Clinical Edge Journal Scan

The class of CDK 4/6 inhibitors represents a significant advance in the treatment of hormone receptor (HR)-positive breast cancer. All three CDK 4/6 inhibitors (palbociclib, abemaciclib, and ribociclib) are approved in combination with endocrine therapy in the metastatic setting. As drugs show promise in later-stage disease, they are then often studied in the curative space. Presently, abemaciclib is the only CDK 4/6 inhibitor that has been approved by the US Food and Drug Administration for the treatment of HR-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, high-risk early breast cancer, based on results from the monarchE trial, which demonstrated invasive disease-free survival benefit with the addition of 2 years of abemaciclib to endocrine therapy. At 4 years, the absolute difference in invasive disease-free survival (IDFS) between the groups was 6.4% (85.8% in the abemaciclib + endocrine therapy group vs 79.4% in the endocrine therapy–alone group).^[3] In contrast, the PENELOPE-B and PALLAS trials did not show benefit with the addition of palbociclib to endocrine therapy in the adjuvant setting.^[4,5] The phase 3 NATALEE trial randomly assigned patients with HR-positive, HER2-negative early breast cancer to ribociclib (400 mg daily for 3 weeks followed by 1 week off for 3 years) plus a nonsteroidal aromatase inhibitor (NSAI) or an NSAI alone. At the time of prespecified interim analysis, among 5101 patients, ribociclib + NSAI led to a significant improvement in IDFS compared with endocrine therapy alone (3-year IDFS was 90.4% vs 87.1%; hazard ratio 0.75; 95% CI 0.62-0.91; P = .003). It is certainly noteworthy that the trial design, endocrine therapies, and patient populations differed between these adjuvant studies; for example, NATALEE included a lower-risk population, and all patients received an NSAI (in monarchE approximately 30% received tamoxifen). The current results of NATALEE are encouraging; an absolute benefit of 3.3% should be considered and weighed against toxicities and cost, and longer follow-up is needed to further elucidate the role of ribociclib in the adjuvant space.

The meaningful impact of achieving a pathologic complete response (pCR) has been demonstrated in various prior studies. Response to neoadjuvant chemotherapy informs prognosis and helps tailor adjuvant therapy, the latter of which is particularly relevant for the HER2-positive subtype. Strategies to identify patients who are more likely to achieve pCR and predictors of early responders may aid in improving efficacy outcomes and limiting toxicities. TRAIN-3 is a single-arm, phase 2 study that included 235 and 232 patients with stage II/III HR-/HER2+ and HR+/HER2+ breast cancer, respectively, undergoing neoadjuvant chemotherapy (weekly paclitaxel D1 and D8/carboplatin AUC 6 D1/trastuzumab D1/pertuzumab D1 every 3 weeks for up to nine cycles), and was designed to evaluate radiologic and pathologic response rates and event-free survival. Response was monitored by breast MRI every 3 cycles and lymph node biopsy. Among patients with HR-/HER2+ tumors, 84 (36%; 95% CI 30-43) achieved a radiologic complete response after one to three cycles, of whom the majority (88%; 95% CI 79-94) had pCR. Patients with HR+/HER2+ tumors did not show the same degree of benefit with an MRI-based monitoring strategy; among the 138 patients (59%; 95% CI 53-66) who had a complete radiologic response after one to nine cycles, 73 (53%; 95% CI 44-61) had pCR. Additional imaging-guided modalities being studied to tailor and optimize treatment include [¹⁸F]fluorodeoxyglucose-PET-CT and volumetric MRI, in the PHERGain and I-SPY trials, respectively.^[6,7]

Additional References:

