could have resulted in more ED visits and lower health care use in men. Better response to treatments could also have resulted in fewer episodes of rheumatology care after diagnosis.

The results aren’t surprising, said Scott Zashin, MD, a rheumatologist in Dallas who wasn’t a part of the study.

“At least in terms of musculoskeletal disorders, my clinical experience suggests that women are more compliant with their follow-up than male patients. Especially with gout, a common type of arthritis in men, male patients may wait until their symptoms are severe before seeking medical attention,” Dr. Zashin said.

The Enid Walker Graduate Student Award for Research in Women’s Health provided funding for this study.

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

Women with inflammatory arthritis (IA) are more likely to use healthcare services than men, a Canadian study found. The results suggest there are biological differences in disease course and sociocultural differences in health care access and patient behavior among the sexes, Sanjana Tarannum said in a presentation at the Lancet Summit on Sex and Gender in Rheumatology.

Ms. Tarannum and colleagues also recently published the study in Annals of the Rheumatic Diseases.

Effectively managing IA patients calls for timely access to and appropriate use of health care resources, said Ms. Tarannum, of the Women’s College Research Institute in Toronto.

Sex and gender are often used interchangeably but they refer to different things. “Sex is the biological characteristic of being male or female. It relates to disease inheritance patterns, pain processing mechanisms, and immune dysregulation in the context of inflammatory arthritis,” Ms. Tarannum said during her presentation.

Gender is a sociocultural construct associated with masculine or feminine traits. In the context of IA, gender relates to coping strategies, pain perception and reporting, and health care–seeking behavior of patients and interaction with care providers.

A patient’s sex relates to healthcare encounters, time to diagnosis, and prescription patterns. These all affect disease outcomes. Previous studies have yielded inconsistent results and mainly focused on rheumatoid arthritis rather than other IA types such as ankylosing spondylitis (AS).

Ms. Tarannum and colleagues sought to compare health care usage between male and female patients for musculoskeletal-related issues before and after IA diagnosis. They used Ontario administrative health data to create three cohorts of patients with RA, AS, and psoriatic arthritis (PsA), the three most common types of IA. The patients were diagnosed during 2010-2017, and outcomes were assessed in each year for 3 years before and after diagnosis.

Health care use indicators included visits to physicians, musculoskeletal imaging, laboratory tests, and dispensation of drugs. Regression models adjusting for sociodemographic factors and comorbidities were used to compare male and female patients.

Sex-related differences emerge in all IA groups

The investigators assessed 41,277 patients with RA (69% female), 8,150 patients with AS (51% female), and 6,446 patients with PsA (54% female). Male patients had more cardiovascular disease, whereas female patients had higher incidences of depression and osteoporosis.

Similar trends of sex-related differences emerged in all three cohorts. Before diagnosis, female patients were more likely to visit rheumatologists or family physicians for musculoskeletal reasons or use musculoskeletal imaging and laboratory tests. Women were also more likely to remain in rheumatology care after diagnosis.

Men were more likely to visit the ED for musculoskeletal reasons immediately before diagnosis.

No sex- or gender-related differences were observed in medication use, although older females with RA or AS were more likely to get prescriptions for NSAIDs and opioids and conventional disease-modifying antirheumatic drugs, respectively.

The findings show that overall musculoskeletal health care use was higher in female patients with IA. “Sex differences were more pronounced the earlier the encounter was from the time of diagnosis and tended to diminish with time,” Ms. Tarannum observed. Sex differences were also more prominent in the RA and AS cohorts.
 

Women seek out care, do repeat visits

Several reasons may explain why utilization was higher in females. Women with IA have a higher overall risk of musculoskeletal conditions such as osteoarthritis, which could have driven the health care encounters. Numerous studies have also reported that female patients have a lower threshold for pain as well as a greater tendency to seek out health care.

Additionally, female patients often present with pain and fatigue, which are often misdiagnosed as fibromyalgia or depression. Therefore, they often require repeated health care encounters to arrive at an IA diagnosis, Ms. Tarannum said.

An early prodromal phase in females could have triggered a health care encounter as well.

Men, by comparison, are more likely to have acute-onset or severe disease. Objective signs and radiologic features can facilitate diagnosis in men, she said. Male patients also show more reluctance in seeking care, have a higher threshold for pain, and are less likely to have a usual source of care such as a family physician.

Higher confidence in hospital-based emergency services also could have resulted in more ED visits and lower health care use in men. Better response to treatments could also have resulted in fewer episodes of rheumatology care after diagnosis.

The results aren’t surprising, said Scott Zashin, MD, a rheumatologist in Dallas who wasn’t a part of the study.

“At least in terms of musculoskeletal disorders, my clinical experience suggests that women are more compliant with their follow-up than male patients. Especially with gout, a common type of arthritis in men, male patients may wait until their symptoms are severe before seeking medical attention,” Dr. Zashin said.

The Enid Walker Graduate Student Award for Research in Women’s Health provided funding for this study.

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

Women with inflammatory arthritis (IA) are more likely to use healthcare services than men, a Canadian study found. The results suggest there are biological differences in disease course and sociocultural differences in health care access and patient behavior among the sexes, Sanjana Tarannum said in a presentation at the Lancet Summit on Sex and Gender in Rheumatology.

Ms. Tarannum and colleagues also recently published the study in Annals of the Rheumatic Diseases.

Effectively managing IA patients calls for timely access to and appropriate use of health care resources, said Ms. Tarannum, of the Women’s College Research Institute in Toronto.

Sex and gender are often used interchangeably but they refer to different things. “Sex is the biological characteristic of being male or female. It relates to disease inheritance patterns, pain processing mechanisms, and immune dysregulation in the context of inflammatory arthritis,” Ms. Tarannum said during her presentation.

Gender is a sociocultural construct associated with masculine or feminine traits. In the context of IA, gender relates to coping strategies, pain perception and reporting, and health care–seeking behavior of patients and interaction with care providers.

A patient’s sex relates to healthcare encounters, time to diagnosis, and prescription patterns. These all affect disease outcomes. Previous studies have yielded inconsistent results and mainly focused on rheumatoid arthritis rather than other IA types such as ankylosing spondylitis (AS).

Ms. Tarannum and colleagues sought to compare health care usage between male and female patients for musculoskeletal-related issues before and after IA diagnosis. They used Ontario administrative health data to create three cohorts of patients with RA, AS, and psoriatic arthritis (PsA), the three most common types of IA. The patients were diagnosed during 2010-2017, and outcomes were assessed in each year for 3 years before and after diagnosis.

Health care use indicators included visits to physicians, musculoskeletal imaging, laboratory tests, and dispensation of drugs. Regression models adjusting for sociodemographic factors and comorbidities were used to compare male and female patients.

Sex-related differences emerge in all IA groups

The investigators assessed 41,277 patients with RA (69% female), 8,150 patients with AS (51% female), and 6,446 patients with PsA (54% female). Male patients had more cardiovascular disease, whereas female patients had higher incidences of depression and osteoporosis.

