Clinical Edge Journal Scan

Key clinical point: Higher dietary intakes of vitamin B₆ and folate were significantly associated with a lower risk for severe headaches or migraines, with a synergistic interaction observed between vitamin B₆ and folate intake and reduced migraine risk.

Major finding: Compared with the lowest quintile of dietary vitamin B₆ (≤1.13 mg/day) and folate (≤240 μg/day) intake, the risk for severe headache or migraine was lower in the highest quintile of vitamin B₆ (≥2.39 mg/day; adjusted odds ratio [aOR] 0.66; P = .01) and folate (≥502.01 μg/day; aOR 0.57; P = .002) intake. A synergistic interaction was observed between the high mass of vitamin B₆ and folate intake and a lower risk for severe headache or migraine (synergy index 0.58; 95% CI 0.40-0.83).

Study details: This cross-sectional study included 7017 adult participants (age ≥ 20 years), of whom 1350 (19.23%) had migraine.

Disclosures: This study was supported by the National Natural Science Foundation of China, Natural Science Foundation of Jiangxi Province, and others. No conflicts of interests were declared.

Source: Tian S et al. Vitamin B₆ and folate intake are associated with lower risk of severe headache or migraine in adults: An analysis based on NHANES 1999-2004. Nutr Res. 2023;121:51-60 (Nov 15). doi: 10.1016/j.nutres.2023.11.008

Key clinical point: Higher dietary intakes of vitamin B₆ and folate were significantly associated with a lower risk for severe headaches or migraines, with a synergistic interaction observed between vitamin B₆ and folate intake and reduced migraine risk.

Major finding: Compared with the lowest quintile of dietary vitamin B₆ (≤1.13 mg/day) and folate (≤240 μg/day) intake, the risk for severe headache or migraine was lower in the highest quintile of vitamin B₆ (≥2.39 mg/day; adjusted odds ratio [aOR] 0.66; P = .01) and folate (≥502.01 μg/day; aOR 0.57; P = .002) intake. A synergistic interaction was observed between the high mass of vitamin B₆ and folate intake and a lower risk for severe headache or migraine (synergy index 0.58; 95% CI 0.40-0.83).

Study details: This cross-sectional study included 7017 adult participants (age ≥ 20 years), of whom 1350 (19.23%) had migraine.

Disclosures: This study was supported by the National Natural Science Foundation of China, Natural Science Foundation of Jiangxi Province, and others. No conflicts of interests were declared.

Source: Tian S et al. Vitamin B₆ and folate intake are associated with lower risk of severe headache or migraine in adults: An analysis based on NHANES 1999-2004. Nutr Res. 2023;121:51-60 (Nov 15). doi: 10.1016/j.nutres.2023.11.008

Key clinical point: Higher dietary intakes of vitamin B₆ and folate were significantly associated with a lower risk for severe headaches or migraines, with a synergistic interaction observed between vitamin B₆ and folate intake and reduced migraine risk.

Major finding: Compared with the lowest quintile of dietary vitamin B₆ (≤1.13 mg/day) and folate (≤240 μg/day) intake, the risk for severe headache or migraine was lower in the highest quintile of vitamin B₆ (≥2.39 mg/day; adjusted odds ratio [aOR] 0.66; P = .01) and folate (≥502.01 μg/day; aOR 0.57; P = .002) intake. A synergistic interaction was observed between the high mass of vitamin B₆ and folate intake and a lower risk for severe headache or migraine (synergy index 0.58; 95% CI 0.40-0.83).

Study details: This cross-sectional study included 7017 adult participants (age ≥ 20 years), of whom 1350 (19.23%) had migraine.

Disclosures: This study was supported by the National Natural Science Foundation of China, Natural Science Foundation of Jiangxi Province, and others. No conflicts of interests were declared.

Source: Tian S et al. Vitamin B₆ and folate intake are associated with lower risk of severe headache or migraine in adults: An analysis based on NHANES 1999-2004. Nutr Res. 2023;121:51-60 (Nov 15). doi: 10.1016/j.nutres.2023.11.008

A significant gap in our understanding of eosinophilic esophagitis (EoE) lies in how environmental factors, such as allergens or food, influence the response to proton pump inhibitor (PPI) therapy. While PPI achieve histologic remission in approximately 50% of patients, the response in the remaining 50% remains unclear. Addressing this, Muftah and colleagues conducted a study to evaluate the relationship between environmental and food allergies and PPI response in newly diagnosed EoE patients.

Between 2012 and 2016, adult patients newly diagnosed with EoE were tested for environmental and food allergies. Following diagnosis, patients participated in an 8-week trial of twice-daily PPI therapy. The treatment's effectiveness was assessed through repeated upper endoscopies with esophageal biopsies.

The study's primary outcome was the histologic remission of EoE, defined as a decrease in eosinophils to < 15 eosinophils/high-powered field (eos/hpf) in all esophageal biopsy samples during repeat endoscopy. Out of 61 patients, 21 achieved histologic remission, while 40 were classified as having PPI-nonresponding EoE. Among PPI-nonresponding EoE patients, positive food allergen testing was significantly more prevalent compared with PPI-responding EoE patients (82.5% vs 42.9%; P = .0003). Additionally, patients with >10 positive environmental allergen tests were significantly less likely to be PPI-responding EoE patients than those with <10 positive results (21% vs 53.9%; P = .03). A similar trend was observed in patients with >5 positive environmental allergens.

This study is not without limitations. It may exhibit a selection bias toward more severe cases and has a relatively small sample size, affecting its statistical power and generalizability.

This research supports the idea of more tailored management for EoE patients, focusing on their allergen profile, potentially leading to more effective treatment strategies and reducing unnecessary PPI trials. The statistically significant results pave the way for further research, providing an additional tool to predict PPI responsiveness and prevent delays in achieving remission.

Clinicians should consider patient characteristics, particularly positive food allergen tests, that might affect treatment response. More studies are needed, however, to understand the effect of environmental allergies on PPI response fully. A notable finding is that specific aeroallergens, such as oak, birch, Hormodendrum mold, dust mite (Dermatophagoides pteronyssinus), tree mix, and grass mix allergens, are associated with a lack of PPI response. This raises questions about whether exposure to these allergens during peak seasons could worsen PPI response in allergic EoE patients.

Key takeaways from this study include: (1) the importance of integrating allergen testing in EoE patients, especially those unresponsive to standard PPI therapy or suspected as having allergic phenotypes; (2) the need to monitor and adjust therapy based on clinical and histologic responses; and (3) the necessity of staying abreast of emerging research in this area.

EoE diagnosis presents unique challenges, particularly when patients exhibit exclusive distal esophageal eosinophilia or when discrepancies arise between endoscopic and histologic findings. Eosinophil-derived neurotoxin (EDN), a molecule previously studied for its role in monitoring allergy-mediated inflammatory diseases such as asthma and eczema, can shed light on these diagnostic difficulties.

Thomas and coworkers conducted a retrospective study in which they reviewed 231 pediatric patients, obtaining a minimum of four biopsies from at least two different levels of the esophagus. The study aimed to evaluate whether EDN concentrations, determined through esophageal epithelial brushing at the time of biopsy, could serve as an adjunctive diagnostic tool for EoE.

EDN levels proved sensitive (84.4%) and specific (94.6%) in evaluating active EoE when several measures of EoE were used in patients with active EoE compared with those with inactive EoE and the control group. Previous studies at the same institution had found EDN useful for differentiating EoE patients from non-EoE patients. Moreover, an EDN concentration > 10 μg/mL, when collected through esophageal epithelial brushing, was highly sensitive (97%) and specific (89%) for active EoE. This finding suggests the potential for using EDN as a biochemical marker, enhancing diagnostic accuracy and reducing the need for additional interventions in complex cases.

EDN as a biomarker could be invaluable for distinguishing difficult cases, such as those involving distal eosinophilia, active vs nonactive EoE, or non-EoE conditions, such as gastroesophageal reflux disease. Of note, lower EDN levels were observed in pediatric EoE patients who responded to PPI, suggesting EDN's potential utility in predicting PPI responsiveness. Incorporating the measurement of eosinophilic activity could add a new dimension to existing criteria, equipping clinicians with more precise diagnostic tools and reducing the reliance on multiple procedures. This approach would strengthen the correlation between symptomatic, endoscopic, and histologic data.

The study by Jensen and colleagues sheds light on a crucial aspect of EoE management: the psychosocial burden. A recent EoE diagnosis can be associated with increased symptom burden, somatization, and anxiety in patients and families, underscoring the need for a multidisciplinary approach to patient care that considers both physical and mental health. To date, numerous studies have focused on understanding the disease, its follow-up, and treatment. However, there has been limited exploration of the psychosocial burden and patient-associated factors in EoE.

In this context, this team aimed to enhance our understanding of the burden of EoE by evaluating psychosocial comorbidities, such as disordered sleep, anxiety, and somatization, in a pediatric population with EoE. The study included 87 patients of age 8-18 years who completed validated assessments during routine clinic visits, encompassing EoE symptoms (Pediatric Eosinophilic Esophagitis Symptom Scores, PEESSv2.0), quality of life (PedsQL-EoE), anxiety state and trait (State-Trait Anxiety Inventory for Children, STAI-C), somatization (Children's Somatic Symptoms Inventory-24, CSSI-24), and sleep-disordered breathing (University of Michigan Pediatric Sleep Questionnaire, PSQ).

The mean age of the participants was 12.8 years, highlighting the importance of addressing psychosocial distress in this age group, which undergoes crucial developmental stages. Most patients (82%, 71) had been diagnosed with EoE at least 12 months prior, and 60% (52) were treated with multiple approaches. Additionally, 34% (29) had undergone seven or more esophagogastroduodenoscopies, and nearly one third (33%, 27) had experienced a gastrointestinal-related emergency department visit. These factors potentially increase patient stress due to the continuous need for repeat procedures and hospital visits. An intriguing finding was that patients with shorter disease durations (6-12 months since diagnosis) experienced higher symptom burdens (P = .03). Patients with public insurance had less favorable scores for sleep-disordered breathing (P = .01).

Significantly, patients with neurodevelopmental comorbidities had higher scores for somatic symptoms, trait anxiety, and sleep-disordered breathing, and lower quality-of-life scores, compared with those without such comorbidities (P < .01 for all), suggesting that patients with neurodevelopmental issues might particularly benefit from tailored treatments addressing these aspects of the disease. Furthermore, patients with shorter disease durations since diagnosis exhibited higher somatic symptoms and trait anxiety (both P < .01). The study also revealed that patients with fewer esophagogastroduodenoscopies (1-3) had higher somatic symptom scores (P < .01), state anxiety (P = .02), and trait anxiety (P = .03). EoE-associated symptom burden was significantly correlated with increased somatic symptoms (0.34; 95% CI 0.23-0.45) and decreased quality of life (-0.42; 95% CI -0.59 to -0.25). Concerns about eating food and EoE-associated symptoms were both linked to the EoE-associated symptom burden.