1. Giuliano AE, Ballman KV, McCall L, et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: The ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA. 2017;318:918-926. doi: 10.1001/jama.2017.11470 Source
2. Bartels SAL, Donker M, Poncet C, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer: 10-year results of the randomized controlled EORTC 10981-22023 AMAROS trial. J Clin Oncol. 2023;41:2159-2165. doi: 10.1200/JCO.22.01565 Source
3. Johnston SRD, Toi M, O'Shaughnessy J, et al, on behalf of the monarchE Committee Members. Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): Results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. Lancet Oncol. 2023;24:77-90. doi: 10.1016/S1470-2045(22)00694-5 Source
4. Loibl S, Marmé F, Martin M, et al. Palbociclib for residual high-risk invasive HR-positive and HER2-negative early breast cancer—The Penelope-B trial. J Clin Oncol. 2021;39:1518-1530. doi: 10.1200/JCO.20.03639 Source
5. Gnant M, Dueck AC, Frantal S, et al, on behalf of the PALLAS groups and investigators. Adjuvant palbociclib for early breast cancer: The PALLAS trial results (ABCSG-42/AFT-05/BIG-14-03). J Clin Oncol. 2022;40:282-293. doi: 10.1200/JCO.21.02554 Source
6. Pérez-García JM, Cortés J, Ruiz-Borrego M, et al, on behalf of the PHERGain trial investigators. 3-year invasive disease-free survival with chemotherapy de-escalation using an 18F-FDG-PET-based, pathological complete response-adapted strategy in HER2-positive early breast cancer (PHERGain): A randomised, open-label, phase 2 trial. Lancet. 2024;403:1649-1659. doi: 10.1016/S0140-6736(24)00054-0 Source
7. Hylton NM, Gatsonis CA, Rosen MA, et al, for the ACRIN 6657 trial team and I-SPY 1 trial investigators. Neoadjuvant chemotherapy for breast cancer: Functional tumor volume by MR imaging predicts recurrence-free survival-results from the ACRIN 6657/CALGB 150007 I-SPY 1 trial. Radiology. 2016;279:44-55. doi: 10.1148/radiol.2015150013 Source

The class of CDK 4/6 inhibitors represents a significant advance in the treatment of hormone receptor (HR)-positive breast cancer. All three CDK 4/6 inhibitors (palbociclib, abemaciclib, and ribociclib) are approved in combination with endocrine therapy in the metastatic setting. As drugs show promise in later-stage disease, they are then often studied in the curative space. Presently, abemaciclib is the only CDK 4/6 inhibitor that has been approved by the US Food and Drug Administration for the treatment of HR-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, high-risk early breast cancer, based on results from the monarchE trial, which demonstrated invasive disease-free survival benefit with the addition of 2 years of abemaciclib to endocrine therapy. At 4 years, the absolute difference in invasive disease-free survival (IDFS) between the groups was 6.4% (85.8% in the abemaciclib + endocrine therapy group vs 79.4% in the endocrine therapy–alone group).^[3] In contrast, the PENELOPE-B and PALLAS trials did not show benefit with the addition of palbociclib to endocrine therapy in the adjuvant setting.^[4,5] The phase 3 NATALEE trial randomly assigned patients with HR-positive, HER2-negative early breast cancer to ribociclib (400 mg daily for 3 weeks followed by 1 week off for 3 years) plus a nonsteroidal aromatase inhibitor (NSAI) or an NSAI alone. At the time of prespecified interim analysis, among 5101 patients, ribociclib + NSAI led to a significant improvement in IDFS compared with endocrine therapy alone (3-year IDFS was 90.4% vs 87.1%; hazard ratio 0.75; 95% CI 0.62-0.91; P = .003). It is certainly noteworthy that the trial design, endocrine therapies, and patient populations differed between these adjuvant studies; for example, NATALEE included a lower-risk population, and all patients received an NSAI (in monarchE approximately 30% received tamoxifen). The current results of NATALEE are encouraging; an absolute benefit of 3.3% should be considered and weighed against toxicities and cost, and longer follow-up is needed to further elucidate the role of ribociclib in the adjuvant space.

