TOPLINE:

Bariatric metabolic surgery (BMS) offers a survival advantage over glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in adults with obesity and diabetes for 10 years or less, which may be explained by greater weight loss with surgery, new research shows.

METHODOLOGY:

• There is limited evidence regarding the relative effectiveness of BMS and GLP-1 RAs in reducing mortality and major adverse cardiovascular events (MACE).
• This observational, retrospective cohort study analyzed the electronic medical records of Clalit Health Services, Israel’s largest healthcare organization.
• Researchers included patients aged 24 years or older who had diabetes and obesity but no prior cardiovascular disease and who either underwent BMS or received a GLP-1 RA.
• The primary outcome was all-cause mortality, assessed by multivariate Cox proportional hazards regression models. The secondary outcome was nonfatal MACE, assessed by multivariate competing risk models.

TAKEAWAY:

• Researchers included 3035 matched pairs of patients (total, 6070; mean age, 51 years; 65% women), who were followed for a median of 6.8 years.
• Among patients with diabetes for 10 years or less, those who underwent BMS had a 62% lower risk for mortality than those treated with a GLP-1 RA (hazard ratio [HR], 0.38).
• The survival advantage associated with BMS vs GLP-1 RA may be explained by the greater relative decrease in body mass index in the surgery group (–31.4% vs –12.8%, respectively).
• Among patients with diabetes for more than 10 years, no survival advantage was observed for BMS over GLP-1 RA (HR, 0.65), which may be explained by the adverse effects of prolonged diabetes duration masking the benefit associated with weight loss.
• The risk for nonfatal MACE did not differ significantly between the treatment groups in both diabetes duration categories.

IN PRACTICE:

“This study suggests that BMS was associated with greater reduced mortality compared with GLP-1 RAs among individuals with a diabetes duration of 10 years or less, mediated via greater weight loss,” the authors wrote.

SOURCE:

The study, with first author Dror Dicker, MD, Hasharon Hospital, Rabin Medical Center, Petah Tikva, Israel, was published online in JAMA Network Open.

LIMITATIONS:

The observational design may have introduced residual confounding despite matching and multivariable adjustment. The analyses did not account for the types of BMS or GLP-1 RAs or the level of adherence to GLP-1 RA treatment. Information regarding cause of death was unavailable.

DISCLOSURES:

The study was funded by the Israel Science Foundation. Dicker reported financial relationships with Novo Nordisk, Eli Lilly, and Boehringer Ingelheim.

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

TOPLINE:

Bariatric metabolic surgery (BMS) offers a survival advantage over glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in adults with obesity and diabetes for 10 years or less, which may be explained by greater weight loss with surgery, new research shows.

METHODOLOGY:

• There is limited evidence regarding the relative effectiveness of BMS and GLP-1 RAs in reducing mortality and major adverse cardiovascular events (MACE).
• This observational, retrospective cohort study analyzed the electronic medical records of Clalit Health Services, Israel’s largest healthcare organization.
• Researchers included patients aged 24 years or older who had diabetes and obesity but no prior cardiovascular disease and who either underwent BMS or received a GLP-1 RA.
• The primary outcome was all-cause mortality, assessed by multivariate Cox proportional hazards regression models. The secondary outcome was nonfatal MACE, assessed by multivariate competing risk models.

TAKEAWAY:

• Researchers included 3035 matched pairs of patients (total, 6070; mean age, 51 years; 65% women), who were followed for a median of 6.8 years.
• Among patients with diabetes for 10 years or less, those who underwent BMS had a 62% lower risk for mortality than those treated with a GLP-1 RA (hazard ratio [HR], 0.38).
• The survival advantage associated with BMS vs GLP-1 RA may be explained by the greater relative decrease in body mass index in the surgery group (–31.4% vs –12.8%, respectively).
• Among patients with diabetes for more than 10 years, no survival advantage was observed for BMS over GLP-1 RA (HR, 0.65), which may be explained by the adverse effects of prolonged diabetes duration masking the benefit associated with weight loss.
• The risk for nonfatal MACE did not differ significantly between the treatment groups in both diabetes duration categories.

IN PRACTICE:

“This study suggests that BMS was associated with greater reduced mortality compared with GLP-1 RAs among individuals with a diabetes duration of 10 years or less, mediated via greater weight loss,” the authors wrote.

SOURCE:

The study, with first author Dror Dicker, MD, Hasharon Hospital, Rabin Medical Center, Petah Tikva, Israel, was published online in JAMA Network Open.

LIMITATIONS:

The observational design may have introduced residual confounding despite matching and multivariable adjustment. The analyses did not account for the types of BMS or GLP-1 RAs or the level of adherence to GLP-1 RA treatment. Information regarding cause of death was unavailable.

DISCLOSURES:

The study was funded by the Israel Science Foundation. Dicker reported financial relationships with Novo Nordisk, Eli Lilly, and Boehringer Ingelheim.

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

TOPLINE:

Bariatric metabolic surgery (BMS) offers a survival advantage over glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in adults with obesity and diabetes for 10 years or less, which may be explained by greater weight loss with surgery, new research shows.

METHODOLOGY:

• There is limited evidence regarding the relative effectiveness of BMS and GLP-1 RAs in reducing mortality and major adverse cardiovascular events (MACE).
• This observational, retrospective cohort study analyzed the electronic medical records of Clalit Health Services, Israel’s largest healthcare organization.
• Researchers included patients aged 24 years or older who had diabetes and obesity but no prior cardiovascular disease and who either underwent BMS or received a GLP-1 RA.
• The primary outcome was all-cause mortality, assessed by multivariate Cox proportional hazards regression models. The secondary outcome was nonfatal MACE, assessed by multivariate competing risk models.

TAKEAWAY:

• Researchers included 3035 matched pairs of patients (total, 6070; mean age, 51 years; 65% women), who were followed for a median of 6.8 years.
• Among patients with diabetes for 10 years or less, those who underwent BMS had a 62% lower risk for mortality than those treated with a GLP-1 RA (hazard ratio [HR], 0.38).
• The survival advantage associated with BMS vs GLP-1 RA may be explained by the greater relative decrease in body mass index in the surgery group (–31.4% vs –12.8%, respectively).
• Among patients with diabetes for more than 10 years, no survival advantage was observed for BMS over GLP-1 RA (HR, 0.65), which may be explained by the adverse effects of prolonged diabetes duration masking the benefit associated with weight loss.
• The risk for nonfatal MACE did not differ significantly between the treatment groups in both diabetes duration categories.

IN PRACTICE:

“This study suggests that BMS was associated with greater reduced mortality compared with GLP-1 RAs among individuals with a diabetes duration of 10 years or less, mediated via greater weight loss,” the authors wrote.

SOURCE:

The study, with first author Dror Dicker, MD, Hasharon Hospital, Rabin Medical Center, Petah Tikva, Israel, was published online in JAMA Network Open.

LIMITATIONS:

The observational design may have introduced residual confounding despite matching and multivariable adjustment. The analyses did not account for the types of BMS or GLP-1 RAs or the level of adherence to GLP-1 RA treatment. Information regarding cause of death was unavailable.

DISCLOSURES:

The study was funded by the Israel Science Foundation. Dicker reported financial relationships with Novo Nordisk, Eli Lilly, and Boehringer Ingelheim.

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

TOPLINE:

Anorexia nervosa (AN) is associated with a 4.5-fold increased risk for mortality — a rate that nearly doubles when AN patients have psychiatric comorbidities.

METHODOLOGY:

• Researchers analyzed data from 14,774 patients diagnosed with AN at age ≥ 6 years from 1977 to 2018.
• Patients were followed-up for a median time of 9.1 years, with some followed-up for ≤ 40 years and matched 1:10 with age- and sex-matched controls.
• Investigators calculated adjusted hazard ratios for mortality, considering psychiatric comorbidity, sex, and age at diagnosis.

TAKEAWAY:

• AN is associated with a 4.5-fold increased mortality risk vs the general population.
• About half of the sample with AN (47%) had a psychiatric comorbidity, which is associated with a 7.7% mortality risk at 10 years.
• Psychiatric comorbidity in anorexia nervosa patients nearly doubles the 10-year mortality risk.
• Suicide was the primary cause of unnatural death (9% died by suicide), and the rate was higher among patients with a psychiatric comorbidity.

IN PRACTICE:

“These findings highlight the crucial need for clinicians to recognize additional mental health disorders in adolescents and adults with anorexia,” author Mette Søeby, MD, Aarhus University/Aarhus University Hospital, in Aarhus, Denmark, said in a press release.

SOURCE:

The study was led by Dr. Søeby and was published online on June 12, 2024, in the International Journal of Eating Disorders.

LIMITATIONS:

The transition from International Classification of Diseases, 8th edition (ICD-8) to ICD-10 and inclusion of outpatient visits may have influenced the study’s results by including more patients with less severe illness. The ICD-10 diagnosis code for anorexia nervosa in Danish registers has not been validated, potentially affecting the accuracy of the study’s findings.

DISCLOSURES:

The study was supported by grants from the Novo Nordic Foundation and The Danish Foundation for Research in Mental Disorders. The authors declared no conflicts of interest.


This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Anorexia nervosa (AN) is associated with a 4.5-fold increased risk for mortality — a rate that nearly doubles when AN patients have psychiatric comorbidities.

METHODOLOGY:

• Researchers analyzed data from 14,774 patients diagnosed with AN at age ≥ 6 years from 1977 to 2018.
• Patients were followed-up for a median time of 9.1 years, with some followed-up for ≤ 40 years and matched 1:10 with age- and sex-matched controls.
• Investigators calculated adjusted hazard ratios for mortality, considering psychiatric comorbidity, sex, and age at diagnosis.

TAKEAWAY:

• AN is associated with a 4.5-fold increased mortality risk vs the general population.
• About half of the sample with AN (47%) had a psychiatric comorbidity, which is associated with a 7.7% mortality risk at 10 years.
• Psychiatric comorbidity in anorexia nervosa patients nearly doubles the 10-year mortality risk.
• Suicide was the primary cause of unnatural death (9% died by suicide), and the rate was higher among patients with a psychiatric comorbidity.

IN PRACTICE:

“These findings highlight the crucial need for clinicians to recognize additional mental health disorders in adolescents and adults with anorexia,” author Mette Søeby, MD, Aarhus University/Aarhus University Hospital, in Aarhus, Denmark, said in a press release.

SOURCE:

The study was led by Dr. Søeby and was published online on June 12, 2024, in the International Journal of Eating Disorders.

LIMITATIONS:

The transition from International Classification of Diseases, 8th edition (ICD-8) to ICD-10 and inclusion of outpatient visits may have influenced the study’s results by including more patients with less severe illness. The ICD-10 diagnosis code for anorexia nervosa in Danish registers has not been validated, potentially affecting the accuracy of the study’s findings.

DISCLOSURES:

The study was supported by grants from the Novo Nordic Foundation and The Danish Foundation for Research in Mental Disorders. The authors declared no conflicts of interest.


This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Anorexia nervosa (AN) is associated with a 4.5-fold increased risk for mortality — a rate that nearly doubles when AN patients have psychiatric comorbidities.

METHODOLOGY:

• Researchers analyzed data from 14,774 patients diagnosed with AN at age ≥ 6 years from 1977 to 2018.
• Patients were followed-up for a median time of 9.1 years, with some followed-up for ≤ 40 years and matched 1:10 with age- and sex-matched controls.
• Investigators calculated adjusted hazard ratios for mortality, considering psychiatric comorbidity, sex, and age at diagnosis.

TAKEAWAY:

• AN is associated with a 4.5-fold increased mortality risk vs the general population.
• About half of the sample with AN (47%) had a psychiatric comorbidity, which is associated with a 7.7% mortality risk at 10 years.
• Psychiatric comorbidity in anorexia nervosa patients nearly doubles the 10-year mortality risk.
• Suicide was the primary cause of unnatural death (9% died by suicide), and the rate was higher among patients with a psychiatric comorbidity.

IN PRACTICE:

“These findings highlight the crucial need for clinicians to recognize additional mental health disorders in adolescents and adults with anorexia,” author Mette Søeby, MD, Aarhus University/Aarhus University Hospital, in Aarhus, Denmark, said in a press release.

SOURCE:

The study was led by Dr. Søeby and was published online on June 12, 2024, in the International Journal of Eating Disorders.

LIMITATIONS:

The transition from International Classification of Diseases, 8th edition (ICD-8) to ICD-10 and inclusion of outpatient visits may have influenced the study’s results by including more patients with less severe illness. The ICD-10 diagnosis code for anorexia nervosa in Danish registers has not been validated, potentially affecting the accuracy of the study’s findings.

DISCLOSURES:

The study was supported by grants from the Novo Nordic Foundation and The Danish Foundation for Research in Mental Disorders. The authors declared no conflicts of interest.


This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
 

A version of this article appeared on Medscape.com.

An intervention combining an individualized walking program and education and significantly reduced low back pain recurrence in adults, compared with controls, based on data from approximately 700 individuals.

Exercise, including walking, is recommended to prevent recurrence of low back pain, but data on the effectiveness and cost-effectiveness of walking as an intervention are lacking, wrote Natasha C. Pocovi, PhD, of Macquarie University, Sydney, Australia, and colleagues.

In a study known as WalkBack, published in the Lancet, the researchers randomized 351 adults aged 18 years and older with a history of more than two prior episodes of low back pain to an intervention and 350 to no intervention.

The intervention consisted of six sessions of education and progressive walking with a physiotherapist over 6 months; both intervention and control groups were followed for a minimum of 12 months and a maximum of 36 months. The mean age of the participants was 54 years, and 81% were female. The primary outcome was the number of days to recurrence of low back pain severe enough to limit activity, based on monthly self-reports.

The intervention was significantly more effective at preventing activity-limiting low back pain recurrence, compared with no intervention (hazard ratio, 0.72; P = .0002), with a median of 208 days and 112 days to recurrence in the intervention and control groups, respectively.

The risk of any low back pain recurrence also was significantly reduced in the intervention group, compared with the controls (HR, 0.80; P = .0066); as was the risk of care-seeking recurrence of low back pain (HR, 0.57; P < .0001).

Overall, the experience of at least one adverse event over 12 months was similar between the intervention and control groups (52% and 54%, respectively), but significantly more adverse events related to lower extremities occurred in the intervention group, compared with the control group (100 vs 54). The intervention also was more likely to be cost effective, compared with a no-treatment control, the researchers wrote.

The findings were limited by several factors including the relatively homogeneous population and that neither the therapists nor participants were masked to group allocation. In addition, the study was conducted during the COVID-19 pandemic, so a telehealth model of video consultations was used instead of in-person meetings, but this protocol change allowed for inclusion of participants from diverse locations including rural and remote areas, the researchers said.

More research is needed to assess the implementation of a walking and exercise intervention as part of a discharge plan after an episode of low back pain and to examine the effectiveness of an intervention involving fewer sessions and a range of healthcare providers, they added. However, the results support the value of the intervention, which has a strong potential for successful implementation because of accessibility and low cost.
 

Preventive Interventions Need More Real-World Research

“Preventive interventions for back pain are an important yet neglected consideration,” Diarmuid Denneny, a doctoral candidate at Brunel University London, and Jackie Walumbe, PhD, of the University of Oxford (England), wrote in an accompanying editorial.

Although recurrence of low back pain is common, guidance on prevention and management is lacking, they said. Strengths of the current study include attention to patient and public preferences in the study design; however, the majority of the participants were of relatively high socioeconomic status and 89% reported post-secondary education.

“Given that pain is known to have a higher impact on marginalized and minoritized groups and those experiencing socioeconomic deprivation, we recommend caution in extrapolating these findings to different contexts,” the editorialists wrote.

They also cautioned that the complex nature of the intervention, which included not only walking but education and physiotherapist appointments, might make it difficult to isolate walking as the key factor in the patients’ improvement. The editorialists also emphasized the need for studies of similar interventions conducted by alternative providers including exercise professionals and digital platforms.

However, the WalkBack trial represents progress toward greater support for individuals with recurrent back pain and may be a foundation for other research involving how other forms of physical activity compare in improving back pain, with attention to the role of publish health in delivering physical activity interventions, they said.

The study was supported by the National Health and Medical Research Council, Australia. Dr. Pocovi disclosed scholarships funded by the National Health and Medical Research Council Low Back Pain Centre of Research Excellence (ANZBACK) and Macquarie University. Mr. Denneny disclosed support from an Economic and Social Research Council fellowship, and disclosed consulting fees from Live Well with Pain and Leva clinic; a grant from the Chartered Society of Physiotherapy. Dr. Walumbe disclosed travel support from the Chartered Society of Physiotherapy Charitable Trust.

An intervention combining an individualized walking program and education and significantly reduced low back pain recurrence in adults, compared with controls, based on data from approximately 700 individuals.

Exercise, including walking, is recommended to prevent recurrence of low back pain, but data on the effectiveness and cost-effectiveness of walking as an intervention are lacking, wrote Natasha C. Pocovi, PhD, of Macquarie University, Sydney, Australia, and colleagues.