Similar trends of sex-related differences emerged in all three cohorts. Before diagnosis, female patients were more likely to visit rheumatologists or family physicians for musculoskeletal reasons or use musculoskeletal imaging and laboratory tests. Women were also more likely to remain in rheumatology care after diagnosis.

Men were more likely to visit the ED for musculoskeletal reasons immediately before diagnosis.

No sex- or gender-related differences were observed in medication use, although older females with RA or AS were more likely to get prescriptions for NSAIDs and opioids and conventional disease-modifying antirheumatic drugs, respectively.

The findings show that overall musculoskeletal health care use was higher in female patients with IA. “Sex differences were more pronounced the earlier the encounter was from the time of diagnosis and tended to diminish with time,” Ms. Tarannum observed. Sex differences were also more prominent in the RA and AS cohorts.
 

Women seek out care, do repeat visits

Several reasons may explain why utilization was higher in females. Women with IA have a higher overall risk of musculoskeletal conditions such as osteoarthritis, which could have driven the health care encounters. Numerous studies have also reported that female patients have a lower threshold for pain as well as a greater tendency to seek out health care.

Additionally, female patients often present with pain and fatigue, which are often misdiagnosed as fibromyalgia or depression. Therefore, they often require repeated health care encounters to arrive at an IA diagnosis, Ms. Tarannum said.

An early prodromal phase in females could have triggered a health care encounter as well.

Men, by comparison, are more likely to have acute-onset or severe disease. Objective signs and radiologic features can facilitate diagnosis in men, she said. Male patients also show more reluctance in seeking care, have a higher threshold for pain, and are less likely to have a usual source of care such as a family physician.

Higher confidence in hospital-based emergency services also could have resulted in more ED visits and lower health care use in men. Better response to treatments could also have resulted in fewer episodes of rheumatology care after diagnosis.

The results aren’t surprising, said Scott Zashin, MD, a rheumatologist in Dallas who wasn’t a part of the study.

“At least in terms of musculoskeletal disorders, my clinical experience suggests that women are more compliant with their follow-up than male patients. Especially with gout, a common type of arthritis in men, male patients may wait until their symptoms are severe before seeking medical attention,” Dr. Zashin said.

The Enid Walker Graduate Student Award for Research in Women’s Health provided funding for this study.

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

This transcript has been edited for clarity.

I’m David Kerr, professor of cancer medicine at Oxford. As I’m gearing up to have my autumnal COVID-19 booster vaccine, there’s a small controversy raging in the United Kingdom about access to a medicine called Evusheld.

This was developed by AstraZeneca. It’s a combination of two relatively long-acting antibodies (tixagevimab and cilgavimab) that bind to the spike protein on the outside of the SARS-CoV-2 virus, the virus that causes COVID-19. The antibody binds to the spike protein and prevents it from binding to and infecting or damaging cells, so it’s what’s called preexposure prophylaxis.

Although vaccination is still the best approach to protecting against and, one would hope, conferring a degree of herd protection to our population as a whole, there are some people who cannot mount an appropriate immune response and we have to take care of these folks. Because the vaccines don’t work very well for them, the vaccine itself is not sufficient to protect them.

Evusheld, in trials that have been done hitherto, can protect people who can’t mount an immune response from being infected. Between 75% and 80% of patients treated with Evusheld didn’t get COVID-19. The duration of effect seemed to be at least for 6 months, possibly longer, so it’s a really good result. This caused our medicines regulatory authority in the United Kingdom to approve the drug in March of this year. Although the drug has been approved, it’s not yet funded and not yet available for vulnerable patients.

These are patients who, for reasons of inborn genetic diseases, cannot mount an immune response; patients who are pharmacologically immune depleted; patients who have had transplants and are on immunosuppressive drugs; and some of our cancer patients, particularly those with blood or hematologic malignancies, who can receive very heavy treatment that can pound the immune system to bits.

These are, in the population as a whole, relatively small numbers, but an important number of people who are still vulnerable to developing COVID-19 despite vaccination.

Why isn’t the drug available? We have a two-stage process in the United Kingdom. We have the scientists and regulatory authorities looking at the evidence and data and saying, “Yes, it stacks up. This drug is effective and safe to some extent.”

The second phase is a health technology assessment undertaken by NICE, our National Institute for Health and Care Excellence – something that I’ve talked about a number of times before and the sometimes seemingly arbitrary decisions that they make. NICE hasn’t evaluated the drug yet, and the British government has held out because they are arguing that we don’t have enough data.

The trials with Evusheld were done before the Omicron variant dominated, as it does now; therefore, they are looking to try to work with AstraZeneca to generate more real-world data to show that Evusheld would prevent infection from the Omicron variant of the virus. Equally as important, how long does that protection last? Is it as protective against Omicron, and what’s the duration of that protection? Those bits of work are going on now.

Some real-world data are starting to emerge, showing that Evusheld will offer some degree of protection against Omicron, but there are still question marks about duration and the proportion of the population that would benefit.

NICE aren’t due to report on this – although the drug was approved in March of this year – until next year some time. That’s what’s caused a degree of consternation in the community of patients that we serve. Some of my clinical colleagues are beating the drum, saying, “We must have this drug now.” We’re still waiting on NICE to announce.

One obvious way to go around this is the government, which has bent over backwards in the United Kingdom to do as much as it can to protect the population from COVID-19. There was fantastic vaccine rollout and an extraordinary economic package to support individuals during lockdown to maintain the workforce, to support families and people at home. They’ve done a fantastic job.

Wanting to damp down this controversy, perhaps the sensible thing would be to ask NICE to evaluate the data that they have just now, to allow AstraZeneca to present whatever real-world evidence they have, and although it may not be perfect, it may be sufficient – we don’t know – to pass the NICE health technology assessment.

Watch this space. Let’s see what happens. If I were government, that’s what I would do. I would ask NICE to bring their appraisal forward. I would ask them to work with AstraZeneca to go over every ounce and iota of data that they have to see if this drug will be sufficiently effective and sufficiently cost-effective to be used before winter comes. I think the whole world is holding its breath, expecting another COVID-19 winter surge. Now would be the time to act.

What do you think? Here we are in the United Kingdom discussing yet another quasi–”health-rationing” problem. It’s not. This is about collecting more data and being as rational as possible. Can we accelerate that process? Perhaps.

Thanks for listening. I’d be very grateful for any comments that you might choose to make.
 

David J. Kerr, MD, DSc, is a professor of cancer medicine at the University of Oxford (England). He disclosed financial relationships with Oxford Cancer Biomarkers, Afrox, GlaxoSmithKline, Bayer HealthCare Pharmaceuticals, Genomic Health, Merck Serono, Roche, and Celleron Therapeutics.

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

This transcript has been edited for clarity.

I’m David Kerr, professor of cancer medicine at Oxford. As I’m gearing up to have my autumnal COVID-19 booster vaccine, there’s a small controversy raging in the United Kingdom about access to a medicine called Evusheld.

This was developed by AstraZeneca. It’s a combination of two relatively long-acting antibodies (tixagevimab and cilgavimab) that bind to the spike protein on the outside of the SARS-CoV-2 virus, the virus that causes COVID-19. The antibody binds to the spike protein and prevents it from binding to and infecting or damaging cells, so it’s what’s called preexposure prophylaxis.

