Evidence summary

Walking’s impact on cholesterol levels is modest, inconsistent

A 2022 systematic review and meta-analysis of 21 studies (n = 1129) evaluated the effects of walking on lipids and lipoproteins in women older than 18 years who were overweight or obese and were not taking any lipid-­lowering medications. Median TC was 206 mg/dL and median LDL was 126 mg/dL.¹

The primary outcome found that walking decreased TC and LDL levels independent of diet and weight loss. Twenty studies reported on TC and showed that walking significantly decreased TC levels compared to the control groups (raw mean difference [RMD] = 6.7 mg/dL; 95% CI, 0.4-12.9; P = .04). Fifteen studies examined LDL and showed a significant decrease in LDL levels with walking compared to control groups (RMD = 7.4 mg/dL; 95% CI, 0.3-14.5; P = .04). However, the small magnitude of the changes may have little clinical impact.¹

There were no significant changes in the walking groups compared to the control groups for triglycerides (17 studies; RMD = 2.2 mg/dL; 95% CI, –8.4 to 12.8; P = .68) or high-density lipoprotein (HDL) (18 studies; RMD = 1.5 mg/dL; 95% CI, –0.4 to 3.3; P = .12). Included studies were required to be controlled but were otherwise not described. The overall risk for bias was determined to be low.¹

A 2020 RCT (n = 22) assessed the effects of a walking intervention on cholesterol and cardiovascular disease (CVD) risk in individuals ages 40 to 65 years with moderate CVD risk but without diabetes or CVD.² Moderate CVD risk was defined as a 2% to 5% ­10-year risk for a CVD event using the European HeartScore, which incorporates age, sex, blood pressure, lipid levels, and smoking status³; however, study participants were not required to have hyperlipidemia. Participants were enrolled in a 12-week, nurse-led intervention of moderate-paced walking for 30 to 45 minutes 5 times weekly.

Individuals in the intervention group had significant decreases in average TC levels from baseline to follow-up (244.6 mg/dL vs 213.7 mg/dL; P = .001). As a result, participants’ average 10-year CVD risk was significantly reduced from moderate risk to low risk (2.6% vs 1.8%; P = 038) and was significantly lower in the intervention group than in the control group at follow-up (1.8% vs 3.1%; P = .019). No blinding was used, and the use of lipid-lowering medications was not reported, which could have impacted the results.²

A 2008 RCT (n = 67) examined the effect of a home-based walking program (12 weeks of brisk walking, at least 30 min/d and at least 5 d/wk, with at least 300 kcal burned per walk) vs a sedentary control group in men ages 45 to 65 years with hyperlipidemia (TC > 240 mg/dL and/or TC/­HDL-C ratio ≥ 6) who were not receiving lipid-lowering medication. There were no significant changes from baseline to follow-up in the walking group compared to the control group in TC (adjusted mean difference [AMD] = –9.3 mg/dL; 95% CI, –22.8 to 4.64; P = .19), HDL-C (AMD = 2.7 mg/dL; 95% CI, –0.4 to 5.4; P = .07) or triglycerides (AMD = –26.6 mg/dL; 95% CI, –56.7 to 2.7; P = .07).⁴

The lipid reductions achieved from walking—if any—are minimal.

A 2002 RCT (n = 111) of sedentary men and women (BMI, 25-35; ages, 40-65 years) with dyslipidemia (LDL of 130-190 mg/dL, or HDL < 40 mg/dL for men or < 45 mg/dL for women) examined the impact of various physical activity levels for 8 months when compared to a control group observed for 6 months. The group assigned to low-amount, moderate-intensity physical activity walked an equivalent of 12 miles per week.⁵

Continue to: In this group...

In this group, there was a significant decrease in average triglyceride concentrations from baseline to follow-up (mean ± standard error = 196.8 ± 30.5 mg/dL vs 145.2 ± 16.0 mg/dL; P < .001). Significance of the change compared with changes in the control group was not reported, although triglycerides in the control group increased from baseline to follow-up (132.1 ± 11.0 vs 155.8 ± 14.9 mg/dL). There were no significant changes from baseline to follow-up in TC (194 ± 4.8 vs 197.9 ± 5.4 mg/dL), LDL (122.7 ± 4.0 vs 127.8 ± 4.1 mg/dL), or HDL (42.0 ± 1.9 vs 43.1 ± 2.5 mg/dL); P values of pre-post changes and comparison to control group were not reported.⁵

Recommendations from others

The Physical Activity Guidelines for Americans, published by the Department of Health and Human Services and updated in 2018, cite adherence to the published guidelines as a protective factor against high LDL and total lipids in both adults and children.⁶ The guidelines for adults recommend 150 to 300 minutes of moderate-intensity or 75 to 150 minutes of vigorous-intensity aerobic exercise per week, as well as muscle-strengthening activities of moderate or greater intensity 2 or more days per week. Brisk walking is included as an example of a moderate-intensity activity. These same guidelines are cited and endorsed by the American College of Sports Medicine and the American Heart Association.^7,8

Editor’s takeaway

The lipid reductions achieved from walking—if any—are minimal. By themselves, these small reductions will not accomplish our ­lipid-lowering goals. However, cholesterol goals are primarily disease oriented. This evidence does not directly inform us of important patient-oriented outcomes, such as morbidity, mortality, and vitality.

Evidence summary

Walking’s impact on cholesterol levels is modest, inconsistent

A 2022 systematic review and meta-analysis of 21 studies (n = 1129) evaluated the effects of walking on lipids and lipoproteins in women older than 18 years who were overweight or obese and were not taking any lipid-­lowering medications. Median TC was 206 mg/dL and median LDL was 126 mg/dL.¹

The primary outcome found that walking decreased TC and LDL levels independent of diet and weight loss. Twenty studies reported on TC and showed that walking significantly decreased TC levels compared to the control groups (raw mean difference [RMD] = 6.7 mg/dL; 95% CI, 0.4-12.9; P = .04). Fifteen studies examined LDL and showed a significant decrease in LDL levels with walking compared to control groups (RMD = 7.4 mg/dL; 95% CI, 0.3-14.5; P = .04). However, the small magnitude of the changes may have little clinical impact.¹

There were no significant changes in the walking groups compared to the control groups for triglycerides (17 studies; RMD = 2.2 mg/dL; 95% CI, –8.4 to 12.8; P = .68) or high-density lipoprotein (HDL) (18 studies; RMD = 1.5 mg/dL; 95% CI, –0.4 to 3.3; P = .12). Included studies were required to be controlled but were otherwise not described. The overall risk for bias was determined to be low.¹

A 2020 RCT (n = 22) assessed the effects of a walking intervention on cholesterol and cardiovascular disease (CVD) risk in individuals ages 40 to 65 years with moderate CVD risk but without diabetes or CVD.² Moderate CVD risk was defined as a 2% to 5% ­10-year risk for a CVD event using the European HeartScore, which incorporates age, sex, blood pressure, lipid levels, and smoking status³; however, study participants were not required to have hyperlipidemia. Participants were enrolled in a 12-week, nurse-led intervention of moderate-paced walking for 30 to 45 minutes 5 times weekly.

Individuals in the intervention group had significant decreases in average TC levels from baseline to follow-up (244.6 mg/dL vs 213.7 mg/dL; P = .001). As a result, participants’ average 10-year CVD risk was significantly reduced from moderate risk to low risk (2.6% vs 1.8%; P = 038) and was significantly lower in the intervention group than in the control group at follow-up (1.8% vs 3.1%; P = .019). No blinding was used, and the use of lipid-lowering medications was not reported, which could have impacted the results.²

A 2008 RCT (n = 67) examined the effect of a home-based walking program (12 weeks of brisk walking, at least 30 min/d and at least 5 d/wk, with at least 300 kcal burned per walk) vs a sedentary control group in men ages 45 to 65 years with hyperlipidemia (TC > 240 mg/dL and/or TC/­HDL-C ratio ≥ 6) who were not receiving lipid-lowering medication. There were no significant changes from baseline to follow-up in the walking group compared to the control group in TC (adjusted mean difference [AMD] = –9.3 mg/dL; 95% CI, –22.8 to 4.64; P = .19), HDL-C (AMD = 2.7 mg/dL; 95% CI, –0.4 to 5.4; P = .07) or triglycerides (AMD = –26.6 mg/dL; 95% CI, –56.7 to 2.7; P = .07).⁴

The lipid reductions achieved from walking—if any—are minimal.

A 2002 RCT (n = 111) of sedentary men and women (BMI, 25-35; ages, 40-65 years) with dyslipidemia (LDL of 130-190 mg/dL, or HDL < 40 mg/dL for men or < 45 mg/dL for women) examined the impact of various physical activity levels for 8 months when compared to a control group observed for 6 months. The group assigned to low-amount, moderate-intensity physical activity walked an equivalent of 12 miles per week.⁵

Continue to: In this group...

In this group, there was a significant decrease in average triglyceride concentrations from baseline to follow-up (mean ± standard error = 196.8 ± 30.5 mg/dL vs 145.2 ± 16.0 mg/dL; P < .001). Significance of the change compared with changes in the control group was not reported, although triglycerides in the control group increased from baseline to follow-up (132.1 ± 11.0 vs 155.8 ± 14.9 mg/dL). There were no significant changes from baseline to follow-up in TC (194 ± 4.8 vs 197.9 ± 5.4 mg/dL), LDL (122.7 ± 4.0 vs 127.8 ± 4.1 mg/dL), or HDL (42.0 ± 1.9 vs 43.1 ± 2.5 mg/dL); P values of pre-post changes and comparison to control group were not reported.⁵

Recommendations from others

The Physical Activity Guidelines for Americans, published by the Department of Health and Human Services and updated in 2018, cite adherence to the published guidelines as a protective factor against high LDL and total lipids in both adults and children.⁶ The guidelines for adults recommend 150 to 300 minutes of moderate-intensity or 75 to 150 minutes of vigorous-intensity aerobic exercise per week, as well as muscle-strengthening activities of moderate or greater intensity 2 or more days per week. Brisk walking is included as an example of a moderate-intensity activity. These same guidelines are cited and endorsed by the American College of Sports Medicine and the American Heart Association.^7,8

Editor’s takeaway

The lipid reductions achieved from walking—if any—are minimal. By themselves, these small reductions will not accomplish our ­lipid-lowering goals. However, cholesterol goals are primarily disease oriented. This evidence does not directly inform us of important patient-oriented outcomes, such as morbidity, mortality, and vitality.

Evidence summary

Walking’s impact on cholesterol levels is modest, inconsistent

A 2022 systematic review and meta-analysis of 21 studies (n = 1129) evaluated the effects of walking on lipids and lipoproteins in women older than 18 years who were overweight or obese and were not taking any lipid-­lowering medications. Median TC was 206 mg/dL and median LDL was 126 mg/dL.¹

The primary outcome found that walking decreased TC and LDL levels independent of diet and weight loss. Twenty studies reported on TC and showed that walking significantly decreased TC levels compared to the control groups (raw mean difference [RMD] = 6.7 mg/dL; 95% CI, 0.4-12.9; P = .04). Fifteen studies examined LDL and showed a significant decrease in LDL levels with walking compared to control groups (RMD = 7.4 mg/dL; 95% CI, 0.3-14.5; P = .04). However, the small magnitude of the changes may have little clinical impact.¹

There were no significant changes in the walking groups compared to the control groups for triglycerides (17 studies; RMD = 2.2 mg/dL; 95% CI, –8.4 to 12.8; P = .68) or high-density lipoprotein (HDL) (18 studies; RMD = 1.5 mg/dL; 95% CI, –0.4 to 3.3; P = .12). Included studies were required to be controlled but were otherwise not described. The overall risk for bias was determined to be low.¹

A 2020 RCT (n = 22) assessed the effects of a walking intervention on cholesterol and cardiovascular disease (CVD) risk in individuals ages 40 to 65 years with moderate CVD risk but without diabetes or CVD.² Moderate CVD risk was defined as a 2% to 5% ­10-year risk for a CVD event using the European HeartScore, which incorporates age, sex, blood pressure, lipid levels, and smoking status³; however, study participants were not required to have hyperlipidemia. Participants were enrolled in a 12-week, nurse-led intervention of moderate-paced walking for 30 to 45 minutes 5 times weekly.

Individuals in the intervention group had significant decreases in average TC levels from baseline to follow-up (244.6 mg/dL vs 213.7 mg/dL; P = .001). As a result, participants’ average 10-year CVD risk was significantly reduced from moderate risk to low risk (2.6% vs 1.8%; P = 038) and was significantly lower in the intervention group than in the control group at follow-up (1.8% vs 3.1%; P = .019). No blinding was used, and the use of lipid-lowering medications was not reported, which could have impacted the results.²

A 2008 RCT (n = 67) examined the effect of a home-based walking program (12 weeks of brisk walking, at least 30 min/d and at least 5 d/wk, with at least 300 kcal burned per walk) vs a sedentary control group in men ages 45 to 65 years with hyperlipidemia (TC > 240 mg/dL and/or TC/­HDL-C ratio ≥ 6) who were not receiving lipid-lowering medication. There were no significant changes from baseline to follow-up in the walking group compared to the control group in TC (adjusted mean difference [AMD] = –9.3 mg/dL; 95% CI, –22.8 to 4.64; P = .19), HDL-C (AMD = 2.7 mg/dL; 95% CI, –0.4 to 5.4; P = .07) or triglycerides (AMD = –26.6 mg/dL; 95% CI, –56.7 to 2.7; P = .07).⁴

The lipid reductions achieved from walking—if any—are minimal.

A 2002 RCT (n = 111) of sedentary men and women (BMI, 25-35; ages, 40-65 years) with dyslipidemia (LDL of 130-190 mg/dL, or HDL < 40 mg/dL for men or < 45 mg/dL for women) examined the impact of various physical activity levels for 8 months when compared to a control group observed for 6 months. The group assigned to low-amount, moderate-intensity physical activity walked an equivalent of 12 miles per week.⁵

Continue to: In this group...