In a study known as WalkBack, published in the Lancet, the researchers randomized 351 adults aged 18 years and older with a history of more than two prior episodes of low back pain to an intervention and 350 to no intervention.

The intervention consisted of six sessions of education and progressive walking with a physiotherapist over 6 months; both intervention and control groups were followed for a minimum of 12 months and a maximum of 36 months. The mean age of the participants was 54 years, and 81% were female. The primary outcome was the number of days to recurrence of low back pain severe enough to limit activity, based on monthly self-reports.

The intervention was significantly more effective at preventing activity-limiting low back pain recurrence, compared with no intervention (hazard ratio, 0.72; P = .0002), with a median of 208 days and 112 days to recurrence in the intervention and control groups, respectively.

The risk of any low back pain recurrence also was significantly reduced in the intervention group, compared with the controls (HR, 0.80; P = .0066); as was the risk of care-seeking recurrence of low back pain (HR, 0.57; P < .0001).

Overall, the experience of at least one adverse event over 12 months was similar between the intervention and control groups (52% and 54%, respectively), but significantly more adverse events related to lower extremities occurred in the intervention group, compared with the control group (100 vs 54). The intervention also was more likely to be cost effective, compared with a no-treatment control, the researchers wrote.

The findings were limited by several factors including the relatively homogeneous population and that neither the therapists nor participants were masked to group allocation. In addition, the study was conducted during the COVID-19 pandemic, so a telehealth model of video consultations was used instead of in-person meetings, but this protocol change allowed for inclusion of participants from diverse locations including rural and remote areas, the researchers said.

More research is needed to assess the implementation of a walking and exercise intervention as part of a discharge plan after an episode of low back pain and to examine the effectiveness of an intervention involving fewer sessions and a range of healthcare providers, they added. However, the results support the value of the intervention, which has a strong potential for successful implementation because of accessibility and low cost.
 

Preventive Interventions Need More Real-World Research

“Preventive interventions for back pain are an important yet neglected consideration,” Diarmuid Denneny, a doctoral candidate at Brunel University London, and Jackie Walumbe, PhD, of the University of Oxford (England), wrote in an accompanying editorial.

Although recurrence of low back pain is common, guidance on prevention and management is lacking, they said. Strengths of the current study include attention to patient and public preferences in the study design; however, the majority of the participants were of relatively high socioeconomic status and 89% reported post-secondary education.

“Given that pain is known to have a higher impact on marginalized and minoritized groups and those experiencing socioeconomic deprivation, we recommend caution in extrapolating these findings to different contexts,” the editorialists wrote.

They also cautioned that the complex nature of the intervention, which included not only walking but education and physiotherapist appointments, might make it difficult to isolate walking as the key factor in the patients’ improvement. The editorialists also emphasized the need for studies of similar interventions conducted by alternative providers including exercise professionals and digital platforms.

However, the WalkBack trial represents progress toward greater support for individuals with recurrent back pain and may be a foundation for other research involving how other forms of physical activity compare in improving back pain, with attention to the role of publish health in delivering physical activity interventions, they said.

The study was supported by the National Health and Medical Research Council, Australia. Dr. Pocovi disclosed scholarships funded by the National Health and Medical Research Council Low Back Pain Centre of Research Excellence (ANZBACK) and Macquarie University. Mr. Denneny disclosed support from an Economic and Social Research Council fellowship, and disclosed consulting fees from Live Well with Pain and Leva clinic; a grant from the Chartered Society of Physiotherapy. Dr. Walumbe disclosed travel support from the Chartered Society of Physiotherapy Charitable Trust.

An intervention combining an individualized walking program and education and significantly reduced low back pain recurrence in adults, compared with controls, based on data from approximately 700 individuals.

Exercise, including walking, is recommended to prevent recurrence of low back pain, but data on the effectiveness and cost-effectiveness of walking as an intervention are lacking, wrote Natasha C. Pocovi, PhD, of Macquarie University, Sydney, Australia, and colleagues.

In a study known as WalkBack, published in the Lancet, the researchers randomized 351 adults aged 18 years and older with a history of more than two prior episodes of low back pain to an intervention and 350 to no intervention.

The intervention consisted of six sessions of education and progressive walking with a physiotherapist over 6 months; both intervention and control groups were followed for a minimum of 12 months and a maximum of 36 months. The mean age of the participants was 54 years, and 81% were female. The primary outcome was the number of days to recurrence of low back pain severe enough to limit activity, based on monthly self-reports.

The intervention was significantly more effective at preventing activity-limiting low back pain recurrence, compared with no intervention (hazard ratio, 0.72; P = .0002), with a median of 208 days and 112 days to recurrence in the intervention and control groups, respectively.

The risk of any low back pain recurrence also was significantly reduced in the intervention group, compared with the controls (HR, 0.80; P = .0066); as was the risk of care-seeking recurrence of low back pain (HR, 0.57; P < .0001).

Overall, the experience of at least one adverse event over 12 months was similar between the intervention and control groups (52% and 54%, respectively), but significantly more adverse events related to lower extremities occurred in the intervention group, compared with the control group (100 vs 54). The intervention also was more likely to be cost effective, compared with a no-treatment control, the researchers wrote.

The findings were limited by several factors including the relatively homogeneous population and that neither the therapists nor participants were masked to group allocation. In addition, the study was conducted during the COVID-19 pandemic, so a telehealth model of video consultations was used instead of in-person meetings, but this protocol change allowed for inclusion of participants from diverse locations including rural and remote areas, the researchers said.

More research is needed to assess the implementation of a walking and exercise intervention as part of a discharge plan after an episode of low back pain and to examine the effectiveness of an intervention involving fewer sessions and a range of healthcare providers, they added. However, the results support the value of the intervention, which has a strong potential for successful implementation because of accessibility and low cost.
 

Preventive Interventions Need More Real-World Research

“Preventive interventions for back pain are an important yet neglected consideration,” Diarmuid Denneny, a doctoral candidate at Brunel University London, and Jackie Walumbe, PhD, of the University of Oxford (England), wrote in an accompanying editorial.

Although recurrence of low back pain is common, guidance on prevention and management is lacking, they said. Strengths of the current study include attention to patient and public preferences in the study design; however, the majority of the participants were of relatively high socioeconomic status and 89% reported post-secondary education.

“Given that pain is known to have a higher impact on marginalized and minoritized groups and those experiencing socioeconomic deprivation, we recommend caution in extrapolating these findings to different contexts,” the editorialists wrote.

They also cautioned that the complex nature of the intervention, which included not only walking but education and physiotherapist appointments, might make it difficult to isolate walking as the key factor in the patients’ improvement. The editorialists also emphasized the need for studies of similar interventions conducted by alternative providers including exercise professionals and digital platforms.

However, the WalkBack trial represents progress toward greater support for individuals with recurrent back pain and may be a foundation for other research involving how other forms of physical activity compare in improving back pain, with attention to the role of publish health in delivering physical activity interventions, they said.

The study was supported by the National Health and Medical Research Council, Australia. Dr. Pocovi disclosed scholarships funded by the National Health and Medical Research Council Low Back Pain Centre of Research Excellence (ANZBACK) and Macquarie University. Mr. Denneny disclosed support from an Economic and Social Research Council fellowship, and disclosed consulting fees from Live Well with Pain and Leva clinic; a grant from the Chartered Society of Physiotherapy. Dr. Walumbe disclosed travel support from the Chartered Society of Physiotherapy Charitable Trust.

The US Food and Drug Administration (FDA) has approved Skyrizi (risankizumab-rzaa; AbbVie) for the treatment of moderately to severely active ulcerative colitis in adults. This approval makes it the first specific anti-interleukin 23 monoclonal antibody indicated for both ulcerative colitis and moderate to severe Crohn’s disease. 

The drug is also approved in the United States for the treatment of adults with active psoriatic arthritis and moderate to severe plaque psoriasis.

The safety and efficacy of Skyrizi for ulcerative colitis is supported by data from two phase 3 clinical trials: a 12-week induction study (INSPIRE) and a 52-week maintenance study (COMMAND). 

The data showed that clinical remission, the primary endpoint in both the induction and maintenance studies, was achieved along with endoscopic improvement, which was a key secondary endpoint.

“When treating patients with ulcerative colitis, it’s important to prioritize both early and sustained clinical remission as well as endoscopic improvement,” Edward V. Loftus Jr., MD, AGAF, gastroenterologist at Mayo Clinic in Rochester, Minnesota, said in a news release. “This approval for Skyrizi is an important step toward addressing these treatment goals.”

For the treatment of ulcerative colitis, dosing includes a 12-week induction period with three 1200-mg doses delivered every 4 weeks followed by maintenance therapy of either 180 mg or 360 mg delivered every 8 weeks.

After the induction period, Skyrizi treatment can be maintained at home using an on-body injector (OBI). “The OBI is a hands-free device designed with patients in mind that adheres to the body and takes about 5 minutes to deliver the medication following preparation steps,” according to the news release. 

Full prescribing information is available online. 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved Skyrizi (risankizumab-rzaa; AbbVie) for the treatment of moderately to severely active ulcerative colitis in adults. This approval makes it the first specific anti-interleukin 23 monoclonal antibody indicated for both ulcerative colitis and moderate to severe Crohn’s disease. 

The drug is also approved in the United States for the treatment of adults with active psoriatic arthritis and moderate to severe plaque psoriasis.

The safety and efficacy of Skyrizi for ulcerative colitis is supported by data from two phase 3 clinical trials: a 12-week induction study (INSPIRE) and a 52-week maintenance study (COMMAND). 

The data showed that clinical remission, the primary endpoint in both the induction and maintenance studies, was achieved along with endoscopic improvement, which was a key secondary endpoint.

“When treating patients with ulcerative colitis, it’s important to prioritize both early and sustained clinical remission as well as endoscopic improvement,” Edward V. Loftus Jr., MD, AGAF, gastroenterologist at Mayo Clinic in Rochester, Minnesota, said in a news release. “This approval for Skyrizi is an important step toward addressing these treatment goals.”

For the treatment of ulcerative colitis, dosing includes a 12-week induction period with three 1200-mg doses delivered every 4 weeks followed by maintenance therapy of either 180 mg or 360 mg delivered every 8 weeks.

After the induction period, Skyrizi treatment can be maintained at home using an on-body injector (OBI). “The OBI is a hands-free device designed with patients in mind that adheres to the body and takes about 5 minutes to deliver the medication following preparation steps,” according to the news release. 

Full prescribing information is available online. 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved Skyrizi (risankizumab-rzaa; AbbVie) for the treatment of moderately to severely active ulcerative colitis in adults. This approval makes it the first specific anti-interleukin 23 monoclonal antibody indicated for both ulcerative colitis and moderate to severe Crohn’s disease. 

The drug is also approved in the United States for the treatment of adults with active psoriatic arthritis and moderate to severe plaque psoriasis.

The safety and efficacy of Skyrizi for ulcerative colitis is supported by data from two phase 3 clinical trials: a 12-week induction study (INSPIRE) and a 52-week maintenance study (COMMAND). 

The data showed that clinical remission, the primary endpoint in both the induction and maintenance studies, was achieved along with endoscopic improvement, which was a key secondary endpoint.

“When treating patients with ulcerative colitis, it’s important to prioritize both early and sustained clinical remission as well as endoscopic improvement,” Edward V. Loftus Jr., MD, AGAF, gastroenterologist at Mayo Clinic in Rochester, Minnesota, said in a news release. “This approval for Skyrizi is an important step toward addressing these treatment goals.”

For the treatment of ulcerative colitis, dosing includes a 12-week induction period with three 1200-mg doses delivered every 4 weeks followed by maintenance therapy of either 180 mg or 360 mg delivered every 8 weeks.

After the induction period, Skyrizi treatment can be maintained at home using an on-body injector (OBI). “The OBI is a hands-free device designed with patients in mind that adheres to the body and takes about 5 minutes to deliver the medication following preparation steps,” according to the news release. 

Full prescribing information is available online. 

A version of this article appeared on Medscape.com.

Glofitamab, a fixed-duration CD20xCD3 bispecific antibody, combined with a chemotherapy regimen of gemcitabine and oxaliplatin (GemOx), shows significant survival benefits in the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), compared with the standard-of-care regimen.

“Glofitamab is the first CD20xCD3 bispecific antibody to demonstrate an overall survival benefit in DLBCL in a randomized phase 3 trial,” said first author Jeremy Abramson, MD, of the Massachusetts General Hospital Cancer Center, Boston, Massachusetts, in a press briefing at the annual meeting of the European Hematology Association (EHA) in Madrid.

“These results support the use of glofitamab GemOx as new, off-the-shelf treatment for relapsed/refractory DLBCL in patients who are transplant ineligible in the second-line or later setting,” he said.

The findings are from the phase 3 STARGLO study involving 274 patients with R/R DLBCL who had previously been treated either with at least two prior lines of therapy, or—if only one prior line of therapy—were determined to be ineligible for autologous stem cell transplant (ASCT).

At a median follow-up of 21 months, those treated with glofitamab combined with GemOx had a significantly higher median overall survival of 25.5 months, compared with those treated with the standard of care of rituximab and GemOx (12.9 months; hazard ratio [HR], 0.62; P = .006).

“The results show a 38% lower risk of death with the glofitamab plus GemOx, compared with [the rituximab regimen],” Dr. Abramson said.

Secondary endpoints showed consistent benefits with the glofitamab regimen, with significant improvements in progression-free survival and complete remission.
 

Unmet Need for Accessible Therapies

Relapsed/refractory DLBCL, the most common form of non-Hodgkin lymphoma (NHL) in the United States, is an aggressive blood cancer. The standard second-line therapy is high-dose chemotherapy followed by ASCT. However, factors including older age or coexisting medical conditions can compromise response, and those who relapse or are refractory to subsequent therapies have poor outcomes.

“Relapsed DLBCL in the second-line setting or later continues to represent an area of medical need,” Dr. Abramson said.

While several CD20xCD3 bispecific antibody drugs are under development to address the need, glofitamab was the first off-the-shelf, fixed-duration bispecific antibody to receive accelerated approval from the US Food and Drug Administration (FDA) for the treatment of R/R DLBCL, specifically as monotherapy after two or more lines of systemic therapy.

That approval was based on results from a pivotal phase 1/2 study, which showed high rates of deep and durable complete remission with the monotherapy.

To further evaluate glofitamab in combination with GemOx, the authors conducted the multicenter, open-label STARGLO trial, which extended enrollment to patients with just one prior therapy if they were determined to be stem cell transplant ineligible. Patients were also required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

Patients were randomized 2:1 either to treatment with glofitamab combined with GemOx, involving 8 cycles, in addition to 4 cycles of glofitamab monotherapy (n = 183), or to the rituximab plus GemOx regimen in 8 cycles (n = 91).

Overall, 153 (55.8%) of patients had primary refractory disease and 166 (60.6%) were refractory to their last therapy. The median age was 68, and 37% had two or more lines of therapy, including some who had received chimeric antigen receptor T-cell (CAR T) therapy (8.8% in the glofitamab group and 7.1% in the rituximab group).

In addition to the significant overall survival benefit, the glofitamab regimen also showed significantly improved progression-free survival at a median follow-up of 16.1 months, as observed by IRC-assessed PFS, with a median progression-free survival rate of 13.8 months vs 3.6 months (HR, 0.40; P < .0001).

The complete remission rate was doubled with glofitamab-GemOx, with a rate of 58.5% vs 25.3%, respectively; P < .0001.

Similar results were observed in subgroups, including relapsed vs refractory patients and those treated as a second or third line of care.

The median number of cycles received was higher among those receiving glofitamab (11 vs four cycles).

Adverse event (AE) rates were higher with glofitamab vs rituximab, including grade 3-4 AEs (69.4 vs 36.4%), grade 5 AEs (8.3 vs 4.5%; primarily driven by an imbalance of COVID-19 AEs), and serious AEs (54.4 vs 17.0%; primarily cytokine release syndrome [CRS]).

CRS was the most frequently reported AE in the glofitamab group (grade 1: 31.4%; grade 2: 10.5%; and grade 3: 2.3%), and events consistent with immune effector cell–associated neurotoxicity syndrome were reported in four patients (2.3%), all of which were concurrent with CRS.

Other AEs were consistent with the known risks associated with the therapy regimens.

“We found that with glofitamab GemOx, the toxicities were manageable, and the most common toxicity of CRS was predominantly low-grade and occurred with step-up dosing in cycle one and was completely reversible,” Dr. Abramson said.

He noted that the higher rate of grade 5 AEs with glofitamab GemOx “was far outweighed by the survival benefit for disease control.”

Overall, “these findings represent the best outcomes observed in a phase 3 trial for relapsed/refractory diffuse large B-cell lymphoma patients who are considered transplant ineligible,” Dr. Abramson said in an interview.
 

Improved Accessibility Vs CAR-T Therapy

Among key developments in the treatment of R/R DLBCL has been the advent and approval of potentially highly effective CAR T-cell therapy, with the anti-CD19 CAR T cell isiocabtagene maraleucel also FDA approved in the non–transplant eligible DLBCL second-line setting.

