VANCOUVER – New evidence from the phase 3 EoE KIDS trial supports the safety and efficacy of dupilumab (Dupixent) treatment for children aged 1-11 years with eosinophilic esophagitis (EoE).

High exposure to dupilumab was associated with significantly improved histologic, endoscopic, and transcriptomic improvements, compared with placebo at week 16. Sustained response or improvements continued to week 52 with continued treatment in the high-exposure dupilumab group. Children in the high-exposure dupilumab group also gained more weight during the study than those initially assigned to placebo.

“Eosinophilic esophagitis is a chronic, aggressive, type 2 inflammatory disease that has a substantial impact on quality of life,” said Mirna Chehade, MD, MPH, of the Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai in New York. And the incidence and prevalence of the disease is increasing.

Dupilumab is already indicated for treating EoE in adolescents aged 12 or older as well as adults, but “there are no approved treatments for EoE in children under 12,” said Dr. Chehade, who presented the results of the late-breaking abstract at the ACG: American College of Gastroenterology 2023 annual scientific meeting.

She and her colleagues randomly assigned 102 children aged 1-11 years with active EoE to three groups for the first 16 weeks of the study: 37 to high-exposure dupilumab; 31 to low-exposure dupilumab; and 34 others to placebo, followed by either high- or low-dose dupilumab. Baseline demographics and disease characteristics were comparable between groups.

During an active 36-week extension period, the 37 participants who were initially assigned to receive high-exposure dupilumab continued the same treatment up to week 52. A total of 29 participants initially assigned to receive low-exposure dupilumab continues their regimen as well. Those initially assigned to receive placebo switched to a preassigned active treatment group; 18 children started to take high-exposure dupilumab, and 14 began to take low-exposure dupilumab.

The children in the study had a high burden of disease, as reflected by the duration of EoE as well as histologic, endoscopic, and clinical scores. The mean age was 7.2 years in the placebo group and 6.8 years in the dupilumab group. They were mostly White boys, Dr. Chehade said.
 

Key outcomes

At week 16, the high-exposure dupilumab group met the primary study endpoint with a peak esophageal intraepithelial eosinophil count ≤ 6 on high-power field assessment. This was significantly different from the placebo group (least squares mean difference, 64.5; 95% confidence interval, 48.19-80.85; P < .0001).

At week 52, 63% of children who remained on high-exposure dupilumab and 53% of those who switched from placebo to high-exposure dupilumab achieved a peak eosinophil count ≤ 6.

The study included multiple secondary outcomes. For example, at week 16, the following measures improved from baseline with high-exposure dupilumab, compared with placebo:

• EoE-Histologic Scoring System grade and stage scores (–0.88 and –0.84 vs. +0.02 and +0.05; both P < .0001).
• EoE-Endoscopic Reference Score (–3.5 vs. +0.3; P < .0001).
• Change in body weight for age percentile (+3.09 vs. +0.29).
• Numeric improvement in caregiver-reported proportion of days experiencing one or more EoE sign (–0.28 vs. –0.17).

At week 52, these outcomes were sustained or improved with continued high-exposure dupilumab. The researchers also saw improvements among the placebo recipients who switched to high-exposure dupilumab.

The reason the children were randomly assigned to high-exposure or low-exposure groups instead of high-dose and low-dose cohorts is because the children grew during the study, Dr. Chehade explained. “As you can see, there was a nice change in weight, and at specific time periods the doses were adjusted to match.”
 

‘Good safety profile’

Dupilumab was well tolerated. “The safety profile is very similar to what has been so far described and published for dupilumab in adults,” said Dr. Chehade. At week 16, adverse events that were more frequent with dupilumab vs. placebo included COVID-19, rash, headache, and injection-site erythema, for example. Similar safety results were seen up to week 52.

“I think it’s promising as we wait for the actual study to be published,” said Asmeen Bhatt, MD, PhD, co-moderator of the session and assistant professor of medicine at University of Texas Health Science Center, Houston. “The drug was recently approved for adult EOE use, just last year, and it has been shown to be effective.”

“There are a lot of adult drugs that are now being tested in the pediatric population, and this is one of them,” Dr. Bhatt added. “It has a very good safety profile. I’m not a pediatric gastroenterologist but I expect that it will have a lot of utility.”

The study was funded by Regeneron and Sanofi. Dr. Chehade is a consultant for Sanofi and Regeneron and receives research funding from Regeneron. Dr. Bhatt had no relevant financial disclosures.

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

VANCOUVER – New evidence from the phase 3 EoE KIDS trial supports the safety and efficacy of dupilumab (Dupixent) treatment for children aged 1-11 years with eosinophilic esophagitis (EoE).

High exposure to dupilumab was associated with significantly improved histologic, endoscopic, and transcriptomic improvements, compared with placebo at week 16. Sustained response or improvements continued to week 52 with continued treatment in the high-exposure dupilumab group. Children in the high-exposure dupilumab group also gained more weight during the study than those initially assigned to placebo.

“Eosinophilic esophagitis is a chronic, aggressive, type 2 inflammatory disease that has a substantial impact on quality of life,” said Mirna Chehade, MD, MPH, of the Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai in New York. And the incidence and prevalence of the disease is increasing.

Dupilumab is already indicated for treating EoE in adolescents aged 12 or older as well as adults, but “there are no approved treatments for EoE in children under 12,” said Dr. Chehade, who presented the results of the late-breaking abstract at the ACG: American College of Gastroenterology 2023 annual scientific meeting.

She and her colleagues randomly assigned 102 children aged 1-11 years with active EoE to three groups for the first 16 weeks of the study: 37 to high-exposure dupilumab; 31 to low-exposure dupilumab; and 34 others to placebo, followed by either high- or low-dose dupilumab. Baseline demographics and disease characteristics were comparable between groups.

During an active 36-week extension period, the 37 participants who were initially assigned to receive high-exposure dupilumab continued the same treatment up to week 52. A total of 29 participants initially assigned to receive low-exposure dupilumab continues their regimen as well. Those initially assigned to receive placebo switched to a preassigned active treatment group; 18 children started to take high-exposure dupilumab, and 14 began to take low-exposure dupilumab.

The children in the study had a high burden of disease, as reflected by the duration of EoE as well as histologic, endoscopic, and clinical scores. The mean age was 7.2 years in the placebo group and 6.8 years in the dupilumab group. They were mostly White boys, Dr. Chehade said.
 

Key outcomes

At week 16, the high-exposure dupilumab group met the primary study endpoint with a peak esophageal intraepithelial eosinophil count ≤ 6 on high-power field assessment. This was significantly different from the placebo group (least squares mean difference, 64.5; 95% confidence interval, 48.19-80.85; P < .0001).

At week 52, 63% of children who remained on high-exposure dupilumab and 53% of those who switched from placebo to high-exposure dupilumab achieved a peak eosinophil count ≤ 6.

The study included multiple secondary outcomes. For example, at week 16, the following measures improved from baseline with high-exposure dupilumab, compared with placebo:

• EoE-Histologic Scoring System grade and stage scores (–0.88 and –0.84 vs. +0.02 and +0.05; both P < .0001).
• EoE-Endoscopic Reference Score (–3.5 vs. +0.3; P < .0001).
• Change in body weight for age percentile (+3.09 vs. +0.29).
• Numeric improvement in caregiver-reported proportion of days experiencing one or more EoE sign (–0.28 vs. –0.17).

At week 52, these outcomes were sustained or improved with continued high-exposure dupilumab. The researchers also saw improvements among the placebo recipients who switched to high-exposure dupilumab.

The reason the children were randomly assigned to high-exposure or low-exposure groups instead of high-dose and low-dose cohorts is because the children grew during the study, Dr. Chehade explained. “As you can see, there was a nice change in weight, and at specific time periods the doses were adjusted to match.”
 

‘Good safety profile’

Dupilumab was well tolerated. “The safety profile is very similar to what has been so far described and published for dupilumab in adults,” said Dr. Chehade. At week 16, adverse events that were more frequent with dupilumab vs. placebo included COVID-19, rash, headache, and injection-site erythema, for example. Similar safety results were seen up to week 52.

“I think it’s promising as we wait for the actual study to be published,” said Asmeen Bhatt, MD, PhD, co-moderator of the session and assistant professor of medicine at University of Texas Health Science Center, Houston. “The drug was recently approved for adult EOE use, just last year, and it has been shown to be effective.”

“There are a lot of adult drugs that are now being tested in the pediatric population, and this is one of them,” Dr. Bhatt added. “It has a very good safety profile. I’m not a pediatric gastroenterologist but I expect that it will have a lot of utility.”

The study was funded by Regeneron and Sanofi. Dr. Chehade is a consultant for Sanofi and Regeneron and receives research funding from Regeneron. Dr. Bhatt had no relevant financial disclosures.

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

VANCOUVER – New evidence from the phase 3 EoE KIDS trial supports the safety and efficacy of dupilumab (Dupixent) treatment for children aged 1-11 years with eosinophilic esophagitis (EoE).

High exposure to dupilumab was associated with significantly improved histologic, endoscopic, and transcriptomic improvements, compared with placebo at week 16. Sustained response or improvements continued to week 52 with continued treatment in the high-exposure dupilumab group. Children in the high-exposure dupilumab group also gained more weight during the study than those initially assigned to placebo.

“Eosinophilic esophagitis is a chronic, aggressive, type 2 inflammatory disease that has a substantial impact on quality of life,” said Mirna Chehade, MD, MPH, of the Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai in New York. And the incidence and prevalence of the disease is increasing.

Dupilumab is already indicated for treating EoE in adolescents aged 12 or older as well as adults, but “there are no approved treatments for EoE in children under 12,” said Dr. Chehade, who presented the results of the late-breaking abstract at the ACG: American College of Gastroenterology 2023 annual scientific meeting.

She and her colleagues randomly assigned 102 children aged 1-11 years with active EoE to three groups for the first 16 weeks of the study: 37 to high-exposure dupilumab; 31 to low-exposure dupilumab; and 34 others to placebo, followed by either high- or low-dose dupilumab. Baseline demographics and disease characteristics were comparable between groups.

During an active 36-week extension period, the 37 participants who were initially assigned to receive high-exposure dupilumab continued the same treatment up to week 52. A total of 29 participants initially assigned to receive low-exposure dupilumab continues their regimen as well. Those initially assigned to receive placebo switched to a preassigned active treatment group; 18 children started to take high-exposure dupilumab, and 14 began to take low-exposure dupilumab.

The children in the study had a high burden of disease, as reflected by the duration of EoE as well as histologic, endoscopic, and clinical scores. The mean age was 7.2 years in the placebo group and 6.8 years in the dupilumab group. They were mostly White boys, Dr. Chehade said.
 

Key outcomes

At week 16, the high-exposure dupilumab group met the primary study endpoint with a peak esophageal intraepithelial eosinophil count ≤ 6 on high-power field assessment. This was significantly different from the placebo group (least squares mean difference, 64.5; 95% confidence interval, 48.19-80.85; P < .0001).

At week 52, 63% of children who remained on high-exposure dupilumab and 53% of those who switched from placebo to high-exposure dupilumab achieved a peak eosinophil count ≤ 6.

The study included multiple secondary outcomes. For example, at week 16, the following measures improved from baseline with high-exposure dupilumab, compared with placebo:

• EoE-Histologic Scoring System grade and stage scores (–0.88 and –0.84 vs. +0.02 and +0.05; both P < .0001).
• EoE-Endoscopic Reference Score (–3.5 vs. +0.3; P < .0001).
• Change in body weight for age percentile (+3.09 vs. +0.29).
• Numeric improvement in caregiver-reported proportion of days experiencing one or more EoE sign (–0.28 vs. –0.17).

At week 52, these outcomes were sustained or improved with continued high-exposure dupilumab. The researchers also saw improvements among the placebo recipients who switched to high-exposure dupilumab.

