The Diagnosis: Epidermodysplasia Verruciformis 

Histopathologic examination of our patient's biopsy specimen revealed mild acanthosis with prominent hypergranulosis and enlarged keratinocytes with blue-gray cytoplasm (Figure). A diagnosis of acquired epidermodysplasia verruciformis (EV) was rendered. The patient was treated with photodynamic therapy utilizing 5-aminolevulinic acid. 

Epidermodysplasia verruciformis is characterized by susceptibility to human papillomavirus (HPV) infections via a defect in cellular immunity. Epidermodysplasia verruciformis was first described as an autosomal-recessive genodermatosis, but it can be acquired in immunosuppressed states with an atypical clinical appearance.¹ There are few case reports in skin of color. Acquired EV appears in patients with acquired immunodeficiencies that are susceptible to EV-causing HPVs via a similar mechanism found in inherited EV.² The most common HPV serotypes involved in EV are HPV-5 and HPV-8. The duration of immunosuppression has been found to be positively correlated with the risk for EV development, with the majority of patients developing lesions after 5 years of immunosuppression.³ There is an approximately 60% risk of malignant transformation of EV lesions into nonmelanoma skin cancer.² This risk is believed to be lower in patients with darker skin.⁴  

Preventative measures including sun protection and annual surveillance are crucial in EV patients given the high rate of malignant transformation in sun-exposed lesions.⁵ Treatment options for EV are anecdotal and have variable results, ranging from topicals including 5-fluorouracil and imiquimod to systemic medications including acitretin and interferon.³ Photodynamic therapy can be used for extensive EV. Surgical modalities and other destructive methods also have been tried.⁶ 

Epidermodysplasia verruciformis often can be confused with similar dermatoses. Porokeratosis appears as annular pink papules with waferlike peripheral scales. Tinea versicolor is a dermatophyte infection caused by Malassezia furfur and presents as multiple dyspigmented, finely scaling, thin papules and plaques. Subacute cutaneous lupus erythematosus presents as pink, scaly, annular or psoriasiform papules and plaques most commonly on the trunk. Discoid lupus erythematosus presents as pink, hypopigmented or depigmented, atrophic plaques with a peripheral rim of erythema that indicates activity. Secondary syphilis, commonly denoted as the "great mimicker," presents as psoriasiform papules and plaques among other variable morphologies. 

The Diagnosis: Epidermodysplasia Verruciformis 

Histopathologic examination of our patient's biopsy specimen revealed mild acanthosis with prominent hypergranulosis and enlarged keratinocytes with blue-gray cytoplasm (Figure). A diagnosis of acquired epidermodysplasia verruciformis (EV) was rendered. The patient was treated with photodynamic therapy utilizing 5-aminolevulinic acid. 

Epidermodysplasia verruciformis is characterized by susceptibility to human papillomavirus (HPV) infections via a defect in cellular immunity. Epidermodysplasia verruciformis was first described as an autosomal-recessive genodermatosis, but it can be acquired in immunosuppressed states with an atypical clinical appearance.¹ There are few case reports in skin of color. Acquired EV appears in patients with acquired immunodeficiencies that are susceptible to EV-causing HPVs via a similar mechanism found in inherited EV.² The most common HPV serotypes involved in EV are HPV-5 and HPV-8. The duration of immunosuppression has been found to be positively correlated with the risk for EV development, with the majority of patients developing lesions after 5 years of immunosuppression.³ There is an approximately 60% risk of malignant transformation of EV lesions into nonmelanoma skin cancer.² This risk is believed to be lower in patients with darker skin.⁴  

Preventative measures including sun protection and annual surveillance are crucial in EV patients given the high rate of malignant transformation in sun-exposed lesions.⁵ Treatment options for EV are anecdotal and have variable results, ranging from topicals including 5-fluorouracil and imiquimod to systemic medications including acitretin and interferon.³ Photodynamic therapy can be used for extensive EV. Surgical modalities and other destructive methods also have been tried.⁶ 

Epidermodysplasia verruciformis often can be confused with similar dermatoses. Porokeratosis appears as annular pink papules with waferlike peripheral scales. Tinea versicolor is a dermatophyte infection caused by Malassezia furfur and presents as multiple dyspigmented, finely scaling, thin papules and plaques. Subacute cutaneous lupus erythematosus presents as pink, scaly, annular or psoriasiform papules and plaques most commonly on the trunk. Discoid lupus erythematosus presents as pink, hypopigmented or depigmented, atrophic plaques with a peripheral rim of erythema that indicates activity. Secondary syphilis, commonly denoted as the "great mimicker," presents as psoriasiform papules and plaques among other variable morphologies. 

The Diagnosis: Epidermodysplasia Verruciformis 

Histopathologic examination of our patient's biopsy specimen revealed mild acanthosis with prominent hypergranulosis and enlarged keratinocytes with blue-gray cytoplasm (Figure). A diagnosis of acquired epidermodysplasia verruciformis (EV) was rendered. The patient was treated with photodynamic therapy utilizing 5-aminolevulinic acid. 

Epidermodysplasia verruciformis is characterized by susceptibility to human papillomavirus (HPV) infections via a defect in cellular immunity. Epidermodysplasia verruciformis was first described as an autosomal-recessive genodermatosis, but it can be acquired in immunosuppressed states with an atypical clinical appearance.¹ There are few case reports in skin of color. Acquired EV appears in patients with acquired immunodeficiencies that are susceptible to EV-causing HPVs via a similar mechanism found in inherited EV.² The most common HPV serotypes involved in EV are HPV-5 and HPV-8. The duration of immunosuppression has been found to be positively correlated with the risk for EV development, with the majority of patients developing lesions after 5 years of immunosuppression.³ There is an approximately 60% risk of malignant transformation of EV lesions into nonmelanoma skin cancer.² This risk is believed to be lower in patients with darker skin.⁴  

Preventative measures including sun protection and annual surveillance are crucial in EV patients given the high rate of malignant transformation in sun-exposed lesions.⁵ Treatment options for EV are anecdotal and have variable results, ranging from topicals including 5-fluorouracil and imiquimod to systemic medications including acitretin and interferon.³ Photodynamic therapy can be used for extensive EV. Surgical modalities and other destructive methods also have been tried.⁶ 

Epidermodysplasia verruciformis often can be confused with similar dermatoses. Porokeratosis appears as annular pink papules with waferlike peripheral scales. Tinea versicolor is a dermatophyte infection caused by Malassezia furfur and presents as multiple dyspigmented, finely scaling, thin papules and plaques. Subacute cutaneous lupus erythematosus presents as pink, scaly, annular or psoriasiform papules and plaques most commonly on the trunk. Discoid lupus erythematosus presents as pink, hypopigmented or depigmented, atrophic plaques with a peripheral rim of erythema that indicates activity. Secondary syphilis, commonly denoted as the "great mimicker," presents as psoriasiform papules and plaques among other variable morphologies. 

Videos on social media showing children using insulin delivery pens to self-inject hyaluronic acid has prompted a safety warning from the American Society for Dermatologic Surgery Association.

In the safety warning, issued on Feb. 18, the ASDSA reported that ASDSA members, all board-certified dermatologists, have seen evidence online of young people using so-called “hyaluron pens” to inject hyaluronic acid filler in the epidermal and upper dermal skin.

The pens being used and promoted in social media for do-it-yourself filler injections are medical devices originally developed for insulin injections. “The use of air pressure technology causes these pens to deliver the hyaluronic acid to insert nanoscale molecules of the filler through the skin,” according to the ASDSA statement. Marketing materials state that the pens can be used to create volume and shape in the lips, and to improve the appearance of nasolabial lines, marionette lines, brow lines known as “elevens,” and forehead wrinkles. Claims that the hyaluronic acid only reaches the papillary layer of the dermis, and is therefore safe, do not alleviate the risk of injury in inexperienced hands, the ASDSA statement points out.

“We are concerned about California children falling prey to products that are not appropriate and safe for them to use,” Elan Newland, MD, member of the ASDSA and the California Society for Dermatology and Dermatological Surgery (CalDerm), said in the statement. “The power of social media is very strong, especially for impressionable teenagers. CalDerm supports alerting consumers and regulators of the dangers of these pens,” he said.  

Videos on social media showing children using insulin delivery pens to self-inject hyaluronic acid has prompted a safety warning from the American Society for Dermatologic Surgery Association.

In the safety warning, issued on Feb. 18, the ASDSA reported that ASDSA members, all board-certified dermatologists, have seen evidence online of young people using so-called “hyaluron pens” to inject hyaluronic acid filler in the epidermal and upper dermal skin.

The pens being used and promoted in social media for do-it-yourself filler injections are medical devices originally developed for insulin injections. “The use of air pressure technology causes these pens to deliver the hyaluronic acid to insert nanoscale molecules of the filler through the skin,” according to the ASDSA statement. Marketing materials state that the pens can be used to create volume and shape in the lips, and to improve the appearance of nasolabial lines, marionette lines, brow lines known as “elevens,” and forehead wrinkles. Claims that the hyaluronic acid only reaches the papillary layer of the dermis, and is therefore safe, do not alleviate the risk of injury in inexperienced hands, the ASDSA statement points out.

“We are concerned about California children falling prey to products that are not appropriate and safe for them to use,” Elan Newland, MD, member of the ASDSA and the California Society for Dermatology and Dermatological Surgery (CalDerm), said in the statement. “The power of social media is very strong, especially for impressionable teenagers. CalDerm supports alerting consumers and regulators of the dangers of these pens,” he said.  

Videos on social media showing children using insulin delivery pens to self-inject hyaluronic acid has prompted a safety warning from the American Society for Dermatologic Surgery Association.

In the safety warning, issued on Feb. 18, the ASDSA reported that ASDSA members, all board-certified dermatologists, have seen evidence online of young people using so-called “hyaluron pens” to inject hyaluronic acid filler in the epidermal and upper dermal skin.

The pens being used and promoted in social media for do-it-yourself filler injections are medical devices originally developed for insulin injections. “The use of air pressure technology causes these pens to deliver the hyaluronic acid to insert nanoscale molecules of the filler through the skin,” according to the ASDSA statement. Marketing materials state that the pens can be used to create volume and shape in the lips, and to improve the appearance of nasolabial lines, marionette lines, brow lines known as “elevens,” and forehead wrinkles. Claims that the hyaluronic acid only reaches the papillary layer of the dermis, and is therefore safe, do not alleviate the risk of injury in inexperienced hands, the ASDSA statement points out.

“We are concerned about California children falling prey to products that are not appropriate and safe for them to use,” Elan Newland, MD, member of the ASDSA and the California Society for Dermatology and Dermatological Surgery (CalDerm), said in the statement. “The power of social media is very strong, especially for impressionable teenagers. CalDerm supports alerting consumers and regulators of the dangers of these pens,” he said.  

Steroids are usually the first choice of therapy for the treatment of patients with graft-vs.-host disease (GVHD), but complications from steroid use may carry a high financial cost, investigators caution.

Among 689 patients with a diagnosis of GVHD following a hematopoietic stem cell transplant (HSCT) who received steroids, 685 (97%) had at least one steroid-related complication, resulting in nearly $165,000 in mean health-care costs over 24 months, said Elizabeth J. Bell, PhD, MPH, an epidemiologist at Optum Inc.

“For both acute and chronic GVHD, the standard of care for first-line treatment is systemic steroids. The complications associated with steroid treatment are well known. However, the health-care resources utilized and the costs incurred by these patients are not well-quantified,” she said at the Transplantation & Cellular Therapies Meetings (Abstract 12).

Dr. Bell reported the results of a retrospective database analysis on costs associated with steroid complications in HSCT recipients at the meeting, which was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

She and colleagues from Optum, Incyte, and the University of Minnesota in Minneapolis looked at data on 689 patients with a diagnosis of GVHD after HSCT who received systemic steroids from July 1, 2010, through Aug. 31, 2019. The data were extracted from the Optum Research database, and included U.S. commercial and Medicare Advantage patients.

They looked at total complications and steroid-associated complications in each of four categories: infections; metabolic or endocrine complications (for example, diabetes, dyslipidemia); gastrointestinal (GI) complications (e.g., peptic ulcer disease); and bone or muscle complications (myopathy, etc).

They estimated costs based on International Classification of Diseases (ICD) codes for any steroid complications during the 24 months after steroid initiation, including those complications that may have been present at the time of GVHD diagnosis.

The median patient age was 55 years, and 60% of the sample were male. The mean Charlson Comorbidity Index score at baseline was 3.

Overall, 22% of patients had only acute GVHD, 21% had only chronic GVHD, and 39% had both acute and chronic disease. The GVHD type was unspecified in the remaining 18%.

