Clinical Edge Journal Scan

Most practitioners recommend a host of non-medical therapeutic options to their patients with migraine. The best studied and safest, most effective supplements remain magnesium, riboflavin/B₂, and CoQ10. Alpha-lipoic acid (ALA) is a supplement with both antioxidant and anti-inflammatory effects that has showed positive protective effects in a number of medical conditions, including diabetes and episodes of oxidative stress. One migraine study¹ evaluated serum ALA levels and found over 90% of people with migraine to deficient. This study sought to observe the potential benefit of supplementation with ALA in patients with episodic migraine.

This was a randomized, double-blind placebo-controlled trial over the course of 3 months. In this study, 92 female subjects with episodic migraine (defined as experiencing >2 but <15 days of headache per month) were recruited and randomized to receiving 300 mg ALA twice daily or placebo. Patients with chronic migraine, in menopause, pregnant, or lactating were excluded, as were patients with the presence of other chronic medical issues, or patients who had taken antioxidant supplements in the previous 4 months.

The primary outcomes of migraine severity, frequency, and Headache Impact Test (HIT-6) score were found to be significantly improved in the intervention group; duration of headache was not significantly different. Biochemical analysis of the two groups did show a difference in the lactate level of the intervention group, and this was considered a secondary outcome. Relevant side effects were primarily gastrointestinal, including stomach pain (higher in the placebo group), increased appetite, and constipation.

There is a great interest in finding effective non-medical treatments for migraine. These are frequently used as an adjunct to other preventive medications, or potentially as a stand-alone treatment for low frequency migraine. Many patients prefer non-medical options as well, and unfortunately many of the treatments they read about online or in less scientific spaces are unproven or unsafe. Supplementation remains an important part of migraine treatment for many practitioners and patients.

This study argues that ALA can be considered a safe and effective treatment for episodic migraine. When patients ask about non-medical options, ALA can be an additional treatment worth considering. Many patients are already taking multiple supplements before seeing their specialist, and this article  informs us that there may be some treatment benefit for this supplement as well. We may not be recommending this supplement alone as a preventive treatment for migraine, but we can add a new non-medical option to consider to our mix.

Using preventive medication in pediatrics is now more controversial than it had been previously. The well known The Childhood and Adolescent Migraine Prevention (CHAMP) trial² surprised many in the field by revealing that were no significant differences in headache frequency or disability when comparing children with migraine who received preventive medications or placebo. The CHAMP trial spotlighted the effect of non-medical therapies (cognitive behavioral therapy, biofeedback) and education. Many pediatric specialists have altered their practice paradigm in response to these results and have been more reticent to prescribe preventive medications for children with migraine. This is due to concern for potential side effects in light of the absence of direct benefit.

In an observational study of pediatric migraine,³ the investigators followed 186 children with migraine over a 3-year period to determine if the use of a number of preventive medications addresses disability (measured by Pediatric Migraine Disability Assessment [PedMIDAS]) as well as frequency, severity and duration of migraine. Other bothersome features of migraine were followed including the presence of nausea, vomiting, photophobia, analgesic use, and the side effects of the preventive medication.

The preventive medications used were cyproheptadine, flunarazine, propranolol, and topiramate—all at weight based doses. It is important to note that amitriptyline was not used in the study and there was no placebo group. This was a Turkish population, the median age was 14, and 63% were female, all of which are appropriate for a pediatric migraine study. Treatment efficacy was defined as a 50% reduction of symptoms. This was achieved in 90% of subjects in the topiramate group, 75% in the propranolol group, and 52-53% in the flunarazine and cyproheptadine groups.

Medication side effects were divided into minor or significant side effects. The only significant side effect noted was 3% of patient with palpitations; minor side effects were changes in appetite and drowsiness. More than half (57%) of patients taking topiramate experienced some side effect, 51% of the cyproheptadine group did as well, and the propranolol and flunarazine groups were noted to have side effects in 22% and 13%, respectively. Overall, 31.7% of patients had some side effect.  

PedMIDAS scores improved significantly with the use of preventive medications; migraine frequency improved significantly as well, especially in the topiramate group. This study argues for the use of preventive medications in pediatric migraine. One of the most commonly used medications for migraine prevention was not investigated unfortunately. Amitriptyline is widely considered a safe and effective migraine prophylactic medication, especially at low doses. One important takeaway is the frequency of side effects at all, and especially with topiramate. It is unclear how many patients stopped their preventive medications due to a side effect. In light of this study, propranolol, which is often overlooked, might be considered a better choice for children with migraine.

Most of the patients with migraine we see are in their most productive years. Migraine disability can be a major difficulty for our patients, especially as it relates to work. The American Migraine Foundation and American Headache Society have both recently taken on initiatives that relate to migraine in the workplace. Migraine epidemiologic studies have shown that people with migraine are more likely to experience a negative impact on their careers, and migraine disability scores weigh time absent from work as well as lower function at work. Many people with migraine are concerned that having migraine may hold them back from being hired or achieving promotion.

Autio et al performed a retrospective analysis of occupationally active patients treated at a single provider (the Finnish health clinic Terveystalo).⁴ The authors first looked for erenumab responders, who they defined as patients who received two prescriptions for erenumab and no other calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) medication. These patients were followed for 12 months, and their data was compared to the 12-month period prior to initiating erenumab. The authors evaluated headache-related sick days, all-cause sick days, healthcare visits, and prescriptions for all medications based on a registry. This registry also provided an age- and sex-matched control group of patients with migraine not taking any CGRP mAb medication.

A total of 162 patients were included, 82 in the erenumab responder group.  Headache-related sick days decreased by 74%, and headache-related healthcare visits decreased by 44%. Triptan prescription use decreased by 31.5%; all-cause sick days and healthcare visits differences were not statistically significant.

Prevention remains key in improving our patients’ quality of life and a large factor in this is their work life. This study shows that intervention with erenumab significantly decreases migraine-related absenteeism. It could be argued that the other CGRP mAb medications may have the same effect, as can many other preventive therapies. It can also be argued that even with this data we can only assume that patients function better at work with preventive therapies. Further studies will also look at the degree that “presenteeism” plays in the workplace—people who show up to work but are functioning at a lesser extent due to migraine. That said, this is an important step towards recognizing the burden migraine disability has on our patients’ work life, and the extent that prevention can improve their quality of life.

References

1. Kelishadi MR et al. The beneficial effect of Alpha-lipoic acid supplementation as a potential adjunct treatment in episodic migraines. Sci Rep. 2022;12:271 (Jan 7).
2. Powers SW et al. Trial of amitriptyline, topiramate, and placebo for pediatric migraine.  N Engl  J Med. 2017;376(2):115-124. Doi: 10.1056/NEJMoa1610384.
3. Tekin H, Edem P. Effects and side effects of migraine prophylaxis in children. Pediatr Int. 2021 (Dec 14).

1. Autio H et al. Erenumab decreases headache-related sick leave days and health care visits: a retrospective real-world study in working patients with migraine. Neurol Ther. 2021 (Dec 10).

Most practitioners recommend a host of non-medical therapeutic options to their patients with migraine. The best studied and safest, most effective supplements remain magnesium, riboflavin/B₂, and CoQ10. Alpha-lipoic acid (ALA) is a supplement with both antioxidant and anti-inflammatory effects that has showed positive protective effects in a number of medical conditions, including diabetes and episodes of oxidative stress. One migraine study¹ evaluated serum ALA levels and found over 90% of people with migraine to deficient. This study sought to observe the potential benefit of supplementation with ALA in patients with episodic migraine.

This was a randomized, double-blind placebo-controlled trial over the course of 3 months. In this study, 92 female subjects with episodic migraine (defined as experiencing >2 but <15 days of headache per month) were recruited and randomized to receiving 300 mg ALA twice daily or placebo. Patients with chronic migraine, in menopause, pregnant, or lactating were excluded, as were patients with the presence of other chronic medical issues, or patients who had taken antioxidant supplements in the previous 4 months.

The primary outcomes of migraine severity, frequency, and Headache Impact Test (HIT-6) score were found to be significantly improved in the intervention group; duration of headache was not significantly different. Biochemical analysis of the two groups did show a difference in the lactate level of the intervention group, and this was considered a secondary outcome. Relevant side effects were primarily gastrointestinal, including stomach pain (higher in the placebo group), increased appetite, and constipation.

There is a great interest in finding effective non-medical treatments for migraine. These are frequently used as an adjunct to other preventive medications, or potentially as a stand-alone treatment for low frequency migraine. Many patients prefer non-medical options as well, and unfortunately many of the treatments they read about online or in less scientific spaces are unproven or unsafe. Supplementation remains an important part of migraine treatment for many practitioners and patients.

This study argues that ALA can be considered a safe and effective treatment for episodic migraine. When patients ask about non-medical options, ALA can be an additional treatment worth considering. Many patients are already taking multiple supplements before seeing their specialist, and this article  informs us that there may be some treatment benefit for this supplement as well. We may not be recommending this supplement alone as a preventive treatment for migraine, but we can add a new non-medical option to consider to our mix.

Using preventive medication in pediatrics is now more controversial than it had been previously. The well known The Childhood and Adolescent Migraine Prevention (CHAMP) trial² surprised many in the field by revealing that were no significant differences in headache frequency or disability when comparing children with migraine who received preventive medications or placebo. The CHAMP trial spotlighted the effect of non-medical therapies (cognitive behavioral therapy, biofeedback) and education. Many pediatric specialists have altered their practice paradigm in response to these results and have been more reticent to prescribe preventive medications for children with migraine. This is due to concern for potential side effects in light of the absence of direct benefit.

In an observational study of pediatric migraine,³ the investigators followed 186 children with migraine over a 3-year period to determine if the use of a number of preventive medications addresses disability (measured by Pediatric Migraine Disability Assessment [PedMIDAS]) as well as frequency, severity and duration of migraine. Other bothersome features of migraine were followed including the presence of nausea, vomiting, photophobia, analgesic use, and the side effects of the preventive medication.

The preventive medications used were cyproheptadine, flunarazine, propranolol, and topiramate—all at weight based doses. It is important to note that amitriptyline was not used in the study and there was no placebo group. This was a Turkish population, the median age was 14, and 63% were female, all of which are appropriate for a pediatric migraine study. Treatment efficacy was defined as a 50% reduction of symptoms. This was achieved in 90% of subjects in the topiramate group, 75% in the propranolol group, and 52-53% in the flunarazine and cyproheptadine groups.

Medication side effects were divided into minor or significant side effects. The only significant side effect noted was 3% of patient with palpitations; minor side effects were changes in appetite and drowsiness. More than half (57%) of patients taking topiramate experienced some side effect, 51% of the cyproheptadine group did as well, and the propranolol and flunarazine groups were noted to have side effects in 22% and 13%, respectively. Overall, 31.7% of patients had some side effect.  

PedMIDAS scores improved significantly with the use of preventive medications; migraine frequency improved significantly as well, especially in the topiramate group. This study argues for the use of preventive medications in pediatric migraine. One of the most commonly used medications for migraine prevention was not investigated unfortunately. Amitriptyline is widely considered a safe and effective migraine prophylactic medication, especially at low doses. One important takeaway is the frequency of side effects at all, and especially with topiramate. It is unclear how many patients stopped their preventive medications due to a side effect. In light of this study, propranolol, which is often overlooked, might be considered a better choice for children with migraine.

Most of the patients with migraine we see are in their most productive years. Migraine disability can be a major difficulty for our patients, especially as it relates to work. The American Migraine Foundation and American Headache Society have both recently taken on initiatives that relate to migraine in the workplace. Migraine epidemiologic studies have shown that people with migraine are more likely to experience a negative impact on their careers, and migraine disability scores weigh time absent from work as well as lower function at work. Many people with migraine are concerned that having migraine may hold them back from being hired or achieving promotion.

Autio et al performed a retrospective analysis of occupationally active patients treated at a single provider (the Finnish health clinic Terveystalo).⁴ The authors first looked for erenumab responders, who they defined as patients who received two prescriptions for erenumab and no other calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) medication. These patients were followed for 12 months, and their data was compared to the 12-month period prior to initiating erenumab. The authors evaluated headache-related sick days, all-cause sick days, healthcare visits, and prescriptions for all medications based on a registry. This registry also provided an age- and sex-matched control group of patients with migraine not taking any CGRP mAb medication.

A total of 162 patients were included, 82 in the erenumab responder group.  Headache-related sick days decreased by 74%, and headache-related healthcare visits decreased by 44%. Triptan prescription use decreased by 31.5%; all-cause sick days and healthcare visits differences were not statistically significant.

Prevention remains key in improving our patients’ quality of life and a large factor in this is their work life. This study shows that intervention with erenumab significantly decreases migraine-related absenteeism. It could be argued that the other CGRP mAb medications may have the same effect, as can many other preventive therapies. It can also be argued that even with this data we can only assume that patients function better at work with preventive therapies. Further studies will also look at the degree that “presenteeism” plays in the workplace—people who show up to work but are functioning at a lesser extent due to migraine. That said, this is an important step towards recognizing the burden migraine disability has on our patients’ work life, and the extent that prevention can improve their quality of life.

References

1. Kelishadi MR et al. The beneficial effect of Alpha-lipoic acid supplementation as a potential adjunct treatment in episodic migraines. Sci Rep. 2022;12:271 (Jan 7).
2. Powers SW et al. Trial of amitriptyline, topiramate, and placebo for pediatric migraine.  N Engl  J Med. 2017;376(2):115-124. Doi: 10.1056/NEJMoa1610384.
3. Tekin H, Edem P. Effects and side effects of migraine prophylaxis in children. Pediatr Int. 2021 (Dec 14).

1. Autio H et al. Erenumab decreases headache-related sick leave days and health care visits: a retrospective real-world study in working patients with migraine. Neurol Ther. 2021 (Dec 10).

Most practitioners recommend a host of non-medical therapeutic options to their patients with migraine. The best studied and safest, most effective supplements remain magnesium, riboflavin/B₂, and CoQ10. Alpha-lipoic acid (ALA) is a supplement with both antioxidant and anti-inflammatory effects that has showed positive protective effects in a number of medical conditions, including diabetes and episodes of oxidative stress. One migraine study¹ evaluated serum ALA levels and found over 90% of people with migraine to deficient. This study sought to observe the potential benefit of supplementation with ALA in patients with episodic migraine.

This was a randomized, double-blind placebo-controlled trial over the course of 3 months. In this study, 92 female subjects with episodic migraine (defined as experiencing >2 but <15 days of headache per month) were recruited and randomized to receiving 300 mg ALA twice daily or placebo. Patients with chronic migraine, in menopause, pregnant, or lactating were excluded, as were patients with the presence of other chronic medical issues, or patients who had taken antioxidant supplements in the previous 4 months.

The primary outcomes of migraine severity, frequency, and Headache Impact Test (HIT-6) score were found to be significantly improved in the intervention group; duration of headache was not significantly different. Biochemical analysis of the two groups did show a difference in the lactate level of the intervention group, and this was considered a secondary outcome. Relevant side effects were primarily gastrointestinal, including stomach pain (higher in the placebo group), increased appetite, and constipation.