The reason the children were randomly assigned to high-exposure or low-exposure groups instead of high-dose and low-dose cohorts is because the children grew during the study, Dr. Chehade explained. “As you can see, there was a nice change in weight, and at specific time periods the doses were adjusted to match.”
 

‘Good safety profile’

Dupilumab was well tolerated. “The safety profile is very similar to what has been so far described and published for dupilumab in adults,” said Dr. Chehade. At week 16, adverse events that were more frequent with dupilumab vs. placebo included COVID-19, rash, headache, and injection-site erythema, for example. Similar safety results were seen up to week 52.

“I think it’s promising as we wait for the actual study to be published,” said Asmeen Bhatt, MD, PhD, co-moderator of the session and assistant professor of medicine at University of Texas Health Science Center, Houston. “The drug was recently approved for adult EOE use, just last year, and it has been shown to be effective.”

“There are a lot of adult drugs that are now being tested in the pediatric population, and this is one of them,” Dr. Bhatt added. “It has a very good safety profile. I’m not a pediatric gastroenterologist but I expect that it will have a lot of utility.”

The study was funded by Regeneron and Sanofi. Dr. Chehade is a consultant for Sanofi and Regeneron and receives research funding from Regeneron. Dr. Bhatt had no relevant financial disclosures.

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

The Diagnosis: Microcystic Lymphatic Malformation

A punch biopsy demonstrated anastomosing fluidfilled spaces within the papillary and reticular dermal layers (Figure), confirming the diagnosis of microcystic lymphatic malformation (LM)(formerly known as lymphangioma circumscriptum), a congenital vascular malformation composed of slow-flow lymphatic channels.1 The patient underwent serial excisions with improvement of the LM, though the treatment course was complicated by hypertrophic scar formation.

The classic clinical presentation of microcystic LM includes a crop of vesicles containing clear or hemorrhagic fluid with associated oozing or bleeding.² When cutaneous lesions resembling microcystic LM develop in response to lymphatic damage and resulting stasis, such as from prior radiotherapy or surgery, the term lymphangiectasia is used to distinguish this entity from congenital microcystic LM.³

Microcystic LMs are histologically indistinguishable from macrocystic LMs; however, macrocystic LMs typically are clinically evident at birth as ill-defined subcutaneous masses.^2,4-6 Dermatitis herpetiformis, a dermatologic manifestation of gluten sensitivity, causes intensely pruritic vesicles in a symmetric distribution on the elbows, knees, and buttocks. Histopathology shows neutrophilic microabscesses in the dermal papillae with subepidermal blistering. Direct immunofluorescence demonstrates the deposition of IgA along the basement membrane with dermal papillae aggregates.⁶ The underlying dermis also may contain a lymphohistiocytic infiltrate rich in neutrophils. The vesicles of herpes zoster virus are painful and present in a dermatomal distribution. A viral cytopathic effect often is observed in keratinocytes, specifically with multinucleation, molding, and margination of chromatin material. The lesions are accompanied by variable lymphocytic inflammation and epithelial necrosis resulting in intraepidermal blistering.⁷ Extragenital lichen sclerosus presents as polygonal white papules merging to form plaques and may include hemorrhagic blisters in some instances. Histopathology shows hyperkeratosis, epidermal atrophy with flattened rete ridges, vacuolar interface changes, loss of elastic fibers, and hyalinization of the lamina propria with lymphocytic infiltrate.⁸

Endothelial cells in LM exhibit activating mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene, PIK3CA, which may lead to proliferation and overgrowth of the lymphatic vasculature, as well as increased production of cyclic guanosine monophosphate.^9,10 Phosphodiesterase 5 (PDE5) is expressed in the perivascular smooth muscle adjacent to lymphatic spaces in LMs but not in the their vasculature. 10 This pattern of PDE5 expression may cause perilesional vasculature to constrict, preventing lymphatic fluid from draining into the veins.¹¹ It is theorized that the PDE5 inhibitor sildenafil leads to relaxation of the vasculature adjacent to LMs, allowing the outflow of the accumulated lymphatic fluid and thus decompression.^11-13

Management of LM should not only take into account the depth and location of involvement but also any associated symptoms or complications, such as pruritus, pain, bleeding, or secondary infections. Magnetic resonance imaging (MRI) typically has been considered the gold standard for determining the size and depth of involvement of the malformation.^1,3,4 However, ultrasonography with Doppler flow may be considered an initial diagnostic and screening test, as it can distinguish between macrocystic and microcystic components and provide superior images of microcystic lesions, which are below the resolution capacity of MRI.4 Notably, our patient’s LM was undetectable on ultrasonography and was found to be largely superficial in nature on MRI.

Serial excision of the microcystic LM was conducted in our patient, but there currently is no consensus on optimal treatment of LM, and many treatment options are complicated by high recurrence rates or complications.⁵ Procedural approaches may include excision, cryotherapy, radiotherapy, sclerotherapy, or laser therapy, while pharmacologic approaches may include sildenafil for its inhibition of PDE5 or sirolimus (oral or topical) for its inhibition of mammalian target of rapamycin.^5,12-14 Because recurrence is highly likely, patients may require repeat treatments or a combination approach to therapy.^1,5 The development of targeted therapies may lead to a shift in management of LMs in the future, as successful use of the PIK3CA inhibitor alpelisib recently has been reported to lead to clinical improvement of PIK3CA-related LMs, including in patients with PIK3CA-related overgrowth syndromes.¹⁵

The Diagnosis: Microcystic Lymphatic Malformation

A punch biopsy demonstrated anastomosing fluidfilled spaces within the papillary and reticular dermal layers (Figure), confirming the diagnosis of microcystic lymphatic malformation (LM)(formerly known as lymphangioma circumscriptum), a congenital vascular malformation composed of slow-flow lymphatic channels.1 The patient underwent serial excisions with improvement of the LM, though the treatment course was complicated by hypertrophic scar formation.

The classic clinical presentation of microcystic LM includes a crop of vesicles containing clear or hemorrhagic fluid with associated oozing or bleeding.² When cutaneous lesions resembling microcystic LM develop in response to lymphatic damage and resulting stasis, such as from prior radiotherapy or surgery, the term lymphangiectasia is used to distinguish this entity from congenital microcystic LM.³

Microcystic LMs are histologically indistinguishable from macrocystic LMs; however, macrocystic LMs typically are clinically evident at birth as ill-defined subcutaneous masses.^2,4-6 Dermatitis herpetiformis, a dermatologic manifestation of gluten sensitivity, causes intensely pruritic vesicles in a symmetric distribution on the elbows, knees, and buttocks. Histopathology shows neutrophilic microabscesses in the dermal papillae with subepidermal blistering. Direct immunofluorescence demonstrates the deposition of IgA along the basement membrane with dermal papillae aggregates.⁶ The underlying dermis also may contain a lymphohistiocytic infiltrate rich in neutrophils. The vesicles of herpes zoster virus are painful and present in a dermatomal distribution. A viral cytopathic effect often is observed in keratinocytes, specifically with multinucleation, molding, and margination of chromatin material. The lesions are accompanied by variable lymphocytic inflammation and epithelial necrosis resulting in intraepidermal blistering.⁷ Extragenital lichen sclerosus presents as polygonal white papules merging to form plaques and may include hemorrhagic blisters in some instances. Histopathology shows hyperkeratosis, epidermal atrophy with flattened rete ridges, vacuolar interface changes, loss of elastic fibers, and hyalinization of the lamina propria with lymphocytic infiltrate.⁸

Endothelial cells in LM exhibit activating mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene, PIK3CA, which may lead to proliferation and overgrowth of the lymphatic vasculature, as well as increased production of cyclic guanosine monophosphate.^9,10 Phosphodiesterase 5 (PDE5) is expressed in the perivascular smooth muscle adjacent to lymphatic spaces in LMs but not in the their vasculature. 10 This pattern of PDE5 expression may cause perilesional vasculature to constrict, preventing lymphatic fluid from draining into the veins.¹¹ It is theorized that the PDE5 inhibitor sildenafil leads to relaxation of the vasculature adjacent to LMs, allowing the outflow of the accumulated lymphatic fluid and thus decompression.^11-13

Management of LM should not only take into account the depth and location of involvement but also any associated symptoms or complications, such as pruritus, pain, bleeding, or secondary infections. Magnetic resonance imaging (MRI) typically has been considered the gold standard for determining the size and depth of involvement of the malformation.^1,3,4 However, ultrasonography with Doppler flow may be considered an initial diagnostic and screening test, as it can distinguish between macrocystic and microcystic components and provide superior images of microcystic lesions, which are below the resolution capacity of MRI.4 Notably, our patient’s LM was undetectable on ultrasonography and was found to be largely superficial in nature on MRI.

Serial excision of the microcystic LM was conducted in our patient, but there currently is no consensus on optimal treatment of LM, and many treatment options are complicated by high recurrence rates or complications.⁵ Procedural approaches may include excision, cryotherapy, radiotherapy, sclerotherapy, or laser therapy, while pharmacologic approaches may include sildenafil for its inhibition of PDE5 or sirolimus (oral or topical) for its inhibition of mammalian target of rapamycin.^5,12-14 Because recurrence is highly likely, patients may require repeat treatments or a combination approach to therapy.^1,5 The development of targeted therapies may lead to a shift in management of LMs in the future, as successful use of the PIK3CA inhibitor alpelisib recently has been reported to lead to clinical improvement of PIK3CA-related LMs, including in patients with PIK3CA-related overgrowth syndromes.¹⁵

The Diagnosis: Microcystic Lymphatic Malformation

A punch biopsy demonstrated anastomosing fluidfilled spaces within the papillary and reticular dermal layers (Figure), confirming the diagnosis of microcystic lymphatic malformation (LM)(formerly known as lymphangioma circumscriptum), a congenital vascular malformation composed of slow-flow lymphatic channels.1 The patient underwent serial excisions with improvement of the LM, though the treatment course was complicated by hypertrophic scar formation.

The classic clinical presentation of microcystic LM includes a crop of vesicles containing clear or hemorrhagic fluid with associated oozing or bleeding.² When cutaneous lesions resembling microcystic LM develop in response to lymphatic damage and resulting stasis, such as from prior radiotherapy or surgery, the term lymphangiectasia is used to distinguish this entity from congenital microcystic LM.³

Microcystic LMs are histologically indistinguishable from macrocystic LMs; however, macrocystic LMs typically are clinically evident at birth as ill-defined subcutaneous masses.^2,4-6 Dermatitis herpetiformis, a dermatologic manifestation of gluten sensitivity, causes intensely pruritic vesicles in a symmetric distribution on the elbows, knees, and buttocks. Histopathology shows neutrophilic microabscesses in the dermal papillae with subepidermal blistering. Direct immunofluorescence demonstrates the deposition of IgA along the basement membrane with dermal papillae aggregates.⁶ The underlying dermis also may contain a lymphohistiocytic infiltrate rich in neutrophils. The vesicles of herpes zoster virus are painful and present in a dermatomal distribution. A viral cytopathic effect often is observed in keratinocytes, specifically with multinucleation, molding, and margination of chromatin material. The lesions are accompanied by variable lymphocytic inflammation and epithelial necrosis resulting in intraepidermal blistering.⁷ Extragenital lichen sclerosus presents as polygonal white papules merging to form plaques and may include hemorrhagic blisters in some instances. Histopathology shows hyperkeratosis, epidermal atrophy with flattened rete ridges, vacuolar interface changes, loss of elastic fibers, and hyalinization of the lamina propria with lymphocytic infiltrate.⁸

Endothelial cells in LM exhibit activating mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene, PIK3CA, which may lead to proliferation and overgrowth of the lymphatic vasculature, as well as increased production of cyclic guanosine monophosphate.^9,10 Phosphodiesterase 5 (PDE5) is expressed in the perivascular smooth muscle adjacent to lymphatic spaces in LMs but not in the their vasculature. 10 This pattern of PDE5 expression may cause perilesional vasculature to constrict, preventing lymphatic fluid from draining into the veins.¹¹ It is theorized that the PDE5 inhibitor sildenafil leads to relaxation of the vasculature adjacent to LMs, allowing the outflow of the accumulated lymphatic fluid and thus decompression.^11-13

Management of LM should not only take into account the depth and location of involvement but also any associated symptoms or complications, such as pruritus, pain, bleeding, or secondary infections. Magnetic resonance imaging (MRI) typically has been considered the gold standard for determining the size and depth of involvement of the malformation.^1,3,4 However, ultrasonography with Doppler flow may be considered an initial diagnostic and screening test, as it can distinguish between macrocystic and microcystic components and provide superior images of microcystic lesions, which are below the resolution capacity of MRI.4 Notably, our patient’s LM was undetectable on ultrasonography and was found to be largely superficial in nature on MRI.