Although vaccination is still the best approach to protecting against and, one would hope, conferring a degree of herd protection to our population as a whole, there are some people who cannot mount an appropriate immune response and we have to take care of these folks. Because the vaccines don’t work very well for them, the vaccine itself is not sufficient to protect them.

Evusheld, in trials that have been done hitherto, can protect people who can’t mount an immune response from being infected. Between 75% and 80% of patients treated with Evusheld didn’t get COVID-19. The duration of effect seemed to be at least for 6 months, possibly longer, so it’s a really good result. This caused our medicines regulatory authority in the United Kingdom to approve the drug in March of this year. Although the drug has been approved, it’s not yet funded and not yet available for vulnerable patients.

These are patients who, for reasons of inborn genetic diseases, cannot mount an immune response; patients who are pharmacologically immune depleted; patients who have had transplants and are on immunosuppressive drugs; and some of our cancer patients, particularly those with blood or hematologic malignancies, who can receive very heavy treatment that can pound the immune system to bits.

These are, in the population as a whole, relatively small numbers, but an important number of people who are still vulnerable to developing COVID-19 despite vaccination.

Why isn’t the drug available? We have a two-stage process in the United Kingdom. We have the scientists and regulatory authorities looking at the evidence and data and saying, “Yes, it stacks up. This drug is effective and safe to some extent.”

The second phase is a health technology assessment undertaken by NICE, our National Institute for Health and Care Excellence – something that I’ve talked about a number of times before and the sometimes seemingly arbitrary decisions that they make. NICE hasn’t evaluated the drug yet, and the British government has held out because they are arguing that we don’t have enough data.

The trials with Evusheld were done before the Omicron variant dominated, as it does now; therefore, they are looking to try to work with AstraZeneca to generate more real-world data to show that Evusheld would prevent infection from the Omicron variant of the virus. Equally as important, how long does that protection last? Is it as protective against Omicron, and what’s the duration of that protection? Those bits of work are going on now.

Some real-world data are starting to emerge, showing that Evusheld will offer some degree of protection against Omicron, but there are still question marks about duration and the proportion of the population that would benefit.

NICE aren’t due to report on this – although the drug was approved in March of this year – until next year some time. That’s what’s caused a degree of consternation in the community of patients that we serve. Some of my clinical colleagues are beating the drum, saying, “We must have this drug now.” We’re still waiting on NICE to announce.

One obvious way to go around this is the government, which has bent over backwards in the United Kingdom to do as much as it can to protect the population from COVID-19. There was fantastic vaccine rollout and an extraordinary economic package to support individuals during lockdown to maintain the workforce, to support families and people at home. They’ve done a fantastic job.

Wanting to damp down this controversy, perhaps the sensible thing would be to ask NICE to evaluate the data that they have just now, to allow AstraZeneca to present whatever real-world evidence they have, and although it may not be perfect, it may be sufficient – we don’t know – to pass the NICE health technology assessment.

Watch this space. Let’s see what happens. If I were government, that’s what I would do. I would ask NICE to bring their appraisal forward. I would ask them to work with AstraZeneca to go over every ounce and iota of data that they have to see if this drug will be sufficiently effective and sufficiently cost-effective to be used before winter comes. I think the whole world is holding its breath, expecting another COVID-19 winter surge. Now would be the time to act.

What do you think? Here we are in the United Kingdom discussing yet another quasi–”health-rationing” problem. It’s not. This is about collecting more data and being as rational as possible. Can we accelerate that process? Perhaps.

Thanks for listening. I’d be very grateful for any comments that you might choose to make.
 

David J. Kerr, MD, DSc, is a professor of cancer medicine at the University of Oxford (England). He disclosed financial relationships with Oxford Cancer Biomarkers, Afrox, GlaxoSmithKline, Bayer HealthCare Pharmaceuticals, Genomic Health, Merck Serono, Roche, and Celleron Therapeutics.

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

This transcript has been edited for clarity.

I’m David Kerr, professor of cancer medicine at Oxford. As I’m gearing up to have my autumnal COVID-19 booster vaccine, there’s a small controversy raging in the United Kingdom about access to a medicine called Evusheld.

This was developed by AstraZeneca. It’s a combination of two relatively long-acting antibodies (tixagevimab and cilgavimab) that bind to the spike protein on the outside of the SARS-CoV-2 virus, the virus that causes COVID-19. The antibody binds to the spike protein and prevents it from binding to and infecting or damaging cells, so it’s what’s called preexposure prophylaxis.

Although vaccination is still the best approach to protecting against and, one would hope, conferring a degree of herd protection to our population as a whole, there are some people who cannot mount an appropriate immune response and we have to take care of these folks. Because the vaccines don’t work very well for them, the vaccine itself is not sufficient to protect them.

Evusheld, in trials that have been done hitherto, can protect people who can’t mount an immune response from being infected. Between 75% and 80% of patients treated with Evusheld didn’t get COVID-19. The duration of effect seemed to be at least for 6 months, possibly longer, so it’s a really good result. This caused our medicines regulatory authority in the United Kingdom to approve the drug in March of this year. Although the drug has been approved, it’s not yet funded and not yet available for vulnerable patients.

These are patients who, for reasons of inborn genetic diseases, cannot mount an immune response; patients who are pharmacologically immune depleted; patients who have had transplants and are on immunosuppressive drugs; and some of our cancer patients, particularly those with blood or hematologic malignancies, who can receive very heavy treatment that can pound the immune system to bits.

These are, in the population as a whole, relatively small numbers, but an important number of people who are still vulnerable to developing COVID-19 despite vaccination.

Why isn’t the drug available? We have a two-stage process in the United Kingdom. We have the scientists and regulatory authorities looking at the evidence and data and saying, “Yes, it stacks up. This drug is effective and safe to some extent.”

The second phase is a health technology assessment undertaken by NICE, our National Institute for Health and Care Excellence – something that I’ve talked about a number of times before and the sometimes seemingly arbitrary decisions that they make. NICE hasn’t evaluated the drug yet, and the British government has held out because they are arguing that we don’t have enough data.

The trials with Evusheld were done before the Omicron variant dominated, as it does now; therefore, they are looking to try to work with AstraZeneca to generate more real-world data to show that Evusheld would prevent infection from the Omicron variant of the virus. Equally as important, how long does that protection last? Is it as protective against Omicron, and what’s the duration of that protection? Those bits of work are going on now.

Some real-world data are starting to emerge, showing that Evusheld will offer some degree of protection against Omicron, but there are still question marks about duration and the proportion of the population that would benefit.

NICE aren’t due to report on this – although the drug was approved in March of this year – until next year some time. That’s what’s caused a degree of consternation in the community of patients that we serve. Some of my clinical colleagues are beating the drum, saying, “We must have this drug now.” We’re still waiting on NICE to announce.

One obvious way to go around this is the government, which has bent over backwards in the United Kingdom to do as much as it can to protect the population from COVID-19. There was fantastic vaccine rollout and an extraordinary economic package to support individuals during lockdown to maintain the workforce, to support families and people at home. They’ve done a fantastic job.