This study has several limitations, including a relatively small sample size, which decreases the power and limits inferences for smaller groups within the sample. There was also an imbalance in gender distribution, with only 26% of patients being female, potentially limiting the generalizability of the findings. Moreover, the study included only EoE patients, lacking a control group for comparison to the general pediatric population.

Highlighting a significant aspect of pediatric EoE treatment, this study illuminates an area that might affect patients' long-term quality of life. It underscores the need for multidisciplinary care for EoE patients, where mental health professionals, such as psychologists or psychiatrists, can play a vital role in improving mental health through early identification and intervention for anxiety and somatization disorders. They can also provide education for patients and families on coping strategies. Peer support groups for children and adolescents could be another beneficial tool, allowing them to share experiences and reduce feelings of isolation.

Physicians who treat chronic diseases such as EoE should consider psychosocial factors, as they can affect both physical and mental quality of life. Using screening tools (such as PEESSv2.0, PedsQL-EoE, STAI-C, CSSI-24, or PSQ) during clinic visits can facilitate a more comprehensive evaluation.

A significant gap in our understanding of eosinophilic esophagitis (EoE) lies in how environmental factors, such as allergens or food, influence the response to proton pump inhibitor (PPI) therapy. While PPI achieve histologic remission in approximately 50% of patients, the response in the remaining 50% remains unclear. Addressing this, Muftah and colleagues conducted a study to evaluate the relationship between environmental and food allergies and PPI response in newly diagnosed EoE patients.

Between 2012 and 2016, adult patients newly diagnosed with EoE were tested for environmental and food allergies. Following diagnosis, patients participated in an 8-week trial of twice-daily PPI therapy. The treatment's effectiveness was assessed through repeated upper endoscopies with esophageal biopsies.

The study's primary outcome was the histologic remission of EoE, defined as a decrease in eosinophils to < 15 eosinophils/high-powered field (eos/hpf) in all esophageal biopsy samples during repeat endoscopy. Out of 61 patients, 21 achieved histologic remission, while 40 were classified as having PPI-nonresponding EoE. Among PPI-nonresponding EoE patients, positive food allergen testing was significantly more prevalent compared with PPI-responding EoE patients (82.5% vs 42.9%; P = .0003). Additionally, patients with >10 positive environmental allergen tests were significantly less likely to be PPI-responding EoE patients than those with <10 positive results (21% vs 53.9%; P = .03). A similar trend was observed in patients with >5 positive environmental allergens.

This study is not without limitations. It may exhibit a selection bias toward more severe cases and has a relatively small sample size, affecting its statistical power and generalizability.

This research supports the idea of more tailored management for EoE patients, focusing on their allergen profile, potentially leading to more effective treatment strategies and reducing unnecessary PPI trials. The statistically significant results pave the way for further research, providing an additional tool to predict PPI responsiveness and prevent delays in achieving remission.

Clinicians should consider patient characteristics, particularly positive food allergen tests, that might affect treatment response. More studies are needed, however, to understand the effect of environmental allergies on PPI response fully. A notable finding is that specific aeroallergens, such as oak, birch, Hormodendrum mold, dust mite (Dermatophagoides pteronyssinus), tree mix, and grass mix allergens, are associated with a lack of PPI response. This raises questions about whether exposure to these allergens during peak seasons could worsen PPI response in allergic EoE patients.

Key takeaways from this study include: (1) the importance of integrating allergen testing in EoE patients, especially those unresponsive to standard PPI therapy or suspected as having allergic phenotypes; (2) the need to monitor and adjust therapy based on clinical and histologic responses; and (3) the necessity of staying abreast of emerging research in this area.

EoE diagnosis presents unique challenges, particularly when patients exhibit exclusive distal esophageal eosinophilia or when discrepancies arise between endoscopic and histologic findings. Eosinophil-derived neurotoxin (EDN), a molecule previously studied for its role in monitoring allergy-mediated inflammatory diseases such as asthma and eczema, can shed light on these diagnostic difficulties.

Thomas and coworkers conducted a retrospective study in which they reviewed 231 pediatric patients, obtaining a minimum of four biopsies from at least two different levels of the esophagus. The study aimed to evaluate whether EDN concentrations, determined through esophageal epithelial brushing at the time of biopsy, could serve as an adjunctive diagnostic tool for EoE.

EDN levels proved sensitive (84.4%) and specific (94.6%) in evaluating active EoE when several measures of EoE were used in patients with active EoE compared with those with inactive EoE and the control group. Previous studies at the same institution had found EDN useful for differentiating EoE patients from non-EoE patients. Moreover, an EDN concentration > 10 μg/mL, when collected through esophageal epithelial brushing, was highly sensitive (97%) and specific (89%) for active EoE. This finding suggests the potential for using EDN as a biochemical marker, enhancing diagnostic accuracy and reducing the need for additional interventions in complex cases.

EDN as a biomarker could be invaluable for distinguishing difficult cases, such as those involving distal eosinophilia, active vs nonactive EoE, or non-EoE conditions, such as gastroesophageal reflux disease. Of note, lower EDN levels were observed in pediatric EoE patients who responded to PPI, suggesting EDN's potential utility in predicting PPI responsiveness. Incorporating the measurement of eosinophilic activity could add a new dimension to existing criteria, equipping clinicians with more precise diagnostic tools and reducing the reliance on multiple procedures. This approach would strengthen the correlation between symptomatic, endoscopic, and histologic data.

The study by Jensen and colleagues sheds light on a crucial aspect of EoE management: the psychosocial burden. A recent EoE diagnosis can be associated with increased symptom burden, somatization, and anxiety in patients and families, underscoring the need for a multidisciplinary approach to patient care that considers both physical and mental health. To date, numerous studies have focused on understanding the disease, its follow-up, and treatment. However, there has been limited exploration of the psychosocial burden and patient-associated factors in EoE.

In this context, this team aimed to enhance our understanding of the burden of EoE by evaluating psychosocial comorbidities, such as disordered sleep, anxiety, and somatization, in a pediatric population with EoE. The study included 87 patients of age 8-18 years who completed validated assessments during routine clinic visits, encompassing EoE symptoms (Pediatric Eosinophilic Esophagitis Symptom Scores, PEESSv2.0), quality of life (PedsQL-EoE), anxiety state and trait (State-Trait Anxiety Inventory for Children, STAI-C), somatization (Children's Somatic Symptoms Inventory-24, CSSI-24), and sleep-disordered breathing (University of Michigan Pediatric Sleep Questionnaire, PSQ).

The mean age of the participants was 12.8 years, highlighting the importance of addressing psychosocial distress in this age group, which undergoes crucial developmental stages. Most patients (82%, 71) had been diagnosed with EoE at least 12 months prior, and 60% (52) were treated with multiple approaches. Additionally, 34% (29) had undergone seven or more esophagogastroduodenoscopies, and nearly one third (33%, 27) had experienced a gastrointestinal-related emergency department visit. These factors potentially increase patient stress due to the continuous need for repeat procedures and hospital visits. An intriguing finding was that patients with shorter disease durations (6-12 months since diagnosis) experienced higher symptom burdens (P = .03). Patients with public insurance had less favorable scores for sleep-disordered breathing (P = .01).

Significantly, patients with neurodevelopmental comorbidities had higher scores for somatic symptoms, trait anxiety, and sleep-disordered breathing, and lower quality-of-life scores, compared with those without such comorbidities (P < .01 for all), suggesting that patients with neurodevelopmental issues might particularly benefit from tailored treatments addressing these aspects of the disease. Furthermore, patients with shorter disease durations since diagnosis exhibited higher somatic symptoms and trait anxiety (both P < .01). The study also revealed that patients with fewer esophagogastroduodenoscopies (1-3) had higher somatic symptom scores (P < .01), state anxiety (P = .02), and trait anxiety (P = .03). EoE-associated symptom burden was significantly correlated with increased somatic symptoms (0.34; 95% CI 0.23-0.45) and decreased quality of life (-0.42; 95% CI -0.59 to -0.25). Concerns about eating food and EoE-associated symptoms were both linked to the EoE-associated symptom burden.

This study has several limitations, including a relatively small sample size, which decreases the power and limits inferences for smaller groups within the sample. There was also an imbalance in gender distribution, with only 26% of patients being female, potentially limiting the generalizability of the findings. Moreover, the study included only EoE patients, lacking a control group for comparison to the general pediatric population.

Highlighting a significant aspect of pediatric EoE treatment, this study illuminates an area that might affect patients' long-term quality of life. It underscores the need for multidisciplinary care for EoE patients, where mental health professionals, such as psychologists or psychiatrists, can play a vital role in improving mental health through early identification and intervention for anxiety and somatization disorders. They can also provide education for patients and families on coping strategies. Peer support groups for children and adolescents could be another beneficial tool, allowing them to share experiences and reduce feelings of isolation.

Physicians who treat chronic diseases such as EoE should consider psychosocial factors, as they can affect both physical and mental quality of life. Using screening tools (such as PEESSv2.0, PedsQL-EoE, STAI-C, CSSI-24, or PSQ) during clinic visits can facilitate a more comprehensive evaluation.

A significant gap in our understanding of eosinophilic esophagitis (EoE) lies in how environmental factors, such as allergens or food, influence the response to proton pump inhibitor (PPI) therapy. While PPI achieve histologic remission in approximately 50% of patients, the response in the remaining 50% remains unclear. Addressing this, Muftah and colleagues conducted a study to evaluate the relationship between environmental and food allergies and PPI response in newly diagnosed EoE patients.

Between 2012 and 2016, adult patients newly diagnosed with EoE were tested for environmental and food allergies. Following diagnosis, patients participated in an 8-week trial of twice-daily PPI therapy. The treatment's effectiveness was assessed through repeated upper endoscopies with esophageal biopsies.

The study's primary outcome was the histologic remission of EoE, defined as a decrease in eosinophils to < 15 eosinophils/high-powered field (eos/hpf) in all esophageal biopsy samples during repeat endoscopy. Out of 61 patients, 21 achieved histologic remission, while 40 were classified as having PPI-nonresponding EoE. Among PPI-nonresponding EoE patients, positive food allergen testing was significantly more prevalent compared with PPI-responding EoE patients (82.5% vs 42.9%; P = .0003). Additionally, patients with >10 positive environmental allergen tests were significantly less likely to be PPI-responding EoE patients than those with <10 positive results (21% vs 53.9%; P = .03). A similar trend was observed in patients with >5 positive environmental allergens.

This study is not without limitations. It may exhibit a selection bias toward more severe cases and has a relatively small sample size, affecting its statistical power and generalizability.

This research supports the idea of more tailored management for EoE patients, focusing on their allergen profile, potentially leading to more effective treatment strategies and reducing unnecessary PPI trials. The statistically significant results pave the way for further research, providing an additional tool to predict PPI responsiveness and prevent delays in achieving remission.