Serial excision of the microcystic LM was conducted in our patient, but there currently is no consensus on optimal treatment of LM, and many treatment options are complicated by high recurrence rates or complications.⁵ Procedural approaches may include excision, cryotherapy, radiotherapy, sclerotherapy, or laser therapy, while pharmacologic approaches may include sildenafil for its inhibition of PDE5 or sirolimus (oral or topical) for its inhibition of mammalian target of rapamycin.^5,12-14 Because recurrence is highly likely, patients may require repeat treatments or a combination approach to therapy.^1,5 The development of targeted therapies may lead to a shift in management of LMs in the future, as successful use of the PIK3CA inhibitor alpelisib recently has been reported to lead to clinical improvement of PIK3CA-related LMs, including in patients with PIK3CA-related overgrowth syndromes.¹⁵

Endoscopic sinus surgery (ESS) has no significant impact on asthma symptoms for patients with chronic rhinosinusitis up to a year after the procedure, a study of 64 patients shows.

Although ESS is effective in relieving chronic rhinosinusitis, whether it leads to improvement of asthma severity for patients with both conditions remains unclear, Anyull Dayanna Bohórquez Caballero said in a presentation at the American Academy of Otolaryngology–Head and Neck Surgery (AAO-HNS) 2023 annual meeting.

The study “offers a unique approach to explore the effects of endoscopic sinus surgery in a real-world context, with valuable insights that differ from previous research,” Dr. Bohórquez Caballero, an international medical graduate and research fellow of the Mayo Clinic, Jacksonville, Fla., said in an interview.

Under the leadership of senior author Angela Donaldson, MD, Dr. Bohórquez Caballero and colleagues at the Mayo Clinic in Jacksonville analyzed data from 185 adults with both asthma and chronic rhinosinusitis who underwent ESS at the clinic between 2013 and 2023. Asthma severity was evaluated up to 3 months before and 1 year after surgery. Patients’ asthma severity was classified as mild, moderate, or severe on the basis of current Global Initiative for Asthma guidelines using medication requirements.

The final study population included 64 patients; 42 of these (66.7%) had chronic rhinosinusitis with nasal polyps. Outcomes included differences in asthma severity, asthma medication doses, and the number of medications.

Overall, there was no significant difference in measures of mild, moderate, or severe asthma before and after ESS in a McNemar paired test (P values: .130, .999, and .288, respectively). Similarly, no difference was found before and after ESS in terms of total inhaled corticosteroid dose (P = .999), number of medications prescribed (P = .157), or control of the disease (P = .078).

The findings were limited by the relatively small number of patients. The study is the first known to assess the real-world impact of ESS on asthma severity, said Bohórquez Caballero.
 

Expected reduction in asthma severity not seen

Past studies have suggested that ESS improves parameters such as pulmonary function test results or sinonasal outcomes, Dr. Bohórquez Caballero told this news organization. “Our findings indicate that ESS does not significantly impact asthma severity or trends in treatment, including the number and/or dose of medications, in everyday practice.

Our study also identified crucial opportunities to reinforce interdisciplinary follow-up after ESS,” she noted, and it provides a comprehensive depiction of the outcomes experienced by patients with chronic rhinosinusitis and asthma who undergo ESS.

“We were expecting a reduction in severity or a decrease in the dose of inhaled corticosteroid therapies, and we expected to see a translation from previous evidence into clinical practice; however, we did not,” said Dr. Bohórquez Caballero.

“The take-home message is that while there is a strong correlation between CRS and asthma, it does not appear that ESS alone improves real-world treatment based on asthma severity,” she said. “However, our findings have shown that patients may experience a longer period without the need for a reliever medication in the early postoperative period.”

Looking ahead, “We want to explore what happens 5 or 6 months after sinus surgery that would explain the sudden need for a reliever medication,” she added. “Future studies are warranted to investigate the long-term effects of ESS on asthma severity as it relates to modifications of asthma regimens.”
 

Data important for patient discussions

The current study is important because of the frequency of comorbid asthma among patients with chronic rhinosinusitis, Megan Durr, MD, of the University of California, San Francisco, said in an interview.

“When we are considering functional endoscopy sinus surgery with patients, we are often asked if the surgery will impact the severity of their asthma symptoms,” said Dr. Durr, who served as a moderator for the session in which the study was presented.

“I am surprised the study did not see any difference in asthma severity after sinus surgery, as we often talk to patients about the unified airway that refers to the shared epidemiologic and pathophysiologic relationship between the upper and lower airways,” she told this news organization.

“This study will allow us to have a more informed evidenced-based discussion with patients and their primary care providers and/or pulmonologists” about what to expect for asthma outcomes following surgery, she said.

The study received no outside funding. Dr. Durr has disclosed no relevant financial relationships.

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

Endoscopic sinus surgery (ESS) has no significant impact on asthma symptoms for patients with chronic rhinosinusitis up to a year after the procedure, a study of 64 patients shows.

Although ESS is effective in relieving chronic rhinosinusitis, whether it leads to improvement of asthma severity for patients with both conditions remains unclear, Anyull Dayanna Bohórquez Caballero said in a presentation at the American Academy of Otolaryngology–Head and Neck Surgery (AAO-HNS) 2023 annual meeting.

The study “offers a unique approach to explore the effects of endoscopic sinus surgery in a real-world context, with valuable insights that differ from previous research,” Dr. Bohórquez Caballero, an international medical graduate and research fellow of the Mayo Clinic, Jacksonville, Fla., said in an interview.

Under the leadership of senior author Angela Donaldson, MD, Dr. Bohórquez Caballero and colleagues at the Mayo Clinic in Jacksonville analyzed data from 185 adults with both asthma and chronic rhinosinusitis who underwent ESS at the clinic between 2013 and 2023. Asthma severity was evaluated up to 3 months before and 1 year after surgery. Patients’ asthma severity was classified as mild, moderate, or severe on the basis of current Global Initiative for Asthma guidelines using medication requirements.

The final study population included 64 patients; 42 of these (66.7%) had chronic rhinosinusitis with nasal polyps. Outcomes included differences in asthma severity, asthma medication doses, and the number of medications.

Overall, there was no significant difference in measures of mild, moderate, or severe asthma before and after ESS in a McNemar paired test (P values: .130, .999, and .288, respectively). Similarly, no difference was found before and after ESS in terms of total inhaled corticosteroid dose (P = .999), number of medications prescribed (P = .157), or control of the disease (P = .078).

The findings were limited by the relatively small number of patients. The study is the first known to assess the real-world impact of ESS on asthma severity, said Bohórquez Caballero.
 

Expected reduction in asthma severity not seen

Past studies have suggested that ESS improves parameters such as pulmonary function test results or sinonasal outcomes, Dr. Bohórquez Caballero told this news organization. “Our findings indicate that ESS does not significantly impact asthma severity or trends in treatment, including the number and/or dose of medications, in everyday practice.

Our study also identified crucial opportunities to reinforce interdisciplinary follow-up after ESS,” she noted, and it provides a comprehensive depiction of the outcomes experienced by patients with chronic rhinosinusitis and asthma who undergo ESS.

“We were expecting a reduction in severity or a decrease in the dose of inhaled corticosteroid therapies, and we expected to see a translation from previous evidence into clinical practice; however, we did not,” said Dr. Bohórquez Caballero.

“The take-home message is that while there is a strong correlation between CRS and asthma, it does not appear that ESS alone improves real-world treatment based on asthma severity,” she said. “However, our findings have shown that patients may experience a longer period without the need for a reliever medication in the early postoperative period.”

Looking ahead, “We want to explore what happens 5 or 6 months after sinus surgery that would explain the sudden need for a reliever medication,” she added. “Future studies are warranted to investigate the long-term effects of ESS on asthma severity as it relates to modifications of asthma regimens.”
 

Data important for patient discussions

The current study is important because of the frequency of comorbid asthma among patients with chronic rhinosinusitis, Megan Durr, MD, of the University of California, San Francisco, said in an interview.

“When we are considering functional endoscopy sinus surgery with patients, we are often asked if the surgery will impact the severity of their asthma symptoms,” said Dr. Durr, who served as a moderator for the session in which the study was presented.

“I am surprised the study did not see any difference in asthma severity after sinus surgery, as we often talk to patients about the unified airway that refers to the shared epidemiologic and pathophysiologic relationship between the upper and lower airways,” she told this news organization.

“This study will allow us to have a more informed evidenced-based discussion with patients and their primary care providers and/or pulmonologists” about what to expect for asthma outcomes following surgery, she said.

The study received no outside funding. Dr. Durr has disclosed no relevant financial relationships.

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

Endoscopic sinus surgery (ESS) has no significant impact on asthma symptoms for patients with chronic rhinosinusitis up to a year after the procedure, a study of 64 patients shows.

Although ESS is effective in relieving chronic rhinosinusitis, whether it leads to improvement of asthma severity for patients with both conditions remains unclear, Anyull Dayanna Bohórquez Caballero said in a presentation at the American Academy of Otolaryngology–Head and Neck Surgery (AAO-HNS) 2023 annual meeting.

The study “offers a unique approach to explore the effects of endoscopic sinus surgery in a real-world context, with valuable insights that differ from previous research,” Dr. Bohórquez Caballero, an international medical graduate and research fellow of the Mayo Clinic, Jacksonville, Fla., said in an interview.

Under the leadership of senior author Angela Donaldson, MD, Dr. Bohórquez Caballero and colleagues at the Mayo Clinic in Jacksonville analyzed data from 185 adults with both asthma and chronic rhinosinusitis who underwent ESS at the clinic between 2013 and 2023. Asthma severity was evaluated up to 3 months before and 1 year after surgery. Patients’ asthma severity was classified as mild, moderate, or severe on the basis of current Global Initiative for Asthma guidelines using medication requirements.

The final study population included 64 patients; 42 of these (66.7%) had chronic rhinosinusitis with nasal polyps. Outcomes included differences in asthma severity, asthma medication doses, and the number of medications.

Overall, there was no significant difference in measures of mild, moderate, or severe asthma before and after ESS in a McNemar paired test (P values: .130, .999, and .288, respectively). Similarly, no difference was found before and after ESS in terms of total inhaled corticosteroid dose (P = .999), number of medications prescribed (P = .157), or control of the disease (P = .078).

The findings were limited by the relatively small number of patients. The study is the first known to assess the real-world impact of ESS on asthma severity, said Bohórquez Caballero.
 

Expected reduction in asthma severity not seen

Past studies have suggested that ESS improves parameters such as pulmonary function test results or sinonasal outcomes, Dr. Bohórquez Caballero told this news organization. “Our findings indicate that ESS does not significantly impact asthma severity or trends in treatment, including the number and/or dose of medications, in everyday practice.

Our study also identified crucial opportunities to reinforce interdisciplinary follow-up after ESS,” she noted, and it provides a comprehensive depiction of the outcomes experienced by patients with chronic rhinosinusitis and asthma who undergo ESS.

“We were expecting a reduction in severity or a decrease in the dose of inhaled corticosteroid therapies, and we expected to see a translation from previous evidence into clinical practice; however, we did not,” said Dr. Bohórquez Caballero.

“The take-home message is that while there is a strong correlation between CRS and asthma, it does not appear that ESS alone improves real-world treatment based on asthma severity,” she said. “However, our findings have shown that patients may experience a longer period without the need for a reliever medication in the early postoperative period.”