Wanting to damp down this controversy, perhaps the sensible thing would be to ask NICE to evaluate the data that they have just now, to allow AstraZeneca to present whatever real-world evidence they have, and although it may not be perfect, it may be sufficient – we don’t know – to pass the NICE health technology assessment.

Watch this space. Let’s see what happens. If I were government, that’s what I would do. I would ask NICE to bring their appraisal forward. I would ask them to work with AstraZeneca to go over every ounce and iota of data that they have to see if this drug will be sufficiently effective and sufficiently cost-effective to be used before winter comes. I think the whole world is holding its breath, expecting another COVID-19 winter surge. Now would be the time to act.

What do you think? Here we are in the United Kingdom discussing yet another quasi–”health-rationing” problem. It’s not. This is about collecting more data and being as rational as possible. Can we accelerate that process? Perhaps.

Thanks for listening. I’d be very grateful for any comments that you might choose to make.
 

David J. Kerr, MD, DSc, is a professor of cancer medicine at the University of Oxford (England). He disclosed financial relationships with Oxford Cancer Biomarkers, Afrox, GlaxoSmithKline, Bayer HealthCare Pharmaceuticals, Genomic Health, Merck Serono, Roche, and Celleron Therapeutics.

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

While efficacy and quality of life outcomes are similar across commonly used treatments for endocrine-refractory or triple-negative metastatic breast cancer, the costs of these agents vary widely, a recent analysis reveals.

Notably, the authors found that using standard chemotherapy agents in specific sequences can help reduce overall costs and improve the value of care.

Given “razor thin” differences in outcomes, cost should become a major consideration, the researchers concluded.

“As a society, we urgently need more strategies to reduce cancer drug costs without compromising outcomes, and our analysis provides quantifiable evidence to help providers choose lower priced, but equally effective sequences of drugs,” first author Stephanie B. Wheeler, PhD, from the University of North Carolina at Chapel Hill, explained in a press release.

Although the drugs Dr. Wheeler and colleagues studied are reimbursed in the metastatic breast cancer setting, “the optimal sequencing of them has been unclear, which has led to considerable variation in physician preference and practice,” Dr. Wheeler said.

In the study, published in the Journal of Clinical Oncology, Dr. Wheeler and colleagues estimated the cost-effectiveness of different therapeutic options from the first- to third-line setting for this patient population.

The researchers used three dynamic microsimulation computer models to predict how hypothetical sets of 10,000 patients with specific types of metastatic breast cancer would respond to various therapy types and sequences. The cohorts were grouped according to prior chemotherapy exposure: cohort 1 had no taxane or anthracycline exposure, cohort 2 had taxane and anthracycline exposure, and cohort 3 had taxane exposure but was anthracycline naive.

On the basis of feedback from oncologists, the investigators focused on different agents in the three cohorts: paclitaxel, capecitabine, or pegylated liposomal doxorubicin for cohort 1; eribulin, capecitabine, or carboplatin for cohort 2; and pegylated liposomal doxorubicin, capecitabine, or eribulin for cohort 3.

Overall, the models showed “nearly indistinguishable differences” in quality of life. In fact, the “razor-thin incremental differences in quality-adjusted survival” across the treatment sequences often amounted to differences of only a few days or weeks, the authors noted, adding that, even in the most extreme of cases, 3 weeks separated the best and worst options for quality-adjusted life-years.

But the models did show considerable differences in costs.

The authors found that, for cohort 1, treatment with paclitaxel followed by capecitabine and then pegylated liposomal doxorubicin corresponded to the highest expected quality-adjusted life-year gain and the lowest costs – $686 per month versus the highest cost option of $1,765.

For cohort 2, treatment with carboplatin followed by capecitabine and then eribulin corresponded to the highest expected quality-adjusted life-year gain and lowest costs.

For cohort 3, treatment sequences beginning with capecitabine or pegylated liposomal doxorubicin followed by eribulin was most cost effective.

Notably, the authors found that eribulin – the most expensive treatment with a high expected adverse event burden – performed particularly poorly in the two cohorts in which it was evaluated, “suggesting it should be used last in a sequence, on the basis of cost-effectiveness alone.”

In other words, “more spending on cancer care does not necessarily confer greater health benefits,” said Dr. Wheeler, also a professor of health policy.

“I hope our study will help expand the framework that we use to make these decisions from one where we just think about the biologic action of the drug to one where we also consider the bigger picture of what the treatment experience is like for the patient, including their financial burden, investment of time, and side effects,” study coauthor Katherine E. Reeder-Hayes, MD, section chief of breast oncology at UNC, said in the press release.

The results demonstrate that therapeutic decisions in the endocrine-refractory or triple-negative metastatic setting “may prioritize costs without affecting clinical outcomes” and highlight the direct impact that a “high-quality, transparent, and accessible economic analysis” can have on patient care, Scott D. Ramsey, MD, PhD, of Fred Hutchinson Cancer Research Center, Seattle, and colleagues wrote in an accompanying editorial.

Following the treatment sequences outlined in this study would “reduce patient financial burden and save our health system hundreds of millions of dollars annually,” the editorialists wrote.

As for next steps, Dr. Wheeler and colleagues have developed a financial navigation program to help patients manage their out-of-pocket cancer care costs and are currently scaling up the intervention in nine rural and nonrural oncology practices across North Carolina.

The study was supported by the Center for Disease Control and Prevention through the Prevention Research Centers Program. Dr. Wheeler has received research funding and payment for travel, accommodations, and expenses from Pfizer. Dr. Ramsey has had consulting or advisory roles and has received research funding and/or payment for travel, accommodations, and expenses from Bayer, Genentech, AstraZeneca, Merck, GRAIL, Seattle Genetics, Biovica, and/or Flatiron Health. Because of their editorial roles at the journal, the Journal of Clinical Oncology recused Dr. Wheeler and Dr. Ramsey from having any role in the peer review of their respective manuscripts.

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

While efficacy and quality of life outcomes are similar across commonly used treatments for endocrine-refractory or triple-negative metastatic breast cancer, the costs of these agents vary widely, a recent analysis reveals.

Notably, the authors found that using standard chemotherapy agents in specific sequences can help reduce overall costs and improve the value of care.

Given “razor thin” differences in outcomes, cost should become a major consideration, the researchers concluded.

“As a society, we urgently need more strategies to reduce cancer drug costs without compromising outcomes, and our analysis provides quantifiable evidence to help providers choose lower priced, but equally effective sequences of drugs,” first author Stephanie B. Wheeler, PhD, from the University of North Carolina at Chapel Hill, explained in a press release.

Although the drugs Dr. Wheeler and colleagues studied are reimbursed in the metastatic breast cancer setting, “the optimal sequencing of them has been unclear, which has led to considerable variation in physician preference and practice,” Dr. Wheeler said.

In the study, published in the Journal of Clinical Oncology, Dr. Wheeler and colleagues estimated the cost-effectiveness of different therapeutic options from the first- to third-line setting for this patient population.