Asked in the press briefing about the role of glofitamab GemOx in relation to CAR T cell’s significant benefits, Dr. Abramson underscored the important limitations in CAR T-cell accessibility.

“What I would say is a rising tide lifts all boats,” he responded. “It’s great to have multiple effective immunotherapy strategies.”

However, “CAR T cells of course are not available to most people in the US or worldwide,” he explained.

“They are more difficult to access, they require lymphodepleting chemotherapy, and so ultimately, the majority of patients who could potentially benefit from a CAR T cell probably don’t have access to them in the first place.”

He noted that “the appeal of a regimen like [glofitamab] is that it is an off-the-shelf, targeted immunotherapy combined with a well-tolerated chemotherapy backbone and should be more broadly accessible outside of just tertiary care centers in major cities.”
 

Long-Term Durability?

Looking ahead, Dr. Abramson noted that a key issue of focus is how long the encouraging results actually last.

“The major ongoing question with this trial is the long-term durability of remissions,” he said.

“Thus far, with a median of 21 months of follow-up for overall survival, the results are encouraging but longer follow-up is needed,” he added.

“Further trials are needed in a broader large B-cell lymphoma population as this trial was limited to DLBCL not otherwise specified, so did not include patients with transformed lymphoma, primary mediastinal B-cell lymphoma, high grade B-cell lymphoma, etc.” 
 

Is Chemo Necessary?

Commenting on the findings, Jonathan W. Friedberg, MD, director of the Wilmot Cancer Institute, University of Rochester School of Medicine, in Rochester, New York, underscored that, “given the overall survival benefit, these findings are clearly clinically significant.”

Noting that “these results add to evidence of high activity of bispecific antibodies in this disease,” Dr. Friedberg speculated on the role of chemotherapy with the therapy.

“Indeed, an important question in this study is whether the addition of chemotherapy to glofitamab is necessary, as high response rates with durable responses in patients who achieve complete remission have been demonstrated with single agent bispecific antibody therapy,” he said. 

With the durability of CAR T therapy shown in long-term follow-up of trials to exceed 5 years, Dr. Friedberg added that “it is not known how bispecific antibody therapy, with or without chemotherapy, compares to CAR T-cell therapy and how to sequence CAR T and bispecific antibody therapy.”

Dr. Friedberg agreed that longer-term results are needed get a clearer, fuller picture of the therapy’s effects.

“I have no doubt that the overall survival benefit will endure, but in DLBCL our goal should be cure, and whether glofitamab cures as many patients as CAR T-cell therapy is not currently known and will require further follow-up of this and other trials.”

The study was sponsored by F. Hoffman-La Roche Ltd. Dr. Abramson reported ties with AbbVie, ADC Therapeutics, AstraZeneca, BeiGene, BMS, Cellectar, Caribou Biosciences, Celgene, Genentech, Gilead, Incyte, Interius, Janssen, Lilly, Novartis, F. Hoffmann-La Roche Ltd, Seagen, and Takeda. Dr. Friedberg had no disclosures.

Glofitamab, a fixed-duration CD20xCD3 bispecific antibody, combined with a chemotherapy regimen of gemcitabine and oxaliplatin (GemOx), shows significant survival benefits in the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), compared with the standard-of-care regimen.

“Glofitamab is the first CD20xCD3 bispecific antibody to demonstrate an overall survival benefit in DLBCL in a randomized phase 3 trial,” said first author Jeremy Abramson, MD, of the Massachusetts General Hospital Cancer Center, Boston, Massachusetts, in a press briefing at the annual meeting of the European Hematology Association (EHA) in Madrid.

“These results support the use of glofitamab GemOx as new, off-the-shelf treatment for relapsed/refractory DLBCL in patients who are transplant ineligible in the second-line or later setting,” he said.

The findings are from the phase 3 STARGLO study involving 274 patients with R/R DLBCL who had previously been treated either with at least two prior lines of therapy, or—if only one prior line of therapy—were determined to be ineligible for autologous stem cell transplant (ASCT).

At a median follow-up of 21 months, those treated with glofitamab combined with GemOx had a significantly higher median overall survival of 25.5 months, compared with those treated with the standard of care of rituximab and GemOx (12.9 months; hazard ratio [HR], 0.62; P = .006).

“The results show a 38% lower risk of death with the glofitamab plus GemOx, compared with [the rituximab regimen],” Dr. Abramson said.

Secondary endpoints showed consistent benefits with the glofitamab regimen, with significant improvements in progression-free survival and complete remission.
 

Unmet Need for Accessible Therapies

Relapsed/refractory DLBCL, the most common form of non-Hodgkin lymphoma (NHL) in the United States, is an aggressive blood cancer. The standard second-line therapy is high-dose chemotherapy followed by ASCT. However, factors including older age or coexisting medical conditions can compromise response, and those who relapse or are refractory to subsequent therapies have poor outcomes.

“Relapsed DLBCL in the second-line setting or later continues to represent an area of medical need,” Dr. Abramson said.

While several CD20xCD3 bispecific antibody drugs are under development to address the need, glofitamab was the first off-the-shelf, fixed-duration bispecific antibody to receive accelerated approval from the US Food and Drug Administration (FDA) for the treatment of R/R DLBCL, specifically as monotherapy after two or more lines of systemic therapy.

That approval was based on results from a pivotal phase 1/2 study, which showed high rates of deep and durable complete remission with the monotherapy.

To further evaluate glofitamab in combination with GemOx, the authors conducted the multicenter, open-label STARGLO trial, which extended enrollment to patients with just one prior therapy if they were determined to be stem cell transplant ineligible. Patients were also required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

Patients were randomized 2:1 either to treatment with glofitamab combined with GemOx, involving 8 cycles, in addition to 4 cycles of glofitamab monotherapy (n = 183), or to the rituximab plus GemOx regimen in 8 cycles (n = 91).

Overall, 153 (55.8%) of patients had primary refractory disease and 166 (60.6%) were refractory to their last therapy. The median age was 68, and 37% had two or more lines of therapy, including some who had received chimeric antigen receptor T-cell (CAR T) therapy (8.8% in the glofitamab group and 7.1% in the rituximab group).

In addition to the significant overall survival benefit, the glofitamab regimen also showed significantly improved progression-free survival at a median follow-up of 16.1 months, as observed by IRC-assessed PFS, with a median progression-free survival rate of 13.8 months vs 3.6 months (HR, 0.40; P < .0001).

The complete remission rate was doubled with glofitamab-GemOx, with a rate of 58.5% vs 25.3%, respectively; P < .0001.

Similar results were observed in subgroups, including relapsed vs refractory patients and those treated as a second or third line of care.

The median number of cycles received was higher among those receiving glofitamab (11 vs four cycles).

Adverse event (AE) rates were higher with glofitamab vs rituximab, including grade 3-4 AEs (69.4 vs 36.4%), grade 5 AEs (8.3 vs 4.5%; primarily driven by an imbalance of COVID-19 AEs), and serious AEs (54.4 vs 17.0%; primarily cytokine release syndrome [CRS]).

CRS was the most frequently reported AE in the glofitamab group (grade 1: 31.4%; grade 2: 10.5%; and grade 3: 2.3%), and events consistent with immune effector cell–associated neurotoxicity syndrome were reported in four patients (2.3%), all of which were concurrent with CRS.

Other AEs were consistent with the known risks associated with the therapy regimens.

“We found that with glofitamab GemOx, the toxicities were manageable, and the most common toxicity of CRS was predominantly low-grade and occurred with step-up dosing in cycle one and was completely reversible,” Dr. Abramson said.

He noted that the higher rate of grade 5 AEs with glofitamab GemOx “was far outweighed by the survival benefit for disease control.”

Overall, “these findings represent the best outcomes observed in a phase 3 trial for relapsed/refractory diffuse large B-cell lymphoma patients who are considered transplant ineligible,” Dr. Abramson said in an interview.
 

Improved Accessibility Vs CAR-T Therapy

Among key developments in the treatment of R/R DLBCL has been the advent and approval of potentially highly effective CAR T-cell therapy, with the anti-CD19 CAR T cell isiocabtagene maraleucel also FDA approved in the non–transplant eligible DLBCL second-line setting.

Asked in the press briefing about the role of glofitamab GemOx in relation to CAR T cell’s significant benefits, Dr. Abramson underscored the important limitations in CAR T-cell accessibility.

“What I would say is a rising tide lifts all boats,” he responded. “It’s great to have multiple effective immunotherapy strategies.”

However, “CAR T cells of course are not available to most people in the US or worldwide,” he explained.

“They are more difficult to access, they require lymphodepleting chemotherapy, and so ultimately, the majority of patients who could potentially benefit from a CAR T cell probably don’t have access to them in the first place.”

He noted that “the appeal of a regimen like [glofitamab] is that it is an off-the-shelf, targeted immunotherapy combined with a well-tolerated chemotherapy backbone and should be more broadly accessible outside of just tertiary care centers in major cities.”
 

Long-Term Durability?

Looking ahead, Dr. Abramson noted that a key issue of focus is how long the encouraging results actually last.

“The major ongoing question with this trial is the long-term durability of remissions,” he said.

“Thus far, with a median of 21 months of follow-up for overall survival, the results are encouraging but longer follow-up is needed,” he added.

“Further trials are needed in a broader large B-cell lymphoma population as this trial was limited to DLBCL not otherwise specified, so did not include patients with transformed lymphoma, primary mediastinal B-cell lymphoma, high grade B-cell lymphoma, etc.” 
 

Is Chemo Necessary?

Commenting on the findings, Jonathan W. Friedberg, MD, director of the Wilmot Cancer Institute, University of Rochester School of Medicine, in Rochester, New York, underscored that, “given the overall survival benefit, these findings are clearly clinically significant.”

Noting that “these results add to evidence of high activity of bispecific antibodies in this disease,” Dr. Friedberg speculated on the role of chemotherapy with the therapy.

“Indeed, an important question in this study is whether the addition of chemotherapy to glofitamab is necessary, as high response rates with durable responses in patients who achieve complete remission have been demonstrated with single agent bispecific antibody therapy,” he said. 

With the durability of CAR T therapy shown in long-term follow-up of trials to exceed 5 years, Dr. Friedberg added that “it is not known how bispecific antibody therapy, with or without chemotherapy, compares to CAR T-cell therapy and how to sequence CAR T and bispecific antibody therapy.”

Dr. Friedberg agreed that longer-term results are needed get a clearer, fuller picture of the therapy’s effects.

“I have no doubt that the overall survival benefit will endure, but in DLBCL our goal should be cure, and whether glofitamab cures as many patients as CAR T-cell therapy is not currently known and will require further follow-up of this and other trials.”

The study was sponsored by F. Hoffman-La Roche Ltd. Dr. Abramson reported ties with AbbVie, ADC Therapeutics, AstraZeneca, BeiGene, BMS, Cellectar, Caribou Biosciences, Celgene, Genentech, Gilead, Incyte, Interius, Janssen, Lilly, Novartis, F. Hoffmann-La Roche Ltd, Seagen, and Takeda. Dr. Friedberg had no disclosures.

Glofitamab, a fixed-duration CD20xCD3 bispecific antibody, combined with a chemotherapy regimen of gemcitabine and oxaliplatin (GemOx), shows significant survival benefits in the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), compared with the standard-of-care regimen.

“Glofitamab is the first CD20xCD3 bispecific antibody to demonstrate an overall survival benefit in DLBCL in a randomized phase 3 trial,” said first author Jeremy Abramson, MD, of the Massachusetts General Hospital Cancer Center, Boston, Massachusetts, in a press briefing at the annual meeting of the European Hematology Association (EHA) in Madrid.

“These results support the use of glofitamab GemOx as new, off-the-shelf treatment for relapsed/refractory DLBCL in patients who are transplant ineligible in the second-line or later setting,” he said.

The findings are from the phase 3 STARGLO study involving 274 patients with R/R DLBCL who had previously been treated either with at least two prior lines of therapy, or—if only one prior line of therapy—were determined to be ineligible for autologous stem cell transplant (ASCT).

At a median follow-up of 21 months, those treated with glofitamab combined with GemOx had a significantly higher median overall survival of 25.5 months, compared with those treated with the standard of care of rituximab and GemOx (12.9 months; hazard ratio [HR], 0.62; P = .006).

“The results show a 38% lower risk of death with the glofitamab plus GemOx, compared with [the rituximab regimen],” Dr. Abramson said.

Secondary endpoints showed consistent benefits with the glofitamab regimen, with significant improvements in progression-free survival and complete remission.
 

Unmet Need for Accessible Therapies

Relapsed/refractory DLBCL, the most common form of non-Hodgkin lymphoma (NHL) in the United States, is an aggressive blood cancer. The standard second-line therapy is high-dose chemotherapy followed by ASCT. However, factors including older age or coexisting medical conditions can compromise response, and those who relapse or are refractory to subsequent therapies have poor outcomes.

“Relapsed DLBCL in the second-line setting or later continues to represent an area of medical need,” Dr. Abramson said.

While several CD20xCD3 bispecific antibody drugs are under development to address the need, glofitamab was the first off-the-shelf, fixed-duration bispecific antibody to receive accelerated approval from the US Food and Drug Administration (FDA) for the treatment of R/R DLBCL, specifically as monotherapy after two or more lines of systemic therapy.

That approval was based on results from a pivotal phase 1/2 study, which showed high rates of deep and durable complete remission with the monotherapy.

To further evaluate glofitamab in combination with GemOx, the authors conducted the multicenter, open-label STARGLO trial, which extended enrollment to patients with just one prior therapy if they were determined to be stem cell transplant ineligible. Patients were also required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

Patients were randomized 2:1 either to treatment with glofitamab combined with GemOx, involving 8 cycles, in addition to 4 cycles of glofitamab monotherapy (n = 183), or to the rituximab plus GemOx regimen in 8 cycles (n = 91).

Overall, 153 (55.8%) of patients had primary refractory disease and 166 (60.6%) were refractory to their last therapy. The median age was 68, and 37% had two or more lines of therapy, including some who had received chimeric antigen receptor T-cell (CAR T) therapy (8.8% in the glofitamab group and 7.1% in the rituximab group).

In addition to the significant overall survival benefit, the glofitamab regimen also showed significantly improved progression-free survival at a median follow-up of 16.1 months, as observed by IRC-assessed PFS, with a median progression-free survival rate of 13.8 months vs 3.6 months (HR, 0.40; P < .0001).

The complete remission rate was doubled with glofitamab-GemOx, with a rate of 58.5% vs 25.3%, respectively; P < .0001.

Similar results were observed in subgroups, including relapsed vs refractory patients and those treated as a second or third line of care.

The median number of cycles received was higher among those receiving glofitamab (11 vs four cycles).

Adverse event (AE) rates were higher with glofitamab vs rituximab, including grade 3-4 AEs (69.4 vs 36.4%), grade 5 AEs (8.3 vs 4.5%; primarily driven by an imbalance of COVID-19 AEs), and serious AEs (54.4 vs 17.0%; primarily cytokine release syndrome [CRS]).

CRS was the most frequently reported AE in the glofitamab group (grade 1: 31.4%; grade 2: 10.5%; and grade 3: 2.3%), and events consistent with immune effector cell–associated neurotoxicity syndrome were reported in four patients (2.3%), all of which were concurrent with CRS.

Other AEs were consistent with the known risks associated with the therapy regimens.

“We found that with glofitamab GemOx, the toxicities were manageable, and the most common toxicity of CRS was predominantly low-grade and occurred with step-up dosing in cycle one and was completely reversible,” Dr. Abramson said.

He noted that the higher rate of grade 5 AEs with glofitamab GemOx “was far outweighed by the survival benefit for disease control.”

Overall, “these findings represent the best outcomes observed in a phase 3 trial for relapsed/refractory diffuse large B-cell lymphoma patients who are considered transplant ineligible,” Dr. Abramson said in an interview.
 

Improved Accessibility Vs CAR-T Therapy

Among key developments in the treatment of R/R DLBCL has been the advent and approval of potentially highly effective CAR T-cell therapy, with the anti-CD19 CAR T cell isiocabtagene maraleucel also FDA approved in the non–transplant eligible DLBCL second-line setting.

Asked in the press briefing about the role of glofitamab GemOx in relation to CAR T cell’s significant benefits, Dr. Abramson underscored the important limitations in CAR T-cell accessibility.

“What I would say is a rising tide lifts all boats,” he responded. “It’s great to have multiple effective immunotherapy strategies.”

However, “CAR T cells of course are not available to most people in the US or worldwide,” he explained.

“They are more difficult to access, they require lymphodepleting chemotherapy, and so ultimately, the majority of patients who could potentially benefit from a CAR T cell probably don’t have access to them in the first place.”

He noted that “the appeal of a regimen like [glofitamab] is that it is an off-the-shelf, targeted immunotherapy combined with a well-tolerated chemotherapy backbone and should be more broadly accessible outside of just tertiary care centers in major cities.”
 

Long-Term Durability?

Looking ahead, Dr. Abramson noted that a key issue of focus is how long the encouraging results actually last.