The meaningful impact of achieving a pathologic complete response (pCR) has been demonstrated in various prior studies. Response to neoadjuvant chemotherapy informs prognosis and helps tailor adjuvant therapy, the latter of which is particularly relevant for the HER2-positive subtype. Strategies to identify patients who are more likely to achieve pCR and predictors of early responders may aid in improving efficacy outcomes and limiting toxicities. TRAIN-3 is a single-arm, phase 2 study that included 235 and 232 patients with stage II/III HR-/HER2+ and HR+/HER2+ breast cancer, respectively, undergoing neoadjuvant chemotherapy (weekly paclitaxel D1 and D8/carboplatin AUC 6 D1/trastuzumab D1/pertuzumab D1 every 3 weeks for up to nine cycles), and was designed to evaluate radiologic and pathologic response rates and event-free survival. Response was monitored by breast MRI every 3 cycles and lymph node biopsy. Among patients with HR-/HER2+ tumors, 84 (36%; 95% CI 30-43) achieved a radiologic complete response after one to three cycles, of whom the majority (88%; 95% CI 79-94) had pCR. Patients with HR+/HER2+ tumors did not show the same degree of benefit with an MRI-based monitoring strategy; among the 138 patients (59%; 95% CI 53-66) who had a complete radiologic response after one to nine cycles, 73 (53%; 95% CI 44-61) had pCR. Additional imaging-guided modalities being studied to tailor and optimize treatment include [¹⁸F]fluorodeoxyglucose-PET-CT and volumetric MRI, in the PHERGain and I-SPY trials, respectively.^[6,7]

Additional References:

1. Giuliano AE, Ballman KV, McCall L, et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: The ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA. 2017;318:918-926. doi: 10.1001/jama.2017.11470 Source
2. Bartels SAL, Donker M, Poncet C, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer: 10-year results of the randomized controlled EORTC 10981-22023 AMAROS trial. J Clin Oncol. 2023;41:2159-2165. doi: 10.1200/JCO.22.01565 Source
3. Johnston SRD, Toi M, O'Shaughnessy J, et al, on behalf of the monarchE Committee Members. Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): Results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. Lancet Oncol. 2023;24:77-90. doi: 10.1016/S1470-2045(22)00694-5 Source
4. Loibl S, Marmé F, Martin M, et al. Palbociclib for residual high-risk invasive HR-positive and HER2-negative early breast cancer—The Penelope-B trial. J Clin Oncol. 2021;39:1518-1530. doi: 10.1200/JCO.20.03639 Source
5. Gnant M, Dueck AC, Frantal S, et al, on behalf of the PALLAS groups and investigators. Adjuvant palbociclib for early breast cancer: The PALLAS trial results (ABCSG-42/AFT-05/BIG-14-03). J Clin Oncol. 2022;40:282-293. doi: 10.1200/JCO.21.02554 Source
6. Pérez-García JM, Cortés J, Ruiz-Borrego M, et al, on behalf of the PHERGain trial investigators. 3-year invasive disease-free survival with chemotherapy de-escalation using an 18F-FDG-PET-based, pathological complete response-adapted strategy in HER2-positive early breast cancer (PHERGain): A randomised, open-label, phase 2 trial. Lancet. 2024;403:1649-1659. doi: 10.1016/S0140-6736(24)00054-0 Source
7. Hylton NM, Gatsonis CA, Rosen MA, et al, for the ACRIN 6657 trial team and I-SPY 1 trial investigators. Neoadjuvant chemotherapy for breast cancer: Functional tumor volume by MR imaging predicts recurrence-free survival-results from the ACRIN 6657/CALGB 150007 I-SPY 1 trial. Radiology. 2016;279:44-55. doi: 10.1148/radiol.2015150013 Source

The class of CDK 4/6 inhibitors represents a significant advance in the treatment of hormone receptor (HR)-positive breast cancer. All three CDK 4/6 inhibitors (palbociclib, abemaciclib, and ribociclib) are approved in combination with endocrine therapy in the metastatic setting. As drugs show promise in later-stage disease, they are then often studied in the curative space. Presently, abemaciclib is the only CDK 4/6 inhibitor that has been approved by the US Food and Drug Administration for the treatment of HR-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, high-risk early breast cancer, based on results from the monarchE trial, which demonstrated invasive disease-free survival benefit with the addition of 2 years of abemaciclib to endocrine therapy. At 4 years, the absolute difference in invasive disease-free survival (IDFS) between the groups was 6.4% (85.8% in the abemaciclib + endocrine therapy group vs 79.4% in the endocrine therapy–alone group).^[3] In contrast, the PENELOPE-B and PALLAS trials did not show benefit with the addition of palbociclib to endocrine therapy in the adjuvant setting.^[4,5] The phase 3 NATALEE trial randomly assigned patients with HR-positive, HER2-negative early breast cancer to ribociclib (400 mg daily for 3 weeks followed by 1 week off for 3 years) plus a nonsteroidal aromatase inhibitor (NSAI) or an NSAI alone. At the time of prespecified interim analysis, among 5101 patients, ribociclib + NSAI led to a significant improvement in IDFS compared with endocrine therapy alone (3-year IDFS was 90.4% vs 87.1%; hazard ratio 0.75; 95% CI 0.62-0.91; P = .003). It is certainly noteworthy that the trial design, endocrine therapies, and patient populations differed between these adjuvant studies; for example, NATALEE included a lower-risk population, and all patients received an NSAI (in monarchE approximately 30% received tamoxifen). The current results of NATALEE are encouraging; an absolute benefit of 3.3% should be considered and weighed against toxicities and cost, and longer follow-up is needed to further elucidate the role of ribociclib in the adjuvant space.