In this group, there was a significant decrease in average triglyceride concentrations from baseline to follow-up (mean ± standard error = 196.8 ± 30.5 mg/dL vs 145.2 ± 16.0 mg/dL; P < .001). Significance of the change compared with changes in the control group was not reported, although triglycerides in the control group increased from baseline to follow-up (132.1 ± 11.0 vs 155.8 ± 14.9 mg/dL). There were no significant changes from baseline to follow-up in TC (194 ± 4.8 vs 197.9 ± 5.4 mg/dL), LDL (122.7 ± 4.0 vs 127.8 ± 4.1 mg/dL), or HDL (42.0 ± 1.9 vs 43.1 ± 2.5 mg/dL); P values of pre-post changes and comparison to control group were not reported.⁵

Recommendations from others

The Physical Activity Guidelines for Americans, published by the Department of Health and Human Services and updated in 2018, cite adherence to the published guidelines as a protective factor against high LDL and total lipids in both adults and children.⁶ The guidelines for adults recommend 150 to 300 minutes of moderate-intensity or 75 to 150 minutes of vigorous-intensity aerobic exercise per week, as well as muscle-strengthening activities of moderate or greater intensity 2 or more days per week. Brisk walking is included as an example of a moderate-intensity activity. These same guidelines are cited and endorsed by the American College of Sports Medicine and the American Heart Association.^7,8

Editor’s takeaway

The lipid reductions achieved from walking—if any—are minimal. By themselves, these small reductions will not accomplish our ­lipid-lowering goals. However, cholesterol goals are primarily disease oriented. This evidence does not directly inform us of important patient-oriented outcomes, such as morbidity, mortality, and vitality.

Although rare, acute hepatic porphyrias (AHPs) may be more common than previously thought, particularly among women between ages 15 and 50, according to a new clinical practice update from the American Gastroenterological Association.

For acute attacks, treatment should include intravenous hemin, and for patients with recurrent attacks, a newly-approved therapy called givosiran should be considered, wrote the authors of the update, which was published Jan. 13 in Gastroenterology.

“Diagnoses of AHPs are often missed, with a delay of more than 15 years from initial presentation. The key to early diagnosis is to consider the diagnosis, especially in patients with recurring severe abdominal pain not ascribable to other causes,” wrote the authors, who were led by Bruce Wang, MD, a hepatologist with the University of California, San Francisco.

AHPs are inherited disorders of heme-metabolism, which include acute intermittent porphyria, hereditary coproporphyria, variegate porphyria, and porphyria due to severe deficiency of 5-aminolevulinic acid dehydratase.

Acute intermittent porphyria (AIP) is the most common type, with an estimated prevalence of symptomatic AHP of 1 in 100,000 patients. However, population-level genetic studies show that the prevalence of pathogenic variants for AIP is between 1 in 1,300 and 1 in 1,785.

The major clinical presentation includes attacks of severe abdominal pain, nausea, vomiting, constipation, muscle weakness, neuropathy, tachycardia, and hypertension, yet without peritoneal signs or abnormalities on cross-sectional imaging.

Recent advances in treatment have improved the outlook for patients with AHP. To provide timely guidance, the authors developed 12 clinical practice advice statements on the diagnosis and management of AHPs based on a review of the published literature and expert opinion.

First, AHP screening should be considered in the evaluation of all patients, particularly among women in their childbearing years between ages 15 and 50 with unexplained, recurrent severe abdominal pain that doesn’t have a clear etiology. About 90% of patients with symptomatic AHP are women, and more than 90% of them experience only one or a few acute attacks in their lifetime, which are often precipitated by factors that increase the activity of the enzyme ALAS1 in the liver.

For initial AHP diagnosis, biochemical testing should measure porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) corrected to creatine on a random urine sample. All patients with significantly elevated urinary PBG or ALA should initially be presumed to have AHP, and during acute attacks, both will be elevated at least five-fold of the upper limit of normal. Because ALA and PBG are porphyrin precursors, urine porphyrin testing should not be used alone for AHP screening.

After that, genetic testing should be used to confirm the AHP diagnosis, as well as the specific type of AHP. Sequencing of the four genes ALAD, HMBS, CPOX, and PPOX leads to aminolevulinic acid dehydrase deficiency, acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria, respectively. When whole-gene sequencing is performed, about 95%-99% of cases can be identified. First-degree family members should be screened with genetic testing, and those who are mutation carriers should be counseled.

For acute attacks of AHP that are severe enough to require hospitalization, the currently approved treatment is intravenous hemin infusion, usually given once daily at a dose of 3-4 mg/kg body weight for 3-5 days. Due to potential thrombophlebitis, it’s best to administer hemin in a high-flow central vein via a peripherally inserted central catheter or central port.

In addition, treatment for acute attacks should include analgesics, antiemetics, and management of systemic arterial hypertension, tachycardia, hyponatremia, and hypomagnesemia. The primary goal of treatment during an acute attack is to decrease ALA production. Patients should be counseled to avoid identifiable triggers, such as porphyrinogenic medications, excess alcohol intake, tobacco use, and caloric deprivation.

Although recent advances have improved treatment for acute attacks, management for patients with frequent attacks remains challenging, the study authors wrote. About 3%-5% of patients with symptomatic AHP experience recurrent attacks, which is defined as four or more attacks per year. These attacks aren’t typically associated with identifiable triggers, although some that occur during the luteal phase of a patient’s menstrual cycle are believed to be triggered by progesterone. However, treatment with hormonal suppression therapy, such as GnRH agonists, has had limited success.

Off-label use of prophylactic intravenous heme therapy is common, although the effectiveness in preventing recurrent attacks isn’t well-established. In addition, chronic hemin use is associated with several complications, including infections, iron overload, and the need for indwelling central venous catheters.

Recently, the Food and Drug Administration approved givosiran, a small interfering RNA-based therapy that targets delta-aminolevulinate synthase 1, for treatment in adults with AHP. Monthly subcutaneous therapy appears to significantly lower rates of acute attacks among patients who experience recurrent attacks.

“We suggest prescribing givosiran only for those patients with recurrent acute attacks that are both biochemically and genetically confirmed,” the authors wrote. “Due to limited safety data, givosiran should not be used in women who are pregnant or planning a pregnancy.”

In the most severe cases, liver transplantation should be limited to patients with intractable symptoms and a significantly decreased quality of life who are refractory to pharmacotherapy. If living donor transplantation is considered, genetic testing should be used to screen related living donors since HMBS pathogenic variants in asymptomatic donors could results in poor posttransplantation outcomes.

In the long-term, patients with AHP should be monitored annually for liver disease and chronic kidney disease with serum creatinine and estimated glomerular filtration rate monitored. Patients also face an increased risk of hepatocellular carcinoma and should start screening at age 50, with a liver ultrasound every 6 months.

“Fortunately, most people with genetic defects never experience severe acute attacks or may experience only one or a few attacks throughout their lives,” the authors wrote.

The authors (Bruce Wang, MD, Herbert L. Bonkovsky, MD, AGAF, and Manisha Balwani, MD, MS) reported that they are part of the Porphyrias Consortium. The Porphyrias Consortium is part of the Rare Diseases Clinical Research Network, an initiative of the Division of Rare Diseases Research Innovation at the National Center for Advancing Translational Sciences. The consortium is funded through a collaboration between the center and the National Institute of Diabetes and Digestive and Kidney Diseases. Several authors disclosed funding support and honoraria for advisory board roles with various pharmaceutical companies, including Alnylam, which makes givosiran.

This article was updated 2/3/23.

Although rare, acute hepatic porphyrias (AHPs) may be more common than previously thought, particularly among women between ages 15 and 50, according to a new clinical practice update from the American Gastroenterological Association.

For acute attacks, treatment should include intravenous hemin, and for patients with recurrent attacks, a newly-approved therapy called givosiran should be considered, wrote the authors of the update, which was published Jan. 13 in Gastroenterology.

“Diagnoses of AHPs are often missed, with a delay of more than 15 years from initial presentation. The key to early diagnosis is to consider the diagnosis, especially in patients with recurring severe abdominal pain not ascribable to other causes,” wrote the authors, who were led by Bruce Wang, MD, a hepatologist with the University of California, San Francisco.

AHPs are inherited disorders of heme-metabolism, which include acute intermittent porphyria, hereditary coproporphyria, variegate porphyria, and porphyria due to severe deficiency of 5-aminolevulinic acid dehydratase.

Acute intermittent porphyria (AIP) is the most common type, with an estimated prevalence of symptomatic AHP of 1 in 100,000 patients. However, population-level genetic studies show that the prevalence of pathogenic variants for AIP is between 1 in 1,300 and 1 in 1,785.

The major clinical presentation includes attacks of severe abdominal pain, nausea, vomiting, constipation, muscle weakness, neuropathy, tachycardia, and hypertension, yet without peritoneal signs or abnormalities on cross-sectional imaging.

Recent advances in treatment have improved the outlook for patients with AHP. To provide timely guidance, the authors developed 12 clinical practice advice statements on the diagnosis and management of AHPs based on a review of the published literature and expert opinion.

First, AHP screening should be considered in the evaluation of all patients, particularly among women in their childbearing years between ages 15 and 50 with unexplained, recurrent severe abdominal pain that doesn’t have a clear etiology. About 90% of patients with symptomatic AHP are women, and more than 90% of them experience only one or a few acute attacks in their lifetime, which are often precipitated by factors that increase the activity of the enzyme ALAS1 in the liver.

For initial AHP diagnosis, biochemical testing should measure porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) corrected to creatine on a random urine sample. All patients with significantly elevated urinary PBG or ALA should initially be presumed to have AHP, and during acute attacks, both will be elevated at least five-fold of the upper limit of normal. Because ALA and PBG are porphyrin precursors, urine porphyrin testing should not be used alone for AHP screening.

After that, genetic testing should be used to confirm the AHP diagnosis, as well as the specific type of AHP. Sequencing of the four genes ALAD, HMBS, CPOX, and PPOX leads to aminolevulinic acid dehydrase deficiency, acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria, respectively. When whole-gene sequencing is performed, about 95%-99% of cases can be identified. First-degree family members should be screened with genetic testing, and those who are mutation carriers should be counseled.

For acute attacks of AHP that are severe enough to require hospitalization, the currently approved treatment is intravenous hemin infusion, usually given once daily at a dose of 3-4 mg/kg body weight for 3-5 days. Due to potential thrombophlebitis, it’s best to administer hemin in a high-flow central vein via a peripherally inserted central catheter or central port.

In addition, treatment for acute attacks should include analgesics, antiemetics, and management of systemic arterial hypertension, tachycardia, hyponatremia, and hypomagnesemia. The primary goal of treatment during an acute attack is to decrease ALA production. Patients should be counseled to avoid identifiable triggers, such as porphyrinogenic medications, excess alcohol intake, tobacco use, and caloric deprivation.

Although recent advances have improved treatment for acute attacks, management for patients with frequent attacks remains challenging, the study authors wrote. About 3%-5% of patients with symptomatic AHP experience recurrent attacks, which is defined as four or more attacks per year. These attacks aren’t typically associated with identifiable triggers, although some that occur during the luteal phase of a patient’s menstrual cycle are believed to be triggered by progesterone. However, treatment with hormonal suppression therapy, such as GnRH agonists, has had limited success.

Off-label use of prophylactic intravenous heme therapy is common, although the effectiveness in preventing recurrent attacks isn’t well-established. In addition, chronic hemin use is associated with several complications, including infections, iron overload, and the need for indwelling central venous catheters.

Recently, the Food and Drug Administration approved givosiran, a small interfering RNA-based therapy that targets delta-aminolevulinate synthase 1, for treatment in adults with AHP. Monthly subcutaneous therapy appears to significantly lower rates of acute attacks among patients who experience recurrent attacks.

“We suggest prescribing givosiran only for those patients with recurrent acute attacks that are both biochemically and genetically confirmed,” the authors wrote. “Due to limited safety data, givosiran should not be used in women who are pregnant or planning a pregnancy.”

In the most severe cases, liver transplantation should be limited to patients with intractable symptoms and a significantly decreased quality of life who are refractory to pharmacotherapy. If living donor transplantation is considered, genetic testing should be used to screen related living donors since HMBS pathogenic variants in asymptomatic donors could results in poor posttransplantation outcomes.

In the long-term, patients with AHP should be monitored annually for liver disease and chronic kidney disease with serum creatinine and estimated glomerular filtration rate monitored. Patients also face an increased risk of hepatocellular carcinoma and should start screening at age 50, with a liver ultrasound every 6 months.

“Fortunately, most people with genetic defects never experience severe acute attacks or may experience only one or a few attacks throughout their lives,” the authors wrote.

The authors (Bruce Wang, MD, Herbert L. Bonkovsky, MD, AGAF, and Manisha Balwani, MD, MS) reported that they are part of the Porphyrias Consortium. The Porphyrias Consortium is part of the Rare Diseases Clinical Research Network, an initiative of the Division of Rare Diseases Research Innovation at the National Center for Advancing Translational Sciences. The consortium is funded through a collaboration between the center and the National Institute of Diabetes and Digestive and Kidney Diseases. Several authors disclosed funding support and honoraria for advisory board roles with various pharmaceutical companies, including Alnylam, which makes givosiran.

This article was updated 2/3/23.

Although rare, acute hepatic porphyrias (AHPs) may be more common than previously thought, particularly among women between ages 15 and 50, according to a new clinical practice update from the American Gastroenterological Association.

For acute attacks, treatment should include intravenous hemin, and for patients with recurrent attacks, a newly-approved therapy called givosiran should be considered, wrote the authors of the update, which was published Jan. 13 in Gastroenterology.

“Diagnoses of AHPs are often missed, with a delay of more than 15 years from initial presentation. The key to early diagnosis is to consider the diagnosis, especially in patients with recurring severe abdominal pain not ascribable to other causes,” wrote the authors, who were led by Bruce Wang, MD, a hepatologist with the University of California, San Francisco.