There is a great interest in finding effective non-medical treatments for migraine. These are frequently used as an adjunct to other preventive medications, or potentially as a stand-alone treatment for low frequency migraine. Many patients prefer non-medical options as well, and unfortunately many of the treatments they read about online or in less scientific spaces are unproven or unsafe. Supplementation remains an important part of migraine treatment for many practitioners and patients.

This study argues that ALA can be considered a safe and effective treatment for episodic migraine. When patients ask about non-medical options, ALA can be an additional treatment worth considering. Many patients are already taking multiple supplements before seeing their specialist, and this article  informs us that there may be some treatment benefit for this supplement as well. We may not be recommending this supplement alone as a preventive treatment for migraine, but we can add a new non-medical option to consider to our mix.

Using preventive medication in pediatrics is now more controversial than it had been previously. The well known The Childhood and Adolescent Migraine Prevention (CHAMP) trial² surprised many in the field by revealing that were no significant differences in headache frequency or disability when comparing children with migraine who received preventive medications or placebo. The CHAMP trial spotlighted the effect of non-medical therapies (cognitive behavioral therapy, biofeedback) and education. Many pediatric specialists have altered their practice paradigm in response to these results and have been more reticent to prescribe preventive medications for children with migraine. This is due to concern for potential side effects in light of the absence of direct benefit.

In an observational study of pediatric migraine,³ the investigators followed 186 children with migraine over a 3-year period to determine if the use of a number of preventive medications addresses disability (measured by Pediatric Migraine Disability Assessment [PedMIDAS]) as well as frequency, severity and duration of migraine. Other bothersome features of migraine were followed including the presence of nausea, vomiting, photophobia, analgesic use, and the side effects of the preventive medication.

The preventive medications used were cyproheptadine, flunarazine, propranolol, and topiramate—all at weight based doses. It is important to note that amitriptyline was not used in the study and there was no placebo group. This was a Turkish population, the median age was 14, and 63% were female, all of which are appropriate for a pediatric migraine study. Treatment efficacy was defined as a 50% reduction of symptoms. This was achieved in 90% of subjects in the topiramate group, 75% in the propranolol group, and 52-53% in the flunarazine and cyproheptadine groups.

Medication side effects were divided into minor or significant side effects. The only significant side effect noted was 3% of patient with palpitations; minor side effects were changes in appetite and drowsiness. More than half (57%) of patients taking topiramate experienced some side effect, 51% of the cyproheptadine group did as well, and the propranolol and flunarazine groups were noted to have side effects in 22% and 13%, respectively. Overall, 31.7% of patients had some side effect.  

PedMIDAS scores improved significantly with the use of preventive medications; migraine frequency improved significantly as well, especially in the topiramate group. This study argues for the use of preventive medications in pediatric migraine. One of the most commonly used medications for migraine prevention was not investigated unfortunately. Amitriptyline is widely considered a safe and effective migraine prophylactic medication, especially at low doses. One important takeaway is the frequency of side effects at all, and especially with topiramate. It is unclear how many patients stopped their preventive medications due to a side effect. In light of this study, propranolol, which is often overlooked, might be considered a better choice for children with migraine.

Most of the patients with migraine we see are in their most productive years. Migraine disability can be a major difficulty for our patients, especially as it relates to work. The American Migraine Foundation and American Headache Society have both recently taken on initiatives that relate to migraine in the workplace. Migraine epidemiologic studies have shown that people with migraine are more likely to experience a negative impact on their careers, and migraine disability scores weigh time absent from work as well as lower function at work. Many people with migraine are concerned that having migraine may hold them back from being hired or achieving promotion.

Autio et al performed a retrospective analysis of occupationally active patients treated at a single provider (the Finnish health clinic Terveystalo).⁴ The authors first looked for erenumab responders, who they defined as patients who received two prescriptions for erenumab and no other calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) medication. These patients were followed for 12 months, and their data was compared to the 12-month period prior to initiating erenumab. The authors evaluated headache-related sick days, all-cause sick days, healthcare visits, and prescriptions for all medications based on a registry. This registry also provided an age- and sex-matched control group of patients with migraine not taking any CGRP mAb medication.

A total of 162 patients were included, 82 in the erenumab responder group.  Headache-related sick days decreased by 74%, and headache-related healthcare visits decreased by 44%. Triptan prescription use decreased by 31.5%; all-cause sick days and healthcare visits differences were not statistically significant.

Prevention remains key in improving our patients’ quality of life and a large factor in this is their work life. This study shows that intervention with erenumab significantly decreases migraine-related absenteeism. It could be argued that the other CGRP mAb medications may have the same effect, as can many other preventive therapies. It can also be argued that even with this data we can only assume that patients function better at work with preventive therapies. Further studies will also look at the degree that “presenteeism” plays in the workplace—people who show up to work but are functioning at a lesser extent due to migraine. That said, this is an important step towards recognizing the burden migraine disability has on our patients’ work life, and the extent that prevention can improve their quality of life.

References

1. Kelishadi MR et al. The beneficial effect of Alpha-lipoic acid supplementation as a potential adjunct treatment in episodic migraines. Sci Rep. 2022;12:271 (Jan 7).
2. Powers SW et al. Trial of amitriptyline, topiramate, and placebo for pediatric migraine.  N Engl  J Med. 2017;376(2):115-124. Doi: 10.1056/NEJMoa1610384.
3. Tekin H, Edem P. Effects and side effects of migraine prophylaxis in children. Pediatr Int. 2021 (Dec 14).

1. Autio H et al. Erenumab decreases headache-related sick leave days and health care visits: a retrospective real-world study in working patients with migraine. Neurol Ther. 2021 (Dec 10).

Most practitioners recommend a host of non-medical therapeutic options to their patients with migraine. The best studied and safest, most effective supplements remain magnesium, riboflavin/B₂, and CoQ10. Alpha-lipoic acid (ALA) is a supplement with both antioxidant and anti-inflammatory effects that has showed positive protective effects in a number of medical conditions, including diabetes and episodes of oxidative stress. One migraine study¹ evaluated serum ALA levels and found over 90% of people with migraine to deficient. This study sought to observe the potential benefit of supplementation with ALA in patients with episodic migraine.

This was a randomized, double-blind placebo-controlled trial over the course of 3 months. In this study, 92 female subjects with episodic migraine (defined as experiencing >2 but <15 days of headache per month) were recruited and randomized to receiving 300 mg ALA twice daily or placebo. Patients with chronic migraine, in menopause, pregnant, or lactating were excluded, as were patients with the presence of other chronic medical issues, or patients who had taken antioxidant supplements in the previous 4 months.

The primary outcomes of migraine severity, frequency, and Headache Impact Test (HIT-6) score were found to be significantly improved in the intervention group; duration of headache was not significantly different. Biochemical analysis of the two groups did show a difference in the lactate level of the intervention group, and this was considered a secondary outcome. Relevant side effects were primarily gastrointestinal, including stomach pain (higher in the placebo group), increased appetite, and constipation.

There is a great interest in finding effective non-medical treatments for migraine. These are frequently used as an adjunct to other preventive medications, or potentially as a stand-alone treatment for low frequency migraine. Many patients prefer non-medical options as well, and unfortunately many of the treatments they read about online or in less scientific spaces are unproven or unsafe. Supplementation remains an important part of migraine treatment for many practitioners and patients.

This study argues that ALA can be considered a safe and effective treatment for episodic migraine. When patients ask about non-medical options, ALA can be an additional treatment worth considering. Many patients are already taking multiple supplements before seeing their specialist, and this article  informs us that there may be some treatment benefit for this supplement as well. We may not be recommending this supplement alone as a preventive treatment for migraine, but we can add a new non-medical option to consider to our mix.

Using preventive medication in pediatrics is now more controversial than it had been previously. The well known The Childhood and Adolescent Migraine Prevention (CHAMP) trial² surprised many in the field by revealing that were no significant differences in headache frequency or disability when comparing children with migraine who received preventive medications or placebo. The CHAMP trial spotlighted the effect of non-medical therapies (cognitive behavioral therapy, biofeedback) and education. Many pediatric specialists have altered their practice paradigm in response to these results and have been more reticent to prescribe preventive medications for children with migraine. This is due to concern for potential side effects in light of the absence of direct benefit.

In an observational study of pediatric migraine,³ the investigators followed 186 children with migraine over a 3-year period to determine if the use of a number of preventive medications addresses disability (measured by Pediatric Migraine Disability Assessment [PedMIDAS]) as well as frequency, severity and duration of migraine. Other bothersome features of migraine were followed including the presence of nausea, vomiting, photophobia, analgesic use, and the side effects of the preventive medication.

The preventive medications used were cyproheptadine, flunarazine, propranolol, and topiramate—all at weight based doses. It is important to note that amitriptyline was not used in the study and there was no placebo group. This was a Turkish population, the median age was 14, and 63% were female, all of which are appropriate for a pediatric migraine study. Treatment efficacy was defined as a 50% reduction of symptoms. This was achieved in 90% of subjects in the topiramate group, 75% in the propranolol group, and 52-53% in the flunarazine and cyproheptadine groups.

Medication side effects were divided into minor or significant side effects. The only significant side effect noted was 3% of patient with palpitations; minor side effects were changes in appetite and drowsiness. More than half (57%) of patients taking topiramate experienced some side effect, 51% of the cyproheptadine group did as well, and the propranolol and flunarazine groups were noted to have side effects in 22% and 13%, respectively. Overall, 31.7% of patients had some side effect.  

PedMIDAS scores improved significantly with the use of preventive medications; migraine frequency improved significantly as well, especially in the topiramate group. This study argues for the use of preventive medications in pediatric migraine. One of the most commonly used medications for migraine prevention was not investigated unfortunately. Amitriptyline is widely considered a safe and effective migraine prophylactic medication, especially at low doses. One important takeaway is the frequency of side effects at all, and especially with topiramate. It is unclear how many patients stopped their preventive medications due to a side effect. In light of this study, propranolol, which is often overlooked, might be considered a better choice for children with migraine.

Most of the patients with migraine we see are in their most productive years. Migraine disability can be a major difficulty for our patients, especially as it relates to work. The American Migraine Foundation and American Headache Society have both recently taken on initiatives that relate to migraine in the workplace. Migraine epidemiologic studies have shown that people with migraine are more likely to experience a negative impact on their careers, and migraine disability scores weigh time absent from work as well as lower function at work. Many people with migraine are concerned that having migraine may hold them back from being hired or achieving promotion.

Autio et al performed a retrospective analysis of occupationally active patients treated at a single provider (the Finnish health clinic Terveystalo).⁴ The authors first looked for erenumab responders, who they defined as patients who received two prescriptions for erenumab and no other calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) medication. These patients were followed for 12 months, and their data was compared to the 12-month period prior to initiating erenumab. The authors evaluated headache-related sick days, all-cause sick days, healthcare visits, and prescriptions for all medications based on a registry. This registry also provided an age- and sex-matched control group of patients with migraine not taking any CGRP mAb medication.

A total of 162 patients were included, 82 in the erenumab responder group.  Headache-related sick days decreased by 74%, and headache-related healthcare visits decreased by 44%. Triptan prescription use decreased by 31.5%; all-cause sick days and healthcare visits differences were not statistically significant.

Prevention remains key in improving our patients’ quality of life and a large factor in this is their work life. This study shows that intervention with erenumab significantly decreases migraine-related absenteeism. It could be argued that the other CGRP mAb medications may have the same effect, as can many other preventive therapies. It can also be argued that even with this data we can only assume that patients function better at work with preventive therapies. Further studies will also look at the degree that “presenteeism” plays in the workplace—people who show up to work but are functioning at a lesser extent due to migraine. That said, this is an important step towards recognizing the burden migraine disability has on our patients’ work life, and the extent that prevention can improve their quality of life.

References

1. Kelishadi MR et al. The beneficial effect of Alpha-lipoic acid supplementation as a potential adjunct treatment in episodic migraines. Sci Rep. 2022;12:271 (Jan 7).
2. Powers SW et al. Trial of amitriptyline, topiramate, and placebo for pediatric migraine.  N Engl  J Med. 2017;376(2):115-124. Doi: 10.1056/NEJMoa1610384.
3. Tekin H, Edem P. Effects and side effects of migraine prophylaxis in children. Pediatr Int. 2021 (Dec 14).

1. Autio H et al. Erenumab decreases headache-related sick leave days and health care visits: a retrospective real-world study in working patients with migraine. Neurol Ther. 2021 (Dec 10).

Most practitioners recommend a host of non-medical therapeutic options to their patients with migraine. The best studied and safest, most effective supplements remain magnesium, riboflavin/B₂, and CoQ10. Alpha-lipoic acid (ALA) is a supplement with both antioxidant and anti-inflammatory effects that has showed positive protective effects in a number of medical conditions, including diabetes and episodes of oxidative stress. One migraine study¹ evaluated serum ALA levels and found over 90% of people with migraine to deficient. This study sought to observe the potential benefit of supplementation with ALA in patients with episodic migraine.

This was a randomized, double-blind placebo-controlled trial over the course of 3 months. In this study, 92 female subjects with episodic migraine (defined as experiencing >2 but <15 days of headache per month) were recruited and randomized to receiving 300 mg ALA twice daily or placebo. Patients with chronic migraine, in menopause, pregnant, or lactating were excluded, as were patients with the presence of other chronic medical issues, or patients who had taken antioxidant supplements in the previous 4 months.

The primary outcomes of migraine severity, frequency, and Headache Impact Test (HIT-6) score were found to be significantly improved in the intervention group; duration of headache was not significantly different. Biochemical analysis of the two groups did show a difference in the lactate level of the intervention group, and this was considered a secondary outcome. Relevant side effects were primarily gastrointestinal, including stomach pain (higher in the placebo group), increased appetite, and constipation.

There is a great interest in finding effective non-medical treatments for migraine. These are frequently used as an adjunct to other preventive medications, or potentially as a stand-alone treatment for low frequency migraine. Many patients prefer non-medical options as well, and unfortunately many of the treatments they read about online or in less scientific spaces are unproven or unsafe. Supplementation remains an important part of migraine treatment for many practitioners and patients.

This study argues that ALA can be considered a safe and effective treatment for episodic migraine. When patients ask about non-medical options, ALA can be an additional treatment worth considering. Many patients are already taking multiple supplements before seeing their specialist, and this article  informs us that there may be some treatment benefit for this supplement as well. We may not be recommending this supplement alone as a preventive treatment for migraine, but we can add a new non-medical option to consider to our mix.

Using preventive medication in pediatrics is now more controversial than it had been previously. The well known The Childhood and Adolescent Migraine Prevention (CHAMP) trial² surprised many in the field by revealing that were no significant differences in headache frequency or disability when comparing children with migraine who received preventive medications or placebo. The CHAMP trial spotlighted the effect of non-medical therapies (cognitive behavioral therapy, biofeedback) and education. Many pediatric specialists have altered their practice paradigm in response to these results and have been more reticent to prescribe preventive medications for children with migraine. This is due to concern for potential side effects in light of the absence of direct benefit.