The meaningful impact of achieving a pathologic complete response (pCR) has been demonstrated in various prior studies. Response to neoadjuvant chemotherapy informs prognosis and helps tailor adjuvant therapy, the latter of which is particularly relevant for the HER2-positive subtype. Strategies to identify patients who are more likely to achieve pCR and predictors of early responders may aid in improving efficacy outcomes and limiting toxicities. TRAIN-3 is a single-arm, phase 2 study that included 235 and 232 patients with stage II/III HR-/HER2+ and HR+/HER2+ breast cancer, respectively, undergoing neoadjuvant chemotherapy (weekly paclitaxel D1 and D8/carboplatin AUC 6 D1/trastuzumab D1/pertuzumab D1 every 3 weeks for up to nine cycles), and was designed to evaluate radiologic and pathologic response rates and event-free survival. Response was monitored by breast MRI every 3 cycles and lymph node biopsy. Among patients with HR-/HER2+ tumors, 84 (36%; 95% CI 30-43) achieved a radiologic complete response after one to three cycles, of whom the majority (88%; 95% CI 79-94) had pCR. Patients with HR+/HER2+ tumors did not show the same degree of benefit with an MRI-based monitoring strategy; among the 138 patients (59%; 95% CI 53-66) who had a complete radiologic response after one to nine cycles, 73 (53%; 95% CI 44-61) had pCR. Additional imaging-guided modalities being studied to tailor and optimize treatment include [¹⁸F]fluorodeoxyglucose-PET-CT and volumetric MRI, in the PHERGain and I-SPY trials, respectively.^[6,7]

Additional References:

1. Giuliano AE, Ballman KV, McCall L, et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: The ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA. 2017;318:918-926. doi: 10.1001/jama.2017.11470 Source
2. Bartels SAL, Donker M, Poncet C, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer: 10-year results of the randomized controlled EORTC 10981-22023 AMAROS trial. J Clin Oncol. 2023;41:2159-2165. doi: 10.1200/JCO.22.01565 Source
3. Johnston SRD, Toi M, O'Shaughnessy J, et al, on behalf of the monarchE Committee Members. Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): Results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. Lancet Oncol. 2023;24:77-90. doi: 10.1016/S1470-2045(22)00694-5 Source
4. Loibl S, Marmé F, Martin M, et al. Palbociclib for residual high-risk invasive HR-positive and HER2-negative early breast cancer—The Penelope-B trial. J Clin Oncol. 2021;39:1518-1530. doi: 10.1200/JCO.20.03639 Source
5. Gnant M, Dueck AC, Frantal S, et al, on behalf of the PALLAS groups and investigators. Adjuvant palbociclib for early breast cancer: The PALLAS trial results (ABCSG-42/AFT-05/BIG-14-03). J Clin Oncol. 2022;40:282-293. doi: 10.1200/JCO.21.02554 Source
6. Pérez-García JM, Cortés J, Ruiz-Borrego M, et al, on behalf of the PHERGain trial investigators. 3-year invasive disease-free survival with chemotherapy de-escalation using an 18F-FDG-PET-based, pathological complete response-adapted strategy in HER2-positive early breast cancer (PHERGain): A randomised, open-label, phase 2 trial. Lancet. 2024;403:1649-1659. doi: 10.1016/S0140-6736(24)00054-0 Source
7. Hylton NM, Gatsonis CA, Rosen MA, et al, for the ACRIN 6657 trial team and I-SPY 1 trial investigators. Neoadjuvant chemotherapy for breast cancer: Functional tumor volume by MR imaging predicts recurrence-free survival-results from the ACRIN 6657/CALGB 150007 I-SPY 1 trial. Radiology. 2016;279:44-55. doi: 10.1148/radiol.2015150013 Source