The median time from GVHD diagnosis to initiating steroids was 30 days for patients with both acute and chronic disease, as well as those with both presentations. The median time to initiation was 36 days for patients with unspecified GVHD type.

The median cumulative duration of steroid use over 24 months was 62 days for patients with acute GVHD, 208 days for those with chronic GVHD, 166 days for those with both, and 74 days for patients with unspecified GVHD type.

As noted before, complications occurred in 97% of patients, with infections being the most common complications, occurring in 80% of patients, followed by metabolic/endocrine complications in 32%, gastrointestinal in 29%, and bone/muscle complications in 20%.

For the 665 patients who had any steroid-related complication, the mean costs of steroid-associated care in the 24 months after they were started on steroids was $164,787, and the median cost was $50,834.

Health care costs were highest among patients with infections, at a mean of $167,473, and a median of $57,680, followed by bone/muscle conditions ($75,289 and $2,057, respectively), GI conditions ($67,861 and $3,360), and metabolic or endocrine conditions ($47, 101 and $1,164).

In all categories, hospitalizations accounted for the large majority of costs.

Two-thirds (66%) of patients who experienced any steroid-related complication required hospitalization, primarily for infections.

Among all patients with complications, the median cumulative hospital stay over 24 months was 20 days, with bone/muscle complications and infections associated with a median of 19 and 18 days of hospitalization, respectively.

Dr. Bell acknowledged that the study was limited by use of ICD coding to identify steroid complication-related health-care utilization and costs, which can be imprecise, and by the fact that the analysis included only complications resulting in health care use as documented in medical claims. In addition, the investigators noted that they could not control for the possibility that steroids exacerbated conditions that existed at baseline.

“These findings emphasize the need to cautiously evaluate the treatment options for patients with GVHD. Future study with medical records is needed to provide insights on the clinical aspects of the complications (e.g., severity and suspected causality),” Dr. Bell and colleagues concluded in the study’s abstract.
 

Definitions questioned

An HSCT specialist approached for comment said that the findings of the study made sense, but she had questions regarding the study methodology.

“I would intuitively think that steroid-associated complications are a major cause of health care use in GVHD patients and it’s interesting to see that there is emerging data to support this hypothesis,” HSCT specialist Hélène Schoemans, MD of the University of Leuven, Belgium, said in an interview.

She noted, however, that “it is surprising that the period of steroid initiation was the same for acute and chronic GVHD,” and questioned whether that anomalous finding could be due to the study’s definition of acute and chronic GVHD or to how the period from baseline to steroid initiation was defined.

The questions about the definitions and timing of therapy make it uncertain as to whether the complications reported were caused by steroids or by some other factor, she suggested.

The study was supported by Optum Inc. Dr. Bell is an employee of the company, and a paid consultant of Incyte. Dr. Schoemans has received travel expenses from Celgene, Abbvie, and Incyte; is part of the advisory boards for Incyte; and has received speakers fees from Novartis, Incyte, Jazz Pharmaceuticals, and Takeda.

Steroids are usually the first choice of therapy for the treatment of patients with graft-vs.-host disease (GVHD), but complications from steroid use may carry a high financial cost, investigators caution.

Among 689 patients with a diagnosis of GVHD following a hematopoietic stem cell transplant (HSCT) who received steroids, 685 (97%) had at least one steroid-related complication, resulting in nearly $165,000 in mean health-care costs over 24 months, said Elizabeth J. Bell, PhD, MPH, an epidemiologist at Optum Inc.

“For both acute and chronic GVHD, the standard of care for first-line treatment is systemic steroids. The complications associated with steroid treatment are well known. However, the health-care resources utilized and the costs incurred by these patients are not well-quantified,” she said at the Transplantation & Cellular Therapies Meetings (Abstract 12).

Dr. Bell reported the results of a retrospective database analysis on costs associated with steroid complications in HSCT recipients at the meeting, which was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

She and colleagues from Optum, Incyte, and the University of Minnesota in Minneapolis looked at data on 689 patients with a diagnosis of GVHD after HSCT who received systemic steroids from July 1, 2010, through Aug. 31, 2019. The data were extracted from the Optum Research database, and included U.S. commercial and Medicare Advantage patients.

They looked at total complications and steroid-associated complications in each of four categories: infections; metabolic or endocrine complications (for example, diabetes, dyslipidemia); gastrointestinal (GI) complications (e.g., peptic ulcer disease); and bone or muscle complications (myopathy, etc).

They estimated costs based on International Classification of Diseases (ICD) codes for any steroid complications during the 24 months after steroid initiation, including those complications that may have been present at the time of GVHD diagnosis.

The median patient age was 55 years, and 60% of the sample were male. The mean Charlson Comorbidity Index score at baseline was 3.

Overall, 22% of patients had only acute GVHD, 21% had only chronic GVHD, and 39% had both acute and chronic disease. The GVHD type was unspecified in the remaining 18%.

The median time from GVHD diagnosis to initiating steroids was 30 days for patients with both acute and chronic disease, as well as those with both presentations. The median time to initiation was 36 days for patients with unspecified GVHD type.

The median cumulative duration of steroid use over 24 months was 62 days for patients with acute GVHD, 208 days for those with chronic GVHD, 166 days for those with both, and 74 days for patients with unspecified GVHD type.

As noted before, complications occurred in 97% of patients, with infections being the most common complications, occurring in 80% of patients, followed by metabolic/endocrine complications in 32%, gastrointestinal in 29%, and bone/muscle complications in 20%.

For the 665 patients who had any steroid-related complication, the mean costs of steroid-associated care in the 24 months after they were started on steroids was $164,787, and the median cost was $50,834.

Health care costs were highest among patients with infections, at a mean of $167,473, and a median of $57,680, followed by bone/muscle conditions ($75,289 and $2,057, respectively), GI conditions ($67,861 and $3,360), and metabolic or endocrine conditions ($47, 101 and $1,164).

In all categories, hospitalizations accounted for the large majority of costs.

Two-thirds (66%) of patients who experienced any steroid-related complication required hospitalization, primarily for infections.

Among all patients with complications, the median cumulative hospital stay over 24 months was 20 days, with bone/muscle complications and infections associated with a median of 19 and 18 days of hospitalization, respectively.

Dr. Bell acknowledged that the study was limited by use of ICD coding to identify steroid complication-related health-care utilization and costs, which can be imprecise, and by the fact that the analysis included only complications resulting in health care use as documented in medical claims. In addition, the investigators noted that they could not control for the possibility that steroids exacerbated conditions that existed at baseline.

“These findings emphasize the need to cautiously evaluate the treatment options for patients with GVHD. Future study with medical records is needed to provide insights on the clinical aspects of the complications (e.g., severity and suspected causality),” Dr. Bell and colleagues concluded in the study’s abstract.
 

Definitions questioned

An HSCT specialist approached for comment said that the findings of the study made sense, but she had questions regarding the study methodology.

“I would intuitively think that steroid-associated complications are a major cause of health care use in GVHD patients and it’s interesting to see that there is emerging data to support this hypothesis,” HSCT specialist Hélène Schoemans, MD of the University of Leuven, Belgium, said in an interview.

She noted, however, that “it is surprising that the period of steroid initiation was the same for acute and chronic GVHD,” and questioned whether that anomalous finding could be due to the study’s definition of acute and chronic GVHD or to how the period from baseline to steroid initiation was defined.

The questions about the definitions and timing of therapy make it uncertain as to whether the complications reported were caused by steroids or by some other factor, she suggested.

The study was supported by Optum Inc. Dr. Bell is an employee of the company, and a paid consultant of Incyte. Dr. Schoemans has received travel expenses from Celgene, Abbvie, and Incyte; is part of the advisory boards for Incyte; and has received speakers fees from Novartis, Incyte, Jazz Pharmaceuticals, and Takeda.

Steroids are usually the first choice of therapy for the treatment of patients with graft-vs.-host disease (GVHD), but complications from steroid use may carry a high financial cost, investigators caution.

Among 689 patients with a diagnosis of GVHD following a hematopoietic stem cell transplant (HSCT) who received steroids, 685 (97%) had at least one steroid-related complication, resulting in nearly $165,000 in mean health-care costs over 24 months, said Elizabeth J. Bell, PhD, MPH, an epidemiologist at Optum Inc.

“For both acute and chronic GVHD, the standard of care for first-line treatment is systemic steroids. The complications associated with steroid treatment are well known. However, the health-care resources utilized and the costs incurred by these patients are not well-quantified,” she said at the Transplantation & Cellular Therapies Meetings (Abstract 12).

Dr. Bell reported the results of a retrospective database analysis on costs associated with steroid complications in HSCT recipients at the meeting, which was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

She and colleagues from Optum, Incyte, and the University of Minnesota in Minneapolis looked at data on 689 patients with a diagnosis of GVHD after HSCT who received systemic steroids from July 1, 2010, through Aug. 31, 2019. The data were extracted from the Optum Research database, and included U.S. commercial and Medicare Advantage patients.

They looked at total complications and steroid-associated complications in each of four categories: infections; metabolic or endocrine complications (for example, diabetes, dyslipidemia); gastrointestinal (GI) complications (e.g., peptic ulcer disease); and bone or muscle complications (myopathy, etc).

They estimated costs based on International Classification of Diseases (ICD) codes for any steroid complications during the 24 months after steroid initiation, including those complications that may have been present at the time of GVHD diagnosis.

The median patient age was 55 years, and 60% of the sample were male. The mean Charlson Comorbidity Index score at baseline was 3.

Overall, 22% of patients had only acute GVHD, 21% had only chronic GVHD, and 39% had both acute and chronic disease. The GVHD type was unspecified in the remaining 18%.

The median time from GVHD diagnosis to initiating steroids was 30 days for patients with both acute and chronic disease, as well as those with both presentations. The median time to initiation was 36 days for patients with unspecified GVHD type.

The median cumulative duration of steroid use over 24 months was 62 days for patients with acute GVHD, 208 days for those with chronic GVHD, 166 days for those with both, and 74 days for patients with unspecified GVHD type.

As noted before, complications occurred in 97% of patients, with infections being the most common complications, occurring in 80% of patients, followed by metabolic/endocrine complications in 32%, gastrointestinal in 29%, and bone/muscle complications in 20%.

For the 665 patients who had any steroid-related complication, the mean costs of steroid-associated care in the 24 months after they were started on steroids was $164,787, and the median cost was $50,834.

Health care costs were highest among patients with infections, at a mean of $167,473, and a median of $57,680, followed by bone/muscle conditions ($75,289 and $2,057, respectively), GI conditions ($67,861 and $3,360), and metabolic or endocrine conditions ($47, 101 and $1,164).

In all categories, hospitalizations accounted for the large majority of costs.

Two-thirds (66%) of patients who experienced any steroid-related complication required hospitalization, primarily for infections.

Among all patients with complications, the median cumulative hospital stay over 24 months was 20 days, with bone/muscle complications and infections associated with a median of 19 and 18 days of hospitalization, respectively.

Dr. Bell acknowledged that the study was limited by use of ICD coding to identify steroid complication-related health-care utilization and costs, which can be imprecise, and by the fact that the analysis included only complications resulting in health care use as documented in medical claims. In addition, the investigators noted that they could not control for the possibility that steroids exacerbated conditions that existed at baseline.

“These findings emphasize the need to cautiously evaluate the treatment options for patients with GVHD. Future study with medical records is needed to provide insights on the clinical aspects of the complications (e.g., severity and suspected causality),” Dr. Bell and colleagues concluded in the study’s abstract.
 

Definitions questioned

An HSCT specialist approached for comment said that the findings of the study made sense, but she had questions regarding the study methodology.

“I would intuitively think that steroid-associated complications are a major cause of health care use in GVHD patients and it’s interesting to see that there is emerging data to support this hypothesis,” HSCT specialist Hélène Schoemans, MD of the University of Leuven, Belgium, said in an interview.

She noted, however, that “it is surprising that the period of steroid initiation was the same for acute and chronic GVHD,” and questioned whether that anomalous finding could be due to the study’s definition of acute and chronic GVHD or to how the period from baseline to steroid initiation was defined.

The questions about the definitions and timing of therapy make it uncertain as to whether the complications reported were caused by steroids or by some other factor, she suggested.

The study was supported by Optum Inc. Dr. Bell is an employee of the company, and a paid consultant of Incyte. Dr. Schoemans has received travel expenses from Celgene, Abbvie, and Incyte; is part of the advisory boards for Incyte; and has received speakers fees from Novartis, Incyte, Jazz Pharmaceuticals, and Takeda.

The heart failure drug ivabradine (Corlanor) can provide relief from the elevated heart rate and often debilitating symptoms associated with postural orthostatic tachycardia syndrome (POTS), a new study suggests.