Looking ahead, “We want to explore what happens 5 or 6 months after sinus surgery that would explain the sudden need for a reliever medication,” she added. “Future studies are warranted to investigate the long-term effects of ESS on asthma severity as it relates to modifications of asthma regimens.”
 

Data important for patient discussions

The current study is important because of the frequency of comorbid asthma among patients with chronic rhinosinusitis, Megan Durr, MD, of the University of California, San Francisco, said in an interview.

“When we are considering functional endoscopy sinus surgery with patients, we are often asked if the surgery will impact the severity of their asthma symptoms,” said Dr. Durr, who served as a moderator for the session in which the study was presented.

“I am surprised the study did not see any difference in asthma severity after sinus surgery, as we often talk to patients about the unified airway that refers to the shared epidemiologic and pathophysiologic relationship between the upper and lower airways,” she told this news organization.

“This study will allow us to have a more informed evidenced-based discussion with patients and their primary care providers and/or pulmonologists” about what to expect for asthma outcomes following surgery, she said.

The study received no outside funding. Dr. Durr has disclosed no relevant financial relationships.

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

WASHINGTON – Get the back story before rushing to diagnose a seizure disorder in a child, Michael Strunc, MD, said in a presentation at the annual meeting of the American Academy of Pediatrics.

Clinicians should ask parents or caregivers about the child’s behavior before the suspected seizure, whether there were any triggers, and if so, what might they have been, according to Dr. Strunc, a child neurologist and sleep medicine specialist at Children’s Hospital of the King’s Daughters, Norfolk, Va.

“Most seizures don’t have triggers,” he said. Rather, patients often become stiff, experience a motor event that builds in intensity then slows and stops, and finally, the patient is sleepy and tired. Clinicians should also find out whether the event had a beginning, middle, and end.

Approximately 0.6% of children younger than 17 years in the United States have active epilepsy, according to the Centers for Disease Control and Prevention.

Dr. Strunc offered a few more tips for diagnosing a child:

• Ask whether the patient’s eyes were open during the event. If the eyes were closed or squished closed, “it is almost never a seizure,” he said.
• Find out whether the patient was awake or asleep, and how, if at all, caregivers attempted to stop the event.
• Ask if the child’s experiences were repeating and predictable, and inquire about a family history of seizures or other events.
• Inquire about any developmental changes and other changes in the child, such as irritability, regression, or ataxia.

The differential diagnosis for a seizure includes nonepileptic events that occur with and without changes in consciousness or sleep. These events range from breath-holding and hyperventilation to night terrors, narcolepsy, migraine, and attention-deficit/hyperactivity disorder, he said.
 

Is it epilepsy?

Dr. Strunc shared several cases of neurologic “events” ranging from simple to severe.

In one case, a 10-month-old infant girl with a potential tonic/staring seizure presented with a history of events that involved getting stuck in a stiff position, usually while sitting in a car seat or highchair, with adducting of legs, redness of face, and “zoned-out” expression. The infant was healthy, smart, and precocious, with no illness, fever, or trauma, but the mother was very concerned, Dr. Strunc said.

The diagnosis: Self-gratification, which is benign and usually outgrown, although it can become extreme, he said.

By contrast, “absence,” also known as idiopathic generalized epilepsy, presents as brief events of 4-10 seconds that may occur up to hundreds of times a day. This type of epilepsy is associated with the sudden onset of impaired consciousness and unresponsiveness. These events end abruptly, and the child may be unaware. Absence is more common in girls. It usually occurs after age 4 and usually remits by about age 12, Dr. Strunc said.

However, the onset of absence in patients younger than age 3 is associated with increased odds of neurodevelopmental abnormalities “and probably represents another epilepsy syndrome,” he said.

Absence symptoms may mirror those of children who are simply daydreamers, Dr. Strunc noted. One way to confirm absence is by provoking hyperventilation, which will bring on an episode of absence if present, he said. EEGs provide evidence as well.

Acute ataxia in children has a wide differential that sends kids and families to the pediatrician or emergency department, Dr. Strunc said. Acute cerebellar ataxia is characterized by abrupt and symmetric symptoms, with no mental status changes, no fever, no meningitis, and no headache. A wide, unstable gait is a distinguishing feature, Dr. Strunc said.

However, other causes of acute ataxia should be ruled out, including toxic ingestion, tick paralysis, central nervous system infections, vascular conditions, and genetic conditions.
 

Don’t miss those ticks

Especially during periods when kids are outdoors, clinicians should consider a tick bite as a source of ataxia and neurologic symptoms in children, Dr. Strunc emphasized. Tick paralysis notably resembles many symptoms of Guillain-Barré syndrome (acute inflammatory demyelinating polyneuropathy).

Dr. Strunc described a case involving a 5-year-old girl who developed sudden problems with gait. The problems worsened quickly and prompted an emergency department visit.

The girl had an unremarkable history, she had not experienced mental status changes, her strength was normal, and she had just returned from a Girl Scouts trip. The patient was presumed to have Guillain-Barré. IVIG was initiated when an emergency nurse found a tick on her scalp. The tick was removed, and the patient left the hospital within 24 hours.

Children with tick paralysis are usually symptomatic after 5-7 days with the tick attached, Dr. Strunc said. They recover within a day after tick removal.

Overall, actual seizures are less common than other neurologic events in children, according to Dr. Strunc. Details on history, lack or presence of neurologic feature, and normal child development can help guide evaluation.

Take advantage of videos, he emphasized, as many parents and caregivers record a child’s neurologic events.

“Ataxia is scary, but exam and associated findings will help you with etiology,” he said.

Dr. Strunc has received research support from Jazz and Harmony and has served on the speakers’ bureau for Jazz Pharmaceuticals, Harmony Biosciences, and Avadel, unrelated to his presentation.

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

WASHINGTON – Get the back story before rushing to diagnose a seizure disorder in a child, Michael Strunc, MD, said in a presentation at the annual meeting of the American Academy of Pediatrics.

Clinicians should ask parents or caregivers about the child’s behavior before the suspected seizure, whether there were any triggers, and if so, what might they have been, according to Dr. Strunc, a child neurologist and sleep medicine specialist at Children’s Hospital of the King’s Daughters, Norfolk, Va.

“Most seizures don’t have triggers,” he said. Rather, patients often become stiff, experience a motor event that builds in intensity then slows and stops, and finally, the patient is sleepy and tired. Clinicians should also find out whether the event had a beginning, middle, and end.

Approximately 0.6% of children younger than 17 years in the United States have active epilepsy, according to the Centers for Disease Control and Prevention.

Dr. Strunc offered a few more tips for diagnosing a child:

• Ask whether the patient’s eyes were open during the event. If the eyes were closed or squished closed, “it is almost never a seizure,” he said.
• Find out whether the patient was awake or asleep, and how, if at all, caregivers attempted to stop the event.
• Ask if the child’s experiences were repeating and predictable, and inquire about a family history of seizures or other events.
• Inquire about any developmental changes and other changes in the child, such as irritability, regression, or ataxia.

The differential diagnosis for a seizure includes nonepileptic events that occur with and without changes in consciousness or sleep. These events range from breath-holding and hyperventilation to night terrors, narcolepsy, migraine, and attention-deficit/hyperactivity disorder, he said.
 

Is it epilepsy?

Dr. Strunc shared several cases of neurologic “events” ranging from simple to severe.

In one case, a 10-month-old infant girl with a potential tonic/staring seizure presented with a history of events that involved getting stuck in a stiff position, usually while sitting in a car seat or highchair, with adducting of legs, redness of face, and “zoned-out” expression. The infant was healthy, smart, and precocious, with no illness, fever, or trauma, but the mother was very concerned, Dr. Strunc said.

The diagnosis: Self-gratification, which is benign and usually outgrown, although it can become extreme, he said.

By contrast, “absence,” also known as idiopathic generalized epilepsy, presents as brief events of 4-10 seconds that may occur up to hundreds of times a day. This type of epilepsy is associated with the sudden onset of impaired consciousness and unresponsiveness. These events end abruptly, and the child may be unaware. Absence is more common in girls. It usually occurs after age 4 and usually remits by about age 12, Dr. Strunc said.

However, the onset of absence in patients younger than age 3 is associated with increased odds of neurodevelopmental abnormalities “and probably represents another epilepsy syndrome,” he said.

Absence symptoms may mirror those of children who are simply daydreamers, Dr. Strunc noted. One way to confirm absence is by provoking hyperventilation, which will bring on an episode of absence if present, he said. EEGs provide evidence as well.

Acute ataxia in children has a wide differential that sends kids and families to the pediatrician or emergency department, Dr. Strunc said. Acute cerebellar ataxia is characterized by abrupt and symmetric symptoms, with no mental status changes, no fever, no meningitis, and no headache. A wide, unstable gait is a distinguishing feature, Dr. Strunc said.

However, other causes of acute ataxia should be ruled out, including toxic ingestion, tick paralysis, central nervous system infections, vascular conditions, and genetic conditions.
 

Don’t miss those ticks

Especially during periods when kids are outdoors, clinicians should consider a tick bite as a source of ataxia and neurologic symptoms in children, Dr. Strunc emphasized. Tick paralysis notably resembles many symptoms of Guillain-Barré syndrome (acute inflammatory demyelinating polyneuropathy).

Dr. Strunc described a case involving a 5-year-old girl who developed sudden problems with gait. The problems worsened quickly and prompted an emergency department visit.

The girl had an unremarkable history, she had not experienced mental status changes, her strength was normal, and she had just returned from a Girl Scouts trip. The patient was presumed to have Guillain-Barré. IVIG was initiated when an emergency nurse found a tick on her scalp. The tick was removed, and the patient left the hospital within 24 hours.

Children with tick paralysis are usually symptomatic after 5-7 days with the tick attached, Dr. Strunc said. They recover within a day after tick removal.

Overall, actual seizures are less common than other neurologic events in children, according to Dr. Strunc. Details on history, lack or presence of neurologic feature, and normal child development can help guide evaluation.

Take advantage of videos, he emphasized, as many parents and caregivers record a child’s neurologic events.

“Ataxia is scary, but exam and associated findings will help you with etiology,” he said.

Dr. Strunc has received research support from Jazz and Harmony and has served on the speakers’ bureau for Jazz Pharmaceuticals, Harmony Biosciences, and Avadel, unrelated to his presentation.

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

WASHINGTON – Get the back story before rushing to diagnose a seizure disorder in a child, Michael Strunc, MD, said in a presentation at the annual meeting of the American Academy of Pediatrics.

Clinicians should ask parents or caregivers about the child’s behavior before the suspected seizure, whether there were any triggers, and if so, what might they have been, according to Dr. Strunc, a child neurologist and sleep medicine specialist at Children’s Hospital of the King’s Daughters, Norfolk, Va.

“Most seizures don’t have triggers,” he said. Rather, patients often become stiff, experience a motor event that builds in intensity then slows and stops, and finally, the patient is sleepy and tired. Clinicians should also find out whether the event had a beginning, middle, and end.

Approximately 0.6% of children younger than 17 years in the United States have active epilepsy, according to the Centers for Disease Control and Prevention.

Dr. Strunc offered a few more tips for diagnosing a child:

• Ask whether the patient’s eyes were open during the event. If the eyes were closed or squished closed, “it is almost never a seizure,” he said.
• Find out whether the patient was awake or asleep, and how, if at all, caregivers attempted to stop the event.
• Ask if the child’s experiences were repeating and predictable, and inquire about a family history of seizures or other events.
• Inquire about any developmental changes and other changes in the child, such as irritability, regression, or ataxia.

The differential diagnosis for a seizure includes nonepileptic events that occur with and without changes in consciousness or sleep. These events range from breath-holding and hyperventilation to night terrors, narcolepsy, migraine, and attention-deficit/hyperactivity disorder, he said.
 

Is it epilepsy?