Migraine and other headache types are common ailments, and there are many stereotypes and stigmas associated with these conditions. One of the prevailing beliefs about headaches and migraines is that they are linked with internalizing mental health conditions — anxiety and depression. These associations can affect pediatric migraine patients and their parents in complicated ways, potentially hindering adequate diagnosis and treatment. Results of a recent prospective study, published in the journal Headache, provided results that challenge the widespread belief that people who have migraines have a higher-than-average rate of internalizing mental health disorders. The authors provided a discussion and data to explain that their initial hypothesis of a relationship between migraine and mental health was disproven. The study included 123 participants age 8-18 years who had been previously diagnosed with migraine. The patients, who were seen in a pediatric neurology clinic, completed headache questionnaires and validated measures of anxiety and depressive symptoms. The final analysis showed no significant association between migraines or headaches with anxiety or depression.

Why does this matter? Stigma can prevent patients and parents from seeking care if parents feel that they will be judged as bad parents for contributing to their children's anxiety, depression, headaches, and migraines. In fact, beyond mental health stigma, children who have migraine can be blamed for having an unhealthy lifestyle.^[1] While advice to get enough sleep, eat healthy, and stay active is worthwhile, there can be an implication that pediatric migraine patients are causing their migraines by living an unhealthy lifestyle.^[1] Additionally, the implication that parents are not properly taking care of their children's health can inhibit an accurate symptom history. Releasing pediatric migraine patients and their parents from myths about migraines and headaches can be a beneficial component of doctor-patient communication regarding migraine care.

It is possible that dietary adjustments or supplements could help improve migraine frequency and severity. Maintaining a healthy diet is a frequent recommendation for people who have headaches, but it can be frustrating for patients to receive general recommendations to follow a healthy lifestyle. Specific direction regarding which foods to avoid and which foods to add to a diet can be helpful for patients as they try to navigate the challenge of adopting migraine-friendly lifestyle changes.

Eicosapentaenoic acid (EPA) is one of the omega-3 fatty acids. A recent study, with results published in Brain, Behavior, and Immunity, examined the effects of EPA on migraines. The 12-week randomized, double-blind, placebo-controlled trial included 70 participants who had been diagnosed with episodic migraine. Participants were randomly assigned to either EPA (2 g fish oil with 1.8 g of EPA/day) or placebo (2 g soybean oil/day). Migraine frequency and severity were assessed using standardized scales. According to the authors, the high-dose-EPA group had significantly reduced migraine frequency and severity, fewer number of days using acute treatment, reduced migraine-associated disability, improved anxiety and depression, and improved quality of life in comparison to the placebo group. The EPA group did not experience notable adverse events.To provide a sense of scale regarding dietary EPA, 3 oz of cooked wild salmon has 0.35 g of EPA, 3 oz of cooked shrimp has 0.2 g of EPA, and 3 oz of light canned tuna has 0.02 g of EPA.^[2] Thus, it's important to note that the amount of EPA used in this study was higher than what would be expected of dietary EPA.

An observational prospective study published in Scientific Reports examined the effects of dietary phytochemical index (DPI) on migraine. DPI is defined as the proportion of daily energy intake derived from foods rich in phytochemicals. Consumption of phytochemical-rich foods has been associated with cardiovascular and metabolic diseases prevention in various populations. These foods include fruits, vegetables, whole grains, seeds, nuts, and legumes. The study included 265 adults age 20-50 who had a diagnosis of migraine. Participants were asked to fill out a questionnaire, which was used to evaluate their diet in the preceding year, and they were asked to complete a diary to track their migraine symptoms. The results showed an inverse relationship between DPI index and migraine frequency. Participants who had the highest DPI had the lowest migraine frequency.^[3] While the authors found the results to be statistically significant, they did not point to a cause and effect. Migraine-associated symptoms such as nausea can have an effect on dietary choices, so patients who experience migraine symptoms may avoid certain foods before, during, or after a migraine episode. They also may consistently avoid foods that they have experienced as migraine triggers.