Pheelings Media/Getty Images

Ivabradine significantly lowered standing heart rate, compared with placebo (77.9 vs. 94.2 beats/min; P < .001). The typical surge in heart rate that occurs upon standing in these patients was also blunted, compared with baseline (13.0 vs. 21.4 beats/min; P = .001).

“There are really not a lot of great options for patients with POTS and, mechanistically, ivabradine just make sense because it’s a drug that lowers heart rate very selectively and doesn’t lower blood pressure,” lead study author Pam R. Taub, MD, told this news organization.

Surprisingly, the reduction in heart rate translated into improved physical (P = .008) and social (P = .021) functioning after just 1 month of ivabradine, without any other background POTS medications or a change in nonpharmacologic therapies, she said. “What’s really nice to see is when you tackle a really significant part of the disease, which is the elevated heart rate, just how much better they feel.”

POTS patients are mostly healthy, active young women, who after some inciting event – such as viral infection, trauma, or surgery – experience an increase in heart rate of at least 30 beats/min upon standing accompanied by a range of symptoms, including dizziness, palpitations, brain fog, and fatigue.
 

A COVID connection?

The study enrolled patients with hyperadrenergic POTS as the predominant subtype, but another group to keep in mind that might benefit is the post-COVID POTS patient, said Dr. Taub, from the University of California, San Diego.

“We’re seeing an incredible number of patients post COVID that meet the criteria for POTS, and a lot of these patients also have COVID fatigue,” she said. “So clinically, myself and many other cardiologists who understand ivabradine have been using it off-label for the COVID patients, as long as they meet the criteria. You don’t want to use it in every COVID patient, but if someone’s predominant complaint is that their heart rate is going up when they’re standing and they’re debilitated by it, this is a drug to consider.”

Anecdotal findings in patients with long-hauler COVID need to be translated into rigorous research protocols, but mechanistically, whether it’s POTS from COVID or from another type of infection – like Lyme disease or some other viral syndrome – it should work the same, Dr. Taub said. “POTS is POTS.”

There are no first-line drugs for POTS, and current class IIb recommendations include midodrine, which increases blood pressure and can make people feel awful, and fludrocortisone, which can cause a lot of weight gain and fluid retention, she observed. Other agents that lower heart rate, like beta-blockers, also lower blood pressure and can aggravate depression and fatigue.

Ivabradine regulates heart rate by specifically blocking the Ifunny channel of the sinoatrial node. It was approved in 2015 in the United States to reduce hospitalizations in patients with systolic heart failure, and it also has a second class IIb recommendation for inappropriate sinus tachycardia.

The present study, reported in the Feb. 23 issue of the Journal of the American College of Cardiology, is the first randomized clinical trial using ivabradine to treat POTS.

A total of 26 patients with POTS were started on ivabradine 5 mg or placebo twice daily for 1 month, then were crossed over to the other treatment for 1 month after a 1-week washout period. Six patients were started on a 2.5-mg twice-daily dose. Doses were adjusted during the study based on the patient’s heart rate response and tolerance. Patients had seven clinic visits in which norepinephrine (NE) levels were measured and head-up tilt testing conducted.

Four patients in the ivabradine arm withdrew because of adverse effects, and one withdrew during crossover.

Among the 22 patients who completed the study, exploratory analyses showed a strong trend for greater reduction in plasma NE upon standing with ivabradine (P = .056). The effect was also more profound in patients with very high baseline standing NE levels (at least 1,000 pg/mL) than in those with lower NE levels (600 to 1,000 pg/mL).

“It makes sense because that means their sympathetic nervous system is more overactive; they have a higher heart rate,” Dr. Taub said. “So it’s a potential clinical tool that people can use in their practice to determine, ‘okay, is this a patient I should be considering ivabradine on?’ ”

Although the present study had only 22 patients, “it should definitely be looked at as a step forward, both in terms of ivabradine specifically and in terms of setting the standard for the types of studies we want to see in our patients,” Satish R. Raj, MD, MSCI, University of Calgary (Alta.), said in an interview.

In a related editorial, however, Dr. Raj and coauthor Robert S. Sheldon, MD, PhD, also from the University of Calgary, point out that the standing heart rate in the placebo phase was only 94 beats/min, “suggesting that these patients may be affected only mildly by their POTS.”

Asked about the point, Dr. Taub said: “I don’t know if I agree with that.” She noted that the diagnosis of POTS was confirmed by tilt-table testing and NE levels and that patients’ symptoms vary from day to day. “The standard deviation was plus or minus 16.8, so there’s variability.”

Both Dr. Raj and Dr. Taub said they expect the results will be included in the next scientific statement for POTS, but in the meantime, it may be a struggle to get the drug covered by insurance.  

“The challenge is that this is a very off-label use for this medication, and the medication’s not cheap,” Dr. Raj observed. The price for 60 tablets, which is about a 1-month supply, is $485 on GoodRx.

Another question going forward, he said, is whether ivabradine is superior to beta-blockers, which will be studied in a 20-patient crossover trial sponsored by the University of Calgary that is about to launch. The primary completion date is set for 2024.

The study was supported by a grant from Amgen. Dr. Taub has served as a consultant for Amgen, Bayer, Esperion, Boehringer Ingelheim, Novo Nordisk, and Sanofi; is a shareholder in Epirium Bio; and has received research grants from the National Institutes of Health, the American Heart Association, and the Department of Homeland Security/FEMA. Dr. Raj has received a research grant from the Canadian Institutes of Health Research and research grants from Dysautonomia International to address the pathophysiology of POTS. Dr. Sheldon has received a research grant from Dysautonomia International for a clinical trial assessing ivabradine and propranolol for the treatment of POTS.

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

The heart failure drug ivabradine (Corlanor) can provide relief from the elevated heart rate and often debilitating symptoms associated with postural orthostatic tachycardia syndrome (POTS), a new study suggests.

Pheelings Media/Getty Images

Ivabradine significantly lowered standing heart rate, compared with placebo (77.9 vs. 94.2 beats/min; P < .001). The typical surge in heart rate that occurs upon standing in these patients was also blunted, compared with baseline (13.0 vs. 21.4 beats/min; P = .001).

“There are really not a lot of great options for patients with POTS and, mechanistically, ivabradine just make sense because it’s a drug that lowers heart rate very selectively and doesn’t lower blood pressure,” lead study author Pam R. Taub, MD, told this news organization.

Surprisingly, the reduction in heart rate translated into improved physical (P = .008) and social (P = .021) functioning after just 1 month of ivabradine, without any other background POTS medications or a change in nonpharmacologic therapies, she said. “What’s really nice to see is when you tackle a really significant part of the disease, which is the elevated heart rate, just how much better they feel.”

POTS patients are mostly healthy, active young women, who after some inciting event – such as viral infection, trauma, or surgery – experience an increase in heart rate of at least 30 beats/min upon standing accompanied by a range of symptoms, including dizziness, palpitations, brain fog, and fatigue.
 

A COVID connection?

The study enrolled patients with hyperadrenergic POTS as the predominant subtype, but another group to keep in mind that might benefit is the post-COVID POTS patient, said Dr. Taub, from the University of California, San Diego.

“We’re seeing an incredible number of patients post COVID that meet the criteria for POTS, and a lot of these patients also have COVID fatigue,” she said. “So clinically, myself and many other cardiologists who understand ivabradine have been using it off-label for the COVID patients, as long as they meet the criteria. You don’t want to use it in every COVID patient, but if someone’s predominant complaint is that their heart rate is going up when they’re standing and they’re debilitated by it, this is a drug to consider.”

Anecdotal findings in patients with long-hauler COVID need to be translated into rigorous research protocols, but mechanistically, whether it’s POTS from COVID or from another type of infection – like Lyme disease or some other viral syndrome – it should work the same, Dr. Taub said. “POTS is POTS.”

There are no first-line drugs for POTS, and current class IIb recommendations include midodrine, which increases blood pressure and can make people feel awful, and fludrocortisone, which can cause a lot of weight gain and fluid retention, she observed. Other agents that lower heart rate, like beta-blockers, also lower blood pressure and can aggravate depression and fatigue.

Ivabradine regulates heart rate by specifically blocking the Ifunny channel of the sinoatrial node. It was approved in 2015 in the United States to reduce hospitalizations in patients with systolic heart failure, and it also has a second class IIb recommendation for inappropriate sinus tachycardia.

The present study, reported in the Feb. 23 issue of the Journal of the American College of Cardiology, is the first randomized clinical trial using ivabradine to treat POTS.

A total of 26 patients with POTS were started on ivabradine 5 mg or placebo twice daily for 1 month, then were crossed over to the other treatment for 1 month after a 1-week washout period. Six patients were started on a 2.5-mg twice-daily dose. Doses were adjusted during the study based on the patient’s heart rate response and tolerance. Patients had seven clinic visits in which norepinephrine (NE) levels were measured and head-up tilt testing conducted.

Four patients in the ivabradine arm withdrew because of adverse effects, and one withdrew during crossover.

Among the 22 patients who completed the study, exploratory analyses showed a strong trend for greater reduction in plasma NE upon standing with ivabradine (P = .056). The effect was also more profound in patients with very high baseline standing NE levels (at least 1,000 pg/mL) than in those with lower NE levels (600 to 1,000 pg/mL).

“It makes sense because that means their sympathetic nervous system is more overactive; they have a higher heart rate,” Dr. Taub said. “So it’s a potential clinical tool that people can use in their practice to determine, ‘okay, is this a patient I should be considering ivabradine on?’ ”

Although the present study had only 22 patients, “it should definitely be looked at as a step forward, both in terms of ivabradine specifically and in terms of setting the standard for the types of studies we want to see in our patients,” Satish R. Raj, MD, MSCI, University of Calgary (Alta.), said in an interview.

In a related editorial, however, Dr. Raj and coauthor Robert S. Sheldon, MD, PhD, also from the University of Calgary, point out that the standing heart rate in the placebo phase was only 94 beats/min, “suggesting that these patients may be affected only mildly by their POTS.”

Asked about the point, Dr. Taub said: “I don’t know if I agree with that.” She noted that the diagnosis of POTS was confirmed by tilt-table testing and NE levels and that patients’ symptoms vary from day to day. “The standard deviation was plus or minus 16.8, so there’s variability.”

Both Dr. Raj and Dr. Taub said they expect the results will be included in the next scientific statement for POTS, but in the meantime, it may be a struggle to get the drug covered by insurance.  

“The challenge is that this is a very off-label use for this medication, and the medication’s not cheap,” Dr. Raj observed. The price for 60 tablets, which is about a 1-month supply, is $485 on GoodRx.

Another question going forward, he said, is whether ivabradine is superior to beta-blockers, which will be studied in a 20-patient crossover trial sponsored by the University of Calgary that is about to launch. The primary completion date is set for 2024.

The study was supported by a grant from Amgen. Dr. Taub has served as a consultant for Amgen, Bayer, Esperion, Boehringer Ingelheim, Novo Nordisk, and Sanofi; is a shareholder in Epirium Bio; and has received research grants from the National Institutes of Health, the American Heart Association, and the Department of Homeland Security/FEMA. Dr. Raj has received a research grant from the Canadian Institutes of Health Research and research grants from Dysautonomia International to address the pathophysiology of POTS. Dr. Sheldon has received a research grant from Dysautonomia International for a clinical trial assessing ivabradine and propranolol for the treatment of POTS.

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

The heart failure drug ivabradine (Corlanor) can provide relief from the elevated heart rate and often debilitating symptoms associated with postural orthostatic tachycardia syndrome (POTS), a new study suggests.

Pheelings Media/Getty Images

Ivabradine significantly lowered standing heart rate, compared with placebo (77.9 vs. 94.2 beats/min; P < .001). The typical surge in heart rate that occurs upon standing in these patients was also blunted, compared with baseline (13.0 vs. 21.4 beats/min; P = .001).

“There are really not a lot of great options for patients with POTS and, mechanistically, ivabradine just make sense because it’s a drug that lowers heart rate very selectively and doesn’t lower blood pressure,” lead study author Pam R. Taub, MD, told this news organization.

Surprisingly, the reduction in heart rate translated into improved physical (P = .008) and social (P = .021) functioning after just 1 month of ivabradine, without any other background POTS medications or a change in nonpharmacologic therapies, she said. “What’s really nice to see is when you tackle a really significant part of the disease, which is the elevated heart rate, just how much better they feel.”

POTS patients are mostly healthy, active young women, who after some inciting event – such as viral infection, trauma, or surgery – experience an increase in heart rate of at least 30 beats/min upon standing accompanied by a range of symptoms, including dizziness, palpitations, brain fog, and fatigue.
 

A COVID connection?

The study enrolled patients with hyperadrenergic POTS as the predominant subtype, but another group to keep in mind that might benefit is the post-COVID POTS patient, said Dr. Taub, from the University of California, San Diego.