In an observational study of pediatric migraine,³ the investigators followed 186 children with migraine over a 3-year period to determine if the use of a number of preventive medications addresses disability (measured by Pediatric Migraine Disability Assessment [PedMIDAS]) as well as frequency, severity and duration of migraine. Other bothersome features of migraine were followed including the presence of nausea, vomiting, photophobia, analgesic use, and the side effects of the preventive medication.

The preventive medications used were cyproheptadine, flunarazine, propranolol, and topiramate—all at weight based doses. It is important to note that amitriptyline was not used in the study and there was no placebo group. This was a Turkish population, the median age was 14, and 63% were female, all of which are appropriate for a pediatric migraine study. Treatment efficacy was defined as a 50% reduction of symptoms. This was achieved in 90% of subjects in the topiramate group, 75% in the propranolol group, and 52-53% in the flunarazine and cyproheptadine groups.

Medication side effects were divided into minor or significant side effects. The only significant side effect noted was 3% of patient with palpitations; minor side effects were changes in appetite and drowsiness. More than half (57%) of patients taking topiramate experienced some side effect, 51% of the cyproheptadine group did as well, and the propranolol and flunarazine groups were noted to have side effects in 22% and 13%, respectively. Overall, 31.7% of patients had some side effect.  

PedMIDAS scores improved significantly with the use of preventive medications; migraine frequency improved significantly as well, especially in the topiramate group. This study argues for the use of preventive medications in pediatric migraine. One of the most commonly used medications for migraine prevention was not investigated unfortunately. Amitriptyline is widely considered a safe and effective migraine prophylactic medication, especially at low doses. One important takeaway is the frequency of side effects at all, and especially with topiramate. It is unclear how many patients stopped their preventive medications due to a side effect. In light of this study, propranolol, which is often overlooked, might be considered a better choice for children with migraine.

Most of the patients with migraine we see are in their most productive years. Migraine disability can be a major difficulty for our patients, especially as it relates to work. The American Migraine Foundation and American Headache Society have both recently taken on initiatives that relate to migraine in the workplace. Migraine epidemiologic studies have shown that people with migraine are more likely to experience a negative impact on their careers, and migraine disability scores weigh time absent from work as well as lower function at work. Many people with migraine are concerned that having migraine may hold them back from being hired or achieving promotion.

Autio et al performed a retrospective analysis of occupationally active patients treated at a single provider (the Finnish health clinic Terveystalo).⁴ The authors first looked for erenumab responders, who they defined as patients who received two prescriptions for erenumab and no other calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) medication. These patients were followed for 12 months, and their data was compared to the 12-month period prior to initiating erenumab. The authors evaluated headache-related sick days, all-cause sick days, healthcare visits, and prescriptions for all medications based on a registry. This registry also provided an age- and sex-matched control group of patients with migraine not taking any CGRP mAb medication.

A total of 162 patients were included, 82 in the erenumab responder group.  Headache-related sick days decreased by 74%, and headache-related healthcare visits decreased by 44%. Triptan prescription use decreased by 31.5%; all-cause sick days and healthcare visits differences were not statistically significant.

Prevention remains key in improving our patients’ quality of life and a large factor in this is their work life. This study shows that intervention with erenumab significantly decreases migraine-related absenteeism. It could be argued that the other CGRP mAb medications may have the same effect, as can many other preventive therapies. It can also be argued that even with this data we can only assume that patients function better at work with preventive therapies. Further studies will also look at the degree that “presenteeism” plays in the workplace—people who show up to work but are functioning at a lesser extent due to migraine. That said, this is an important step towards recognizing the burden migraine disability has on our patients’ work life, and the extent that prevention can improve their quality of life.

References

1. Kelishadi MR et al. The beneficial effect of Alpha-lipoic acid supplementation as a potential adjunct treatment in episodic migraines. Sci Rep. 2022;12:271 (Jan 7).
2. Powers SW et al. Trial of amitriptyline, topiramate, and placebo for pediatric migraine.  N Engl  J Med. 2017;376(2):115-124. Doi: 10.1056/NEJMoa1610384.
3. Tekin H, Edem P. Effects and side effects of migraine prophylaxis in children. Pediatr Int. 2021 (Dec 14).

1. Autio H et al. Erenumab decreases headache-related sick leave days and health care visits: a retrospective real-world study in working patients with migraine. Neurol Ther. 2021 (Dec 10).

Most practitioners recommend a host of non-medical therapeutic options to their patients with migraine. The best studied and safest, most effective supplements remain magnesium, riboflavin/B₂, and CoQ10. Alpha-lipoic acid (ALA) is a supplement with both antioxidant and anti-inflammatory effects that has showed positive protective effects in a number of medical conditions, including diabetes and episodes of oxidative stress. One migraine study¹ evaluated serum ALA levels and found over 90% of people with migraine to deficient. This study sought to observe the potential benefit of supplementation with ALA in patients with episodic migraine.

This was a randomized, double-blind placebo-controlled trial over the course of 3 months. In this study, 92 female subjects with episodic migraine (defined as experiencing >2 but <15 days of headache per month) were recruited and randomized to receiving 300 mg ALA twice daily or placebo. Patients with chronic migraine, in menopause, pregnant, or lactating were excluded, as were patients with the presence of other chronic medical issues, or patients who had taken antioxidant supplements in the previous 4 months.

The primary outcomes of migraine severity, frequency, and Headache Impact Test (HIT-6) score were found to be significantly improved in the intervention group; duration of headache was not significantly different. Biochemical analysis of the two groups did show a difference in the lactate level of the intervention group, and this was considered a secondary outcome. Relevant side effects were primarily gastrointestinal, including stomach pain (higher in the placebo group), increased appetite, and constipation.

There is a great interest in finding effective non-medical treatments for migraine. These are frequently used as an adjunct to other preventive medications, or potentially as a stand-alone treatment for low frequency migraine. Many patients prefer non-medical options as well, and unfortunately many of the treatments they read about online or in less scientific spaces are unproven or unsafe. Supplementation remains an important part of migraine treatment for many practitioners and patients.

This study argues that ALA can be considered a safe and effective treatment for episodic migraine. When patients ask about non-medical options, ALA can be an additional treatment worth considering. Many patients are already taking multiple supplements before seeing their specialist, and this article  informs us that there may be some treatment benefit for this supplement as well. We may not be recommending this supplement alone as a preventive treatment for migraine, but we can add a new non-medical option to consider to our mix.

Using preventive medication in pediatrics is now more controversial than it had been previously. The well known The Childhood and Adolescent Migraine Prevention (CHAMP) trial² surprised many in the field by revealing that were no significant differences in headache frequency or disability when comparing children with migraine who received preventive medications or placebo. The CHAMP trial spotlighted the effect of non-medical therapies (cognitive behavioral therapy, biofeedback) and education. Many pediatric specialists have altered their practice paradigm in response to these results and have been more reticent to prescribe preventive medications for children with migraine. This is due to concern for potential side effects in light of the absence of direct benefit.

In an observational study of pediatric migraine,³ the investigators followed 186 children with migraine over a 3-year period to determine if the use of a number of preventive medications addresses disability (measured by Pediatric Migraine Disability Assessment [PedMIDAS]) as well as frequency, severity and duration of migraine. Other bothersome features of migraine were followed including the presence of nausea, vomiting, photophobia, analgesic use, and the side effects of the preventive medication.

The preventive medications used were cyproheptadine, flunarazine, propranolol, and topiramate—all at weight based doses. It is important to note that amitriptyline was not used in the study and there was no placebo group. This was a Turkish population, the median age was 14, and 63% were female, all of which are appropriate for a pediatric migraine study. Treatment efficacy was defined as a 50% reduction of symptoms. This was achieved in 90% of subjects in the topiramate group, 75% in the propranolol group, and 52-53% in the flunarazine and cyproheptadine groups.

Medication side effects were divided into minor or significant side effects. The only significant side effect noted was 3% of patient with palpitations; minor side effects were changes in appetite and drowsiness. More than half (57%) of patients taking topiramate experienced some side effect, 51% of the cyproheptadine group did as well, and the propranolol and flunarazine groups were noted to have side effects in 22% and 13%, respectively. Overall, 31.7% of patients had some side effect.  

PedMIDAS scores improved significantly with the use of preventive medications; migraine frequency improved significantly as well, especially in the topiramate group. This study argues for the use of preventive medications in pediatric migraine. One of the most commonly used medications for migraine prevention was not investigated unfortunately. Amitriptyline is widely considered a safe and effective migraine prophylactic medication, especially at low doses. One important takeaway is the frequency of side effects at all, and especially with topiramate. It is unclear how many patients stopped their preventive medications due to a side effect. In light of this study, propranolol, which is often overlooked, might be considered a better choice for children with migraine.

Most of the patients with migraine we see are in their most productive years. Migraine disability can be a major difficulty for our patients, especially as it relates to work. The American Migraine Foundation and American Headache Society have both recently taken on initiatives that relate to migraine in the workplace. Migraine epidemiologic studies have shown that people with migraine are more likely to experience a negative impact on their careers, and migraine disability scores weigh time absent from work as well as lower function at work. Many people with migraine are concerned that having migraine may hold them back from being hired or achieving promotion.

Autio et al performed a retrospective analysis of occupationally active patients treated at a single provider (the Finnish health clinic Terveystalo).⁴ The authors first looked for erenumab responders, who they defined as patients who received two prescriptions for erenumab and no other calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) medication. These patients were followed for 12 months, and their data was compared to the 12-month period prior to initiating erenumab. The authors evaluated headache-related sick days, all-cause sick days, healthcare visits, and prescriptions for all medications based on a registry. This registry also provided an age- and sex-matched control group of patients with migraine not taking any CGRP mAb medication.

A total of 162 patients were included, 82 in the erenumab responder group.  Headache-related sick days decreased by 74%, and headache-related healthcare visits decreased by 44%. Triptan prescription use decreased by 31.5%; all-cause sick days and healthcare visits differences were not statistically significant.

Prevention remains key in improving our patients’ quality of life and a large factor in this is their work life. This study shows that intervention with erenumab significantly decreases migraine-related absenteeism. It could be argued that the other CGRP mAb medications may have the same effect, as can many other preventive therapies. It can also be argued that even with this data we can only assume that patients function better at work with preventive therapies. Further studies will also look at the degree that “presenteeism” plays in the workplace—people who show up to work but are functioning at a lesser extent due to migraine. That said, this is an important step towards recognizing the burden migraine disability has on our patients’ work life, and the extent that prevention can improve their quality of life.

References

1. Kelishadi MR et al. The beneficial effect of Alpha-lipoic acid supplementation as a potential adjunct treatment in episodic migraines. Sci Rep. 2022;12:271 (Jan 7).
2. Powers SW et al. Trial of amitriptyline, topiramate, and placebo for pediatric migraine.  N Engl  J Med. 2017;376(2):115-124. Doi: 10.1056/NEJMoa1610384.
3. Tekin H, Edem P. Effects and side effects of migraine prophylaxis in children. Pediatr Int. 2021 (Dec 14).

1. Autio H et al. Erenumab decreases headache-related sick leave days and health care visits: a retrospective real-world study in working patients with migraine. Neurol Ther. 2021 (Dec 10).

Atopic dermatitis can really mess with patients’ lives

Atopic dermatitis (AD) is a multi-faceted disease that can cause major burden to the lives of patients. Chronic itch is the most common and burdensome symptom of AD and can be very distressing and debilitating for patients.¹ Visible skin lesions of AD can be embarrassing and contribute to decreased self-esteem and psychosocial distress (ref). Recent studies uncovered many additional impacts and sequelae of AD.

• While itch has been long recognized as a burdensome symptom in AD, skin pain was recently shown to be an important symptom of AD. Cheng et al² performed a cross-sectional national survey of 240 children with AD and their parents, of which 200 had moderate-to-very severe disease. They found that skin pain intensity was associated with increased skin bleeding (adjusted β [95% CI]: 1.47 [0.61-2.33]), weeping/oozing (adjusted β [95% CI]: 1.18 [0.47-1.90]), and cracking (adjusted β [95% CI]: 1.00 [0.27-1.73]). These relationships may be indirectly related to scratching of the skin leading to open sores that hurt but also bleed, weep/ooze, and crack. On the other hand, patients may experience cracking of skin on hands and feet secondary to dryness and inflammation that can cause skin pain. The authors also found that parent-reported pain intensity was associated with impaired quality of life in infants aged 1-4 years (adjusted β [95% CI]: 1.16 [0.18-2.14]) and children aged 5-17 years (adjusted β [95% CI]: 1.68 [1.00-2.36]). These results show that skin pain is a burdensome symptom in children and adolescents with AD.

• Sleep disturbance is a major problem in patients with AD, especially in those with moderate-to-severe AD. Zhou et al³ conducted a cross-sectional study of 60 children aged 1-4 years with mild-to-severe AD. They found that eczema caused sleep disturbance on 5 or more nights in the past week in 76% of children with severe AD, 24% children with moderate AD, but none with mild AD. Children with more severe AD had greater attention dysregulation (correlation coefficient 0.65). AD severity was a significant predictor of both poor sleep health (β = 0.79) and attention dysregulation (β = 1.22). These results have important ramifications for pediatric health. Previous studies found associations of AD with attention-deficit disorder and attention-deficit hyperactivity disorder. The results of Zhou et al. suggest that AD is associated with symptoms of attention dysregulation, likely secondary to distraction from itch, chronic sleep deprivation, skin pain, etc.

• AD can affect individuals of all age groups, though there may be distinct ramifications when this debilitating disease occurs in childhood during the formative years of life. Manjunath et al⁴ examined data from the Fragile Families and Child Wellbeing Study, which is a prospective, longitudinal birth cohort including 4,898 children aged 1, 3, 5, 9, or 15 years. They found that AD in children aged 5 years (adjusted odds ratio [aOR] [95% CI]: 1.31 [1.04-1.64]) or 9 years (aOR [95% CI]: 1.38 [1.14-1.67]) was associated with ≥75th percentile of mean delinquent behavior scores at age 9 or 15 years. At 9 years of age, a 1-year history of AD was associated with smoking at age 15 years (aOR [95% CI]: 1.46 [1.00-2.13]), damaging property (aOR [95% CI]: 1.38 [1.08-1.77]), cheating on a test (aOR [95% CI]: 1.62 [1.17-2.26]), and school suspension (aOR [95% CI]: 1.36 [1.08-1.71]). These results are provocative and suggest that AD negatively impacts children’s behavior. This study was not able to examine specific clinical aspects of AD that led to delinquent behaviors. However, it is likely that multiple factors contribute to this association, including chronic itch, skin pain, sleep deprivation, attention dysregulation, psychosocial distress, teasing, and bullying.