The researchers used three dynamic microsimulation computer models to predict how hypothetical sets of 10,000 patients with specific types of metastatic breast cancer would respond to various therapy types and sequences. The cohorts were grouped according to prior chemotherapy exposure: cohort 1 had no taxane or anthracycline exposure, cohort 2 had taxane and anthracycline exposure, and cohort 3 had taxane exposure but was anthracycline naive.

On the basis of feedback from oncologists, the investigators focused on different agents in the three cohorts: paclitaxel, capecitabine, or pegylated liposomal doxorubicin for cohort 1; eribulin, capecitabine, or carboplatin for cohort 2; and pegylated liposomal doxorubicin, capecitabine, or eribulin for cohort 3.

Overall, the models showed “nearly indistinguishable differences” in quality of life. In fact, the “razor-thin incremental differences in quality-adjusted survival” across the treatment sequences often amounted to differences of only a few days or weeks, the authors noted, adding that, even in the most extreme of cases, 3 weeks separated the best and worst options for quality-adjusted life-years.

But the models did show considerable differences in costs.

The authors found that, for cohort 1, treatment with paclitaxel followed by capecitabine and then pegylated liposomal doxorubicin corresponded to the highest expected quality-adjusted life-year gain and the lowest costs – $686 per month versus the highest cost option of $1,765.

For cohort 2, treatment with carboplatin followed by capecitabine and then eribulin corresponded to the highest expected quality-adjusted life-year gain and lowest costs.

For cohort 3, treatment sequences beginning with capecitabine or pegylated liposomal doxorubicin followed by eribulin was most cost effective.

Notably, the authors found that eribulin – the most expensive treatment with a high expected adverse event burden – performed particularly poorly in the two cohorts in which it was evaluated, “suggesting it should be used last in a sequence, on the basis of cost-effectiveness alone.”

In other words, “more spending on cancer care does not necessarily confer greater health benefits,” said Dr. Wheeler, also a professor of health policy.

“I hope our study will help expand the framework that we use to make these decisions from one where we just think about the biologic action of the drug to one where we also consider the bigger picture of what the treatment experience is like for the patient, including their financial burden, investment of time, and side effects,” study coauthor Katherine E. Reeder-Hayes, MD, section chief of breast oncology at UNC, said in the press release.

The results demonstrate that therapeutic decisions in the endocrine-refractory or triple-negative metastatic setting “may prioritize costs without affecting clinical outcomes” and highlight the direct impact that a “high-quality, transparent, and accessible economic analysis” can have on patient care, Scott D. Ramsey, MD, PhD, of Fred Hutchinson Cancer Research Center, Seattle, and colleagues wrote in an accompanying editorial.

Following the treatment sequences outlined in this study would “reduce patient financial burden and save our health system hundreds of millions of dollars annually,” the editorialists wrote.

As for next steps, Dr. Wheeler and colleagues have developed a financial navigation program to help patients manage their out-of-pocket cancer care costs and are currently scaling up the intervention in nine rural and nonrural oncology practices across North Carolina.

The study was supported by the Center for Disease Control and Prevention through the Prevention Research Centers Program. Dr. Wheeler has received research funding and payment for travel, accommodations, and expenses from Pfizer. Dr. Ramsey has had consulting or advisory roles and has received research funding and/or payment for travel, accommodations, and expenses from Bayer, Genentech, AstraZeneca, Merck, GRAIL, Seattle Genetics, Biovica, and/or Flatiron Health. Because of their editorial roles at the journal, the Journal of Clinical Oncology recused Dr. Wheeler and Dr. Ramsey from having any role in the peer review of their respective manuscripts.

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

While efficacy and quality of life outcomes are similar across commonly used treatments for endocrine-refractory or triple-negative metastatic breast cancer, the costs of these agents vary widely, a recent analysis reveals.

Notably, the authors found that using standard chemotherapy agents in specific sequences can help reduce overall costs and improve the value of care.

Given “razor thin” differences in outcomes, cost should become a major consideration, the researchers concluded.

“As a society, we urgently need more strategies to reduce cancer drug costs without compromising outcomes, and our analysis provides quantifiable evidence to help providers choose lower priced, but equally effective sequences of drugs,” first author Stephanie B. Wheeler, PhD, from the University of North Carolina at Chapel Hill, explained in a press release.

Although the drugs Dr. Wheeler and colleagues studied are reimbursed in the metastatic breast cancer setting, “the optimal sequencing of them has been unclear, which has led to considerable variation in physician preference and practice,” Dr. Wheeler said.

In the study, published in the Journal of Clinical Oncology, Dr. Wheeler and colleagues estimated the cost-effectiveness of different therapeutic options from the first- to third-line setting for this patient population.

The researchers used three dynamic microsimulation computer models to predict how hypothetical sets of 10,000 patients with specific types of metastatic breast cancer would respond to various therapy types and sequences. The cohorts were grouped according to prior chemotherapy exposure: cohort 1 had no taxane or anthracycline exposure, cohort 2 had taxane and anthracycline exposure, and cohort 3 had taxane exposure but was anthracycline naive.

On the basis of feedback from oncologists, the investigators focused on different agents in the three cohorts: paclitaxel, capecitabine, or pegylated liposomal doxorubicin for cohort 1; eribulin, capecitabine, or carboplatin for cohort 2; and pegylated liposomal doxorubicin, capecitabine, or eribulin for cohort 3.

Overall, the models showed “nearly indistinguishable differences” in quality of life. In fact, the “razor-thin incremental differences in quality-adjusted survival” across the treatment sequences often amounted to differences of only a few days or weeks, the authors noted, adding that, even in the most extreme of cases, 3 weeks separated the best and worst options for quality-adjusted life-years.

But the models did show considerable differences in costs.

The authors found that, for cohort 1, treatment with paclitaxel followed by capecitabine and then pegylated liposomal doxorubicin corresponded to the highest expected quality-adjusted life-year gain and the lowest costs – $686 per month versus the highest cost option of $1,765.

For cohort 2, treatment with carboplatin followed by capecitabine and then eribulin corresponded to the highest expected quality-adjusted life-year gain and lowest costs.

For cohort 3, treatment sequences beginning with capecitabine or pegylated liposomal doxorubicin followed by eribulin was most cost effective.

Notably, the authors found that eribulin – the most expensive treatment with a high expected adverse event burden – performed particularly poorly in the two cohorts in which it was evaluated, “suggesting it should be used last in a sequence, on the basis of cost-effectiveness alone.”

In other words, “more spending on cancer care does not necessarily confer greater health benefits,” said Dr. Wheeler, also a professor of health policy.

“I hope our study will help expand the framework that we use to make these decisions from one where we just think about the biologic action of the drug to one where we also consider the bigger picture of what the treatment experience is like for the patient, including their financial burden, investment of time, and side effects,” study coauthor Katherine E. Reeder-Hayes, MD, section chief of breast oncology at UNC, said in the press release.

The results demonstrate that therapeutic decisions in the endocrine-refractory or triple-negative metastatic setting “may prioritize costs without affecting clinical outcomes” and highlight the direct impact that a “high-quality, transparent, and accessible economic analysis” can have on patient care, Scott D. Ramsey, MD, PhD, of Fred Hutchinson Cancer Research Center, Seattle, and colleagues wrote in an accompanying editorial.