“The major ongoing question with this trial is the long-term durability of remissions,” he said.

“Thus far, with a median of 21 months of follow-up for overall survival, the results are encouraging but longer follow-up is needed,” he added.

“Further trials are needed in a broader large B-cell lymphoma population as this trial was limited to DLBCL not otherwise specified, so did not include patients with transformed lymphoma, primary mediastinal B-cell lymphoma, high grade B-cell lymphoma, etc.” 
 

Is Chemo Necessary?

Commenting on the findings, Jonathan W. Friedberg, MD, director of the Wilmot Cancer Institute, University of Rochester School of Medicine, in Rochester, New York, underscored that, “given the overall survival benefit, these findings are clearly clinically significant.”

Noting that “these results add to evidence of high activity of bispecific antibodies in this disease,” Dr. Friedberg speculated on the role of chemotherapy with the therapy.

“Indeed, an important question in this study is whether the addition of chemotherapy to glofitamab is necessary, as high response rates with durable responses in patients who achieve complete remission have been demonstrated with single agent bispecific antibody therapy,” he said. 

With the durability of CAR T therapy shown in long-term follow-up of trials to exceed 5 years, Dr. Friedberg added that “it is not known how bispecific antibody therapy, with or without chemotherapy, compares to CAR T-cell therapy and how to sequence CAR T and bispecific antibody therapy.”

Dr. Friedberg agreed that longer-term results are needed get a clearer, fuller picture of the therapy’s effects.

“I have no doubt that the overall survival benefit will endure, but in DLBCL our goal should be cure, and whether glofitamab cures as many patients as CAR T-cell therapy is not currently known and will require further follow-up of this and other trials.”

The study was sponsored by F. Hoffman-La Roche Ltd. Dr. Abramson reported ties with AbbVie, ADC Therapeutics, AstraZeneca, BeiGene, BMS, Cellectar, Caribou Biosciences, Celgene, Genentech, Gilead, Incyte, Interius, Janssen, Lilly, Novartis, F. Hoffmann-La Roche Ltd, Seagen, and Takeda. Dr. Friedberg had no disclosures.

Editor’s note: This is Dr. Eastern’s last “Managing Your Practice” column for Dermatology News. After his first column was published in 1986, Dr. Eastern continued writing his column monthly until the mid-1990s, resuming in 2005. In total, he has written over 300 columns on topics relevant to medical practice, ranging from hiring employees, selling and merging practices, complying with OSHA, and avoiding embezzlement, to electronic health records, burnout, medical assistants, negative online reviews, artificial intelligence in the office, and more. In the future, he will continue to provide commentary on practice issues with an occasional guest editorial.

Medicare reimbursement cuts, increasing overhead and staff salaries, and inflation have made running a profitable private practice increasingly challenging, particularly for rural and smaller offices. Medical credit cards are an increasingly popular choice to fill this gap.

Unlike a conventional credit card, a medical credit card is used only to pay for medical services.

alexialex/Getty Images

Traditionally, these cards were used to help cover procedures insurance didn’t cover — such as cosmetic procedures — but over the years, they have been expanded to cover other healthcare charges, mostly for patients who are paying out of pocket due to inadequate insurance or other reasons.

Advantages for physicians include immediate payment from the credit card company and reduced billing and collection costs. Patients are also less likely to delay or defer treatment if they can charge the payment and pay it back in installments.

The first step in offering medical credit cards is signing up with one or more third-party card companies. CareCredit is the most common provider in the medical credit card market. Other vendors include Wells Fargo, AccessOne, Alphaeon Credit, and iCare Financial. (As always, I have no financial interest in any product or service mentioned in this column.) A member of your staff signs patients up, and the credit card company checks their credit. If approved, the card company pays you your fee and assumes responsibility for collecting from the patient.

The interest charge on medical credit cards is often deferred for a period of time, typically between 6 and 24 months. If patients pay off the debt within this time, they can avoid paying interest. But, like other credit cards, if they make late payments or have an unpaid balance once the promotional period ends, they may end up with interest and fees totaling 25%-30% or more. It is important to make it very clear to your patients that payments are interest-free only if they are all made on time and within the promotional period.

According to a Consumer Financial Protection Bureau report released earlier this year, deferred interest medical credit cards or loans were used to pay nearly $23 billion in healthcare expenses from 2018 to 2020. Individuals unable to complete payment during the promotional period paid $1 billion in deferred interest payments during that period.

Despite the growing popularity of medical credit cards among physicians, it is worth noting that some consumer groups view them as predatory financial products, marketed toward people in tough financial situations. A coalition of 60 health advocacy groups has urged the Biden Administration to ban deferred interest medical credit cards. So there is that much more reason to choose candidates for medical credit cards carefully, and to make them fully aware of what obligations they are assuming.

Patients who do not think they can pay off the balance within the interest-free time frame should probably be advised to pursue an alternative payment method, such as using a conventional credit card, taking out a personal or home-equity loan, or borrowing from a retirement savings account. Some physicians are willing to negotiate a reduced fee for patients who agree to pay cash at the time of service.

Those who do choose to apply for a medical credit card should be informed of their options, which can vary considerably depending on the product and the third-party vendor. Some medical credit products can be used only for elective procedures, but some can be used more broadly for various medical expenses. Check to make sure that each patient’s financing option can be used for his or her desired medical service.

Some payment products can only be used at specific practices or groups, while others can be used at a variety of medical offices and hospitals. If a patient arrives with a medical credit card already in hand, confirm that it is one that your office accepts.

Interest rates generally vary with each card and vendor. Make patients aware of when interest rates start accruing and if the plan offers a fixed or variable APR, or if it charges compounding interest. Confirm if there is a deferred interest option, and if so, for how long.

Different medical credit products also have varying fees and payment schedules. See that each patient reads the terms of the agreement to understand when interest may start to accrue or change, as well as when certain fees may apply. Understanding when the payments are due will help them avoid additional fees, including late fees. Some medical payment plans may also have administrative or processing fees. If so, patients should be made aware of them.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, New Jersey. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

Editor’s note: This is Dr. Eastern’s last “Managing Your Practice” column for Dermatology News. After his first column was published in 1986, Dr. Eastern continued writing his column monthly until the mid-1990s, resuming in 2005. In total, he has written over 300 columns on topics relevant to medical practice, ranging from hiring employees, selling and merging practices, complying with OSHA, and avoiding embezzlement, to electronic health records, burnout, medical assistants, negative online reviews, artificial intelligence in the office, and more. In the future, he will continue to provide commentary on practice issues with an occasional guest editorial.

Medicare reimbursement cuts, increasing overhead and staff salaries, and inflation have made running a profitable private practice increasingly challenging, particularly for rural and smaller offices. Medical credit cards are an increasingly popular choice to fill this gap.

Unlike a conventional credit card, a medical credit card is used only to pay for medical services.

alexialex/Getty Images

Traditionally, these cards were used to help cover procedures insurance didn’t cover — such as cosmetic procedures — but over the years, they have been expanded to cover other healthcare charges, mostly for patients who are paying out of pocket due to inadequate insurance or other reasons.

Advantages for physicians include immediate payment from the credit card company and reduced billing and collection costs. Patients are also less likely to delay or defer treatment if they can charge the payment and pay it back in installments.

The first step in offering medical credit cards is signing up with one or more third-party card companies. CareCredit is the most common provider in the medical credit card market. Other vendors include Wells Fargo, AccessOne, Alphaeon Credit, and iCare Financial. (As always, I have no financial interest in any product or service mentioned in this column.) A member of your staff signs patients up, and the credit card company checks their credit. If approved, the card company pays you your fee and assumes responsibility for collecting from the patient.

The interest charge on medical credit cards is often deferred for a period of time, typically between 6 and 24 months. If patients pay off the debt within this time, they can avoid paying interest. But, like other credit cards, if they make late payments or have an unpaid balance once the promotional period ends, they may end up with interest and fees totaling 25%-30% or more. It is important to make it very clear to your patients that payments are interest-free only if they are all made on time and within the promotional period.

According to a Consumer Financial Protection Bureau report released earlier this year, deferred interest medical credit cards or loans were used to pay nearly $23 billion in healthcare expenses from 2018 to 2020. Individuals unable to complete payment during the promotional period paid $1 billion in deferred interest payments during that period.

Despite the growing popularity of medical credit cards among physicians, it is worth noting that some consumer groups view them as predatory financial products, marketed toward people in tough financial situations. A coalition of 60 health advocacy groups has urged the Biden Administration to ban deferred interest medical credit cards. So there is that much more reason to choose candidates for medical credit cards carefully, and to make them fully aware of what obligations they are assuming.

Patients who do not think they can pay off the balance within the interest-free time frame should probably be advised to pursue an alternative payment method, such as using a conventional credit card, taking out a personal or home-equity loan, or borrowing from a retirement savings account. Some physicians are willing to negotiate a reduced fee for patients who agree to pay cash at the time of service.

Those who do choose to apply for a medical credit card should be informed of their options, which can vary considerably depending on the product and the third-party vendor. Some medical credit products can be used only for elective procedures, but some can be used more broadly for various medical expenses. Check to make sure that each patient’s financing option can be used for his or her desired medical service.

Some payment products can only be used at specific practices or groups, while others can be used at a variety of medical offices and hospitals. If a patient arrives with a medical credit card already in hand, confirm that it is one that your office accepts.

Interest rates generally vary with each card and vendor. Make patients aware of when interest rates start accruing and if the plan offers a fixed or variable APR, or if it charges compounding interest. Confirm if there is a deferred interest option, and if so, for how long.

Different medical credit products also have varying fees and payment schedules. See that each patient reads the terms of the agreement to understand when interest may start to accrue or change, as well as when certain fees may apply. Understanding when the payments are due will help them avoid additional fees, including late fees. Some medical payment plans may also have administrative or processing fees. If so, patients should be made aware of them.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, New Jersey. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

Editor’s note: This is Dr. Eastern’s last “Managing Your Practice” column for Dermatology News. After his first column was published in 1986, Dr. Eastern continued writing his column monthly until the mid-1990s, resuming in 2005. In total, he has written over 300 columns on topics relevant to medical practice, ranging from hiring employees, selling and merging practices, complying with OSHA, and avoiding embezzlement, to electronic health records, burnout, medical assistants, negative online reviews, artificial intelligence in the office, and more. In the future, he will continue to provide commentary on practice issues with an occasional guest editorial.

Medicare reimbursement cuts, increasing overhead and staff salaries, and inflation have made running a profitable private practice increasingly challenging, particularly for rural and smaller offices. Medical credit cards are an increasingly popular choice to fill this gap.

Unlike a conventional credit card, a medical credit card is used only to pay for medical services.

alexialex/Getty Images

Traditionally, these cards were used to help cover procedures insurance didn’t cover — such as cosmetic procedures — but over the years, they have been expanded to cover other healthcare charges, mostly for patients who are paying out of pocket due to inadequate insurance or other reasons.

Advantages for physicians include immediate payment from the credit card company and reduced billing and collection costs. Patients are also less likely to delay or defer treatment if they can charge the payment and pay it back in installments.

The first step in offering medical credit cards is signing up with one or more third-party card companies. CareCredit is the most common provider in the medical credit card market. Other vendors include Wells Fargo, AccessOne, Alphaeon Credit, and iCare Financial. (As always, I have no financial interest in any product or service mentioned in this column.) A member of your staff signs patients up, and the credit card company checks their credit. If approved, the card company pays you your fee and assumes responsibility for collecting from the patient.

The interest charge on medical credit cards is often deferred for a period of time, typically between 6 and 24 months. If patients pay off the debt within this time, they can avoid paying interest. But, like other credit cards, if they make late payments or have an unpaid balance once the promotional period ends, they may end up with interest and fees totaling 25%-30% or more. It is important to make it very clear to your patients that payments are interest-free only if they are all made on time and within the promotional period.

According to a Consumer Financial Protection Bureau report released earlier this year, deferred interest medical credit cards or loans were used to pay nearly $23 billion in healthcare expenses from 2018 to 2020. Individuals unable to complete payment during the promotional period paid $1 billion in deferred interest payments during that period.

Despite the growing popularity of medical credit cards among physicians, it is worth noting that some consumer groups view them as predatory financial products, marketed toward people in tough financial situations. A coalition of 60 health advocacy groups has urged the Biden Administration to ban deferred interest medical credit cards. So there is that much more reason to choose candidates for medical credit cards carefully, and to make them fully aware of what obligations they are assuming.

Patients who do not think they can pay off the balance within the interest-free time frame should probably be advised to pursue an alternative payment method, such as using a conventional credit card, taking out a personal or home-equity loan, or borrowing from a retirement savings account. Some physicians are willing to negotiate a reduced fee for patients who agree to pay cash at the time of service.

Those who do choose to apply for a medical credit card should be informed of their options, which can vary considerably depending on the product and the third-party vendor. Some medical credit products can be used only for elective procedures, but some can be used more broadly for various medical expenses. Check to make sure that each patient’s financing option can be used for his or her desired medical service.

Some payment products can only be used at specific practices or groups, while others can be used at a variety of medical offices and hospitals. If a patient arrives with a medical credit card already in hand, confirm that it is one that your office accepts.

Interest rates generally vary with each card and vendor. Make patients aware of when interest rates start accruing and if the plan offers a fixed or variable APR, or if it charges compounding interest. Confirm if there is a deferred interest option, and if so, for how long.

Different medical credit products also have varying fees and payment schedules. See that each patient reads the terms of the agreement to understand when interest may start to accrue or change, as well as when certain fees may apply. Understanding when the payments are due will help them avoid additional fees, including late fees. Some medical payment plans may also have administrative or processing fees. If so, patients should be made aware of them.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, New Jersey. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

CHICAGO — Prominent Chinese oncologist Tony Shu-Kam Mok, MD, who presented as first author of a phase 3 non–small cell lung cancer study at ASCO 2024, made a dramatic swerve in his career path at age 36.

After 20 years in Canada — 7 spent practicing community oncology near Toronto — Dr. Mok was visiting family in his native Hong Kong back in 1996 when a job offer there enabled him to revive his early dream of doing academic research. Dr. Mok and his family moved back home just before the former British colony was returned to China in 1997.

courtesy of Dr. Tony Mok

That leap of faith helped Dr. Mok play a role in the global paradigm shift on treating lung cancer. He chairs the department of clinical oncology at the Chinese University of Hong Kong. A leader in ushering in targeted therapies and personalized medicine in China and globally, he has helped advance the goal of transforming lung cancer from a death sentence to a chronic disease.

Among Dr. Mok’s other accomplishments, he has published eight books and more than 200 journal articles. Since 2006, he has been writing a twice-weekly column in the Hong Kong Economic Times. At the annual meeting of the American Society of Clinical Oncology (ASCO), Dr. Mok sat down with this news organization to discuss his latest findings, his career path, and China’s ever-growing presence in multinational clinical trials, pharmaceuticals, and cancer research in general.
 

Question: At ASCO 2024 in Chicago, you presented as first author of the KRYSTAL-12 study. Can you give a short “elevator speech” summarizing those findings?

Dr. Mok: KRYSTAL-12 is a randomized phase 3 study comparing adagrasib with docetaxel in patients with previously treated advanced/metastatic non–small cell lung cancer harboring a KRAS G12C-mutation. And the findings are positive, with a median progression free survival of 5.5 months vs 3.8 months, with a significant hazard ratio [of 0.58]. And then there are also differences in their response rates of 32% versus 9%, and that gives you an [odds] ratio of 4.86. So yes, it’s significant.

Question: Now that you’ve given this presentation and perhaps taken some good, meaningful questions about it, are there any further points you’d like to make — anything you’d like to add?

Dr. Mok: You have to understand that whatever I said has been scrutinized by the pharmaceutical company, but now I can say whatever I like. I think the key point is that we actually have made the first so-called achievement in the KRAS G12C space. But this is only the beginning.

I want to note that the median progression-free survival is different, but not the best. The median 5.5 months result is good, but not good enough. So, we still have to work hard to answer the question: How can we best deliver care to patients with KRAS G12C?
 

Question: Speaking more generally about the challenges of targeting KRAS, what issues arise in terms of biomarker testing for KRAS mutations in the clinic? Dr. Mok: In colorectal cancer, there has been testing for KRAS [mutations] for a long, long time. So, most of the laboratories, as long as they are well equipped, will be able to test for KRAS. Usually, the cheaper way is to buy PCR [polymerase chain reaction]. However, these days it’s getting trendier to use NGS [next-generation sequencing]. So, one way or another, specificity is very high. I don’t think we have too much of a problem. The only difference between colorectal cancer and lung cancer is that the tissue sample may not be as good for lung cancer with a small biopsy, but otherwise testing is not an issue.

Question: What clinical trials should oncologist be watching to come into this space?Dr. Mok: There are a lot. Right now, there is the so-called first-line study that’s coming up. So, I can cite you some examples for the KRYSTAL-7 trial, which is the combination of pembrolizumab together with adagrasib in the PD-L1 Tumor Proportion Score ≥ 50%.