AHPs are inherited disorders of heme-metabolism, which include acute intermittent porphyria, hereditary coproporphyria, variegate porphyria, and porphyria due to severe deficiency of 5-aminolevulinic acid dehydratase.

Acute intermittent porphyria (AIP) is the most common type, with an estimated prevalence of symptomatic AHP of 1 in 100,000 patients. However, population-level genetic studies show that the prevalence of pathogenic variants for AIP is between 1 in 1,300 and 1 in 1,785.

The major clinical presentation includes attacks of severe abdominal pain, nausea, vomiting, constipation, muscle weakness, neuropathy, tachycardia, and hypertension, yet without peritoneal signs or abnormalities on cross-sectional imaging.

Recent advances in treatment have improved the outlook for patients with AHP. To provide timely guidance, the authors developed 12 clinical practice advice statements on the diagnosis and management of AHPs based on a review of the published literature and expert opinion.

First, AHP screening should be considered in the evaluation of all patients, particularly among women in their childbearing years between ages 15 and 50 with unexplained, recurrent severe abdominal pain that doesn’t have a clear etiology. About 90% of patients with symptomatic AHP are women, and more than 90% of them experience only one or a few acute attacks in their lifetime, which are often precipitated by factors that increase the activity of the enzyme ALAS1 in the liver.

For initial AHP diagnosis, biochemical testing should measure porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) corrected to creatine on a random urine sample. All patients with significantly elevated urinary PBG or ALA should initially be presumed to have AHP, and during acute attacks, both will be elevated at least five-fold of the upper limit of normal. Because ALA and PBG are porphyrin precursors, urine porphyrin testing should not be used alone for AHP screening.

After that, genetic testing should be used to confirm the AHP diagnosis, as well as the specific type of AHP. Sequencing of the four genes ALAD, HMBS, CPOX, and PPOX leads to aminolevulinic acid dehydrase deficiency, acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria, respectively. When whole-gene sequencing is performed, about 95%-99% of cases can be identified. First-degree family members should be screened with genetic testing, and those who are mutation carriers should be counseled.

For acute attacks of AHP that are severe enough to require hospitalization, the currently approved treatment is intravenous hemin infusion, usually given once daily at a dose of 3-4 mg/kg body weight for 3-5 days. Due to potential thrombophlebitis, it’s best to administer hemin in a high-flow central vein via a peripherally inserted central catheter or central port.

In addition, treatment for acute attacks should include analgesics, antiemetics, and management of systemic arterial hypertension, tachycardia, hyponatremia, and hypomagnesemia. The primary goal of treatment during an acute attack is to decrease ALA production. Patients should be counseled to avoid identifiable triggers, such as porphyrinogenic medications, excess alcohol intake, tobacco use, and caloric deprivation.

Although recent advances have improved treatment for acute attacks, management for patients with frequent attacks remains challenging, the study authors wrote. About 3%-5% of patients with symptomatic AHP experience recurrent attacks, which is defined as four or more attacks per year. These attacks aren’t typically associated with identifiable triggers, although some that occur during the luteal phase of a patient’s menstrual cycle are believed to be triggered by progesterone. However, treatment with hormonal suppression therapy, such as GnRH agonists, has had limited success.

Off-label use of prophylactic intravenous heme therapy is common, although the effectiveness in preventing recurrent attacks isn’t well-established. In addition, chronic hemin use is associated with several complications, including infections, iron overload, and the need for indwelling central venous catheters.

Recently, the Food and Drug Administration approved givosiran, a small interfering RNA-based therapy that targets delta-aminolevulinate synthase 1, for treatment in adults with AHP. Monthly subcutaneous therapy appears to significantly lower rates of acute attacks among patients who experience recurrent attacks.

“We suggest prescribing givosiran only for those patients with recurrent acute attacks that are both biochemically and genetically confirmed,” the authors wrote. “Due to limited safety data, givosiran should not be used in women who are pregnant or planning a pregnancy.”

In the most severe cases, liver transplantation should be limited to patients with intractable symptoms and a significantly decreased quality of life who are refractory to pharmacotherapy. If living donor transplantation is considered, genetic testing should be used to screen related living donors since HMBS pathogenic variants in asymptomatic donors could results in poor posttransplantation outcomes.

In the long-term, patients with AHP should be monitored annually for liver disease and chronic kidney disease with serum creatinine and estimated glomerular filtration rate monitored. Patients also face an increased risk of hepatocellular carcinoma and should start screening at age 50, with a liver ultrasound every 6 months.

“Fortunately, most people with genetic defects never experience severe acute attacks or may experience only one or a few attacks throughout their lives,” the authors wrote.

The authors (Bruce Wang, MD, Herbert L. Bonkovsky, MD, AGAF, and Manisha Balwani, MD, MS) reported that they are part of the Porphyrias Consortium. The Porphyrias Consortium is part of the Rare Diseases Clinical Research Network, an initiative of the Division of Rare Diseases Research Innovation at the National Center for Advancing Translational Sciences. The consortium is funded through a collaboration between the center and the National Institute of Diabetes and Digestive and Kidney Diseases. Several authors disclosed funding support and honoraria for advisory board roles with various pharmaceutical companies, including Alnylam, which makes givosiran.

This article was updated 2/3/23.

The Food and Drug Administration has granted accelerated approval to pirtobrutinib (Jaypirca) for relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a Bruton’s tyrosine kinase inhibitor.

Pirtobrutinib is the first and only noncovalent Bruton’s tyrosine kinase inhibitor approved for use in this MCL setting, manufacturer Eli Lilly noted in a press release.

“The approval of Jaypirca represents an important advance for patients with relapsed or refractory MCL, who currently have limited options and historically have had a poor prognosis following discontinuation of treatment with a covalent Bruton’s tyrosine kinase inhibitor,” senior author Michael Wang, MD, University of Texas MD Anderson Cancer Center, Houston, said in the release.

The approval was based on efficacy demonstrated in the open-label, single-arm, phase 1/2 BRUIN trial – a multicenter study assessing 200 mg once-daily oral pirtobrutinib monotherapy in 120 patients with MCL who had previously received a Bruton’s tyrosine kinase inhibitor, most often ibrutinib (Imbruvica, 67%) acalabrutinib (Calquence, 30%) and zanubrutinib (Brukinsa, 8%). Pirtobrutinib was continued until disease progression or unacceptable toxicity.

Study participants had a median of three prior lines of therapy, and 83% discontinued their last Bruton’s tyrosine kinase inhibitor because of refractory or progressive disease.

The overall response rate in pirtobrutinib-treated patients was 50% with a complete response rate of 13%. Estimated median duration of response was 8.3 months, and the estimated duration of response at 6 months occurred in nearly two-thirds of patients.

Adverse reactions that occurred in at least 15% of patients included fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, and bruising. Grade 3 or 4 laboratory abnormalities occurring in at least 10% of patients included decreased neutrophil counts, lymphocyte counts, and platelet counts.

Prescribing information for pirtobrutinib includes warnings and precautions for infections, hemorrhage, cytopenias, atrial fibrillation and flutter, and second primary malignancies, noted the FDA, which granted priority review, fast track designation, and orphan drug designation for the application submitted by Eli Lilly.

“Jaypirca can reestablish Bruton’s tyrosine kinase inhibition in MCL patients previously treated with a covalent Bruton’s tyrosine kinase inhibitor (ibrutinib, acalabrutinib, or zanubrutinib) and extend the benefit of targeting the Bruton’s tyrosine kinase pathway,” according to Eli Lilly’s release.

Dr. Wang added that the agent “has the potential to meaningfully impact the treatment paradigm for relapsed and refractory MCL patients.”

Meghan Gutierrez, CEO at the Lymphoma Research Foundation, also noted that “the approval of Jaypirca brings a new treatment option and, along with that, new hope for people with relapsed or refractory MCL.”

The drug is expected to be available in the United States in the coming weeks, and the confirmatory phase 3 BRUIN trial is currently enrolling patients, Eli Lilly announced. The company also indicated the list price would be $21,000 for a 30-day supply of the 200-mg dose.

Serious adverse events believed to be associated with the use of pirtobrutinib or any medicine or device should be reported to the FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

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

The Food and Drug Administration has granted accelerated approval to pirtobrutinib (Jaypirca) for relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a Bruton’s tyrosine kinase inhibitor.

Pirtobrutinib is the first and only noncovalent Bruton’s tyrosine kinase inhibitor approved for use in this MCL setting, manufacturer Eli Lilly noted in a press release.

“The approval of Jaypirca represents an important advance for patients with relapsed or refractory MCL, who currently have limited options and historically have had a poor prognosis following discontinuation of treatment with a covalent Bruton’s tyrosine kinase inhibitor,” senior author Michael Wang, MD, University of Texas MD Anderson Cancer Center, Houston, said in the release.

The approval was based on efficacy demonstrated in the open-label, single-arm, phase 1/2 BRUIN trial – a multicenter study assessing 200 mg once-daily oral pirtobrutinib monotherapy in 120 patients with MCL who had previously received a Bruton’s tyrosine kinase inhibitor, most often ibrutinib (Imbruvica, 67%) acalabrutinib (Calquence, 30%) and zanubrutinib (Brukinsa, 8%). Pirtobrutinib was continued until disease progression or unacceptable toxicity.

Study participants had a median of three prior lines of therapy, and 83% discontinued their last Bruton’s tyrosine kinase inhibitor because of refractory or progressive disease.

The overall response rate in pirtobrutinib-treated patients was 50% with a complete response rate of 13%. Estimated median duration of response was 8.3 months, and the estimated duration of response at 6 months occurred in nearly two-thirds of patients.

Adverse reactions that occurred in at least 15% of patients included fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, and bruising. Grade 3 or 4 laboratory abnormalities occurring in at least 10% of patients included decreased neutrophil counts, lymphocyte counts, and platelet counts.

Prescribing information for pirtobrutinib includes warnings and precautions for infections, hemorrhage, cytopenias, atrial fibrillation and flutter, and second primary malignancies, noted the FDA, which granted priority review, fast track designation, and orphan drug designation for the application submitted by Eli Lilly.

“Jaypirca can reestablish Bruton’s tyrosine kinase inhibition in MCL patients previously treated with a covalent Bruton’s tyrosine kinase inhibitor (ibrutinib, acalabrutinib, or zanubrutinib) and extend the benefit of targeting the Bruton’s tyrosine kinase pathway,” according to Eli Lilly’s release.

Dr. Wang added that the agent “has the potential to meaningfully impact the treatment paradigm for relapsed and refractory MCL patients.”

Meghan Gutierrez, CEO at the Lymphoma Research Foundation, also noted that “the approval of Jaypirca brings a new treatment option and, along with that, new hope for people with relapsed or refractory MCL.”

The drug is expected to be available in the United States in the coming weeks, and the confirmatory phase 3 BRUIN trial is currently enrolling patients, Eli Lilly announced. The company also indicated the list price would be $21,000 for a 30-day supply of the 200-mg dose.

Serious adverse events believed to be associated with the use of pirtobrutinib or any medicine or device should be reported to the FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

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

The Food and Drug Administration has granted accelerated approval to pirtobrutinib (Jaypirca) for relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a Bruton’s tyrosine kinase inhibitor.

Pirtobrutinib is the first and only noncovalent Bruton’s tyrosine kinase inhibitor approved for use in this MCL setting, manufacturer Eli Lilly noted in a press release.

“The approval of Jaypirca represents an important advance for patients with relapsed or refractory MCL, who currently have limited options and historically have had a poor prognosis following discontinuation of treatment with a covalent Bruton’s tyrosine kinase inhibitor,” senior author Michael Wang, MD, University of Texas MD Anderson Cancer Center, Houston, said in the release.

The approval was based on efficacy demonstrated in the open-label, single-arm, phase 1/2 BRUIN trial – a multicenter study assessing 200 mg once-daily oral pirtobrutinib monotherapy in 120 patients with MCL who had previously received a Bruton’s tyrosine kinase inhibitor, most often ibrutinib (Imbruvica, 67%) acalabrutinib (Calquence, 30%) and zanubrutinib (Brukinsa, 8%). Pirtobrutinib was continued until disease progression or unacceptable toxicity.

Study participants had a median of three prior lines of therapy, and 83% discontinued their last Bruton’s tyrosine kinase inhibitor because of refractory or progressive disease.

The overall response rate in pirtobrutinib-treated patients was 50% with a complete response rate of 13%. Estimated median duration of response was 8.3 months, and the estimated duration of response at 6 months occurred in nearly two-thirds of patients.

Adverse reactions that occurred in at least 15% of patients included fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, and bruising. Grade 3 or 4 laboratory abnormalities occurring in at least 10% of patients included decreased neutrophil counts, lymphocyte counts, and platelet counts.

Prescribing information for pirtobrutinib includes warnings and precautions for infections, hemorrhage, cytopenias, atrial fibrillation and flutter, and second primary malignancies, noted the FDA, which granted priority review, fast track designation, and orphan drug designation for the application submitted by Eli Lilly.

“Jaypirca can reestablish Bruton’s tyrosine kinase inhibition in MCL patients previously treated with a covalent Bruton’s tyrosine kinase inhibitor (ibrutinib, acalabrutinib, or zanubrutinib) and extend the benefit of targeting the Bruton’s tyrosine kinase pathway,” according to Eli Lilly’s release.

Dr. Wang added that the agent “has the potential to meaningfully impact the treatment paradigm for relapsed and refractory MCL patients.”

Meghan Gutierrez, CEO at the Lymphoma Research Foundation, also noted that “the approval of Jaypirca brings a new treatment option and, along with that, new hope for people with relapsed or refractory MCL.”

The drug is expected to be available in the United States in the coming weeks, and the confirmatory phase 3 BRUIN trial is currently enrolling patients, Eli Lilly announced. The company also indicated the list price would be $21,000 for a 30-day supply of the 200-mg dose.