“We’re seeing an incredible number of patients post COVID that meet the criteria for POTS, and a lot of these patients also have COVID fatigue,” she said. “So clinically, myself and many other cardiologists who understand ivabradine have been using it off-label for the COVID patients, as long as they meet the criteria. You don’t want to use it in every COVID patient, but if someone’s predominant complaint is that their heart rate is going up when they’re standing and they’re debilitated by it, this is a drug to consider.”

Anecdotal findings in patients with long-hauler COVID need to be translated into rigorous research protocols, but mechanistically, whether it’s POTS from COVID or from another type of infection – like Lyme disease or some other viral syndrome – it should work the same, Dr. Taub said. “POTS is POTS.”

There are no first-line drugs for POTS, and current class IIb recommendations include midodrine, which increases blood pressure and can make people feel awful, and fludrocortisone, which can cause a lot of weight gain and fluid retention, she observed. Other agents that lower heart rate, like beta-blockers, also lower blood pressure and can aggravate depression and fatigue.

Ivabradine regulates heart rate by specifically blocking the Ifunny channel of the sinoatrial node. It was approved in 2015 in the United States to reduce hospitalizations in patients with systolic heart failure, and it also has a second class IIb recommendation for inappropriate sinus tachycardia.

The present study, reported in the Feb. 23 issue of the Journal of the American College of Cardiology, is the first randomized clinical trial using ivabradine to treat POTS.

A total of 26 patients with POTS were started on ivabradine 5 mg or placebo twice daily for 1 month, then were crossed over to the other treatment for 1 month after a 1-week washout period. Six patients were started on a 2.5-mg twice-daily dose. Doses were adjusted during the study based on the patient’s heart rate response and tolerance. Patients had seven clinic visits in which norepinephrine (NE) levels were measured and head-up tilt testing conducted.

Four patients in the ivabradine arm withdrew because of adverse effects, and one withdrew during crossover.

Among the 22 patients who completed the study, exploratory analyses showed a strong trend for greater reduction in plasma NE upon standing with ivabradine (P = .056). The effect was also more profound in patients with very high baseline standing NE levels (at least 1,000 pg/mL) than in those with lower NE levels (600 to 1,000 pg/mL).

“It makes sense because that means their sympathetic nervous system is more overactive; they have a higher heart rate,” Dr. Taub said. “So it’s a potential clinical tool that people can use in their practice to determine, ‘okay, is this a patient I should be considering ivabradine on?’ ”

Although the present study had only 22 patients, “it should definitely be looked at as a step forward, both in terms of ivabradine specifically and in terms of setting the standard for the types of studies we want to see in our patients,” Satish R. Raj, MD, MSCI, University of Calgary (Alta.), said in an interview.

In a related editorial, however, Dr. Raj and coauthor Robert S. Sheldon, MD, PhD, also from the University of Calgary, point out that the standing heart rate in the placebo phase was only 94 beats/min, “suggesting that these patients may be affected only mildly by their POTS.”

Asked about the point, Dr. Taub said: “I don’t know if I agree with that.” She noted that the diagnosis of POTS was confirmed by tilt-table testing and NE levels and that patients’ symptoms vary from day to day. “The standard deviation was plus or minus 16.8, so there’s variability.”

Both Dr. Raj and Dr. Taub said they expect the results will be included in the next scientific statement for POTS, but in the meantime, it may be a struggle to get the drug covered by insurance.  

“The challenge is that this is a very off-label use for this medication, and the medication’s not cheap,” Dr. Raj observed. The price for 60 tablets, which is about a 1-month supply, is $485 on GoodRx.

Another question going forward, he said, is whether ivabradine is superior to beta-blockers, which will be studied in a 20-patient crossover trial sponsored by the University of Calgary that is about to launch. The primary completion date is set for 2024.

The study was supported by a grant from Amgen. Dr. Taub has served as a consultant for Amgen, Bayer, Esperion, Boehringer Ingelheim, Novo Nordisk, and Sanofi; is a shareholder in Epirium Bio; and has received research grants from the National Institutes of Health, the American Heart Association, and the Department of Homeland Security/FEMA. Dr. Raj has received a research grant from the Canadian Institutes of Health Research and research grants from Dysautonomia International to address the pathophysiology of POTS. Dr. Sheldon has received a research grant from Dysautonomia International for a clinical trial assessing ivabradine and propranolol for the treatment of POTS.

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

In the days since recreational sales of marijuana became legal in Colorado in January 2014, concerning trends have emerged among the state’s young cannabis users.

Courtesy Dr. Paula D. Riggs

According to a report from the Rocky Mountain High Intensity Drug Trafficking Area, between 2014 and 2017, the number of suicides positive for marijuana increased 250% among those aged 10-19 years (from 4 to 14) and 22% among those aged 20 and older (from 118 to 144). “Other states are seeing something similar, and there is an emerging research showing a relationship between suicidality and the use of marijuana, especially high-potency products that are available in legalized markets,” Paula D. Riggs, MD, reported during an annual psychopharmacology update held by the Nevada Psychiatric Association.

 During that same 3-year time span, the proportion of Colorado youth aged 12 years and older who used marijuana in the past month jumped by 45%, which is more than 85% above the national average. “Similarly, among college-age students, we’ve seen an 18% increase in past-month marijuana use, which is 60% above the national average,” said Dr. Riggs, professor and vice chair of psychiatry at the University of Colorado at Denver, Aurora.

Among adolescents, state health officials have observed a 5% increase in the proportion of those who used marijuana in the past month, which is more than 54% above the national average. “But a concerning trend is that we’re seeing an increase in the use of concentrates such as dabs and waxes,” she said. “That’s worrisome in terms of exposure to high-potency products.”

In other findings, 48% of young marijuana users reported going to work high (40% at least once per week), and there has been a 170% increase in youth ED urgent care visits for marijuana-related illnesses such as cannabinoid hyperemesis syndrome or first-episode psychosis. State health officials have also observed a 148% increase in marijuana-related hospitalizations.

According to Dr. Riggs, who also directs the University of Colorado’s division of addiction science, prevention, and treatment, the average marijuana joint in the 1960s contained about 3% tetrahydrocannabinol (THC), a level that crept up to the 4%-6% range in 2002. In today’s postlegalization era, the average joint now contains 13%-23% THC. “What’s concerning is that the concentrates – the dabs, waxes, shatter, and butane hash oils – contain upward of 70%-95% THC,” Dr. Riggs said. “Those are highly potent products that represent about 25% of the market share now. That’s a very big concern because the higher the potency the cannabis product used, the greater the abuse liability and addictive potential.”

The use of high-potency products also doubles the risk of developing generalized anxiety disorder, triples the risk of tobacco dependence, doubles the risk of other illicit substance disorders, and it at least quadruples the risk of developing first-episode psychosis in young people. “So, when you’re taking a cannabis use history, it’s important to ask patients about the potency of the products being used,” she said.

In the 2019 Monitoring the Future survey, 12% of U.S. 8th graders self-reported marijuana use in the past year and 7% in the past month, compared with 29% and 18% of 10th graders, respectively. Self-reported use by 12th graders was even more elevated (36% in the past year and 29% in the past month). “The concern is, this survey doesn’t really capture what’s happening with marijuana concentrates,” Dr. Riggs said.

A survey of Colorado youth conducted by the state’s Department of Public Health and Environment found that the percentage of students who reported using concentrated forms of marijuana has risen steadily in recent years and now stands at roughly 34%. “The use of edibles has also crept up,” said Dr. Riggs, who noted that marijuana dispensaries in Colorado outnumber Starbucks locations and McDonald’s restaurants. “You might not think that’s particularly concerning, except that the use of edibles is even more associated with onset of psychosis than other forms. This is probably because when you eat a marijuana product, you can’t control the exposure or the dose that you’re ingesting. We need to be concerned about these trends.”

European studies report that 30%-50% of new cases of first-onset psychosis are attributed to high-potency cannabis. “There is a dose-response relationship between cannabis and psychosis,” Dr. Riggs said. “That is, the frequency and duration of cannabis use, or the use of high-potency products, and the age of onset, are strongly associated with the risk of first-episode psychosis.

Researchers have known for some time that alterations in the endocannabinoid system are associated with psychosis independent of cannabis exposure. “Dysregulation of that endocannabinoid system occurs in patients at all stages of the psychosis continuum,” she continued. “It also means that the endocannabinoid system is a potential therapeutic target for psychosis.”

According to Dr. Riggs, THC exposure acutely increases dopamine in the ventral striatum and it can produce transient psychotomimetic effects in clinical and nonclinical populations. Genetic differences in the dopaminergic system can also interact with cannabis use to increase the risk of psychosis.

“For example, the COMT (catechol-O-methyltransferase) breaks down catecholamines such as dopamine in the prefrontal cortex,” she explained. “If you have a COMT gene polymorphism, that increases your risk of developing psychosis due to increased levels of dopamine signaling.”

She emphasized the importance of clinicians to understand that the age of cannabis use onset, the duration, frequency, and THC potency is related to the psychosis risk and worse prognosis. The earlier the initiation of marijuana use, the greater potential for first-episode psychosis. “Those who continue using cannabis after a first-episode psychosis have greater severity of psychotic illness and more treatment resistance, and they’re less likely to engage or be compliant with treatment recommendations,” Dr. Riggs said. “So, after that first-episode psychosis, it’s important to help a patient get abstinent. Because if they resume cannabis use, this can turn into a more chronic psychotic disorder.”

She added that, while insufficient evidence exists to determine whether cannabis plays a causal role in the development of schizophrenia or not, mounting evidence suggests that cannabis use may precipitate earlier onset of schizophrenia in those with other risk factors for the disorder. “There is considerable evidence that cannabis use increases the risk of psychosis in a dose-related manner, especially with an onset before age 16,” Dr. Riggs said. “However, this does not mean that cannabis is safe for young adults. Cannabis-induced psychotic symptoms often develop during young adulthood and may become chronic.”

Dr. Riggs disclosed that she had received grant funding from the National Institute on Drug Abuse. She is also executive director for Encompass, which provides integrated treatment for adolescents and young adults.

[email protected]

In the days since recreational sales of marijuana became legal in Colorado in January 2014, concerning trends have emerged among the state’s young cannabis users.

Courtesy Dr. Paula D. Riggs

According to a report from the Rocky Mountain High Intensity Drug Trafficking Area, between 2014 and 2017, the number of suicides positive for marijuana increased 250% among those aged 10-19 years (from 4 to 14) and 22% among those aged 20 and older (from 118 to 144). “Other states are seeing something similar, and there is an emerging research showing a relationship between suicidality and the use of marijuana, especially high-potency products that are available in legalized markets,” Paula D. Riggs, MD, reported during an annual psychopharmacology update held by the Nevada Psychiatric Association.

 During that same 3-year time span, the proportion of Colorado youth aged 12 years and older who used marijuana in the past month jumped by 45%, which is more than 85% above the national average. “Similarly, among college-age students, we’ve seen an 18% increase in past-month marijuana use, which is 60% above the national average,” said Dr. Riggs, professor and vice chair of psychiatry at the University of Colorado at Denver, Aurora.

Among adolescents, state health officials have observed a 5% increase in the proportion of those who used marijuana in the past month, which is more than 54% above the national average. “But a concerning trend is that we’re seeing an increase in the use of concentrates such as dabs and waxes,” she said. “That’s worrisome in terms of exposure to high-potency products.”

In other findings, 48% of young marijuana users reported going to work high (40% at least once per week), and there has been a 170% increase in youth ED urgent care visits for marijuana-related illnesses such as cannabinoid hyperemesis syndrome or first-episode psychosis. State health officials have also observed a 148% increase in marijuana-related hospitalizations.

According to Dr. Riggs, who also directs the University of Colorado’s division of addiction science, prevention, and treatment, the average marijuana joint in the 1960s contained about 3% tetrahydrocannabinol (THC), a level that crept up to the 4%-6% range in 2002. In today’s postlegalization era, the average joint now contains 13%-23% THC. “What’s concerning is that the concentrates – the dabs, waxes, shatter, and butane hash oils – contain upward of 70%-95% THC,” Dr. Riggs said. “Those are highly potent products that represent about 25% of the market share now. That’s a very big concern because the higher the potency the cannabis product used, the greater the abuse liability and addictive potential.”

The use of high-potency products also doubles the risk of developing generalized anxiety disorder, triples the risk of tobacco dependence, doubles the risk of other illicit substance disorders, and it at least quadruples the risk of developing first-episode psychosis in young people. “So, when you’re taking a cannabis use history, it’s important to ask patients about the potency of the products being used,” she said.