That’s one example. And then there is the CodeBreaK 202 trial, which is actually the combination of chemotherapy with sotorasib versus chemotherapy and I-O [immune-oncology]. That is also an ongoing study.
 

Question: I also want to ask you some background questions about yourself. Back in the day, you lived in Canada and were a community oncologist. Then you made a very big change in your life and moved back home to Hong Kong in 1996, on the eve of its return to China the following year.

Dr. Mok: Well, I was born and raised in Hong Kong, but I left for Canada for education when I was 16 and kind of stayed there and got medical school oncology training and then started my practice. At that time, I never imagined myself going back. But 1996 was a big year. Incidentally, I went back to Hong Kong then to visit my friends and was offered a job at the Chinese University of Hong Kong. Then 1997 was coming. I found it very exciting that we could work with China. So that’s why I decided to return. And this was probably one of my best decisions I ever made in my life.

Question: And you went from being a community oncologist to academic research?

Dr. Mok: Here’s a personal thing that I can share with you: When I finished my oncology training at Princess Margaret Hospital in Toronto, I thought of going into research and becoming an academic. However, my son was born. Household costs went up, and I didn’t want to be a low-income, poor PhD student, so I decided that I may as well go into private practice. Returning to Hong Kong [in 1996] gave me a second chance. I went from being a community oncologist for seven years in Canada to a totally new environment in Hong Kong, where I started my academic work at age 36. It has been a good journey.

Question: Why do you say that was the best decision you ever made?Dr. Mok: At that time, it took me about 2 weeks to make this important decision. Basically: I had to give up my big house and my big car in Canada and move back to a small apartment in Hong Kong. That was a tough decision to make. However, it was a matter of certainty versus uncertainty.

In Canada, I actually had a very stable situation. I had a big practice in the Scarborough area [of Toronto], with a lot of Chinese patients, so I had a better, more comfortable life. It was predictable. But then I asked myself what I would be like in 10 years if I stayed in Canada versus Hong Kong. My answer is that I had no idea what would happen to me 10 years later in Hong Kong. In certain parts of life, you have to decide between certainty and uncertainty. And this time, uncertainty brought me great adventure. I definitely would not have done the things I’ve done if I’d stayed in Canada.



Question: At this ASCO, you’ve spoken primarily about your latest research on non–small cell lung cancer with KRAS G12C mutation.Dr. Mok: Actually, my research has been mostly on targeted therapy. My first break was on the EGFR [epidermal growth factor receptor] mutation. I was one of the first to help define personalized medicine according to the EGFR mutation in the IPASS study [2009]. That’s how I started my academic career.



Question: I read some quotes from your writing some years back about “living with imperfection,” and where you wrote about the whole continuum of cancer research. Years ago, you noted that lung cancer was moving from being a death sentence to becoming a chronic condition.

Dr. Mok: The objective is this: A lot of cancer patients, especially lung cancer patients, had a very short survival, but now we are able to identify a subgroup of patients with a driver oncogene.

And with that, we can use a tyrosine kinase inhibitor — which although it has toxicity, it’s manageable toxicity — such that you can take one pill a day and continue to live a normal life. So that would be not so different from diabetes or hypertension: You live with the disease. So that’s what we like to see: the conversion of a fatal disease into a chronic disease.
 

Question: So many countries now, including the United States and many others, are facing the challenges of cancer care in rural versus urban areas. Is this a topic you’d be willing to address? Dr. Mok: Well, in Hong Kong we don’t have rural areas! But in China, this is a major problem. There most of the cancer care is focused on the so-called three major cities [Shanghai, Beijing, Guangzhou]. And after that, there are second-tier cities that also have reasonably good care. But when you filter down to the third and fourth layer, the oncology care actually deteriorates. So that’s why we end up with a lot of people from the more rural areas moving and going to the city looking for care and consultation. So yes, the disparity is significant.

But China is a growing country. It takes time to change. Right now, we can see at ASCO this year, there are a lot of investigators from China sharing their new findings, which is a major development, compared to 10 years ago. Therefore, I think that when you have this type of proliferative development, eventually the good care, the high-quality care will filter down to more rural areas. So, at this moment, I think there is still a lot of work to do.
 

Question: You’ve talked about how oncologists from China are coming up in the field, and this year they have an even greater presence at ASCO, as well as oncologists from elsewhere in Asia, including South Korea, Japan, and Vietnam. You’ve been coming to ASCO for many years. Can you talk about the factors behind China’s increasing presence? Dr. Mok: I think it’s a combination of factors. First of all, I had the honor of working with lung cancer researchers from China from way back, 25 years ago. At that time, we all had nothing. Then with the development of multitargeted therapies, they managed to build up a very good infrastructure for clinical trials. And then, based on that good infrastructure, they were able to do international collaborative studies and provide a supply of patient resources and high-quality data. So, they’ve learned the trick, done a good job, but they cannot have so-called independence until there is a development of pharmaceuticals in China.

And then over the past 10 years, there’s been a proliferation — actually an explosion I would even say — of high-quality pharmaceutical companies in China. First, they’ve got the resources to build the companies. Second, they’ve got the talent resources returning from the United States. So, putting all that together, these were able to go from start-ups to full-fledged functional companies in a very short time.

And with that, they actually sponsored a lot of trials within China. And you can see that putting all the components together: you’ve got high-quality researchers, you’ve got the infrastructure, and now you’ve got your drugs and the money to do the trials. As a result, you’ve got a lot of good data coming from China.
 

Question: There’s also a population with these mutations.Dr. Mok: That for one, but most have multitargeted therapies, but they also have immunotherapies that have nothing to do with the high incidence. But I think in a sense, in the beginning, they were doing `me-too’ compounds, but now I think they are starting to do ‘me-better’ compounds.

Question: Is there anything you want to say about some of the other presentations that have your name on them at ASCO this year?Dr. Mok: I think the most important one I was engaged in is the CROWN study. The CROWN study is actually a phase 3 study that compares lorlatinib versus crizotinib in patients with advanced, ALK-positive non–small cell lung cancer.

This is a 5-year follow-up, and we were actually able to report an outrageously encouraging 5-year progression-free rate at 60%, meaning that the patient is walking in the door 5 years later when they are on the drug, and 60% of them actually do not have progression, not death, just not progression, just staying on the same pill—which is quite outrageously good for lung cancer.

CHICAGO — Prominent Chinese oncologist Tony Shu-Kam Mok, MD, who presented as first author of a phase 3 non–small cell lung cancer study at ASCO 2024, made a dramatic swerve in his career path at age 36.

After 20 years in Canada — 7 spent practicing community oncology near Toronto — Dr. Mok was visiting family in his native Hong Kong back in 1996 when a job offer there enabled him to revive his early dream of doing academic research. Dr. Mok and his family moved back home just before the former British colony was returned to China in 1997.

courtesy of Dr. Tony Mok

That leap of faith helped Dr. Mok play a role in the global paradigm shift on treating lung cancer. He chairs the department of clinical oncology at the Chinese University of Hong Kong. A leader in ushering in targeted therapies and personalized medicine in China and globally, he has helped advance the goal of transforming lung cancer from a death sentence to a chronic disease.

Among Dr. Mok’s other accomplishments, he has published eight books and more than 200 journal articles. Since 2006, he has been writing a twice-weekly column in the Hong Kong Economic Times. At the annual meeting of the American Society of Clinical Oncology (ASCO), Dr. Mok sat down with this news organization to discuss his latest findings, his career path, and China’s ever-growing presence in multinational clinical trials, pharmaceuticals, and cancer research in general.
 

Question: At ASCO 2024 in Chicago, you presented as first author of the KRYSTAL-12 study. Can you give a short “elevator speech” summarizing those findings?

Dr. Mok: KRYSTAL-12 is a randomized phase 3 study comparing adagrasib with docetaxel in patients with previously treated advanced/metastatic non–small cell lung cancer harboring a KRAS G12C-mutation. And the findings are positive, with a median progression free survival of 5.5 months vs 3.8 months, with a significant hazard ratio [of 0.58]. And then there are also differences in their response rates of 32% versus 9%, and that gives you an [odds] ratio of 4.86. So yes, it’s significant.

Question: Now that you’ve given this presentation and perhaps taken some good, meaningful questions about it, are there any further points you’d like to make — anything you’d like to add?

Dr. Mok: You have to understand that whatever I said has been scrutinized by the pharmaceutical company, but now I can say whatever I like. I think the key point is that we actually have made the first so-called achievement in the KRAS G12C space. But this is only the beginning.

I want to note that the median progression-free survival is different, but not the best. The median 5.5 months result is good, but not good enough. So, we still have to work hard to answer the question: How can we best deliver care to patients with KRAS G12C?
 

Question: Speaking more generally about the challenges of targeting KRAS, what issues arise in terms of biomarker testing for KRAS mutations in the clinic? Dr. Mok: In colorectal cancer, there has been testing for KRAS [mutations] for a long, long time. So, most of the laboratories, as long as they are well equipped, will be able to test for KRAS. Usually, the cheaper way is to buy PCR [polymerase chain reaction]. However, these days it’s getting trendier to use NGS [next-generation sequencing]. So, one way or another, specificity is very high. I don’t think we have too much of a problem. The only difference between colorectal cancer and lung cancer is that the tissue sample may not be as good for lung cancer with a small biopsy, but otherwise testing is not an issue.

Question: What clinical trials should oncologist be watching to come into this space?Dr. Mok: There are a lot. Right now, there is the so-called first-line study that’s coming up. So, I can cite you some examples for the KRYSTAL-7 trial, which is the combination of pembrolizumab together with adagrasib in the PD-L1 Tumor Proportion Score ≥ 50%.

That’s one example. And then there is the CodeBreaK 202 trial, which is actually the combination of chemotherapy with sotorasib versus chemotherapy and I-O [immune-oncology]. That is also an ongoing study.
 

Question: I also want to ask you some background questions about yourself. Back in the day, you lived in Canada and were a community oncologist. Then you made a very big change in your life and moved back home to Hong Kong in 1996, on the eve of its return to China the following year.

Dr. Mok: Well, I was born and raised in Hong Kong, but I left for Canada for education when I was 16 and kind of stayed there and got medical school oncology training and then started my practice. At that time, I never imagined myself going back. But 1996 was a big year. Incidentally, I went back to Hong Kong then to visit my friends and was offered a job at the Chinese University of Hong Kong. Then 1997 was coming. I found it very exciting that we could work with China. So that’s why I decided to return. And this was probably one of my best decisions I ever made in my life.

Question: And you went from being a community oncologist to academic research?

Dr. Mok: Here’s a personal thing that I can share with you: When I finished my oncology training at Princess Margaret Hospital in Toronto, I thought of going into research and becoming an academic. However, my son was born. Household costs went up, and I didn’t want to be a low-income, poor PhD student, so I decided that I may as well go into private practice. Returning to Hong Kong [in 1996] gave me a second chance. I went from being a community oncologist for seven years in Canada to a totally new environment in Hong Kong, where I started my academic work at age 36. It has been a good journey.

Question: Why do you say that was the best decision you ever made?Dr. Mok: At that time, it took me about 2 weeks to make this important decision. Basically: I had to give up my big house and my big car in Canada and move back to a small apartment in Hong Kong. That was a tough decision to make. However, it was a matter of certainty versus uncertainty.

In Canada, I actually had a very stable situation. I had a big practice in the Scarborough area [of Toronto], with a lot of Chinese patients, so I had a better, more comfortable life. It was predictable. But then I asked myself what I would be like in 10 years if I stayed in Canada versus Hong Kong. My answer is that I had no idea what would happen to me 10 years later in Hong Kong. In certain parts of life, you have to decide between certainty and uncertainty. And this time, uncertainty brought me great adventure. I definitely would not have done the things I’ve done if I’d stayed in Canada.



Question: At this ASCO, you’ve spoken primarily about your latest research on non–small cell lung cancer with KRAS G12C mutation.Dr. Mok: Actually, my research has been mostly on targeted therapy. My first break was on the EGFR [epidermal growth factor receptor] mutation. I was one of the first to help define personalized medicine according to the EGFR mutation in the IPASS study [2009]. That’s how I started my academic career.



Question: I read some quotes from your writing some years back about “living with imperfection,” and where you wrote about the whole continuum of cancer research. Years ago, you noted that lung cancer was moving from being a death sentence to becoming a chronic condition.

Dr. Mok: The objective is this: A lot of cancer patients, especially lung cancer patients, had a very short survival, but now we are able to identify a subgroup of patients with a driver oncogene.

And with that, we can use a tyrosine kinase inhibitor — which although it has toxicity, it’s manageable toxicity — such that you can take one pill a day and continue to live a normal life. So that would be not so different from diabetes or hypertension: You live with the disease. So that’s what we like to see: the conversion of a fatal disease into a chronic disease.
 

Question: So many countries now, including the United States and many others, are facing the challenges of cancer care in rural versus urban areas. Is this a topic you’d be willing to address? Dr. Mok: Well, in Hong Kong we don’t have rural areas! But in China, this is a major problem. There most of the cancer care is focused on the so-called three major cities [Shanghai, Beijing, Guangzhou]. And after that, there are second-tier cities that also have reasonably good care. But when you filter down to the third and fourth layer, the oncology care actually deteriorates. So that’s why we end up with a lot of people from the more rural areas moving and going to the city looking for care and consultation. So yes, the disparity is significant.

But China is a growing country. It takes time to change. Right now, we can see at ASCO this year, there are a lot of investigators from China sharing their new findings, which is a major development, compared to 10 years ago. Therefore, I think that when you have this type of proliferative development, eventually the good care, the high-quality care will filter down to more rural areas. So, at this moment, I think there is still a lot of work to do.
 

Question: You’ve talked about how oncologists from China are coming up in the field, and this year they have an even greater presence at ASCO, as well as oncologists from elsewhere in Asia, including South Korea, Japan, and Vietnam. You’ve been coming to ASCO for many years. Can you talk about the factors behind China’s increasing presence? Dr. Mok: I think it’s a combination of factors. First of all, I had the honor of working with lung cancer researchers from China from way back, 25 years ago. At that time, we all had nothing. Then with the development of multitargeted therapies, they managed to build up a very good infrastructure for clinical trials. And then, based on that good infrastructure, they were able to do international collaborative studies and provide a supply of patient resources and high-quality data. So, they’ve learned the trick, done a good job, but they cannot have so-called independence until there is a development of pharmaceuticals in China.

And then over the past 10 years, there’s been a proliferation — actually an explosion I would even say — of high-quality pharmaceutical companies in China. First, they’ve got the resources to build the companies. Second, they’ve got the talent resources returning from the United States. So, putting all that together, these were able to go from start-ups to full-fledged functional companies in a very short time.

And with that, they actually sponsored a lot of trials within China. And you can see that putting all the components together: you’ve got high-quality researchers, you’ve got the infrastructure, and now you’ve got your drugs and the money to do the trials. As a result, you’ve got a lot of good data coming from China.
 

Question: There’s also a population with these mutations.Dr. Mok: That for one, but most have multitargeted therapies, but they also have immunotherapies that have nothing to do with the high incidence. But I think in a sense, in the beginning, they were doing `me-too’ compounds, but now I think they are starting to do ‘me-better’ compounds.

Question: Is there anything you want to say about some of the other presentations that have your name on them at ASCO this year?Dr. Mok: I think the most important one I was engaged in is the CROWN study. The CROWN study is actually a phase 3 study that compares lorlatinib versus crizotinib in patients with advanced, ALK-positive non–small cell lung cancer.

This is a 5-year follow-up, and we were actually able to report an outrageously encouraging 5-year progression-free rate at 60%, meaning that the patient is walking in the door 5 years later when they are on the drug, and 60% of them actually do not have progression, not death, just not progression, just staying on the same pill—which is quite outrageously good for lung cancer.

CHICAGO — Prominent Chinese oncologist Tony Shu-Kam Mok, MD, who presented as first author of a phase 3 non–small cell lung cancer study at ASCO 2024, made a dramatic swerve in his career path at age 36.

After 20 years in Canada — 7 spent practicing community oncology near Toronto — Dr. Mok was visiting family in his native Hong Kong back in 1996 when a job offer there enabled him to revive his early dream of doing academic research. Dr. Mok and his family moved back home just before the former British colony was returned to China in 1997.

courtesy of Dr. Tony Mok

That leap of faith helped Dr. Mok play a role in the global paradigm shift on treating lung cancer. He chairs the department of clinical oncology at the Chinese University of Hong Kong. A leader in ushering in targeted therapies and personalized medicine in China and globally, he has helped advance the goal of transforming lung cancer from a death sentence to a chronic disease.

Among Dr. Mok’s other accomplishments, he has published eight books and more than 200 journal articles. Since 2006, he has been writing a twice-weekly column in the Hong Kong Economic Times. At the annual meeting of the American Society of Clinical Oncology (ASCO), Dr. Mok sat down with this news organization to discuss his latest findings, his career path, and China’s ever-growing presence in multinational clinical trials, pharmaceuticals, and cancer research in general.
 

Question: At ASCO 2024 in Chicago, you presented as first author of the KRYSTAL-12 study. Can you give a short “elevator speech” summarizing those findings?