Serious adverse events believed to be associated with the use of pirtobrutinib or any medicine or device should be reported to the FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

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

Two out of three patients diagnosed with breast cancer are found to have the HR+/HER2- subtype, and over time, at least one third of patients with this subtype develop metastatic disease. But recent advances in the treatment of both early and metastatic HR+/HER2- disease have resulted in significant improvement in outcomes.

In this panel ReCAP, Drs Kathy Miller from Indiana University and Alexandra Thomas from Wake Forest University review how progress in treatment has affected outcomes across all stages of HR+/HER2- breast cancer.

They report that the use of trastuzumab deruxtecan in the metastatic setting improves overall survival. They also discuss how adjuvant use of abemaciclib in early-stage breast cancer improves disease-free survival, as evidenced by the latest updates of the monarchE trial, now providing 4 years of follow-up.

--

Ballvé-Lantero Professor of Oncology, Indiana University School of Medicine, Indianapolis, Indiana

Kathy D. Miller, MD, has disclosed the following relevant financial relationships:

Serve on independent Data Monitoring Committees for ongoing trials for: Merck; Genentech/Roche; AstraZeneca; Celcuity

Two out of three patients diagnosed with breast cancer are found to have the HR+/HER2- subtype, and over time, at least one third of patients with this subtype develop metastatic disease. But recent advances in the treatment of both early and metastatic HR+/HER2- disease have resulted in significant improvement in outcomes.

In this panel ReCAP, Drs Kathy Miller from Indiana University and Alexandra Thomas from Wake Forest University review how progress in treatment has affected outcomes across all stages of HR+/HER2- breast cancer.

They report that the use of trastuzumab deruxtecan in the metastatic setting improves overall survival. They also discuss how adjuvant use of abemaciclib in early-stage breast cancer improves disease-free survival, as evidenced by the latest updates of the monarchE trial, now providing 4 years of follow-up.

--

Ballvé-Lantero Professor of Oncology, Indiana University School of Medicine, Indianapolis, Indiana

Kathy D. Miller, MD, has disclosed the following relevant financial relationships:

Serve on independent Data Monitoring Committees for ongoing trials for: Merck; Genentech/Roche; AstraZeneca; Celcuity

Two out of three patients diagnosed with breast cancer are found to have the HR+/HER2- subtype, and over time, at least one third of patients with this subtype develop metastatic disease. But recent advances in the treatment of both early and metastatic HR+/HER2- disease have resulted in significant improvement in outcomes.

In this panel ReCAP, Drs Kathy Miller from Indiana University and Alexandra Thomas from Wake Forest University review how progress in treatment has affected outcomes across all stages of HR+/HER2- breast cancer.

They report that the use of trastuzumab deruxtecan in the metastatic setting improves overall survival. They also discuss how adjuvant use of abemaciclib in early-stage breast cancer improves disease-free survival, as evidenced by the latest updates of the monarchE trial, now providing 4 years of follow-up.

--

Ballvé-Lantero Professor of Oncology, Indiana University School of Medicine, Indianapolis, Indiana

Kathy D. Miller, MD, has disclosed the following relevant financial relationships:

Serve on independent Data Monitoring Committees for ongoing trials for: Merck; Genentech/Roche; AstraZeneca; Celcuity

An international group of physicians has issued consensus recommendations for the diagnosis and management of patients with early-onset colorectal cancer (eoCRC).

Led by Giulia Martina Cavestro, MD, PhD, a gastroenterologist with the University Vita Salute San Raffaele Hospital, Milan, the Delphi Initiative for Early-Onset Colorectal Cancer group penned 31 recommendations for treating patients 50 years and younger, several of which were highlighted as “strong.” The recommendations are based on a review of 145 studies.

“There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery,” the authors wrote.

Colorectal cancer in men and women under age 50 years has been increasing since the 1990s in both low and high-income countries even as cases decline among individuals over 50 years old because of changes in lifestyle and screening programs.

Published in Clinical Gastroenterology and Hepatology, it represents the first consensus statement for eoCRC. Current knowledge gaps include determination of the need for surgical, adjuvant, neoadjuvant, and supportive treatment.

The recommendations include 31 statements spread over seven broad categories: Diagnosis, risk factors, genetics, patho-oncology, therapy, endoscopy, and supportive care.

In regards to diagnosis, any individual with alarming symptoms under the age of 50 should be assessed for CRC. Alarming symptoms include, but are not limited to, hematochezia, unexplained iron-deficiency anemia, or unexplained weight loss. A colonoscopy should be scheduled ideally within 30 days of seeing a physician. The preferred method is high-quality, high-definition white-light endoscopy.

Also, a risk assessment should be included. Any family history of CRC and/or a personal history of risk factors and comorbidities could identify high-risk individuals. About 28% of patients with early onset disease have a family history of colorectal cancer, which is similar to the frequency seen in late onset CRC.

After diagnosis, all patients should undergo germline genetic testing, ideally before surgery because it may influence treatment decisions. All tumors should be evaluated for mismatch repair phenotype (with either immunohistochemistry staining for MMR proteins or microsatellite instability testing) preferably before treatment. Age alone, the authors emphasized, shouldn’t drive decisions on endoscopic, surgical, and oncologic treatment.

Germline genetic testing should include APC, BMPR1A, EPCAM, MLH1, MSH2, MSH6, MUTYH, POLD1, POLE, PMS2, PTEN, SMAD4, STK11, and TP53. Other testing candidates, when not cost prohibitive, include genes that are somewhat common and can influence clinical management: BRCA1, BRCA2, ATM, CHEK2, and PALB2. Testing could also include genes that are less prevalent but that can also influence clinical management: BRIP1, BARD1, CDKN2A, CDH1, RAD51C and RAD51D. When not cost prohibitive, genetic testing can also include genes associated with CRC or polyposis, which include AXIN2, GREM1, MLH3, MSH3, MBD4, NTHL1, RNF43, and RPS20.

In terms of treatment, there is no evidence that neoadjuvant, adjuvant, or systemic therapies should differ between eoCRC and late-onset patients. Endoscopic, surgical, and oncologic treatment should be similar to older patients, but treatment options should be individualized based on factors that could include greater risk of metachronous CRC, germline and somatic testing results, concerns about fertility, concomitant indications for gynecologic cancer, and heightened risk of chemotherapy-induced nausea and vomiting.

After treatment, patients should receive standard surveillance at 1 and 3 years, and colonoscopies should be performed at least every 5 years. Those with hereditary CRC should receive surveillance based on their specific variant and phenotype.

All eoCRC patients should be counseled regarding fertility preservation and the potential impacts of treatments on fertility, and they should also receive psychosocial support. Patients who are at high risk of gynecologic cancers resulting from pathogenic or syndromic probable pathogenic variants can undergo prophylactic hysterectomy with or without bilateral oophorectomy. Fertility preservation options can be considered based on the estimated risk of gonadotoxicity, known risks of the treatment plan, and disease stage and severity.

Supportive care for eoCRC should be similar to the general population, though they may be at greater risk of chemotherapy-induced nausea and vomiting than late-onset patients, especially females with low body mass index. Other supportive interventions can include early personalized physical activity and nutritional support to maintain and recover muscle mass, as well as psychosocial or psychosexual counseling regarding the impact of treatments and the illness on sexual health.

The authors call for more research, specifically in the areas of risks and benefits of screening young populations who are at average or increased risk for CRC; identifying risk factors for eoCRC; outcomes research on neoadjuvant, adjuvant, and systemic therapies in eoCRC populations; comparison of long-term outcomes following surgical and endoscopic resections; and optimal follow-up and surveillance strategies following curative resection.

The recommendations were endorsed by the Associazione Italiana Familiarità, Ereditarietà Tumori, the Collaborative Group of the Americas on Inherited Gastrointestinal Cancers, the European Hereditary Tumor Group, and the International Society for Gastrointestinal Hereditary Tumours.

An international group of physicians has issued consensus recommendations for the diagnosis and management of patients with early-onset colorectal cancer (eoCRC).

Led by Giulia Martina Cavestro, MD, PhD, a gastroenterologist with the University Vita Salute San Raffaele Hospital, Milan, the Delphi Initiative for Early-Onset Colorectal Cancer group penned 31 recommendations for treating patients 50 years and younger, several of which were highlighted as “strong.” The recommendations are based on a review of 145 studies.

“There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery,” the authors wrote.

Colorectal cancer in men and women under age 50 years has been increasing since the 1990s in both low and high-income countries even as cases decline among individuals over 50 years old because of changes in lifestyle and screening programs.

Published in Clinical Gastroenterology and Hepatology, it represents the first consensus statement for eoCRC. Current knowledge gaps include determination of the need for surgical, adjuvant, neoadjuvant, and supportive treatment.

The recommendations include 31 statements spread over seven broad categories: Diagnosis, risk factors, genetics, patho-oncology, therapy, endoscopy, and supportive care.

In regards to diagnosis, any individual with alarming symptoms under the age of 50 should be assessed for CRC. Alarming symptoms include, but are not limited to, hematochezia, unexplained iron-deficiency anemia, or unexplained weight loss. A colonoscopy should be scheduled ideally within 30 days of seeing a physician. The preferred method is high-quality, high-definition white-light endoscopy.

Also, a risk assessment should be included. Any family history of CRC and/or a personal history of risk factors and comorbidities could identify high-risk individuals. About 28% of patients with early onset disease have a family history of colorectal cancer, which is similar to the frequency seen in late onset CRC.

After diagnosis, all patients should undergo germline genetic testing, ideally before surgery because it may influence treatment decisions. All tumors should be evaluated for mismatch repair phenotype (with either immunohistochemistry staining for MMR proteins or microsatellite instability testing) preferably before treatment. Age alone, the authors emphasized, shouldn’t drive decisions on endoscopic, surgical, and oncologic treatment.

Germline genetic testing should include APC, BMPR1A, EPCAM, MLH1, MSH2, MSH6, MUTYH, POLD1, POLE, PMS2, PTEN, SMAD4, STK11, and TP53. Other testing candidates, when not cost prohibitive, include genes that are somewhat common and can influence clinical management: BRCA1, BRCA2, ATM, CHEK2, and PALB2. Testing could also include genes that are less prevalent but that can also influence clinical management: BRIP1, BARD1, CDKN2A, CDH1, RAD51C and RAD51D. When not cost prohibitive, genetic testing can also include genes associated with CRC or polyposis, which include AXIN2, GREM1, MLH3, MSH3, MBD4, NTHL1, RNF43, and RPS20.

In terms of treatment, there is no evidence that neoadjuvant, adjuvant, or systemic therapies should differ between eoCRC and late-onset patients. Endoscopic, surgical, and oncologic treatment should be similar to older patients, but treatment options should be individualized based on factors that could include greater risk of metachronous CRC, germline and somatic testing results, concerns about fertility, concomitant indications for gynecologic cancer, and heightened risk of chemotherapy-induced nausea and vomiting.

After treatment, patients should receive standard surveillance at 1 and 3 years, and colonoscopies should be performed at least every 5 years. Those with hereditary CRC should receive surveillance based on their specific variant and phenotype.

All eoCRC patients should be counseled regarding fertility preservation and the potential impacts of treatments on fertility, and they should also receive psychosocial support. Patients who are at high risk of gynecologic cancers resulting from pathogenic or syndromic probable pathogenic variants can undergo prophylactic hysterectomy with or without bilateral oophorectomy. Fertility preservation options can be considered based on the estimated risk of gonadotoxicity, known risks of the treatment plan, and disease stage and severity.

Supportive care for eoCRC should be similar to the general population, though they may be at greater risk of chemotherapy-induced nausea and vomiting than late-onset patients, especially females with low body mass index. Other supportive interventions can include early personalized physical activity and nutritional support to maintain and recover muscle mass, as well as psychosocial or psychosexual counseling regarding the impact of treatments and the illness on sexual health.

The authors call for more research, specifically in the areas of risks and benefits of screening young populations who are at average or increased risk for CRC; identifying risk factors for eoCRC; outcomes research on neoadjuvant, adjuvant, and systemic therapies in eoCRC populations; comparison of long-term outcomes following surgical and endoscopic resections; and optimal follow-up and surveillance strategies following curative resection.

The recommendations were endorsed by the Associazione Italiana Familiarità, Ereditarietà Tumori, the Collaborative Group of the Americas on Inherited Gastrointestinal Cancers, the European Hereditary Tumor Group, and the International Society for Gastrointestinal Hereditary Tumours.

An international group of physicians has issued consensus recommendations for the diagnosis and management of patients with early-onset colorectal cancer (eoCRC).

Led by Giulia Martina Cavestro, MD, PhD, a gastroenterologist with the University Vita Salute San Raffaele Hospital, Milan, the Delphi Initiative for Early-Onset Colorectal Cancer group penned 31 recommendations for treating patients 50 years and younger, several of which were highlighted as “strong.” The recommendations are based on a review of 145 studies.

“There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery,” the authors wrote.

Colorectal cancer in men and women under age 50 years has been increasing since the 1990s in both low and high-income countries even as cases decline among individuals over 50 years old because of changes in lifestyle and screening programs.

Published in Clinical Gastroenterology and Hepatology, it represents the first consensus statement for eoCRC. Current knowledge gaps include determination of the need for surgical, adjuvant, neoadjuvant, and supportive treatment.

The recommendations include 31 statements spread over seven broad categories: Diagnosis, risk factors, genetics, patho-oncology, therapy, endoscopy, and supportive care.

In regards to diagnosis, any individual with alarming symptoms under the age of 50 should be assessed for CRC. Alarming symptoms include, but are not limited to, hematochezia, unexplained iron-deficiency anemia, or unexplained weight loss. A colonoscopy should be scheduled ideally within 30 days of seeing a physician. The preferred method is high-quality, high-definition white-light endoscopy.

Also, a risk assessment should be included. Any family history of CRC and/or a personal history of risk factors and comorbidities could identify high-risk individuals. About 28% of patients with early onset disease have a family history of colorectal cancer, which is similar to the frequency seen in late onset CRC.