Clinicians should consider patient characteristics, particularly positive food allergen tests, that might affect treatment response. More studies are needed, however, to understand the effect of environmental allergies on PPI response fully. A notable finding is that specific aeroallergens, such as oak, birch, Hormodendrum mold, dust mite (Dermatophagoides pteronyssinus), tree mix, and grass mix allergens, are associated with a lack of PPI response. This raises questions about whether exposure to these allergens during peak seasons could worsen PPI response in allergic EoE patients.

Key takeaways from this study include: (1) the importance of integrating allergen testing in EoE patients, especially those unresponsive to standard PPI therapy or suspected as having allergic phenotypes; (2) the need to monitor and adjust therapy based on clinical and histologic responses; and (3) the necessity of staying abreast of emerging research in this area.

EoE diagnosis presents unique challenges, particularly when patients exhibit exclusive distal esophageal eosinophilia or when discrepancies arise between endoscopic and histologic findings. Eosinophil-derived neurotoxin (EDN), a molecule previously studied for its role in monitoring allergy-mediated inflammatory diseases such as asthma and eczema, can shed light on these diagnostic difficulties.

Thomas and coworkers conducted a retrospective study in which they reviewed 231 pediatric patients, obtaining a minimum of four biopsies from at least two different levels of the esophagus. The study aimed to evaluate whether EDN concentrations, determined through esophageal epithelial brushing at the time of biopsy, could serve as an adjunctive diagnostic tool for EoE.

EDN levels proved sensitive (84.4%) and specific (94.6%) in evaluating active EoE when several measures of EoE were used in patients with active EoE compared with those with inactive EoE and the control group. Previous studies at the same institution had found EDN useful for differentiating EoE patients from non-EoE patients. Moreover, an EDN concentration > 10 μg/mL, when collected through esophageal epithelial brushing, was highly sensitive (97%) and specific (89%) for active EoE. This finding suggests the potential for using EDN as a biochemical marker, enhancing diagnostic accuracy and reducing the need for additional interventions in complex cases.

EDN as a biomarker could be invaluable for distinguishing difficult cases, such as those involving distal eosinophilia, active vs nonactive EoE, or non-EoE conditions, such as gastroesophageal reflux disease. Of note, lower EDN levels were observed in pediatric EoE patients who responded to PPI, suggesting EDN's potential utility in predicting PPI responsiveness. Incorporating the measurement of eosinophilic activity could add a new dimension to existing criteria, equipping clinicians with more precise diagnostic tools and reducing the reliance on multiple procedures. This approach would strengthen the correlation between symptomatic, endoscopic, and histologic data.

The study by Jensen and colleagues sheds light on a crucial aspect of EoE management: the psychosocial burden. A recent EoE diagnosis can be associated with increased symptom burden, somatization, and anxiety in patients and families, underscoring the need for a multidisciplinary approach to patient care that considers both physical and mental health. To date, numerous studies have focused on understanding the disease, its follow-up, and treatment. However, there has been limited exploration of the psychosocial burden and patient-associated factors in EoE.

In this context, this team aimed to enhance our understanding of the burden of EoE by evaluating psychosocial comorbidities, such as disordered sleep, anxiety, and somatization, in a pediatric population with EoE. The study included 87 patients of age 8-18 years who completed validated assessments during routine clinic visits, encompassing EoE symptoms (Pediatric Eosinophilic Esophagitis Symptom Scores, PEESSv2.0), quality of life (PedsQL-EoE), anxiety state and trait (State-Trait Anxiety Inventory for Children, STAI-C), somatization (Children's Somatic Symptoms Inventory-24, CSSI-24), and sleep-disordered breathing (University of Michigan Pediatric Sleep Questionnaire, PSQ).

The mean age of the participants was 12.8 years, highlighting the importance of addressing psychosocial distress in this age group, which undergoes crucial developmental stages. Most patients (82%, 71) had been diagnosed with EoE at least 12 months prior, and 60% (52) were treated with multiple approaches. Additionally, 34% (29) had undergone seven or more esophagogastroduodenoscopies, and nearly one third (33%, 27) had experienced a gastrointestinal-related emergency department visit. These factors potentially increase patient stress due to the continuous need for repeat procedures and hospital visits. An intriguing finding was that patients with shorter disease durations (6-12 months since diagnosis) experienced higher symptom burdens (P = .03). Patients with public insurance had less favorable scores for sleep-disordered breathing (P = .01).

Significantly, patients with neurodevelopmental comorbidities had higher scores for somatic symptoms, trait anxiety, and sleep-disordered breathing, and lower quality-of-life scores, compared with those without such comorbidities (P < .01 for all), suggesting that patients with neurodevelopmental issues might particularly benefit from tailored treatments addressing these aspects of the disease. Furthermore, patients with shorter disease durations since diagnosis exhibited higher somatic symptoms and trait anxiety (both P < .01). The study also revealed that patients with fewer esophagogastroduodenoscopies (1-3) had higher somatic symptom scores (P < .01), state anxiety (P = .02), and trait anxiety (P = .03). EoE-associated symptom burden was significantly correlated with increased somatic symptoms (0.34; 95% CI 0.23-0.45) and decreased quality of life (-0.42; 95% CI -0.59 to -0.25). Concerns about eating food and EoE-associated symptoms were both linked to the EoE-associated symptom burden.

This study has several limitations, including a relatively small sample size, which decreases the power and limits inferences for smaller groups within the sample. There was also an imbalance in gender distribution, with only 26% of patients being female, potentially limiting the generalizability of the findings. Moreover, the study included only EoE patients, lacking a control group for comparison to the general pediatric population.

Highlighting a significant aspect of pediatric EoE treatment, this study illuminates an area that might affect patients' long-term quality of life. It underscores the need for multidisciplinary care for EoE patients, where mental health professionals, such as psychologists or psychiatrists, can play a vital role in improving mental health through early identification and intervention for anxiety and somatization disorders. They can also provide education for patients and families on coping strategies. Peer support groups for children and adolescents could be another beneficial tool, allowing them to share experiences and reduce feelings of isolation.

Physicians who treat chronic diseases such as EoE should consider psychosocial factors, as they can affect both physical and mental quality of life. Using screening tools (such as PEESSv2.0, PedsQL-EoE, STAI-C, CSSI-24, or PSQ) during clinic visits can facilitate a more comprehensive evaluation.

The authors of a study published in the December 2023 issue of the Scandinavian Journal of Gastroenterology analyzed data to examine the potential link between gut microbiota and migraine. According to the statistical analysis, the researchers found that "a greater abundance of genus Lactobacillus was associated with a higher risk of migraine and a higher abundance of family Prevotellaceae was related to a decreased risk of migraine." Furthermore, they noted that these gut microbial patterns could be due to a genetic predisposition. The authors suggested that stool sampling could potentially be helpful in the diagnosis of migraine, and that measures to modify gut microbiota in the context of migraine therapy could be identified with future research.

While it is not clear whether migraine is a cause or effect of these alterations, or whether there is another confounding variable, the idea of using diet as a means of reducing migraine risk would be appealing for many patients. This offers hope, but it also leaves a window open for exaggeration and excessive reliance on certain foods or supplements before reliable links are established.

Further examining the genetic factors that might play a role in migraine, a large Korean data analysis published in the December 2023 issue of Epidemiology and Health described a link between migraine and Parkinson's disease. The researchers included 214,193 patients with migraine and 5,879,711 individuals without migraine. According to the statistical analysis, the patients who had migraine with aura showed a 1.35-fold higher risk for Parkinson's disease than individuals without migraine. However, the researchers did not note a statistically significant difference between the risk for Parkinson's disease among patients who had migraine without aura and individuals without migraine.

They also examined other factors, and noted that among individuals with migraine, those who had preexisting dyslipidemia had a higher risk for Parkinson's disease than those who did not have dyslipidemia. Other factors that were not correlated with an association between migraine and Parkinson's disease included cardiovascular risk factors, hypertension, diabetes, smoking status, and high body mass index.

The study authors noted that factors associated with the activity of calcitonin gene-related peptide (CGRP), which is known to play a significant role in the pathophysiology of migraine, could play a role in the link between migraine and Parkinson's disease. They pointed to previous studies that found evidence of elevated CGRP levels in the cerebrospinal fluid of patients with Parkinson's disease as possible evidence of a pathophysiologic link.

An earlier commentary, published in the April 2020 issue of Headache, suggested an implication of CGRP antagonists in the development of neurodegenerative disorders such as Parkinson's disease. The commentary authors noted that previous research correlated midlife migraine to late-life parkinsonism, suggesting a conceivable common pathology, which could include a genetic or environmental predisposition.^[1] They also noted that studies suggest a possible link between CGRP and multiple system atrophy, a parkinsonian disorder.^[1] They considered the possibility that one of the ways that CGRP could contribute to these disorders is through its role in the recruitment of inflammatory mediators, which can alter the function of nicotinic receptors in the dopaminergic system in Parkinson's disease pathogenesis.^[2]

Recent research published in the December 2023 issue of Headache suggests that CGRP responsiveness in migraine therapy could be mediated by genetics. The study included 198 patients who had been typed for genes involved in CGRP signaling or pharmacologic response and were given genetic and polygenic risk scores. Responders were defined as patients who experienced ≥ 50% reduction in migraine days per month at 5.7-month follow-up.

The analysis revealed an association between nonresponder status and rs12615320-G in RAMP1, a gene that encodes a component of high-affinity CGRP receptors, which increased the risk for nonresponder status. The researchers also identified an association between nonresponder status and rs4680-A in COMT, a gene that has been associated with lower COMT enzymatic activity, chronic pain/fibromyalgia, and a "worrier" phenotype. Nonresponders also had a lower mean genetic risk score than responders. These genetic associations could help identify which patients would be most likely to benefit from anti-CGRP therapies.

Given that CGRP responsiveness may have a genetic component, it is possible that one of the contributors to the link between migraine and Parkinson's disease could lie in patients' genetic predisposition to CGRP activity. Yet, the association between these two common conditions is not thoroughly established, and the role of CGRP in the pathogenesis of Parkinson's disease is not fully validated. Nevertheless, the new developments in treatments that modify CGRP activity could have implications beyond migraine.

Additional References

1. Alexoudi A, Deftereos S. CGRP antagonists: side effects and potential Parkinson's disease development. Headache. 2020;60:789-790. doi: 10.1111/head.13770 Source

2. Blumenfeld A, Durham PL, Feoktistov A, et al. Hypervigilance, allostatic load, and migraine prevention: Antibodies to CGRP or receptor. Neurol Ther. 2021;10:469-497. doi:10.1007/s40120-021-00250-7 Source

The authors of a study published in the December 2023 issue of the Scandinavian Journal of Gastroenterology analyzed data to examine the potential link between gut microbiota and migraine. According to the statistical analysis, the researchers found that "a greater abundance of genus Lactobacillus was associated with a higher risk of migraine and a higher abundance of family Prevotellaceae was related to a decreased risk of migraine." Furthermore, they noted that these gut microbial patterns could be due to a genetic predisposition. The authors suggested that stool sampling could potentially be helpful in the diagnosis of migraine, and that measures to modify gut microbiota in the context of migraine therapy could be identified with future research.