Dr. Mok: KRYSTAL-12 is a randomized phase 3 study comparing adagrasib with docetaxel in patients with previously treated advanced/metastatic non–small cell lung cancer harboring a KRAS G12C-mutation. And the findings are positive, with a median progression free survival of 5.5 months vs 3.8 months, with a significant hazard ratio [of 0.58]. And then there are also differences in their response rates of 32% versus 9%, and that gives you an [odds] ratio of 4.86. So yes, it’s significant.

Question: Now that you’ve given this presentation and perhaps taken some good, meaningful questions about it, are there any further points you’d like to make — anything you’d like to add?

Dr. Mok: You have to understand that whatever I said has been scrutinized by the pharmaceutical company, but now I can say whatever I like. I think the key point is that we actually have made the first so-called achievement in the KRAS G12C space. But this is only the beginning.

I want to note that the median progression-free survival is different, but not the best. The median 5.5 months result is good, but not good enough. So, we still have to work hard to answer the question: How can we best deliver care to patients with KRAS G12C?
 

Question: Speaking more generally about the challenges of targeting KRAS, what issues arise in terms of biomarker testing for KRAS mutations in the clinic? Dr. Mok: In colorectal cancer, there has been testing for KRAS [mutations] for a long, long time. So, most of the laboratories, as long as they are well equipped, will be able to test for KRAS. Usually, the cheaper way is to buy PCR [polymerase chain reaction]. However, these days it’s getting trendier to use NGS [next-generation sequencing]. So, one way or another, specificity is very high. I don’t think we have too much of a problem. The only difference between colorectal cancer and lung cancer is that the tissue sample may not be as good for lung cancer with a small biopsy, but otherwise testing is not an issue.

Question: What clinical trials should oncologist be watching to come into this space?Dr. Mok: There are a lot. Right now, there is the so-called first-line study that’s coming up. So, I can cite you some examples for the KRYSTAL-7 trial, which is the combination of pembrolizumab together with adagrasib in the PD-L1 Tumor Proportion Score ≥ 50%.

That’s one example. And then there is the CodeBreaK 202 trial, which is actually the combination of chemotherapy with sotorasib versus chemotherapy and I-O [immune-oncology]. That is also an ongoing study.
 

Question: I also want to ask you some background questions about yourself. Back in the day, you lived in Canada and were a community oncologist. Then you made a very big change in your life and moved back home to Hong Kong in 1996, on the eve of its return to China the following year.

Dr. Mok: Well, I was born and raised in Hong Kong, but I left for Canada for education when I was 16 and kind of stayed there and got medical school oncology training and then started my practice. At that time, I never imagined myself going back. But 1996 was a big year. Incidentally, I went back to Hong Kong then to visit my friends and was offered a job at the Chinese University of Hong Kong. Then 1997 was coming. I found it very exciting that we could work with China. So that’s why I decided to return. And this was probably one of my best decisions I ever made in my life.

Question: And you went from being a community oncologist to academic research?

Dr. Mok: Here’s a personal thing that I can share with you: When I finished my oncology training at Princess Margaret Hospital in Toronto, I thought of going into research and becoming an academic. However, my son was born. Household costs went up, and I didn’t want to be a low-income, poor PhD student, so I decided that I may as well go into private practice. Returning to Hong Kong [in 1996] gave me a second chance. I went from being a community oncologist for seven years in Canada to a totally new environment in Hong Kong, where I started my academic work at age 36. It has been a good journey.

Question: Why do you say that was the best decision you ever made?Dr. Mok: At that time, it took me about 2 weeks to make this important decision. Basically: I had to give up my big house and my big car in Canada and move back to a small apartment in Hong Kong. That was a tough decision to make. However, it was a matter of certainty versus uncertainty.

In Canada, I actually had a very stable situation. I had a big practice in the Scarborough area [of Toronto], with a lot of Chinese patients, so I had a better, more comfortable life. It was predictable. But then I asked myself what I would be like in 10 years if I stayed in Canada versus Hong Kong. My answer is that I had no idea what would happen to me 10 years later in Hong Kong. In certain parts of life, you have to decide between certainty and uncertainty. And this time, uncertainty brought me great adventure. I definitely would not have done the things I’ve done if I’d stayed in Canada.



Question: At this ASCO, you’ve spoken primarily about your latest research on non–small cell lung cancer with KRAS G12C mutation.Dr. Mok: Actually, my research has been mostly on targeted therapy. My first break was on the EGFR [epidermal growth factor receptor] mutation. I was one of the first to help define personalized medicine according to the EGFR mutation in the IPASS study [2009]. That’s how I started my academic career.



Question: I read some quotes from your writing some years back about “living with imperfection,” and where you wrote about the whole continuum of cancer research. Years ago, you noted that lung cancer was moving from being a death sentence to becoming a chronic condition.

Dr. Mok: The objective is this: A lot of cancer patients, especially lung cancer patients, had a very short survival, but now we are able to identify a subgroup of patients with a driver oncogene.

And with that, we can use a tyrosine kinase inhibitor — which although it has toxicity, it’s manageable toxicity — such that you can take one pill a day and continue to live a normal life. So that would be not so different from diabetes or hypertension: You live with the disease. So that’s what we like to see: the conversion of a fatal disease into a chronic disease.
 

Question: So many countries now, including the United States and many others, are facing the challenges of cancer care in rural versus urban areas. Is this a topic you’d be willing to address? Dr. Mok: Well, in Hong Kong we don’t have rural areas! But in China, this is a major problem. There most of the cancer care is focused on the so-called three major cities [Shanghai, Beijing, Guangzhou]. And after that, there are second-tier cities that also have reasonably good care. But when you filter down to the third and fourth layer, the oncology care actually deteriorates. So that’s why we end up with a lot of people from the more rural areas moving and going to the city looking for care and consultation. So yes, the disparity is significant.

But China is a growing country. It takes time to change. Right now, we can see at ASCO this year, there are a lot of investigators from China sharing their new findings, which is a major development, compared to 10 years ago. Therefore, I think that when you have this type of proliferative development, eventually the good care, the high-quality care will filter down to more rural areas. So, at this moment, I think there is still a lot of work to do.
 

Question: You’ve talked about how oncologists from China are coming up in the field, and this year they have an even greater presence at ASCO, as well as oncologists from elsewhere in Asia, including South Korea, Japan, and Vietnam. You’ve been coming to ASCO for many years. Can you talk about the factors behind China’s increasing presence? Dr. Mok: I think it’s a combination of factors. First of all, I had the honor of working with lung cancer researchers from China from way back, 25 years ago. At that time, we all had nothing. Then with the development of multitargeted therapies, they managed to build up a very good infrastructure for clinical trials. And then, based on that good infrastructure, they were able to do international collaborative studies and provide a supply of patient resources and high-quality data. So, they’ve learned the trick, done a good job, but they cannot have so-called independence until there is a development of pharmaceuticals in China.

And then over the past 10 years, there’s been a proliferation — actually an explosion I would even say — of high-quality pharmaceutical companies in China. First, they’ve got the resources to build the companies. Second, they’ve got the talent resources returning from the United States. So, putting all that together, these were able to go from start-ups to full-fledged functional companies in a very short time.

And with that, they actually sponsored a lot of trials within China. And you can see that putting all the components together: you’ve got high-quality researchers, you’ve got the infrastructure, and now you’ve got your drugs and the money to do the trials. As a result, you’ve got a lot of good data coming from China.
 

Question: There’s also a population with these mutations.Dr. Mok: That for one, but most have multitargeted therapies, but they also have immunotherapies that have nothing to do with the high incidence. But I think in a sense, in the beginning, they were doing `me-too’ compounds, but now I think they are starting to do ‘me-better’ compounds.

Question: Is there anything you want to say about some of the other presentations that have your name on them at ASCO this year?Dr. Mok: I think the most important one I was engaged in is the CROWN study. The CROWN study is actually a phase 3 study that compares lorlatinib versus crizotinib in patients with advanced, ALK-positive non–small cell lung cancer.

This is a 5-year follow-up, and we were actually able to report an outrageously encouraging 5-year progression-free rate at 60%, meaning that the patient is walking in the door 5 years later when they are on the drug, and 60% of them actually do not have progression, not death, just not progression, just staying on the same pill—which is quite outrageously good for lung cancer.

Overall, persons with schizophrenia are more likely than the general population to be overweight and have cardiovascular risk factors before starting treatment with antipsychotics, and such treatment generally worsens these measures. Weight gain and associated morbidity and mortality are common side effects of antipsychotic medications. Olanzapine is associated with significant weight gain of 7% or more, higher than other second-generation antipsychotics. Olanzapine treatment is the major contributor to this patient's additional weight gain over the past 2 years. This added weight has translated to excess wear and tear on her joints, leading to evidence of osteoarthritis. Treatment with olanzapine is also independently associated with detrimental changes in cardiometabolic parameters.

Interventions to prevent or mitigate weight gain with antipsychotics are limited. In general, the American Psychiatric Association does not recommend switching antipsychotics for patients whose schizophrenia is well managed. However, there is increasing evidence that metformin may have a role in mitigating weight gain as well as beneficially modifying cardiometabolic factors in patients with schizophrenia being treated with olanzapine. A systematic review of emerging evidence with metformin in patients with schizophrenia suggests that metformin may also improve some cognitive symptoms of the illness, although further research is needed. The randomized, double-blind MELIA trial of metformin plus lifestyle intervention in antipsychotic-induced weight gain is ongoing. Starting metformin as a preventive measure at the same time as antipsychotic therapy may help to limit excess weight gain. 

Research continues on the potential benefit of adding weight loss medications, including glucagon-like peptide-1 (GLP-1) receptor agonists, to antipsychotics. Daily liraglutide is most widely studied, but a published case series with weekly semaglutide also demonstrated weight loss in this setting. Liraglutide also has shown beneficial cardiometabolic effects in patients using antipsychotic medications. More studies of these drugs and of GLP-1/glucose-dependent insulinotropic polypeptide agonists are needed to elucidate the optimal use of these therapies for patients with schizophrenia.

There are few other effective ways to mitigate weight gain with olanzapine. Patients should be counseled on nutrition and lifestyle modifications. Evidence supports improvement with structured lifestyle modifications across a range of patients with less severe mental health issues, and structured programs combined with motivational interviewing were associated with reductions in antipsychotic-induced weight gain in patients with severe mental illness. As with any patient with obesity, however, the success of lifestyle modifications is heavily dependent on the individual's ability and motivation to comply with recommended interventions. 

Nonpharmacologic interventions to address joint pain include heat or cold compresses, physical therapy, and strength and resistance training to improve the strength of muscles supporting the joints. If these measures are ineffective, nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen, naproxen, meloxicam, diclofenac, or celecoxib may be used with regular follow-up to assess cardiovascular and gastrointestinal health. Topical NSAIDs also may be useful. For more intractable joint pain, options include injecting a corticosteroid or sodium hyaluronate into the affected joints or joint replacement. 

Carolyn Newberry, MD, Assistant Professor of Medicine, Director of GI Nutrition, Innovative Center for Health and Nutrition in Gastroenterology (ICHANGE), Division of Gastroenterology, Weill Cornell Medical Center, New York, NY.

Disclosure: Carolyn Newberry, MD, has disclosed the following relevant financial relationships:

Serve(d) as a speaker or a member of a speakers bureau for: Baster International; InBody.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

Overall, persons with schizophrenia are more likely than the general population to be overweight and have cardiovascular risk factors before starting treatment with antipsychotics, and such treatment generally worsens these measures. Weight gain and associated morbidity and mortality are common side effects of antipsychotic medications. Olanzapine is associated with significant weight gain of 7% or more, higher than other second-generation antipsychotics. Olanzapine treatment is the major contributor to this patient's additional weight gain over the past 2 years. This added weight has translated to excess wear and tear on her joints, leading to evidence of osteoarthritis. Treatment with olanzapine is also independently associated with detrimental changes in cardiometabolic parameters.

Interventions to prevent or mitigate weight gain with antipsychotics are limited. In general, the American Psychiatric Association does not recommend switching antipsychotics for patients whose schizophrenia is well managed. However, there is increasing evidence that metformin may have a role in mitigating weight gain as well as beneficially modifying cardiometabolic factors in patients with schizophrenia being treated with olanzapine. A systematic review of emerging evidence with metformin in patients with schizophrenia suggests that metformin may also improve some cognitive symptoms of the illness, although further research is needed. The randomized, double-blind MELIA trial of metformin plus lifestyle intervention in antipsychotic-induced weight gain is ongoing. Starting metformin as a preventive measure at the same time as antipsychotic therapy may help to limit excess weight gain. 

Research continues on the potential benefit of adding weight loss medications, including glucagon-like peptide-1 (GLP-1) receptor agonists, to antipsychotics. Daily liraglutide is most widely studied, but a published case series with weekly semaglutide also demonstrated weight loss in this setting. Liraglutide also has shown beneficial cardiometabolic effects in patients using antipsychotic medications. More studies of these drugs and of GLP-1/glucose-dependent insulinotropic polypeptide agonists are needed to elucidate the optimal use of these therapies for patients with schizophrenia.

There are few other effective ways to mitigate weight gain with olanzapine. Patients should be counseled on nutrition and lifestyle modifications. Evidence supports improvement with structured lifestyle modifications across a range of patients with less severe mental health issues, and structured programs combined with motivational interviewing were associated with reductions in antipsychotic-induced weight gain in patients with severe mental illness. As with any patient with obesity, however, the success of lifestyle modifications is heavily dependent on the individual's ability and motivation to comply with recommended interventions. 

Nonpharmacologic interventions to address joint pain include heat or cold compresses, physical therapy, and strength and resistance training to improve the strength of muscles supporting the joints. If these measures are ineffective, nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen, naproxen, meloxicam, diclofenac, or celecoxib may be used with regular follow-up to assess cardiovascular and gastrointestinal health. Topical NSAIDs also may be useful. For more intractable joint pain, options include injecting a corticosteroid or sodium hyaluronate into the affected joints or joint replacement. 

Carolyn Newberry, MD, Assistant Professor of Medicine, Director of GI Nutrition, Innovative Center for Health and Nutrition in Gastroenterology (ICHANGE), Division of Gastroenterology, Weill Cornell Medical Center, New York, NY.

Disclosure: Carolyn Newberry, MD, has disclosed the following relevant financial relationships:

Serve(d) as a speaker or a member of a speakers bureau for: Baster International; InBody.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

Overall, persons with schizophrenia are more likely than the general population to be overweight and have cardiovascular risk factors before starting treatment with antipsychotics, and such treatment generally worsens these measures. Weight gain and associated morbidity and mortality are common side effects of antipsychotic medications. Olanzapine is associated with significant weight gain of 7% or more, higher than other second-generation antipsychotics. Olanzapine treatment is the major contributor to this patient's additional weight gain over the past 2 years. This added weight has translated to excess wear and tear on her joints, leading to evidence of osteoarthritis. Treatment with olanzapine is also independently associated with detrimental changes in cardiometabolic parameters.

Interventions to prevent or mitigate weight gain with antipsychotics are limited. In general, the American Psychiatric Association does not recommend switching antipsychotics for patients whose schizophrenia is well managed. However, there is increasing evidence that metformin may have a role in mitigating weight gain as well as beneficially modifying cardiometabolic factors in patients with schizophrenia being treated with olanzapine. A systematic review of emerging evidence with metformin in patients with schizophrenia suggests that metformin may also improve some cognitive symptoms of the illness, although further research is needed. The randomized, double-blind MELIA trial of metformin plus lifestyle intervention in antipsychotic-induced weight gain is ongoing. Starting metformin as a preventive measure at the same time as antipsychotic therapy may help to limit excess weight gain. 

Research continues on the potential benefit of adding weight loss medications, including glucagon-like peptide-1 (GLP-1) receptor agonists, to antipsychotics. Daily liraglutide is most widely studied, but a published case series with weekly semaglutide also demonstrated weight loss in this setting. Liraglutide also has shown beneficial cardiometabolic effects in patients using antipsychotic medications. More studies of these drugs and of GLP-1/glucose-dependent insulinotropic polypeptide agonists are needed to elucidate the optimal use of these therapies for patients with schizophrenia.

There are few other effective ways to mitigate weight gain with olanzapine. Patients should be counseled on nutrition and lifestyle modifications. Evidence supports improvement with structured lifestyle modifications across a range of patients with less severe mental health issues, and structured programs combined with motivational interviewing were associated with reductions in antipsychotic-induced weight gain in patients with severe mental illness. As with any patient with obesity, however, the success of lifestyle modifications is heavily dependent on the individual's ability and motivation to comply with recommended interventions. 

Nonpharmacologic interventions to address joint pain include heat or cold compresses, physical therapy, and strength and resistance training to improve the strength of muscles supporting the joints. If these measures are ineffective, nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen, naproxen, meloxicam, diclofenac, or celecoxib may be used with regular follow-up to assess cardiovascular and gastrointestinal health. Topical NSAIDs also may be useful. For more intractable joint pain, options include injecting a corticosteroid or sodium hyaluronate into the affected joints or joint replacement. 

