Article

Obesity is a major health problem in the United States. The Centers for Disease Control and Prevention (CDC) defines the problem as weight that is higher than what is healthy for a given height, with quantitative definitions of overweight and obesity as body mass indices (BMIs) of 25 to 29.9 kg/m² and ≥ 30 kg/m², respectively.¹ The prevalence of obesity among adults in 2017 ̶ 2018 was reported by the CDC to be 42.4%.² Among women, the reported prevalence of obesity was lowest among Asian individuals (17.2%) and greatest among non-Hispanic Black individuals (56.9%), with White (39.8%) and Hispanic individuals (43.7%) having rates in between.² In a meta-analysis of prospective studies that included 4 million people who were never smokers and had no chronic disease at baseline, age- and sex-adjusted mortality rates were studied over a median of 14 years of follow-up.³ Compared with those with a BMI of 20 to 25 kg/m², people with a BMI of 30 to 34.9 kg/m² or a BMI of 35 to 39.9 kg/m² had increased risks of death of 46% and 94%, respectively, demonstrating that obesity increases this risk.³

The increased risk of death associated with obesity is caused by obesity-related diseases that cause early mortality, including diabetes mellitus (DM), dyslipidemia, hypertension, coronary heart disease, heart failure, atrial fibrillation, stroke, and venous thromboembolic events.⁴ Obesity is also associated with an increased risk of many cancers, including cancer of the endometrium, kidney, esophagus, stomach, colon, rectum, gallbladder, pancreas, liver, and breast.⁵ With regard to gynecologic disease, obesity is associated with an increased risk of fibroids and heavy menstrual bleeding.⁶ For pregnant patients, obesity is associated with increased risks of⁷:

• miscarriage and stillbirth
• preeclampsia and gestational hypertension
• gestational diabetes
• severe maternal morbidity
• postterm pregnancy
• venous thromboembolism
• endometritis.

For obese patients, weight loss can normalize blood pressure, reduce the risk of cardiovascular events, decrease the risk of cancer, and cure type 2 DM.⁸

Bariatric surgery: The gold standard treatment for reliable and sustained weight loss

All patients with obesity should be counseled to reduce caloric intake and increase physical activity. Dietary counseling provided by a nutritionist may help reinforce advice given by a provider. However, lifestyle interventions are associated with modest weight loss (<5% of bodyweight; FIGURE).⁹ The gold standard treatment for reliable and sustained weight loss is bariatric surgery.

In the Swedish Obese Subjects study, involving 2,010 people, following bariatric surgery the mean decrease in bodyweight was 23% at 2 years, with a slow increase in weight thereafter, resulting in a sustained mean weight loss of 18% at 10 years.⁸ In this study, people in the diet and exercise control group had no change in bodyweight over 10 years of follow-up.⁸ Not all eligible obese patients want to undergo bariatric surgery because it is an arduous sequential process involving 6 months of intensive preoperative preparation, bariatric surgery, recovery, and intensive postoperative follow-up. The perioperative mortality rate is 0.03% to 0.2%.¹⁰ Following bariatric surgery, additional operations may be necessary for more than 10% of patients.¹⁰ With recent breakthroughs in the medication management of obesity, patients who do not want bariatric surgery can achieve reliable weight loss of greater than 10% of body weight with glucagon-like peptide -1 (GLP-1) agonists.

ILLUSTRATION: KIMBERLY MARTENS FOR OBG MANAGEMENT

GLP-1 agonist analogues: Practice-changing breakthrough in medication treatment

GLP-1, a 30 amino acid peptide, is produced by intestinal enteroendocrine cells and neurons in the medulla and hypothalamus.¹¹ GLP-1 reduces hunger cravings and causes satiety, reducing daily food intake.¹² GLP-1 also enhances the secretion of insulin, making GLP-1 agonists an effective treatment for type 2 DM. In humans and experimental animals, the administration of exogenous GLP-1 agonists decreases hunger cravings and causes satiety, reducing food intake, resulting in weight loss.¹² The synthetic GLP-1 agonists, liraglutide (Saxenda) and semaglutide (Wegovy) are approved by the US Food and Drug Administration (FDA) as anti-obesity medications.

Native GLP-1 has a short circulating half-life of approximately 2 minutes. The synthetic GLP-1 agonist medications liraglutide and semaglutide are modified to significantly increase their half-life. Liraglutide is a modified version of GLP-1 with a palmitic acid side chain and an amino acid spacer resulting in reduced degradation and a 15-hour half-life, necessitating daily administration. Semaglutide has a steric acid diacid at Lys26, a large synthetic spacer, a modification of amino acid 8 with the addition of α-aminobutyric acid and a 165-hour half-life, permitting weekly administration.¹³ For weight loss, liraglutide and semaglultide are administered by subcutaneous injection. Tirzepatide (Mounjaro) is a novel GLP-1 agonist. It is also a gastric inhibitory peptide, is FDA approved to treat type 2 DM, and is awaiting FDA approval as a weight loss medication.Tirzepatide causes substantial weight loss, similar to the effect of semaglutide.¹⁴

Semaglutide and weight loss

Semaglutide is approved by the FDA for chronic weight management as an adjunct to a reduced-calorie diet and increased physical activity in adults with a BMI ≥ 30 kg/m² or ≥ 27 kg/m² in the presence of a weight-related comorbidity. It is also FDA approved to treat type 2 DM.

In a weight loss trial, 1,961 overweight and obese patients with a mean BMI of 38 kg/m², were randomly assigned to semaglutide or placebo treatment for 68 weeks. All the participants were following a regimen that included a calorie-reduced diet and increased physical activity. The mean changes in body weight for the patients in the semaglutide and placebo treatment groups were -14.9% and -2.4%, respectively. The treatment difference was -12.4% (95% confidence interval [CI], -13.4% to -11.5%; P <.001). In this study, compared with placebo, semaglutide treatment resulted in a greater decrease in waist circumference, -5.3 in versus -1.6 in.¹⁵ A network meta-analysis of the efficacy of weight loss medicines indicates that semaglutide is the most effective medication currently FDA approved for weight loss, reliably producing substantial weight loss (FIGURE).⁹

In one randomized clinical trial, investigators directly compared the efficacy of semaglutide and liraglutide in achieving weight loss. In this trial, 338 patients were assigned randomly to treatment with semaglutide 2.4 mg weekly subcutaneous injection, liraglutide 3.0 mg daily subcutaneous injection, or placebo. All the participants were following a regimen that included a calorie-reduced diet and increased physical activity.¹⁶ After 68 weeks of treatment, the mean weight changes were -15.8%, -6.4%, and -1.9% in the semaglutide, liraglutide, and placebo groups, respectively. The difference between the semaglutide and liraglutide groups was -9.4% (95% CI, -12% to -6.8%; P <.001).¹⁶

Continue to: Semaglutide dose-escalation and contraindications...

 

 

Semaglutide dose-escalation and contraindications

For weight loss, the target dose of semaglutide is 2.4 mg once weekly subcutaneous injection achieved by sequential dose escalation. To give patients time to adjust to adverse effects caused by the medication, a standardized dose-escalation regimen is recommended. The FDA-approved escalation regimen for semaglutide treatment begins with a weekly subcutaneous dose of 0.25 mg for 4 weeks, followed by an increase in the weekly dosage every 4 weeks: 0.5 mg, 1.0 mg, 1.7 mg, and 2.4 mg.¹⁷ To support the dose-escalation process there are 5 unique autoinjectors that deliver the appropriate dose for the current step.

Semaglutide is contraindicated if the patient has an allergy to the medication or if there is a personal or family history of medullary thyroid cancer.¹⁷ In animal toxicology studies, semaglutide at clinically relevant dosing was associated with an increased risk of developing medullary thyroid cancer. Patients with a personal history of multiple endocrine neoplasia syndrome type 2, (medullary thyroid cancer, pheochromocytoma, and primary hyperparathyroidism) should not take semaglutide. Semaglutide may cause fetal harm and the FDA recommends discontinuing semaglutide at least 2 months before pregnancy.¹⁷ According to the FDA, the safety of semaglutide during breastfeeding has not been established. In Canada, breastfeeding is a contraindication to semaglutide treatment.¹⁸

Limitations of medication treatment of obesity

There are important limitations to semaglutide treatment of obesity, including:

• weight gain after stopping treatment
• limited medical insurance supportfor an expensive medication treatment
• bothersome adverse effects.

Weight gain posttreatment. After stopping medication treatment of obesity, weight gain occurs in most patients. However, patients may remain below baseline weight for a long time after stopping medication therapy. In one trial of 803 patients, after 20 weeks of semaglutide treatment (16-week dose-escalation phase, followed by 4 weeks on a weekly dose of 2.4 mg), the participants were randomized to 48 additional weeks of semaglutide or placebo.¹⁹ All the participants were following a regimen that included a calorie-reduced diet and increased physical activity. At the initial 20 weeks of treatment time point the mean weight change was -10.6%. Over the following 48 weeks, the patients treated with semaglutidehad an additional mean weight change of -7.9%, while the mean weight change for the placebo group was +6.9%.

Medical insurance coverage. A major barrier to semaglutide treatment of obesity is the medication’s cost. At the website GoodRx (https://www.goodrx.com/), the estimated price for a 1-month supply of semaglutide (Wegovy) is $1,350.²⁰ By contrast, a 1-month supply of phentermine-topiramate (Qsymia) is approximately $205. Currently, many medical insurance plans do not cover the cost of semaglutide treatment for weight loss. Patent protection for liraglutide may expire in the next few years, permitting the marketing of a lower-cost generic formulation, increasing the availability of the medication. However, as noted above, compared with liraglutide, semaglutide treatment results in much greater weight loss.

The most common adverse effects associated with semaglutide treatment are nausea, vomiting, diarrhea, and constipation. In one randomized clinical trial involving 1,961 patients, the frequency of adverse effects reported by patients taking semaglutide incrementally above the frequency of the same adverse effect reported by patients on placebo was: nausea (27%), vomiting (18%), diarrhea (16%), constipation (14%), dyspepsia (7%), and abdominal pain (5%).¹⁵ In this study, treatment was discontinued due to adverse effects in 7% and 3% of the patients in the semaglutide and placebo groups, respectively. Experts believe that adverse effects can be minimized by increasing the dose slowly and decreasing the dose if adverse effects are bothersome to the patient.