While it is not clear whether migraine is a cause or effect of these alterations, or whether there is another confounding variable, the idea of using diet as a means of reducing migraine risk would be appealing for many patients. This offers hope, but it also leaves a window open for exaggeration and excessive reliance on certain foods or supplements before reliable links are established.

Further examining the genetic factors that might play a role in migraine, a large Korean data analysis published in the December 2023 issue of Epidemiology and Health described a link between migraine and Parkinson's disease. The researchers included 214,193 patients with migraine and 5,879,711 individuals without migraine. According to the statistical analysis, the patients who had migraine with aura showed a 1.35-fold higher risk for Parkinson's disease than individuals without migraine. However, the researchers did not note a statistically significant difference between the risk for Parkinson's disease among patients who had migraine without aura and individuals without migraine.

They also examined other factors, and noted that among individuals with migraine, those who had preexisting dyslipidemia had a higher risk for Parkinson's disease than those who did not have dyslipidemia. Other factors that were not correlated with an association between migraine and Parkinson's disease included cardiovascular risk factors, hypertension, diabetes, smoking status, and high body mass index.

The study authors noted that factors associated with the activity of calcitonin gene-related peptide (CGRP), which is known to play a significant role in the pathophysiology of migraine, could play a role in the link between migraine and Parkinson's disease. They pointed to previous studies that found evidence of elevated CGRP levels in the cerebrospinal fluid of patients with Parkinson's disease as possible evidence of a pathophysiologic link.

An earlier commentary, published in the April 2020 issue of Headache, suggested an implication of CGRP antagonists in the development of neurodegenerative disorders such as Parkinson's disease. The commentary authors noted that previous research correlated midlife migraine to late-life parkinsonism, suggesting a conceivable common pathology, which could include a genetic or environmental predisposition.^[1] They also noted that studies suggest a possible link between CGRP and multiple system atrophy, a parkinsonian disorder.^[1] They considered the possibility that one of the ways that CGRP could contribute to these disorders is through its role in the recruitment of inflammatory mediators, which can alter the function of nicotinic receptors in the dopaminergic system in Parkinson's disease pathogenesis.^[2]

Recent research published in the December 2023 issue of Headache suggests that CGRP responsiveness in migraine therapy could be mediated by genetics. The study included 198 patients who had been typed for genes involved in CGRP signaling or pharmacologic response and were given genetic and polygenic risk scores. Responders were defined as patients who experienced ≥ 50% reduction in migraine days per month at 5.7-month follow-up.

The analysis revealed an association between nonresponder status and rs12615320-G in RAMP1, a gene that encodes a component of high-affinity CGRP receptors, which increased the risk for nonresponder status. The researchers also identified an association between nonresponder status and rs4680-A in COMT, a gene that has been associated with lower COMT enzymatic activity, chronic pain/fibromyalgia, and a "worrier" phenotype. Nonresponders also had a lower mean genetic risk score than responders. These genetic associations could help identify which patients would be most likely to benefit from anti-CGRP therapies.

Given that CGRP responsiveness may have a genetic component, it is possible that one of the contributors to the link between migraine and Parkinson's disease could lie in patients' genetic predisposition to CGRP activity. Yet, the association between these two common conditions is not thoroughly established, and the role of CGRP in the pathogenesis of Parkinson's disease is not fully validated. Nevertheless, the new developments in treatments that modify CGRP activity could have implications beyond migraine.

Additional References

1. Alexoudi A, Deftereos S. CGRP antagonists: side effects and potential Parkinson's disease development. Headache. 2020;60:789-790. doi: 10.1111/head.13770 Source

2. Blumenfeld A, Durham PL, Feoktistov A, et al. Hypervigilance, allostatic load, and migraine prevention: Antibodies to CGRP or receptor. Neurol Ther. 2021;10:469-497. doi:10.1007/s40120-021-00250-7 Source

The authors of a study published in the December 2023 issue of the Scandinavian Journal of Gastroenterology analyzed data to examine the potential link between gut microbiota and migraine. According to the statistical analysis, the researchers found that "a greater abundance of genus Lactobacillus was associated with a higher risk of migraine and a higher abundance of family Prevotellaceae was related to a decreased risk of migraine." Furthermore, they noted that these gut microbial patterns could be due to a genetic predisposition. The authors suggested that stool sampling could potentially be helpful in the diagnosis of migraine, and that measures to modify gut microbiota in the context of migraine therapy could be identified with future research.

While it is not clear whether migraine is a cause or effect of these alterations, or whether there is another confounding variable, the idea of using diet as a means of reducing migraine risk would be appealing for many patients. This offers hope, but it also leaves a window open for exaggeration and excessive reliance on certain foods or supplements before reliable links are established.

Further examining the genetic factors that might play a role in migraine, a large Korean data analysis published in the December 2023 issue of Epidemiology and Health described a link between migraine and Parkinson's disease. The researchers included 214,193 patients with migraine and 5,879,711 individuals without migraine. According to the statistical analysis, the patients who had migraine with aura showed a 1.35-fold higher risk for Parkinson's disease than individuals without migraine. However, the researchers did not note a statistically significant difference between the risk for Parkinson's disease among patients who had migraine without aura and individuals without migraine.

They also examined other factors, and noted that among individuals with migraine, those who had preexisting dyslipidemia had a higher risk for Parkinson's disease than those who did not have dyslipidemia. Other factors that were not correlated with an association between migraine and Parkinson's disease included cardiovascular risk factors, hypertension, diabetes, smoking status, and high body mass index.

The study authors noted that factors associated with the activity of calcitonin gene-related peptide (CGRP), which is known to play a significant role in the pathophysiology of migraine, could play a role in the link between migraine and Parkinson's disease. They pointed to previous studies that found evidence of elevated CGRP levels in the cerebrospinal fluid of patients with Parkinson's disease as possible evidence of a pathophysiologic link.

An earlier commentary, published in the April 2020 issue of Headache, suggested an implication of CGRP antagonists in the development of neurodegenerative disorders such as Parkinson's disease. The commentary authors noted that previous research correlated midlife migraine to late-life parkinsonism, suggesting a conceivable common pathology, which could include a genetic or environmental predisposition.^[1] They also noted that studies suggest a possible link between CGRP and multiple system atrophy, a parkinsonian disorder.^[1] They considered the possibility that one of the ways that CGRP could contribute to these disorders is through its role in the recruitment of inflammatory mediators, which can alter the function of nicotinic receptors in the dopaminergic system in Parkinson's disease pathogenesis.^[2]

Recent research published in the December 2023 issue of Headache suggests that CGRP responsiveness in migraine therapy could be mediated by genetics. The study included 198 patients who had been typed for genes involved in CGRP signaling or pharmacologic response and were given genetic and polygenic risk scores. Responders were defined as patients who experienced ≥ 50% reduction in migraine days per month at 5.7-month follow-up.

The analysis revealed an association between nonresponder status and rs12615320-G in RAMP1, a gene that encodes a component of high-affinity CGRP receptors, which increased the risk for nonresponder status. The researchers also identified an association between nonresponder status and rs4680-A in COMT, a gene that has been associated with lower COMT enzymatic activity, chronic pain/fibromyalgia, and a "worrier" phenotype. Nonresponders also had a lower mean genetic risk score than responders. These genetic associations could help identify which patients would be most likely to benefit from anti-CGRP therapies.

Given that CGRP responsiveness may have a genetic component, it is possible that one of the contributors to the link between migraine and Parkinson's disease could lie in patients' genetic predisposition to CGRP activity. Yet, the association between these two common conditions is not thoroughly established, and the role of CGRP in the pathogenesis of Parkinson's disease is not fully validated. Nevertheless, the new developments in treatments that modify CGRP activity could have implications beyond migraine.

Additional References

1. Alexoudi A, Deftereos S. CGRP antagonists: side effects and potential Parkinson's disease development. Headache. 2020;60:789-790. doi: 10.1111/head.13770 Source

2. Blumenfeld A, Durham PL, Feoktistov A, et al. Hypervigilance, allostatic load, and migraine prevention: Antibodies to CGRP or receptor. Neurol Ther. 2021;10:469-497. doi:10.1007/s40120-021-00250-7 Source

Another study investigated the persistence of targeted therapies for PsA in women compared with men. In a nationwide cohort study using administrative information from French health insurance, the study looked at 14,778 patients (57% women) with PsA who were new users of targeted therapies. The study showed that women had 20%-40% lower treatment persistence rates than men for tumour necrosis factor (TNF) inhibitors (adjusted hazard ratio [aHR] 1.4; 99% CI 1.3-1.5) and interleukin (IL)-17 inhibitors (aHR 1.2; 99% CI 1.1-1.3). However, the treatment persistence between both sexes was comparable for IL-12/23 inhibitor (aHR 1.1; 99% CI 0.9-1.3), IL-23 inhibitor (aHR 1.1; 99% CI 0.7-1.5), and Janus kinase (JAK) inhibitor (aHR 1.2; 99% CI 0.9-1.6) therapies. The paradigm that women have lower treatment persistence is based on studies done primarily in patients treated with TNF inhibitors. This study and a few other recent studies challenge this paradigm by indicating that other targeted therapies, especially JAK inhibitors, may not have lower persistence in women. Sex should be taken into consideration while choosing and counseling women about PsA therapies.

There are few studies on exercise and its impact on PsA. Functional training (FT) and resistance training (RT) may improve functional capacity and quality of life of patients with PsA. The safety of exercise is also not known, given that (micro)trauma is a risk factor for PsA. To evaluate this, Silva and colleagues conducted a 12-week, single-blind trial including 41 patients with PsA who were randomly assigned to undergo FT with elastic bands or RT with weight machines. They demonstrated that FT and RT led to similar improvements in functional capacity measured by the Bath Ankylosing Spondylitis Functional Index (P = .919), functional status measured by the Health Assessment Questionnaire for Spondyloarthritis (P = .932), disease activity measured by the Bath Ankylosing Spondylitis Disease Activity Index (P = .700), and muscle strength. No adverse events occurred in either group. Thus, FT and RT improved functional capacity, functional status, disease activity, and muscle strength to a comparable extent in patients with PsA, with no adverse events. Both modalities may be recommended for PsA patients.