Dr. Strunc shared several cases of neurologic “events” ranging from simple to severe.

In one case, a 10-month-old infant girl with a potential tonic/staring seizure presented with a history of events that involved getting stuck in a stiff position, usually while sitting in a car seat or highchair, with adducting of legs, redness of face, and “zoned-out” expression. The infant was healthy, smart, and precocious, with no illness, fever, or trauma, but the mother was very concerned, Dr. Strunc said.

The diagnosis: Self-gratification, which is benign and usually outgrown, although it can become extreme, he said.

By contrast, “absence,” also known as idiopathic generalized epilepsy, presents as brief events of 4-10 seconds that may occur up to hundreds of times a day. This type of epilepsy is associated with the sudden onset of impaired consciousness and unresponsiveness. These events end abruptly, and the child may be unaware. Absence is more common in girls. It usually occurs after age 4 and usually remits by about age 12, Dr. Strunc said.

However, the onset of absence in patients younger than age 3 is associated with increased odds of neurodevelopmental abnormalities “and probably represents another epilepsy syndrome,” he said.

Absence symptoms may mirror those of children who are simply daydreamers, Dr. Strunc noted. One way to confirm absence is by provoking hyperventilation, which will bring on an episode of absence if present, he said. EEGs provide evidence as well.

Acute ataxia in children has a wide differential that sends kids and families to the pediatrician or emergency department, Dr. Strunc said. Acute cerebellar ataxia is characterized by abrupt and symmetric symptoms, with no mental status changes, no fever, no meningitis, and no headache. A wide, unstable gait is a distinguishing feature, Dr. Strunc said.

However, other causes of acute ataxia should be ruled out, including toxic ingestion, tick paralysis, central nervous system infections, vascular conditions, and genetic conditions.
 

Don’t miss those ticks

Especially during periods when kids are outdoors, clinicians should consider a tick bite as a source of ataxia and neurologic symptoms in children, Dr. Strunc emphasized. Tick paralysis notably resembles many symptoms of Guillain-Barré syndrome (acute inflammatory demyelinating polyneuropathy).

Dr. Strunc described a case involving a 5-year-old girl who developed sudden problems with gait. The problems worsened quickly and prompted an emergency department visit.

The girl had an unremarkable history, she had not experienced mental status changes, her strength was normal, and she had just returned from a Girl Scouts trip. The patient was presumed to have Guillain-Barré. IVIG was initiated when an emergency nurse found a tick on her scalp. The tick was removed, and the patient left the hospital within 24 hours.

Children with tick paralysis are usually symptomatic after 5-7 days with the tick attached, Dr. Strunc said. They recover within a day after tick removal.

Overall, actual seizures are less common than other neurologic events in children, according to Dr. Strunc. Details on history, lack or presence of neurologic feature, and normal child development can help guide evaluation.

Take advantage of videos, he emphasized, as many parents and caregivers record a child’s neurologic events.

“Ataxia is scary, but exam and associated findings will help you with etiology,” he said.

Dr. Strunc has received research support from Jazz and Harmony and has served on the speakers’ bureau for Jazz Pharmaceuticals, Harmony Biosciences, and Avadel, unrelated to his presentation.

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

VANCOUVER – Use of sodium glucose cotransporter-2 (SGLT2) inhibitors is associated with a reduced risk of gastrointestinal cancers among patients with type 2 diabetes, compared with dipeptidyl peptidase IV (DPP4) inhibitors, new evidence reveals.

The SGLT2 inhibitors emerged superior to DPP4 inhibitors for reducing risk of colorectal, hepatic, esophageal, and other GI cancers except pancreatic cancer, said study investigator Shu-Yen Emily Chan, MD, a gastroenterologist in the departments of medicine and epidemiology at Weiss Memorial Hospital, Chicago.

On the basis of the findings, physicians could consider the SGLT2s canagliflozin, dapagliflozin, and empagliflozin or a GLP-1 as first-line therapy, particularly for people with T2D who are at elevated risk for GI cancers, Dr. Chan said in an interview at the American College of Gastroenterology (ACG): 2023 Annual Scientific Meeting.

Previous research focused on potential cardiovascular or renal benefits associated with SGLT2s, “but there are few looking at GI cancer risk and these medications,” she added. Most earlier studies in cancer have been preclinical and observational studies on colorectal cancer or hepatocellular carcinoma.

Using the TriNetX database of millions of medical claims from 92 hospitals across the United States, Dr. Chan and colleagues identified 706,390 adults who began first-line SGLT2 inhibitor therapy. They used propensity matching to link these patients with 706,390 other adults who began taking a DDP4 inhibitor (sitagliptin, saxagliptin, linagliptin, or alogliptin).

All participants had been diagnosed with type 2 diabetes. Patients were prescribed an SGLT2 inhibitor at least three times, and any cancer diagnosis that occurred at least 6 months after starting therapy was noted. Anyone with a history of cancer, cancer recurrence, or metastatic disease was excluded from the population-based cohort study.

In addition to evaluating a large number of patients, the study is notable for including people with ulcerative colitis and Crohn’s disease and for evaluating every GI cancer – esophageal, gastric, small intestinal, colorectal, rectal, anal, hepatic, biliary, and gallbladder malignancies.
 

Key findings

Among adults who received an SGLT2 inhibitor, there was a 15% decrease in overall risk of developing any GI cancer, compared with those who received a DPP4 inhibitor (hazard ratio, 0.85; 95% confidence interval, 0.82-0.88).

Colon cancer was the most common malignancy in the study. Dr. Chan and colleagues identified colon cancer among 1,789 people, or 0.25% of those taking an SGLT2 inhibitor, compared with 3,283 people, or 0.46%, of those taking a DPP4 inhibitor.

SGLT2 inhibitors were associated with a 16% decrease in risk of gastric cancer (HR, 0.84; 95% CI; 0.74-0.945; P = .005), a 13% decrease in risk of liver and intrahepatic bile duct cancer (HR, 0.87; 95% CI, 0.81-0.95), and a 22% decrease in risk of colon cancer (HR, 0.781; 95% CI, 0.74-0.83; P < .001), compared with the DPP4 medications.

The only cancer more likely in the SGLT2 inhibitor group than in the DPP4 inhibitor group was pancreatic cancer (HR, 1.035; 95% CI, 0.964-1.111; P = .340).

The SLGT2 inhibitor class also was superior to metformin for reducing risk of GI cancers.

Asked whether the study findings should alter current practice, Dr. Chan said that the study is new and hasn’t yet been published. “More studies will be needed and included in official guidelines before the findings become practice-changing,” she said.

Limitations of the study include residual confounding, absence of family cancer history, and information bias. Strengths include the large, national database and propensity score matching.
 

‘Eye-opening’ study

“It is a good study, and eye-opening because it shows that one class of diabetes medications is better than another one,” said session co-moderator Kenneth J. Vega, MD, professor of medicine and chief of the division of gastroenterology and hepatology at Augusta University–Medical College of Georgia.

Dr. Vega shared his theory on why diabetes medications could reduce risk of GI cancers. “I would think reducing diabetes means you can control inflammation ... and better controlling inflammation leads you to have less cancers.”

He added, “I think we need more long-term studies.”

The study was independently supported. Dr. Chan and Dr. Vega report no relevant financial relationships.

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

VANCOUVER – Use of sodium glucose cotransporter-2 (SGLT2) inhibitors is associated with a reduced risk of gastrointestinal cancers among patients with type 2 diabetes, compared with dipeptidyl peptidase IV (DPP4) inhibitors, new evidence reveals.

The SGLT2 inhibitors emerged superior to DPP4 inhibitors for reducing risk of colorectal, hepatic, esophageal, and other GI cancers except pancreatic cancer, said study investigator Shu-Yen Emily Chan, MD, a gastroenterologist in the departments of medicine and epidemiology at Weiss Memorial Hospital, Chicago.

On the basis of the findings, physicians could consider the SGLT2s canagliflozin, dapagliflozin, and empagliflozin or a GLP-1 as first-line therapy, particularly for people with T2D who are at elevated risk for GI cancers, Dr. Chan said in an interview at the American College of Gastroenterology (ACG): 2023 Annual Scientific Meeting.

Previous research focused on potential cardiovascular or renal benefits associated with SGLT2s, “but there are few looking at GI cancer risk and these medications,” she added. Most earlier studies in cancer have been preclinical and observational studies on colorectal cancer or hepatocellular carcinoma.

Using the TriNetX database of millions of medical claims from 92 hospitals across the United States, Dr. Chan and colleagues identified 706,390 adults who began first-line SGLT2 inhibitor therapy. They used propensity matching to link these patients with 706,390 other adults who began taking a DDP4 inhibitor (sitagliptin, saxagliptin, linagliptin, or alogliptin).

All participants had been diagnosed with type 2 diabetes. Patients were prescribed an SGLT2 inhibitor at least three times, and any cancer diagnosis that occurred at least 6 months after starting therapy was noted. Anyone with a history of cancer, cancer recurrence, or metastatic disease was excluded from the population-based cohort study.

In addition to evaluating a large number of patients, the study is notable for including people with ulcerative colitis and Crohn’s disease and for evaluating every GI cancer – esophageal, gastric, small intestinal, colorectal, rectal, anal, hepatic, biliary, and gallbladder malignancies.
 

Key findings

Among adults who received an SGLT2 inhibitor, there was a 15% decrease in overall risk of developing any GI cancer, compared with those who received a DPP4 inhibitor (hazard ratio, 0.85; 95% confidence interval, 0.82-0.88).

Colon cancer was the most common malignancy in the study. Dr. Chan and colleagues identified colon cancer among 1,789 people, or 0.25% of those taking an SGLT2 inhibitor, compared with 3,283 people, or 0.46%, of those taking a DPP4 inhibitor.

SGLT2 inhibitors were associated with a 16% decrease in risk of gastric cancer (HR, 0.84; 95% CI; 0.74-0.945; P = .005), a 13% decrease in risk of liver and intrahepatic bile duct cancer (HR, 0.87; 95% CI, 0.81-0.95), and a 22% decrease in risk of colon cancer (HR, 0.781; 95% CI, 0.74-0.83; P < .001), compared with the DPP4 medications.

The only cancer more likely in the SGLT2 inhibitor group than in the DPP4 inhibitor group was pancreatic cancer (HR, 1.035; 95% CI, 0.964-1.111; P = .340).

The SLGT2 inhibitor class also was superior to metformin for reducing risk of GI cancers.

Asked whether the study findings should alter current practice, Dr. Chan said that the study is new and hasn’t yet been published. “More studies will be needed and included in official guidelines before the findings become practice-changing,” she said.

Limitations of the study include residual confounding, absence of family cancer history, and information bias. Strengths include the large, national database and propensity score matching.
 

‘Eye-opening’ study

“It is a good study, and eye-opening because it shows that one class of diabetes medications is better than another one,” said session co-moderator Kenneth J. Vega, MD, professor of medicine and chief of the division of gastroenterology and hepatology at Augusta University–Medical College of Georgia.

Dr. Vega shared his theory on why diabetes medications could reduce risk of GI cancers. “I would think reducing diabetes means you can control inflammation ... and better controlling inflammation leads you to have less cancers.”

He added, “I think we need more long-term studies.”

The study was independently supported. Dr. Chan and Dr. Vega report no relevant financial relationships.

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

VANCOUVER – Use of sodium glucose cotransporter-2 (SGLT2) inhibitors is associated with a reduced risk of gastrointestinal cancers among patients with type 2 diabetes, compared with dipeptidyl peptidase IV (DPP4) inhibitors, new evidence reveals.

The SGLT2 inhibitors emerged superior to DPP4 inhibitors for reducing risk of colorectal, hepatic, esophageal, and other GI cancers except pancreatic cancer, said study investigator Shu-Yen Emily Chan, MD, a gastroenterologist in the departments of medicine and epidemiology at Weiss Memorial Hospital, Chicago.