Measuring the benefits of semaglutide weight loss

Overweight and obesity are prevalent problems with many adverse consequences, including an increased risk of death. In population studies, weight loss following bariatric surgery is associated with a substantial reduction in mortality, cancer, and heart disease compared with conventional therapy.²¹ Over the next few years, the effect of semaglutide-induced weight loss on the rate of cancer and heart disease should become clear. If semaglutide treatment of obesity is associated with a reduction in cancer and heart disease, it would be a truly breakthrough medication. ●

Obesity is a major health problem in the United States. The Centers for Disease Control and Prevention (CDC) defines the problem as weight that is higher than what is healthy for a given height, with quantitative definitions of overweight and obesity as body mass indices (BMIs) of 25 to 29.9 kg/m² and ≥ 30 kg/m², respectively.¹ The prevalence of obesity among adults in 2017 ̶ 2018 was reported by the CDC to be 42.4%.² Among women, the reported prevalence of obesity was lowest among Asian individuals (17.2%) and greatest among non-Hispanic Black individuals (56.9%), with White (39.8%) and Hispanic individuals (43.7%) having rates in between.² In a meta-analysis of prospective studies that included 4 million people who were never smokers and had no chronic disease at baseline, age- and sex-adjusted mortality rates were studied over a median of 14 years of follow-up.³ Compared with those with a BMI of 20 to 25 kg/m², people with a BMI of 30 to 34.9 kg/m² or a BMI of 35 to 39.9 kg/m² had increased risks of death of 46% and 94%, respectively, demonstrating that obesity increases this risk.³

The increased risk of death associated with obesity is caused by obesity-related diseases that cause early mortality, including diabetes mellitus (DM), dyslipidemia, hypertension, coronary heart disease, heart failure, atrial fibrillation, stroke, and venous thromboembolic events.⁴ Obesity is also associated with an increased risk of many cancers, including cancer of the endometrium, kidney, esophagus, stomach, colon, rectum, gallbladder, pancreas, liver, and breast.⁵ With regard to gynecologic disease, obesity is associated with an increased risk of fibroids and heavy menstrual bleeding.⁶ For pregnant patients, obesity is associated with increased risks of⁷:

• miscarriage and stillbirth
• preeclampsia and gestational hypertension
• gestational diabetes
• severe maternal morbidity
• postterm pregnancy
• venous thromboembolism
• endometritis.

For obese patients, weight loss can normalize blood pressure, reduce the risk of cardiovascular events, decrease the risk of cancer, and cure type 2 DM.⁸

Bariatric surgery: The gold standard treatment for reliable and sustained weight loss

All patients with obesity should be counseled to reduce caloric intake and increase physical activity. Dietary counseling provided by a nutritionist may help reinforce advice given by a provider. However, lifestyle interventions are associated with modest weight loss (<5% of bodyweight; FIGURE).⁹ The gold standard treatment for reliable and sustained weight loss is bariatric surgery.

In the Swedish Obese Subjects study, involving 2,010 people, following bariatric surgery the mean decrease in bodyweight was 23% at 2 years, with a slow increase in weight thereafter, resulting in a sustained mean weight loss of 18% at 10 years.⁸ In this study, people in the diet and exercise control group had no change in bodyweight over 10 years of follow-up.⁸ Not all eligible obese patients want to undergo bariatric surgery because it is an arduous sequential process involving 6 months of intensive preoperative preparation, bariatric surgery, recovery, and intensive postoperative follow-up. The perioperative mortality rate is 0.03% to 0.2%.¹⁰ Following bariatric surgery, additional operations may be necessary for more than 10% of patients.¹⁰ With recent breakthroughs in the medication management of obesity, patients who do not want bariatric surgery can achieve reliable weight loss of greater than 10% of body weight with glucagon-like peptide -1 (GLP-1) agonists.

ILLUSTRATION: KIMBERLY MARTENS FOR OBG MANAGEMENT

GLP-1 agonist analogues: Practice-changing breakthrough in medication treatment

GLP-1, a 30 amino acid peptide, is produced by intestinal enteroendocrine cells and neurons in the medulla and hypothalamus.¹¹ GLP-1 reduces hunger cravings and causes satiety, reducing daily food intake.¹² GLP-1 also enhances the secretion of insulin, making GLP-1 agonists an effective treatment for type 2 DM. In humans and experimental animals, the administration of exogenous GLP-1 agonists decreases hunger cravings and causes satiety, reducing food intake, resulting in weight loss.¹² The synthetic GLP-1 agonists, liraglutide (Saxenda) and semaglutide (Wegovy) are approved by the US Food and Drug Administration (FDA) as anti-obesity medications.

Native GLP-1 has a short circulating half-life of approximately 2 minutes. The synthetic GLP-1 agonist medications liraglutide and semaglutide are modified to significantly increase their half-life. Liraglutide is a modified version of GLP-1 with a palmitic acid side chain and an amino acid spacer resulting in reduced degradation and a 15-hour half-life, necessitating daily administration. Semaglutide has a steric acid diacid at Lys26, a large synthetic spacer, a modification of amino acid 8 with the addition of α-aminobutyric acid and a 165-hour half-life, permitting weekly administration.¹³ For weight loss, liraglutide and semaglultide are administered by subcutaneous injection. Tirzepatide (Mounjaro) is a novel GLP-1 agonist. It is also a gastric inhibitory peptide, is FDA approved to treat type 2 DM, and is awaiting FDA approval as a weight loss medication.Tirzepatide causes substantial weight loss, similar to the effect of semaglutide.¹⁴

Semaglutide and weight loss

Semaglutide is approved by the FDA for chronic weight management as an adjunct to a reduced-calorie diet and increased physical activity in adults with a BMI ≥ 30 kg/m² or ≥ 27 kg/m² in the presence of a weight-related comorbidity. It is also FDA approved to treat type 2 DM.

In a weight loss trial, 1,961 overweight and obese patients with a mean BMI of 38 kg/m², were randomly assigned to semaglutide or placebo treatment for 68 weeks. All the participants were following a regimen that included a calorie-reduced diet and increased physical activity. The mean changes in body weight for the patients in the semaglutide and placebo treatment groups were -14.9% and -2.4%, respectively. The treatment difference was -12.4% (95% confidence interval [CI], -13.4% to -11.5%; P <.001). In this study, compared with placebo, semaglutide treatment resulted in a greater decrease in waist circumference, -5.3 in versus -1.6 in.¹⁵ A network meta-analysis of the efficacy of weight loss medicines indicates that semaglutide is the most effective medication currently FDA approved for weight loss, reliably producing substantial weight loss (FIGURE).⁹

In one randomized clinical trial, investigators directly compared the efficacy of semaglutide and liraglutide in achieving weight loss. In this trial, 338 patients were assigned randomly to treatment with semaglutide 2.4 mg weekly subcutaneous injection, liraglutide 3.0 mg daily subcutaneous injection, or placebo. All the participants were following a regimen that included a calorie-reduced diet and increased physical activity.¹⁶ After 68 weeks of treatment, the mean weight changes were -15.8%, -6.4%, and -1.9% in the semaglutide, liraglutide, and placebo groups, respectively. The difference between the semaglutide and liraglutide groups was -9.4% (95% CI, -12% to -6.8%; P <.001).¹⁶

Continue to: Semaglutide dose-escalation and contraindications...

 

 

Semaglutide dose-escalation and contraindications

For weight loss, the target dose of semaglutide is 2.4 mg once weekly subcutaneous injection achieved by sequential dose escalation. To give patients time to adjust to adverse effects caused by the medication, a standardized dose-escalation regimen is recommended. The FDA-approved escalation regimen for semaglutide treatment begins with a weekly subcutaneous dose of 0.25 mg for 4 weeks, followed by an increase in the weekly dosage every 4 weeks: 0.5 mg, 1.0 mg, 1.7 mg, and 2.4 mg.¹⁷ To support the dose-escalation process there are 5 unique autoinjectors that deliver the appropriate dose for the current step.

Semaglutide is contraindicated if the patient has an allergy to the medication or if there is a personal or family history of medullary thyroid cancer.¹⁷ In animal toxicology studies, semaglutide at clinically relevant dosing was associated with an increased risk of developing medullary thyroid cancer. Patients with a personal history of multiple endocrine neoplasia syndrome type 2, (medullary thyroid cancer, pheochromocytoma, and primary hyperparathyroidism) should not take semaglutide. Semaglutide may cause fetal harm and the FDA recommends discontinuing semaglutide at least 2 months before pregnancy.¹⁷ According to the FDA, the safety of semaglutide during breastfeeding has not been established. In Canada, breastfeeding is a contraindication to semaglutide treatment.¹⁸

Limitations of medication treatment of obesity

There are important limitations to semaglutide treatment of obesity, including:

• weight gain after stopping treatment
• limited medical insurance supportfor an expensive medication treatment
• bothersome adverse effects.

Weight gain posttreatment. After stopping medication treatment of obesity, weight gain occurs in most patients. However, patients may remain below baseline weight for a long time after stopping medication therapy. In one trial of 803 patients, after 20 weeks of semaglutide treatment (16-week dose-escalation phase, followed by 4 weeks on a weekly dose of 2.4 mg), the participants were randomized to 48 additional weeks of semaglutide or placebo.¹⁹ All the participants were following a regimen that included a calorie-reduced diet and increased physical activity. At the initial 20 weeks of treatment time point the mean weight change was -10.6%. Over the following 48 weeks, the patients treated with semaglutidehad an additional mean weight change of -7.9%, while the mean weight change for the placebo group was +6.9%.

Medical insurance coverage. A major barrier to semaglutide treatment of obesity is the medication’s cost. At the website GoodRx (https://www.goodrx.com/), the estimated price for a 1-month supply of semaglutide (Wegovy) is $1,350.²⁰ By contrast, a 1-month supply of phentermine-topiramate (Qsymia) is approximately $205. Currently, many medical insurance plans do not cover the cost of semaglutide treatment for weight loss. Patent protection for liraglutide may expire in the next few years, permitting the marketing of a lower-cost generic formulation, increasing the availability of the medication. However, as noted above, compared with liraglutide, semaglutide treatment results in much greater weight loss.

The most common adverse effects associated with semaglutide treatment are nausea, vomiting, diarrhea, and constipation. In one randomized clinical trial involving 1,961 patients, the frequency of adverse effects reported by patients taking semaglutide incrementally above the frequency of the same adverse effect reported by patients on placebo was: nausea (27%), vomiting (18%), diarrhea (16%), constipation (14%), dyspepsia (7%), and abdominal pain (5%).¹⁵ In this study, treatment was discontinued due to adverse effects in 7% and 3% of the patients in the semaglutide and placebo groups, respectively. Experts believe that adverse effects can be minimized by increasing the dose slowly and decreasing the dose if adverse effects are bothersome to the patient.

Measuring the benefits of semaglutide weight loss

Overweight and obesity are prevalent problems with many adverse consequences, including an increased risk of death. In population studies, weight loss following bariatric surgery is associated with a substantial reduction in mortality, cancer, and heart disease compared with conventional therapy.²¹ Over the next few years, the effect of semaglutide-induced weight loss on the rate of cancer and heart disease should become clear. If semaglutide treatment of obesity is associated with a reduction in cancer and heart disease, it would be a truly breakthrough medication. ●

Obesity is a major health problem in the United States. The Centers for Disease Control and Prevention (CDC) defines the problem as weight that is higher than what is healthy for a given height, with quantitative definitions of overweight and obesity as body mass indices (BMIs) of 25 to 29.9 kg/m² and ≥ 30 kg/m², respectively.¹ The prevalence of obesity among adults in 2017 ̶ 2018 was reported by the CDC to be 42.4%.² Among women, the reported prevalence of obesity was lowest among Asian individuals (17.2%) and greatest among non-Hispanic Black individuals (56.9%), with White (39.8%) and Hispanic individuals (43.7%) having rates in between.² In a meta-analysis of prospective studies that included 4 million people who were never smokers and had no chronic disease at baseline, age- and sex-adjusted mortality rates were studied over a median of 14 years of follow-up.³ Compared with those with a BMI of 20 to 25 kg/m², people with a BMI of 30 to 34.9 kg/m² or a BMI of 35 to 39.9 kg/m² had increased risks of death of 46% and 94%, respectively, demonstrating that obesity increases this risk.³

The increased risk of death associated with obesity is caused by obesity-related diseases that cause early mortality, including diabetes mellitus (DM), dyslipidemia, hypertension, coronary heart disease, heart failure, atrial fibrillation, stroke, and venous thromboembolic events.⁴ Obesity is also associated with an increased risk of many cancers, including cancer of the endometrium, kidney, esophagus, stomach, colon, rectum, gallbladder, pancreas, liver, and breast.⁵ With regard to gynecologic disease, obesity is associated with an increased risk of fibroids and heavy menstrual bleeding.⁶ For pregnant patients, obesity is associated with increased risks of⁷:

• miscarriage and stillbirth
• preeclampsia and gestational hypertension
• gestational diabetes
• severe maternal morbidity
• postterm pregnancy
• venous thromboembolism
• endometritis.