Following the treatment sequences outlined in this study would “reduce patient financial burden and save our health system hundreds of millions of dollars annually,” the editorialists wrote.

As for next steps, Dr. Wheeler and colleagues have developed a financial navigation program to help patients manage their out-of-pocket cancer care costs and are currently scaling up the intervention in nine rural and nonrural oncology practices across North Carolina.

The study was supported by the Center for Disease Control and Prevention through the Prevention Research Centers Program. Dr. Wheeler has received research funding and payment for travel, accommodations, and expenses from Pfizer. Dr. Ramsey has had consulting or advisory roles and has received research funding and/or payment for travel, accommodations, and expenses from Bayer, Genentech, AstraZeneca, Merck, GRAIL, Seattle Genetics, Biovica, and/or Flatiron Health. Because of their editorial roles at the journal, the Journal of Clinical Oncology recused Dr. Wheeler and Dr. Ramsey from having any role in the peer review of their respective manuscripts.

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

Black and Hispanic adults with spina bifida or cerebral palsy are less likely to attend wellness visits than are White adults with the same pediatric-onset disabilities, a new study finds.

Black adults also had lower odds of having a bone density screening, compared with White adults. Plus, comorbidities were highest among the Black patients, according to the paper, which was published in Annals of Family Medicine.

Elham Mahmoudi, PhD, and her coauthors examined private insurance claims from 11,635 patients with cerebral palsy (CP) or spina bifida over ten years from 2007 to 2017. The researchers analyzed comorbidities and compared the rates of different psychological, cardiometabolic, and musculoskeletal conditions among these patients.

Only 23% of Hispanic participants and 18% of Black participants attended an annual wellness visit, compared with 32% of the White participants.

Only 1% of Black and 2% of White participants received any bone density screening (odds ratio = 0.54, 95% confidence interval [CI], 0.31-0.95), a service that is essential for catching a patient’s potential risk for osteoporosis and fractures.

According to the researchers, patients accessed services such as bone density scans, cholesterol assessments, diabetes screenings, and annual wellness visits less than recommended for people with those chronic conditions.

“People with spina bifida and cerebral palsy have complex care needs. We know through our work that chronic conditions are much higher among them compared with adults without disabilities,” Dr. Mahmoudi, associate professor in the department of family medicine at University of Michigan, Ann Arbor, said in an interview. “I was surprised to see even with private insurance, the rate of using preventative services is so low among White people and minority populations.”
 

Comorbidities highest in Black participants

Black adults had the highest comorbidity score of 2.5, and Hispanic adults had the lowest comorbidity score of 1.8. For White adults in the study, the comorbidity score was 2.0.

Osteoporosis, a common concern for people with spina bifida or cerebral palsy, was detected in around 4% of all participants. Osteoarthritis was detected in 13.38% of Black participants, versus 8.53% of Hispanic participants and 11.09% of White participants.

Diabetes and hypertension were more common among Black participants than among Hispanic and White participants. The percentages of Black patients with hypertension and diabetes were 16.5% and 39.89%, respectively. Among the Hispanic and White adults, the percentages with hypertension were 22.3% and 28.2%, respectively, according to the paper.
 

Disparities in access

Jamil Paden, racial and health equity manager at the Christopher and Dana Reeve Foundation, said getting access to literature, transportation, tables, chairs, weigh scales, and imaging equipment that accommodate the needs of people with disabilities are some of the biggest challenges for people with disabilities who are trying to receive care.

“It’s not a one size fits all, we have to recognize that if someone doesn’t see themselves in a particular place, then it makes it more challenging for them to feel comfortable speaking up and saying things about their health, which would prevent a person from saying something early on,” Mr. Paden said in an interview. “That particular issue will continue to grow and become more of a health risk, or health challenge down the line.”

Mr. Paden emphasized intersections between class, race, and circumstances which can, together, make health care less equitable for people with disabilities, especially in underserved communities and communities of color. He urged health care providers to distance their practices from a “one size fits all” approach to treatment and engage in their patients’ individual lives and communities.

“It’s not enough to just say, Hey, you have a disability. So let me treat your disability ... You have to recognize that although a patient may have a dire diagnosis, they also are a person of color, and they have to navigate different aspects of life from their counterparts,” he said.

Dr. Mahmoudi said patient and provider understanding of the disability is often lacking. She recommended advocating for patients, noting that giving both patients and providers the tools to further educate themselves and apply that to their regular visits is a good first step.

“Just having access to a facility doesn’t mean they will get the services they need. Preventative services that are recommended for people with disabilities differ from the general population. Providers should be educated about that and the patient needs to be educated about that,” she added.

“Patients who do not approach clinicians get lost in the system. Maybe many facilities are not disability friendly, or they need health literacy. If they don’t know they are at risk for osteoporosis, for example, then they won’t ask,” Dr. Mahmoudi said.

The study was funded by The National Institute on Disability, Independent Living, and Rehabilitation Research. Dr. Mahmoudi and Mr. Paden report no relevant financial relationships.

Black and Hispanic adults with spina bifida or cerebral palsy are less likely to attend wellness visits than are White adults with the same pediatric-onset disabilities, a new study finds.

Black adults also had lower odds of having a bone density screening, compared with White adults. Plus, comorbidities were highest among the Black patients, according to the paper, which was published in Annals of Family Medicine.

Elham Mahmoudi, PhD, and her coauthors examined private insurance claims from 11,635 patients with cerebral palsy (CP) or spina bifida over ten years from 2007 to 2017. The researchers analyzed comorbidities and compared the rates of different psychological, cardiometabolic, and musculoskeletal conditions among these patients.

Only 23% of Hispanic participants and 18% of Black participants attended an annual wellness visit, compared with 32% of the White participants.

Only 1% of Black and 2% of White participants received any bone density screening (odds ratio = 0.54, 95% confidence interval [CI], 0.31-0.95), a service that is essential for catching a patient’s potential risk for osteoporosis and fractures.

According to the researchers, patients accessed services such as bone density scans, cholesterol assessments, diabetes screenings, and annual wellness visits less than recommended for people with those chronic conditions.

“People with spina bifida and cerebral palsy have complex care needs. We know through our work that chronic conditions are much higher among them compared with adults without disabilities,” Dr. Mahmoudi, associate professor in the department of family medicine at University of Michigan, Ann Arbor, said in an interview. “I was surprised to see even with private insurance, the rate of using preventative services is so low among White people and minority populations.”
 

Comorbidities highest in Black participants

Black adults had the highest comorbidity score of 2.5, and Hispanic adults had the lowest comorbidity score of 1.8. For White adults in the study, the comorbidity score was 2.0.

Osteoporosis, a common concern for people with spina bifida or cerebral palsy, was detected in around 4% of all participants. Osteoarthritis was detected in 13.38% of Black participants, versus 8.53% of Hispanic participants and 11.09% of White participants.