Carolyn Newberry, MD, Assistant Professor of Medicine, Director of GI Nutrition, Innovative Center for Health and Nutrition in Gastroenterology (ICHANGE), Division of Gastroenterology, Weill Cornell Medical Center, New York, NY.

Disclosure: Carolyn Newberry, MD, has disclosed the following relevant financial relationships:

Serve(d) as a speaker or a member of a speakers bureau for: Baster International; InBody.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The chemotherapy-free combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) that is standard in treating low-risk acute promyelocytic leukemia (APL) also shows superior benefits in the high-risk APL population, suggesting the regimen should become the standard in those patients as well, new research shows.

“First-line therapy with ATRA-ATO with two initial doses of idarubicin results in superior event-free survival, compared to conventional ATRA-chemotherapy in patients with high-risk APL,” said first author Uwe Platzbecker, MD, of the University Hospital Leipzig, department for hematology, cellular therapy, hemostaseology, and infectious diseases, in Leipzig, Germany, at the annual meeting of the European Hematology Association (EHA) in Madrid, Spain.

“We believe that the trial may support the implementation of this regimen as a new standard of care in all patients with high-risk APL,” he said.

In the treatment of low and intermediate risk APL, a subtype of acute myeloid leukemia (AML), the combination of ATRA and ATO has become standard since being shown in a pivotal 2013 study to be superior versus ATRA and chemotherapy. The approach is approved by the Food and Drug Administration in the treatment of adults with newly diagnosed low-risk APL.

Importantly, the improved survival with ATRA/ATO approach may result from “reduced severe hematologic toxicity together with similar antileukemic efficacy,” compared with the regimen that include chemotherapy, the authors of the 2013 study speculated.

However, the treatment regimen has not been evaluated in randomized trials in patients with high-risk APL, defined as having a white blood cell count of more than 10,000 cells per μL.

For those patients, the conventional treatment remains ATRA with a chemotherapy backbone, Dr. Platzbecker explained.

To evaluate if the improvements extend to high-risk APL patients without compromising safety, Dr. Platzbecker and colleagues conducted the open-label, prospective APOLLO trial, involving newly diagnosed high-risk APL who were enrolled between 2016 and 2022 at 143 sites in six European countries.

The patients were randomized into one of two groups: ATRA/ATO, involving treatment consisting of two doses of idarubicin (12 mg/m²) on days 1 and 3 at the time of induction therapy, in addition to ATO 0.15 mg/kg and ATRA 45 mg/m², daily until complete remission, or the ATRA-chemotherapy arm, involving standard ATRA also with idarubicin induction, followed by three cycles of chemotherapy-based consolidation as well as 2 years of maintenance treatment.

While the study was prematurely discontinued in August 2022 because of COVID-19–related recruitment delays and expiration of the study drug, the maintenance and observational periods are ongoing.

Of 131 patients with high-risk APL who were evaluable for the outcome analysis, 68 were in the ATRA/ATO group and 63 in the ATRA-chemotherapy arm.

Overall, participants had a mean age of 46, 50% were female, their median Eastern Cooperative Oncology Group score was 1. Their median white blood cell count was 36 × 10⁹/L, with 39% having a white blood cell count greater than 50 × 10⁹/L.

Molecular resistance occurred in 1.7% in the ATRA/ATO arm vs 5.5% in the ATRA chemotherapy arm, which was not statistically significant (P = .268); however, the incidence of molecular relapse was much lower without chemotherapy, at 1.6% with ATRA/ATO vs 14% with ATRA and chemotherapy.

For the primary endpoint, with a median follow-up of 31 months, the 2-year rate of event-free survival those in the ATRA/ATO arm was 88% vs 70% in the ATRA plus chemotherapy regimen (P = .02). The 5-year event-free survival continued to favor ATRA-ATO (87% vs 55%; P = .0034).

The estimated 5-year overall survival was 93% vs 82% for ATRA/ATO vs ATRA-chemotherapy, respectively, which was not significantly different (P = .17).

There were no significant differences between the arms in complete response (93% with ATRA/ATO vs 91% with ATRA-chemotherapy; P = .65), and rates of early death (within the first 30 days) were also similar across arms, at 7% vs 10%, respectively.

Death while in complete remission occurred in zero patients in the ATRA/ATO arm and three in the ATRA chemotherapy arm.

In terms of toxicities, the ATRA/ATO group had significantly lower rates of hematologic toxicity versus ATRA-chemotherapy, including rates of thrombocytopenia grade 1-4 and neutropenia grade 3-4 (P < .001), while there were no significant differences between the groups in hepatic toxicities (11.8% and 14.3%, respectively; P = .08) or differentiation syndrome (1.5% vs 4.8%; P = .27).

QTc prolongation grade 3-4 occurred in 4.4 patients receiving ATRA/ATO, compared with 0 in the ATRA-chemotherapy group; however, Dr. Platzbecker said the cases had no clinical implications.

Asked to elaborate on the regimens’ toxicities in the press briefing, Dr. Platzbecker noted that “what is very important especially for patients, is [lower rates] of issues such as hair loss and constipation that are much less common with the ATRO/ATO regimen.”

“In addition, we know from the early experiences with this that younger patients are being cured by this regimen,” hence improving pregnancy prospects for women.

A take-home message from the overall results is that the ATRO/ATO regimen for high-risk APL patients should represent “a new treatment paradigm” that will “hopefully soon” be reflected in guideline recommendations, Dr. Platzbecker said in an interview.
 

Concerns Included Relapse, Differentiation Syndrome

Commenting on the research, Mikkael A. Sekeres, MD, explained that, while the “less is more” non-chemotherapy approach was adopted in widespread utilization in low-risk APL because of superior outcomes, a variety of concerns surrounded its use in high-risk patients.

“In high-risk patients, there were concerns that a durable response would be lower and that relapse would be higher for patients receiving ATRA and ATO than those receiving standard chemotherapy,” Dr. Sekeres, who is chief of the division of hematology, department of medicine, Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida, said in an interview.

“In addition, it was theoretically possible that patients receiving the differentiating agents ATRA and ATO could suffer higher rates of differentiation syndrome, which could contribute to early death,” he explained. “These fears were simply not realized in the trial.”

Caveats of the trial “include the relatively small sample size and that the trial was stopped prematurely due to low enrollment during the COVID pandemic,” he noted.

Another limitation was the median follow-up of about 2.5 years.

However, Dr. Sekeres said he agreed that, “with further follow-up and continued superiority of the idarubicin, ATRA, and ATO combination, this could become a new standard of care for high-risk patients with APL.”

Dr. Platzbecker’s disclosures include ties with Teva, BMS, Curis, Janssen, AbbVie, and Takeda. Dr. Sekeres had no disclosures.

The chemotherapy-free combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) that is standard in treating low-risk acute promyelocytic leukemia (APL) also shows superior benefits in the high-risk APL population, suggesting the regimen should become the standard in those patients as well, new research shows.

“First-line therapy with ATRA-ATO with two initial doses of idarubicin results in superior event-free survival, compared to conventional ATRA-chemotherapy in patients with high-risk APL,” said first author Uwe Platzbecker, MD, of the University Hospital Leipzig, department for hematology, cellular therapy, hemostaseology, and infectious diseases, in Leipzig, Germany, at the annual meeting of the European Hematology Association (EHA) in Madrid, Spain.

“We believe that the trial may support the implementation of this regimen as a new standard of care in all patients with high-risk APL,” he said.

In the treatment of low and intermediate risk APL, a subtype of acute myeloid leukemia (AML), the combination of ATRA and ATO has become standard since being shown in a pivotal 2013 study to be superior versus ATRA and chemotherapy. The approach is approved by the Food and Drug Administration in the treatment of adults with newly diagnosed low-risk APL.

Importantly, the improved survival with ATRA/ATO approach may result from “reduced severe hematologic toxicity together with similar antileukemic efficacy,” compared with the regimen that include chemotherapy, the authors of the 2013 study speculated.

However, the treatment regimen has not been evaluated in randomized trials in patients with high-risk APL, defined as having a white blood cell count of more than 10,000 cells per μL.

For those patients, the conventional treatment remains ATRA with a chemotherapy backbone, Dr. Platzbecker explained.

To evaluate if the improvements extend to high-risk APL patients without compromising safety, Dr. Platzbecker and colleagues conducted the open-label, prospective APOLLO trial, involving newly diagnosed high-risk APL who were enrolled between 2016 and 2022 at 143 sites in six European countries.

The patients were randomized into one of two groups: ATRA/ATO, involving treatment consisting of two doses of idarubicin (12 mg/m²) on days 1 and 3 at the time of induction therapy, in addition to ATO 0.15 mg/kg and ATRA 45 mg/m², daily until complete remission, or the ATRA-chemotherapy arm, involving standard ATRA also with idarubicin induction, followed by three cycles of chemotherapy-based consolidation as well as 2 years of maintenance treatment.

While the study was prematurely discontinued in August 2022 because of COVID-19–related recruitment delays and expiration of the study drug, the maintenance and observational periods are ongoing.

Of 131 patients with high-risk APL who were evaluable for the outcome analysis, 68 were in the ATRA/ATO group and 63 in the ATRA-chemotherapy arm.

Overall, participants had a mean age of 46, 50% were female, their median Eastern Cooperative Oncology Group score was 1. Their median white blood cell count was 36 × 10⁹/L, with 39% having a white blood cell count greater than 50 × 10⁹/L.

Molecular resistance occurred in 1.7% in the ATRA/ATO arm vs 5.5% in the ATRA chemotherapy arm, which was not statistically significant (P = .268); however, the incidence of molecular relapse was much lower without chemotherapy, at 1.6% with ATRA/ATO vs 14% with ATRA and chemotherapy.

For the primary endpoint, with a median follow-up of 31 months, the 2-year rate of event-free survival those in the ATRA/ATO arm was 88% vs 70% in the ATRA plus chemotherapy regimen (P = .02). The 5-year event-free survival continued to favor ATRA-ATO (87% vs 55%; P = .0034).

The estimated 5-year overall survival was 93% vs 82% for ATRA/ATO vs ATRA-chemotherapy, respectively, which was not significantly different (P = .17).

There were no significant differences between the arms in complete response (93% with ATRA/ATO vs 91% with ATRA-chemotherapy; P = .65), and rates of early death (within the first 30 days) were also similar across arms, at 7% vs 10%, respectively.

Death while in complete remission occurred in zero patients in the ATRA/ATO arm and three in the ATRA chemotherapy arm.

In terms of toxicities, the ATRA/ATO group had significantly lower rates of hematologic toxicity versus ATRA-chemotherapy, including rates of thrombocytopenia grade 1-4 and neutropenia grade 3-4 (P < .001), while there were no significant differences between the groups in hepatic toxicities (11.8% and 14.3%, respectively; P = .08) or differentiation syndrome (1.5% vs 4.8%; P = .27).

QTc prolongation grade 3-4 occurred in 4.4 patients receiving ATRA/ATO, compared with 0 in the ATRA-chemotherapy group; however, Dr. Platzbecker said the cases had no clinical implications.

Asked to elaborate on the regimens’ toxicities in the press briefing, Dr. Platzbecker noted that “what is very important especially for patients, is [lower rates] of issues such as hair loss and constipation that are much less common with the ATRO/ATO regimen.”

“In addition, we know from the early experiences with this that younger patients are being cured by this regimen,” hence improving pregnancy prospects for women.

A take-home message from the overall results is that the ATRO/ATO regimen for high-risk APL patients should represent “a new treatment paradigm” that will “hopefully soon” be reflected in guideline recommendations, Dr. Platzbecker said in an interview.
 

Concerns Included Relapse, Differentiation Syndrome

Commenting on the research, Mikkael A. Sekeres, MD, explained that, while the “less is more” non-chemotherapy approach was adopted in widespread utilization in low-risk APL because of superior outcomes, a variety of concerns surrounded its use in high-risk patients.

“In high-risk patients, there were concerns that a durable response would be lower and that relapse would be higher for patients receiving ATRA and ATO than those receiving standard chemotherapy,” Dr. Sekeres, who is chief of the division of hematology, department of medicine, Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida, said in an interview.

“In addition, it was theoretically possible that patients receiving the differentiating agents ATRA and ATO could suffer higher rates of differentiation syndrome, which could contribute to early death,” he explained. “These fears were simply not realized in the trial.”

Caveats of the trial “include the relatively small sample size and that the trial was stopped prematurely due to low enrollment during the COVID pandemic,” he noted.

Another limitation was the median follow-up of about 2.5 years.

However, Dr. Sekeres said he agreed that, “with further follow-up and continued superiority of the idarubicin, ATRA, and ATO combination, this could become a new standard of care for high-risk patients with APL.”

Dr. Platzbecker’s disclosures include ties with Teva, BMS, Curis, Janssen, AbbVie, and Takeda. Dr. Sekeres had no disclosures.

The chemotherapy-free combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) that is standard in treating low-risk acute promyelocytic leukemia (APL) also shows superior benefits in the high-risk APL population, suggesting the regimen should become the standard in those patients as well, new research shows.

“First-line therapy with ATRA-ATO with two initial doses of idarubicin results in superior event-free survival, compared to conventional ATRA-chemotherapy in patients with high-risk APL,” said first author Uwe Platzbecker, MD, of the University Hospital Leipzig, department for hematology, cellular therapy, hemostaseology, and infectious diseases, in Leipzig, Germany, at the annual meeting of the European Hematology Association (EHA) in Madrid, Spain.

“We believe that the trial may support the implementation of this regimen as a new standard of care in all patients with high-risk APL,” he said.

In the treatment of low and intermediate risk APL, a subtype of acute myeloid leukemia (AML), the combination of ATRA and ATO has become standard since being shown in a pivotal 2013 study to be superior versus ATRA and chemotherapy. The approach is approved by the Food and Drug Administration in the treatment of adults with newly diagnosed low-risk APL.

Importantly, the improved survival with ATRA/ATO approach may result from “reduced severe hematologic toxicity together with similar antileukemic efficacy,” compared with the regimen that include chemotherapy, the authors of the 2013 study speculated.

However, the treatment regimen has not been evaluated in randomized trials in patients with high-risk APL, defined as having a white blood cell count of more than 10,000 cells per μL.

For those patients, the conventional treatment remains ATRA with a chemotherapy backbone, Dr. Platzbecker explained.

To evaluate if the improvements extend to high-risk APL patients without compromising safety, Dr. Platzbecker and colleagues conducted the open-label, prospective APOLLO trial, involving newly diagnosed high-risk APL who were enrolled between 2016 and 2022 at 143 sites in six European countries.

The patients were randomized into one of two groups: ATRA/ATO, involving treatment consisting of two doses of idarubicin (12 mg/m²) on days 1 and 3 at the time of induction therapy, in addition to ATO 0.15 mg/kg and ATRA 45 mg/m², daily until complete remission, or the ATRA-chemotherapy arm, involving standard ATRA also with idarubicin induction, followed by three cycles of chemotherapy-based consolidation as well as 2 years of maintenance treatment.

While the study was prematurely discontinued in August 2022 because of COVID-19–related recruitment delays and expiration of the study drug, the maintenance and observational periods are ongoing.

Of 131 patients with high-risk APL who were evaluable for the outcome analysis, 68 were in the ATRA/ATO group and 63 in the ATRA-chemotherapy arm.

Overall, participants had a mean age of 46, 50% were female, their median Eastern Cooperative Oncology Group score was 1. Their median white blood cell count was 36 × 10⁹/L, with 39% having a white blood cell count greater than 50 × 10⁹/L.

Molecular resistance occurred in 1.7% in the ATRA/ATO arm vs 5.5% in the ATRA chemotherapy arm, which was not statistically significant (P = .268); however, the incidence of molecular relapse was much lower without chemotherapy, at 1.6% with ATRA/ATO vs 14% with ATRA and chemotherapy.

For the primary endpoint, with a median follow-up of 31 months, the 2-year rate of event-free survival those in the ATRA/ATO arm was 88% vs 70% in the ATRA plus chemotherapy regimen (P = .02). The 5-year event-free survival continued to favor ATRA-ATO (87% vs 55%; P = .0034).

The estimated 5-year overall survival was 93% vs 82% for ATRA/ATO vs ATRA-chemotherapy, respectively, which was not significantly different (P = .17).

There were no significant differences between the arms in complete response (93% with ATRA/ATO vs 91% with ATRA-chemotherapy; P = .65), and rates of early death (within the first 30 days) were also similar across arms, at 7% vs 10%, respectively.

Death while in complete remission occurred in zero patients in the ATRA/ATO arm and three in the ATRA chemotherapy arm.

In terms of toxicities, the ATRA/ATO group had significantly lower rates of hematologic toxicity versus ATRA-chemotherapy, including rates of thrombocytopenia grade 1-4 and neutropenia grade 3-4 (P < .001), while there were no significant differences between the groups in hepatic toxicities (11.8% and 14.3%, respectively; P = .08) or differentiation syndrome (1.5% vs 4.8%; P = .27).