For obese patients, weight loss can normalize blood pressure, reduce the risk of cardiovascular events, decrease the risk of cancer, and cure type 2 DM.⁸

Bariatric surgery: The gold standard treatment for reliable and sustained weight loss

All patients with obesity should be counseled to reduce caloric intake and increase physical activity. Dietary counseling provided by a nutritionist may help reinforce advice given by a provider. However, lifestyle interventions are associated with modest weight loss (<5% of bodyweight; FIGURE).⁹ The gold standard treatment for reliable and sustained weight loss is bariatric surgery.

In the Swedish Obese Subjects study, involving 2,010 people, following bariatric surgery the mean decrease in bodyweight was 23% at 2 years, with a slow increase in weight thereafter, resulting in a sustained mean weight loss of 18% at 10 years.⁸ In this study, people in the diet and exercise control group had no change in bodyweight over 10 years of follow-up.⁸ Not all eligible obese patients want to undergo bariatric surgery because it is an arduous sequential process involving 6 months of intensive preoperative preparation, bariatric surgery, recovery, and intensive postoperative follow-up. The perioperative mortality rate is 0.03% to 0.2%.¹⁰ Following bariatric surgery, additional operations may be necessary for more than 10% of patients.¹⁰ With recent breakthroughs in the medication management of obesity, patients who do not want bariatric surgery can achieve reliable weight loss of greater than 10% of body weight with glucagon-like peptide -1 (GLP-1) agonists.

ILLUSTRATION: KIMBERLY MARTENS FOR OBG MANAGEMENT

GLP-1 agonist analogues: Practice-changing breakthrough in medication treatment

GLP-1, a 30 amino acid peptide, is produced by intestinal enteroendocrine cells and neurons in the medulla and hypothalamus.¹¹ GLP-1 reduces hunger cravings and causes satiety, reducing daily food intake.¹² GLP-1 also enhances the secretion of insulin, making GLP-1 agonists an effective treatment for type 2 DM. In humans and experimental animals, the administration of exogenous GLP-1 agonists decreases hunger cravings and causes satiety, reducing food intake, resulting in weight loss.¹² The synthetic GLP-1 agonists, liraglutide (Saxenda) and semaglutide (Wegovy) are approved by the US Food and Drug Administration (FDA) as anti-obesity medications.

Native GLP-1 has a short circulating half-life of approximately 2 minutes. The synthetic GLP-1 agonist medications liraglutide and semaglutide are modified to significantly increase their half-life. Liraglutide is a modified version of GLP-1 with a palmitic acid side chain and an amino acid spacer resulting in reduced degradation and a 15-hour half-life, necessitating daily administration. Semaglutide has a steric acid diacid at Lys26, a large synthetic spacer, a modification of amino acid 8 with the addition of α-aminobutyric acid and a 165-hour half-life, permitting weekly administration.¹³ For weight loss, liraglutide and semaglultide are administered by subcutaneous injection. Tirzepatide (Mounjaro) is a novel GLP-1 agonist. It is also a gastric inhibitory peptide, is FDA approved to treat type 2 DM, and is awaiting FDA approval as a weight loss medication.Tirzepatide causes substantial weight loss, similar to the effect of semaglutide.¹⁴

Semaglutide and weight loss

Semaglutide is approved by the FDA for chronic weight management as an adjunct to a reduced-calorie diet and increased physical activity in adults with a BMI ≥ 30 kg/m² or ≥ 27 kg/m² in the presence of a weight-related comorbidity. It is also FDA approved to treat type 2 DM.

In a weight loss trial, 1,961 overweight and obese patients with a mean BMI of 38 kg/m², were randomly assigned to semaglutide or placebo treatment for 68 weeks. All the participants were following a regimen that included a calorie-reduced diet and increased physical activity. The mean changes in body weight for the patients in the semaglutide and placebo treatment groups were -14.9% and -2.4%, respectively. The treatment difference was -12.4% (95% confidence interval [CI], -13.4% to -11.5%; P <.001). In this study, compared with placebo, semaglutide treatment resulted in a greater decrease in waist circumference, -5.3 in versus -1.6 in.¹⁵ A network meta-analysis of the efficacy of weight loss medicines indicates that semaglutide is the most effective medication currently FDA approved for weight loss, reliably producing substantial weight loss (FIGURE).⁹

In one randomized clinical trial, investigators directly compared the efficacy of semaglutide and liraglutide in achieving weight loss. In this trial, 338 patients were assigned randomly to treatment with semaglutide 2.4 mg weekly subcutaneous injection, liraglutide 3.0 mg daily subcutaneous injection, or placebo. All the participants were following a regimen that included a calorie-reduced diet and increased physical activity.¹⁶ After 68 weeks of treatment, the mean weight changes were -15.8%, -6.4%, and -1.9% in the semaglutide, liraglutide, and placebo groups, respectively. The difference between the semaglutide and liraglutide groups was -9.4% (95% CI, -12% to -6.8%; P <.001).¹⁶

Continue to: Semaglutide dose-escalation and contraindications...

 

 

Semaglutide dose-escalation and contraindications

For weight loss, the target dose of semaglutide is 2.4 mg once weekly subcutaneous injection achieved by sequential dose escalation. To give patients time to adjust to adverse effects caused by the medication, a standardized dose-escalation regimen is recommended. The FDA-approved escalation regimen for semaglutide treatment begins with a weekly subcutaneous dose of 0.25 mg for 4 weeks, followed by an increase in the weekly dosage every 4 weeks: 0.5 mg, 1.0 mg, 1.7 mg, and 2.4 mg.¹⁷ To support the dose-escalation process there are 5 unique autoinjectors that deliver the appropriate dose for the current step.

Semaglutide is contraindicated if the patient has an allergy to the medication or if there is a personal or family history of medullary thyroid cancer.¹⁷ In animal toxicology studies, semaglutide at clinically relevant dosing was associated with an increased risk of developing medullary thyroid cancer. Patients with a personal history of multiple endocrine neoplasia syndrome type 2, (medullary thyroid cancer, pheochromocytoma, and primary hyperparathyroidism) should not take semaglutide. Semaglutide may cause fetal harm and the FDA recommends discontinuing semaglutide at least 2 months before pregnancy.¹⁷ According to the FDA, the safety of semaglutide during breastfeeding has not been established. In Canada, breastfeeding is a contraindication to semaglutide treatment.¹⁸

Limitations of medication treatment of obesity

There are important limitations to semaglutide treatment of obesity, including:

• weight gain after stopping treatment
• limited medical insurance supportfor an expensive medication treatment
• bothersome adverse effects.

Weight gain posttreatment. After stopping medication treatment of obesity, weight gain occurs in most patients. However, patients may remain below baseline weight for a long time after stopping medication therapy. In one trial of 803 patients, after 20 weeks of semaglutide treatment (16-week dose-escalation phase, followed by 4 weeks on a weekly dose of 2.4 mg), the participants were randomized to 48 additional weeks of semaglutide or placebo.¹⁹ All the participants were following a regimen that included a calorie-reduced diet and increased physical activity. At the initial 20 weeks of treatment time point the mean weight change was -10.6%. Over the following 48 weeks, the patients treated with semaglutidehad an additional mean weight change of -7.9%, while the mean weight change for the placebo group was +6.9%.

Medical insurance coverage. A major barrier to semaglutide treatment of obesity is the medication’s cost. At the website GoodRx (https://www.goodrx.com/), the estimated price for a 1-month supply of semaglutide (Wegovy) is $1,350.²⁰ By contrast, a 1-month supply of phentermine-topiramate (Qsymia) is approximately $205. Currently, many medical insurance plans do not cover the cost of semaglutide treatment for weight loss. Patent protection for liraglutide may expire in the next few years, permitting the marketing of a lower-cost generic formulation, increasing the availability of the medication. However, as noted above, compared with liraglutide, semaglutide treatment results in much greater weight loss.

The most common adverse effects associated with semaglutide treatment are nausea, vomiting, diarrhea, and constipation. In one randomized clinical trial involving 1,961 patients, the frequency of adverse effects reported by patients taking semaglutide incrementally above the frequency of the same adverse effect reported by patients on placebo was: nausea (27%), vomiting (18%), diarrhea (16%), constipation (14%), dyspepsia (7%), and abdominal pain (5%).¹⁵ In this study, treatment was discontinued due to adverse effects in 7% and 3% of the patients in the semaglutide and placebo groups, respectively. Experts believe that adverse effects can be minimized by increasing the dose slowly and decreasing the dose if adverse effects are bothersome to the patient.

Measuring the benefits of semaglutide weight loss

Overweight and obesity are prevalent problems with many adverse consequences, including an increased risk of death. In population studies, weight loss following bariatric surgery is associated with a substantial reduction in mortality, cancer, and heart disease compared with conventional therapy.²¹ Over the next few years, the effect of semaglutide-induced weight loss on the rate of cancer and heart disease should become clear. If semaglutide treatment of obesity is associated with a reduction in cancer and heart disease, it would be a truly breakthrough medication. ●

McElwee ER, Oliver EA, McFarling K, et al. Risk of stillbirth in pregnancies complicated by diabetes, stratified by fetal growth. Obstet Gynecol. 2023;141:801-809. doi:10.1097/AOG.0000000000005102.

EXPERT COMMENTARY 

Stillbirth is defined as intrauterine demise at or beyond 20 weeks’ gestation. Pregestational DM and GDM significantly increase the risk of stillbirth. Both fetal growth restriction and macrosomia are common complications of pregnancies affected by diabetes, and they further increase the risk of stillbirth. While maternal variables such as glycemic control and medication requirement are currently used to assess the risks of expectant management and inform delivery timing, abnormal fetal growth is not.

Investigators sought to evaluate the stillbirth rates per week of expectant management during the late third trimester stratified by birth weight (as a surrogate for fetal growth) in pregnancies complicated by PG-DM or GDM.

Details of the study

McElwee and colleagues used the US National Vital Statistics System to identify nonanomalous singleton pregnancies complicated by PG-DM or GDM from 2014 to 2017.¹ Pregnancies were stratified by birth weight and categorized as being LGA (birth weight > 90th percentile for gestational age), SGA (birth weight < 10th percentile for gestational age), or AGA. Stillbirths were identified from 34 0/7 through 39 6/7 weeks of gestation, and conditional stillbirth rates per 10,000 pregnancies were calculated for each week of gestation.