• A major question on everyone’s mind these days is which individuals have a higher risk of developing COVID-19 infections. There have been many studies since the pandemic began on whether specific immune-mediated disorders are associated with higher risk of COVID-19 or worse outcomes from COVID-19 infections. Previous studies found mixed results about whether individuals with AD have higher risk of COVID-19. Fan et al⁵ performed a case-control study from a large healthcare system database, including 11,752 patients with AD and 47,008 age, sex and race matched healthy controls. They found that patients with AD were more likely to have a diagnosis of COVID-19 compared to those without AD (4.2% vs. 2.8%; P < .001). This association remained significant even after adjusting for demographic factors and comorbidities (odds ratio 1.29; P < .001). Of note, the effect-size was relatively modest in multivariable models. Residual confounding always remains a possibility, ie, that there are other unexplained factors in common with COVID-19 and AD that explain the association. Nevertheless, the results raise important questions about whether immune dysregulation or different treatments used in AD increase risk of COVID-19. Future studies are certainly warranted. Better yet, I look forward to the end of the pandemic when we will no longer have to worry about the potential harms of COVID-19 on AD patients.

References

1. Kim BS. Atopic Dermatitis Clinical Presentation. Medscape (Jan 10, 2022). https://emedicine.medscape.com/article/1049085-clinical (accessed Jan 28, 2022).
2. Cheng BT et al. Burden and characteristics of skin pain among children with atopic dermatitis. J Allergy Clin Immunol Pract. 2021 (Dec 23).
3. Zhou et al. Parent report of sleep health and attention regulation in a cross-sectional study of infants and preschool-aged children with atopic dermatitis. Pediatr Dermatol. 2021 (Dec 21).
4. Manjunath et al. Association of atopic dermatitis with delinquent behaviors in US children and adolescents. Arch Dermatol Res. 2022 (Jan 10).
5. Fan et al. Association between atopic dermatitis and COVID-19 infection: A case-control study in the All of Us research program. JAAD Int. 2021;6:P77-81 (Dec 27).

Atopic dermatitis can really mess with patients’ lives

Atopic dermatitis (AD) is a multi-faceted disease that can cause major burden to the lives of patients. Chronic itch is the most common and burdensome symptom of AD and can be very distressing and debilitating for patients.¹ Visible skin lesions of AD can be embarrassing and contribute to decreased self-esteem and psychosocial distress (ref). Recent studies uncovered many additional impacts and sequelae of AD.

• While itch has been long recognized as a burdensome symptom in AD, skin pain was recently shown to be an important symptom of AD. Cheng et al² performed a cross-sectional national survey of 240 children with AD and their parents, of which 200 had moderate-to-very severe disease. They found that skin pain intensity was associated with increased skin bleeding (adjusted β [95% CI]: 1.47 [0.61-2.33]), weeping/oozing (adjusted β [95% CI]: 1.18 [0.47-1.90]), and cracking (adjusted β [95% CI]: 1.00 [0.27-1.73]). These relationships may be indirectly related to scratching of the skin leading to open sores that hurt but also bleed, weep/ooze, and crack. On the other hand, patients may experience cracking of skin on hands and feet secondary to dryness and inflammation that can cause skin pain. The authors also found that parent-reported pain intensity was associated with impaired quality of life in infants aged 1-4 years (adjusted β [95% CI]: 1.16 [0.18-2.14]) and children aged 5-17 years (adjusted β [95% CI]: 1.68 [1.00-2.36]). These results show that skin pain is a burdensome symptom in children and adolescents with AD.

• Sleep disturbance is a major problem in patients with AD, especially in those with moderate-to-severe AD. Zhou et al³ conducted a cross-sectional study of 60 children aged 1-4 years with mild-to-severe AD. They found that eczema caused sleep disturbance on 5 or more nights in the past week in 76% of children with severe AD, 24% children with moderate AD, but none with mild AD. Children with more severe AD had greater attention dysregulation (correlation coefficient 0.65). AD severity was a significant predictor of both poor sleep health (β = 0.79) and attention dysregulation (β = 1.22). These results have important ramifications for pediatric health. Previous studies found associations of AD with attention-deficit disorder and attention-deficit hyperactivity disorder. The results of Zhou et al. suggest that AD is associated with symptoms of attention dysregulation, likely secondary to distraction from itch, chronic sleep deprivation, skin pain, etc.

• AD can affect individuals of all age groups, though there may be distinct ramifications when this debilitating disease occurs in childhood during the formative years of life. Manjunath et al⁴ examined data from the Fragile Families and Child Wellbeing Study, which is a prospective, longitudinal birth cohort including 4,898 children aged 1, 3, 5, 9, or 15 years. They found that AD in children aged 5 years (adjusted odds ratio [aOR] [95% CI]: 1.31 [1.04-1.64]) or 9 years (aOR [95% CI]: 1.38 [1.14-1.67]) was associated with ≥75th percentile of mean delinquent behavior scores at age 9 or 15 years. At 9 years of age, a 1-year history of AD was associated with smoking at age 15 years (aOR [95% CI]: 1.46 [1.00-2.13]), damaging property (aOR [95% CI]: 1.38 [1.08-1.77]), cheating on a test (aOR [95% CI]: 1.62 [1.17-2.26]), and school suspension (aOR [95% CI]: 1.36 [1.08-1.71]). These results are provocative and suggest that AD negatively impacts children’s behavior. This study was not able to examine specific clinical aspects of AD that led to delinquent behaviors. However, it is likely that multiple factors contribute to this association, including chronic itch, skin pain, sleep deprivation, attention dysregulation, psychosocial distress, teasing, and bullying.

• A major question on everyone’s mind these days is which individuals have a higher risk of developing COVID-19 infections. There have been many studies since the pandemic began on whether specific immune-mediated disorders are associated with higher risk of COVID-19 or worse outcomes from COVID-19 infections. Previous studies found mixed results about whether individuals with AD have higher risk of COVID-19. Fan et al⁵ performed a case-control study from a large healthcare system database, including 11,752 patients with AD and 47,008 age, sex and race matched healthy controls. They found that patients with AD were more likely to have a diagnosis of COVID-19 compared to those without AD (4.2% vs. 2.8%; P < .001). This association remained significant even after adjusting for demographic factors and comorbidities (odds ratio 1.29; P < .001). Of note, the effect-size was relatively modest in multivariable models. Residual confounding always remains a possibility, ie, that there are other unexplained factors in common with COVID-19 and AD that explain the association. Nevertheless, the results raise important questions about whether immune dysregulation or different treatments used in AD increase risk of COVID-19. Future studies are certainly warranted. Better yet, I look forward to the end of the pandemic when we will no longer have to worry about the potential harms of COVID-19 on AD patients.

References

1. Kim BS. Atopic Dermatitis Clinical Presentation. Medscape (Jan 10, 2022). https://emedicine.medscape.com/article/1049085-clinical (accessed Jan 28, 2022).
2. Cheng BT et al. Burden and characteristics of skin pain among children with atopic dermatitis. J Allergy Clin Immunol Pract. 2021 (Dec 23).
3. Zhou et al. Parent report of sleep health and attention regulation in a cross-sectional study of infants and preschool-aged children with atopic dermatitis. Pediatr Dermatol. 2021 (Dec 21).
4. Manjunath et al. Association of atopic dermatitis with delinquent behaviors in US children and adolescents. Arch Dermatol Res. 2022 (Jan 10).
5. Fan et al. Association between atopic dermatitis and COVID-19 infection: A case-control study in the All of Us research program. JAAD Int. 2021;6:P77-81 (Dec 27).

Atopic dermatitis can really mess with patients’ lives

Atopic dermatitis (AD) is a multi-faceted disease that can cause major burden to the lives of patients. Chronic itch is the most common and burdensome symptom of AD and can be very distressing and debilitating for patients.¹ Visible skin lesions of AD can be embarrassing and contribute to decreased self-esteem and psychosocial distress (ref). Recent studies uncovered many additional impacts and sequelae of AD.

• While itch has been long recognized as a burdensome symptom in AD, skin pain was recently shown to be an important symptom of AD. Cheng et al² performed a cross-sectional national survey of 240 children with AD and their parents, of which 200 had moderate-to-very severe disease. They found that skin pain intensity was associated with increased skin bleeding (adjusted β [95% CI]: 1.47 [0.61-2.33]), weeping/oozing (adjusted β [95% CI]: 1.18 [0.47-1.90]), and cracking (adjusted β [95% CI]: 1.00 [0.27-1.73]). These relationships may be indirectly related to scratching of the skin leading to open sores that hurt but also bleed, weep/ooze, and crack. On the other hand, patients may experience cracking of skin on hands and feet secondary to dryness and inflammation that can cause skin pain. The authors also found that parent-reported pain intensity was associated with impaired quality of life in infants aged 1-4 years (adjusted β [95% CI]: 1.16 [0.18-2.14]) and children aged 5-17 years (adjusted β [95% CI]: 1.68 [1.00-2.36]). These results show that skin pain is a burdensome symptom in children and adolescents with AD.

• Sleep disturbance is a major problem in patients with AD, especially in those with moderate-to-severe AD. Zhou et al³ conducted a cross-sectional study of 60 children aged 1-4 years with mild-to-severe AD. They found that eczema caused sleep disturbance on 5 or more nights in the past week in 76% of children with severe AD, 24% children with moderate AD, but none with mild AD. Children with more severe AD had greater attention dysregulation (correlation coefficient 0.65). AD severity was a significant predictor of both poor sleep health (β = 0.79) and attention dysregulation (β = 1.22). These results have important ramifications for pediatric health. Previous studies found associations of AD with attention-deficit disorder and attention-deficit hyperactivity disorder. The results of Zhou et al. suggest that AD is associated with symptoms of attention dysregulation, likely secondary to distraction from itch, chronic sleep deprivation, skin pain, etc.

• AD can affect individuals of all age groups, though there may be distinct ramifications when this debilitating disease occurs in childhood during the formative years of life. Manjunath et al⁴ examined data from the Fragile Families and Child Wellbeing Study, which is a prospective, longitudinal birth cohort including 4,898 children aged 1, 3, 5, 9, or 15 years. They found that AD in children aged 5 years (adjusted odds ratio [aOR] [95% CI]: 1.31 [1.04-1.64]) or 9 years (aOR [95% CI]: 1.38 [1.14-1.67]) was associated with ≥75th percentile of mean delinquent behavior scores at age 9 or 15 years. At 9 years of age, a 1-year history of AD was associated with smoking at age 15 years (aOR [95% CI]: 1.46 [1.00-2.13]), damaging property (aOR [95% CI]: 1.38 [1.08-1.77]), cheating on a test (aOR [95% CI]: 1.62 [1.17-2.26]), and school suspension (aOR [95% CI]: 1.36 [1.08-1.71]). These results are provocative and suggest that AD negatively impacts children’s behavior. This study was not able to examine specific clinical aspects of AD that led to delinquent behaviors. However, it is likely that multiple factors contribute to this association, including chronic itch, skin pain, sleep deprivation, attention dysregulation, psychosocial distress, teasing, and bullying.

• A major question on everyone’s mind these days is which individuals have a higher risk of developing COVID-19 infections. There have been many studies since the pandemic began on whether specific immune-mediated disorders are associated with higher risk of COVID-19 or worse outcomes from COVID-19 infections. Previous studies found mixed results about whether individuals with AD have higher risk of COVID-19. Fan et al⁵ performed a case-control study from a large healthcare system database, including 11,752 patients with AD and 47,008 age, sex and race matched healthy controls. They found that patients with AD were more likely to have a diagnosis of COVID-19 compared to those without AD (4.2% vs. 2.8%; P < .001). This association remained significant even after adjusting for demographic factors and comorbidities (odds ratio 1.29; P < .001). Of note, the effect-size was relatively modest in multivariable models. Residual confounding always remains a possibility, ie, that there are other unexplained factors in common with COVID-19 and AD that explain the association. Nevertheless, the results raise important questions about whether immune dysregulation or different treatments used in AD increase risk of COVID-19. Future studies are certainly warranted. Better yet, I look forward to the end of the pandemic when we will no longer have to worry about the potential harms of COVID-19 on AD patients.

References

1. Kim BS. Atopic Dermatitis Clinical Presentation. Medscape (Jan 10, 2022). https://emedicine.medscape.com/article/1049085-clinical (accessed Jan 28, 2022).
2. Cheng BT et al. Burden and characteristics of skin pain among children with atopic dermatitis. J Allergy Clin Immunol Pract. 2021 (Dec 23).
3. Zhou et al. Parent report of sleep health and attention regulation in a cross-sectional study of infants and preschool-aged children with atopic dermatitis. Pediatr Dermatol. 2021 (Dec 21).
4. Manjunath et al. Association of atopic dermatitis with delinquent behaviors in US children and adolescents. Arch Dermatol Res. 2022 (Jan 10).
5. Fan et al. Association between atopic dermatitis and COVID-19 infection: A case-control study in the All of Us research program. JAAD Int. 2021;6:P77-81 (Dec 27).

In another study (Maniscalco GT et al) exploring vaccine efficacy in 149 PwMS, treatment with interferon (IFN)-beta 1A resulted in improved anti-spike IgG specific humoral response levels than was seen in healthy controls response (median, 1,916 vs 1,089; P = .029) whereas reduced anti-spike IgG levels were significantly lower in patients treated with Cladribine (P = .002), Fingolimod (P < .0001), or Ocrelizumab (P < .0001). Clinical decisions regarding DMT treatment choice and DMT change focused solely on relapse rate and MRI are now insufficient without considering and incorporating vaccine response into the decision-making process. Further information across all DMT’s is needed to allow improved decision making regarding DMT choice.  Confounding this problem is the frequency of unrecognized cognitive impairment (CI) in PwMS and the impact CI has on the shared decision-making process beyond EDSS. 

In another study (Cavaco S et al) regarding CI in 408 PwMS, the presence of cognitive dysfunction was not only predictive of a higher risk for conversion from relapsing-remitting disease to progressive disease (adjusted odds ratio, 2.29; P = .043) and shorter survival (e.g. higher risk for death), (adjusted hazard ratio, 3.07; P = .006). The impact of such CI and progressive CI on vaccine hesitancy is unknown. Monitoring disease impact and change in cognitive function in PwMS remains another great unmet need in routine care of PwMS and evaluating the impact of CI on vaccine hesitancy and the shared decision-making process also requires further exploration and incorporation into routine care. Care of PwMS and the choice of DMT should hinge not only considerations about efficacy and safety but now must also incorporate patient vaccine hesitancy and response to vaccination.

In another study (Maniscalco GT et al) exploring vaccine efficacy in 149 PwMS, treatment with interferon (IFN)-beta 1A resulted in improved anti-spike IgG specific humoral response levels than was seen in healthy controls response (median, 1,916 vs 1,089; P = .029) whereas reduced anti-spike IgG levels were significantly lower in patients treated with Cladribine (P = .002), Fingolimod (P < .0001), or Ocrelizumab (P < .0001). Clinical decisions regarding DMT treatment choice and DMT change focused solely on relapse rate and MRI are now insufficient without considering and incorporating vaccine response into the decision-making process. Further information across all DMT’s is needed to allow improved decision making regarding DMT choice.  Confounding this problem is the frequency of unrecognized cognitive impairment (CI) in PwMS and the impact CI has on the shared decision-making process beyond EDSS. 