Finally, a cross-sectional study that included 503 patients with PsA, of whom 160 patients underwent treatment escalation, evaluated whether the patient-reported outcome (PsA Impact of Disease questionnaire [PsAID-12]) affected treatment decisions by the treating rheumatologist. Coyle and colleagues demonstrated that although PsAID-12 scores were higher in patients who did vs did not have a treatment escalation, physicians relied more on their assessment of disease activity rather than the PsAID-12 scores when making treatment-related decisions. Of note, physicians also reported that PsAID-12 scores influenced treatment reduction decisions.

Another study investigated the persistence of targeted therapies for PsA in women compared with men. In a nationwide cohort study using administrative information from French health insurance, the study looked at 14,778 patients (57% women) with PsA who were new users of targeted therapies. The study showed that women had 20%-40% lower treatment persistence rates than men for tumour necrosis factor (TNF) inhibitors (adjusted hazard ratio [aHR] 1.4; 99% CI 1.3-1.5) and interleukin (IL)-17 inhibitors (aHR 1.2; 99% CI 1.1-1.3). However, the treatment persistence between both sexes was comparable for IL-12/23 inhibitor (aHR 1.1; 99% CI 0.9-1.3), IL-23 inhibitor (aHR 1.1; 99% CI 0.7-1.5), and Janus kinase (JAK) inhibitor (aHR 1.2; 99% CI 0.9-1.6) therapies. The paradigm that women have lower treatment persistence is based on studies done primarily in patients treated with TNF inhibitors. This study and a few other recent studies challenge this paradigm by indicating that other targeted therapies, especially JAK inhibitors, may not have lower persistence in women. Sex should be taken into consideration while choosing and counseling women about PsA therapies.

There are few studies on exercise and its impact on PsA. Functional training (FT) and resistance training (RT) may improve functional capacity and quality of life of patients with PsA. The safety of exercise is also not known, given that (micro)trauma is a risk factor for PsA. To evaluate this, Silva and colleagues conducted a 12-week, single-blind trial including 41 patients with PsA who were randomly assigned to undergo FT with elastic bands or RT with weight machines. They demonstrated that FT and RT led to similar improvements in functional capacity measured by the Bath Ankylosing Spondylitis Functional Index (P = .919), functional status measured by the Health Assessment Questionnaire for Spondyloarthritis (P = .932), disease activity measured by the Bath Ankylosing Spondylitis Disease Activity Index (P = .700), and muscle strength. No adverse events occurred in either group. Thus, FT and RT improved functional capacity, functional status, disease activity, and muscle strength to a comparable extent in patients with PsA, with no adverse events. Both modalities may be recommended for PsA patients.

Finally, a cross-sectional study that included 503 patients with PsA, of whom 160 patients underwent treatment escalation, evaluated whether the patient-reported outcome (PsA Impact of Disease questionnaire [PsAID-12]) affected treatment decisions by the treating rheumatologist. Coyle and colleagues demonstrated that although PsAID-12 scores were higher in patients who did vs did not have a treatment escalation, physicians relied more on their assessment of disease activity rather than the PsAID-12 scores when making treatment-related decisions. Of note, physicians also reported that PsAID-12 scores influenced treatment reduction decisions.

Another study investigated the persistence of targeted therapies for PsA in women compared with men. In a nationwide cohort study using administrative information from French health insurance, the study looked at 14,778 patients (57% women) with PsA who were new users of targeted therapies. The study showed that women had 20%-40% lower treatment persistence rates than men for tumour necrosis factor (TNF) inhibitors (adjusted hazard ratio [aHR] 1.4; 99% CI 1.3-1.5) and interleukin (IL)-17 inhibitors (aHR 1.2; 99% CI 1.1-1.3). However, the treatment persistence between both sexes was comparable for IL-12/23 inhibitor (aHR 1.1; 99% CI 0.9-1.3), IL-23 inhibitor (aHR 1.1; 99% CI 0.7-1.5), and Janus kinase (JAK) inhibitor (aHR 1.2; 99% CI 0.9-1.6) therapies. The paradigm that women have lower treatment persistence is based on studies done primarily in patients treated with TNF inhibitors. This study and a few other recent studies challenge this paradigm by indicating that other targeted therapies, especially JAK inhibitors, may not have lower persistence in women. Sex should be taken into consideration while choosing and counseling women about PsA therapies.

There are few studies on exercise and its impact on PsA. Functional training (FT) and resistance training (RT) may improve functional capacity and quality of life of patients with PsA. The safety of exercise is also not known, given that (micro)trauma is a risk factor for PsA. To evaluate this, Silva and colleagues conducted a 12-week, single-blind trial including 41 patients with PsA who were randomly assigned to undergo FT with elastic bands or RT with weight machines. They demonstrated that FT and RT led to similar improvements in functional capacity measured by the Bath Ankylosing Spondylitis Functional Index (P = .919), functional status measured by the Health Assessment Questionnaire for Spondyloarthritis (P = .932), disease activity measured by the Bath Ankylosing Spondylitis Disease Activity Index (P = .700), and muscle strength. No adverse events occurred in either group. Thus, FT and RT improved functional capacity, functional status, disease activity, and muscle strength to a comparable extent in patients with PsA, with no adverse events. Both modalities may be recommended for PsA patients.

Finally, a cross-sectional study that included 503 patients with PsA, of whom 160 patients underwent treatment escalation, evaluated whether the patient-reported outcome (PsA Impact of Disease questionnaire [PsAID-12]) affected treatment decisions by the treating rheumatologist. Coyle and colleagues demonstrated that although PsAID-12 scores were higher in patients who did vs did not have a treatment escalation, physicians relied more on their assessment of disease activity rather than the PsAID-12 scores when making treatment-related decisions. Of note, physicians also reported that PsAID-12 scores influenced treatment reduction decisions.

The benefit of immunotherapy in combination with chemotherapy for programmed death–ligand 1–positive (PD-L1+) metastatic triple-negative breast cancer (mTNBC) has been shown in both the IMpassion130 and KEYNOTE-355 trials.^[2,3] However, the IMpassion131 trial, which evaluated atezolizumab plus paclitaxel, did not show a progression-free survival (PFS) or overall survival (OS) benefit vs paclitaxel alone in PD-L1+ mTNBC.^[4] Various explanations for these divergent results have been proposed, including the inherent properties of the chemotherapy backbone, patient populations, and the heterogenous nature of TNBC, which can affect response to immunotherapy. Of present, the various KEYNOTE-355 regimens (pembrolizumab plus investigator's choice chemotherapy [nab-paclitaxel, paclitaxel, or gemcitabine-carboplatin]) are US Food and Drug Administration approved for PD-L1+ mTNBC in the first-line setting. The phase 2 randomized TBCRC 043 trial investigated the effect of atezolizumab with carboplatin in patients with mTNBC and further looked at clinical and molecular correlates of response (Lehmann et al). A total of 106 patients were randomly assigned to carboplatin or carboplatin plus atezolizumab; the combination improved PFS (median PFS, 4.1 vs 2.2 mo; hazard ratio [HR] 0.66; P = .05) and OS (12.6 vs 8.6 mo; HR 0.60; P = .03). Grade 3/4 serious adverse events were more common with carboplatin-atezolizumab vs carboplatin alone (41% vs 8%). In addition, an association of better responses with PD-L1 immunotherapy was seen in patients with obesity, uncontrolled blood glucose levels, high tumor mutation burden, and increased tumor infiltrating lymphocytes. These data support the role of immunotherapy in mTNBC, highlight tumor heterogeneity within this subtype and encourage correlative studies to better define which patients benefit from immunotherapy.

Various studies have demonstrated the favorable impact of physical activity on breast cancer risk in postmenopausal women.^[5] However, data in premenopausal women is less clear. Various mechanisms connecting physical activity to premenopausal breast cancer risk have been proposed including the effect of exercise on sex steroid hormones, fasting insulin levels, and inflammation.^[6] A pooled analysis from 19 cohort studies including 547,601 premenopausal women, with 10,231 incident cases of breast cancer, aimed to examine the relationship between leisure-time physical activity (sports, exercise, recreational walking) and breast cancer risk in young women (Timmins et al). Higher (90th percentile) vs lower (10th percentile) levels of leisure-time physical activity were associated with a 10% reduction in breast cancer risk after adjustment for body mass index (BMI; adjusted HR 0.90; 95% CI 0.85-0.95; P < .001). They also found a significant reduction in risk: 32% (HR 0.68; P = .01) and 9% (HR 0.91; P = .005) for women with underweight (BMI < 18.5) and with average weight (BMI 18.5-24.9), respectively. Further, the effect of physical activity was most pronounced in the human epidermal growth factor receptor 2 (HER2)–enriched breast cancer subtype, wherein higher vs lower levels of activity were associated with an estimated 45% reduction in breast cancer risk (adjusted HR 0.55; 95% CI 0.37-0.82). These findings support the beneficial role of aerobic exercise and healthy body weight on breast cancer risk among premenopausal women and highlight the value of incorporating this information into counseling for our patients.

Additional References

1. Figueroa JD, Gierach GL, Duggan MA, et al. Risk factors for breast cancer development by tumor characteristics among women with benign breast disease. Breast Cancer Res. 2021;23:34. doi: 10.1186/s13058-021-01410-1 Source
2. Schmid P, Adams S, Rugo HS, et al, for the IMpassion130 Trial Investigators. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 2018;379:2108-2121. doi: 10.1056/nejmoa1809615 Source
3. Cortes J, Rugo HS, Cescon DW, et al, for the KEYNOTE-355 Investigators. Pembrolizumab plus chemotherapy in advanced triple-negative breast cancer. N Engl J Med. 2022;387:217-226. doi: 10.1056/NEJMoa2202809 Source
4. Miles D, Gligorov J, André F, et al, on behalf of the IMpassion131 investigators. Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. Ann Oncol. 2021;32:994-1004. doi: 10.1016/j.annonc.2021.05.801 Source
5. Eliassen AH, Hankinson SE, Rosner B, et al. Physical activity and risk of breast cancer among postmenopausal women. Arch Intern Med. 2010;170:1758-1764. doi: 10.1001/archinternmed.2010.363 Source
6. Swain CTV, Drummond AE, Boing L, et al. Linking physical activity to breast cancer via sex hormones, part 1: The effect of physical activity on sex steroid hormones. Cancer Epidemiol Biomarkers Prev. 2022;31:16-27. doi: 10.1158/1055-9965.EPI-21-0437 Source

The benefit of immunotherapy in combination with chemotherapy for programmed death–ligand 1–positive (PD-L1+) metastatic triple-negative breast cancer (mTNBC) has been shown in both the IMpassion130 and KEYNOTE-355 trials.^[2,3] However, the IMpassion131 trial, which evaluated atezolizumab plus paclitaxel, did not show a progression-free survival (PFS) or overall survival (OS) benefit vs paclitaxel alone in PD-L1+ mTNBC.^[4] Various explanations for these divergent results have been proposed, including the inherent properties of the chemotherapy backbone, patient populations, and the heterogenous nature of TNBC, which can affect response to immunotherapy. Of present, the various KEYNOTE-355 regimens (pembrolizumab plus investigator's choice chemotherapy [nab-paclitaxel, paclitaxel, or gemcitabine-carboplatin]) are US Food and Drug Administration approved for PD-L1+ mTNBC in the first-line setting. The phase 2 randomized TBCRC 043 trial investigated the effect of atezolizumab with carboplatin in patients with mTNBC and further looked at clinical and molecular correlates of response (Lehmann et al). A total of 106 patients were randomly assigned to carboplatin or carboplatin plus atezolizumab; the combination improved PFS (median PFS, 4.1 vs 2.2 mo; hazard ratio [HR] 0.66; P = .05) and OS (12.6 vs 8.6 mo; HR 0.60; P = .03). Grade 3/4 serious adverse events were more common with carboplatin-atezolizumab vs carboplatin alone (41% vs 8%). In addition, an association of better responses with PD-L1 immunotherapy was seen in patients with obesity, uncontrolled blood glucose levels, high tumor mutation burden, and increased tumor infiltrating lymphocytes. These data support the role of immunotherapy in mTNBC, highlight tumor heterogeneity within this subtype and encourage correlative studies to better define which patients benefit from immunotherapy.