In the 2019 Monitoring the Future survey, 12% of U.S. 8th graders self-reported marijuana use in the past year and 7% in the past month, compared with 29% and 18% of 10th graders, respectively. Self-reported use by 12th graders was even more elevated (36% in the past year and 29% in the past month). “The concern is, this survey doesn’t really capture what’s happening with marijuana concentrates,” Dr. Riggs said.

A survey of Colorado youth conducted by the state’s Department of Public Health and Environment found that the percentage of students who reported using concentrated forms of marijuana has risen steadily in recent years and now stands at roughly 34%. “The use of edibles has also crept up,” said Dr. Riggs, who noted that marijuana dispensaries in Colorado outnumber Starbucks locations and McDonald’s restaurants. “You might not think that’s particularly concerning, except that the use of edibles is even more associated with onset of psychosis than other forms. This is probably because when you eat a marijuana product, you can’t control the exposure or the dose that you’re ingesting. We need to be concerned about these trends.”

European studies report that 30%-50% of new cases of first-onset psychosis are attributed to high-potency cannabis. “There is a dose-response relationship between cannabis and psychosis,” Dr. Riggs said. “That is, the frequency and duration of cannabis use, or the use of high-potency products, and the age of onset, are strongly associated with the risk of first-episode psychosis.

Researchers have known for some time that alterations in the endocannabinoid system are associated with psychosis independent of cannabis exposure. “Dysregulation of that endocannabinoid system occurs in patients at all stages of the psychosis continuum,” she continued. “It also means that the endocannabinoid system is a potential therapeutic target for psychosis.”

According to Dr. Riggs, THC exposure acutely increases dopamine in the ventral striatum and it can produce transient psychotomimetic effects in clinical and nonclinical populations. Genetic differences in the dopaminergic system can also interact with cannabis use to increase the risk of psychosis.

“For example, the COMT (catechol-O-methyltransferase) breaks down catecholamines such as dopamine in the prefrontal cortex,” she explained. “If you have a COMT gene polymorphism, that increases your risk of developing psychosis due to increased levels of dopamine signaling.”

She emphasized the importance of clinicians to understand that the age of cannabis use onset, the duration, frequency, and THC potency is related to the psychosis risk and worse prognosis. The earlier the initiation of marijuana use, the greater potential for first-episode psychosis. “Those who continue using cannabis after a first-episode psychosis have greater severity of psychotic illness and more treatment resistance, and they’re less likely to engage or be compliant with treatment recommendations,” Dr. Riggs said. “So, after that first-episode psychosis, it’s important to help a patient get abstinent. Because if they resume cannabis use, this can turn into a more chronic psychotic disorder.”

She added that, while insufficient evidence exists to determine whether cannabis plays a causal role in the development of schizophrenia or not, mounting evidence suggests that cannabis use may precipitate earlier onset of schizophrenia in those with other risk factors for the disorder. “There is considerable evidence that cannabis use increases the risk of psychosis in a dose-related manner, especially with an onset before age 16,” Dr. Riggs said. “However, this does not mean that cannabis is safe for young adults. Cannabis-induced psychotic symptoms often develop during young adulthood and may become chronic.”

Dr. Riggs disclosed that she had received grant funding from the National Institute on Drug Abuse. She is also executive director for Encompass, which provides integrated treatment for adolescents and young adults.

[email protected]

In the days since recreational sales of marijuana became legal in Colorado in January 2014, concerning trends have emerged among the state’s young cannabis users.

Courtesy Dr. Paula D. Riggs

According to a report from the Rocky Mountain High Intensity Drug Trafficking Area, between 2014 and 2017, the number of suicides positive for marijuana increased 250% among those aged 10-19 years (from 4 to 14) and 22% among those aged 20 and older (from 118 to 144). “Other states are seeing something similar, and there is an emerging research showing a relationship between suicidality and the use of marijuana, especially high-potency products that are available in legalized markets,” Paula D. Riggs, MD, reported during an annual psychopharmacology update held by the Nevada Psychiatric Association.

 During that same 3-year time span, the proportion of Colorado youth aged 12 years and older who used marijuana in the past month jumped by 45%, which is more than 85% above the national average. “Similarly, among college-age students, we’ve seen an 18% increase in past-month marijuana use, which is 60% above the national average,” said Dr. Riggs, professor and vice chair of psychiatry at the University of Colorado at Denver, Aurora.

Among adolescents, state health officials have observed a 5% increase in the proportion of those who used marijuana in the past month, which is more than 54% above the national average. “But a concerning trend is that we’re seeing an increase in the use of concentrates such as dabs and waxes,” she said. “That’s worrisome in terms of exposure to high-potency products.”

In other findings, 48% of young marijuana users reported going to work high (40% at least once per week), and there has been a 170% increase in youth ED urgent care visits for marijuana-related illnesses such as cannabinoid hyperemesis syndrome or first-episode psychosis. State health officials have also observed a 148% increase in marijuana-related hospitalizations.

According to Dr. Riggs, who also directs the University of Colorado’s division of addiction science, prevention, and treatment, the average marijuana joint in the 1960s contained about 3% tetrahydrocannabinol (THC), a level that crept up to the 4%-6% range in 2002. In today’s postlegalization era, the average joint now contains 13%-23% THC. “What’s concerning is that the concentrates – the dabs, waxes, shatter, and butane hash oils – contain upward of 70%-95% THC,” Dr. Riggs said. “Those are highly potent products that represent about 25% of the market share now. That’s a very big concern because the higher the potency the cannabis product used, the greater the abuse liability and addictive potential.”

The use of high-potency products also doubles the risk of developing generalized anxiety disorder, triples the risk of tobacco dependence, doubles the risk of other illicit substance disorders, and it at least quadruples the risk of developing first-episode psychosis in young people. “So, when you’re taking a cannabis use history, it’s important to ask patients about the potency of the products being used,” she said.

In the 2019 Monitoring the Future survey, 12% of U.S. 8th graders self-reported marijuana use in the past year and 7% in the past month, compared with 29% and 18% of 10th graders, respectively. Self-reported use by 12th graders was even more elevated (36% in the past year and 29% in the past month). “The concern is, this survey doesn’t really capture what’s happening with marijuana concentrates,” Dr. Riggs said.

A survey of Colorado youth conducted by the state’s Department of Public Health and Environment found that the percentage of students who reported using concentrated forms of marijuana has risen steadily in recent years and now stands at roughly 34%. “The use of edibles has also crept up,” said Dr. Riggs, who noted that marijuana dispensaries in Colorado outnumber Starbucks locations and McDonald’s restaurants. “You might not think that’s particularly concerning, except that the use of edibles is even more associated with onset of psychosis than other forms. This is probably because when you eat a marijuana product, you can’t control the exposure or the dose that you’re ingesting. We need to be concerned about these trends.”

European studies report that 30%-50% of new cases of first-onset psychosis are attributed to high-potency cannabis. “There is a dose-response relationship between cannabis and psychosis,” Dr. Riggs said. “That is, the frequency and duration of cannabis use, or the use of high-potency products, and the age of onset, are strongly associated with the risk of first-episode psychosis.

Researchers have known for some time that alterations in the endocannabinoid system are associated with psychosis independent of cannabis exposure. “Dysregulation of that endocannabinoid system occurs in patients at all stages of the psychosis continuum,” she continued. “It also means that the endocannabinoid system is a potential therapeutic target for psychosis.”

According to Dr. Riggs, THC exposure acutely increases dopamine in the ventral striatum and it can produce transient psychotomimetic effects in clinical and nonclinical populations. Genetic differences in the dopaminergic system can also interact with cannabis use to increase the risk of psychosis.

“For example, the COMT (catechol-O-methyltransferase) breaks down catecholamines such as dopamine in the prefrontal cortex,” she explained. “If you have a COMT gene polymorphism, that increases your risk of developing psychosis due to increased levels of dopamine signaling.”

She emphasized the importance of clinicians to understand that the age of cannabis use onset, the duration, frequency, and THC potency is related to the psychosis risk and worse prognosis. The earlier the initiation of marijuana use, the greater potential for first-episode psychosis. “Those who continue using cannabis after a first-episode psychosis have greater severity of psychotic illness and more treatment resistance, and they’re less likely to engage or be compliant with treatment recommendations,” Dr. Riggs said. “So, after that first-episode psychosis, it’s important to help a patient get abstinent. Because if they resume cannabis use, this can turn into a more chronic psychotic disorder.”

She added that, while insufficient evidence exists to determine whether cannabis plays a causal role in the development of schizophrenia or not, mounting evidence suggests that cannabis use may precipitate earlier onset of schizophrenia in those with other risk factors for the disorder. “There is considerable evidence that cannabis use increases the risk of psychosis in a dose-related manner, especially with an onset before age 16,” Dr. Riggs said. “However, this does not mean that cannabis is safe for young adults. Cannabis-induced psychotic symptoms often develop during young adulthood and may become chronic.”

Dr. Riggs disclosed that she had received grant funding from the National Institute on Drug Abuse. She is also executive director for Encompass, which provides integrated treatment for adolescents and young adults.

[email protected]

There were no significant differences in COVID-19 outcomes between cases caught by routine screening and screening based on symptoms/exposure history among cancer outpatients treated at Mayo Clinic facilities, according to a review of 224 cases.

The finding led to a shift away from routine COVID-19 screening to screening based on symptoms and exposures, said lead investigator Zhuoer Xie, MD, a hematology/oncology fellow at Mayo’s Rochester, Minn., campus.

“We are so happy” to see these results and be able to move away from routine screening. It’s burdensome and uncomfortable for patients and expensive to administer, Dr. Xie said at the AACR Virtual Meeting: COVID-19 and Cancer (Abstract S06-03).

Also, “our results provide reassurance that cancer care may safely continue during the pandemic with appropriate precautions,” she said.

Like many institutions, Mayo instituted routine COVID-19 screening for cancer outpatients at the start of the pandemic, requiring patients be tested 24 hours before systemic treatment, radiation therapy, or surgery. People on multiday regimens were screened twice a week.

Among 5,452 patients at the Rochester campus and its surrounding satellites, plus Mayo’s facilities in Phoenix and Jacksonville, Fla., routine screening picked up 63 COVID-19 cases (1.2%) from March 18 to July 31, 2020.

The outcomes were compared with 161 COVID-19 cases screened due to symptoms and exposure history. Most of the patients were on cancer surveillance as opposed to active treatment with routine testing.

Overall, 17.5% of cases caught by routine screening (11/63) were hospitalized versus 26.7% of patients screened for risk factors (43/161).

There was one COVID-19-related ICU admission among the 63 routine screening cases (1.6%) and nine ICU admissions (5.6%) among the risk-factor screening group. Three people diagnosed by routine screening (4.8%) died, compared with six deaths in the risk factor screening group (3.7%). The differences were not statistically significant, and there was no difference in treatment delay based on screening method.

The mortality rate was substantially lower than previously reported for COVID-19 among cancer patients, perhaps in part because Mayo facilities were not overwhelmed with cases early in the pandemic, so there was never a shortage of hospital beds and other resources, Dr. Xie said.

“Many of us are glad to see your data. It’s comforting,” said presentation moderator Solange Peters, MD, PhD, head of medical oncology at the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.

With proper precautions, “we can firmly encourage patients to come” in for their “cancer treatment without any hesitation,” Dr. Peters said.

“We feel the same way. We tell our patients this might be the safest place for you to be. Everybody is masked; everybody is taking all the precautions,” said Sheena Bhalla, MD, a hematology/oncology fellow as the Icahn School of Medicine at Mount Sinai, New York.

“We are [also] reaching out to patients who have been hesitant” about the COVID-19 vaccine, Dr. Bhalla said, “and trying to get them vaccinated. We are still learning how cancer patients will do with the vaccine, but we think that some protection is better than no protection.”

Currently at Mayo’s main campus in Rochester and its surrounding clinics, COVID-19 screening is based on symptoms, exposure, and factors such as high risk for neutropenic fever.

Mayo’s Arizona and Florida campuses had a surge of cases a few months ago, so routine screening is still used there but only on a monthly basis for people on active treatment.

Consistent with previous reports, older age and lymphopenia increased the risk of COVID-19 hospitalization in Mayo’s study, but comorbidities and active cancer treatment did not.

COVID-19 patients were a median of 62 years old, and 42% were women. Breast, genitourinary, and gastrointestinal tumors were the most common cancers.

Respiratory failure and sepsis were the most common complications among the 54 hospital admissions; eight patients required intubation.

The funding source wasn’t reported. The speakers had no relevant disclosures.

[email protected]

There were no significant differences in COVID-19 outcomes between cases caught by routine screening and screening based on symptoms/exposure history among cancer outpatients treated at Mayo Clinic facilities, according to a review of 224 cases.