In another study (Cavaco S et al) regarding CI in 408 PwMS, the presence of cognitive dysfunction was not only predictive of a higher risk for conversion from relapsing-remitting disease to progressive disease (adjusted odds ratio, 2.29; P = .043) and shorter survival (e.g. higher risk for death), (adjusted hazard ratio, 3.07; P = .006). The impact of such CI and progressive CI on vaccine hesitancy is unknown. Monitoring disease impact and change in cognitive function in PwMS remains another great unmet need in routine care of PwMS and evaluating the impact of CI on vaccine hesitancy and the shared decision-making process also requires further exploration and incorporation into routine care. Care of PwMS and the choice of DMT should hinge not only considerations about efficacy and safety but now must also incorporate patient vaccine hesitancy and response to vaccination.

In another study (Maniscalco GT et al) exploring vaccine efficacy in 149 PwMS, treatment with interferon (IFN)-beta 1A resulted in improved anti-spike IgG specific humoral response levels than was seen in healthy controls response (median, 1,916 vs 1,089; P = .029) whereas reduced anti-spike IgG levels were significantly lower in patients treated with Cladribine (P = .002), Fingolimod (P < .0001), or Ocrelizumab (P < .0001). Clinical decisions regarding DMT treatment choice and DMT change focused solely on relapse rate and MRI are now insufficient without considering and incorporating vaccine response into the decision-making process. Further information across all DMT’s is needed to allow improved decision making regarding DMT choice.  Confounding this problem is the frequency of unrecognized cognitive impairment (CI) in PwMS and the impact CI has on the shared decision-making process beyond EDSS. 

In another study (Cavaco S et al) regarding CI in 408 PwMS, the presence of cognitive dysfunction was not only predictive of a higher risk for conversion from relapsing-remitting disease to progressive disease (adjusted odds ratio, 2.29; P = .043) and shorter survival (e.g. higher risk for death), (adjusted hazard ratio, 3.07; P = .006). The impact of such CI and progressive CI on vaccine hesitancy is unknown. Monitoring disease impact and change in cognitive function in PwMS remains another great unmet need in routine care of PwMS and evaluating the impact of CI on vaccine hesitancy and the shared decision-making process also requires further exploration and incorporation into routine care. Care of PwMS and the choice of DMT should hinge not only considerations about efficacy and safety but now must also incorporate patient vaccine hesitancy and response to vaccination.

Takayama et al evaluated 301 Japanese HCC patients who had a Child-Pugh score ≤ 7, no more than 3 HCC nodules (none more than 3 cm in greatest diameter), who were then randomly assigned to undergo either surgery (n=150) or RFA (n=151). The authors reported that though the median procedure duration was longer in the surgery group than in the RFA group (274 versus 40 minutes, P < 0.01) as was the median duration of hospital stay (17 days versus 10 days, P < 0.01), recurrence free survival (RFS) did not differ significantly between the groups. The median RFS was 3.5 years (95% confidence interval [CI], 2.6–5.1) in the surgery group and 3.0 years (95% CI, 2.4–5.6) in the RFA group (hazard ratio, 0.92; 95% CI, 0.67–1.25; P = 0.58). The overall survival (OS) data for this study are not yet mature.

Cao et al looked at outcomes of patients with periportal HCCs who were treated with RFA. They evaluated 233 patients who had a single nodular HCC that was ≤ 5 cm in greatest diameter who underwent RFA with or without transarterial chemoembolization (TACE) as first-line therapy. In that group, 56 patients had a periportal HCC. The authors reported that patients with periportal HCCs had worse outcomes. Local recurrence rates at 1, 3, and 5 years were significantly higher with periportal HCCs than with nonperiportal HCCs (15.7, 33.7, and 46.9% vs 6.0, 15.7, and 28.7%, respectively, P = 0.0067). The 1-, 3- and 5-year OS rates with periportal HCCs were significantly worse than with nonperiportal HCCs (81.3, 65.1 and 42.9% vs 99.3, 90.4 and 78.1%, respectively, P < 0.0001). In the subgroup of HCC ≤ 3 cm, patients with periportal HCCs showed significantly higher local recurrence rates (P = 0.0006) and OS (P < 0.0001) after RFA than patients with single nonperiportal HCCs. Subgroup analyses revealed that tumor size, periportal HCC and AFP ≥ 400ug/ml were independent prognostic factors for tumor progression after RFA. The authors concluded that periportal HCCs have a worse prognosis, and need better treatment options than are currently available.

Lee at al report a retrospective evaluation of Korean patients with HCC who were either treated with RFA or microwave ablation (MWA). Of 150 HCC patients (100 in the RFA group and 50 in the MWA group), the complete response rate, two-year survival rate, and complication rate were similar between the two groups. However, the MWA group had better one- and two-year disease-free survival than the RFA group (P = 0.035 and P = 0.032, respectively). In addition, there were fewer major complications in the MWA group (P = 0.043). In a subgroup analysis, patients with perivascular tumors, high risk of recurrence, and small tumor size (≤3 cm) were more suitable for MWA than RFA. The authors concluded that in patients with HCC, initial treatment with microwave ablation leads to better 1- and 2-year disease-free survival and a lower risk of major complications than RFA.

Takayama et al evaluated 301 Japanese HCC patients who had a Child-Pugh score ≤ 7, no more than 3 HCC nodules (none more than 3 cm in greatest diameter), who were then randomly assigned to undergo either surgery (n=150) or RFA (n=151). The authors reported that though the median procedure duration was longer in the surgery group than in the RFA group (274 versus 40 minutes, P < 0.01) as was the median duration of hospital stay (17 days versus 10 days, P < 0.01), recurrence free survival (RFS) did not differ significantly between the groups. The median RFS was 3.5 years (95% confidence interval [CI], 2.6–5.1) in the surgery group and 3.0 years (95% CI, 2.4–5.6) in the RFA group (hazard ratio, 0.92; 95% CI, 0.67–1.25; P = 0.58). The overall survival (OS) data for this study are not yet mature.

Cao et al looked at outcomes of patients with periportal HCCs who were treated with RFA. They evaluated 233 patients who had a single nodular HCC that was ≤ 5 cm in greatest diameter who underwent RFA with or without transarterial chemoembolization (TACE) as first-line therapy. In that group, 56 patients had a periportal HCC. The authors reported that patients with periportal HCCs had worse outcomes. Local recurrence rates at 1, 3, and 5 years were significantly higher with periportal HCCs than with nonperiportal HCCs (15.7, 33.7, and 46.9% vs 6.0, 15.7, and 28.7%, respectively, P = 0.0067). The 1-, 3- and 5-year OS rates with periportal HCCs were significantly worse than with nonperiportal HCCs (81.3, 65.1 and 42.9% vs 99.3, 90.4 and 78.1%, respectively, P < 0.0001). In the subgroup of HCC ≤ 3 cm, patients with periportal HCCs showed significantly higher local recurrence rates (P = 0.0006) and OS (P < 0.0001) after RFA than patients with single nonperiportal HCCs. Subgroup analyses revealed that tumor size, periportal HCC and AFP ≥ 400ug/ml were independent prognostic factors for tumor progression after RFA. The authors concluded that periportal HCCs have a worse prognosis, and need better treatment options than are currently available.

Lee at al report a retrospective evaluation of Korean patients with HCC who were either treated with RFA or microwave ablation (MWA). Of 150 HCC patients (100 in the RFA group and 50 in the MWA group), the complete response rate, two-year survival rate, and complication rate were similar between the two groups. However, the MWA group had better one- and two-year disease-free survival than the RFA group (P = 0.035 and P = 0.032, respectively). In addition, there were fewer major complications in the MWA group (P = 0.043). In a subgroup analysis, patients with perivascular tumors, high risk of recurrence, and small tumor size (≤3 cm) were more suitable for MWA than RFA. The authors concluded that in patients with HCC, initial treatment with microwave ablation leads to better 1- and 2-year disease-free survival and a lower risk of major complications than RFA.

Takayama et al evaluated 301 Japanese HCC patients who had a Child-Pugh score ≤ 7, no more than 3 HCC nodules (none more than 3 cm in greatest diameter), who were then randomly assigned to undergo either surgery (n=150) or RFA (n=151). The authors reported that though the median procedure duration was longer in the surgery group than in the RFA group (274 versus 40 minutes, P < 0.01) as was the median duration of hospital stay (17 days versus 10 days, P < 0.01), recurrence free survival (RFS) did not differ significantly between the groups. The median RFS was 3.5 years (95% confidence interval [CI], 2.6–5.1) in the surgery group and 3.0 years (95% CI, 2.4–5.6) in the RFA group (hazard ratio, 0.92; 95% CI, 0.67–1.25; P = 0.58). The overall survival (OS) data for this study are not yet mature.

Cao et al looked at outcomes of patients with periportal HCCs who were treated with RFA. They evaluated 233 patients who had a single nodular HCC that was ≤ 5 cm in greatest diameter who underwent RFA with or without transarterial chemoembolization (TACE) as first-line therapy. In that group, 56 patients had a periportal HCC. The authors reported that patients with periportal HCCs had worse outcomes. Local recurrence rates at 1, 3, and 5 years were significantly higher with periportal HCCs than with nonperiportal HCCs (15.7, 33.7, and 46.9% vs 6.0, 15.7, and 28.7%, respectively, P = 0.0067). The 1-, 3- and 5-year OS rates with periportal HCCs were significantly worse than with nonperiportal HCCs (81.3, 65.1 and 42.9% vs 99.3, 90.4 and 78.1%, respectively, P < 0.0001). In the subgroup of HCC ≤ 3 cm, patients with periportal HCCs showed significantly higher local recurrence rates (P = 0.0006) and OS (P < 0.0001) after RFA than patients with single nonperiportal HCCs. Subgroup analyses revealed that tumor size, periportal HCC and AFP ≥ 400ug/ml were independent prognostic factors for tumor progression after RFA. The authors concluded that periportal HCCs have a worse prognosis, and need better treatment options than are currently available.

Lee at al report a retrospective evaluation of Korean patients with HCC who were either treated with RFA or microwave ablation (MWA). Of 150 HCC patients (100 in the RFA group and 50 in the MWA group), the complete response rate, two-year survival rate, and complication rate were similar between the two groups. However, the MWA group had better one- and two-year disease-free survival than the RFA group (P = 0.035 and P = 0.032, respectively). In addition, there were fewer major complications in the MWA group (P = 0.043). In a subgroup analysis, patients with perivascular tumors, high risk of recurrence, and small tumor size (≤3 cm) were more suitable for MWA than RFA. The authors concluded that in patients with HCC, initial treatment with microwave ablation leads to better 1- and 2-year disease-free survival and a lower risk of major complications than RFA.

Takayama et al evaluated 301 Japanese HCC patients who had a Child-Pugh score ≤ 7, no more than 3 HCC nodules (none more than 3 cm in greatest diameter), who were then randomly assigned to undergo either surgery (n=150) or RFA (n=151). The authors reported that though the median procedure duration was longer in the surgery group than in the RFA group (274 versus 40 minutes, P < 0.01) as was the median duration of hospital stay (17 days versus 10 days, P < 0.01), recurrence free survival (RFS) did not differ significantly between the groups. The median RFS was 3.5 years (95% confidence interval [CI], 2.6–5.1) in the surgery group and 3.0 years (95% CI, 2.4–5.6) in the RFA group (hazard ratio, 0.92; 95% CI, 0.67–1.25; P = 0.58). The overall survival (OS) data for this study are not yet mature.

Cao et al looked at outcomes of patients with periportal HCCs who were treated with RFA. They evaluated 233 patients who had a single nodular HCC that was ≤ 5 cm in greatest diameter who underwent RFA with or without transarterial chemoembolization (TACE) as first-line therapy. In that group, 56 patients had a periportal HCC. The authors reported that patients with periportal HCCs had worse outcomes. Local recurrence rates at 1, 3, and 5 years were significantly higher with periportal HCCs than with nonperiportal HCCs (15.7, 33.7, and 46.9% vs 6.0, 15.7, and 28.7%, respectively, P = 0.0067). The 1-, 3- and 5-year OS rates with periportal HCCs were significantly worse than with nonperiportal HCCs (81.3, 65.1 and 42.9% vs 99.3, 90.4 and 78.1%, respectively, P < 0.0001). In the subgroup of HCC ≤ 3 cm, patients with periportal HCCs showed significantly higher local recurrence rates (P = 0.0006) and OS (P < 0.0001) after RFA than patients with single nonperiportal HCCs. Subgroup analyses revealed that tumor size, periportal HCC and AFP ≥ 400ug/ml were independent prognostic factors for tumor progression after RFA. The authors concluded that periportal HCCs have a worse prognosis, and need better treatment options than are currently available.

Lee at al report a retrospective evaluation of Korean patients with HCC who were either treated with RFA or microwave ablation (MWA). Of 150 HCC patients (100 in the RFA group and 50 in the MWA group), the complete response rate, two-year survival rate, and complication rate were similar between the two groups. However, the MWA group had better one- and two-year disease-free survival than the RFA group (P = 0.035 and P = 0.032, respectively). In addition, there were fewer major complications in the MWA group (P = 0.043). In a subgroup analysis, patients with perivascular tumors, high risk of recurrence, and small tumor size (≤3 cm) were more suitable for MWA than RFA. The authors concluded that in patients with HCC, initial treatment with microwave ablation leads to better 1- and 2-year disease-free survival and a lower risk of major complications than RFA.

Takayama et al evaluated 301 Japanese HCC patients who had a Child-Pugh score ≤ 7, no more than 3 HCC nodules (none more than 3 cm in greatest diameter), who were then randomly assigned to undergo either surgery (n=150) or RFA (n=151). The authors reported that though the median procedure duration was longer in the surgery group than in the RFA group (274 versus 40 minutes, P < 0.01) as was the median duration of hospital stay (17 days versus 10 days, P < 0.01), recurrence free survival (RFS) did not differ significantly between the groups. The median RFS was 3.5 years (95% confidence interval [CI], 2.6–5.1) in the surgery group and 3.0 years (95% CI, 2.4–5.6) in the RFA group (hazard ratio, 0.92; 95% CI, 0.67–1.25; P = 0.58). The overall survival (OS) data for this study are not yet mature.

Cao et al looked at outcomes of patients with periportal HCCs who were treated with RFA. They evaluated 233 patients who had a single nodular HCC that was ≤ 5 cm in greatest diameter who underwent RFA with or without transarterial chemoembolization (TACE) as first-line therapy. In that group, 56 patients had a periportal HCC. The authors reported that patients with periportal HCCs had worse outcomes. Local recurrence rates at 1, 3, and 5 years were significantly higher with periportal HCCs than with nonperiportal HCCs (15.7, 33.7, and 46.9% vs 6.0, 15.7, and 28.7%, respectively, P = 0.0067). The 1-, 3- and 5-year OS rates with periportal HCCs were significantly worse than with nonperiportal HCCs (81.3, 65.1 and 42.9% vs 99.3, 90.4 and 78.1%, respectively, P < 0.0001). In the subgroup of HCC ≤ 3 cm, patients with periportal HCCs showed significantly higher local recurrence rates (P = 0.0006) and OS (P < 0.0001) after RFA than patients with single nonperiportal HCCs. Subgroup analyses revealed that tumor size, periportal HCC and AFP ≥ 400ug/ml were independent prognostic factors for tumor progression after RFA. The authors concluded that periportal HCCs have a worse prognosis, and need better treatment options than are currently available.