On the basis of the findings, physicians could consider the SGLT2s canagliflozin, dapagliflozin, and empagliflozin or a GLP-1 as first-line therapy, particularly for people with T2D who are at elevated risk for GI cancers, Dr. Chan said in an interview at the American College of Gastroenterology (ACG): 2023 Annual Scientific Meeting.

Previous research focused on potential cardiovascular or renal benefits associated with SGLT2s, “but there are few looking at GI cancer risk and these medications,” she added. Most earlier studies in cancer have been preclinical and observational studies on colorectal cancer or hepatocellular carcinoma.

Using the TriNetX database of millions of medical claims from 92 hospitals across the United States, Dr. Chan and colleagues identified 706,390 adults who began first-line SGLT2 inhibitor therapy. They used propensity matching to link these patients with 706,390 other adults who began taking a DDP4 inhibitor (sitagliptin, saxagliptin, linagliptin, or alogliptin).

All participants had been diagnosed with type 2 diabetes. Patients were prescribed an SGLT2 inhibitor at least three times, and any cancer diagnosis that occurred at least 6 months after starting therapy was noted. Anyone with a history of cancer, cancer recurrence, or metastatic disease was excluded from the population-based cohort study.

In addition to evaluating a large number of patients, the study is notable for including people with ulcerative colitis and Crohn’s disease and for evaluating every GI cancer – esophageal, gastric, small intestinal, colorectal, rectal, anal, hepatic, biliary, and gallbladder malignancies.
 

Key findings

Among adults who received an SGLT2 inhibitor, there was a 15% decrease in overall risk of developing any GI cancer, compared with those who received a DPP4 inhibitor (hazard ratio, 0.85; 95% confidence interval, 0.82-0.88).

Colon cancer was the most common malignancy in the study. Dr. Chan and colleagues identified colon cancer among 1,789 people, or 0.25% of those taking an SGLT2 inhibitor, compared with 3,283 people, or 0.46%, of those taking a DPP4 inhibitor.

SGLT2 inhibitors were associated with a 16% decrease in risk of gastric cancer (HR, 0.84; 95% CI; 0.74-0.945; P = .005), a 13% decrease in risk of liver and intrahepatic bile duct cancer (HR, 0.87; 95% CI, 0.81-0.95), and a 22% decrease in risk of colon cancer (HR, 0.781; 95% CI, 0.74-0.83; P < .001), compared with the DPP4 medications.

The only cancer more likely in the SGLT2 inhibitor group than in the DPP4 inhibitor group was pancreatic cancer (HR, 1.035; 95% CI, 0.964-1.111; P = .340).

The SLGT2 inhibitor class also was superior to metformin for reducing risk of GI cancers.

Asked whether the study findings should alter current practice, Dr. Chan said that the study is new and hasn’t yet been published. “More studies will be needed and included in official guidelines before the findings become practice-changing,” she said.

Limitations of the study include residual confounding, absence of family cancer history, and information bias. Strengths include the large, national database and propensity score matching.
 

‘Eye-opening’ study

“It is a good study, and eye-opening because it shows that one class of diabetes medications is better than another one,” said session co-moderator Kenneth J. Vega, MD, professor of medicine and chief of the division of gastroenterology and hepatology at Augusta University–Medical College of Georgia.

Dr. Vega shared his theory on why diabetes medications could reduce risk of GI cancers. “I would think reducing diabetes means you can control inflammation ... and better controlling inflammation leads you to have less cancers.”

He added, “I think we need more long-term studies.”

The study was independently supported. Dr. Chan and Dr. Vega report no relevant financial relationships.

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

I have a cold.

This is nothing new. Like most of us, I’ve probably gotten two or three a year for most of my life. I load up on Tylenol, Sudafed, cough syrup, and ginger ale (I’m not a chicken soup person), and I power through.

I may be sick, but there are patients to see. For better or worse, the idea of calling in sick never seems to apply to the health care profession. So I put on a mask to protect my patients and go ahead with my day.

But, as I blow my nose and accept my fate for the next week, I realize that I haven’t been sick with anything since 2019. Really.

Somewhere, with the masks, extra hand washing, Purell, and some good luck, I’d managed to dodge the rhinoviruses for 4 years.

I have no idea how many times in the last week I’ve told someone “I’d forgotten how much I hated being sick.” Certainly there are far worse things to have (colds are high on the “annoying” but low on the “serious” scales), but it’s odd to find myself back in the familiar pattern of coughing, sneezing, and low-grade fever that used to be a semi-annual occurrence.

So I look at myself in the mirror and wonder if the masks were that bad an idea? Certainly I have my share of patients, usually with immune diseases, who still wear them, and I see people at the store doing the same. There are countries where it was common to have them on even before the pandemic, though that was more for pollution.

I’m still pretty careful about hand washing, but that’s the nature of my job, anyway.

I keep coming back to the mask, though. Obviously, nothing is 100% successful, but certainly it puts a respiratory filter of sorts between us and the world (and vice versa). We use them in surgery and isolation rooms. It’s probably not the only reason I went 4 years without a cold, but it likely helped.

On the other hand, it has its drawbacks. A lot of my patients have hearing issues, and the mask doesn’t improve that. It also limits communication by facial expression, which is always important. It fogs up my classes (during the pandemic it became quite clear that any mask that claimed to be fog-free was lying).

I’m not saying everyone should wear them. This is up to me, that’s up to them.

But, for myself, it’s something to think about.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I have a cold.

This is nothing new. Like most of us, I’ve probably gotten two or three a year for most of my life. I load up on Tylenol, Sudafed, cough syrup, and ginger ale (I’m not a chicken soup person), and I power through.

I may be sick, but there are patients to see. For better or worse, the idea of calling in sick never seems to apply to the health care profession. So I put on a mask to protect my patients and go ahead with my day.

But, as I blow my nose and accept my fate for the next week, I realize that I haven’t been sick with anything since 2019. Really.

Somewhere, with the masks, extra hand washing, Purell, and some good luck, I’d managed to dodge the rhinoviruses for 4 years.

I have no idea how many times in the last week I’ve told someone “I’d forgotten how much I hated being sick.” Certainly there are far worse things to have (colds are high on the “annoying” but low on the “serious” scales), but it’s odd to find myself back in the familiar pattern of coughing, sneezing, and low-grade fever that used to be a semi-annual occurrence.

So I look at myself in the mirror and wonder if the masks were that bad an idea? Certainly I have my share of patients, usually with immune diseases, who still wear them, and I see people at the store doing the same. There are countries where it was common to have them on even before the pandemic, though that was more for pollution.

I’m still pretty careful about hand washing, but that’s the nature of my job, anyway.

I keep coming back to the mask, though. Obviously, nothing is 100% successful, but certainly it puts a respiratory filter of sorts between us and the world (and vice versa). We use them in surgery and isolation rooms. It’s probably not the only reason I went 4 years without a cold, but it likely helped.

On the other hand, it has its drawbacks. A lot of my patients have hearing issues, and the mask doesn’t improve that. It also limits communication by facial expression, which is always important. It fogs up my classes (during the pandemic it became quite clear that any mask that claimed to be fog-free was lying).

I’m not saying everyone should wear them. This is up to me, that’s up to them.

But, for myself, it’s something to think about.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I have a cold.

This is nothing new. Like most of us, I’ve probably gotten two or three a year for most of my life. I load up on Tylenol, Sudafed, cough syrup, and ginger ale (I’m not a chicken soup person), and I power through.

I may be sick, but there are patients to see. For better or worse, the idea of calling in sick never seems to apply to the health care profession. So I put on a mask to protect my patients and go ahead with my day.

But, as I blow my nose and accept my fate for the next week, I realize that I haven’t been sick with anything since 2019. Really.

Somewhere, with the masks, extra hand washing, Purell, and some good luck, I’d managed to dodge the rhinoviruses for 4 years.

I have no idea how many times in the last week I’ve told someone “I’d forgotten how much I hated being sick.” Certainly there are far worse things to have (colds are high on the “annoying” but low on the “serious” scales), but it’s odd to find myself back in the familiar pattern of coughing, sneezing, and low-grade fever that used to be a semi-annual occurrence.

So I look at myself in the mirror and wonder if the masks were that bad an idea? Certainly I have my share of patients, usually with immune diseases, who still wear them, and I see people at the store doing the same. There are countries where it was common to have them on even before the pandemic, though that was more for pollution.

I’m still pretty careful about hand washing, but that’s the nature of my job, anyway.

I keep coming back to the mask, though. Obviously, nothing is 100% successful, but certainly it puts a respiratory filter of sorts between us and the world (and vice versa). We use them in surgery and isolation rooms. It’s probably not the only reason I went 4 years without a cold, but it likely helped.

On the other hand, it has its drawbacks. A lot of my patients have hearing issues, and the mask doesn’t improve that. It also limits communication by facial expression, which is always important. It fogs up my classes (during the pandemic it became quite clear that any mask that claimed to be fog-free was lying).

I’m not saying everyone should wear them. This is up to me, that’s up to them.

But, for myself, it’s something to think about.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

When Haley Naik, MD, joined the University of California, San Francisco, as a dermatologist in 2015, she was struck by the dearth of data in the medical literature about hidradenitis suppurativa (HS).

“For decades there were no datasets to begin to understand HS – its clinical course, how patients respond to medications, and how quality of life improves for patients with therapy,” Dr. Naik, who directs the HS program at UCSF, said in an interview. Inspired to improve the bleak HS knowledge landscape, she began to systematically collect information from HS patient visits, “to try to better understand how treatments were helping them or not and also to better understand their quality-of-life impact,” she said. “This also facilitated research in HS, but over time it became clear that there was a growing need for a larger effort.”

But in 2020, Dr. Naik teamed up with investigative dermatologist Michelle Lowes, MBBS, PhD, to launch The Hidradenitis Suppurativa Prospective Observational Registry and Biospecimen Repository (HS PROGRESS), a national multicenter study designed to prospectively collect high-quality longitudinal clinical and biological data on patients with HS across major academic institutions and to care for HS patients. To date, more than 500 patients are enrolled at 12 participating sites, and 4 more sites plan to join the consortium by the end of 2023. The goal is to enroll a total of 8,000 patients, which will make it the largest dataset of its kind.

“Each site investigator is a physician who specializes in taking care of HS patients,” said Dr. Naik, who is the study’s principal investigator. “These are people who are conducting active research in various aspects of HS, and they’re trusted members of the medical community.”

She highlighted the three main objectives of HS PROGRESS. The first objective is to develop a longitudinal cohort of HS patients so that investigators can understand the clinical course of HS and effectiveness of treatments. The second is to collect biospecimens from patients with HS for translational studies “that can help to drive drug development, help us identify biomarkers that can help us predict disease course and predict patient response to therapies, so we know exactly what to give them,” she explained. The third objective is to provide patients with HS with the opportunity to be recruited for clinical trials, “so they have access to cutting-edge therapies and know what’s happening in this space.”
 

Collecting biospecimens

The goal of collecting biospecimens is to provide them to multiple investigators to improve the understanding of HS biology and treatment. “Our thought is to apply next generation techniques to these biospecimens to get metagenomic, transcriptomic, and genomic data to better understand HS biology so that we can identify targets for novel therapy,” Dr. Naik said.

Although HS is estimated to affect 1% of Western populations, the tumor necrosis alpha (TNF)-inhibitor adalimumab remains the only Food and Drug Administration-approved therapy for the condition.

However, Dr. Naik said that there are many promising drugs on the horizon for HS, especially interleukin (IL)-17 inhibitors. “One of the most exciting things about these drugs is that they set the bar higher for what we can expect out of therapies for HS, such as reporting a HiSCR (HS Clinical Response) score 75, which is the equivalent of 75% improvement in inflammatory HS lesions without an increase in draining tunnels,” she said. “This is well beyond what adalimumab had demonstrated in landmark trials in 2015. The safety profile on IL-17 inhibitors looks great, too.”