The finding led to a shift away from routine COVID-19 screening to screening based on symptoms and exposures, said lead investigator Zhuoer Xie, MD, a hematology/oncology fellow at Mayo’s Rochester, Minn., campus.

“We are so happy” to see these results and be able to move away from routine screening. It’s burdensome and uncomfortable for patients and expensive to administer, Dr. Xie said at the AACR Virtual Meeting: COVID-19 and Cancer (Abstract S06-03).

Also, “our results provide reassurance that cancer care may safely continue during the pandemic with appropriate precautions,” she said.

Like many institutions, Mayo instituted routine COVID-19 screening for cancer outpatients at the start of the pandemic, requiring patients be tested 24 hours before systemic treatment, radiation therapy, or surgery. People on multiday regimens were screened twice a week.

Among 5,452 patients at the Rochester campus and its surrounding satellites, plus Mayo’s facilities in Phoenix and Jacksonville, Fla., routine screening picked up 63 COVID-19 cases (1.2%) from March 18 to July 31, 2020.

The outcomes were compared with 161 COVID-19 cases screened due to symptoms and exposure history. Most of the patients were on cancer surveillance as opposed to active treatment with routine testing.

Overall, 17.5% of cases caught by routine screening (11/63) were hospitalized versus 26.7% of patients screened for risk factors (43/161).

There was one COVID-19-related ICU admission among the 63 routine screening cases (1.6%) and nine ICU admissions (5.6%) among the risk-factor screening group. Three people diagnosed by routine screening (4.8%) died, compared with six deaths in the risk factor screening group (3.7%). The differences were not statistically significant, and there was no difference in treatment delay based on screening method.

The mortality rate was substantially lower than previously reported for COVID-19 among cancer patients, perhaps in part because Mayo facilities were not overwhelmed with cases early in the pandemic, so there was never a shortage of hospital beds and other resources, Dr. Xie said.

“Many of us are glad to see your data. It’s comforting,” said presentation moderator Solange Peters, MD, PhD, head of medical oncology at the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.

With proper precautions, “we can firmly encourage patients to come” in for their “cancer treatment without any hesitation,” Dr. Peters said.

“We feel the same way. We tell our patients this might be the safest place for you to be. Everybody is masked; everybody is taking all the precautions,” said Sheena Bhalla, MD, a hematology/oncology fellow as the Icahn School of Medicine at Mount Sinai, New York.

“We are [also] reaching out to patients who have been hesitant” about the COVID-19 vaccine, Dr. Bhalla said, “and trying to get them vaccinated. We are still learning how cancer patients will do with the vaccine, but we think that some protection is better than no protection.”

Currently at Mayo’s main campus in Rochester and its surrounding clinics, COVID-19 screening is based on symptoms, exposure, and factors such as high risk for neutropenic fever.

Mayo’s Arizona and Florida campuses had a surge of cases a few months ago, so routine screening is still used there but only on a monthly basis for people on active treatment.

Consistent with previous reports, older age and lymphopenia increased the risk of COVID-19 hospitalization in Mayo’s study, but comorbidities and active cancer treatment did not.

COVID-19 patients were a median of 62 years old, and 42% were women. Breast, genitourinary, and gastrointestinal tumors were the most common cancers.

Respiratory failure and sepsis were the most common complications among the 54 hospital admissions; eight patients required intubation.

The funding source wasn’t reported. The speakers had no relevant disclosures.

[email protected]

There were no significant differences in COVID-19 outcomes between cases caught by routine screening and screening based on symptoms/exposure history among cancer outpatients treated at Mayo Clinic facilities, according to a review of 224 cases.

The finding led to a shift away from routine COVID-19 screening to screening based on symptoms and exposures, said lead investigator Zhuoer Xie, MD, a hematology/oncology fellow at Mayo’s Rochester, Minn., campus.

“We are so happy” to see these results and be able to move away from routine screening. It’s burdensome and uncomfortable for patients and expensive to administer, Dr. Xie said at the AACR Virtual Meeting: COVID-19 and Cancer (Abstract S06-03).

Also, “our results provide reassurance that cancer care may safely continue during the pandemic with appropriate precautions,” she said.

Like many institutions, Mayo instituted routine COVID-19 screening for cancer outpatients at the start of the pandemic, requiring patients be tested 24 hours before systemic treatment, radiation therapy, or surgery. People on multiday regimens were screened twice a week.

Among 5,452 patients at the Rochester campus and its surrounding satellites, plus Mayo’s facilities in Phoenix and Jacksonville, Fla., routine screening picked up 63 COVID-19 cases (1.2%) from March 18 to July 31, 2020.

The outcomes were compared with 161 COVID-19 cases screened due to symptoms and exposure history. Most of the patients were on cancer surveillance as opposed to active treatment with routine testing.

Overall, 17.5% of cases caught by routine screening (11/63) were hospitalized versus 26.7% of patients screened for risk factors (43/161).

There was one COVID-19-related ICU admission among the 63 routine screening cases (1.6%) and nine ICU admissions (5.6%) among the risk-factor screening group. Three people diagnosed by routine screening (4.8%) died, compared with six deaths in the risk factor screening group (3.7%). The differences were not statistically significant, and there was no difference in treatment delay based on screening method.

The mortality rate was substantially lower than previously reported for COVID-19 among cancer patients, perhaps in part because Mayo facilities were not overwhelmed with cases early in the pandemic, so there was never a shortage of hospital beds and other resources, Dr. Xie said.

“Many of us are glad to see your data. It’s comforting,” said presentation moderator Solange Peters, MD, PhD, head of medical oncology at the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.

With proper precautions, “we can firmly encourage patients to come” in for their “cancer treatment without any hesitation,” Dr. Peters said.

“We feel the same way. We tell our patients this might be the safest place for you to be. Everybody is masked; everybody is taking all the precautions,” said Sheena Bhalla, MD, a hematology/oncology fellow as the Icahn School of Medicine at Mount Sinai, New York.

“We are [also] reaching out to patients who have been hesitant” about the COVID-19 vaccine, Dr. Bhalla said, “and trying to get them vaccinated. We are still learning how cancer patients will do with the vaccine, but we think that some protection is better than no protection.”

Currently at Mayo’s main campus in Rochester and its surrounding clinics, COVID-19 screening is based on symptoms, exposure, and factors such as high risk for neutropenic fever.

Mayo’s Arizona and Florida campuses had a surge of cases a few months ago, so routine screening is still used there but only on a monthly basis for people on active treatment.

Consistent with previous reports, older age and lymphopenia increased the risk of COVID-19 hospitalization in Mayo’s study, but comorbidities and active cancer treatment did not.

COVID-19 patients were a median of 62 years old, and 42% were women. Breast, genitourinary, and gastrointestinal tumors were the most common cancers.

Respiratory failure and sepsis were the most common complications among the 54 hospital admissions; eight patients required intubation.

The funding source wasn’t reported. The speakers had no relevant disclosures.

[email protected]

The findings of a new randomized trial support the rapid tapering of prednisone in patients with generalized myasthenia gravis requiring combined corticosteroid and azathioprine therapy. The trial showed that the conventional slow tapering regimen enabled discontinuation of prednisone earlier than previously reported but the new rapid-tapering regimen enabled an even faster discontinuation.

Noting that although both regimens led to a comparable myasthenia gravis status and prednisone dose at 15 months, the authors stated: “We think that the reduction of the cumulative dose over a year (equivalent to 5 mg/day) is a clinically relevant reduction, since the risk of complications is proportional to the daily or cumulative doses of prednisone.

“Our results warrant testing of a more rapid-tapering regimen in a future trial. In the meantime, our trial provides useful information on how prednisone tapering could be managed in patients with generalized myasthenia gravis treated with azathioprine,” they concluded.

The trial was published online Feb. 8 in JAMA Neurology.

Myasthenia gravis is a disorder of neuromuscular transmission, resulting from autoantibodies to components of the neuromuscular junction, most commonly the acetylcholine receptor. The incidence ranges from 0.3 to 2.8 per 100,000, and it is estimated to affect more than 700,000 people worldwide.

The authors of the current paper, led by Tarek Sharshar, MD, PhD, Groupe Hospitalier Universitaire, Paris, explained that many patients whose symptoms are not controlled by cholinesterase inhibitors are treated with corticosteroids and an immunosuppressant, usually azathioprine. No specific dosing protocol for prednisone has been validated, but it is commonly gradually increased to 0.75 mg/kg on alternate days and reduced progressively when minimal manifestation status (MMS; no symptoms or functional limitations) is reached.  

They noted that this regimen leads to high and prolonged corticosteroid treatment – often for several years – with the mean daily prednisone dose exceeding 30 mg/day at 15 months and 20 mg/day at 36 months. As long-term use of corticosteroids is often associated with significant complications, reducing or even discontinuing prednisone treatment without destabilizing myasthenia gravis is therefore a therapeutic goal.


 

Evaluating dosage regimens

To investigate whether different dosage regimens could help wean patients with generalized myasthenia gravis from corticosteroid therapy without compromising efficacy, the researchers conducted this study in which the current recommended regimen was compared with an approach using higher initial corticosteroid doses followed by rapid tapering.

In the conventional slow-tapering group (control group), prednisone was given on alternate days, starting at a dose of 10 mg then increased by increments of 10 mg every 2 days up to 1.5 mg/kg on alternate days without exceeding 100 mg. This dose was maintained until MMS was reached and then reduced by 10 mg every 2 weeks until a dosage of 40 mg was reached, with subsequent slowing of the taper to 5 mg monthly. If MMS was not maintained, the alternate-day prednisone dose was increased by 10 mg every 2 weeks until MMS was restored, and the tapering resumed 4 weeks later.

In the new rapid-tapering group, oral prednisone was immediately started at 0.75 mg/kg per day, and this was followed by an earlier and rapid decrease once improved myasthenia gravis status was attained. Three different tapering schedules were applied dependent on the improvement status of the patient.

First, If the patient reached MMS at 1 month, the dose of prednisone was reduced by 0.1 mg/kg every 10 days up to 0.45 mg/kg per day, then 0.05 mg/kg every 10 days up to 0.25 mg/kg per day, then in decrements of 1 mg by adjusting the duration of the decrements according to the participant’s weight with the aim of achieving complete cessation of corticosteroid therapy within 18-20 weeks for this third stage of tapering.

Second, if the state of MMS was not reached at 1 month but the participant had improved, a slower tapering was conducted, with the dosage reduced in a similar way to the first instance but with each reduction introduced every 20 days. If the participant reached MMS during this tapering process, the tapering of prednisone was similar to the sequence described in the first group.

Third, if MMS was not reached and the participant had not improved, the initial dose was maintained for the first 3 months; beyond that time, a decrease in the prednisone dose was undertaken as in the second group to a minimum dose of 0.25 mg/kg per day, after which the prednisone dose was not reduced further. If the patient improved, the tapering of prednisone followed the sequence described in the second category.

Reductions in prednisone dose could be accelerated in the case of severe prednisone adverse effects, according to the prescriber’s decision.

In the event of a myasthenia gravis exacerbation, the patient was hospitalized and the dose of prednisone was routinely doubled, or for a more moderate aggravation, the dose was increased to the previous dose recommended in the tapering regimen.

Azathioprine, up to a maximum dose of 3 mg/kg per day, was prescribed for all participants. In all, 117 patients were randomly assigned, and 113 completed the study.

The primary outcome was the proportion of participants having reached MMS without prednisone at 12 months and having not relapsed or taken prednisone between months 12 and 15. This was achieved by significantly more patients in the rapid-tapering group (39% vs. 9%; risk ratio, 3.61; P < .001).

Rapid tapering allowed sparing of a mean of 1,898 mg of prednisone over 1 year (5.3 mg/day) per patient.

The rate of myasthenia gravis exacerbation or worsening did not differ significantly between the two groups, nor did the use of plasmapheresis or IVIG or the doses of azathioprine.

The overall number of serious adverse events did not differ significantly between the two groups (slow tapering, 22% vs. rapid-tapering, 36%; P = .15).

The researchers said it is possible that prednisone tapering would differ with another immunosuppressive agent but as azathioprine is the first-line immunosuppressant usually recommended, these results are relevant for a large proportion of patients.

They said the better outcome of the intervention group could have been related to one or more of four differences in prednisone administration: An immediate high dose versus a slow increase of the prednisone dose; daily versus alternate-day dosing; earlier tapering initiation; and faster tapering. However, the structure of the study did not allow identification of which of these factors was responsible.

“Researching the best prednisone-tapering scheme is not only a major issue for patients with myasthenia gravis but also for other autoimmune or inflammatory diseases, because validated prednisone-tapering regimens are scarce,” the authors said.

The rapid tapering of prednisone therapy appears to be feasible, beneficial, and safe in patients with generalized myasthenia gravis and “warrants testing in other autoimmune diseases,” they added.
 