Various studies have demonstrated the favorable impact of physical activity on breast cancer risk in postmenopausal women.^[5] However, data in premenopausal women is less clear. Various mechanisms connecting physical activity to premenopausal breast cancer risk have been proposed including the effect of exercise on sex steroid hormones, fasting insulin levels, and inflammation.^[6] A pooled analysis from 19 cohort studies including 547,601 premenopausal women, with 10,231 incident cases of breast cancer, aimed to examine the relationship between leisure-time physical activity (sports, exercise, recreational walking) and breast cancer risk in young women (Timmins et al). Higher (90th percentile) vs lower (10th percentile) levels of leisure-time physical activity were associated with a 10% reduction in breast cancer risk after adjustment for body mass index (BMI; adjusted HR 0.90; 95% CI 0.85-0.95; P < .001). They also found a significant reduction in risk: 32% (HR 0.68; P = .01) and 9% (HR 0.91; P = .005) for women with underweight (BMI < 18.5) and with average weight (BMI 18.5-24.9), respectively. Further, the effect of physical activity was most pronounced in the human epidermal growth factor receptor 2 (HER2)–enriched breast cancer subtype, wherein higher vs lower levels of activity were associated with an estimated 45% reduction in breast cancer risk (adjusted HR 0.55; 95% CI 0.37-0.82). These findings support the beneficial role of aerobic exercise and healthy body weight on breast cancer risk among premenopausal women and highlight the value of incorporating this information into counseling for our patients.

Additional References

1. Figueroa JD, Gierach GL, Duggan MA, et al. Risk factors for breast cancer development by tumor characteristics among women with benign breast disease. Breast Cancer Res. 2021;23:34. doi: 10.1186/s13058-021-01410-1 Source
2. Schmid P, Adams S, Rugo HS, et al, for the IMpassion130 Trial Investigators. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 2018;379:2108-2121. doi: 10.1056/nejmoa1809615 Source
3. Cortes J, Rugo HS, Cescon DW, et al, for the KEYNOTE-355 Investigators. Pembrolizumab plus chemotherapy in advanced triple-negative breast cancer. N Engl J Med. 2022;387:217-226. doi: 10.1056/NEJMoa2202809 Source
4. Miles D, Gligorov J, André F, et al, on behalf of the IMpassion131 investigators. Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. Ann Oncol. 2021;32:994-1004. doi: 10.1016/j.annonc.2021.05.801 Source
5. Eliassen AH, Hankinson SE, Rosner B, et al. Physical activity and risk of breast cancer among postmenopausal women. Arch Intern Med. 2010;170:1758-1764. doi: 10.1001/archinternmed.2010.363 Source
6. Swain CTV, Drummond AE, Boing L, et al. Linking physical activity to breast cancer via sex hormones, part 1: The effect of physical activity on sex steroid hormones. Cancer Epidemiol Biomarkers Prev. 2022;31:16-27. doi: 10.1158/1055-9965.EPI-21-0437 Source

The benefit of immunotherapy in combination with chemotherapy for programmed death–ligand 1–positive (PD-L1+) metastatic triple-negative breast cancer (mTNBC) has been shown in both the IMpassion130 and KEYNOTE-355 trials.^[2,3] However, the IMpassion131 trial, which evaluated atezolizumab plus paclitaxel, did not show a progression-free survival (PFS) or overall survival (OS) benefit vs paclitaxel alone in PD-L1+ mTNBC.^[4] Various explanations for these divergent results have been proposed, including the inherent properties of the chemotherapy backbone, patient populations, and the heterogenous nature of TNBC, which can affect response to immunotherapy. Of present, the various KEYNOTE-355 regimens (pembrolizumab plus investigator's choice chemotherapy [nab-paclitaxel, paclitaxel, or gemcitabine-carboplatin]) are US Food and Drug Administration approved for PD-L1+ mTNBC in the first-line setting. The phase 2 randomized TBCRC 043 trial investigated the effect of atezolizumab with carboplatin in patients with mTNBC and further looked at clinical and molecular correlates of response (Lehmann et al). A total of 106 patients were randomly assigned to carboplatin or carboplatin plus atezolizumab; the combination improved PFS (median PFS, 4.1 vs 2.2 mo; hazard ratio [HR] 0.66; P = .05) and OS (12.6 vs 8.6 mo; HR 0.60; P = .03). Grade 3/4 serious adverse events were more common with carboplatin-atezolizumab vs carboplatin alone (41% vs 8%). In addition, an association of better responses with PD-L1 immunotherapy was seen in patients with obesity, uncontrolled blood glucose levels, high tumor mutation burden, and increased tumor infiltrating lymphocytes. These data support the role of immunotherapy in mTNBC, highlight tumor heterogeneity within this subtype and encourage correlative studies to better define which patients benefit from immunotherapy.

Various studies have demonstrated the favorable impact of physical activity on breast cancer risk in postmenopausal women.^[5] However, data in premenopausal women is less clear. Various mechanisms connecting physical activity to premenopausal breast cancer risk have been proposed including the effect of exercise on sex steroid hormones, fasting insulin levels, and inflammation.^[6] A pooled analysis from 19 cohort studies including 547,601 premenopausal women, with 10,231 incident cases of breast cancer, aimed to examine the relationship between leisure-time physical activity (sports, exercise, recreational walking) and breast cancer risk in young women (Timmins et al). Higher (90th percentile) vs lower (10th percentile) levels of leisure-time physical activity were associated with a 10% reduction in breast cancer risk after adjustment for body mass index (BMI; adjusted HR 0.90; 95% CI 0.85-0.95; P < .001). They also found a significant reduction in risk: 32% (HR 0.68; P = .01) and 9% (HR 0.91; P = .005) for women with underweight (BMI < 18.5) and with average weight (BMI 18.5-24.9), respectively. Further, the effect of physical activity was most pronounced in the human epidermal growth factor receptor 2 (HER2)–enriched breast cancer subtype, wherein higher vs lower levels of activity were associated with an estimated 45% reduction in breast cancer risk (adjusted HR 0.55; 95% CI 0.37-0.82). These findings support the beneficial role of aerobic exercise and healthy body weight on breast cancer risk among premenopausal women and highlight the value of incorporating this information into counseling for our patients.

Additional References

1. Figueroa JD, Gierach GL, Duggan MA, et al. Risk factors for breast cancer development by tumor characteristics among women with benign breast disease. Breast Cancer Res. 2021;23:34. doi: 10.1186/s13058-021-01410-1 Source
2. Schmid P, Adams S, Rugo HS, et al, for the IMpassion130 Trial Investigators. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 2018;379:2108-2121. doi: 10.1056/nejmoa1809615 Source
3. Cortes J, Rugo HS, Cescon DW, et al, for the KEYNOTE-355 Investigators. Pembrolizumab plus chemotherapy in advanced triple-negative breast cancer. N Engl J Med. 2022;387:217-226. doi: 10.1056/NEJMoa2202809 Source
4. Miles D, Gligorov J, André F, et al, on behalf of the IMpassion131 investigators. Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. Ann Oncol. 2021;32:994-1004. doi: 10.1016/j.annonc.2021.05.801 Source
5. Eliassen AH, Hankinson SE, Rosner B, et al. Physical activity and risk of breast cancer among postmenopausal women. Arch Intern Med. 2010;170:1758-1764. doi: 10.1001/archinternmed.2010.363 Source
6. Swain CTV, Drummond AE, Boing L, et al. Linking physical activity to breast cancer via sex hormones, part 1: The effect of physical activity on sex steroid hormones. Cancer Epidemiol Biomarkers Prev. 2022;31:16-27. doi: 10.1158/1055-9965.EPI-21-0437 Source

TOPLINE:

Once-weekly insulin icodec shows a higher glycated A1c reduction than once-daily basal insulin analogs in patients with type 2 diabetes (T2D), without major safety concerns.

METHODOLOGY:

• A meta-analysis of five phase 3 ONWARDS randomized controlled trials included 3764 patients with T2D.
• The trials compared the effects of the weekly insulin icodec with those of the daily basal insulin analogs glargine and degludec over 26-78 months.
• The primary outcome was the change in A1c levels.
• Secondary outcomes included fasting plasma glucose levels, A1c levels < 7%, time in target glycemic range, body weight changes, insulin dose, hypoglycemia events, and adverse events.

TAKEAWAY:

• A1c levels < 7% were observed in a higher percentage of patients in the insulin icodec group than in the comparator group (odds ratio, 1.51; P = .004).
• In subgroup analyses, insulin icodec was superior to insulin degludec by several measures but comparatively similar to glargine.
• Insulin icodec was associated with no major safety concerns and had a slightly higher incidence of levels 1, 2, and combined 2/3 than degludec but no significant differences compared with glargine.

IN PRACTICE:

“Sustained glycemic control with once-weekly injections of insulin icodec would lead to better patient acceptance and treatment satisfaction,” the authors wrote.

SOURCE:

This study, authored by Sahana Shetty, MD, and Renuka Suvarna, MSc, Manipal Academy of Higher Education, Department of Endocrinology, Kasturba Medical College, Manipal, Karnataka, was published online on January 8, 2024, in Diabetes, Obesity and Metabolism.

LIMITATIONS:

The comparator group included individuals who used different basal insulin analogs. This heterogeneity in the comparator group introduced a potential source of variability, making it challenging to isolate the specific effects of insulin icodec compared with a standardized comparator. Blinding or masking of participants was performed in only one of the five trials.

DISCLOSURES:

The authors declared no conflicts of interest. All five clinical trials in the meta-analysis were sponsored by Novo Nordisk.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Once-weekly insulin icodec shows a higher glycated A1c reduction than once-daily basal insulin analogs in patients with type 2 diabetes (T2D), without major safety concerns.