Results. Among 834,631 pregnancies complicated by PG-DM (13.1%) or GDM (86.9%), there were 3,033 stillbirths, of which 61% were in pregnancies with PG-DM. Stillbirth rates increased with advancing gestational age for both PG-DM and GDM regardless of birth weight. In pregnancies with PG-DM, fetuses that were LGA or SGA had a higher relative risk of stillbirth compared with their AGA counterparts at each gestational age. This stillbirth risk was highest in pregnancies with PG-DM that were LGA. At 39 weeks, the stillbirth rate in this population was 96.9/10,000 ongoing pregnancies and was 5 times higher than pregnancies with PG-DM that were AGA. When the GDM-related AGA group was selected as the referent (as the lowest-risk comparison group), pregnancies with PG-DM that were LGA had a 21-times higher relative risk of stillbirth at 37 and 38 weeks of gestation.

Study strengths and limitations

Decisions on the optimal timing of delivery seek to strike a balance between the increased neonatal morbidity with delivery before 39 weeks’ gestation and the increased risk of stillbirth with expectant management. In pregnancies complicated by diabetes, current guidelines from the American College of Obstetricians and Gynecologists recommend consideration of maternal variables, such as medication requirement, glycemic control, and vascular sequelae, to inform decisions on delivery timing, as these factors have been postulated to influence the risk of stillbirth with pregnancy prolongation.² These recommendations are based largely on expert opinion and retrospective data.

The question of how fetal growth abnormalities factor into this complicated decision making is also an area of low-quality evidence despite studies that demonstrate that both SGA and LGA fetuses in pregnancies complicated by diabetes are at increased risk of stillbirth.³

The large population-based study design by McElwee and colleagues allowed the investigators to examine a rare event (stillbirth) with multiple stratification levels and sufficient statistical power and to contribute to this literature.

Significant limitations, however, must be considered before generalizing these results. The data were restricted to variables available on birth and death certificates, and more granular information—such as the type of DM, level of glycemic control, frequency of antenatal testing, and stillbirth work-up—could not be assessed. Ultrasonographic estimations of fetal weight also were not included. Birth weight data were used as a proxy, although we know that these variables do not always correlate well given the limited accuracy of ultrasonography in assessing projected birth weight, particularly later in pregnancy. The authors also did not control for highly prevalent variables (for example, hypertension, obesity) that are likely associated with abnormal fetal growth and stillbirth in these populations. ●

McElwee ER, Oliver EA, McFarling K, et al. Risk of stillbirth in pregnancies complicated by diabetes, stratified by fetal growth. Obstet Gynecol. 2023;141:801-809. doi:10.1097/AOG.0000000000005102.

EXPERT COMMENTARY 

Stillbirth is defined as intrauterine demise at or beyond 20 weeks’ gestation. Pregestational DM and GDM significantly increase the risk of stillbirth. Both fetal growth restriction and macrosomia are common complications of pregnancies affected by diabetes, and they further increase the risk of stillbirth. While maternal variables such as glycemic control and medication requirement are currently used to assess the risks of expectant management and inform delivery timing, abnormal fetal growth is not.

Investigators sought to evaluate the stillbirth rates per week of expectant management during the late third trimester stratified by birth weight (as a surrogate for fetal growth) in pregnancies complicated by PG-DM or GDM.

Details of the study

McElwee and colleagues used the US National Vital Statistics System to identify nonanomalous singleton pregnancies complicated by PG-DM or GDM from 2014 to 2017.¹ Pregnancies were stratified by birth weight and categorized as being LGA (birth weight > 90th percentile for gestational age), SGA (birth weight < 10th percentile for gestational age), or AGA. Stillbirths were identified from 34 0/7 through 39 6/7 weeks of gestation, and conditional stillbirth rates per 10,000 pregnancies were calculated for each week of gestation.

Results. Among 834,631 pregnancies complicated by PG-DM (13.1%) or GDM (86.9%), there were 3,033 stillbirths, of which 61% were in pregnancies with PG-DM. Stillbirth rates increased with advancing gestational age for both PG-DM and GDM regardless of birth weight. In pregnancies with PG-DM, fetuses that were LGA or SGA had a higher relative risk of stillbirth compared with their AGA counterparts at each gestational age. This stillbirth risk was highest in pregnancies with PG-DM that were LGA. At 39 weeks, the stillbirth rate in this population was 96.9/10,000 ongoing pregnancies and was 5 times higher than pregnancies with PG-DM that were AGA. When the GDM-related AGA group was selected as the referent (as the lowest-risk comparison group), pregnancies with PG-DM that were LGA had a 21-times higher relative risk of stillbirth at 37 and 38 weeks of gestation.

Study strengths and limitations

Decisions on the optimal timing of delivery seek to strike a balance between the increased neonatal morbidity with delivery before 39 weeks’ gestation and the increased risk of stillbirth with expectant management. In pregnancies complicated by diabetes, current guidelines from the American College of Obstetricians and Gynecologists recommend consideration of maternal variables, such as medication requirement, glycemic control, and vascular sequelae, to inform decisions on delivery timing, as these factors have been postulated to influence the risk of stillbirth with pregnancy prolongation.² These recommendations are based largely on expert opinion and retrospective data.

The question of how fetal growth abnormalities factor into this complicated decision making is also an area of low-quality evidence despite studies that demonstrate that both SGA and LGA fetuses in pregnancies complicated by diabetes are at increased risk of stillbirth.³

The large population-based study design by McElwee and colleagues allowed the investigators to examine a rare event (stillbirth) with multiple stratification levels and sufficient statistical power and to contribute to this literature.

Significant limitations, however, must be considered before generalizing these results. The data were restricted to variables available on birth and death certificates, and more granular information—such as the type of DM, level of glycemic control, frequency of antenatal testing, and stillbirth work-up—could not be assessed. Ultrasonographic estimations of fetal weight also were not included. Birth weight data were used as a proxy, although we know that these variables do not always correlate well given the limited accuracy of ultrasonography in assessing projected birth weight, particularly later in pregnancy. The authors also did not control for highly prevalent variables (for example, hypertension, obesity) that are likely associated with abnormal fetal growth and stillbirth in these populations. ●

McElwee ER, Oliver EA, McFarling K, et al. Risk of stillbirth in pregnancies complicated by diabetes, stratified by fetal growth. Obstet Gynecol. 2023;141:801-809. doi:10.1097/AOG.0000000000005102.

EXPERT COMMENTARY 

Stillbirth is defined as intrauterine demise at or beyond 20 weeks’ gestation. Pregestational DM and GDM significantly increase the risk of stillbirth. Both fetal growth restriction and macrosomia are common complications of pregnancies affected by diabetes, and they further increase the risk of stillbirth. While maternal variables such as glycemic control and medication requirement are currently used to assess the risks of expectant management and inform delivery timing, abnormal fetal growth is not.

Investigators sought to evaluate the stillbirth rates per week of expectant management during the late third trimester stratified by birth weight (as a surrogate for fetal growth) in pregnancies complicated by PG-DM or GDM.

Details of the study

McElwee and colleagues used the US National Vital Statistics System to identify nonanomalous singleton pregnancies complicated by PG-DM or GDM from 2014 to 2017.¹ Pregnancies were stratified by birth weight and categorized as being LGA (birth weight > 90th percentile for gestational age), SGA (birth weight < 10th percentile for gestational age), or AGA. Stillbirths were identified from 34 0/7 through 39 6/7 weeks of gestation, and conditional stillbirth rates per 10,000 pregnancies were calculated for each week of gestation.

Results. Among 834,631 pregnancies complicated by PG-DM (13.1%) or GDM (86.9%), there were 3,033 stillbirths, of which 61% were in pregnancies with PG-DM. Stillbirth rates increased with advancing gestational age for both PG-DM and GDM regardless of birth weight. In pregnancies with PG-DM, fetuses that were LGA or SGA had a higher relative risk of stillbirth compared with their AGA counterparts at each gestational age. This stillbirth risk was highest in pregnancies with PG-DM that were LGA. At 39 weeks, the stillbirth rate in this population was 96.9/10,000 ongoing pregnancies and was 5 times higher than pregnancies with PG-DM that were AGA. When the GDM-related AGA group was selected as the referent (as the lowest-risk comparison group), pregnancies with PG-DM that were LGA had a 21-times higher relative risk of stillbirth at 37 and 38 weeks of gestation.

Study strengths and limitations

Decisions on the optimal timing of delivery seek to strike a balance between the increased neonatal morbidity with delivery before 39 weeks’ gestation and the increased risk of stillbirth with expectant management. In pregnancies complicated by diabetes, current guidelines from the American College of Obstetricians and Gynecologists recommend consideration of maternal variables, such as medication requirement, glycemic control, and vascular sequelae, to inform decisions on delivery timing, as these factors have been postulated to influence the risk of stillbirth with pregnancy prolongation.² These recommendations are based largely on expert opinion and retrospective data.

The question of how fetal growth abnormalities factor into this complicated decision making is also an area of low-quality evidence despite studies that demonstrate that both SGA and LGA fetuses in pregnancies complicated by diabetes are at increased risk of stillbirth.³

The large population-based study design by McElwee and colleagues allowed the investigators to examine a rare event (stillbirth) with multiple stratification levels and sufficient statistical power and to contribute to this literature.

Significant limitations, however, must be considered before generalizing these results. The data were restricted to variables available on birth and death certificates, and more granular information—such as the type of DM, level of glycemic control, frequency of antenatal testing, and stillbirth work-up—could not be assessed. Ultrasonographic estimations of fetal weight also were not included. Birth weight data were used as a proxy, although we know that these variables do not always correlate well given the limited accuracy of ultrasonography in assessing projected birth weight, particularly later in pregnancy. The authors also did not control for highly prevalent variables (for example, hypertension, obesity) that are likely associated with abnormal fetal growth and stillbirth in these populations. ●

Hidradenitis suppurativa (HS), a chronic inflammatory disease that is characterized by tender inflamed nodules of the skin and subcutaneous tissue, disproportionately affects postpubertal females as well as Black/African American individuals. The nodules can rupture, form sinus tracts, and scar. ¹ Hidradenitis suppurativa has been associated with cardiovascular disease, type 2 diabetes mellitus, polycystic ovary syndrome, depression, suicide, and substance use disorders. Because of the symptom burden and associated conditions, HS can be a painful and distressing disease that substantially impairs the quality of life for individuals with this condition. ²

Pain is a commonly reported symptom in HS that often goes untreated. Furthermore, HS-related pain is complex due to the involvement of different pain types that require various treatment modalities.³ According to Savage et al,⁴ recognizing whether HS-related pain is acute, chronic, neuropathic, or nociceptive is vital in establishing a framework for an effective pain management scheme. Currently, such established multimodal pain management strategies in dermatology do not exist. In 2021, dermatology-specific pain management strategies proposed the use of a multimodal regimen to address the multifaceted nature of HS-related pain.⁴ However, these strategies failed to recognize the systemic racial and ethnic biases in the US health care system that undermine pain management care for minority groups.^5,6 One approach to combatting racial disparities in pain management is determining average pain levels across racial groups.⁷ This study sought to compare HS-related pain scores by racial groups. Furthermore, we assessed differences in perception of patients’ respective pain management regimens by race. We hypothesized that the average HS-related pain intensities and pain management would differ between self-reported racial groups.