QTc prolongation grade 3-4 occurred in 4.4 patients receiving ATRA/ATO, compared with 0 in the ATRA-chemotherapy group; however, Dr. Platzbecker said the cases had no clinical implications.

Asked to elaborate on the regimens’ toxicities in the press briefing, Dr. Platzbecker noted that “what is very important especially for patients, is [lower rates] of issues such as hair loss and constipation that are much less common with the ATRO/ATO regimen.”

“In addition, we know from the early experiences with this that younger patients are being cured by this regimen,” hence improving pregnancy prospects for women.

A take-home message from the overall results is that the ATRO/ATO regimen for high-risk APL patients should represent “a new treatment paradigm” that will “hopefully soon” be reflected in guideline recommendations, Dr. Platzbecker said in an interview.
 

Concerns Included Relapse, Differentiation Syndrome

Commenting on the research, Mikkael A. Sekeres, MD, explained that, while the “less is more” non-chemotherapy approach was adopted in widespread utilization in low-risk APL because of superior outcomes, a variety of concerns surrounded its use in high-risk patients.

“In high-risk patients, there were concerns that a durable response would be lower and that relapse would be higher for patients receiving ATRA and ATO than those receiving standard chemotherapy,” Dr. Sekeres, who is chief of the division of hematology, department of medicine, Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida, said in an interview.

“In addition, it was theoretically possible that patients receiving the differentiating agents ATRA and ATO could suffer higher rates of differentiation syndrome, which could contribute to early death,” he explained. “These fears were simply not realized in the trial.”

Caveats of the trial “include the relatively small sample size and that the trial was stopped prematurely due to low enrollment during the COVID pandemic,” he noted.

Another limitation was the median follow-up of about 2.5 years.

However, Dr. Sekeres said he agreed that, “with further follow-up and continued superiority of the idarubicin, ATRA, and ATO combination, this could become a new standard of care for high-risk patients with APL.”

Dr. Platzbecker’s disclosures include ties with Teva, BMS, Curis, Janssen, AbbVie, and Takeda. Dr. Sekeres had no disclosures.

VIENNA — The investigational interleukin (IL)-17 inhibitor izokibep hit its mark when it came to improving overall disease activity in people with active psoriatic arthritis (PsA) in a phase 2b/3 trial, but it was no better than placebo at reducing inflammation of the entheses. 

This apparent and unexpected lack of effect in the entheses was a key talking point after Philip J. Mease, MD, presented the late-breaking trial findings at the annual European Congress of Rheumatology.

Sara Freeman/Medscape Medical News

At just 18.6 kilodaltons in size, izokibep is just “one tenth the size of a standard monoclonal antibody” and is classed as a small protein therapeutic, Dr. Mease said. It has a “very tight” binding affinity for IL-17A, and because it also binds to albumin, it has a prolonged half-life compared with other IL-17 inhibitors. Potentially, it should be able to “penetrate into difficult areas,” such as the entheses, he said.
 

Prespecified Enthesitis Analysis

However, results of a prespecified secondary analysis conducted in 209 of the 343 trial participants who had received treatment showed no significant difference in the proportions with enthesis resolution at 16 weeks, defined as a Leeds Enthesitis Index (LEI) of 0.

Comparing two dosing regimens of izokibep 160 mg once weekly (QW) vs every other week (Q2W) with placebo, enthesitis resolution was seen in 45%, 56%, and 47%, respectively, of patients.

The LEI is “sometimes subject to problems with evaluation because of placebo response, which is what we see here,” noted Dr. Mease, director of rheumatology research at the Providence Swedish Medical Center and a rheumatology professor at the University of Washington School of Medicine in Seattle.

An exploratory analysis showed that there was a better response for izokibep vs placebo if the analysis included only patients with higher LEI scores at baseline, at 8.0% (n = 12) for placebo, 22.0% (n = 9) for izokibep 160 mg QW, and 50.0% (n = 12) for izokibep 160 mg Q2W.
 

Main Efficacy Data

The primary endpoint for the trial was the proportion of patients who had 50% improvement in American College of Rheumatology response criteria (ACR50) at 16 weeks. This showed a clear advantage for treatment with izokibep 160 QW and Q2W compared with placebo, with a respective 40%, 43%, and 15% of patients meeting this endpoint.

Corresponding ACR20 response rates were 59%, 64%, and 35%, respectively; ACR70 response rates were a respective 25%, 23%, and 5%.

In addition to ACR70, izokibep 160 QW and Q2W met a number of other “high hurdle” efficacy endpoints better than did placebo, Dr. Mease reported. A 90% reduction from baseline in the Psoriasis Area and Severity Index (PASI90) was achieved by a respective 64%, 58%, and 12% of patients, and a 100% reduction in this index (PASI100) was achieved by a respective 51%, 47%, and 12%. And 41%, 42%, and 14% of patients, respectively, met the criteria for minimal disease activity.
 

Patient Population

Mease pointed out during his presentation that the trial included patients with adult-onset PsA that had been ongoing for ≥ 6 months. Patients had to have at least three tender or swollen joints and an inadequate response, intolerance, or contraindication to commonly used front-line therapies such as nonsteroidal anti-inflammatory drugs, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and tumor necrosis factor inhibitors (TNFi).

In fact, around half of the participants across the three treatment arms had received prior csDMARDs, and almost a quarter had received a TNFi.

The mean duration of disease was around 7 years, the average age was about 50 years, and the majority of the participants were White individuals. There were more women than men in the placebo vs the izokibep arms (43.4% vs about 60.0%).
 

Adverse Events

Injection site reactions were the most common adverse events, most of which were mild to moderate. Very few (< 1% to 4%) led to any need to discontinue the drug.

Serious adverse events occurred at low rates in all study arms: 0.8% for placebo, 2.7% for izokibep QW, and 1.8% for izokibep Q2W.

One patient each (0.9%) in the izokibep arms developed ulcerative colitis, whereas none in the placebo group did. Only two patients developed candidiasis. One was in the placebo group and had a skin infection, and the other was an oral infection in the QW izokibep arm.

There were no cases of uveitis, suicidal ideation, or deaths reported.
 

Comments on the Study

During the discussion that followed the presentation, Walter P. Maksymowych, MBChB, of the University of Alberta in Edmonton, Alberta, Canada, addressed the dosing regimens used.

“Looking at the side effect profile and then looking at the response rate, comparing the weekly dosing and every 2 weeks, do you think, in hindsight, you might be remiss that there wasn’t an additional dosing on a monthly basis, especially since this is a construct that is meant to prolong the half-life of the molecule?” he asked, adding that perhaps this should be something to consider in future studies.

Mease responded that there had been a fourth dosing arm in the trial — izokibep 80 mg once a month — but because there were only eight patients, the data were not sufficiently robust to analyze. 

Commenting on the study, Laura C. Coates, MBChB, PhD, said: “It’s a pretty standard phase 2b/3 study,” and the outcomes were not wildly different from what has been seen with other IL-17A inhibitors.

“In phase 2, the enthesitis data looked really good; in phase 3, the enthesitis data looks the same as for any other IL-17 inhibitor,” Dr. Coates said.

A version of this article appeared on Medscape.com.

VIENNA — The investigational interleukin (IL)-17 inhibitor izokibep hit its mark when it came to improving overall disease activity in people with active psoriatic arthritis (PsA) in a phase 2b/3 trial, but it was no better than placebo at reducing inflammation of the entheses. 

This apparent and unexpected lack of effect in the entheses was a key talking point after Philip J. Mease, MD, presented the late-breaking trial findings at the annual European Congress of Rheumatology.

Sara Freeman/Medscape Medical News

At just 18.6 kilodaltons in size, izokibep is just “one tenth the size of a standard monoclonal antibody” and is classed as a small protein therapeutic, Dr. Mease said. It has a “very tight” binding affinity for IL-17A, and because it also binds to albumin, it has a prolonged half-life compared with other IL-17 inhibitors. Potentially, it should be able to “penetrate into difficult areas,” such as the entheses, he said.
 

Prespecified Enthesitis Analysis

However, results of a prespecified secondary analysis conducted in 209 of the 343 trial participants who had received treatment showed no significant difference in the proportions with enthesis resolution at 16 weeks, defined as a Leeds Enthesitis Index (LEI) of 0.

Comparing two dosing regimens of izokibep 160 mg once weekly (QW) vs every other week (Q2W) with placebo, enthesitis resolution was seen in 45%, 56%, and 47%, respectively, of patients.

The LEI is “sometimes subject to problems with evaluation because of placebo response, which is what we see here,” noted Dr. Mease, director of rheumatology research at the Providence Swedish Medical Center and a rheumatology professor at the University of Washington School of Medicine in Seattle.

An exploratory analysis showed that there was a better response for izokibep vs placebo if the analysis included only patients with higher LEI scores at baseline, at 8.0% (n = 12) for placebo, 22.0% (n = 9) for izokibep 160 mg QW, and 50.0% (n = 12) for izokibep 160 mg Q2W.
 

Main Efficacy Data

The primary endpoint for the trial was the proportion of patients who had 50% improvement in American College of Rheumatology response criteria (ACR50) at 16 weeks. This showed a clear advantage for treatment with izokibep 160 QW and Q2W compared with placebo, with a respective 40%, 43%, and 15% of patients meeting this endpoint.

Corresponding ACR20 response rates were 59%, 64%, and 35%, respectively; ACR70 response rates were a respective 25%, 23%, and 5%.

In addition to ACR70, izokibep 160 QW and Q2W met a number of other “high hurdle” efficacy endpoints better than did placebo, Dr. Mease reported. A 90% reduction from baseline in the Psoriasis Area and Severity Index (PASI90) was achieved by a respective 64%, 58%, and 12% of patients, and a 100% reduction in this index (PASI100) was achieved by a respective 51%, 47%, and 12%. And 41%, 42%, and 14% of patients, respectively, met the criteria for minimal disease activity.
 

Patient Population

Mease pointed out during his presentation that the trial included patients with adult-onset PsA that had been ongoing for ≥ 6 months. Patients had to have at least three tender or swollen joints and an inadequate response, intolerance, or contraindication to commonly used front-line therapies such as nonsteroidal anti-inflammatory drugs, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and tumor necrosis factor inhibitors (TNFi).

In fact, around half of the participants across the three treatment arms had received prior csDMARDs, and almost a quarter had received a TNFi.

The mean duration of disease was around 7 years, the average age was about 50 years, and the majority of the participants were White individuals. There were more women than men in the placebo vs the izokibep arms (43.4% vs about 60.0%).
 

Adverse Events

Injection site reactions were the most common adverse events, most of which were mild to moderate. Very few (< 1% to 4%) led to any need to discontinue the drug.

Serious adverse events occurred at low rates in all study arms: 0.8% for placebo, 2.7% for izokibep QW, and 1.8% for izokibep Q2W.

One patient each (0.9%) in the izokibep arms developed ulcerative colitis, whereas none in the placebo group did. Only two patients developed candidiasis. One was in the placebo group and had a skin infection, and the other was an oral infection in the QW izokibep arm.

There were no cases of uveitis, suicidal ideation, or deaths reported.
 

Comments on the Study

During the discussion that followed the presentation, Walter P. Maksymowych, MBChB, of the University of Alberta in Edmonton, Alberta, Canada, addressed the dosing regimens used.

“Looking at the side effect profile and then looking at the response rate, comparing the weekly dosing and every 2 weeks, do you think, in hindsight, you might be remiss that there wasn’t an additional dosing on a monthly basis, especially since this is a construct that is meant to prolong the half-life of the molecule?” he asked, adding that perhaps this should be something to consider in future studies.

Mease responded that there had been a fourth dosing arm in the trial — izokibep 80 mg once a month — but because there were only eight patients, the data were not sufficiently robust to analyze. 

Commenting on the study, Laura C. Coates, MBChB, PhD, said: “It’s a pretty standard phase 2b/3 study,” and the outcomes were not wildly different from what has been seen with other IL-17A inhibitors.

“In phase 2, the enthesitis data looked really good; in phase 3, the enthesitis data looks the same as for any other IL-17 inhibitor,” Dr. Coates said.

A version of this article appeared on Medscape.com.

VIENNA — The investigational interleukin (IL)-17 inhibitor izokibep hit its mark when it came to improving overall disease activity in people with active psoriatic arthritis (PsA) in a phase 2b/3 trial, but it was no better than placebo at reducing inflammation of the entheses. 

This apparent and unexpected lack of effect in the entheses was a key talking point after Philip J. Mease, MD, presented the late-breaking trial findings at the annual European Congress of Rheumatology.

Sara Freeman/Medscape Medical News

At just 18.6 kilodaltons in size, izokibep is just “one tenth the size of a standard monoclonal antibody” and is classed as a small protein therapeutic, Dr. Mease said. It has a “very tight” binding affinity for IL-17A, and because it also binds to albumin, it has a prolonged half-life compared with other IL-17 inhibitors. Potentially, it should be able to “penetrate into difficult areas,” such as the entheses, he said.
 

Prespecified Enthesitis Analysis

However, results of a prespecified secondary analysis conducted in 209 of the 343 trial participants who had received treatment showed no significant difference in the proportions with enthesis resolution at 16 weeks, defined as a Leeds Enthesitis Index (LEI) of 0.

Comparing two dosing regimens of izokibep 160 mg once weekly (QW) vs every other week (Q2W) with placebo, enthesitis resolution was seen in 45%, 56%, and 47%, respectively, of patients.

The LEI is “sometimes subject to problems with evaluation because of placebo response, which is what we see here,” noted Dr. Mease, director of rheumatology research at the Providence Swedish Medical Center and a rheumatology professor at the University of Washington School of Medicine in Seattle.

An exploratory analysis showed that there was a better response for izokibep vs placebo if the analysis included only patients with higher LEI scores at baseline, at 8.0% (n = 12) for placebo, 22.0% (n = 9) for izokibep 160 mg QW, and 50.0% (n = 12) for izokibep 160 mg Q2W.
 

Main Efficacy Data

The primary endpoint for the trial was the proportion of patients who had 50% improvement in American College of Rheumatology response criteria (ACR50) at 16 weeks. This showed a clear advantage for treatment with izokibep 160 QW and Q2W compared with placebo, with a respective 40%, 43%, and 15% of patients meeting this endpoint.

Corresponding ACR20 response rates were 59%, 64%, and 35%, respectively; ACR70 response rates were a respective 25%, 23%, and 5%.

In addition to ACR70, izokibep 160 QW and Q2W met a number of other “high hurdle” efficacy endpoints better than did placebo, Dr. Mease reported. A 90% reduction from baseline in the Psoriasis Area and Severity Index (PASI90) was achieved by a respective 64%, 58%, and 12% of patients, and a 100% reduction in this index (PASI100) was achieved by a respective 51%, 47%, and 12%. And 41%, 42%, and 14% of patients, respectively, met the criteria for minimal disease activity.
 

Patient Population

Mease pointed out during his presentation that the trial included patients with adult-onset PsA that had been ongoing for ≥ 6 months. Patients had to have at least three tender or swollen joints and an inadequate response, intolerance, or contraindication to commonly used front-line therapies such as nonsteroidal anti-inflammatory drugs, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and tumor necrosis factor inhibitors (TNFi).

In fact, around half of the participants across the three treatment arms had received prior csDMARDs, and almost a quarter had received a TNFi.

The mean duration of disease was around 7 years, the average age was about 50 years, and the majority of the participants were White individuals. There were more women than men in the placebo vs the izokibep arms (43.4% vs about 60.0%).
 

Adverse Events

Injection site reactions were the most common adverse events, most of which were mild to moderate. Very few (< 1% to 4%) led to any need to discontinue the drug.

Serious adverse events occurred at low rates in all study arms: 0.8% for placebo, 2.7% for izokibep QW, and 1.8% for izokibep Q2W.

One patient each (0.9%) in the izokibep arms developed ulcerative colitis, whereas none in the placebo group did. Only two patients developed candidiasis. One was in the placebo group and had a skin infection, and the other was an oral infection in the QW izokibep arm.

There were no cases of uveitis, suicidal ideation, or deaths reported.
 

Comments on the Study

During the discussion that followed the presentation, Walter P. Maksymowych, MBChB, of the University of Alberta in Edmonton, Alberta, Canada, addressed the dosing regimens used.

“Looking at the side effect profile and then looking at the response rate, comparing the weekly dosing and every 2 weeks, do you think, in hindsight, you might be remiss that there wasn’t an additional dosing on a monthly basis, especially since this is a construct that is meant to prolong the half-life of the molecule?” he asked, adding that perhaps this should be something to consider in future studies.

Mease responded that there had been a fourth dosing arm in the trial — izokibep 80 mg once a month — but because there were only eight patients, the data were not sufficiently robust to analyze. 

Commenting on the study, Laura C. Coates, MBChB, PhD, said: “It’s a pretty standard phase 2b/3 study,” and the outcomes were not wildly different from what has been seen with other IL-17A inhibitors.

“In phase 2, the enthesitis data looked really good; in phase 3, the enthesitis data looks the same as for any other IL-17 inhibitor,” Dr. Coates said.

A version of this article appeared on Medscape.com.