METHODOLOGY:

• A meta-analysis of five phase 3 ONWARDS randomized controlled trials included 3764 patients with T2D.
• The trials compared the effects of the weekly insulin icodec with those of the daily basal insulin analogs glargine and degludec over 26-78 months.
• The primary outcome was the change in A1c levels.
• Secondary outcomes included fasting plasma glucose levels, A1c levels < 7%, time in target glycemic range, body weight changes, insulin dose, hypoglycemia events, and adverse events.

TAKEAWAY:

• A1c levels < 7% were observed in a higher percentage of patients in the insulin icodec group than in the comparator group (odds ratio, 1.51; P = .004).
• In subgroup analyses, insulin icodec was superior to insulin degludec by several measures but comparatively similar to glargine.
• Insulin icodec was associated with no major safety concerns and had a slightly higher incidence of levels 1, 2, and combined 2/3 than degludec but no significant differences compared with glargine.

IN PRACTICE:

“Sustained glycemic control with once-weekly injections of insulin icodec would lead to better patient acceptance and treatment satisfaction,” the authors wrote.

SOURCE:

This study, authored by Sahana Shetty, MD, and Renuka Suvarna, MSc, Manipal Academy of Higher Education, Department of Endocrinology, Kasturba Medical College, Manipal, Karnataka, was published online on January 8, 2024, in Diabetes, Obesity and Metabolism.

LIMITATIONS:

The comparator group included individuals who used different basal insulin analogs. This heterogeneity in the comparator group introduced a potential source of variability, making it challenging to isolate the specific effects of insulin icodec compared with a standardized comparator. Blinding or masking of participants was performed in only one of the five trials.

DISCLOSURES:

The authors declared no conflicts of interest. All five clinical trials in the meta-analysis were sponsored by Novo Nordisk.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Once-weekly insulin icodec shows a higher glycated A1c reduction than once-daily basal insulin analogs in patients with type 2 diabetes (T2D), without major safety concerns.

METHODOLOGY:

• A meta-analysis of five phase 3 ONWARDS randomized controlled trials included 3764 patients with T2D.
• The trials compared the effects of the weekly insulin icodec with those of the daily basal insulin analogs glargine and degludec over 26-78 months.
• The primary outcome was the change in A1c levels.
• Secondary outcomes included fasting plasma glucose levels, A1c levels < 7%, time in target glycemic range, body weight changes, insulin dose, hypoglycemia events, and adverse events.

TAKEAWAY:

• A1c levels < 7% were observed in a higher percentage of patients in the insulin icodec group than in the comparator group (odds ratio, 1.51; P = .004).
• In subgroup analyses, insulin icodec was superior to insulin degludec by several measures but comparatively similar to glargine.
• Insulin icodec was associated with no major safety concerns and had a slightly higher incidence of levels 1, 2, and combined 2/3 than degludec but no significant differences compared with glargine.

IN PRACTICE:

“Sustained glycemic control with once-weekly injections of insulin icodec would lead to better patient acceptance and treatment satisfaction,” the authors wrote.

SOURCE:

This study, authored by Sahana Shetty, MD, and Renuka Suvarna, MSc, Manipal Academy of Higher Education, Department of Endocrinology, Kasturba Medical College, Manipal, Karnataka, was published online on January 8, 2024, in Diabetes, Obesity and Metabolism.

LIMITATIONS:

The comparator group included individuals who used different basal insulin analogs. This heterogeneity in the comparator group introduced a potential source of variability, making it challenging to isolate the specific effects of insulin icodec compared with a standardized comparator. Blinding or masking of participants was performed in only one of the five trials.

DISCLOSURES:

The authors declared no conflicts of interest. All five clinical trials in the meta-analysis were sponsored by Novo Nordisk.
 

A version of this article appeared on Medscape.com.

But here's the thing: We should not be making clinical judgments on the basis of differences in relative risk; clinical decisions should be based on absolute risks. Should we worry about VTE risk when treating patients with AD? This paper did not focus on absolute risk, but we can get an idea of the absolute risk by looking at the data presented in the figures in the paper. The risk for VTE in patients without AD was about 1 in 400, whereas with AD the risk was about 1 in 300, even before controlling for risk factors. This rate is sufficiently low for both groups that it doesn't seem like this risk would affect whether we would use a drug that might be associated with some minimal or theoretical increased risk for VTE.

The bottom line is that the findings of this study are reassuring, at least to me.

I'm already convinced that dupilumab is a very safe treatment for our patients with AD. The study by Simpson and colleagues looked at data from a registry of patients followed in real-life practice. The 2-year study showed no new concerns for dupilumab treatment of AD. The most common adverse event was conjunctivitis, and that was seen in only 2.4% of the patients. Perhaps the most interesting finding was that 83% of the patients who started in the study were still on dupilumab treatment at the end of 2 years. Dupilumab has a good level of efficacy and safety such that the great majority of patients who start on it seem to do well.

Dupilumab is a highly effective, very safe treatment for AD. Rademikibart Is another interleukin-4 receptor alpha-chain blocker. Not surprisingly, rademikibart also seems to be an effective, safe treatment for AD (Silverberg et al). Rademikibart may serve as another option for AD, and I imagine that it could be used if a patient on dupilumab were to develop an anti-drug antibody and lose effectiveness.

The very interesting analysis by Silverberg and colleagues looks at a new way to compare the effectiveness of different drugs for AD. They use this new approach to compare upadacitinib and dupilumab. What they found, not surprisingly, was that upadacitinib was generally more effective for AD than dupilumab. I used to think I would never see anything more effective for AD than dupilumab, but, clearly, based on head-to-head trials, upadacitinib is more effective for AD than is dupilumab. But does that greater efficacy mean that we should use upadacitinib first? We need to consider safety, too. Dupilumab works well enough for the great majority of patients and is extremely safe. I think upadacitinib is a great choice for patients who did not respond to dupilumab and could also be considered for those patients who want to take the most effective treatment option.

Trimeche and colleagues' study of contact allergens in patients with AD may change how I practice. In this study, 60% of the AD patients had positive patch test results of which 71% were considered relevant. The most frequent allergens included textile dye mix (25%), nickel (20%), cobalt (13%), isothiazolinone (9%), quanterium-15 (4%), and balsam of Peru (4%). Two patients were allergic to corticosteroids. Avoidance of relevant allergens resulted in improvement. I need to warn my AD patients to be on the lookout for contact allergens that may be causing or exacerbating their skin disease.

But here's the thing: We should not be making clinical judgments on the basis of differences in relative risk; clinical decisions should be based on absolute risks. Should we worry about VTE risk when treating patients with AD? This paper did not focus on absolute risk, but we can get an idea of the absolute risk by looking at the data presented in the figures in the paper. The risk for VTE in patients without AD was about 1 in 400, whereas with AD the risk was about 1 in 300, even before controlling for risk factors. This rate is sufficiently low for both groups that it doesn't seem like this risk would affect whether we would use a drug that might be associated with some minimal or theoretical increased risk for VTE.

The bottom line is that the findings of this study are reassuring, at least to me.

I'm already convinced that dupilumab is a very safe treatment for our patients with AD. The study by Simpson and colleagues looked at data from a registry of patients followed in real-life practice. The 2-year study showed no new concerns for dupilumab treatment of AD. The most common adverse event was conjunctivitis, and that was seen in only 2.4% of the patients. Perhaps the most interesting finding was that 83% of the patients who started in the study were still on dupilumab treatment at the end of 2 years. Dupilumab has a good level of efficacy and safety such that the great majority of patients who start on it seem to do well.

Dupilumab is a highly effective, very safe treatment for AD. Rademikibart Is another interleukin-4 receptor alpha-chain blocker. Not surprisingly, rademikibart also seems to be an effective, safe treatment for AD (Silverberg et al). Rademikibart may serve as another option for AD, and I imagine that it could be used if a patient on dupilumab were to develop an anti-drug antibody and lose effectiveness.

The very interesting analysis by Silverberg and colleagues looks at a new way to compare the effectiveness of different drugs for AD. They use this new approach to compare upadacitinib and dupilumab. What they found, not surprisingly, was that upadacitinib was generally more effective for AD than dupilumab. I used to think I would never see anything more effective for AD than dupilumab, but, clearly, based on head-to-head trials, upadacitinib is more effective for AD than is dupilumab. But does that greater efficacy mean that we should use upadacitinib first? We need to consider safety, too. Dupilumab works well enough for the great majority of patients and is extremely safe. I think upadacitinib is a great choice for patients who did not respond to dupilumab and could also be considered for those patients who want to take the most effective treatment option.

Trimeche and colleagues' study of contact allergens in patients with AD may change how I practice. In this study, 60% of the AD patients had positive patch test results of which 71% were considered relevant. The most frequent allergens included textile dye mix (25%), nickel (20%), cobalt (13%), isothiazolinone (9%), quanterium-15 (4%), and balsam of Peru (4%). Two patients were allergic to corticosteroids. Avoidance of relevant allergens resulted in improvement. I need to warn my AD patients to be on the lookout for contact allergens that may be causing or exacerbating their skin disease.

But here's the thing: We should not be making clinical judgments on the basis of differences in relative risk; clinical decisions should be based on absolute risks. Should we worry about VTE risk when treating patients with AD? This paper did not focus on absolute risk, but we can get an idea of the absolute risk by looking at the data presented in the figures in the paper. The risk for VTE in patients without AD was about 1 in 400, whereas with AD the risk was about 1 in 300, even before controlling for risk factors. This rate is sufficiently low for both groups that it doesn't seem like this risk would affect whether we would use a drug that might be associated with some minimal or theoretical increased risk for VTE.

The bottom line is that the findings of this study are reassuring, at least to me.

I'm already convinced that dupilumab is a very safe treatment for our patients with AD. The study by Simpson and colleagues looked at data from a registry of patients followed in real-life practice. The 2-year study showed no new concerns for dupilumab treatment of AD. The most common adverse event was conjunctivitis, and that was seen in only 2.4% of the patients. Perhaps the most interesting finding was that 83% of the patients who started in the study were still on dupilumab treatment at the end of 2 years. Dupilumab has a good level of efficacy and safety such that the great majority of patients who start on it seem to do well.

Dupilumab is a highly effective, very safe treatment for AD. Rademikibart Is another interleukin-4 receptor alpha-chain blocker. Not surprisingly, rademikibart also seems to be an effective, safe treatment for AD (Silverberg et al). Rademikibart may serve as another option for AD, and I imagine that it could be used if a patient on dupilumab were to develop an anti-drug antibody and lose effectiveness.