Methods  

This cross-sectional study took place over 5 months (August through December 2021). A survey was emailed to 2198 adult patients with HS in the University of Alabama Health System. The survey consisted of demographic and general questions about a patient’s HS. Pain scores were captured using the numeric rating scale (NRS), a measurement tool for pain intensity on a scale from 0 to 10. ⁸ Age at diagnosis, gender, education level, household income, total body areas affected by HS, disease severity (categorized as mild, moderate, and severe), comorbidities including mood disorders, tobacco use, and HS and HS-related pain medication regimens also were collected. Additionally, participants were asked about their level of agreement with the following statements: “I am satisfied with how my pain related to HS is being managed by my doctors” and “My pain related to HS is under control.” The level of agreement was measured using a 5-point Likert scale, with responses ranging from strongly disagree to strongly agree. All data included in the analysis were self-reported. The study received institutional review board approval for the University of Alabama at Birmingham.

Statistical Analysis—Descriptive statistics were used to assess statistical differences in patient characteristics of Black/African American participants compared to other participants, including White, Asian, and Hispanic/Latino participants. Thirteen participants were excluded from the final analysis: 2 participants were missing data, and 11 biracial participants were excluded due to overlapping White and Black/African American races that may have confounded the analysis. Categorical variables were reported as frequencies and percentages, and χ² and Fisher exact tests, when necessary, were used to test for statistically significant differences. Continuous variables were summarized with means and standard deviations, and a t test was used for statistically significant differences.

Logistic regression was performed to assess the relationship between race and pain after adjusting for confounding variables such as obesity, current tobacco use, self-reported HS severity, and the presence of comorbidities. A total of 204 patient records were included in the analysis, of which 70 (34.3%) had a pain score of 8 or higher, which indicates very severe pain intensity levels on the NRS,⁸ and were selected as a cut point based on the distribution of responses. For this cross-sectional cohort, our approach was to compare characteristics of those classified with a top score of 8 or higher (n=70) vs a top score of 0 to 7 (n=134)(cases vs noncases). Statistical analyses were performed using JMP Pro 16 (JMP Statistical Discovery LLC) at an α=.05 significance level; logistic regression was performed using SPSS Statistics (IBM). For the logistic regression, we grouped patient race into 2 categories: Black/African American and Other, which included White, Asian, and Hispanic/Latino participants.

Crude and adjusted multivariable logistic regression analyses were used to calculate prevalence odds ratios with 95% confidence intervals. Covariate inclusion in the multivariable logistic regression was based on a priori hypothesis/knowledge and was meant to estimate the independent effect of race after adjustment for income, HS severity, and history of prescription pain medication use. Other variables, including tobacco use, obesity, mood disorders, and current HS treatments, were all individually tested in the multivariate analysis and did not significantly impact the odds ratio for high pain. Statistical adjustment slightly decreased (19%) the magnitude between crude and adjusted prevalence odds ratios for the association between Black/African American race and high pain score.

Results  

Survey Demographics —The final analysis included 204 survey respondents. Most respondents were Black/African American (58.82%), and nearly all were female (89.71%)(Table 1). The mean age (SD) of respondents was 37.37 (11.29) years (range, 19-70 years). Many respondents reported having completed some college (36.27%) or receiving a bachelor’s degree (19.12%). Of patients who were not Black/African American, 10.71% had higher than a master’s degree, whereas no Black/African American patients held a degree higher than a master’s ( P = .0052). Additionally, more Black/African American respondents (35.83%) reported an annual household income level of less than $25,000 compared with respondents who were not Black/African American (19.05%, P = .0001). Most respondents rated the severity of their HS as moderate or severe (46.57% and 41.67%, respectively), and there was no significant difference in reported severity of HS between racial groups ( P = .5395).

Pain Scores—As documented in the Methods, respondents were asked to rate their HS-related pain intensity from 0 to 10 using the NRS. The average pain score (SD)—the level of pain intensity over the prior month—was 6.39 (2.56)(range, 0–10). The mean pain score (SD) at the time of the survey was 3.61 (2.98)(range, 0–10)(Table 1). These data revealed that Black/African American patients had a significantly higher average pain score (SD) than patients with HS who were not Black/African American (7.08 [2.49] and 5.40 [2.35], respectively; P<.0001). After adjustment with multivariable logistical regression, Black/African American patients had 4-fold increased odds for very severe levels of pain (score of ≥8) compared with patients who were not Black/African American.

Pain Management—Although pain scores were higher for Black/African American patients with HS, there was no significant difference in the perception of pain control between racial groups (P=.0761). Additionally, we found low income (adjusted prevalence odds ratio [POR], 0.22; 95% CI, 0.05-0.91), a history of prescription pain medication use (adjusted POR, 2.25; 95% CI, 1.13-4.51), and HS severity (adjusted POR, 4.40; 95% CI, 1.11-17.36) all to be independent risk factors contributing to higher pain scores in patients with HS (Table 2). Lastly, we noted current or reported history of pain medication use was significantly correlated with higher pain scores (P=.0280 and P=.0213, respectively).

Satisfaction With Pain Management—The level of satisfaction with physician management of HS-related pain was significantly different between Black/African American patients and those who were not Black/African American (P=.0129). Of those who identified as Black/African American, 26.7% (n=32) strongly disagreed with the statement, “I am satisfied with how my pain related to HS is being managed by my doctors,” whereas only 15.5% (n=13) of patients who were not Black/African American strongly disagreed. 

Comment

There is no cure for HS, and a large focus of treatment is pain management. Because racial disparities in the treatment of chronic pain will affect those with HS, we conducted a cross-sectional analysis of pain and pain management among HS patients. We found that Black/African American patients with HS have higher average pain scores than those who are not Black/African American and were 4 times more likely to experience very severe pain. Prior studies have established that patients with HS often report higher pain levels than patients with other chronic inflammatory skin conditions, ^7,8 and our study identified racial disparities in HS-related pain management.

Measuring pain is challenging because of its multidimensional and subjective nature, making it essential to consider underlying causes and patients’ emotional responses to pain.⁹ By adjusting for confounding factors that may influence pain, such as mood disorders, disease severity, comorbidities, and medication use, we were able to gain better insight into fundamental differences in average pain intensity levels among racial groups and assess what factors may be contributing to a patient’s pain perception. Our study determined that lower income levels, higher HS disease severity, and a history of prescription pain medication use were all independent risk factors for high pain. Of note, obesity, tobacco use, and mood disorders such as anxiety and depression did not significantly differ between racial groups or increase the odds of high pain between racial groups identified.

With low income being an independent risk factor for high pain, we must consider the social determinants of health and how they may influence the pain experience in HS. We speculate that low income may be associated with other social determinants of health for the patients assessed in this study, such as lack of social and community support or limited health care access that contribute to worse health outcomes.^10,11 In addition, low income contributes to limited access to medical care or treatments¹²; without access to effective HS management, lower-income patients may be at risk for higher disease severity and thus higher pain levels. However, economic stability is only a part of the whole picture; therefore, assessing the other social determinants of health in patients with HS may lead to better health outcomes and quality of life.

Another identified risk factor for high pain was a reported history of prescription pain medication use. This finding suggests that patients with moderate to severe pain likely have required stronger analgesic medications in the past. We further speculate that high pain levels in patients who have received prescription pain medications indicate either undertreatment, mistreatment, or recalcitrant pain. More research is needed to assess the relationship between HS-related pain intensity, analgesic medications, and providers who manage HS-related pain.

We also found that Black/African American patients with HS had a significantly higher dissatisfaction with their physician’s management of their pain, which could be attributable to several factors, including biological differences in medication metabolism (in which the patient has medication-resistant HS), undertreatment of pain, and/or poor doctor-patient relations. These reasons coincide with other diseases where health disparities are found.^13-15 Recognizing these factors will be key to dismantling the disparities in HS that are noted within this study. The limitations of this work include the cross-sectional study design and its inability to evaluate causal factors of high pain levels across racial groups, the NRS lack of insight on pain chronicity or pain experience,⁷ the lack of provider or institution perspectives, and self-reported data. Additionally, only patients with email access were included, which may have excluded vulnerable populations with more pain associated with their HS.

Our findings highlight an area for further investigation to assess why these racial differences exist in HS-related pain. The results also emphasize the need for research evaluating whether systemic or health care provider biases contribute to racial differences in HS-related pain management.

Acknowledgment — Dr. Weir was supported by the Predoctoral Clinical/Translational Research Program (TL1), a National Institutes of Health Ruth L. Kirschstein National Research Service Award (NRSA), through the University of Alabama at Birmingham (UAB) Center for Clinical and Translational Science (CCTS).  

Hidradenitis suppurativa (HS), a chronic inflammatory disease that is characterized by tender inflamed nodules of the skin and subcutaneous tissue, disproportionately affects postpubertal females as well as Black/African American individuals. The nodules can rupture, form sinus tracts, and scar. ¹ Hidradenitis suppurativa has been associated with cardiovascular disease, type 2 diabetes mellitus, polycystic ovary syndrome, depression, suicide, and substance use disorders. Because of the symptom burden and associated conditions, HS can be a painful and distressing disease that substantially impairs the quality of life for individuals with this condition. ²

Pain is a commonly reported symptom in HS that often goes untreated. Furthermore, HS-related pain is complex due to the involvement of different pain types that require various treatment modalities.³ According to Savage et al,⁴ recognizing whether HS-related pain is acute, chronic, neuropathic, or nociceptive is vital in establishing a framework for an effective pain management scheme. Currently, such established multimodal pain management strategies in dermatology do not exist. In 2021, dermatology-specific pain management strategies proposed the use of a multimodal regimen to address the multifaceted nature of HS-related pain.⁴ However, these strategies failed to recognize the systemic racial and ethnic biases in the US health care system that undermine pain management care for minority groups.^5,6 One approach to combatting racial disparities in pain management is determining average pain levels across racial groups.⁷ This study sought to compare HS-related pain scores by racial groups. Furthermore, we assessed differences in perception of patients’ respective pain management regimens by race. We hypothesized that the average HS-related pain intensities and pain management would differ between self-reported racial groups.

Methods  

This cross-sectional study took place over 5 months (August through December 2021). A survey was emailed to 2198 adult patients with HS in the University of Alabama Health System. The survey consisted of demographic and general questions about a patient’s HS. Pain scores were captured using the numeric rating scale (NRS), a measurement tool for pain intensity on a scale from 0 to 10. ⁸ Age at diagnosis, gender, education level, household income, total body areas affected by HS, disease severity (categorized as mild, moderate, and severe), comorbidities including mood disorders, tobacco use, and HS and HS-related pain medication regimens also were collected. Additionally, participants were asked about their level of agreement with the following statements: “I am satisfied with how my pain related to HS is being managed by my doctors” and “My pain related to HS is under control.” The level of agreement was measured using a 5-point Likert scale, with responses ranging from strongly disagree to strongly agree. All data included in the analysis were self-reported. The study received institutional review board approval for the University of Alabama at Birmingham.