Particularly relevant to late-onset disease

Commenting on the study, Raffi Topakian, MD, Klinikum Wels-Grieskirchen, Wels, Austria, said the results showed that in patients with moderate to severe generalized myasthenia gravis requiring high-dose prednisone, azathioprine, a widely used immunosuppressant, may have a quicker steroid-sparing effect than previously thought, and that rapid steroid tapering can be achieved safely, resulting in a reduction of the cumulative steroid dose over a year despite higher initial doses.

Dr. Topakian, who was not involved with the research, pointed out that the median age was advanced (around 56 years), and the benefit of a regimen that leads to a reduction of the cumulative steroid dose over a year may be disproportionately larger for older, sicker patients with many comorbidities who are at considerably higher risk for a prednisone-induced increase in cardiovascular complications, osteoporotic fractures, and gastrointestinal bleeding. 

“The study findings are particularly relevant for the management of late-onset myasthenia gravis (when first symptoms start after age 45-50 years), which is being encountered more frequently over the past years,” he said.

“But the holy grail of myasthenia gravis treatment has not been found yet,” Dr. Topakian noted. “Disappointingly, rapid tapering of steroids (compared to slow tapering) resulted in a reduction of the cumulative steroid dose only, but was not associated with better myasthenia gravis functional status or lower doses of steroids at 15 months. To my view, this finding points to the limited immunosuppressive efficacy of azathioprine.”

He added that the study findings should not be extrapolated to patients with mild presentations or to those with muscle-specific kinase myasthenia gravis.

Dr. Sharshar disclosed no relevant financial relationships. Disclosures for the study coauthors appear in the original article.
 

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

The findings of a new randomized trial support the rapid tapering of prednisone in patients with generalized myasthenia gravis requiring combined corticosteroid and azathioprine therapy. The trial showed that the conventional slow tapering regimen enabled discontinuation of prednisone earlier than previously reported but the new rapid-tapering regimen enabled an even faster discontinuation.

Noting that although both regimens led to a comparable myasthenia gravis status and prednisone dose at 15 months, the authors stated: “We think that the reduction of the cumulative dose over a year (equivalent to 5 mg/day) is a clinically relevant reduction, since the risk of complications is proportional to the daily or cumulative doses of prednisone.

“Our results warrant testing of a more rapid-tapering regimen in a future trial. In the meantime, our trial provides useful information on how prednisone tapering could be managed in patients with generalized myasthenia gravis treated with azathioprine,” they concluded.

The trial was published online Feb. 8 in JAMA Neurology.

Myasthenia gravis is a disorder of neuromuscular transmission, resulting from autoantibodies to components of the neuromuscular junction, most commonly the acetylcholine receptor. The incidence ranges from 0.3 to 2.8 per 100,000, and it is estimated to affect more than 700,000 people worldwide.

The authors of the current paper, led by Tarek Sharshar, MD, PhD, Groupe Hospitalier Universitaire, Paris, explained that many patients whose symptoms are not controlled by cholinesterase inhibitors are treated with corticosteroids and an immunosuppressant, usually azathioprine. No specific dosing protocol for prednisone has been validated, but it is commonly gradually increased to 0.75 mg/kg on alternate days and reduced progressively when minimal manifestation status (MMS; no symptoms or functional limitations) is reached.  

They noted that this regimen leads to high and prolonged corticosteroid treatment – often for several years – with the mean daily prednisone dose exceeding 30 mg/day at 15 months and 20 mg/day at 36 months. As long-term use of corticosteroids is often associated with significant complications, reducing or even discontinuing prednisone treatment without destabilizing myasthenia gravis is therefore a therapeutic goal.


 

Evaluating dosage regimens

To investigate whether different dosage regimens could help wean patients with generalized myasthenia gravis from corticosteroid therapy without compromising efficacy, the researchers conducted this study in which the current recommended regimen was compared with an approach using higher initial corticosteroid doses followed by rapid tapering.

In the conventional slow-tapering group (control group), prednisone was given on alternate days, starting at a dose of 10 mg then increased by increments of 10 mg every 2 days up to 1.5 mg/kg on alternate days without exceeding 100 mg. This dose was maintained until MMS was reached and then reduced by 10 mg every 2 weeks until a dosage of 40 mg was reached, with subsequent slowing of the taper to 5 mg monthly. If MMS was not maintained, the alternate-day prednisone dose was increased by 10 mg every 2 weeks until MMS was restored, and the tapering resumed 4 weeks later.

In the new rapid-tapering group, oral prednisone was immediately started at 0.75 mg/kg per day, and this was followed by an earlier and rapid decrease once improved myasthenia gravis status was attained. Three different tapering schedules were applied dependent on the improvement status of the patient.

First, If the patient reached MMS at 1 month, the dose of prednisone was reduced by 0.1 mg/kg every 10 days up to 0.45 mg/kg per day, then 0.05 mg/kg every 10 days up to 0.25 mg/kg per day, then in decrements of 1 mg by adjusting the duration of the decrements according to the participant’s weight with the aim of achieving complete cessation of corticosteroid therapy within 18-20 weeks for this third stage of tapering.

Second, if the state of MMS was not reached at 1 month but the participant had improved, a slower tapering was conducted, with the dosage reduced in a similar way to the first instance but with each reduction introduced every 20 days. If the participant reached MMS during this tapering process, the tapering of prednisone was similar to the sequence described in the first group.

Third, if MMS was not reached and the participant had not improved, the initial dose was maintained for the first 3 months; beyond that time, a decrease in the prednisone dose was undertaken as in the second group to a minimum dose of 0.25 mg/kg per day, after which the prednisone dose was not reduced further. If the patient improved, the tapering of prednisone followed the sequence described in the second category.

Reductions in prednisone dose could be accelerated in the case of severe prednisone adverse effects, according to the prescriber’s decision.

In the event of a myasthenia gravis exacerbation, the patient was hospitalized and the dose of prednisone was routinely doubled, or for a more moderate aggravation, the dose was increased to the previous dose recommended in the tapering regimen.

Azathioprine, up to a maximum dose of 3 mg/kg per day, was prescribed for all participants. In all, 117 patients were randomly assigned, and 113 completed the study.

The primary outcome was the proportion of participants having reached MMS without prednisone at 12 months and having not relapsed or taken prednisone between months 12 and 15. This was achieved by significantly more patients in the rapid-tapering group (39% vs. 9%; risk ratio, 3.61; P < .001).

Rapid tapering allowed sparing of a mean of 1,898 mg of prednisone over 1 year (5.3 mg/day) per patient.

The rate of myasthenia gravis exacerbation or worsening did not differ significantly between the two groups, nor did the use of plasmapheresis or IVIG or the doses of azathioprine.

The overall number of serious adverse events did not differ significantly between the two groups (slow tapering, 22% vs. rapid-tapering, 36%; P = .15).

The researchers said it is possible that prednisone tapering would differ with another immunosuppressive agent but as azathioprine is the first-line immunosuppressant usually recommended, these results are relevant for a large proportion of patients.

They said the better outcome of the intervention group could have been related to one or more of four differences in prednisone administration: An immediate high dose versus a slow increase of the prednisone dose; daily versus alternate-day dosing; earlier tapering initiation; and faster tapering. However, the structure of the study did not allow identification of which of these factors was responsible.

“Researching the best prednisone-tapering scheme is not only a major issue for patients with myasthenia gravis but also for other autoimmune or inflammatory diseases, because validated prednisone-tapering regimens are scarce,” the authors said.

The rapid tapering of prednisone therapy appears to be feasible, beneficial, and safe in patients with generalized myasthenia gravis and “warrants testing in other autoimmune diseases,” they added.
 

Particularly relevant to late-onset disease

Commenting on the study, Raffi Topakian, MD, Klinikum Wels-Grieskirchen, Wels, Austria, said the results showed that in patients with moderate to severe generalized myasthenia gravis requiring high-dose prednisone, azathioprine, a widely used immunosuppressant, may have a quicker steroid-sparing effect than previously thought, and that rapid steroid tapering can be achieved safely, resulting in a reduction of the cumulative steroid dose over a year despite higher initial doses.

Dr. Topakian, who was not involved with the research, pointed out that the median age was advanced (around 56 years), and the benefit of a regimen that leads to a reduction of the cumulative steroid dose over a year may be disproportionately larger for older, sicker patients with many comorbidities who are at considerably higher risk for a prednisone-induced increase in cardiovascular complications, osteoporotic fractures, and gastrointestinal bleeding. 

“The study findings are particularly relevant for the management of late-onset myasthenia gravis (when first symptoms start after age 45-50 years), which is being encountered more frequently over the past years,” he said.

“But the holy grail of myasthenia gravis treatment has not been found yet,” Dr. Topakian noted. “Disappointingly, rapid tapering of steroids (compared to slow tapering) resulted in a reduction of the cumulative steroid dose only, but was not associated with better myasthenia gravis functional status or lower doses of steroids at 15 months. To my view, this finding points to the limited immunosuppressive efficacy of azathioprine.”

He added that the study findings should not be extrapolated to patients with mild presentations or to those with muscle-specific kinase myasthenia gravis.

Dr. Sharshar disclosed no relevant financial relationships. Disclosures for the study coauthors appear in the original article.
 

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

The findings of a new randomized trial support the rapid tapering of prednisone in patients with generalized myasthenia gravis requiring combined corticosteroid and azathioprine therapy. The trial showed that the conventional slow tapering regimen enabled discontinuation of prednisone earlier than previously reported but the new rapid-tapering regimen enabled an even faster discontinuation.

Noting that although both regimens led to a comparable myasthenia gravis status and prednisone dose at 15 months, the authors stated: “We think that the reduction of the cumulative dose over a year (equivalent to 5 mg/day) is a clinically relevant reduction, since the risk of complications is proportional to the daily or cumulative doses of prednisone.

“Our results warrant testing of a more rapid-tapering regimen in a future trial. In the meantime, our trial provides useful information on how prednisone tapering could be managed in patients with generalized myasthenia gravis treated with azathioprine,” they concluded.

The trial was published online Feb. 8 in JAMA Neurology.

Myasthenia gravis is a disorder of neuromuscular transmission, resulting from autoantibodies to components of the neuromuscular junction, most commonly the acetylcholine receptor. The incidence ranges from 0.3 to 2.8 per 100,000, and it is estimated to affect more than 700,000 people worldwide.

The authors of the current paper, led by Tarek Sharshar, MD, PhD, Groupe Hospitalier Universitaire, Paris, explained that many patients whose symptoms are not controlled by cholinesterase inhibitors are treated with corticosteroids and an immunosuppressant, usually azathioprine. No specific dosing protocol for prednisone has been validated, but it is commonly gradually increased to 0.75 mg/kg on alternate days and reduced progressively when minimal manifestation status (MMS; no symptoms or functional limitations) is reached.  

They noted that this regimen leads to high and prolonged corticosteroid treatment – often for several years – with the mean daily prednisone dose exceeding 30 mg/day at 15 months and 20 mg/day at 36 months. As long-term use of corticosteroids is often associated with significant complications, reducing or even discontinuing prednisone treatment without destabilizing myasthenia gravis is therefore a therapeutic goal.


 

Evaluating dosage regimens

To investigate whether different dosage regimens could help wean patients with generalized myasthenia gravis from corticosteroid therapy without compromising efficacy, the researchers conducted this study in which the current recommended regimen was compared with an approach using higher initial corticosteroid doses followed by rapid tapering.

In the conventional slow-tapering group (control group), prednisone was given on alternate days, starting at a dose of 10 mg then increased by increments of 10 mg every 2 days up to 1.5 mg/kg on alternate days without exceeding 100 mg. This dose was maintained until MMS was reached and then reduced by 10 mg every 2 weeks until a dosage of 40 mg was reached, with subsequent slowing of the taper to 5 mg monthly. If MMS was not maintained, the alternate-day prednisone dose was increased by 10 mg every 2 weeks until MMS was restored, and the tapering resumed 4 weeks later.

In the new rapid-tapering group, oral prednisone was immediately started at 0.75 mg/kg per day, and this was followed by an earlier and rapid decrease once improved myasthenia gravis status was attained. Three different tapering schedules were applied dependent on the improvement status of the patient.

First, If the patient reached MMS at 1 month, the dose of prednisone was reduced by 0.1 mg/kg every 10 days up to 0.45 mg/kg per day, then 0.05 mg/kg every 10 days up to 0.25 mg/kg per day, then in decrements of 1 mg by adjusting the duration of the decrements according to the participant’s weight with the aim of achieving complete cessation of corticosteroid therapy within 18-20 weeks for this third stage of tapering.