The very interesting analysis by Silverberg and colleagues looks at a new way to compare the effectiveness of different drugs for AD. They use this new approach to compare upadacitinib and dupilumab. What they found, not surprisingly, was that upadacitinib was generally more effective for AD than dupilumab. I used to think I would never see anything more effective for AD than dupilumab, but, clearly, based on head-to-head trials, upadacitinib is more effective for AD than is dupilumab. But does that greater efficacy mean that we should use upadacitinib first? We need to consider safety, too. Dupilumab works well enough for the great majority of patients and is extremely safe. I think upadacitinib is a great choice for patients who did not respond to dupilumab and could also be considered for those patients who want to take the most effective treatment option.

Trimeche and colleagues' study of contact allergens in patients with AD may change how I practice. In this study, 60% of the AD patients had positive patch test results of which 71% were considered relevant. The most frequent allergens included textile dye mix (25%), nickel (20%), cobalt (13%), isothiazolinone (9%), quanterium-15 (4%), and balsam of Peru (4%). Two patients were allergic to corticosteroids. Avoidance of relevant allergens resulted in improvement. I need to warn my AD patients to be on the lookout for contact allergens that may be causing or exacerbating their skin disease.

Key clinical point: Patients with migraine initiating calcitonin gene-related peptide (CGRP) monoclonal antibody treatment with galcanezumab showed higher treatment persistence, lower treatment discontinuation, and similar adherence compared with those initiating fremanezumab or erenumab.

Major finding: Compared with fremanezumab, galcanezumab initiators showed higher rates of treatment persistence (P = .001) and lower treatment discontinuation (P = .005). Compared with erenumab, galcanezumab initiators had lower treatment discontinuation (P = .040). Patient adherence was similar among those who initiated galcanezumab vs fremanezumab or erenumab.

Study details: This retrospective real-world study included patients with migraine initiating galcanezumab treatment who were matched with those initiating fremanezumab (n = 2674) or erenumab (n = 3503) treatment using propensity score matching.

Disclosures: This study was funded by Eli Lilly and Company. The authors declared no conflicts of interest.

Source: Varnado OJ et al. Comparison of treatment patterns in patients with migraine initiating calcitonin gene-related peptide monoclonal antibodies: A Retrospective Real-World US Study. Patient Preference and Adherence. 2024;18:69-88 (Jan 9). doi: 10.2147/PPA.S437396

Key clinical point: Patients with migraine initiating calcitonin gene-related peptide (CGRP) monoclonal antibody treatment with galcanezumab showed higher treatment persistence, lower treatment discontinuation, and similar adherence compared with those initiating fremanezumab or erenumab.

Major finding: Compared with fremanezumab, galcanezumab initiators showed higher rates of treatment persistence (P = .001) and lower treatment discontinuation (P = .005). Compared with erenumab, galcanezumab initiators had lower treatment discontinuation (P = .040). Patient adherence was similar among those who initiated galcanezumab vs fremanezumab or erenumab.

Study details: This retrospective real-world study included patients with migraine initiating galcanezumab treatment who were matched with those initiating fremanezumab (n = 2674) or erenumab (n = 3503) treatment using propensity score matching.

Disclosures: This study was funded by Eli Lilly and Company. The authors declared no conflicts of interest.

Source: Varnado OJ et al. Comparison of treatment patterns in patients with migraine initiating calcitonin gene-related peptide monoclonal antibodies: A Retrospective Real-World US Study. Patient Preference and Adherence. 2024;18:69-88 (Jan 9). doi: 10.2147/PPA.S437396

Key clinical point: Patients with migraine initiating calcitonin gene-related peptide (CGRP) monoclonal antibody treatment with galcanezumab showed higher treatment persistence, lower treatment discontinuation, and similar adherence compared with those initiating fremanezumab or erenumab.

Major finding: Compared with fremanezumab, galcanezumab initiators showed higher rates of treatment persistence (P = .001) and lower treatment discontinuation (P = .005). Compared with erenumab, galcanezumab initiators had lower treatment discontinuation (P = .040). Patient adherence was similar among those who initiated galcanezumab vs fremanezumab or erenumab.

Study details: This retrospective real-world study included patients with migraine initiating galcanezumab treatment who were matched with those initiating fremanezumab (n = 2674) or erenumab (n = 3503) treatment using propensity score matching.

Disclosures: This study was funded by Eli Lilly and Company. The authors declared no conflicts of interest.

Source: Varnado OJ et al. Comparison of treatment patterns in patients with migraine initiating calcitonin gene-related peptide monoclonal antibodies: A Retrospective Real-World US Study. Patient Preference and Adherence. 2024;18:69-88 (Jan 9). doi: 10.2147/PPA.S437396

Key clinical point: Patients with episodic migraine without aura (EMoA) presented a higher delayed discounting rate, which was positively associated with the migraine history.

Major finding: Patients with EMoA vs control individuals showed a significantly higher subjective discount rate (F = 4.74; P = .032), which was positively correlated with migraine history (r = 0.742; P < .001). The resting-state functional connectivity between the left ventral striatum and middle occipital gyrus was significantly associated with migraine history (r′ = 0.294; P = .036) and subjective discount rate (r′ = 0.380; P = .006).

Study details: This study included 51 patients with EMoA and 45 control individuals who underwent task-based and multi-model magnetic resonance imaging.

Disclosures: This study was supported by the National Natural Science Foundation of China, Foundation for the Cultivation of Doctoral Research Talents, and the 2021 Youth Foundation Training Program of the First Affiliated Hospital of Anhui Medical University. The authors declared no conflicts of interest.

Source: Wang L et al. Patients with episodic migraine without aura have an increased rate of delayed discounting. Brain Behav. 2024;14(1):e3367 (Jan 2). doi: 10.1002/brb3.3367

Key clinical point: Patients with episodic migraine without aura (EMoA) presented a higher delayed discounting rate, which was positively associated with the migraine history.

Major finding: Patients with EMoA vs control individuals showed a significantly higher subjective discount rate (F = 4.74; P = .032), which was positively correlated with migraine history (r = 0.742; P < .001). The resting-state functional connectivity between the left ventral striatum and middle occipital gyrus was significantly associated with migraine history (r′ = 0.294; P = .036) and subjective discount rate (r′ = 0.380; P = .006).

Study details: This study included 51 patients with EMoA and 45 control individuals who underwent task-based and multi-model magnetic resonance imaging.

Disclosures: This study was supported by the National Natural Science Foundation of China, Foundation for the Cultivation of Doctoral Research Talents, and the 2021 Youth Foundation Training Program of the First Affiliated Hospital of Anhui Medical University. The authors declared no conflicts of interest.

Source: Wang L et al. Patients with episodic migraine without aura have an increased rate of delayed discounting. Brain Behav. 2024;14(1):e3367 (Jan 2). doi: 10.1002/brb3.3367

Key clinical point: Patients with episodic migraine without aura (EMoA) presented a higher delayed discounting rate, which was positively associated with the migraine history.

Major finding: Patients with EMoA vs control individuals showed a significantly higher subjective discount rate (F = 4.74; P = .032), which was positively correlated with migraine history (r = 0.742; P < .001). The resting-state functional connectivity between the left ventral striatum and middle occipital gyrus was significantly associated with migraine history (r′ = 0.294; P = .036) and subjective discount rate (r′ = 0.380; P = .006).

Study details: This study included 51 patients with EMoA and 45 control individuals who underwent task-based and multi-model magnetic resonance imaging.

Disclosures: This study was supported by the National Natural Science Foundation of China, Foundation for the Cultivation of Doctoral Research Talents, and the 2021 Youth Foundation Training Program of the First Affiliated Hospital of Anhui Medical University. The authors declared no conflicts of interest.

Source: Wang L et al. Patients with episodic migraine without aura have an increased rate of delayed discounting. Brain Behav. 2024;14(1):e3367 (Jan 2). doi: 10.1002/brb3.3367

Key clinical point: Patients with migraine have increased risk for incident Parkinson's disease (PD), with younger age and underlying dyslipidemia aggravating the risk for PD among women and men with migraine, respectively.

Major finding: The risk of incident PD was 1.35-fold (adjusted hazard ratio 1.35; 95% CI 1.29-1.41) higher in patients with vs without migraine, with the risk of PD being significantly higher among younger vs older women (age < 65 years vs ≥ 65 years; P = .038) and men with vs without dyslipidemia (P = .012).

Study details: This retrospective, nationwide, population-based cohort study included 214,193 individuals with migraine and 5,879,711 individuals without migraine, of whom 1973 (0.92%) and 30,664 (0.52%) individuals with and without migraine, respectively, were diagnosed with PD.

Disclosures: This research was supported by a grant from the National Research Foundation, Technology Development Program, and Technology Innovation Program. Korea. The authors declared no conflicts of interest.

Source: Ha WS et al. The association between migraine and Parkinson's disease: A nationwide cohort study. Epidemiol Health. 2023 (Dec 18). doi: 10.4178/epih.e2024010

Key clinical point: Patients with migraine have increased risk for incident Parkinson's disease (PD), with younger age and underlying dyslipidemia aggravating the risk for PD among women and men with migraine, respectively.

Major finding: The risk of incident PD was 1.35-fold (adjusted hazard ratio 1.35; 95% CI 1.29-1.41) higher in patients with vs without migraine, with the risk of PD being significantly higher among younger vs older women (age < 65 years vs ≥ 65 years; P = .038) and men with vs without dyslipidemia (P = .012).

Study details: This retrospective, nationwide, population-based cohort study included 214,193 individuals with migraine and 5,879,711 individuals without migraine, of whom 1973 (0.92%) and 30,664 (0.52%) individuals with and without migraine, respectively, were diagnosed with PD.

Disclosures: This research was supported by a grant from the National Research Foundation, Technology Development Program, and Technology Innovation Program. Korea. The authors declared no conflicts of interest.

Source: Ha WS et al. The association between migraine and Parkinson's disease: A nationwide cohort study. Epidemiol Health. 2023 (Dec 18). doi: 10.4178/epih.e2024010

Key clinical point: Patients with migraine have increased risk for incident Parkinson's disease (PD), with younger age and underlying dyslipidemia aggravating the risk for PD among women and men with migraine, respectively.

Major finding: The risk of incident PD was 1.35-fold (adjusted hazard ratio 1.35; 95% CI 1.29-1.41) higher in patients with vs without migraine, with the risk of PD being significantly higher among younger vs older women (age < 65 years vs ≥ 65 years; P = .038) and men with vs without dyslipidemia (P = .012).

Study details: This retrospective, nationwide, population-based cohort study included 214,193 individuals with migraine and 5,879,711 individuals without migraine, of whom 1973 (0.92%) and 30,664 (0.52%) individuals with and without migraine, respectively, were diagnosed with PD.

Disclosures: This research was supported by a grant from the National Research Foundation, Technology Development Program, and Technology Innovation Program. Korea. The authors declared no conflicts of interest.

Source: Ha WS et al. The association between migraine and Parkinson's disease: A nationwide cohort study. Epidemiol Health. 2023 (Dec 18). doi: 10.4178/epih.e2024010