Statistical Analysis—Descriptive statistics were used to assess statistical differences in patient characteristics of Black/African American participants compared to other participants, including White, Asian, and Hispanic/Latino participants. Thirteen participants were excluded from the final analysis: 2 participants were missing data, and 11 biracial participants were excluded due to overlapping White and Black/African American races that may have confounded the analysis. Categorical variables were reported as frequencies and percentages, and χ² and Fisher exact tests, when necessary, were used to test for statistically significant differences. Continuous variables were summarized with means and standard deviations, and a t test was used for statistically significant differences.

Logistic regression was performed to assess the relationship between race and pain after adjusting for confounding variables such as obesity, current tobacco use, self-reported HS severity, and the presence of comorbidities. A total of 204 patient records were included in the analysis, of which 70 (34.3%) had a pain score of 8 or higher, which indicates very severe pain intensity levels on the NRS,⁸ and were selected as a cut point based on the distribution of responses. For this cross-sectional cohort, our approach was to compare characteristics of those classified with a top score of 8 or higher (n=70) vs a top score of 0 to 7 (n=134)(cases vs noncases). Statistical analyses were performed using JMP Pro 16 (JMP Statistical Discovery LLC) at an α=.05 significance level; logistic regression was performed using SPSS Statistics (IBM). For the logistic regression, we grouped patient race into 2 categories: Black/African American and Other, which included White, Asian, and Hispanic/Latino participants.

Crude and adjusted multivariable logistic regression analyses were used to calculate prevalence odds ratios with 95% confidence intervals. Covariate inclusion in the multivariable logistic regression was based on a priori hypothesis/knowledge and was meant to estimate the independent effect of race after adjustment for income, HS severity, and history of prescription pain medication use. Other variables, including tobacco use, obesity, mood disorders, and current HS treatments, were all individually tested in the multivariate analysis and did not significantly impact the odds ratio for high pain. Statistical adjustment slightly decreased (19%) the magnitude between crude and adjusted prevalence odds ratios for the association between Black/African American race and high pain score.

Results  

Survey Demographics —The final analysis included 204 survey respondents. Most respondents were Black/African American (58.82%), and nearly all were female (89.71%)(Table 1). The mean age (SD) of respondents was 37.37 (11.29) years (range, 19-70 years). Many respondents reported having completed some college (36.27%) or receiving a bachelor’s degree (19.12%). Of patients who were not Black/African American, 10.71% had higher than a master’s degree, whereas no Black/African American patients held a degree higher than a master’s ( P = .0052). Additionally, more Black/African American respondents (35.83%) reported an annual household income level of less than $25,000 compared with respondents who were not Black/African American (19.05%, P = .0001). Most respondents rated the severity of their HS as moderate or severe (46.57% and 41.67%, respectively), and there was no significant difference in reported severity of HS between racial groups ( P = .5395).

Pain Scores—As documented in the Methods, respondents were asked to rate their HS-related pain intensity from 0 to 10 using the NRS. The average pain score (SD)—the level of pain intensity over the prior month—was 6.39 (2.56)(range, 0–10). The mean pain score (SD) at the time of the survey was 3.61 (2.98)(range, 0–10)(Table 1). These data revealed that Black/African American patients had a significantly higher average pain score (SD) than patients with HS who were not Black/African American (7.08 [2.49] and 5.40 [2.35], respectively; P<.0001). After adjustment with multivariable logistical regression, Black/African American patients had 4-fold increased odds for very severe levels of pain (score of ≥8) compared with patients who were not Black/African American.

Pain Management—Although pain scores were higher for Black/African American patients with HS, there was no significant difference in the perception of pain control between racial groups (P=.0761). Additionally, we found low income (adjusted prevalence odds ratio [POR], 0.22; 95% CI, 0.05-0.91), a history of prescription pain medication use (adjusted POR, 2.25; 95% CI, 1.13-4.51), and HS severity (adjusted POR, 4.40; 95% CI, 1.11-17.36) all to be independent risk factors contributing to higher pain scores in patients with HS (Table 2). Lastly, we noted current or reported history of pain medication use was significantly correlated with higher pain scores (P=.0280 and P=.0213, respectively).

Satisfaction With Pain Management—The level of satisfaction with physician management of HS-related pain was significantly different between Black/African American patients and those who were not Black/African American (P=.0129). Of those who identified as Black/African American, 26.7% (n=32) strongly disagreed with the statement, “I am satisfied with how my pain related to HS is being managed by my doctors,” whereas only 15.5% (n=13) of patients who were not Black/African American strongly disagreed. 

Comment

There is no cure for HS, and a large focus of treatment is pain management. Because racial disparities in the treatment of chronic pain will affect those with HS, we conducted a cross-sectional analysis of pain and pain management among HS patients. We found that Black/African American patients with HS have higher average pain scores than those who are not Black/African American and were 4 times more likely to experience very severe pain. Prior studies have established that patients with HS often report higher pain levels than patients with other chronic inflammatory skin conditions, ^7,8 and our study identified racial disparities in HS-related pain management.

Measuring pain is challenging because of its multidimensional and subjective nature, making it essential to consider underlying causes and patients’ emotional responses to pain.⁹ By adjusting for confounding factors that may influence pain, such as mood disorders, disease severity, comorbidities, and medication use, we were able to gain better insight into fundamental differences in average pain intensity levels among racial groups and assess what factors may be contributing to a patient’s pain perception. Our study determined that lower income levels, higher HS disease severity, and a history of prescription pain medication use were all independent risk factors for high pain. Of note, obesity, tobacco use, and mood disorders such as anxiety and depression did not significantly differ between racial groups or increase the odds of high pain between racial groups identified.

With low income being an independent risk factor for high pain, we must consider the social determinants of health and how they may influence the pain experience in HS. We speculate that low income may be associated with other social determinants of health for the patients assessed in this study, such as lack of social and community support or limited health care access that contribute to worse health outcomes.^10,11 In addition, low income contributes to limited access to medical care or treatments¹²; without access to effective HS management, lower-income patients may be at risk for higher disease severity and thus higher pain levels. However, economic stability is only a part of the whole picture; therefore, assessing the other social determinants of health in patients with HS may lead to better health outcomes and quality of life.

Another identified risk factor for high pain was a reported history of prescription pain medication use. This finding suggests that patients with moderate to severe pain likely have required stronger analgesic medications in the past. We further speculate that high pain levels in patients who have received prescription pain medications indicate either undertreatment, mistreatment, or recalcitrant pain. More research is needed to assess the relationship between HS-related pain intensity, analgesic medications, and providers who manage HS-related pain.

We also found that Black/African American patients with HS had a significantly higher dissatisfaction with their physician’s management of their pain, which could be attributable to several factors, including biological differences in medication metabolism (in which the patient has medication-resistant HS), undertreatment of pain, and/or poor doctor-patient relations. These reasons coincide with other diseases where health disparities are found.^13-15 Recognizing these factors will be key to dismantling the disparities in HS that are noted within this study. The limitations of this work include the cross-sectional study design and its inability to evaluate causal factors of high pain levels across racial groups, the NRS lack of insight on pain chronicity or pain experience,⁷ the lack of provider or institution perspectives, and self-reported data. Additionally, only patients with email access were included, which may have excluded vulnerable populations with more pain associated with their HS.

Our findings highlight an area for further investigation to assess why these racial differences exist in HS-related pain. The results also emphasize the need for research evaluating whether systemic or health care provider biases contribute to racial differences in HS-related pain management.

Acknowledgment — Dr. Weir was supported by the Predoctoral Clinical/Translational Research Program (TL1), a National Institutes of Health Ruth L. Kirschstein National Research Service Award (NRSA), through the University of Alabama at Birmingham (UAB) Center for Clinical and Translational Science (CCTS).  

Hidradenitis suppurativa (HS), a chronic inflammatory disease that is characterized by tender inflamed nodules of the skin and subcutaneous tissue, disproportionately affects postpubertal females as well as Black/African American individuals. The nodules can rupture, form sinus tracts, and scar. ¹ Hidradenitis suppurativa has been associated with cardiovascular disease, type 2 diabetes mellitus, polycystic ovary syndrome, depression, suicide, and substance use disorders. Because of the symptom burden and associated conditions, HS can be a painful and distressing disease that substantially impairs the quality of life for individuals with this condition. ²

Pain is a commonly reported symptom in HS that often goes untreated. Furthermore, HS-related pain is complex due to the involvement of different pain types that require various treatment modalities.³ According to Savage et al,⁴ recognizing whether HS-related pain is acute, chronic, neuropathic, or nociceptive is vital in establishing a framework for an effective pain management scheme. Currently, such established multimodal pain management strategies in dermatology do not exist. In 2021, dermatology-specific pain management strategies proposed the use of a multimodal regimen to address the multifaceted nature of HS-related pain.⁴ However, these strategies failed to recognize the systemic racial and ethnic biases in the US health care system that undermine pain management care for minority groups.^5,6 One approach to combatting racial disparities in pain management is determining average pain levels across racial groups.⁷ This study sought to compare HS-related pain scores by racial groups. Furthermore, we assessed differences in perception of patients’ respective pain management regimens by race. We hypothesized that the average HS-related pain intensities and pain management would differ between self-reported racial groups.

Methods  

This cross-sectional study took place over 5 months (August through December 2021). A survey was emailed to 2198 adult patients with HS in the University of Alabama Health System. The survey consisted of demographic and general questions about a patient’s HS. Pain scores were captured using the numeric rating scale (NRS), a measurement tool for pain intensity on a scale from 0 to 10. ⁸ Age at diagnosis, gender, education level, household income, total body areas affected by HS, disease severity (categorized as mild, moderate, and severe), comorbidities including mood disorders, tobacco use, and HS and HS-related pain medication regimens also were collected. Additionally, participants were asked about their level of agreement with the following statements: “I am satisfied with how my pain related to HS is being managed by my doctors” and “My pain related to HS is under control.” The level of agreement was measured using a 5-point Likert scale, with responses ranging from strongly disagree to strongly agree. All data included in the analysis were self-reported. The study received institutional review board approval for the University of Alabama at Birmingham.

Statistical Analysis—Descriptive statistics were used to assess statistical differences in patient characteristics of Black/African American participants compared to other participants, including White, Asian, and Hispanic/Latino participants. Thirteen participants were excluded from the final analysis: 2 participants were missing data, and 11 biracial participants were excluded due to overlapping White and Black/African American races that may have confounded the analysis. Categorical variables were reported as frequencies and percentages, and χ² and Fisher exact tests, when necessary, were used to test for statistically significant differences. Continuous variables were summarized with means and standard deviations, and a t test was used for statistically significant differences.

Logistic regression was performed to assess the relationship between race and pain after adjusting for confounding variables such as obesity, current tobacco use, self-reported HS severity, and the presence of comorbidities. A total of 204 patient records were included in the analysis, of which 70 (34.3%) had a pain score of 8 or higher, which indicates very severe pain intensity levels on the NRS,⁸ and were selected as a cut point based on the distribution of responses. For this cross-sectional cohort, our approach was to compare characteristics of those classified with a top score of 8 or higher (n=70) vs a top score of 0 to 7 (n=134)(cases vs noncases). Statistical analyses were performed using JMP Pro 16 (JMP Statistical Discovery LLC) at an α=.05 significance level; logistic regression was performed using SPSS Statistics (IBM). For the logistic regression, we grouped patient race into 2 categories: Black/African American and Other, which included White, Asian, and Hispanic/Latino participants.