After diagnosis, all patients should undergo germline genetic testing, ideally before surgery because it may influence treatment decisions. All tumors should be evaluated for mismatch repair phenotype (with either immunohistochemistry staining for MMR proteins or microsatellite instability testing) preferably before treatment. Age alone, the authors emphasized, shouldn’t drive decisions on endoscopic, surgical, and oncologic treatment.

Germline genetic testing should include APC, BMPR1A, EPCAM, MLH1, MSH2, MSH6, MUTYH, POLD1, POLE, PMS2, PTEN, SMAD4, STK11, and TP53. Other testing candidates, when not cost prohibitive, include genes that are somewhat common and can influence clinical management: BRCA1, BRCA2, ATM, CHEK2, and PALB2. Testing could also include genes that are less prevalent but that can also influence clinical management: BRIP1, BARD1, CDKN2A, CDH1, RAD51C and RAD51D. When not cost prohibitive, genetic testing can also include genes associated with CRC or polyposis, which include AXIN2, GREM1, MLH3, MSH3, MBD4, NTHL1, RNF43, and RPS20.

In terms of treatment, there is no evidence that neoadjuvant, adjuvant, or systemic therapies should differ between eoCRC and late-onset patients. Endoscopic, surgical, and oncologic treatment should be similar to older patients, but treatment options should be individualized based on factors that could include greater risk of metachronous CRC, germline and somatic testing results, concerns about fertility, concomitant indications for gynecologic cancer, and heightened risk of chemotherapy-induced nausea and vomiting.

After treatment, patients should receive standard surveillance at 1 and 3 years, and colonoscopies should be performed at least every 5 years. Those with hereditary CRC should receive surveillance based on their specific variant and phenotype.

All eoCRC patients should be counseled regarding fertility preservation and the potential impacts of treatments on fertility, and they should also receive psychosocial support. Patients who are at high risk of gynecologic cancers resulting from pathogenic or syndromic probable pathogenic variants can undergo prophylactic hysterectomy with or without bilateral oophorectomy. Fertility preservation options can be considered based on the estimated risk of gonadotoxicity, known risks of the treatment plan, and disease stage and severity.

Supportive care for eoCRC should be similar to the general population, though they may be at greater risk of chemotherapy-induced nausea and vomiting than late-onset patients, especially females with low body mass index. Other supportive interventions can include early personalized physical activity and nutritional support to maintain and recover muscle mass, as well as psychosocial or psychosexual counseling regarding the impact of treatments and the illness on sexual health.

The authors call for more research, specifically in the areas of risks and benefits of screening young populations who are at average or increased risk for CRC; identifying risk factors for eoCRC; outcomes research on neoadjuvant, adjuvant, and systemic therapies in eoCRC populations; comparison of long-term outcomes following surgical and endoscopic resections; and optimal follow-up and surveillance strategies following curative resection.

The recommendations were endorsed by the Associazione Italiana Familiarità, Ereditarietà Tumori, the Collaborative Group of the Americas on Inherited Gastrointestinal Cancers, the European Hereditary Tumor Group, and the International Society for Gastrointestinal Hereditary Tumours.

Vidyard Video

Additional videos from SGS are available here, including these recent offerings:

• Tips and tricks for a successful rollerball endometrial ablation
• Resection of infected sacrohysteropexy mesh
• Surgical techniques for excision of juvenile cystic adenomyoma

Vidyard Video

Additional videos from SGS are available here, including these recent offerings:

• Tips and tricks for a successful rollerball endometrial ablation
• Resection of infected sacrohysteropexy mesh
• Surgical techniques for excision of juvenile cystic adenomyoma

Vidyard Video

Additional videos from SGS are available here, including these recent offerings:

• Tips and tricks for a successful rollerball endometrial ablation
• Resection of infected sacrohysteropexy mesh
• Surgical techniques for excision of juvenile cystic adenomyoma

The elevated risk for recurrence in young women with HR+ early breast cancer highlights the importance of aggressive endocrine therapy in the majority of patients in this population. Examples of approaches to maximize endocrine therapy benefit include the addition of ovarian suppression to either tamoxifen or an aromatase inhibitor (AI) as well as an extended duration of adjuvant endocrine therapy.^4,5 Among 3047 premenopausal women included in SOFT study, at 12 years follow-up, the addition of ovarian function suppression (OFS) to tamoxifen significantly improved disease-free survival (DFS) compared with tamoxifen alone (hazard ratio 0.82; P = .03) with a more pronounced DFS benefit with exemestane plus OFS compared with tamoxifen (hazard ratio 0.69) (Francis et al). In the HER2- subgroup, those who received prior chemotherapy had 12-year OFS rates of 78.8% with tamoxifen, 81.1% with tamoxifen plus OFS and 84.4% with exemestane plus OFS. Furthermore, in the HER2- subgroup, women younger than 35 years had absolute improvements in 12-year OS of 9.1% with tamoxifen plus OFS and 16.5% with exemestane plus OFS compared with tamoxifen. These updated results provide further support for OFS added to tamoxifen or an AI (with more benefit seen with an AI) in the treatment of HR+ early breast cancer in young women who are at high risk for recurrence. Longer follow-up will be important to better define the treatment effect considering recurrence patterns for this subtype of breast cancer.

Various guidelines recommend the use of adjuvant bisphosphonates for postmenopausal patients with early breast cancer on the basis of disease-free and bone metastasis-free survival benefits.⁶ A regimen of zolendronic acid every 6 months for 3 years is commonly used in clinical practice. A substudy of ABCSG-12, including 725 premenopausal patients with HR+ early breast cancer on ovarian suppression randomly assigned to receive tamoxifen or anastrozole with or without zolendronic acid every 6 months, investigated the effect of shorter duration of bisphosphonate therapy on breast cancer outcomes (Beltran-Bless et al). After a median follow-up of 96 months, there was no statistically significant difference in DFS (hazard ratio 0.88; log-rank P = .642) or OS (stratified hazard ratio 1.16; log-rank P = .796) between patients who received ≤6 or ≥7 infusions. Rates of adverse events were increased in the patients who received ≥7 or ≤6 infusions (arthralgia, 20.1% vs 12.4%; nausea, 12.8% vs 7.3%; bone pain, 41.6% vs 34.9%). Modifications to adjuvant breast cancer regimens that can provide more ease for patients with less toxicity while maintaining efficacy are greatly desired to simultaneously support quality of life and disease outcomes.

Additional References

1. Swain SM, Baselga J, Kim SB, et al; for the CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015;372:724-734. Doi: 10.1056/NEJMoa1413513
2. Miles D, Ciruelos E, Schneeweiss A, et al; for the PERUSE investigators. Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication. Ann Oncol. 2021;32:1245-1255. Doi: 10.1016/j.annonc.2021.06.024
3. Hua X, Bi X-W, Zhao J-L, et al; for the South China Breast Cancer Group (SCBCG). Trastuzumab plus endocrine therapy or chemotherapy as first-line treatment for patients with hormone receptor-positive and HER2-positive metastatic breast cancer (SYSUCC-002). Clin Cancer Res. 2022;28:637-645. Doi: 10.1158/1078-0432.CCR-21-3435
4. Kim H-A, Lee JW, Nam SJ, et al; for the Korean Breast Cancer Study Group. Adding ovarian suppression to tamoxifen for premenopausal breast Cancer: a randomized phase III trial. J Clin Oncol. 2020;38:434-443. Doi: 10.1200/JCO.19.00126
5. Davies C, Pan H, Godwin J, et al; for the Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) Collaborative Group. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013;381:805-816. Doi: 10.1016/S0140-6736(12)61963-1
6. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials. Lancet. 2015;386:1353-1361. Doi: 10.1016/S0140-6736(15)60908-4

The elevated risk for recurrence in young women with HR+ early breast cancer highlights the importance of aggressive endocrine therapy in the majority of patients in this population. Examples of approaches to maximize endocrine therapy benefit include the addition of ovarian suppression to either tamoxifen or an aromatase inhibitor (AI) as well as an extended duration of adjuvant endocrine therapy.^4,5 Among 3047 premenopausal women included in SOFT study, at 12 years follow-up, the addition of ovarian function suppression (OFS) to tamoxifen significantly improved disease-free survival (DFS) compared with tamoxifen alone (hazard ratio 0.82; P = .03) with a more pronounced DFS benefit with exemestane plus OFS compared with tamoxifen (hazard ratio 0.69) (Francis et al). In the HER2- subgroup, those who received prior chemotherapy had 12-year OFS rates of 78.8% with tamoxifen, 81.1% with tamoxifen plus OFS and 84.4% with exemestane plus OFS. Furthermore, in the HER2- subgroup, women younger than 35 years had absolute improvements in 12-year OS of 9.1% with tamoxifen plus OFS and 16.5% with exemestane plus OFS compared with tamoxifen. These updated results provide further support for OFS added to tamoxifen or an AI (with more benefit seen with an AI) in the treatment of HR+ early breast cancer in young women who are at high risk for recurrence. Longer follow-up will be important to better define the treatment effect considering recurrence patterns for this subtype of breast cancer.

Various guidelines recommend the use of adjuvant bisphosphonates for postmenopausal patients with early breast cancer on the basis of disease-free and bone metastasis-free survival benefits.⁶ A regimen of zolendronic acid every 6 months for 3 years is commonly used in clinical practice. A substudy of ABCSG-12, including 725 premenopausal patients with HR+ early breast cancer on ovarian suppression randomly assigned to receive tamoxifen or anastrozole with or without zolendronic acid every 6 months, investigated the effect of shorter duration of bisphosphonate therapy on breast cancer outcomes (Beltran-Bless et al). After a median follow-up of 96 months, there was no statistically significant difference in DFS (hazard ratio 0.88; log-rank P = .642) or OS (stratified hazard ratio 1.16; log-rank P = .796) between patients who received ≤6 or ≥7 infusions. Rates of adverse events were increased in the patients who received ≥7 or ≤6 infusions (arthralgia, 20.1% vs 12.4%; nausea, 12.8% vs 7.3%; bone pain, 41.6% vs 34.9%). Modifications to adjuvant breast cancer regimens that can provide more ease for patients with less toxicity while maintaining efficacy are greatly desired to simultaneously support quality of life and disease outcomes.

Additional References

1. Swain SM, Baselga J, Kim SB, et al; for the CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015;372:724-734. Doi: 10.1056/NEJMoa1413513
2. Miles D, Ciruelos E, Schneeweiss A, et al; for the PERUSE investigators. Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication. Ann Oncol. 2021;32:1245-1255. Doi: 10.1016/j.annonc.2021.06.024
3. Hua X, Bi X-W, Zhao J-L, et al; for the South China Breast Cancer Group (SCBCG). Trastuzumab plus endocrine therapy or chemotherapy as first-line treatment for patients with hormone receptor-positive and HER2-positive metastatic breast cancer (SYSUCC-002). Clin Cancer Res. 2022;28:637-645. Doi: 10.1158/1078-0432.CCR-21-3435
4. Kim H-A, Lee JW, Nam SJ, et al; for the Korean Breast Cancer Study Group. Adding ovarian suppression to tamoxifen for premenopausal breast Cancer: a randomized phase III trial. J Clin Oncol. 2020;38:434-443. Doi: 10.1200/JCO.19.00126
5. Davies C, Pan H, Godwin J, et al; for the Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) Collaborative Group. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013;381:805-816. Doi: 10.1016/S0140-6736(12)61963-1
6. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials. Lancet. 2015;386:1353-1361. Doi: 10.1016/S0140-6736(15)60908-4

The elevated risk for recurrence in young women with HR+ early breast cancer highlights the importance of aggressive endocrine therapy in the majority of patients in this population. Examples of approaches to maximize endocrine therapy benefit include the addition of ovarian suppression to either tamoxifen or an aromatase inhibitor (AI) as well as an extended duration of adjuvant endocrine therapy.^4,5 Among 3047 premenopausal women included in SOFT study, at 12 years follow-up, the addition of ovarian function suppression (OFS) to tamoxifen significantly improved disease-free survival (DFS) compared with tamoxifen alone (hazard ratio 0.82; P = .03) with a more pronounced DFS benefit with exemestane plus OFS compared with tamoxifen (hazard ratio 0.69) (Francis et al). In the HER2- subgroup, those who received prior chemotherapy had 12-year OFS rates of 78.8% with tamoxifen, 81.1% with tamoxifen plus OFS and 84.4% with exemestane plus OFS. Furthermore, in the HER2- subgroup, women younger than 35 years had absolute improvements in 12-year OS of 9.1% with tamoxifen plus OFS and 16.5% with exemestane plus OFS compared with tamoxifen. These updated results provide further support for OFS added to tamoxifen or an AI (with more benefit seen with an AI) in the treatment of HR+ early breast cancer in young women who are at high risk for recurrence. Longer follow-up will be important to better define the treatment effect considering recurrence patterns for this subtype of breast cancer.

Various guidelines recommend the use of adjuvant bisphosphonates for postmenopausal patients with early breast cancer on the basis of disease-free and bone metastasis-free survival benefits.⁶ A regimen of zolendronic acid every 6 months for 3 years is commonly used in clinical practice. A substudy of ABCSG-12, including 725 premenopausal patients with HR+ early breast cancer on ovarian suppression randomly assigned to receive tamoxifen or anastrozole with or without zolendronic acid every 6 months, investigated the effect of shorter duration of bisphosphonate therapy on breast cancer outcomes (Beltran-Bless et al). After a median follow-up of 96 months, there was no statistically significant difference in DFS (hazard ratio 0.88; log-rank P = .642) or OS (stratified hazard ratio 1.16; log-rank P = .796) between patients who received ≤6 or ≥7 infusions. Rates of adverse events were increased in the patients who received ≥7 or ≤6 infusions (arthralgia, 20.1% vs 12.4%; nausea, 12.8% vs 7.3%; bone pain, 41.6% vs 34.9%). Modifications to adjuvant breast cancer regimens that can provide more ease for patients with less toxicity while maintaining efficacy are greatly desired to simultaneously support quality of life and disease outcomes.