Diabetes and hypertension were more common among Black participants than among Hispanic and White participants. The percentages of Black patients with hypertension and diabetes were 16.5% and 39.89%, respectively. Among the Hispanic and White adults, the percentages with hypertension were 22.3% and 28.2%, respectively, according to the paper.
 

Disparities in access

Jamil Paden, racial and health equity manager at the Christopher and Dana Reeve Foundation, said getting access to literature, transportation, tables, chairs, weigh scales, and imaging equipment that accommodate the needs of people with disabilities are some of the biggest challenges for people with disabilities who are trying to receive care.

“It’s not a one size fits all, we have to recognize that if someone doesn’t see themselves in a particular place, then it makes it more challenging for them to feel comfortable speaking up and saying things about their health, which would prevent a person from saying something early on,” Mr. Paden said in an interview. “That particular issue will continue to grow and become more of a health risk, or health challenge down the line.”

Mr. Paden emphasized intersections between class, race, and circumstances which can, together, make health care less equitable for people with disabilities, especially in underserved communities and communities of color. He urged health care providers to distance their practices from a “one size fits all” approach to treatment and engage in their patients’ individual lives and communities.

“It’s not enough to just say, Hey, you have a disability. So let me treat your disability ... You have to recognize that although a patient may have a dire diagnosis, they also are a person of color, and they have to navigate different aspects of life from their counterparts,” he said.

Dr. Mahmoudi said patient and provider understanding of the disability is often lacking. She recommended advocating for patients, noting that giving both patients and providers the tools to further educate themselves and apply that to their regular visits is a good first step.

“Just having access to a facility doesn’t mean they will get the services they need. Preventative services that are recommended for people with disabilities differ from the general population. Providers should be educated about that and the patient needs to be educated about that,” she added.

“Patients who do not approach clinicians get lost in the system. Maybe many facilities are not disability friendly, or they need health literacy. If they don’t know they are at risk for osteoporosis, for example, then they won’t ask,” Dr. Mahmoudi said.

The study was funded by The National Institute on Disability, Independent Living, and Rehabilitation Research. Dr. Mahmoudi and Mr. Paden report no relevant financial relationships.

Black and Hispanic adults with spina bifida or cerebral palsy are less likely to attend wellness visits than are White adults with the same pediatric-onset disabilities, a new study finds.

Black adults also had lower odds of having a bone density screening, compared with White adults. Plus, comorbidities were highest among the Black patients, according to the paper, which was published in Annals of Family Medicine.

Elham Mahmoudi, PhD, and her coauthors examined private insurance claims from 11,635 patients with cerebral palsy (CP) or spina bifida over ten years from 2007 to 2017. The researchers analyzed comorbidities and compared the rates of different psychological, cardiometabolic, and musculoskeletal conditions among these patients.

Only 23% of Hispanic participants and 18% of Black participants attended an annual wellness visit, compared with 32% of the White participants.

Only 1% of Black and 2% of White participants received any bone density screening (odds ratio = 0.54, 95% confidence interval [CI], 0.31-0.95), a service that is essential for catching a patient’s potential risk for osteoporosis and fractures.

According to the researchers, patients accessed services such as bone density scans, cholesterol assessments, diabetes screenings, and annual wellness visits less than recommended for people with those chronic conditions.

“People with spina bifida and cerebral palsy have complex care needs. We know through our work that chronic conditions are much higher among them compared with adults without disabilities,” Dr. Mahmoudi, associate professor in the department of family medicine at University of Michigan, Ann Arbor, said in an interview. “I was surprised to see even with private insurance, the rate of using preventative services is so low among White people and minority populations.”
 

Comorbidities highest in Black participants

Black adults had the highest comorbidity score of 2.5, and Hispanic adults had the lowest comorbidity score of 1.8. For White adults in the study, the comorbidity score was 2.0.

Osteoporosis, a common concern for people with spina bifida or cerebral palsy, was detected in around 4% of all participants. Osteoarthritis was detected in 13.38% of Black participants, versus 8.53% of Hispanic participants and 11.09% of White participants.

Diabetes and hypertension were more common among Black participants than among Hispanic and White participants. The percentages of Black patients with hypertension and diabetes were 16.5% and 39.89%, respectively. Among the Hispanic and White adults, the percentages with hypertension were 22.3% and 28.2%, respectively, according to the paper.
 

Disparities in access

Jamil Paden, racial and health equity manager at the Christopher and Dana Reeve Foundation, said getting access to literature, transportation, tables, chairs, weigh scales, and imaging equipment that accommodate the needs of people with disabilities are some of the biggest challenges for people with disabilities who are trying to receive care.

“It’s not a one size fits all, we have to recognize that if someone doesn’t see themselves in a particular place, then it makes it more challenging for them to feel comfortable speaking up and saying things about their health, which would prevent a person from saying something early on,” Mr. Paden said in an interview. “That particular issue will continue to grow and become more of a health risk, or health challenge down the line.”

Mr. Paden emphasized intersections between class, race, and circumstances which can, together, make health care less equitable for people with disabilities, especially in underserved communities and communities of color. He urged health care providers to distance their practices from a “one size fits all” approach to treatment and engage in their patients’ individual lives and communities.

“It’s not enough to just say, Hey, you have a disability. So let me treat your disability ... You have to recognize that although a patient may have a dire diagnosis, they also are a person of color, and they have to navigate different aspects of life from their counterparts,” he said.

Dr. Mahmoudi said patient and provider understanding of the disability is often lacking. She recommended advocating for patients, noting that giving both patients and providers the tools to further educate themselves and apply that to their regular visits is a good first step.

“Just having access to a facility doesn’t mean they will get the services they need. Preventative services that are recommended for people with disabilities differ from the general population. Providers should be educated about that and the patient needs to be educated about that,” she added.

“Patients who do not approach clinicians get lost in the system. Maybe many facilities are not disability friendly, or they need health literacy. If they don’t know they are at risk for osteoporosis, for example, then they won’t ask,” Dr. Mahmoudi said.

The study was funded by The National Institute on Disability, Independent Living, and Rehabilitation Research. Dr. Mahmoudi and Mr. Paden report no relevant financial relationships.

Gender-affirming hormone therapy’s effect on transgender patients with rheumatic disease is unclear but does not appear to modulate its course and does not need to be strictly contraindicated in most patients, according to a case series and systematic literature review.

More doctors are practicing transgender medicine, yet a limited amount of information is available on rheumatic disease in transgender and gender diverse (TGGD) individuals, Kristen Mathias, MD, a rheumatology fellow at Johns Hopkins University, Baltimore, said in her presentation of the study at the Lancet Summit on Sex and Gender in Rheumatology.

“This is important, as it is well known that sex hormones affect the pathogenesis and expression of autoimmune diseases,” Dr. Mathias said. Knowing more about the effects of gender-affirming hormone therapy (GAHT) and gender-affirming surgery on disease activity in TGGD individuals could better inform decisions about care in this population.

Dr. Mathias and colleagues identified 7 transgender patients with rheumatic diseases from a pool of 1,053 patients seen at the Los Angeles County and University of Southern California Medical Center, Los Angeles, from June 2019 to June 2021. This included five transgender males and two transgender females. They ranged in age from 13 to 52 years.