Crude and adjusted multivariable logistic regression analyses were used to calculate prevalence odds ratios with 95% confidence intervals. Covariate inclusion in the multivariable logistic regression was based on a priori hypothesis/knowledge and was meant to estimate the independent effect of race after adjustment for income, HS severity, and history of prescription pain medication use. Other variables, including tobacco use, obesity, mood disorders, and current HS treatments, were all individually tested in the multivariate analysis and did not significantly impact the odds ratio for high pain. Statistical adjustment slightly decreased (19%) the magnitude between crude and adjusted prevalence odds ratios for the association between Black/African American race and high pain score.

Results  

Survey Demographics —The final analysis included 204 survey respondents. Most respondents were Black/African American (58.82%), and nearly all were female (89.71%)(Table 1). The mean age (SD) of respondents was 37.37 (11.29) years (range, 19-70 years). Many respondents reported having completed some college (36.27%) or receiving a bachelor’s degree (19.12%). Of patients who were not Black/African American, 10.71% had higher than a master’s degree, whereas no Black/African American patients held a degree higher than a master’s ( P = .0052). Additionally, more Black/African American respondents (35.83%) reported an annual household income level of less than $25,000 compared with respondents who were not Black/African American (19.05%, P = .0001). Most respondents rated the severity of their HS as moderate or severe (46.57% and 41.67%, respectively), and there was no significant difference in reported severity of HS between racial groups ( P = .5395).

Pain Scores—As documented in the Methods, respondents were asked to rate their HS-related pain intensity from 0 to 10 using the NRS. The average pain score (SD)—the level of pain intensity over the prior month—was 6.39 (2.56)(range, 0–10). The mean pain score (SD) at the time of the survey was 3.61 (2.98)(range, 0–10)(Table 1). These data revealed that Black/African American patients had a significantly higher average pain score (SD) than patients with HS who were not Black/African American (7.08 [2.49] and 5.40 [2.35], respectively; P<.0001). After adjustment with multivariable logistical regression, Black/African American patients had 4-fold increased odds for very severe levels of pain (score of ≥8) compared with patients who were not Black/African American.

Pain Management—Although pain scores were higher for Black/African American patients with HS, there was no significant difference in the perception of pain control between racial groups (P=.0761). Additionally, we found low income (adjusted prevalence odds ratio [POR], 0.22; 95% CI, 0.05-0.91), a history of prescription pain medication use (adjusted POR, 2.25; 95% CI, 1.13-4.51), and HS severity (adjusted POR, 4.40; 95% CI, 1.11-17.36) all to be independent risk factors contributing to higher pain scores in patients with HS (Table 2). Lastly, we noted current or reported history of pain medication use was significantly correlated with higher pain scores (P=.0280 and P=.0213, respectively).

Satisfaction With Pain Management—The level of satisfaction with physician management of HS-related pain was significantly different between Black/African American patients and those who were not Black/African American (P=.0129). Of those who identified as Black/African American, 26.7% (n=32) strongly disagreed with the statement, “I am satisfied with how my pain related to HS is being managed by my doctors,” whereas only 15.5% (n=13) of patients who were not Black/African American strongly disagreed. 

Comment

There is no cure for HS, and a large focus of treatment is pain management. Because racial disparities in the treatment of chronic pain will affect those with HS, we conducted a cross-sectional analysis of pain and pain management among HS patients. We found that Black/African American patients with HS have higher average pain scores than those who are not Black/African American and were 4 times more likely to experience very severe pain. Prior studies have established that patients with HS often report higher pain levels than patients with other chronic inflammatory skin conditions, ^7,8 and our study identified racial disparities in HS-related pain management.

Measuring pain is challenging because of its multidimensional and subjective nature, making it essential to consider underlying causes and patients’ emotional responses to pain.⁹ By adjusting for confounding factors that may influence pain, such as mood disorders, disease severity, comorbidities, and medication use, we were able to gain better insight into fundamental differences in average pain intensity levels among racial groups and assess what factors may be contributing to a patient’s pain perception. Our study determined that lower income levels, higher HS disease severity, and a history of prescription pain medication use were all independent risk factors for high pain. Of note, obesity, tobacco use, and mood disorders such as anxiety and depression did not significantly differ between racial groups or increase the odds of high pain between racial groups identified.

With low income being an independent risk factor for high pain, we must consider the social determinants of health and how they may influence the pain experience in HS. We speculate that low income may be associated with other social determinants of health for the patients assessed in this study, such as lack of social and community support or limited health care access that contribute to worse health outcomes.^10,11 In addition, low income contributes to limited access to medical care or treatments¹²; without access to effective HS management, lower-income patients may be at risk for higher disease severity and thus higher pain levels. However, economic stability is only a part of the whole picture; therefore, assessing the other social determinants of health in patients with HS may lead to better health outcomes and quality of life.

Another identified risk factor for high pain was a reported history of prescription pain medication use. This finding suggests that patients with moderate to severe pain likely have required stronger analgesic medications in the past. We further speculate that high pain levels in patients who have received prescription pain medications indicate either undertreatment, mistreatment, or recalcitrant pain. More research is needed to assess the relationship between HS-related pain intensity, analgesic medications, and providers who manage HS-related pain.

We also found that Black/African American patients with HS had a significantly higher dissatisfaction with their physician’s management of their pain, which could be attributable to several factors, including biological differences in medication metabolism (in which the patient has medication-resistant HS), undertreatment of pain, and/or poor doctor-patient relations. These reasons coincide with other diseases where health disparities are found.^13-15 Recognizing these factors will be key to dismantling the disparities in HS that are noted within this study. The limitations of this work include the cross-sectional study design and its inability to evaluate causal factors of high pain levels across racial groups, the NRS lack of insight on pain chronicity or pain experience,⁷ the lack of provider or institution perspectives, and self-reported data. Additionally, only patients with email access were included, which may have excluded vulnerable populations with more pain associated with their HS.

Our findings highlight an area for further investigation to assess why these racial differences exist in HS-related pain. The results also emphasize the need for research evaluating whether systemic or health care provider biases contribute to racial differences in HS-related pain management.

Acknowledgment — Dr. Weir was supported by the Predoctoral Clinical/Translational Research Program (TL1), a National Institutes of Health Ruth L. Kirschstein National Research Service Award (NRSA), through the University of Alabama at Birmingham (UAB) Center for Clinical and Translational Science (CCTS).  

Calcitonin gene-related peptide (CGRP) antagonist medications have revolutionized migraine therapy since being introduced in 2018. The initial preventive trials for monoclonal antibodies (mAb) excluded older adults, with a cutoff in all studies at age 65 years. Long-term safety studies have not revealed signals for concern related to vascular or other adverse events. The study by Muñoz-Vendrell and colleagues investigated the efficacy of CGRP mAb in treatment-refractory older adults.

This was an observational retrospective study in participants older than 65 years that had previously used three or more prior migraine preventives unsuccessfully. The primary endpoints were reduction in monthly migraine days after 6 months of treatment and the presence of adverse effects. Secondary endpoints were reductions in headache and acute medication frequency as well as improvement in patient reported outcomes.

A total of 162 participants were followed at 18 different headache centers throughout Spain. All patients had at least 8 headache days per month and had been treated unsuccessfully with three prior medications for migraine prevention, one of which was botulinum toxin. The median age was 68 years, and over 80% had chronic migraine. The reduction in mean headache days was 10 days per month; 72% continued to use their CGRP mAb after using it for 6 months. Participants were compared relative to medication overuse but no significant differences were found between those who overused medication and others.

This study highlights the efficacy of CGRP medications in those outside of the initially studied population. Other preventive medications may be contraindicated in this population, but CGRP antagonists do appear to be safe and effective options for older adults.

Opiate medications are typically considered inappropriate as an acute treatment for migraine. Even infrequent use of opiate medications has been shown to be associated with worse migraine outcomes, specifically higher frequency and a higher likelihood to convert from episodic to chronic migraine. Van Welie and colleagues performed a cross-sectional questionnaire-based study assessing levels of opioid use in patients with migraine.

Participants were selected from the Leiden Headache Center and fit the diagnostic criteria of migraine. They were given an e-questionnaire to determine their use of these opiates: buprenorphine, fentanyl, hydromorphone, morphine, oxycodone, tapentadol, and tramadol (codeine was not included in this list). Patients were separately divided between chronic and episodic migraine groups. The primary outcome was assessing for current acute treatment of migraine with an opiate; secondary outcomes were association of chronicity of migraine and likelihood of medication overuse with opiate use.

Only approximately 1.8% of participants reported that they currently use an opiate for acute migraine treatment; 12.5% reported that they previously have used an opiate and 25.7% reported using an opiate for another pain condition. Tramadol was the most commonly used opiate medication, followed by oxycodone and morphine; 2.4% of patients reported that their opiate use was not prescribed by their doctor. Primary care doctors were the most common prescribers of the opiate medications; 16% of the time, patients were told that it was a preventive treatment for migraine. Opiate use was more frequent in patients with a diagnosis of chronic migraine, and the duration of use was greater.

Opiate medications remain a poor acute choice of treatment for migraine, and this study shows a correlation between higher opiate use and chronic migraine. There are many other acute medications now available for migraine, many of them migraine-specific treatments, such as triptans, gepants, and ditans. This research again shows that opiates should be avoided if at all possible for migraine.

Patients with medication overuse headache are more likely to be treatment-refractory, and the addition of acute medications often can be less effective if they remain on the overused medication. There has been a long-standing debate whether it is best to wean medications first or start a preventive initially when faced with medication overuse. The CGRP antagonists may be one of the better preventive options in this situation, and one mAb (fremenezumab) reported positive data in a small medication overuse trial. The study by Guerzoni and colleagues investigated the effectiveness of galcanezumab in chronic migraine with medication overuse.

This was a prospective trial conducted at the University Hospital of Modena. A total of 78 patients with a diagnosis of chronic migraine and medication overuse were enrolled for 15 months, with follow-up every 3 months. At each follow-up appointment, they completed a questionnaire asking them details about: mean migraine days per month, mean number of painkillers taken per month, mean days per month taking a painkiller, average migraine severity, and the Headache Impact Test (HIT-6) and Migraine Disability Assessment (MIDAS) questions. Patients were given the standard-dosing regimen of glacanezumab for migraine and were not blinded; this was an open-label study.

The mean migraine days per month were significantly reduced after 3, 6, 9, and 12 months. The amount of painkillers used per month and days of painkillers per month both reduced significantly as well. Migraine-related disability on HIT-6 and MIDAS were all reduced significantly as well. The most significant improvement long-term was noted in patients who improved the most during the initial 3 months of treatment.

The debate regarding the best treatment for patients with medication overuse will continue, but this study highlights the effectiveness of CGRP mAb use in this population. Patients were able to decrease the use of acute medications without a strict wean off of their previous medication. Ideally, a similar study should also be done for additional mAb and oral CGRP antagonists.

Calcitonin gene-related peptide (CGRP) antagonist medications have revolutionized migraine therapy since being introduced in 2018. The initial preventive trials for monoclonal antibodies (mAb) excluded older adults, with a cutoff in all studies at age 65 years. Long-term safety studies have not revealed signals for concern related to vascular or other adverse events. The study by Muñoz-Vendrell and colleagues investigated the efficacy of CGRP mAb in treatment-refractory older adults.