Additional References

1. Swain SM, Baselga J, Kim SB, et al; for the CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015;372:724-734. Doi: 10.1056/NEJMoa1413513
2. Miles D, Ciruelos E, Schneeweiss A, et al; for the PERUSE investigators. Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication. Ann Oncol. 2021;32:1245-1255. Doi: 10.1016/j.annonc.2021.06.024
3. Hua X, Bi X-W, Zhao J-L, et al; for the South China Breast Cancer Group (SCBCG). Trastuzumab plus endocrine therapy or chemotherapy as first-line treatment for patients with hormone receptor-positive and HER2-positive metastatic breast cancer (SYSUCC-002). Clin Cancer Res. 2022;28:637-645. Doi: 10.1158/1078-0432.CCR-21-3435
4. Kim H-A, Lee JW, Nam SJ, et al; for the Korean Breast Cancer Study Group. Adding ovarian suppression to tamoxifen for premenopausal breast Cancer: a randomized phase III trial. J Clin Oncol. 2020;38:434-443. Doi: 10.1200/JCO.19.00126
5. Davies C, Pan H, Godwin J, et al; for the Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) Collaborative Group. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013;381:805-816. Doi: 10.1016/S0140-6736(12)61963-1
6. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials. Lancet. 2015;386:1353-1361. Doi: 10.1016/S0140-6736(15)60908-4

I love registries! With large numbers of participants, registries can be very helpful to identify rare side effects and to assess the efficacy and safety of medications in populations that may not be fully represented in clinical trials. I also love dupilumab; it was revolutionary in the management of patients with AD.

Vittrup and colleagues have created a registry of 347 participants treated with dupilumab. This does not yet have the large number of participants needed to identify new issues that wouldn't have been detected in clinical trials, but the study is informative about real-life use. The dramatic improvement in the Eczema Area and Severity Index (EASI) score is consistent with the high efficacy of dupilumab. The high rate of treatment persistence is also consistent with dupilumab being a very effective and safe treatment (because if the drug wasn't working well or was causing a severe problem, patients would probably stop the treatment). Though the study reported persistent head and neck involvement, the residual involvement may be quite minimal.

The EASI-75 and Investigator Global Assessment response rates reported in dupilumab trials underestimate the value of this drug. With a 2-year persistence rate of nearly 90%, it's clear that dupilumab is making a huge difference in the lives of patients with AD.

Fatigue is a fascinating issue in AD. We might wonder if all the inflammation in patients with AD would directly cause fatigue. Almost certainly all the itching in AD adversely affects sleep and would cause tremendous fatigue. It surprised me that most of the children in the study by Rangel and colleagues were reported as having no or mild fatigue; severe fatigue was very uncommon. It leaves me wondering whether the assessments of fatigue fully capture what's happening. Also, since the fatigue score was reported by the parents, I (as the parent of a child with AD) am wondering whether the parents were projecting, with the score more reflective of the parents' fatigue than with that of the child; alternatively, perhaps the child's hyperactivity leaves parents thinking there is no fatigue when there actually is (and possibly even causing the perceived hyperactivity).

The lack of a control group without AD is another major limitation in our ability to interpret the study findings. Is fatigue more common or less common in children with AD than in children without AD? I cannot tell from these findings. Does fatigue warrant, as the authors suggest, more attention in clinical practice? I don't know. If we are already treating our patients based on patients' global impressions of how they are doing — combined, of course, with our observations of their objective disease severity — I'm not sure how asking about fatigue would change anything, even if future studies were to definitively show that AD is associated with fatigue.

I hate new drugs (well, maybe not hate, but I worry about unknown long-term risks). Clinical trials that help a drug get approved can tell us a lot about a drug's efficacy, but these studies are generally limited in what they tell us about a drug's safety. Clinical trials are generally not powered enough (not enough participants and not followed for long enough) to be informative about rare risks. I love long-term studies of new drugs in large numbers of people because those studies can be very reassuring about the risks of medications. Studying nearly 10,000 patients for 5 years is quite reassuring, confirming my impression that dupilumab has a remarkable, excellent safety profile (Owji et al). Blocking interleukin 4 and interleukin 13 seems to be very specific to AD. Finding no association to cancer is what I would have expected; being able to share this information with patients is likely to be reassuring to them.

Oh, lord help me, another study that claims we should change our disease management because they've identified an increased risk for something. When you compare 70,000 patients with 270,000 controls, you have huge power to detect statistically significant associations of no clinical consequence. Let's assume for the moment that the detected association the authors found between AD and juvenile idiopathic arthritis (JIA) is real. The odds ratio is 2; the odds ratio for smoking causing cancer is on the order of 100.

In this study, over 99% of individuals in both AD and control groups did not have JIA. The difference between rates of JIA in patients with AD compared with controls was 0.3%! The authors conclude "it is important to inquire actively about symptoms not directly linked to the patients' skin disease"; based on the findings of this study, I would conclude that we don't need to worry about JIA in patients with AD even if there is a (marginally) higher prevalence of JIA in this group.

I love registries! With large numbers of participants, registries can be very helpful to identify rare side effects and to assess the efficacy and safety of medications in populations that may not be fully represented in clinical trials. I also love dupilumab; it was revolutionary in the management of patients with AD.

Vittrup and colleagues have created a registry of 347 participants treated with dupilumab. This does not yet have the large number of participants needed to identify new issues that wouldn't have been detected in clinical trials, but the study is informative about real-life use. The dramatic improvement in the Eczema Area and Severity Index (EASI) score is consistent with the high efficacy of dupilumab. The high rate of treatment persistence is also consistent with dupilumab being a very effective and safe treatment (because if the drug wasn't working well or was causing a severe problem, patients would probably stop the treatment). Though the study reported persistent head and neck involvement, the residual involvement may be quite minimal.

The EASI-75 and Investigator Global Assessment response rates reported in dupilumab trials underestimate the value of this drug. With a 2-year persistence rate of nearly 90%, it's clear that dupilumab is making a huge difference in the lives of patients with AD.

Fatigue is a fascinating issue in AD. We might wonder if all the inflammation in patients with AD would directly cause fatigue. Almost certainly all the itching in AD adversely affects sleep and would cause tremendous fatigue. It surprised me that most of the children in the study by Rangel and colleagues were reported as having no or mild fatigue; severe fatigue was very uncommon. It leaves me wondering whether the assessments of fatigue fully capture what's happening. Also, since the fatigue score was reported by the parents, I (as the parent of a child with AD) am wondering whether the parents were projecting, with the score more reflective of the parents' fatigue than with that of the child; alternatively, perhaps the child's hyperactivity leaves parents thinking there is no fatigue when there actually is (and possibly even causing the perceived hyperactivity).

The lack of a control group without AD is another major limitation in our ability to interpret the study findings. Is fatigue more common or less common in children with AD than in children without AD? I cannot tell from these findings. Does fatigue warrant, as the authors suggest, more attention in clinical practice? I don't know. If we are already treating our patients based on patients' global impressions of how they are doing — combined, of course, with our observations of their objective disease severity — I'm not sure how asking about fatigue would change anything, even if future studies were to definitively show that AD is associated with fatigue.

I hate new drugs (well, maybe not hate, but I worry about unknown long-term risks). Clinical trials that help a drug get approved can tell us a lot about a drug's efficacy, but these studies are generally limited in what they tell us about a drug's safety. Clinical trials are generally not powered enough (not enough participants and not followed for long enough) to be informative about rare risks. I love long-term studies of new drugs in large numbers of people because those studies can be very reassuring about the risks of medications. Studying nearly 10,000 patients for 5 years is quite reassuring, confirming my impression that dupilumab has a remarkable, excellent safety profile (Owji et al). Blocking interleukin 4 and interleukin 13 seems to be very specific to AD. Finding no association to cancer is what I would have expected; being able to share this information with patients is likely to be reassuring to them.

Oh, lord help me, another study that claims we should change our disease management because they've identified an increased risk for something. When you compare 70,000 patients with 270,000 controls, you have huge power to detect statistically significant associations of no clinical consequence. Let's assume for the moment that the detected association the authors found between AD and juvenile idiopathic arthritis (JIA) is real. The odds ratio is 2; the odds ratio for smoking causing cancer is on the order of 100.

In this study, over 99% of individuals in both AD and control groups did not have JIA. The difference between rates of JIA in patients with AD compared with controls was 0.3%! The authors conclude "it is important to inquire actively about symptoms not directly linked to the patients' skin disease"; based on the findings of this study, I would conclude that we don't need to worry about JIA in patients with AD even if there is a (marginally) higher prevalence of JIA in this group.

I love registries! With large numbers of participants, registries can be very helpful to identify rare side effects and to assess the efficacy and safety of medications in populations that may not be fully represented in clinical trials. I also love dupilumab; it was revolutionary in the management of patients with AD.

Vittrup and colleagues have created a registry of 347 participants treated with dupilumab. This does not yet have the large number of participants needed to identify new issues that wouldn't have been detected in clinical trials, but the study is informative about real-life use. The dramatic improvement in the Eczema Area and Severity Index (EASI) score is consistent with the high efficacy of dupilumab. The high rate of treatment persistence is also consistent with dupilumab being a very effective and safe treatment (because if the drug wasn't working well or was causing a severe problem, patients would probably stop the treatment). Though the study reported persistent head and neck involvement, the residual involvement may be quite minimal.

The EASI-75 and Investigator Global Assessment response rates reported in dupilumab trials underestimate the value of this drug. With a 2-year persistence rate of nearly 90%, it's clear that dupilumab is making a huge difference in the lives of patients with AD.

Fatigue is a fascinating issue in AD. We might wonder if all the inflammation in patients with AD would directly cause fatigue. Almost certainly all the itching in AD adversely affects sleep and would cause tremendous fatigue. It surprised me that most of the children in the study by Rangel and colleagues were reported as having no or mild fatigue; severe fatigue was very uncommon. It leaves me wondering whether the assessments of fatigue fully capture what's happening. Also, since the fatigue score was reported by the parents, I (as the parent of a child with AD) am wondering whether the parents were projecting, with the score more reflective of the parents' fatigue than with that of the child; alternatively, perhaps the child's hyperactivity leaves parents thinking there is no fatigue when there actually is (and possibly even causing the perceived hyperactivity).

The lack of a control group without AD is another major limitation in our ability to interpret the study findings. Is fatigue more common or less common in children with AD than in children without AD? I cannot tell from these findings. Does fatigue warrant, as the authors suggest, more attention in clinical practice? I don't know. If we are already treating our patients based on patients' global impressions of how they are doing — combined, of course, with our observations of their objective disease severity — I'm not sure how asking about fatigue would change anything, even if future studies were to definitively show that AD is associated with fatigue.

I hate new drugs (well, maybe not hate, but I worry about unknown long-term risks). Clinical trials that help a drug get approved can tell us a lot about a drug's efficacy, but these studies are generally limited in what they tell us about a drug's safety. Clinical trials are generally not powered enough (not enough participants and not followed for long enough) to be informative about rare risks. I love long-term studies of new drugs in large numbers of people because those studies can be very reassuring about the risks of medications. Studying nearly 10,000 patients for 5 years is quite reassuring, confirming my impression that dupilumab has a remarkable, excellent safety profile (Owji et al). Blocking interleukin 4 and interleukin 13 seems to be very specific to AD. Finding no association to cancer is what I would have expected; being able to share this information with patients is likely to be reassuring to them.

Oh, lord help me, another study that claims we should change our disease management because they've identified an increased risk for something. When you compare 70,000 patients with 270,000 controls, you have huge power to detect statistically significant associations of no clinical consequence. Let's assume for the moment that the detected association the authors found between AD and juvenile idiopathic arthritis (JIA) is real. The odds ratio is 2; the odds ratio for smoking causing cancer is on the order of 100.

In this study, over 99% of individuals in both AD and control groups did not have JIA. The difference between rates of JIA in patients with AD compared with controls was 0.3%! The authors conclude "it is important to inquire actively about symptoms not directly linked to the patients' skin disease"; based on the findings of this study, I would conclude that we don't need to worry about JIA in patients with AD even if there is a (marginally) higher prevalence of JIA in this group.

Fluorescence-optical imaging (FOI) identified early signs of psoriatic arthritis, based on data from 2 years of follow-up of a cohort of 389 adults at 14 rheumatology centers.

Approximately 25% of individuals with psoriasis go on to develop psoriatic arthritis (PsA), but there are no validated biomarkers to identify patients at risk for progression to PsA, Michaela Koehm, MD, of Goethe University, Frankfurt am Main, Germany, and colleagues wrote in RMD Open.

FOI is a technique that allows assessment of changes in microvascularization and subdermal skin inflammation, and because individuals with psoriasis who develop PsA have shown changes in blood vessel formation in the early stages of disease, the researchers sought to determine if FOI could be used to predict early PsA.

The researchers conducted a multicenter, two-part observational cohort study. The two parts, known as XCITING and XTEND, included 389 adults aged 18-75 years with plaque psoriasis deemed at increased risk for PsA. The patients were seen at rheumatology sites in Germany between Jan. 28, 2014, and March 16, 2017. The XTEND study included clinic visits 18-24 months after the XCITING study.

Participants underwent a complete clinical examination, with musculoskeletal ultrasound (MSUS) and FOI on both hands at a single visit. Those with positive FOI findings not seen with clinical exam or MSUS underwent MRI within 7 days. Patients with positive FOI but negative findings on clinical exam, MSUS, and MRI were followed for 2 years in the XTEND study.

The primary outcome was the ability of FOI to detect musculoskeletal inflammation, compared with clinical examination and MSUS.

Overall, 50% of the patients were diagnosed with PsA. A total of 116 (30%) had positive FOI findings; complete MRI data were available for 108 of these patients, including 68 negative MRIs and 40 positive MRIs.

In the XTEND study, another 12% of patients who were positive on FOI but not on MRI also developed PsA by the end of the 2-year follow-up. In comparison, the researchers noted that “literature data on yearly incidence rates [of PsA] in different national cohorts indicate an incidence rate of approximately 4.3% per year.”