JAK inhibitors also hold promise for HS. “It’s going to be key to see how these drugs perform in the real-world setting in our average HS patients who may have comorbidities,” Dr. Naik said. “This is where an effort like HS PROGRESS will carry weight, because in a dataset like this, we’re going to be able to ask questions like, is there a class of drugs that works better for one specific phenotype of HS, or for patients who have a younger age of onset, or who are earlier in their disease course? These are questions we can’t ask in the context of a clinical trial, but we can ask in the context of real-world data from many practices.”

In addition to USCF, the 11 study locations participating in HS PROGRESS are the University of North Carolina at Chapel Hill; Mayo Clinic; Penn State University, Hershey; University of Virginia, Charlottesville; Washington University in St. Louis; University of Southern California, Los Angeles; Henry Ford Health, Detroit; University of Minnesota; University of Pennsylvania, Philadelphia; Duke University, Durham, N.C.; and University of Miami.

Dr. Naik disclosed that she has received grant support from AbbVie; consulting fees from 23andme, AbbVie, Aristea Therapeutics, Nimbus Therapeutics, Medscape, Sonoma Biotherapeutics, DAVA Oncology, Boehringer Ingelheim, UCB, and Novartis; and investigator fees from Pfizer; and holds shares in Radera. She is also an associate editor for JAMA Dermatology and a board member of the Hidradenitis Suppurativa Foundation.

When Haley Naik, MD, joined the University of California, San Francisco, as a dermatologist in 2015, she was struck by the dearth of data in the medical literature about hidradenitis suppurativa (HS).

“For decades there were no datasets to begin to understand HS – its clinical course, how patients respond to medications, and how quality of life improves for patients with therapy,” Dr. Naik, who directs the HS program at UCSF, said in an interview. Inspired to improve the bleak HS knowledge landscape, she began to systematically collect information from HS patient visits, “to try to better understand how treatments were helping them or not and also to better understand their quality-of-life impact,” she said. “This also facilitated research in HS, but over time it became clear that there was a growing need for a larger effort.”

But in 2020, Dr. Naik teamed up with investigative dermatologist Michelle Lowes, MBBS, PhD, to launch The Hidradenitis Suppurativa Prospective Observational Registry and Biospecimen Repository (HS PROGRESS), a national multicenter study designed to prospectively collect high-quality longitudinal clinical and biological data on patients with HS across major academic institutions and to care for HS patients. To date, more than 500 patients are enrolled at 12 participating sites, and 4 more sites plan to join the consortium by the end of 2023. The goal is to enroll a total of 8,000 patients, which will make it the largest dataset of its kind.

“Each site investigator is a physician who specializes in taking care of HS patients,” said Dr. Naik, who is the study’s principal investigator. “These are people who are conducting active research in various aspects of HS, and they’re trusted members of the medical community.”

She highlighted the three main objectives of HS PROGRESS. The first objective is to develop a longitudinal cohort of HS patients so that investigators can understand the clinical course of HS and effectiveness of treatments. The second is to collect biospecimens from patients with HS for translational studies “that can help to drive drug development, help us identify biomarkers that can help us predict disease course and predict patient response to therapies, so we know exactly what to give them,” she explained. The third objective is to provide patients with HS with the opportunity to be recruited for clinical trials, “so they have access to cutting-edge therapies and know what’s happening in this space.”
 

Collecting biospecimens

The goal of collecting biospecimens is to provide them to multiple investigators to improve the understanding of HS biology and treatment. “Our thought is to apply next generation techniques to these biospecimens to get metagenomic, transcriptomic, and genomic data to better understand HS biology so that we can identify targets for novel therapy,” Dr. Naik said.

Although HS is estimated to affect 1% of Western populations, the tumor necrosis alpha (TNF)-inhibitor adalimumab remains the only Food and Drug Administration-approved therapy for the condition.

However, Dr. Naik said that there are many promising drugs on the horizon for HS, especially interleukin (IL)-17 inhibitors. “One of the most exciting things about these drugs is that they set the bar higher for what we can expect out of therapies for HS, such as reporting a HiSCR (HS Clinical Response) score 75, which is the equivalent of 75% improvement in inflammatory HS lesions without an increase in draining tunnels,” she said. “This is well beyond what adalimumab had demonstrated in landmark trials in 2015. The safety profile on IL-17 inhibitors looks great, too.”

JAK inhibitors also hold promise for HS. “It’s going to be key to see how these drugs perform in the real-world setting in our average HS patients who may have comorbidities,” Dr. Naik said. “This is where an effort like HS PROGRESS will carry weight, because in a dataset like this, we’re going to be able to ask questions like, is there a class of drugs that works better for one specific phenotype of HS, or for patients who have a younger age of onset, or who are earlier in their disease course? These are questions we can’t ask in the context of a clinical trial, but we can ask in the context of real-world data from many practices.”

In addition to USCF, the 11 study locations participating in HS PROGRESS are the University of North Carolina at Chapel Hill; Mayo Clinic; Penn State University, Hershey; University of Virginia, Charlottesville; Washington University in St. Louis; University of Southern California, Los Angeles; Henry Ford Health, Detroit; University of Minnesota; University of Pennsylvania, Philadelphia; Duke University, Durham, N.C.; and University of Miami.

Dr. Naik disclosed that she has received grant support from AbbVie; consulting fees from 23andme, AbbVie, Aristea Therapeutics, Nimbus Therapeutics, Medscape, Sonoma Biotherapeutics, DAVA Oncology, Boehringer Ingelheim, UCB, and Novartis; and investigator fees from Pfizer; and holds shares in Radera. She is also an associate editor for JAMA Dermatology and a board member of the Hidradenitis Suppurativa Foundation.

When Haley Naik, MD, joined the University of California, San Francisco, as a dermatologist in 2015, she was struck by the dearth of data in the medical literature about hidradenitis suppurativa (HS).

“For decades there were no datasets to begin to understand HS – its clinical course, how patients respond to medications, and how quality of life improves for patients with therapy,” Dr. Naik, who directs the HS program at UCSF, said in an interview. Inspired to improve the bleak HS knowledge landscape, she began to systematically collect information from HS patient visits, “to try to better understand how treatments were helping them or not and also to better understand their quality-of-life impact,” she said. “This also facilitated research in HS, but over time it became clear that there was a growing need for a larger effort.”

But in 2020, Dr. Naik teamed up with investigative dermatologist Michelle Lowes, MBBS, PhD, to launch The Hidradenitis Suppurativa Prospective Observational Registry and Biospecimen Repository (HS PROGRESS), a national multicenter study designed to prospectively collect high-quality longitudinal clinical and biological data on patients with HS across major academic institutions and to care for HS patients. To date, more than 500 patients are enrolled at 12 participating sites, and 4 more sites plan to join the consortium by the end of 2023. The goal is to enroll a total of 8,000 patients, which will make it the largest dataset of its kind.

“Each site investigator is a physician who specializes in taking care of HS patients,” said Dr. Naik, who is the study’s principal investigator. “These are people who are conducting active research in various aspects of HS, and they’re trusted members of the medical community.”

She highlighted the three main objectives of HS PROGRESS. The first objective is to develop a longitudinal cohort of HS patients so that investigators can understand the clinical course of HS and effectiveness of treatments. The second is to collect biospecimens from patients with HS for translational studies “that can help to drive drug development, help us identify biomarkers that can help us predict disease course and predict patient response to therapies, so we know exactly what to give them,” she explained. The third objective is to provide patients with HS with the opportunity to be recruited for clinical trials, “so they have access to cutting-edge therapies and know what’s happening in this space.”
 

Collecting biospecimens

The goal of collecting biospecimens is to provide them to multiple investigators to improve the understanding of HS biology and treatment. “Our thought is to apply next generation techniques to these biospecimens to get metagenomic, transcriptomic, and genomic data to better understand HS biology so that we can identify targets for novel therapy,” Dr. Naik said.

Although HS is estimated to affect 1% of Western populations, the tumor necrosis alpha (TNF)-inhibitor adalimumab remains the only Food and Drug Administration-approved therapy for the condition.

However, Dr. Naik said that there are many promising drugs on the horizon for HS, especially interleukin (IL)-17 inhibitors. “One of the most exciting things about these drugs is that they set the bar higher for what we can expect out of therapies for HS, such as reporting a HiSCR (HS Clinical Response) score 75, which is the equivalent of 75% improvement in inflammatory HS lesions without an increase in draining tunnels,” she said. “This is well beyond what adalimumab had demonstrated in landmark trials in 2015. The safety profile on IL-17 inhibitors looks great, too.”

JAK inhibitors also hold promise for HS. “It’s going to be key to see how these drugs perform in the real-world setting in our average HS patients who may have comorbidities,” Dr. Naik said. “This is where an effort like HS PROGRESS will carry weight, because in a dataset like this, we’re going to be able to ask questions like, is there a class of drugs that works better for one specific phenotype of HS, or for patients who have a younger age of onset, or who are earlier in their disease course? These are questions we can’t ask in the context of a clinical trial, but we can ask in the context of real-world data from many practices.”

In addition to USCF, the 11 study locations participating in HS PROGRESS are the University of North Carolina at Chapel Hill; Mayo Clinic; Penn State University, Hershey; University of Virginia, Charlottesville; Washington University in St. Louis; University of Southern California, Los Angeles; Henry Ford Health, Detroit; University of Minnesota; University of Pennsylvania, Philadelphia; Duke University, Durham, N.C.; and University of Miami.

Dr. Naik disclosed that she has received grant support from AbbVie; consulting fees from 23andme, AbbVie, Aristea Therapeutics, Nimbus Therapeutics, Medscape, Sonoma Biotherapeutics, DAVA Oncology, Boehringer Ingelheim, UCB, and Novartis; and investigator fees from Pfizer; and holds shares in Radera. She is also an associate editor for JAMA Dermatology and a board member of the Hidradenitis Suppurativa Foundation.

The Food and Drug Administration has approved mirikizumab-mrkz (Omvoh, Eli Lilly) for the treatment of moderately to severely active ulcerative colitis (UC) in adults.

Mirikizumab is a humanized monoclonal antibody that targets the p19 subunit of IL-23, a key player in UC-related inflammation. It’s the first IL-23 inhibitor to be approved in the United States for UC. The drug is administered intravenously.

The approval of mirikizumab represents a “novel scientific advancement, providing a treatment that may offer relief from three key symptoms – stool frequency, rectal bleeding, and bowel urgency – regardless of past biologic use,” Bruce Sands, MD, chief of the division of gastroenterology, Icahn School of Medicine at Mount Sinai, who worked on the pivotal trials, said in a news release.

Last April, the FDA withheld approval of the drug, citing issues related to the proposed manufacturing of the drug. The agency did not express concerns about safety or efficacy data, Eli Lilly confirmed.

The FDA approval was based on results from the phase 3 LUCENT-1 induction and LUCENT-2 maintenance trials, published in the New England Journal of Medicine.

All patients in the LUCENT program had moderately to severely active UC and had experienced treatment failure or could not tolerate past treatments, including biologic therapies.

The induction trial enrolled 1,281 patients; 544 patients who had a response to mirikizumab were enrolled in the maintenance phase.

The trials showed that mirikizumab achieved primary and secondary endpoints, including sustained clinical remission and significantly improved bowel urgency.

“Bowel urgency is one of the most disruptive symptoms for patients with ulcerative colitis,” Michael Osso, president and chief executive officer of the Crohn’s and Colitis Foundation, said in the news release.

Mirikizumab offers “new hope for those who have tried other therapies and still find themselves making accommodations for the uncertainty of bowel urgency–related accidents and other symptoms associated with ulcerative colitis,” Mr. Osso added.

The most common adverse reactions associated with mirikizumab were upper respiratory infections, injection site reactions, arthralgia, rash, headache, and herpes viral infection.

The drug label contains warnings and precautions related to hypersensitivity reactions, risk of infection, tuberculosis, hepatotoxicity, and immunizations.

A version of this article was originally published on Medscape.com .

The Food and Drug Administration has approved mirikizumab-mrkz (Omvoh, Eli Lilly) for the treatment of moderately to severely active ulcerative colitis (UC) in adults.