This was an observational retrospective study in participants older than 65 years that had previously used three or more prior migraine preventives unsuccessfully. The primary endpoints were reduction in monthly migraine days after 6 months of treatment and the presence of adverse effects. Secondary endpoints were reductions in headache and acute medication frequency as well as improvement in patient reported outcomes.

A total of 162 participants were followed at 18 different headache centers throughout Spain. All patients had at least 8 headache days per month and had been treated unsuccessfully with three prior medications for migraine prevention, one of which was botulinum toxin. The median age was 68 years, and over 80% had chronic migraine. The reduction in mean headache days was 10 days per month; 72% continued to use their CGRP mAb after using it for 6 months. Participants were compared relative to medication overuse but no significant differences were found between those who overused medication and others.

This study highlights the efficacy of CGRP medications in those outside of the initially studied population. Other preventive medications may be contraindicated in this population, but CGRP antagonists do appear to be safe and effective options for older adults.

Opiate medications are typically considered inappropriate as an acute treatment for migraine. Even infrequent use of opiate medications has been shown to be associated with worse migraine outcomes, specifically higher frequency and a higher likelihood to convert from episodic to chronic migraine. Van Welie and colleagues performed a cross-sectional questionnaire-based study assessing levels of opioid use in patients with migraine.

Participants were selected from the Leiden Headache Center and fit the diagnostic criteria of migraine. They were given an e-questionnaire to determine their use of these opiates: buprenorphine, fentanyl, hydromorphone, morphine, oxycodone, tapentadol, and tramadol (codeine was not included in this list). Patients were separately divided between chronic and episodic migraine groups. The primary outcome was assessing for current acute treatment of migraine with an opiate; secondary outcomes were association of chronicity of migraine and likelihood of medication overuse with opiate use.

Only approximately 1.8% of participants reported that they currently use an opiate for acute migraine treatment; 12.5% reported that they previously have used an opiate and 25.7% reported using an opiate for another pain condition. Tramadol was the most commonly used opiate medication, followed by oxycodone and morphine; 2.4% of patients reported that their opiate use was not prescribed by their doctor. Primary care doctors were the most common prescribers of the opiate medications; 16% of the time, patients were told that it was a preventive treatment for migraine. Opiate use was more frequent in patients with a diagnosis of chronic migraine, and the duration of use was greater.

Opiate medications remain a poor acute choice of treatment for migraine, and this study shows a correlation between higher opiate use and chronic migraine. There are many other acute medications now available for migraine, many of them migraine-specific treatments, such as triptans, gepants, and ditans. This research again shows that opiates should be avoided if at all possible for migraine.

Patients with medication overuse headache are more likely to be treatment-refractory, and the addition of acute medications often can be less effective if they remain on the overused medication. There has been a long-standing debate whether it is best to wean medications first or start a preventive initially when faced with medication overuse. The CGRP antagonists may be one of the better preventive options in this situation, and one mAb (fremenezumab) reported positive data in a small medication overuse trial. The study by Guerzoni and colleagues investigated the effectiveness of galcanezumab in chronic migraine with medication overuse.

This was a prospective trial conducted at the University Hospital of Modena. A total of 78 patients with a diagnosis of chronic migraine and medication overuse were enrolled for 15 months, with follow-up every 3 months. At each follow-up appointment, they completed a questionnaire asking them details about: mean migraine days per month, mean number of painkillers taken per month, mean days per month taking a painkiller, average migraine severity, and the Headache Impact Test (HIT-6) and Migraine Disability Assessment (MIDAS) questions. Patients were given the standard-dosing regimen of glacanezumab for migraine and were not blinded; this was an open-label study.

The mean migraine days per month were significantly reduced after 3, 6, 9, and 12 months. The amount of painkillers used per month and days of painkillers per month both reduced significantly as well. Migraine-related disability on HIT-6 and MIDAS were all reduced significantly as well. The most significant improvement long-term was noted in patients who improved the most during the initial 3 months of treatment.

The debate regarding the best treatment for patients with medication overuse will continue, but this study highlights the effectiveness of CGRP mAb use in this population. Patients were able to decrease the use of acute medications without a strict wean off of their previous medication. Ideally, a similar study should also be done for additional mAb and oral CGRP antagonists.

Calcitonin gene-related peptide (CGRP) antagonist medications have revolutionized migraine therapy since being introduced in 2018. The initial preventive trials for monoclonal antibodies (mAb) excluded older adults, with a cutoff in all studies at age 65 years. Long-term safety studies have not revealed signals for concern related to vascular or other adverse events. The study by Muñoz-Vendrell and colleagues investigated the efficacy of CGRP mAb in treatment-refractory older adults.

This was an observational retrospective study in participants older than 65 years that had previously used three or more prior migraine preventives unsuccessfully. The primary endpoints were reduction in monthly migraine days after 6 months of treatment and the presence of adverse effects. Secondary endpoints were reductions in headache and acute medication frequency as well as improvement in patient reported outcomes.

A total of 162 participants were followed at 18 different headache centers throughout Spain. All patients had at least 8 headache days per month and had been treated unsuccessfully with three prior medications for migraine prevention, one of which was botulinum toxin. The median age was 68 years, and over 80% had chronic migraine. The reduction in mean headache days was 10 days per month; 72% continued to use their CGRP mAb after using it for 6 months. Participants were compared relative to medication overuse but no significant differences were found between those who overused medication and others.

This study highlights the efficacy of CGRP medications in those outside of the initially studied population. Other preventive medications may be contraindicated in this population, but CGRP antagonists do appear to be safe and effective options for older adults.

Opiate medications are typically considered inappropriate as an acute treatment for migraine. Even infrequent use of opiate medications has been shown to be associated with worse migraine outcomes, specifically higher frequency and a higher likelihood to convert from episodic to chronic migraine. Van Welie and colleagues performed a cross-sectional questionnaire-based study assessing levels of opioid use in patients with migraine.

Participants were selected from the Leiden Headache Center and fit the diagnostic criteria of migraine. They were given an e-questionnaire to determine their use of these opiates: buprenorphine, fentanyl, hydromorphone, morphine, oxycodone, tapentadol, and tramadol (codeine was not included in this list). Patients were separately divided between chronic and episodic migraine groups. The primary outcome was assessing for current acute treatment of migraine with an opiate; secondary outcomes were association of chronicity of migraine and likelihood of medication overuse with opiate use.

Only approximately 1.8% of participants reported that they currently use an opiate for acute migraine treatment; 12.5% reported that they previously have used an opiate and 25.7% reported using an opiate for another pain condition. Tramadol was the most commonly used opiate medication, followed by oxycodone and morphine; 2.4% of patients reported that their opiate use was not prescribed by their doctor. Primary care doctors were the most common prescribers of the opiate medications; 16% of the time, patients were told that it was a preventive treatment for migraine. Opiate use was more frequent in patients with a diagnosis of chronic migraine, and the duration of use was greater.

Opiate medications remain a poor acute choice of treatment for migraine, and this study shows a correlation between higher opiate use and chronic migraine. There are many other acute medications now available for migraine, many of them migraine-specific treatments, such as triptans, gepants, and ditans. This research again shows that opiates should be avoided if at all possible for migraine.

Patients with medication overuse headache are more likely to be treatment-refractory, and the addition of acute medications often can be less effective if they remain on the overused medication. There has been a long-standing debate whether it is best to wean medications first or start a preventive initially when faced with medication overuse. The CGRP antagonists may be one of the better preventive options in this situation, and one mAb (fremenezumab) reported positive data in a small medication overuse trial. The study by Guerzoni and colleagues investigated the effectiveness of galcanezumab in chronic migraine with medication overuse.

This was a prospective trial conducted at the University Hospital of Modena. A total of 78 patients with a diagnosis of chronic migraine and medication overuse were enrolled for 15 months, with follow-up every 3 months. At each follow-up appointment, they completed a questionnaire asking them details about: mean migraine days per month, mean number of painkillers taken per month, mean days per month taking a painkiller, average migraine severity, and the Headache Impact Test (HIT-6) and Migraine Disability Assessment (MIDAS) questions. Patients were given the standard-dosing regimen of glacanezumab for migraine and were not blinded; this was an open-label study.

The mean migraine days per month were significantly reduced after 3, 6, 9, and 12 months. The amount of painkillers used per month and days of painkillers per month both reduced significantly as well. Migraine-related disability on HIT-6 and MIDAS were all reduced significantly as well. The most significant improvement long-term was noted in patients who improved the most during the initial 3 months of treatment.

The debate regarding the best treatment for patients with medication overuse will continue, but this study highlights the effectiveness of CGRP mAb use in this population. Patients were able to decrease the use of acute medications without a strict wean off of their previous medication. Ideally, a similar study should also be done for additional mAb and oral CGRP antagonists.

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Federal Practitioner and the Association of VA Hematology/Oncology (AVAHO) present the 2023 edition of Cancer Data Trends (click to view the digital edition). This special issue provides updates on some of the top cancers and related concerns affecting veterans through original infographics and visual storytelling.

In this issue:

• COVID-19 Outcomes in Veterans With Hematologic Cancers
• Promising New Approaches for Testicular and Prostate Cancer
• Screening Guideline Updates and New Treatments in Colon Cancer
• Exposure-Related Cancers: A Look at the PACT Act
• New Classifications and Emerging Treatments in Brain Cancer
• Gender Disparity in Breast Cancer Among US Veterans
• Lung Cancer Screening in Veterans
• Necessary Updates to Skin Cancer Risk Stratification
• Innovation in Cancer Treatment

Federal Practitioner and the Association of VA Hematology/Oncology (AVAHO) present the 2023 edition of Cancer Data Trends (click to view the digital edition). This special issue provides updates on some of the top cancers and related concerns affecting veterans through original infographics and visual storytelling.

In this issue:

• COVID-19 Outcomes in Veterans With Hematologic Cancers
• Promising New Approaches for Testicular and Prostate Cancer
• Screening Guideline Updates and New Treatments in Colon Cancer
• Exposure-Related Cancers: A Look at the PACT Act
• New Classifications and Emerging Treatments in Brain Cancer
• Gender Disparity in Breast Cancer Among US Veterans
• Lung Cancer Screening in Veterans
• Necessary Updates to Skin Cancer Risk Stratification
• Innovation in Cancer Treatment

Federal Practitioner and the Association of VA Hematology/Oncology (AVAHO) present the 2023 edition of Cancer Data Trends (click to view the digital edition). This special issue provides updates on some of the top cancers and related concerns affecting veterans through original infographics and visual storytelling.

In this issue:

• COVID-19 Outcomes in Veterans With Hematologic Cancers
• Promising New Approaches for Testicular and Prostate Cancer
• Screening Guideline Updates and New Treatments in Colon Cancer
• Exposure-Related Cancers: A Look at the PACT Act
• New Classifications and Emerging Treatments in Brain Cancer
• Gender Disparity in Breast Cancer Among US Veterans
• Lung Cancer Screening in Veterans
• Necessary Updates to Skin Cancer Risk Stratification
• Innovation in Cancer Treatment

Click here to view more from Cancer Data Trends 2023.

Click here to view more from Cancer Data Trends 2023.

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