A total of 149 of the 196 patients with PsA confirmed by either clinical exam or MSUS were also positive on FOI, yielding a sensitivity of 76.0%. The specificity of FOI was 39.5%.

The sensitive visualization of musculoskeletal inflammation possible with FOI “may exceed its ability to detect clinically manifest PsA at high sensitivity or specificity, but early visualization is arguably of greater value as other imaging methods are currently available for detection of later stages of PsA,” the researchers wrote in their discussion. “A technique allowing early identification of PsA may be especially valuable for nonrheumatologists, including dermatologists and general practitioners, and help expedite more efficient referral to specialists.”

The findings were limited by several factors, including the nonrandomized design and small subgroup numbers, the researchers noted. Other limitations include the presence of alternative conditions such as osteoarthritis that might have complicated the imaging; the focus only on the hands; and potential variation in FOI assessment related to technical standards such as temperature and positioning.

However, the results support FOI as a safe and effective method of detecting early signs of joint inflammation that could predict increased risk for PsA in psoriasis patients, the researchers said.

The researchers added that more work is needed to evaluate FOI in clinical practice, but FOI has the potential to identify vascularization changes earlier than other imaging modalities and in advance of clinical symptoms.

“Accordingly, FOI may have the potential to improve patient outcomes in PsA by reducing the time to initiation of early treatment,” they concluded.

The study was supported by Fraunhofer ITMP, a nonprofit organization, and a research grant from Pfizer Germany. Some of the researchers disclosed financial relationships with many pharmaceutical companies, including Pfizer.

Fluorescence-optical imaging (FOI) identified early signs of psoriatic arthritis, based on data from 2 years of follow-up of a cohort of 389 adults at 14 rheumatology centers.

Approximately 25% of individuals with psoriasis go on to develop psoriatic arthritis (PsA), but there are no validated biomarkers to identify patients at risk for progression to PsA, Michaela Koehm, MD, of Goethe University, Frankfurt am Main, Germany, and colleagues wrote in RMD Open.

FOI is a technique that allows assessment of changes in microvascularization and subdermal skin inflammation, and because individuals with psoriasis who develop PsA have shown changes in blood vessel formation in the early stages of disease, the researchers sought to determine if FOI could be used to predict early PsA.

The researchers conducted a multicenter, two-part observational cohort study. The two parts, known as XCITING and XTEND, included 389 adults aged 18-75 years with plaque psoriasis deemed at increased risk for PsA. The patients were seen at rheumatology sites in Germany between Jan. 28, 2014, and March 16, 2017. The XTEND study included clinic visits 18-24 months after the XCITING study.

Participants underwent a complete clinical examination, with musculoskeletal ultrasound (MSUS) and FOI on both hands at a single visit. Those with positive FOI findings not seen with clinical exam or MSUS underwent MRI within 7 days. Patients with positive FOI but negative findings on clinical exam, MSUS, and MRI were followed for 2 years in the XTEND study.

The primary outcome was the ability of FOI to detect musculoskeletal inflammation, compared with clinical examination and MSUS.

Overall, 50% of the patients were diagnosed with PsA. A total of 116 (30%) had positive FOI findings; complete MRI data were available for 108 of these patients, including 68 negative MRIs and 40 positive MRIs.

In the XTEND study, another 12% of patients who were positive on FOI but not on MRI also developed PsA by the end of the 2-year follow-up. In comparison, the researchers noted that “literature data on yearly incidence rates [of PsA] in different national cohorts indicate an incidence rate of approximately 4.3% per year.”

A total of 149 of the 196 patients with PsA confirmed by either clinical exam or MSUS were also positive on FOI, yielding a sensitivity of 76.0%. The specificity of FOI was 39.5%.

The sensitive visualization of musculoskeletal inflammation possible with FOI “may exceed its ability to detect clinically manifest PsA at high sensitivity or specificity, but early visualization is arguably of greater value as other imaging methods are currently available for detection of later stages of PsA,” the researchers wrote in their discussion. “A technique allowing early identification of PsA may be especially valuable for nonrheumatologists, including dermatologists and general practitioners, and help expedite more efficient referral to specialists.”

The findings were limited by several factors, including the nonrandomized design and small subgroup numbers, the researchers noted. Other limitations include the presence of alternative conditions such as osteoarthritis that might have complicated the imaging; the focus only on the hands; and potential variation in FOI assessment related to technical standards such as temperature and positioning.

However, the results support FOI as a safe and effective method of detecting early signs of joint inflammation that could predict increased risk for PsA in psoriasis patients, the researchers said.

The researchers added that more work is needed to evaluate FOI in clinical practice, but FOI has the potential to identify vascularization changes earlier than other imaging modalities and in advance of clinical symptoms.

“Accordingly, FOI may have the potential to improve patient outcomes in PsA by reducing the time to initiation of early treatment,” they concluded.

The study was supported by Fraunhofer ITMP, a nonprofit organization, and a research grant from Pfizer Germany. Some of the researchers disclosed financial relationships with many pharmaceutical companies, including Pfizer.

Fluorescence-optical imaging (FOI) identified early signs of psoriatic arthritis, based on data from 2 years of follow-up of a cohort of 389 adults at 14 rheumatology centers.

Approximately 25% of individuals with psoriasis go on to develop psoriatic arthritis (PsA), but there are no validated biomarkers to identify patients at risk for progression to PsA, Michaela Koehm, MD, of Goethe University, Frankfurt am Main, Germany, and colleagues wrote in RMD Open.

FOI is a technique that allows assessment of changes in microvascularization and subdermal skin inflammation, and because individuals with psoriasis who develop PsA have shown changes in blood vessel formation in the early stages of disease, the researchers sought to determine if FOI could be used to predict early PsA.

The researchers conducted a multicenter, two-part observational cohort study. The two parts, known as XCITING and XTEND, included 389 adults aged 18-75 years with plaque psoriasis deemed at increased risk for PsA. The patients were seen at rheumatology sites in Germany between Jan. 28, 2014, and March 16, 2017. The XTEND study included clinic visits 18-24 months after the XCITING study.

Participants underwent a complete clinical examination, with musculoskeletal ultrasound (MSUS) and FOI on both hands at a single visit. Those with positive FOI findings not seen with clinical exam or MSUS underwent MRI within 7 days. Patients with positive FOI but negative findings on clinical exam, MSUS, and MRI were followed for 2 years in the XTEND study.

The primary outcome was the ability of FOI to detect musculoskeletal inflammation, compared with clinical examination and MSUS.

Overall, 50% of the patients were diagnosed with PsA. A total of 116 (30%) had positive FOI findings; complete MRI data were available for 108 of these patients, including 68 negative MRIs and 40 positive MRIs.

In the XTEND study, another 12% of patients who were positive on FOI but not on MRI also developed PsA by the end of the 2-year follow-up. In comparison, the researchers noted that “literature data on yearly incidence rates [of PsA] in different national cohorts indicate an incidence rate of approximately 4.3% per year.”

A total of 149 of the 196 patients with PsA confirmed by either clinical exam or MSUS were also positive on FOI, yielding a sensitivity of 76.0%. The specificity of FOI was 39.5%.

The sensitive visualization of musculoskeletal inflammation possible with FOI “may exceed its ability to detect clinically manifest PsA at high sensitivity or specificity, but early visualization is arguably of greater value as other imaging methods are currently available for detection of later stages of PsA,” the researchers wrote in their discussion. “A technique allowing early identification of PsA may be especially valuable for nonrheumatologists, including dermatologists and general practitioners, and help expedite more efficient referral to specialists.”

The findings were limited by several factors, including the nonrandomized design and small subgroup numbers, the researchers noted. Other limitations include the presence of alternative conditions such as osteoarthritis that might have complicated the imaging; the focus only on the hands; and potential variation in FOI assessment related to technical standards such as temperature and positioning.

However, the results support FOI as a safe and effective method of detecting early signs of joint inflammation that could predict increased risk for PsA in psoriasis patients, the researchers said.

The researchers added that more work is needed to evaluate FOI in clinical practice, but FOI has the potential to identify vascularization changes earlier than other imaging modalities and in advance of clinical symptoms.

“Accordingly, FOI may have the potential to improve patient outcomes in PsA by reducing the time to initiation of early treatment,” they concluded.

The study was supported by Fraunhofer ITMP, a nonprofit organization, and a research grant from Pfizer Germany. Some of the researchers disclosed financial relationships with many pharmaceutical companies, including Pfizer.

The introduction of the soft drinks industry levy (SDIL) – dubbed the ‘sugar tax’ – in England was followed by a drop in the number of older primary school girls succumbing to obesity, according to researchers from the Universities of Cambridge, Oxford, and Bath, with colleagues at the London School of Hygiene and Tropical Medicine.

The study, published in PLOS Medicine, has led to calls to extend the levy to other unhealthy foods and drinks

Obesity has become a global public health problem, the researchers said. In England, around 10% of 4- to 5-year-old children and 20% of 10- to 11-year-olds were recorded as obese in 2020. Childhood obesity is associated with depression in children and the adults into which they maturate, as well as with serious health problems in later life including high blood pressure and type 2 diabetes.

In the United Kingdom, young people consume significantly more added sugars than are recommended – by late adolescence, typically 70 g of added sugar per day, more than double the recommended 30g. The team said that sugar-sweetened beverages (SSB) are the primary sources of dietary added sugars in children, with high consumption commonly observed in more deprived areas where obesity prevalence is also highest.
 

Protecting children from excessive sugar

The two-tier SDIL on drinks manufacturers was implemented in April 2018 and aimed to protect children from excessive sugar consumption and tackle childhood obesity by incentivizing reformulation of SSBs in the U.K. with reduced sugar content.

To assess the effects of SDIL, the researchers used data from the National Child Measurement Programme on over 1 million children at ages 4 to 5 years (reception class) and 10 to 11 years (school year 6) in state-maintained English primary schools. The surveillance program includes annual repeat cross-sectional measurements, enabling the researchers to examine trajectories in monthly prevalence of obesity from September 2013 to November 2019, 19 months after the implementation of the SDIL.

Taking account of previous trends in obesity levels, they estimated both absolute and relative changes in obesity prevalence, both overall and by sex and deprivation, and compared obesity levels after the SDIL with predicted levels had the tax not been introduced, controlling for children’s sex and the level of deprivation of their school area.

Although they found no significant association with obesity levels in reception-age children or year-6 boys, they noted an overall absolute reduction in obesity prevalence of 1.6 percentage points (PPs) (95% confidence interval, 1.1-2.1) in 10- to 11-year-old (year 6) girls. This equated to an 8% relative reduction in obesity rates compared with a counterfactual estimated from the trend prior to the SDIL announcement in March 2016, adjusted for temporal variations in obesity prevalence.

The researchers estimated that this was equivalent to preventing 5,234 cases of obesity per year in this group of year-6 girls alone.
 

Obesity reductions greatest in most deprived areas

Reductions were greatest in girls whose schools were in the most deprived areas, where children are known to consume the largest amount of sugary drinks. The greatest reductions in obesity were observed in the two most deprived quintiles – such that in the lowest quintile the absolute obesity prevalence reduction was 2.4 PP (95% CI, 1.6-3.2), equivalent to a 9% reduction in those living in the most deprived areas.

There are several reasons why the sugar tax did not lead to changes in levels of obesity among the younger children, the researchers said. Very young children consume fewer sugar-sweetened drinks than older children, so the soft drinks levy would have had a smaller effect. Also, fruit juices are not included in the levy, but contribute similar amounts of sugar in young children’s diets as do sugar-sweetened beverages.
 

Advertising may impact consumption in boys

It’s also unclear why the sugar tax might affect obesity prevalence in girls and boys differently, they said, especially since boys are higher consumers of sugar-sweetened beverages. One explanation is the possible impact of advertising – numerous studies have found that boys are often exposed to more food advertising than girls, both through higher levels of TV viewing and in how adverts are framed. Physical activity is often used to promote junk food and boys, compared with girls, have been shown to be more likely to believe that energy-dense junk foods depicted in adverts will boost physical performance, and so are more likely to choose energy-dense, nutrient-poor products following celebrity endorsements.

Tax ‘led to positive health impacts’

“Our findings suggest that the U.K. SDIL led to positive health impacts in the form of reduced obesity levels in girls aged 10-11 years,” the authors said. However: “Additional strategies beyond SSB taxation will be needed to reduce obesity prevalence overall, and particularly in older boys and younger children.”

Dr. Nina Rogers from the MRC Epidemiology Unit at Cambridge (England), who led the study, said: “We urgently need to find ways to tackle the increasing numbers of children living with obesity, otherwise we risk our children growing up to face significant health problems. That was one reason why the U.K.’s SDIL was introduced, and the evidence so far is promising. We’ve shown for the first time that it is likely to have helped prevent thousands of children each year becoming obese.

“It isn’t a straightforward picture, though, as it was mainly older girls who benefited. But the fact that we saw the biggest difference among girls from areas of high deprivation is important and is a step towards reducing the health inequalities they face.”

Although the researchers found an association rather than a causal link, this study adds to previous findings that the levy was associated with a substantial reduction in the amount of sugar in soft drinks.

Senior author Professor Jean Adams from the MRC Epidemiology Unit said: “We know that consuming too many sugary drinks contributes to obesity and that the U.K. soft drinks levy led to a drop in the amount of sugar in soft drinks available in the U.K., so it makes sense that we also see a drop in cases of obesity, although we only found this in girls. Children from more deprived backgrounds tend to consume the largest amount of sugary drinks, and it was among girls in this group that we saw the biggest change.”

Tom Sanders, professor emeritus of nutrition and dietetics at King’s College London, said: “The claim that the soft drink levy might have prevented 5,000 children from becoming obese is speculative because it is based on an association not actual measurements of consumption.”

He added that: “As well as continuing to discourage the consumption of sugar sweetened beverages and sweets, wider recognition should be given to foods such as biscuits [and] deep-fried foods (crisps, corn snacks, chips) that make [a] bigger contribution to excess calorie intake in children. Tackling poverty, however, is probably [the] best way to improve the diets of socially deprived children.”
 