All seven were on GAHT, and its impact on disease activity was considered “possible” in two of the seven patients.

In a systematic literature review, investigators found 11 studies that included 11 transgender women and 2 transgender men, ranging in age from 22 to 49 years. All the patients were on GAHT. In 12 of 13 patients, the hormones were considered possibly related to their rheumatic disease activity.

The 20 patients had diagnoses of rheumatoid arthritis, cutaneous and systemic lupus erythematosus, adult-onset Still disease, spondyloarthritis, myositis, and systemic sclerosis.

GAHT should not be a strict contraindication in these patients, based on these findings, Dr. Mathias noted. Information to clarify the effect of GAHT on rheumatic disease is sparse, however. Physicians should adopt a personalized, shared decision-making approach when consulting patients.

“During patient encounters, they should be screened for psychosocial barriers when appropriate,” Dr. Mathias recommended.

Findings could pave way for larger studies, more data

Studies on the impact and consequences of rheumatic disease in TGGD individuals are sorely lacking, said Vagishwari Murugesan, MBBS, a clinical fellow in rheumatology at the University of Toronto.

“While this is a small study of only seven patients and no conclusive results can be drawn, studies like these can help pave the way for larger multicentric studies, which can give us more definitive data on gender-affirming hormone therapy and its consequences on rheumatic diseases,” said Dr. Murugesan, who was not involved in the study.

A registry would be a great way to collaborate with other stakeholders interested in the same topic and conduct larger studies, she said. “I would recommend that not only do we screen for psychosocial barriers but also actively engage as a health care community in addressing how we can overcome the barriers for patients to access effective health care.”

No external funding was obtained for the study.

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

Gender-affirming hormone therapy’s effect on transgender patients with rheumatic disease is unclear but does not appear to modulate its course and does not need to be strictly contraindicated in most patients, according to a case series and systematic literature review.

More doctors are practicing transgender medicine, yet a limited amount of information is available on rheumatic disease in transgender and gender diverse (TGGD) individuals, Kristen Mathias, MD, a rheumatology fellow at Johns Hopkins University, Baltimore, said in her presentation of the study at the Lancet Summit on Sex and Gender in Rheumatology.

“This is important, as it is well known that sex hormones affect the pathogenesis and expression of autoimmune diseases,” Dr. Mathias said. Knowing more about the effects of gender-affirming hormone therapy (GAHT) and gender-affirming surgery on disease activity in TGGD individuals could better inform decisions about care in this population.

Dr. Mathias and colleagues identified 7 transgender patients with rheumatic diseases from a pool of 1,053 patients seen at the Los Angeles County and University of Southern California Medical Center, Los Angeles, from June 2019 to June 2021. This included five transgender males and two transgender females. They ranged in age from 13 to 52 years.

All seven were on GAHT, and its impact on disease activity was considered “possible” in two of the seven patients.

In a systematic literature review, investigators found 11 studies that included 11 transgender women and 2 transgender men, ranging in age from 22 to 49 years. All the patients were on GAHT. In 12 of 13 patients, the hormones were considered possibly related to their rheumatic disease activity.

The 20 patients had diagnoses of rheumatoid arthritis, cutaneous and systemic lupus erythematosus, adult-onset Still disease, spondyloarthritis, myositis, and systemic sclerosis.

GAHT should not be a strict contraindication in these patients, based on these findings, Dr. Mathias noted. Information to clarify the effect of GAHT on rheumatic disease is sparse, however. Physicians should adopt a personalized, shared decision-making approach when consulting patients.

“During patient encounters, they should be screened for psychosocial barriers when appropriate,” Dr. Mathias recommended.

Findings could pave way for larger studies, more data

Studies on the impact and consequences of rheumatic disease in TGGD individuals are sorely lacking, said Vagishwari Murugesan, MBBS, a clinical fellow in rheumatology at the University of Toronto.

“While this is a small study of only seven patients and no conclusive results can be drawn, studies like these can help pave the way for larger multicentric studies, which can give us more definitive data on gender-affirming hormone therapy and its consequences on rheumatic diseases,” said Dr. Murugesan, who was not involved in the study.

A registry would be a great way to collaborate with other stakeholders interested in the same topic and conduct larger studies, she said. “I would recommend that not only do we screen for psychosocial barriers but also actively engage as a health care community in addressing how we can overcome the barriers for patients to access effective health care.”

No external funding was obtained for the study.

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

Gender-affirming hormone therapy’s effect on transgender patients with rheumatic disease is unclear but does not appear to modulate its course and does not need to be strictly contraindicated in most patients, according to a case series and systematic literature review.

More doctors are practicing transgender medicine, yet a limited amount of information is available on rheumatic disease in transgender and gender diverse (TGGD) individuals, Kristen Mathias, MD, a rheumatology fellow at Johns Hopkins University, Baltimore, said in her presentation of the study at the Lancet Summit on Sex and Gender in Rheumatology.

“This is important, as it is well known that sex hormones affect the pathogenesis and expression of autoimmune diseases,” Dr. Mathias said. Knowing more about the effects of gender-affirming hormone therapy (GAHT) and gender-affirming surgery on disease activity in TGGD individuals could better inform decisions about care in this population.

Dr. Mathias and colleagues identified 7 transgender patients with rheumatic diseases from a pool of 1,053 patients seen at the Los Angeles County and University of Southern California Medical Center, Los Angeles, from June 2019 to June 2021. This included five transgender males and two transgender females. They ranged in age from 13 to 52 years.

All seven were on GAHT, and its impact on disease activity was considered “possible” in two of the seven patients.

In a systematic literature review, investigators found 11 studies that included 11 transgender women and 2 transgender men, ranging in age from 22 to 49 years. All the patients were on GAHT. In 12 of 13 patients, the hormones were considered possibly related to their rheumatic disease activity.

The 20 patients had diagnoses of rheumatoid arthritis, cutaneous and systemic lupus erythematosus, adult-onset Still disease, spondyloarthritis, myositis, and systemic sclerosis.

GAHT should not be a strict contraindication in these patients, based on these findings, Dr. Mathias noted. Information to clarify the effect of GAHT on rheumatic disease is sparse, however. Physicians should adopt a personalized, shared decision-making approach when consulting patients.

“During patient encounters, they should be screened for psychosocial barriers when appropriate,” Dr. Mathias recommended.

Findings could pave way for larger studies, more data

Studies on the impact and consequences of rheumatic disease in TGGD individuals are sorely lacking, said Vagishwari Murugesan, MBBS, a clinical fellow in rheumatology at the University of Toronto.

“While this is a small study of only seven patients and no conclusive results can be drawn, studies like these can help pave the way for larger multicentric studies, which can give us more definitive data on gender-affirming hormone therapy and its consequences on rheumatic diseases,” said Dr. Murugesan, who was not involved in the study.

A registry would be a great way to collaborate with other stakeholders interested in the same topic and conduct larger studies, she said. “I would recommend that not only do we screen for psychosocial barriers but also actively engage as a health care community in addressing how we can overcome the barriers for patients to access effective health care.”

No external funding was obtained for the study.

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