Mirikizumab is a humanized monoclonal antibody that targets the p19 subunit of IL-23, a key player in UC-related inflammation. It’s the first IL-23 inhibitor to be approved in the United States for UC. The drug is administered intravenously.

The approval of mirikizumab represents a “novel scientific advancement, providing a treatment that may offer relief from three key symptoms – stool frequency, rectal bleeding, and bowel urgency – regardless of past biologic use,” Bruce Sands, MD, chief of the division of gastroenterology, Icahn School of Medicine at Mount Sinai, who worked on the pivotal trials, said in a news release.

Last April, the FDA withheld approval of the drug, citing issues related to the proposed manufacturing of the drug. The agency did not express concerns about safety or efficacy data, Eli Lilly confirmed.

The FDA approval was based on results from the phase 3 LUCENT-1 induction and LUCENT-2 maintenance trials, published in the New England Journal of Medicine.

All patients in the LUCENT program had moderately to severely active UC and had experienced treatment failure or could not tolerate past treatments, including biologic therapies.

The induction trial enrolled 1,281 patients; 544 patients who had a response to mirikizumab were enrolled in the maintenance phase.

The trials showed that mirikizumab achieved primary and secondary endpoints, including sustained clinical remission and significantly improved bowel urgency.

“Bowel urgency is one of the most disruptive symptoms for patients with ulcerative colitis,” Michael Osso, president and chief executive officer of the Crohn’s and Colitis Foundation, said in the news release.

Mirikizumab offers “new hope for those who have tried other therapies and still find themselves making accommodations for the uncertainty of bowel urgency–related accidents and other symptoms associated with ulcerative colitis,” Mr. Osso added.

The most common adverse reactions associated with mirikizumab were upper respiratory infections, injection site reactions, arthralgia, rash, headache, and herpes viral infection.

The drug label contains warnings and precautions related to hypersensitivity reactions, risk of infection, tuberculosis, hepatotoxicity, and immunizations.

A version of this article was originally published on Medscape.com .

The Food and Drug Administration has approved mirikizumab-mrkz (Omvoh, Eli Lilly) for the treatment of moderately to severely active ulcerative colitis (UC) in adults.

Mirikizumab is a humanized monoclonal antibody that targets the p19 subunit of IL-23, a key player in UC-related inflammation. It’s the first IL-23 inhibitor to be approved in the United States for UC. The drug is administered intravenously.

The approval of mirikizumab represents a “novel scientific advancement, providing a treatment that may offer relief from three key symptoms – stool frequency, rectal bleeding, and bowel urgency – regardless of past biologic use,” Bruce Sands, MD, chief of the division of gastroenterology, Icahn School of Medicine at Mount Sinai, who worked on the pivotal trials, said in a news release.

Last April, the FDA withheld approval of the drug, citing issues related to the proposed manufacturing of the drug. The agency did not express concerns about safety or efficacy data, Eli Lilly confirmed.

The FDA approval was based on results from the phase 3 LUCENT-1 induction and LUCENT-2 maintenance trials, published in the New England Journal of Medicine.

All patients in the LUCENT program had moderately to severely active UC and had experienced treatment failure or could not tolerate past treatments, including biologic therapies.

The induction trial enrolled 1,281 patients; 544 patients who had a response to mirikizumab were enrolled in the maintenance phase.

The trials showed that mirikizumab achieved primary and secondary endpoints, including sustained clinical remission and significantly improved bowel urgency.

“Bowel urgency is one of the most disruptive symptoms for patients with ulcerative colitis,” Michael Osso, president and chief executive officer of the Crohn’s and Colitis Foundation, said in the news release.

Mirikizumab offers “new hope for those who have tried other therapies and still find themselves making accommodations for the uncertainty of bowel urgency–related accidents and other symptoms associated with ulcerative colitis,” Mr. Osso added.

The most common adverse reactions associated with mirikizumab were upper respiratory infections, injection site reactions, arthralgia, rash, headache, and herpes viral infection.

The drug label contains warnings and precautions related to hypersensitivity reactions, risk of infection, tuberculosis, hepatotoxicity, and immunizations.

A version of this article was originally published on Medscape.com .

Key clinical point: Methotrexate remains the anchor untargeted conventional treatment for rheumatoid arthritis (RA); however, several alternatives are now available in case of suboptimal outcomes or unacceptable adverse events with methotrexate.

Major finding: Methotrexate reduced the imputed tender joint count (TJCi) by 5.18 joints (95% credible interval [CrI] 4.07-6.28 joints) compared with placebo. Cyclophosphamide fared better than methotrexate in terms of TJCi reduction (6.08 joints; 95% CrI 0.44-11.66 joints), but glucocorticoids (−2.54 joints; 95% CrI −5.16 to 0.08 joints) and the remaining drugs showed similar or lower reductions in the TJCi.

Study details: Findings are from a network meta-analysis of 29 interventions investigated in 132 randomized clinical trials including 13,260 patients with RA who were randomly assigned to receive conventional synthetic disease-modifying antirheumatic drugs, glucocorticoids, placebo, or a pharmacologic non-disease-modifying comparator.

Disclosures: This study was funded by grants from the Danish Regions Medicine Fund and other sources. The authors declared no conflicts of interest.

Source: Guski LS et al. Monotreatment with conventional antirheumatic drugs or glucocorticoids in rheumatoid arthritis: A network meta-analysis. JAMA Netw Open. 2023;6(10):e2335950 (Oct 6). doi: 10.1001/jamanetworkopen.2023.35950

Key clinical point: Methotrexate remains the anchor untargeted conventional treatment for rheumatoid arthritis (RA); however, several alternatives are now available in case of suboptimal outcomes or unacceptable adverse events with methotrexate.

Major finding: Methotrexate reduced the imputed tender joint count (TJCi) by 5.18 joints (95% credible interval [CrI] 4.07-6.28 joints) compared with placebo. Cyclophosphamide fared better than methotrexate in terms of TJCi reduction (6.08 joints; 95% CrI 0.44-11.66 joints), but glucocorticoids (−2.54 joints; 95% CrI −5.16 to 0.08 joints) and the remaining drugs showed similar or lower reductions in the TJCi.

Study details: Findings are from a network meta-analysis of 29 interventions investigated in 132 randomized clinical trials including 13,260 patients with RA who were randomly assigned to receive conventional synthetic disease-modifying antirheumatic drugs, glucocorticoids, placebo, or a pharmacologic non-disease-modifying comparator.

Disclosures: This study was funded by grants from the Danish Regions Medicine Fund and other sources. The authors declared no conflicts of interest.

Source: Guski LS et al. Monotreatment with conventional antirheumatic drugs or glucocorticoids in rheumatoid arthritis: A network meta-analysis. JAMA Netw Open. 2023;6(10):e2335950 (Oct 6). doi: 10.1001/jamanetworkopen.2023.35950

Key clinical point: Methotrexate remains the anchor untargeted conventional treatment for rheumatoid arthritis (RA); however, several alternatives are now available in case of suboptimal outcomes or unacceptable adverse events with methotrexate.

Major finding: Methotrexate reduced the imputed tender joint count (TJCi) by 5.18 joints (95% credible interval [CrI] 4.07-6.28 joints) compared with placebo. Cyclophosphamide fared better than methotrexate in terms of TJCi reduction (6.08 joints; 95% CrI 0.44-11.66 joints), but glucocorticoids (−2.54 joints; 95% CrI −5.16 to 0.08 joints) and the remaining drugs showed similar or lower reductions in the TJCi.

Study details: Findings are from a network meta-analysis of 29 interventions investigated in 132 randomized clinical trials including 13,260 patients with RA who were randomly assigned to receive conventional synthetic disease-modifying antirheumatic drugs, glucocorticoids, placebo, or a pharmacologic non-disease-modifying comparator.

Disclosures: This study was funded by grants from the Danish Regions Medicine Fund and other sources. The authors declared no conflicts of interest.

Source: Guski LS et al. Monotreatment with conventional antirheumatic drugs or glucocorticoids in rheumatoid arthritis: A network meta-analysis. JAMA Netw Open. 2023;6(10):e2335950 (Oct 6). doi: 10.1001/jamanetworkopen.2023.35950

Key clinical point: The risk for cardiovascular events was similar with Janus kinase inhibitors (JAKi) and biologic disease-modifying antirheumatic drugs (bDMARD) in patients with rheumatoid arthritis (RA), although the risk may be slightly higher in elderly patients.

Major finding: JAKi vs bDMARD were not associated with a significantly different risk for cardiovascular events (adjusted incidence rate ratio [aIRR] 1.01; P  =  .965), but with a trend for a higher cardiovascular risk among patients > 65 years old (aIRR 1.24; 95% CI 0.80-1.91) and a lower risk among patients < 65 years old (aIRR 0.70; 95% CI 0.39-1.28).

Study details: Findings are from a retrospective inception cohort study including 15,191 patients with RA from the IQVIA’s Real-World Data Longitudinal Prescription database who had started a new bDMARD or JAKi.

Disclosures: This study was supported by an unrestricted educational grant from Pfizer BV. Two authors declared receiving past grants to the institution from various sources, including Pfizer. The other authors declared no conflicts of interest.

Source: Popa CD et al. Therapy with JAK inhibitors or bDMARDs and the risk of cardiovascular events in the Dutch rheumatoid arthritis population. Rheumatology (Oxford). 2023 (Oct 5). doi: 10.1093/rheumatology/kead531

Key clinical point: The risk for cardiovascular events was similar with Janus kinase inhibitors (JAKi) and biologic disease-modifying antirheumatic drugs (bDMARD) in patients with rheumatoid arthritis (RA), although the risk may be slightly higher in elderly patients.

Major finding: JAKi vs bDMARD were not associated with a significantly different risk for cardiovascular events (adjusted incidence rate ratio [aIRR] 1.01; P  =  .965), but with a trend for a higher cardiovascular risk among patients > 65 years old (aIRR 1.24; 95% CI 0.80-1.91) and a lower risk among patients < 65 years old (aIRR 0.70; 95% CI 0.39-1.28).

Study details: Findings are from a retrospective inception cohort study including 15,191 patients with RA from the IQVIA’s Real-World Data Longitudinal Prescription database who had started a new bDMARD or JAKi.

Disclosures: This study was supported by an unrestricted educational grant from Pfizer BV. Two authors declared receiving past grants to the institution from various sources, including Pfizer. The other authors declared no conflicts of interest.

Source: Popa CD et al. Therapy with JAK inhibitors or bDMARDs and the risk of cardiovascular events in the Dutch rheumatoid arthritis population. Rheumatology (Oxford). 2023 (Oct 5). doi: 10.1093/rheumatology/kead531

Key clinical point: The risk for cardiovascular events was similar with Janus kinase inhibitors (JAKi) and biologic disease-modifying antirheumatic drugs (bDMARD) in patients with rheumatoid arthritis (RA), although the risk may be slightly higher in elderly patients.

Major finding: JAKi vs bDMARD were not associated with a significantly different risk for cardiovascular events (adjusted incidence rate ratio [aIRR] 1.01; P  =  .965), but with a trend for a higher cardiovascular risk among patients > 65 years old (aIRR 1.24; 95% CI 0.80-1.91) and a lower risk among patients < 65 years old (aIRR 0.70; 95% CI 0.39-1.28).

Study details: Findings are from a retrospective inception cohort study including 15,191 patients with RA from the IQVIA’s Real-World Data Longitudinal Prescription database who had started a new bDMARD or JAKi.

Disclosures: This study was supported by an unrestricted educational grant from Pfizer BV. Two authors declared receiving past grants to the institution from various sources, including Pfizer. The other authors declared no conflicts of interest.

Source: Popa CD et al. Therapy with JAK inhibitors or bDMARDs and the risk of cardiovascular events in the Dutch rheumatoid arthritis population. Rheumatology (Oxford). 2023 (Oct 5). doi: 10.1093/rheumatology/kead531