Lee at al report a retrospective evaluation of Korean patients with HCC who were either treated with RFA or microwave ablation (MWA). Of 150 HCC patients (100 in the RFA group and 50 in the MWA group), the complete response rate, two-year survival rate, and complication rate were similar between the two groups. However, the MWA group had better one- and two-year disease-free survival than the RFA group (P = 0.035 and P = 0.032, respectively). In addition, there were fewer major complications in the MWA group (P = 0.043). In a subgroup analysis, patients with perivascular tumors, high risk of recurrence, and small tumor size (≤3 cm) were more suitable for MWA than RFA. The authors concluded that in patients with HCC, initial treatment with microwave ablation leads to better 1- and 2-year disease-free survival and a lower risk of major complications than RFA.

Takayama et al evaluated 301 Japanese HCC patients who had a Child-Pugh score ≤ 7, no more than 3 HCC nodules (none more than 3 cm in greatest diameter), who were then randomly assigned to undergo either surgery (n=150) or RFA (n=151). The authors reported that though the median procedure duration was longer in the surgery group than in the RFA group (274 versus 40 minutes, P < 0.01) as was the median duration of hospital stay (17 days versus 10 days, P < 0.01), recurrence free survival (RFS) did not differ significantly between the groups. The median RFS was 3.5 years (95% confidence interval [CI], 2.6–5.1) in the surgery group and 3.0 years (95% CI, 2.4–5.6) in the RFA group (hazard ratio, 0.92; 95% CI, 0.67–1.25; P = 0.58). The overall survival (OS) data for this study are not yet mature.

Cao et al looked at outcomes of patients with periportal HCCs who were treated with RFA. They evaluated 233 patients who had a single nodular HCC that was ≤ 5 cm in greatest diameter who underwent RFA with or without transarterial chemoembolization (TACE) as first-line therapy. In that group, 56 patients had a periportal HCC. The authors reported that patients with periportal HCCs had worse outcomes. Local recurrence rates at 1, 3, and 5 years were significantly higher with periportal HCCs than with nonperiportal HCCs (15.7, 33.7, and 46.9% vs 6.0, 15.7, and 28.7%, respectively, P = 0.0067). The 1-, 3- and 5-year OS rates with periportal HCCs were significantly worse than with nonperiportal HCCs (81.3, 65.1 and 42.9% vs 99.3, 90.4 and 78.1%, respectively, P < 0.0001). In the subgroup of HCC ≤ 3 cm, patients with periportal HCCs showed significantly higher local recurrence rates (P = 0.0006) and OS (P < 0.0001) after RFA than patients with single nonperiportal HCCs. Subgroup analyses revealed that tumor size, periportal HCC and AFP ≥ 400ug/ml were independent prognostic factors for tumor progression after RFA. The authors concluded that periportal HCCs have a worse prognosis, and need better treatment options than are currently available.

Lee at al report a retrospective evaluation of Korean patients with HCC who were either treated with RFA or microwave ablation (MWA). Of 150 HCC patients (100 in the RFA group and 50 in the MWA group), the complete response rate, two-year survival rate, and complication rate were similar between the two groups. However, the MWA group had better one- and two-year disease-free survival than the RFA group (P = 0.035 and P = 0.032, respectively). In addition, there were fewer major complications in the MWA group (P = 0.043). In a subgroup analysis, patients with perivascular tumors, high risk of recurrence, and small tumor size (≤3 cm) were more suitable for MWA than RFA. The authors concluded that in patients with HCC, initial treatment with microwave ablation leads to better 1- and 2-year disease-free survival and a lower risk of major complications than RFA.

The STAMPEDE platform included a multiple arm and multiple stage protocol to evaluate abiraterone and enzalutamide in high risk non-metastatic and metastatic disease in separate trials. In the accompanying article by Attard et. al, a meta-analysis of two separate trials conducted as part of the STAMPEDE platform was undertaken. In the first trial, patients with high-risk localized prostate cancer were randomized to androgen deprivation therapy (ADT) with or without abiraterone. In the second trial, similar patients were randomized to ADT versus ADT plus abiraterone plus enzalutamide. The primary outcome of metastasis-free survival and secondary outcome of overall survival [OS] were significantly longer for the treatment arms over ADT; however, the addition of enzalutamide to abiraterone did not result in additional benefit. In appropriately selected patients with high risk localized prostate cancer, abiraterone is a reasonable option to consider in appropriately selected patients.

While bone is the most frequent site of metastasis in men with prostate cancer, visceral metastases (predominantly liver or lung) has been associated with worse outcomes. However, lower incidence of visceral metastases makes conduct of studies focused on visceral disease challenging. Baciarello et al conducted a post-hoc analysis of the LATITUDE study (where men with metastatic castrate-sensitive disease were treated with ADT plus abiraterone or ADT alone) in participants with visceral disease. Overall, patients with visceral metastases derived OS benefit (55.4 versus 33 months). Patients with lung metastases had similar OS to the entire cohort; however, those with liver metastases still derived benefit but had lower OS (36.8 versus 25.6 months). These post-hoc findings suggest that liver metastases present unique challenges compare to other metastatic disease sites, but further study is needed.

In the ENZAMET trial, enzalutamide plus ADT was compared to ADT alone in patients with metastatic castrate-sensitive disease, and enzalutamide treatment was associated with improved OS. In the report by Stockler et al, quality of life metrics as assessed by periodic evaluation utilizing standard questionnaires were reported. Patients who received enzalutamide reported more fatigue and lower cognitive and physical function than those receiving placebo. However, the overall quality of life did not decrease. These important quality of life findings, which are increasingly being reported in similar studies, support the overall net benefit of utilization of enzalutamide in patients with metastatic castrate-sensitive disease.

The STAMPEDE platform included a multiple arm and multiple stage protocol to evaluate abiraterone and enzalutamide in high risk non-metastatic and metastatic disease in separate trials. In the accompanying article by Attard et. al, a meta-analysis of two separate trials conducted as part of the STAMPEDE platform was undertaken. In the first trial, patients with high-risk localized prostate cancer were randomized to androgen deprivation therapy (ADT) with or without abiraterone. In the second trial, similar patients were randomized to ADT versus ADT plus abiraterone plus enzalutamide. The primary outcome of metastasis-free survival and secondary outcome of overall survival [OS] were significantly longer for the treatment arms over ADT; however, the addition of enzalutamide to abiraterone did not result in additional benefit. In appropriately selected patients with high risk localized prostate cancer, abiraterone is a reasonable option to consider in appropriately selected patients.

While bone is the most frequent site of metastasis in men with prostate cancer, visceral metastases (predominantly liver or lung) has been associated with worse outcomes. However, lower incidence of visceral metastases makes conduct of studies focused on visceral disease challenging. Baciarello et al conducted a post-hoc analysis of the LATITUDE study (where men with metastatic castrate-sensitive disease were treated with ADT plus abiraterone or ADT alone) in participants with visceral disease. Overall, patients with visceral metastases derived OS benefit (55.4 versus 33 months). Patients with lung metastases had similar OS to the entire cohort; however, those with liver metastases still derived benefit but had lower OS (36.8 versus 25.6 months). These post-hoc findings suggest that liver metastases present unique challenges compare to other metastatic disease sites, but further study is needed.

In the ENZAMET trial, enzalutamide plus ADT was compared to ADT alone in patients with metastatic castrate-sensitive disease, and enzalutamide treatment was associated with improved OS. In the report by Stockler et al, quality of life metrics as assessed by periodic evaluation utilizing standard questionnaires were reported. Patients who received enzalutamide reported more fatigue and lower cognitive and physical function than those receiving placebo. However, the overall quality of life did not decrease. These important quality of life findings, which are increasingly being reported in similar studies, support the overall net benefit of utilization of enzalutamide in patients with metastatic castrate-sensitive disease.

The STAMPEDE platform included a multiple arm and multiple stage protocol to evaluate abiraterone and enzalutamide in high risk non-metastatic and metastatic disease in separate trials. In the accompanying article by Attard et. al, a meta-analysis of two separate trials conducted as part of the STAMPEDE platform was undertaken. In the first trial, patients with high-risk localized prostate cancer were randomized to androgen deprivation therapy (ADT) with or without abiraterone. In the second trial, similar patients were randomized to ADT versus ADT plus abiraterone plus enzalutamide. The primary outcome of metastasis-free survival and secondary outcome of overall survival [OS] were significantly longer for the treatment arms over ADT; however, the addition of enzalutamide to abiraterone did not result in additional benefit. In appropriately selected patients with high risk localized prostate cancer, abiraterone is a reasonable option to consider in appropriately selected patients.

While bone is the most frequent site of metastasis in men with prostate cancer, visceral metastases (predominantly liver or lung) has been associated with worse outcomes. However, lower incidence of visceral metastases makes conduct of studies focused on visceral disease challenging. Baciarello et al conducted a post-hoc analysis of the LATITUDE study (where men with metastatic castrate-sensitive disease were treated with ADT plus abiraterone or ADT alone) in participants with visceral disease. Overall, patients with visceral metastases derived OS benefit (55.4 versus 33 months). Patients with lung metastases had similar OS to the entire cohort; however, those with liver metastases still derived benefit but had lower OS (36.8 versus 25.6 months). These post-hoc findings suggest that liver metastases present unique challenges compare to other metastatic disease sites, but further study is needed.

In the ENZAMET trial, enzalutamide plus ADT was compared to ADT alone in patients with metastatic castrate-sensitive disease, and enzalutamide treatment was associated with improved OS. In the report by Stockler et al, quality of life metrics as assessed by periodic evaluation utilizing standard questionnaires were reported. Patients who received enzalutamide reported more fatigue and lower cognitive and physical function than those receiving placebo. However, the overall quality of life did not decrease. These important quality of life findings, which are increasingly being reported in similar studies, support the overall net benefit of utilization of enzalutamide in patients with metastatic castrate-sensitive disease.

Several recent RA studies have addressed aspects of systemic illness other than joint pain and inflammation, including sleep, fatigue, psychosocial burden, and well-being. A cohort study by Lyne et al¹ evaluated sleep duration and quality in 3,265 patients in the Swedish EIRA registry from 1-12 years after RA diagnosis. About 40% had problems in at least one sleep domain and the frequency of sleep problems increased somewhat with disease duration, but the strongest correlations with poor sleep were pain and functional impairment, suggesting that the overall activity of the RA was most important. Further research on improving sleep quality with improved control of disease activity would be helpful in supporting this hypothesis.

A systematic review by Shamail et al² examined mental health outcomes in patients with RA taking Janus kinase (JAK) inhibitors, limiting the review to studies reporting SF-36 mental health outcomes. The resulting 19 studies encompassed over 14,000 patients and did demonstrate clinically meaningful changes in SF-36 scores compared to baseline in patients treated with JAK inhibitors. When compared to changes with placebo or disease-modifying antirheumatic drug (DMARD) treatment, JAK inhibitors appeared to have a benefit, though few studies showed a clinically meaningful difference. Given that other studies have shown improvement in mental health outcomes with other classes of RA treatments, it is not clear that this is an effect of the JAK inhibitor class rather than related to overall improvement in quality of life.

Fatigue is a prevalent concern among patients with RA and may significantly impact quality of life; its origins in RA are not well-understood but thought to be related to inflammation. A UK study of an inception cohort by Ifeseman et al³ examines fatigue in early RA; about 75% of participants reported a decreased vitality score compared to the mean in the UK general population. Of the approximately 729 study participants in the longitudinal analysis, trajectory modeling was used to identify two groups of people: one with an “average” vitality score and another with a score that was significantly reduced compared to average. This group had worse disease activity scores, Health Assessment Questionnaire (HAQ) scores, and pain, though as with the other studies mentioned above, it is not clear if fatigue is a feature of worse control of RA or related to ongoing central sensitization or “non-inflammatory” mechanisms.

Doumen et al⁴ analyzed interaction between psychosocial variables and disease activity in an early RA cohort and found that better baseline short form-36 (SF-36) scores as well as other measures of psychosocial burden and coping were associated with sustained Disease Activity Score 28 for Rheumatoid Arthritis with C-Reactive Protein (DAS-28-CRP) remission, while negative illness perception was associated with lower probability of sustained remission. Of the 287 patients who achieved DAS-28-CRP remission at week 16, the 231 patients who had a low psychosocial burden were more likely to remain in remission. Causality and direction are not established in this small study, so while evaluating psychosocial needs is relevant, as with the other studies mentioned above, caution must be used in attributing lack of improvement in disease activity to psychosocial burden or mood disorders.

References

1. Lyne L et al. Sleep problems in rheumatoid arthritis over 12 years from diagnosis: results from the Swedish EIRA study. RMD Open. 2022;8:e001800 (Jan 5).
2. Shamail GMH et al. Association between janus kinase inhibitors therapy and mental health outcome in rheumatoid arthritis: A systematic review and meta-analysis. Rheumatol Ther. 2021 (Dec 13).
3. Ifesemen OS et al. Fatigue in early rheumatoid arthritis: data from the Early Rheumatoid Arthritis Network. Rheumatology (Oxford). 2021;keab861 (Dec 27).
4. Doumen M et al. Psychosocial burden predicts sustained remission in early rheumatoid arthritis: unraveling the complex interplay of wellbeing and disease activity. Arthritis Care Res (Hoboken). 2021 (Dec 20).

Several recent RA studies have addressed aspects of systemic illness other than joint pain and inflammation, including sleep, fatigue, psychosocial burden, and well-being. A cohort study by Lyne et al¹ evaluated sleep duration and quality in 3,265 patients in the Swedish EIRA registry from 1-12 years after RA diagnosis. About 40% had problems in at least one sleep domain and the frequency of sleep problems increased somewhat with disease duration, but the strongest correlations with poor sleep were pain and functional impairment, suggesting that the overall activity of the RA was most important. Further research on improving sleep quality with improved control of disease activity would be helpful in supporting this hypothesis.

A systematic review by Shamail et al² examined mental health outcomes in patients with RA taking Janus kinase (JAK) inhibitors, limiting the review to studies reporting SF-36 mental health outcomes. The resulting 19 studies encompassed over 14,000 patients and did demonstrate clinically meaningful changes in SF-36 scores compared to baseline in patients treated with JAK inhibitors. When compared to changes with placebo or disease-modifying antirheumatic drug (DMARD) treatment, JAK inhibitors appeared to have a benefit, though few studies showed a clinically meaningful difference. Given that other studies have shown improvement in mental health outcomes with other classes of RA treatments, it is not clear that this is an effect of the JAK inhibitor class rather than related to overall improvement in quality of life.