Second, if the state of MMS was not reached at 1 month but the participant had improved, a slower tapering was conducted, with the dosage reduced in a similar way to the first instance but with each reduction introduced every 20 days. If the participant reached MMS during this tapering process, the tapering of prednisone was similar to the sequence described in the first group.

Third, if MMS was not reached and the participant had not improved, the initial dose was maintained for the first 3 months; beyond that time, a decrease in the prednisone dose was undertaken as in the second group to a minimum dose of 0.25 mg/kg per day, after which the prednisone dose was not reduced further. If the patient improved, the tapering of prednisone followed the sequence described in the second category.

Reductions in prednisone dose could be accelerated in the case of severe prednisone adverse effects, according to the prescriber’s decision.

In the event of a myasthenia gravis exacerbation, the patient was hospitalized and the dose of prednisone was routinely doubled, or for a more moderate aggravation, the dose was increased to the previous dose recommended in the tapering regimen.

Azathioprine, up to a maximum dose of 3 mg/kg per day, was prescribed for all participants. In all, 117 patients were randomly assigned, and 113 completed the study.

The primary outcome was the proportion of participants having reached MMS without prednisone at 12 months and having not relapsed or taken prednisone between months 12 and 15. This was achieved by significantly more patients in the rapid-tapering group (39% vs. 9%; risk ratio, 3.61; P < .001).

Rapid tapering allowed sparing of a mean of 1,898 mg of prednisone over 1 year (5.3 mg/day) per patient.

The rate of myasthenia gravis exacerbation or worsening did not differ significantly between the two groups, nor did the use of plasmapheresis or IVIG or the doses of azathioprine.

The overall number of serious adverse events did not differ significantly between the two groups (slow tapering, 22% vs. rapid-tapering, 36%; P = .15).

The researchers said it is possible that prednisone tapering would differ with another immunosuppressive agent but as azathioprine is the first-line immunosuppressant usually recommended, these results are relevant for a large proportion of patients.

They said the better outcome of the intervention group could have been related to one or more of four differences in prednisone administration: An immediate high dose versus a slow increase of the prednisone dose; daily versus alternate-day dosing; earlier tapering initiation; and faster tapering. However, the structure of the study did not allow identification of which of these factors was responsible.

“Researching the best prednisone-tapering scheme is not only a major issue for patients with myasthenia gravis but also for other autoimmune or inflammatory diseases, because validated prednisone-tapering regimens are scarce,” the authors said.

The rapid tapering of prednisone therapy appears to be feasible, beneficial, and safe in patients with generalized myasthenia gravis and “warrants testing in other autoimmune diseases,” they added.
 

Particularly relevant to late-onset disease

Commenting on the study, Raffi Topakian, MD, Klinikum Wels-Grieskirchen, Wels, Austria, said the results showed that in patients with moderate to severe generalized myasthenia gravis requiring high-dose prednisone, azathioprine, a widely used immunosuppressant, may have a quicker steroid-sparing effect than previously thought, and that rapid steroid tapering can be achieved safely, resulting in a reduction of the cumulative steroid dose over a year despite higher initial doses.

Dr. Topakian, who was not involved with the research, pointed out that the median age was advanced (around 56 years), and the benefit of a regimen that leads to a reduction of the cumulative steroid dose over a year may be disproportionately larger for older, sicker patients with many comorbidities who are at considerably higher risk for a prednisone-induced increase in cardiovascular complications, osteoporotic fractures, and gastrointestinal bleeding. 

“The study findings are particularly relevant for the management of late-onset myasthenia gravis (when first symptoms start after age 45-50 years), which is being encountered more frequently over the past years,” he said.

“But the holy grail of myasthenia gravis treatment has not been found yet,” Dr. Topakian noted. “Disappointingly, rapid tapering of steroids (compared to slow tapering) resulted in a reduction of the cumulative steroid dose only, but was not associated with better myasthenia gravis functional status or lower doses of steroids at 15 months. To my view, this finding points to the limited immunosuppressive efficacy of azathioprine.”

He added that the study findings should not be extrapolated to patients with mild presentations or to those with muscle-specific kinase myasthenia gravis.

Dr. Sharshar disclosed no relevant financial relationships. Disclosures for the study coauthors appear in the original article.
 

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

Key clinical point: Treatment with erenumab significantly improved functional outcomes in 3 months in patients with episodic migraine refractory to previous prophylactic therapies.

Major finding: At 12 weeks, erenumab significantly improved “Migraine Physical Function Impact Diary”-“Physical Impairment” and “Everyday Activities” scores compared with placebo (treatment difference [TD], −3.5; P = .003 and TD, −3.9; P less than .001, respectively). A significantly higher proportion of patients had a 5 or more point reduction in the Headache Impact Test score from baseline compared with placebo (odds ratio, 2.4; P = .002).

Study details: Data come from the 12-week, double-blind, multicenter, Liberty study involving 246 episodic migraine patients who did not previously benefit from 2-4 prophylactic treatments. They were randomly assigned to receive either erenumab 140 mg (n = 121) or placebo (n = 125) once every 4 weeks for 12 weeks.

Disclosures: The study was supported by Novartis Pharma AG, Basel, Switzerland. S Wen, P Hours-Zesiger, and J Klatt were employees of, and hold stocks in, Novartis. M Lanteri-Minet, PJ Goadsby, U Reuter, and MD Ferrari reported relationships with various pharmaceutical companies and/or research organizations.

Source:Lanteri-Minet M et al. J Neurol Neurosurg Psychiatry. 2021 Jan 5. doi: 10.1136/jnnp-2020-324396.

Key clinical point: Treatment with erenumab significantly improved functional outcomes in 3 months in patients with episodic migraine refractory to previous prophylactic therapies.

Major finding: At 12 weeks, erenumab significantly improved “Migraine Physical Function Impact Diary”-“Physical Impairment” and “Everyday Activities” scores compared with placebo (treatment difference [TD], −3.5; P = .003 and TD, −3.9; P less than .001, respectively). A significantly higher proportion of patients had a 5 or more point reduction in the Headache Impact Test score from baseline compared with placebo (odds ratio, 2.4; P = .002).

Study details: Data come from the 12-week, double-blind, multicenter, Liberty study involving 246 episodic migraine patients who did not previously benefit from 2-4 prophylactic treatments. They were randomly assigned to receive either erenumab 140 mg (n = 121) or placebo (n = 125) once every 4 weeks for 12 weeks.

Disclosures: The study was supported by Novartis Pharma AG, Basel, Switzerland. S Wen, P Hours-Zesiger, and J Klatt were employees of, and hold stocks in, Novartis. M Lanteri-Minet, PJ Goadsby, U Reuter, and MD Ferrari reported relationships with various pharmaceutical companies and/or research organizations.

Source:Lanteri-Minet M et al. J Neurol Neurosurg Psychiatry. 2021 Jan 5. doi: 10.1136/jnnp-2020-324396.

Key clinical point: Treatment with erenumab significantly improved functional outcomes in 3 months in patients with episodic migraine refractory to previous prophylactic therapies.

Major finding: At 12 weeks, erenumab significantly improved “Migraine Physical Function Impact Diary”-“Physical Impairment” and “Everyday Activities” scores compared with placebo (treatment difference [TD], −3.5; P = .003 and TD, −3.9; P less than .001, respectively). A significantly higher proportion of patients had a 5 or more point reduction in the Headache Impact Test score from baseline compared with placebo (odds ratio, 2.4; P = .002).

Study details: Data come from the 12-week, double-blind, multicenter, Liberty study involving 246 episodic migraine patients who did not previously benefit from 2-4 prophylactic treatments. They were randomly assigned to receive either erenumab 140 mg (n = 121) or placebo (n = 125) once every 4 weeks for 12 weeks.

Disclosures: The study was supported by Novartis Pharma AG, Basel, Switzerland. S Wen, P Hours-Zesiger, and J Klatt were employees of, and hold stocks in, Novartis. M Lanteri-Minet, PJ Goadsby, U Reuter, and MD Ferrari reported relationships with various pharmaceutical companies and/or research organizations.

Source:Lanteri-Minet M et al. J Neurol Neurosurg Psychiatry. 2021 Jan 5. doi: 10.1136/jnnp-2020-324396.

Key clinical point: Erenumab treatment significantly improved the number of headache days in patients with onabotulinumtoxinA-resistant chronic migraine.

Major finding: Erenumab significantly reduced the number of headache days that limited activities of daily living at 3 months (−6.4 days), 6 months (−6.8 days), and 9 months (−6.5 days; P for all = .001).

Study details: Real-world outcomes were assessed in 98 patients with difficult-to-control chronic migraine and a prior unsatisfactory response to onabotulinumtoxinA.

Disclosures: This study did not receive any funding. Erenumab was provided free of charge by Novartis. S Weatherby attended conferences/received speakers fees from Novartis.

Source:Talbot J et al. J Headache Pain. 2021 Jan 9. doi: 10.1186/s10194-020-01214-2.

Key clinical point: Erenumab treatment significantly improved the number of headache days in patients with onabotulinumtoxinA-resistant chronic migraine.

Major finding: Erenumab significantly reduced the number of headache days that limited activities of daily living at 3 months (−6.4 days), 6 months (−6.8 days), and 9 months (−6.5 days; P for all = .001).

Study details: Real-world outcomes were assessed in 98 patients with difficult-to-control chronic migraine and a prior unsatisfactory response to onabotulinumtoxinA.

Disclosures: This study did not receive any funding. Erenumab was provided free of charge by Novartis. S Weatherby attended conferences/received speakers fees from Novartis.

Source:Talbot J et al. J Headache Pain. 2021 Jan 9. doi: 10.1186/s10194-020-01214-2.

Key clinical point: Erenumab treatment significantly improved the number of headache days in patients with onabotulinumtoxinA-resistant chronic migraine.

Major finding: Erenumab significantly reduced the number of headache days that limited activities of daily living at 3 months (−6.4 days), 6 months (−6.8 days), and 9 months (−6.5 days; P for all = .001).

Study details: Real-world outcomes were assessed in 98 patients with difficult-to-control chronic migraine and a prior unsatisfactory response to onabotulinumtoxinA.

Disclosures: This study did not receive any funding. Erenumab was provided free of charge by Novartis. S Weatherby attended conferences/received speakers fees from Novartis.

Source:Talbot J et al. J Headache Pain. 2021 Jan 9. doi: 10.1186/s10194-020-01214-2.

Key clinical point: People with a history of migraine are more than twice as likely as those with no such history to have irritable bowel syndrome (IBS).

Major finding: IBS odds were significantly higher in patients with migraine vs. those without: overall (pooled odds ratio [OR], 2.49; 95% confidence interval [CI], 2.22-2.78); migraine with aura (pooled OR, 3.03; 95% CI, 1.72-5.35); and migraine without aura (pooled OR, 2.20; 95% CI, 1.49-3.25).

Study details: Meta-analysis of 11 studies including 28,336 migraineurs and 1,535,758 nonmigraineurs.

Disclosures: The study did not receive any funding. The authors declared no conflicts of interest.

Source:Wongtrakul W et al. Eur J Gastroenterol Hepatol. 2021 Jan 18. doi: 10.1097/MEG.0000000000002065.

Key clinical point: People with a history of migraine are more than twice as likely as those with no such history to have irritable bowel syndrome (IBS).

Major finding: IBS odds were significantly higher in patients with migraine vs. those without: overall (pooled odds ratio [OR], 2.49; 95% confidence interval [CI], 2.22-2.78); migraine with aura (pooled OR, 3.03; 95% CI, 1.72-5.35); and migraine without aura (pooled OR, 2.20; 95% CI, 1.49-3.25).

Study details: Meta-analysis of 11 studies including 28,336 migraineurs and 1,535,758 nonmigraineurs.

Disclosures: The study did not receive any funding. The authors declared no conflicts of interest.

Source:Wongtrakul W et al. Eur J Gastroenterol Hepatol. 2021 Jan 18. doi: 10.1097/MEG.0000000000002065.

Key clinical point: People with a history of migraine are more than twice as likely as those with no such history to have irritable bowel syndrome (IBS).

Major finding: IBS odds were significantly higher in patients with migraine vs. those without: overall (pooled odds ratio [OR], 2.49; 95% confidence interval [CI], 2.22-2.78); migraine with aura (pooled OR, 3.03; 95% CI, 1.72-5.35); and migraine without aura (pooled OR, 2.20; 95% CI, 1.49-3.25).

Study details: Meta-analysis of 11 studies including 28,336 migraineurs and 1,535,758 nonmigraineurs.

Disclosures: The study did not receive any funding. The authors declared no conflicts of interest.

Source:Wongtrakul W et al. Eur J Gastroenterol Hepatol. 2021 Jan 18. doi: 10.1097/MEG.0000000000002065.