Government ‘should learn from this success’

Asked to comment by this news organization, Katharine Jenner, director of the Obesity Health Alliance, said: “Government should be heartened that their soft drinks policy is already improving the health of young girls, regardless of where they live. The government should learn from this success, especially when compared with the many unsuccessful attempts to persuade industry to change their products voluntarily.  They must now press ahead with policies that make it easier for everyone to eat a healthier diet, including extending the soft drinks industry levy to include other less healthy foods and drinks and measures to take junk food out of the spotlight. 

“The research notes that numerous studies have found that boys are often exposed to more food advertising content than girls, negating the impact of the soft drinks levy [so] we need restriction on junk food marketing now, to put healthy food back in the spotlight.”

The research was supported by the National Institute of Health and Care Research and the Medical Research Council.

A version of this article originally appeared on MedscapeUK.

The introduction of the soft drinks industry levy (SDIL) – dubbed the ‘sugar tax’ – in England was followed by a drop in the number of older primary school girls succumbing to obesity, according to researchers from the Universities of Cambridge, Oxford, and Bath, with colleagues at the London School of Hygiene and Tropical Medicine.

The study, published in PLOS Medicine, has led to calls to extend the levy to other unhealthy foods and drinks

Obesity has become a global public health problem, the researchers said. In England, around 10% of 4- to 5-year-old children and 20% of 10- to 11-year-olds were recorded as obese in 2020. Childhood obesity is associated with depression in children and the adults into which they maturate, as well as with serious health problems in later life including high blood pressure and type 2 diabetes.

In the United Kingdom, young people consume significantly more added sugars than are recommended – by late adolescence, typically 70 g of added sugar per day, more than double the recommended 30g. The team said that sugar-sweetened beverages (SSB) are the primary sources of dietary added sugars in children, with high consumption commonly observed in more deprived areas where obesity prevalence is also highest.
 

Protecting children from excessive sugar

The two-tier SDIL on drinks manufacturers was implemented in April 2018 and aimed to protect children from excessive sugar consumption and tackle childhood obesity by incentivizing reformulation of SSBs in the U.K. with reduced sugar content.

To assess the effects of SDIL, the researchers used data from the National Child Measurement Programme on over 1 million children at ages 4 to 5 years (reception class) and 10 to 11 years (school year 6) in state-maintained English primary schools. The surveillance program includes annual repeat cross-sectional measurements, enabling the researchers to examine trajectories in monthly prevalence of obesity from September 2013 to November 2019, 19 months after the implementation of the SDIL.

Taking account of previous trends in obesity levels, they estimated both absolute and relative changes in obesity prevalence, both overall and by sex and deprivation, and compared obesity levels after the SDIL with predicted levels had the tax not been introduced, controlling for children’s sex and the level of deprivation of their school area.

Although they found no significant association with obesity levels in reception-age children or year-6 boys, they noted an overall absolute reduction in obesity prevalence of 1.6 percentage points (PPs) (95% confidence interval, 1.1-2.1) in 10- to 11-year-old (year 6) girls. This equated to an 8% relative reduction in obesity rates compared with a counterfactual estimated from the trend prior to the SDIL announcement in March 2016, adjusted for temporal variations in obesity prevalence.

The researchers estimated that this was equivalent to preventing 5,234 cases of obesity per year in this group of year-6 girls alone.
 

Obesity reductions greatest in most deprived areas

Reductions were greatest in girls whose schools were in the most deprived areas, where children are known to consume the largest amount of sugary drinks. The greatest reductions in obesity were observed in the two most deprived quintiles – such that in the lowest quintile the absolute obesity prevalence reduction was 2.4 PP (95% CI, 1.6-3.2), equivalent to a 9% reduction in those living in the most deprived areas.

There are several reasons why the sugar tax did not lead to changes in levels of obesity among the younger children, the researchers said. Very young children consume fewer sugar-sweetened drinks than older children, so the soft drinks levy would have had a smaller effect. Also, fruit juices are not included in the levy, but contribute similar amounts of sugar in young children’s diets as do sugar-sweetened beverages.
 

Advertising may impact consumption in boys

It’s also unclear why the sugar tax might affect obesity prevalence in girls and boys differently, they said, especially since boys are higher consumers of sugar-sweetened beverages. One explanation is the possible impact of advertising – numerous studies have found that boys are often exposed to more food advertising than girls, both through higher levels of TV viewing and in how adverts are framed. Physical activity is often used to promote junk food and boys, compared with girls, have been shown to be more likely to believe that energy-dense junk foods depicted in adverts will boost physical performance, and so are more likely to choose energy-dense, nutrient-poor products following celebrity endorsements.

Tax ‘led to positive health impacts’

“Our findings suggest that the U.K. SDIL led to positive health impacts in the form of reduced obesity levels in girls aged 10-11 years,” the authors said. However: “Additional strategies beyond SSB taxation will be needed to reduce obesity prevalence overall, and particularly in older boys and younger children.”

Dr. Nina Rogers from the MRC Epidemiology Unit at Cambridge (England), who led the study, said: “We urgently need to find ways to tackle the increasing numbers of children living with obesity, otherwise we risk our children growing up to face significant health problems. That was one reason why the U.K.’s SDIL was introduced, and the evidence so far is promising. We’ve shown for the first time that it is likely to have helped prevent thousands of children each year becoming obese.

“It isn’t a straightforward picture, though, as it was mainly older girls who benefited. But the fact that we saw the biggest difference among girls from areas of high deprivation is important and is a step towards reducing the health inequalities they face.”

Although the researchers found an association rather than a causal link, this study adds to previous findings that the levy was associated with a substantial reduction in the amount of sugar in soft drinks.

Senior author Professor Jean Adams from the MRC Epidemiology Unit said: “We know that consuming too many sugary drinks contributes to obesity and that the U.K. soft drinks levy led to a drop in the amount of sugar in soft drinks available in the U.K., so it makes sense that we also see a drop in cases of obesity, although we only found this in girls. Children from more deprived backgrounds tend to consume the largest amount of sugary drinks, and it was among girls in this group that we saw the biggest change.”

Tom Sanders, professor emeritus of nutrition and dietetics at King’s College London, said: “The claim that the soft drink levy might have prevented 5,000 children from becoming obese is speculative because it is based on an association not actual measurements of consumption.”

He added that: “As well as continuing to discourage the consumption of sugar sweetened beverages and sweets, wider recognition should be given to foods such as biscuits [and] deep-fried foods (crisps, corn snacks, chips) that make [a] bigger contribution to excess calorie intake in children. Tackling poverty, however, is probably [the] best way to improve the diets of socially deprived children.”
 

Government ‘should learn from this success’

Asked to comment by this news organization, Katharine Jenner, director of the Obesity Health Alliance, said: “Government should be heartened that their soft drinks policy is already improving the health of young girls, regardless of where they live. The government should learn from this success, especially when compared with the many unsuccessful attempts to persuade industry to change their products voluntarily.  They must now press ahead with policies that make it easier for everyone to eat a healthier diet, including extending the soft drinks industry levy to include other less healthy foods and drinks and measures to take junk food out of the spotlight. 

“The research notes that numerous studies have found that boys are often exposed to more food advertising content than girls, negating the impact of the soft drinks levy [so] we need restriction on junk food marketing now, to put healthy food back in the spotlight.”

The research was supported by the National Institute of Health and Care Research and the Medical Research Council.

A version of this article originally appeared on MedscapeUK.

The introduction of the soft drinks industry levy (SDIL) – dubbed the ‘sugar tax’ – in England was followed by a drop in the number of older primary school girls succumbing to obesity, according to researchers from the Universities of Cambridge, Oxford, and Bath, with colleagues at the London School of Hygiene and Tropical Medicine.

The study, published in PLOS Medicine, has led to calls to extend the levy to other unhealthy foods and drinks

Obesity has become a global public health problem, the researchers said. In England, around 10% of 4- to 5-year-old children and 20% of 10- to 11-year-olds were recorded as obese in 2020. Childhood obesity is associated with depression in children and the adults into which they maturate, as well as with serious health problems in later life including high blood pressure and type 2 diabetes.

In the United Kingdom, young people consume significantly more added sugars than are recommended – by late adolescence, typically 70 g of added sugar per day, more than double the recommended 30g. The team said that sugar-sweetened beverages (SSB) are the primary sources of dietary added sugars in children, with high consumption commonly observed in more deprived areas where obesity prevalence is also highest.
 

Protecting children from excessive sugar

The two-tier SDIL on drinks manufacturers was implemented in April 2018 and aimed to protect children from excessive sugar consumption and tackle childhood obesity by incentivizing reformulation of SSBs in the U.K. with reduced sugar content.

To assess the effects of SDIL, the researchers used data from the National Child Measurement Programme on over 1 million children at ages 4 to 5 years (reception class) and 10 to 11 years (school year 6) in state-maintained English primary schools. The surveillance program includes annual repeat cross-sectional measurements, enabling the researchers to examine trajectories in monthly prevalence of obesity from September 2013 to November 2019, 19 months after the implementation of the SDIL.

Taking account of previous trends in obesity levels, they estimated both absolute and relative changes in obesity prevalence, both overall and by sex and deprivation, and compared obesity levels after the SDIL with predicted levels had the tax not been introduced, controlling for children’s sex and the level of deprivation of their school area.

Although they found no significant association with obesity levels in reception-age children or year-6 boys, they noted an overall absolute reduction in obesity prevalence of 1.6 percentage points (PPs) (95% confidence interval, 1.1-2.1) in 10- to 11-year-old (year 6) girls. This equated to an 8% relative reduction in obesity rates compared with a counterfactual estimated from the trend prior to the SDIL announcement in March 2016, adjusted for temporal variations in obesity prevalence.

The researchers estimated that this was equivalent to preventing 5,234 cases of obesity per year in this group of year-6 girls alone.
 

Obesity reductions greatest in most deprived areas

Reductions were greatest in girls whose schools were in the most deprived areas, where children are known to consume the largest amount of sugary drinks. The greatest reductions in obesity were observed in the two most deprived quintiles – such that in the lowest quintile the absolute obesity prevalence reduction was 2.4 PP (95% CI, 1.6-3.2), equivalent to a 9% reduction in those living in the most deprived areas.

There are several reasons why the sugar tax did not lead to changes in levels of obesity among the younger children, the researchers said. Very young children consume fewer sugar-sweetened drinks than older children, so the soft drinks levy would have had a smaller effect. Also, fruit juices are not included in the levy, but contribute similar amounts of sugar in young children’s diets as do sugar-sweetened beverages.
 

Advertising may impact consumption in boys

It’s also unclear why the sugar tax might affect obesity prevalence in girls and boys differently, they said, especially since boys are higher consumers of sugar-sweetened beverages. One explanation is the possible impact of advertising – numerous studies have found that boys are often exposed to more food advertising than girls, both through higher levels of TV viewing and in how adverts are framed. Physical activity is often used to promote junk food and boys, compared with girls, have been shown to be more likely to believe that energy-dense junk foods depicted in adverts will boost physical performance, and so are more likely to choose energy-dense, nutrient-poor products following celebrity endorsements.

Tax ‘led to positive health impacts’

“Our findings suggest that the U.K. SDIL led to positive health impacts in the form of reduced obesity levels in girls aged 10-11 years,” the authors said. However: “Additional strategies beyond SSB taxation will be needed to reduce obesity prevalence overall, and particularly in older boys and younger children.”

Dr. Nina Rogers from the MRC Epidemiology Unit at Cambridge (England), who led the study, said: “We urgently need to find ways to tackle the increasing numbers of children living with obesity, otherwise we risk our children growing up to face significant health problems. That was one reason why the U.K.’s SDIL was introduced, and the evidence so far is promising. We’ve shown for the first time that it is likely to have helped prevent thousands of children each year becoming obese.

“It isn’t a straightforward picture, though, as it was mainly older girls who benefited. But the fact that we saw the biggest difference among girls from areas of high deprivation is important and is a step towards reducing the health inequalities they face.”

Although the researchers found an association rather than a causal link, this study adds to previous findings that the levy was associated with a substantial reduction in the amount of sugar in soft drinks.

Senior author Professor Jean Adams from the MRC Epidemiology Unit said: “We know that consuming too many sugary drinks contributes to obesity and that the U.K. soft drinks levy led to a drop in the amount of sugar in soft drinks available in the U.K., so it makes sense that we also see a drop in cases of obesity, although we only found this in girls. Children from more deprived backgrounds tend to consume the largest amount of sugary drinks, and it was among girls in this group that we saw the biggest change.”

Tom Sanders, professor emeritus of nutrition and dietetics at King’s College London, said: “The claim that the soft drink levy might have prevented 5,000 children from becoming obese is speculative because it is based on an association not actual measurements of consumption.”

He added that: “As well as continuing to discourage the consumption of sugar sweetened beverages and sweets, wider recognition should be given to foods such as biscuits [and] deep-fried foods (crisps, corn snacks, chips) that make [a] bigger contribution to excess calorie intake in children. Tackling poverty, however, is probably [the] best way to improve the diets of socially deprived children.”
 

Government ‘should learn from this success’

Asked to comment by this news organization, Katharine Jenner, director of the Obesity Health Alliance, said: “Government should be heartened that their soft drinks policy is already improving the health of young girls, regardless of where they live. The government should learn from this success, especially when compared with the many unsuccessful attempts to persuade industry to change their products voluntarily.  They must now press ahead with policies that make it easier for everyone to eat a healthier diet, including extending the soft drinks industry levy to include other less healthy foods and drinks and measures to take junk food out of the spotlight. 

“The research notes that numerous studies have found that boys are often exposed to more food advertising content than girls, negating the impact of the soft drinks levy [so] we need restriction on junk food marketing now, to put healthy food back in the spotlight.”

The research was supported by the National Institute of Health and Care Research and the Medical Research Council.

A version of this article originally appeared on MedscapeUK.