Fatigue is a prevalent concern among patients with RA and may significantly impact quality of life; its origins in RA are not well-understood but thought to be related to inflammation. A UK study of an inception cohort by Ifeseman et al³ examines fatigue in early RA; about 75% of participants reported a decreased vitality score compared to the mean in the UK general population. Of the approximately 729 study participants in the longitudinal analysis, trajectory modeling was used to identify two groups of people: one with an “average” vitality score and another with a score that was significantly reduced compared to average. This group had worse disease activity scores, Health Assessment Questionnaire (HAQ) scores, and pain, though as with the other studies mentioned above, it is not clear if fatigue is a feature of worse control of RA or related to ongoing central sensitization or “non-inflammatory” mechanisms.

Doumen et al⁴ analyzed interaction between psychosocial variables and disease activity in an early RA cohort and found that better baseline short form-36 (SF-36) scores as well as other measures of psychosocial burden and coping were associated with sustained Disease Activity Score 28 for Rheumatoid Arthritis with C-Reactive Protein (DAS-28-CRP) remission, while negative illness perception was associated with lower probability of sustained remission. Of the 287 patients who achieved DAS-28-CRP remission at week 16, the 231 patients who had a low psychosocial burden were more likely to remain in remission. Causality and direction are not established in this small study, so while evaluating psychosocial needs is relevant, as with the other studies mentioned above, caution must be used in attributing lack of improvement in disease activity to psychosocial burden or mood disorders.

References

1. Lyne L et al. Sleep problems in rheumatoid arthritis over 12 years from diagnosis: results from the Swedish EIRA study. RMD Open. 2022;8:e001800 (Jan 5).
2. Shamail GMH et al. Association between janus kinase inhibitors therapy and mental health outcome in rheumatoid arthritis: A systematic review and meta-analysis. Rheumatol Ther. 2021 (Dec 13).
3. Ifesemen OS et al. Fatigue in early rheumatoid arthritis: data from the Early Rheumatoid Arthritis Network. Rheumatology (Oxford). 2021;keab861 (Dec 27).
4. Doumen M et al. Psychosocial burden predicts sustained remission in early rheumatoid arthritis: unraveling the complex interplay of wellbeing and disease activity. Arthritis Care Res (Hoboken). 2021 (Dec 20).

Several recent RA studies have addressed aspects of systemic illness other than joint pain and inflammation, including sleep, fatigue, psychosocial burden, and well-being. A cohort study by Lyne et al¹ evaluated sleep duration and quality in 3,265 patients in the Swedish EIRA registry from 1-12 years after RA diagnosis. About 40% had problems in at least one sleep domain and the frequency of sleep problems increased somewhat with disease duration, but the strongest correlations with poor sleep were pain and functional impairment, suggesting that the overall activity of the RA was most important. Further research on improving sleep quality with improved control of disease activity would be helpful in supporting this hypothesis.

A systematic review by Shamail et al² examined mental health outcomes in patients with RA taking Janus kinase (JAK) inhibitors, limiting the review to studies reporting SF-36 mental health outcomes. The resulting 19 studies encompassed over 14,000 patients and did demonstrate clinically meaningful changes in SF-36 scores compared to baseline in patients treated with JAK inhibitors. When compared to changes with placebo or disease-modifying antirheumatic drug (DMARD) treatment, JAK inhibitors appeared to have a benefit, though few studies showed a clinically meaningful difference. Given that other studies have shown improvement in mental health outcomes with other classes of RA treatments, it is not clear that this is an effect of the JAK inhibitor class rather than related to overall improvement in quality of life.

Fatigue is a prevalent concern among patients with RA and may significantly impact quality of life; its origins in RA are not well-understood but thought to be related to inflammation. A UK study of an inception cohort by Ifeseman et al³ examines fatigue in early RA; about 75% of participants reported a decreased vitality score compared to the mean in the UK general population. Of the approximately 729 study participants in the longitudinal analysis, trajectory modeling was used to identify two groups of people: one with an “average” vitality score and another with a score that was significantly reduced compared to average. This group had worse disease activity scores, Health Assessment Questionnaire (HAQ) scores, and pain, though as with the other studies mentioned above, it is not clear if fatigue is a feature of worse control of RA or related to ongoing central sensitization or “non-inflammatory” mechanisms.

Doumen et al⁴ analyzed interaction between psychosocial variables and disease activity in an early RA cohort and found that better baseline short form-36 (SF-36) scores as well as other measures of psychosocial burden and coping were associated with sustained Disease Activity Score 28 for Rheumatoid Arthritis with C-Reactive Protein (DAS-28-CRP) remission, while negative illness perception was associated with lower probability of sustained remission. Of the 287 patients who achieved DAS-28-CRP remission at week 16, the 231 patients who had a low psychosocial burden were more likely to remain in remission. Causality and direction are not established in this small study, so while evaluating psychosocial needs is relevant, as with the other studies mentioned above, caution must be used in attributing lack of improvement in disease activity to psychosocial burden or mood disorders.

References

1. Lyne L et al. Sleep problems in rheumatoid arthritis over 12 years from diagnosis: results from the Swedish EIRA study. RMD Open. 2022;8:e001800 (Jan 5).
2. Shamail GMH et al. Association between janus kinase inhibitors therapy and mental health outcome in rheumatoid arthritis: A systematic review and meta-analysis. Rheumatol Ther. 2021 (Dec 13).
3. Ifesemen OS et al. Fatigue in early rheumatoid arthritis: data from the Early Rheumatoid Arthritis Network. Rheumatology (Oxford). 2021;keab861 (Dec 27).
4. Doumen M et al. Psychosocial burden predicts sustained remission in early rheumatoid arthritis: unraveling the complex interplay of wellbeing and disease activity. Arthritis Care Res (Hoboken). 2021 (Dec 20).

Identifying risk factors associated with transition from cutaneous psoriasis to arthritic psoriasis remains a hot area of research. In a retrospective nested case-control study using the resources of the Rochester Epidemiology Project, Karmacharya et al¹ identified 164 patients with incident PsA between 2000 and 2017. Among the 158 total patients satisfying study criteria, 64 (41%) had concurrent psoriasis and PsA and 94 (59%) had onset of psoriasis before PsA. The median time from psoriasis diagnosis to the incidence of PsA was 35.5 months with age at psoriasis onset (odds ratio [OR] per 10-year decrease 1.63; 95% CI 1.26-2.11) and its severity (OR for severe vs. mild 3.65; 95% CI 1.18-11.32) being associated with having a psoriasis diagnosis >1 year prior to incident PsA. Early onset as well as severe psoriasis is associated with the HLA- C*06 allele as is longer psoriasis-PsA latency. Although not evaluated in this study, this genetic factor, or other factors such as detection bias, may underly these observations.

Once diagnosed, stratification of PsA severity is important for planning treatment. Towards this goal, Dubash et al² demonstrated that the presence of dactylitis indicates a more severe PsA phenotype. In a study of 177 disease-modifying antirheumatic drug (DMARD)-naive patients with early PsA, they found that those with dactylitis (46%) had significantly higher tender and swollen joint counts and C-reactive protein than those with non-dactylitic PsA. Ultrasound synovitis and erosions were also significantly more prevalent in dactylitic PsA. Thus, the presence of dactylitis indicates a more severe phenotype, and patients with dactylitis should be treated aggressively to improve long-term outcomes.

Novel therapies are being frequently evaluated in PsA and a recent target is interleukin (IL)-23, a key cytokine in the T-helper 17 (Th17) pathway and in the pathogenesis of psoriatic disease. Risankizumab is a novel monoclonal antibody targeting IL-23. In the double-blind phase 3 KEEPsAKE 1 study including 964 patients with active PsA and inadequate response to one or more conventional synthetic (cs) DMARDs. They were randomly assigned to receive 150 mg risankizumab or placebo, Kristensen et al³ demonstrated that, at week 24, at least a 20% improvement in the American College of Rheumatology score (ACR20) was achieved by a significantly higher proportion of patients receiving risankizumab vs. placebo (57.3% vs. 33.5%; P < .001). Treatment-emergent adverse events were mild-to-moderate and reported at similar frequencies in the risankizumab (40.4%) and placebo (38.7%) groups. Thus, risankizumab was efficacious in reducing clinical manifestations of PsA in patients with inadequate response to csDMARDs with no new adverse events. An important question when treating patients with PsA with targeted therapies is the need for concomitant therapy with csDMARDs. In a pooled analysis of 2 phase 3 trials, SELECT-PsA 1 and SELECT-PsA 2,  1,916 patients with active PsA with an inadequate response to ≥1 non-biologic (nb) DMARDs or biologic DMARDs were randomly assigned to placebo, 15 mg upadacitinib, or 30 mg upadacitinib as monotherapy or in combination with ≤2 nbDMARDs for 24 weeks, Nash et al⁴ demonstrated that at week 12, ACR20 response was achieved by a similar proportion of patients receiving 15 mg upadacitinib or 30 mg upadacitinib as monotherapy (15 mg: 33.7%; 95% CI 24.4%-43.1%; 30 mg: 45.7%; 95% CI 36.9%-54.5%) or combination therapy (15 mg: 34.0%; 95% CI 27.9%-40.1%; 30 mg: 39.6%; 95% CI 33.7%-45.5%). Adverse events were generally similar between monotherapy and combination therapy. Although, we don’t have information regarding the sustainability of the response, these data indicate that upadacitinib may be used without concomitant csDMARDs in PsA.

References

1. Karmacharya P et al. Time to transition from psoriasis to psoriatic arthritis: A population-based study. Semin Arthritis Rheum. 2021(Dec 31):S0049-0172(21)00230-4.
2. Dubash S et al. Dactylitis is an indicator of a more severe phenotype independently associated with greater SJC, CRP, ultrasound synovitis and erosive damage in DMARD-naive early psoriatic arthritis. Ann Rheum Dis. 2021(Dec 10):annrheumdis-2021-220964.
3. Kristensen LE et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 1 trial. Ann Rheum Dis. 2022(Feb);81(2):225-231.
4. Nash P et al. Upadacitinib as monotherapy and in combination with non-biologic disease-modifying antirheumatic drugs for psoriatic arthritis. Rheumatology (Oxford). 2021(Dec 3):keab905.

Identifying risk factors associated with transition from cutaneous psoriasis to arthritic psoriasis remains a hot area of research. In a retrospective nested case-control study using the resources of the Rochester Epidemiology Project, Karmacharya et al¹ identified 164 patients with incident PsA between 2000 and 2017. Among the 158 total patients satisfying study criteria, 64 (41%) had concurrent psoriasis and PsA and 94 (59%) had onset of psoriasis before PsA. The median time from psoriasis diagnosis to the incidence of PsA was 35.5 months with age at psoriasis onset (odds ratio [OR] per 10-year decrease 1.63; 95% CI 1.26-2.11) and its severity (OR for severe vs. mild 3.65; 95% CI 1.18-11.32) being associated with having a psoriasis diagnosis >1 year prior to incident PsA. Early onset as well as severe psoriasis is associated with the HLA- C*06 allele as is longer psoriasis-PsA latency. Although not evaluated in this study, this genetic factor, or other factors such as detection bias, may underly these observations.

Once diagnosed, stratification of PsA severity is important for planning treatment. Towards this goal, Dubash et al² demonstrated that the presence of dactylitis indicates a more severe PsA phenotype. In a study of 177 disease-modifying antirheumatic drug (DMARD)-naive patients with early PsA, they found that those with dactylitis (46%) had significantly higher tender and swollen joint counts and C-reactive protein than those with non-dactylitic PsA. Ultrasound synovitis and erosions were also significantly more prevalent in dactylitic PsA. Thus, the presence of dactylitis indicates a more severe phenotype, and patients with dactylitis should be treated aggressively to improve long-term outcomes.

Novel therapies are being frequently evaluated in PsA and a recent target is interleukin (IL)-23, a key cytokine in the T-helper 17 (Th17) pathway and in the pathogenesis of psoriatic disease. Risankizumab is a novel monoclonal antibody targeting IL-23. In the double-blind phase 3 KEEPsAKE 1 study including 964 patients with active PsA and inadequate response to one or more conventional synthetic (cs) DMARDs. They were randomly assigned to receive 150 mg risankizumab or placebo, Kristensen et al³ demonstrated that, at week 24, at least a 20% improvement in the American College of Rheumatology score (ACR20) was achieved by a significantly higher proportion of patients receiving risankizumab vs. placebo (57.3% vs. 33.5%; P < .001). Treatment-emergent adverse events were mild-to-moderate and reported at similar frequencies in the risankizumab (40.4%) and placebo (38.7%) groups. Thus, risankizumab was efficacious in reducing clinical manifestations of PsA in patients with inadequate response to csDMARDs with no new adverse events. An important question when treating patients with PsA with targeted therapies is the need for concomitant therapy with csDMARDs. In a pooled analysis of 2 phase 3 trials, SELECT-PsA 1 and SELECT-PsA 2,  1,916 patients with active PsA with an inadequate response to ≥1 non-biologic (nb) DMARDs or biologic DMARDs were randomly assigned to placebo, 15 mg upadacitinib, or 30 mg upadacitinib as monotherapy or in combination with ≤2 nbDMARDs for 24 weeks, Nash et al⁴ demonstrated that at week 12, ACR20 response was achieved by a similar proportion of patients receiving 15 mg upadacitinib or 30 mg upadacitinib as monotherapy (15 mg: 33.7%; 95% CI 24.4%-43.1%; 30 mg: 45.7%; 95% CI 36.9%-54.5%) or combination therapy (15 mg: 34.0%; 95% CI 27.9%-40.1%; 30 mg: 39.6%; 95% CI 33.7%-45.5%). Adverse events were generally similar between monotherapy and combination therapy. Although, we don’t have information regarding the sustainability of the response, these data indicate that upadacitinib may be used without concomitant csDMARDs in PsA.

References

1. Karmacharya P et al. Time to transition from psoriasis to psoriatic arthritis: A population-based study. Semin Arthritis Rheum. 2021(Dec 31):S0049-0172(21)00230-4.
2. Dubash S et al. Dactylitis is an indicator of a more severe phenotype independently associated with greater SJC, CRP, ultrasound synovitis and erosive damage in DMARD-naive early psoriatic arthritis. Ann Rheum Dis. 2021(Dec 10):annrheumdis-2021-220964.
3. Kristensen LE et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 1 trial. Ann Rheum Dis. 2022(Feb);81(2):225-231.
4. Nash P et al. Upadacitinib as monotherapy and in combination with non-biologic disease-modifying antirheumatic drugs for psoriatic arthritis. Rheumatology (Oxford). 2021(Dec 3):keab905.

Identifying risk factors associated with transition from cutaneous psoriasis to arthritic psoriasis remains a hot area of research. In a retrospective nested case-control study using the resources of the Rochester Epidemiology Project, Karmacharya et al¹ identified 164 patients with incident PsA between 2000 and 2017. Among the 158 total patients satisfying study criteria, 64 (41%) had concurrent psoriasis and PsA and 94 (59%) had onset of psoriasis before PsA. The median time from psoriasis diagnosis to the incidence of PsA was 35.5 months with age at psoriasis onset (odds ratio [OR] per 10-year decrease 1.63; 95% CI 1.26-2.11) and its severity (OR for severe vs. mild 3.65; 95% CI 1.18-11.32) being associated with having a psoriasis diagnosis >1 year prior to incident PsA. Early onset as well as severe psoriasis is associated with the HLA- C*06 allele as is longer psoriasis-PsA latency. Although not evaluated in this study, this genetic factor, or other factors such as detection bias, may underly these observations.

Once diagnosed, stratification of PsA severity is important for planning treatment. Towards this goal, Dubash et al² demonstrated that the presence of dactylitis indicates a more severe PsA phenotype. In a study of 177 disease-modifying antirheumatic drug (DMARD)-naive patients with early PsA, they found that those with dactylitis (46%) had significantly higher tender and swollen joint counts and C-reactive protein than those with non-dactylitic PsA. Ultrasound synovitis and erosions were also significantly more prevalent in dactylitic PsA. Thus, the presence of dactylitis indicates a more severe phenotype, and patients with dactylitis should be treated aggressively to improve long-term outcomes.

Novel therapies are being frequently evaluated in PsA and a recent target is interleukin (IL)-23, a key cytokine in the T-helper 17 (Th17) pathway and in the pathogenesis of psoriatic disease. Risankizumab is a novel monoclonal antibody targeting IL-23. In the double-blind phase 3 KEEPsAKE 1 study including 964 patients with active PsA and inadequate response to one or more conventional synthetic (cs) DMARDs. They were randomly assigned to receive 150 mg risankizumab or placebo, Kristensen et al³ demonstrated that, at week 24, at least a 20% improvement in the American College of Rheumatology score (ACR20) was achieved by a significantly higher proportion of patients receiving risankizumab vs. placebo (57.3% vs. 33.5%; P < .001). Treatment-emergent adverse events were mild-to-moderate and reported at similar frequencies in the risankizumab (40.4%) and placebo (38.7%) groups. Thus, risankizumab was efficacious in reducing clinical manifestations of PsA in patients with inadequate response to csDMARDs with no new adverse events. An important question when treating patients with PsA with targeted therapies is the need for concomitant therapy with csDMARDs. In a pooled analysis of 2 phase 3 trials, SELECT-PsA 1 and SELECT-PsA 2,  1,916 patients with active PsA with an inadequate response to ≥1 non-biologic (nb) DMARDs or biologic DMARDs were randomly assigned to placebo, 15 mg upadacitinib, or 30 mg upadacitinib as monotherapy or in combination with ≤2 nbDMARDs for 24 weeks, Nash et al⁴ demonstrated that at week 12, ACR20 response was achieved by a similar proportion of patients receiving 15 mg upadacitinib or 30 mg upadacitinib as monotherapy (15 mg: 33.7%; 95% CI 24.4%-43.1%; 30 mg: 45.7%; 95% CI 36.9%-54.5%) or combination therapy (15 mg: 34.0%; 95% CI 27.9%-40.1%; 30 mg: 39.6%; 95% CI 33.7%-45.5%). Adverse events were generally similar between monotherapy and combination therapy. Although, we don’t have information regarding the sustainability of the response, these data indicate that upadacitinib may be used without concomitant csDMARDs in PsA.

References

1. Karmacharya P et al. Time to transition from psoriasis to psoriatic arthritis: A population-based study. Semin Arthritis Rheum. 2021(Dec 31):S0049-0172(21)00230-4.
2. Dubash S et al. Dactylitis is an indicator of a more severe phenotype independently associated with greater SJC, CRP, ultrasound synovitis and erosive damage in DMARD-naive early psoriatic arthritis. Ann Rheum Dis. 2021(Dec 10):annrheumdis-2021-220964.
3. Kristensen LE et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 1 trial. Ann Rheum Dis. 2022(Feb);81(2):225-231.
4. Nash P et al. Upadacitinib as monotherapy and in combination with non-biologic disease-modifying antirheumatic drugs for psoriatic arthritis. Rheumatology (Oxford). 2021(Dec 3):keab905.

Breast cancer diagnosis and treatment in young women can present unique challenges based on their life stage, including potential impact on fertility and future pregnancy. The role of GnRH analogues for ovarian protection during chemotherapy has been shown in both the POEMS-SWOG S0230 and PROMISE-GIM6 studies. Zong and colleagues conducted a phase 3 trial in China among premenopausal women with stage I-III breast cancer receiving cyclophosphamide-containing chemotherapy, with randomization to GnRHa + chemotherapy vs chemotherapy alone. Among 301 patients eligible for primary endpoint analysis, the premature ovarian insufficiency rate at 12 months was 10.3% for the GnRHa group vs 44.5% for the control group (odds ratio 0.23; P < 0.001). The rate of ovarian function recovery was also 46.4% higher in the GnRHa group. Furthermore, although survival outcomes were similar between groups, in patients <35 years of age, the tumor-free survival was higher in the GnRHa group vs control (93% vs 62%, P = 0.004) (Zong et al). These data reinforce the role of GnRHa as a means to reduce POI risk and support ovarian function recovery in young women undergoing chemotherapy for breast cancer. Measures of fertility and timing of pregnancy after breast cancer diagnosis continue to be areas of active research.

The treatment landscape for early-stage HER2-positive breast cancer continues to rapidly evolve with efforts to enhance efficacy and minimize toxicity for patients. The phase 3 KAITLIN study included 1846 patients with early-stage HER2-positive breast cancer (node-positive or node-negative, hormone receptor-negative and ≥T2 primary tumor) with randomization after surgery to adjuvant AC followed by taxane + trastuzumab + pertuzumab (AC-THP) or AC followed by T-DM1 + pertuzumab (AC-KP). In both the overall and node-positive populations, there was no significant difference in IDFS between the arms (stratified HR 0.98 and 0.97, respectively). In the overall population, the 3-year IDFS was 93.1% for AC-KP and 94.2% for AC-THP. Treatment completion rates were lower for AC-KP vs AC-THP (65.0% vs 88.4%), with T-DM1 discontinuation driven mostly by lab abnormalities (elevated liver function tests and thrombocytopenia) (Krop et al). Many patients diagnosed with early HER2-positive breast cancer (specifically those with tumors >2cm or node-positive) are treated with neoadjuvant chemotherapy + HER2-targeted therapy with subsequent tailoring of adjuvant treatment pending response, including use of T-DM1 if residual disease present. Future escalation and de-escalation strategies are being explored to further optimize outcomes and decrease side effects.

The addition of CDK 4/6 inhibitors to endocrine therapy has led to improved survival outcomes for patients diagnosed with advanced HR-positive-HER2-negative breast cancer. Lu and colleagues presented exploratory updated OS results among 672 patients with extended follow-up (median 53.5 months) from MONALEESA-7, which was a phase 3 randomized trial of ribociclib + endocrine therapy vs endocrine therapy alone among peri/pre-menopausal patients with HR-positive/HER2-negative advanced breast cancer. Median OS was 58.7 months vs 48.0 months for the ribociclib and placebo arms, respectively (HR 0.76), and a more pronounced benefit was seen in patients <40 years of age (median OS 51.3 months vs 40.5 months for ribociclib vs placebo arm; HR 0.65) (Lu et al). Furthermore, there was a significant delay in time to chemotherapy with ribociclib vs placebo (50.9 months vs 36.8 months; HR 0.69) which can certainly impact quality of life. A prior pooled analysis of the various MONALEESA trials demonstrated consistent PFS benefit with ribociclib across all intrinsic breast cancer subtypes, with the exception of basal-like and a more pronounced favorable impact in HER2-enriched. Future research to elucidate differences among CDK 4/6 inhibitors, influence of breast cancer subtype on their effect and how this can be translated to routine clinical practice are warranted.

Breast cancer diagnosis and treatment in young women can present unique challenges based on their life stage, including potential impact on fertility and future pregnancy. The role of GnRH analogues for ovarian protection during chemotherapy has been shown in both the POEMS-SWOG S0230 and PROMISE-GIM6 studies. Zong and colleagues conducted a phase 3 trial in China among premenopausal women with stage I-III breast cancer receiving cyclophosphamide-containing chemotherapy, with randomization to GnRHa + chemotherapy vs chemotherapy alone. Among 301 patients eligible for primary endpoint analysis, the premature ovarian insufficiency rate at 12 months was 10.3% for the GnRHa group vs 44.5% for the control group (odds ratio 0.23; P < 0.001). The rate of ovarian function recovery was also 46.4% higher in the GnRHa group. Furthermore, although survival outcomes were similar between groups, in patients <35 years of age, the tumor-free survival was higher in the GnRHa group vs control (93% vs 62%, P = 0.004) (Zong et al). These data reinforce the role of GnRHa as a means to reduce POI risk and support ovarian function recovery in young women undergoing chemotherapy for breast cancer. Measures of fertility and timing of pregnancy after breast cancer diagnosis continue to be areas of active research.

The treatment landscape for early-stage HER2-positive breast cancer continues to rapidly evolve with efforts to enhance efficacy and minimize toxicity for patients. The phase 3 KAITLIN study included 1846 patients with early-stage HER2-positive breast cancer (node-positive or node-negative, hormone receptor-negative and ≥T2 primary tumor) with randomization after surgery to adjuvant AC followed by taxane + trastuzumab + pertuzumab (AC-THP) or AC followed by T-DM1 + pertuzumab (AC-KP). In both the overall and node-positive populations, there was no significant difference in IDFS between the arms (stratified HR 0.98 and 0.97, respectively). In the overall population, the 3-year IDFS was 93.1% for AC-KP and 94.2% for AC-THP. Treatment completion rates were lower for AC-KP vs AC-THP (65.0% vs 88.4%), with T-DM1 discontinuation driven mostly by lab abnormalities (elevated liver function tests and thrombocytopenia) (Krop et al). Many patients diagnosed with early HER2-positive breast cancer (specifically those with tumors >2cm or node-positive) are treated with neoadjuvant chemotherapy + HER2-targeted therapy with subsequent tailoring of adjuvant treatment pending response, including use of T-DM1 if residual disease present. Future escalation and de-escalation strategies are being explored to further optimize outcomes and decrease side effects.

The addition of CDK 4/6 inhibitors to endocrine therapy has led to improved survival outcomes for patients diagnosed with advanced HR-positive-HER2-negative breast cancer. Lu and colleagues presented exploratory updated OS results among 672 patients with extended follow-up (median 53.5 months) from MONALEESA-7, which was a phase 3 randomized trial of ribociclib + endocrine therapy vs endocrine therapy alone among peri/pre-menopausal patients with HR-positive/HER2-negative advanced breast cancer. Median OS was 58.7 months vs 48.0 months for the ribociclib and placebo arms, respectively (HR 0.76), and a more pronounced benefit was seen in patients <40 years of age (median OS 51.3 months vs 40.5 months for ribociclib vs placebo arm; HR 0.65) (Lu et al). Furthermore, there was a significant delay in time to chemotherapy with ribociclib vs placebo (50.9 months vs 36.8 months; HR 0.69) which can certainly impact quality of life. A prior pooled analysis of the various MONALEESA trials demonstrated consistent PFS benefit with ribociclib across all intrinsic breast cancer subtypes, with the exception of basal-like and a more pronounced favorable impact in HER2-enriched. Future research to elucidate differences among CDK 4/6 inhibitors, influence of breast cancer subtype on their effect and how this can be translated to routine clinical practice are warranted.

Breast cancer diagnosis and treatment in young women can present unique challenges based on their life stage, including potential impact on fertility and future pregnancy. The role of GnRH analogues for ovarian protection during chemotherapy has been shown in both the POEMS-SWOG S0230 and PROMISE-GIM6 studies. Zong and colleagues conducted a phase 3 trial in China among premenopausal women with stage I-III breast cancer receiving cyclophosphamide-containing chemotherapy, with randomization to GnRHa + chemotherapy vs chemotherapy alone. Among 301 patients eligible for primary endpoint analysis, the premature ovarian insufficiency rate at 12 months was 10.3% for the GnRHa group vs 44.5% for the control group (odds ratio 0.23; P < 0.001). The rate of ovarian function recovery was also 46.4% higher in the GnRHa group. Furthermore, although survival outcomes were similar between groups, in patients <35 years of age, the tumor-free survival was higher in the GnRHa group vs control (93% vs 62%, P = 0.004) (Zong et al). These data reinforce the role of GnRHa as a means to reduce POI risk and support ovarian function recovery in young women undergoing chemotherapy for breast cancer. Measures of fertility and timing of pregnancy after breast cancer diagnosis continue to be areas of active research.

The treatment landscape for early-stage HER2-positive breast cancer continues to rapidly evolve with efforts to enhance efficacy and minimize toxicity for patients. The phase 3 KAITLIN study included 1846 patients with early-stage HER2-positive breast cancer (node-positive or node-negative, hormone receptor-negative and ≥T2 primary tumor) with randomization after surgery to adjuvant AC followed by taxane + trastuzumab + pertuzumab (AC-THP) or AC followed by T-DM1 + pertuzumab (AC-KP). In both the overall and node-positive populations, there was no significant difference in IDFS between the arms (stratified HR 0.98 and 0.97, respectively). In the overall population, the 3-year IDFS was 93.1% for AC-KP and 94.2% for AC-THP. Treatment completion rates were lower for AC-KP vs AC-THP (65.0% vs 88.4%), with T-DM1 discontinuation driven mostly by lab abnormalities (elevated liver function tests and thrombocytopenia) (Krop et al). Many patients diagnosed with early HER2-positive breast cancer (specifically those with tumors >2cm or node-positive) are treated with neoadjuvant chemotherapy + HER2-targeted therapy with subsequent tailoring of adjuvant treatment pending response, including use of T-DM1 if residual disease present. Future escalation and de-escalation strategies are being explored to further optimize outcomes and decrease side effects.

The addition of CDK 4/6 inhibitors to endocrine therapy has led to improved survival outcomes for patients diagnosed with advanced HR-positive-HER2-negative breast cancer. Lu and colleagues presented exploratory updated OS results among 672 patients with extended follow-up (median 53.5 months) from MONALEESA-7, which was a phase 3 randomized trial of ribociclib + endocrine therapy vs endocrine therapy alone among peri/pre-menopausal patients with HR-positive/HER2-negative advanced breast cancer. Median OS was 58.7 months vs 48.0 months for the ribociclib and placebo arms, respectively (HR 0.76), and a more pronounced benefit was seen in patients <40 years of age (median OS 51.3 months vs 40.5 months for ribociclib vs placebo arm; HR 0.65) (Lu et al). Furthermore, there was a significant delay in time to chemotherapy with ribociclib vs placebo (50.9 months vs 36.8 months; HR 0.69) which can certainly impact quality of life. A prior pooled analysis of the various MONALEESA trials demonstrated consistent PFS benefit with ribociclib across all intrinsic breast cancer subtypes, with the exception of basal-like and a more pronounced favorable impact in HER2-enriched. Future research to elucidate differences among CDK 4/6 inhibitors, influence of breast cancer subtype on their effect and how this can be translated to routine clinical practice are warranted.