Diet and lifestyle can have an effect on migraine frequency, severity, and overall migraine-associated quality of life. Beyond general recommendations, however, it is not yet well established which foods or supplements could potentially help alleviate migraines. Advice to maintain a healthy lifestyle is definitely worthwhile for migraine patients, but it is important to avoid conveying blame or stigma when it comes to communication about the effect of lifestyle on migraine. This is especially important for pediatric migraine patients because the stigma extends beyond children to parents and could potentially interfere with clear communication and adequate care.

Additional References

1. Gelfand AA, Irwin SL. Lifestyle advice for pediatric migraine: Blaming the patient, or evidence based? Semin Neurol. 2020;40:277-285. doi: 10.1055/s-0040-1708868 Source

2. National Institutes of Health. Office of Dietary Supplements. Omega-3 fatty acids. Updated February 15, 2023. Source

3. Hamedi-Shahraki S, Jowshan M-R, Zolghadrpour M-A, et al. Dietary phytochemical index is favorably associated with oxidative stress status and cardiovascular risk factors in adults with obesity. Sci Rep. 2023;13:7035. doi: 10.1038/s41598-023-34064-4 Source

Migraine and other headache types are common ailments, and there are many stereotypes and stigmas associated with these conditions. One of the prevailing beliefs about headaches and migraines is that they are linked with internalizing mental health conditions — anxiety and depression. These associations can affect pediatric migraine patients and their parents in complicated ways, potentially hindering adequate diagnosis and treatment. Results of a recent prospective study, published in the journal Headache, provided results that challenge the widespread belief that people who have migraines have a higher-than-average rate of internalizing mental health disorders. The authors provided a discussion and data to explain that their initial hypothesis of a relationship between migraine and mental health was disproven. The study included 123 participants age 8-18 years who had been previously diagnosed with migraine. The patients, who were seen in a pediatric neurology clinic, completed headache questionnaires and validated measures of anxiety and depressive symptoms. The final analysis showed no significant association between migraines or headaches with anxiety or depression.

Why does this matter? Stigma can prevent patients and parents from seeking care if parents feel that they will be judged as bad parents for contributing to their children's anxiety, depression, headaches, and migraines. In fact, beyond mental health stigma, children who have migraine can be blamed for having an unhealthy lifestyle.^[1] While advice to get enough sleep, eat healthy, and stay active is worthwhile, there can be an implication that pediatric migraine patients are causing their migraines by living an unhealthy lifestyle.^[1] Additionally, the implication that parents are not properly taking care of their children's health can inhibit an accurate symptom history. Releasing pediatric migraine patients and their parents from myths about migraines and headaches can be a beneficial component of doctor-patient communication regarding migraine care.

It is possible that dietary adjustments or supplements could help improve migraine frequency and severity. Maintaining a healthy diet is a frequent recommendation for people who have headaches, but it can be frustrating for patients to receive general recommendations to follow a healthy lifestyle. Specific direction regarding which foods to avoid and which foods to add to a diet can be helpful for patients as they try to navigate the challenge of adopting migraine-friendly lifestyle changes.

Eicosapentaenoic acid (EPA) is one of the omega-3 fatty acids. A recent study, with results published in Brain, Behavior, and Immunity, examined the effects of EPA on migraines. The 12-week randomized, double-blind, placebo-controlled trial included 70 participants who had been diagnosed with episodic migraine. Participants were randomly assigned to either EPA (2 g fish oil with 1.8 g of EPA/day) or placebo (2 g soybean oil/day). Migraine frequency and severity were assessed using standardized scales. According to the authors, the high-dose-EPA group had significantly reduced migraine frequency and severity, fewer number of days using acute treatment, reduced migraine-associated disability, improved anxiety and depression, and improved quality of life in comparison to the placebo group. The EPA group did not experience notable adverse events.To provide a sense of scale regarding dietary EPA, 3 oz of cooked wild salmon has 0.35 g of EPA, 3 oz of cooked shrimp has 0.2 g of EPA, and 3 oz of light canned tuna has 0.02 g of EPA.^[2] Thus, it's important to note that the amount of EPA used in this study was higher than what would be expected of dietary EPA.

An observational prospective study published in Scientific Reports examined the effects of dietary phytochemical index (DPI) on migraine. DPI is defined as the proportion of daily energy intake derived from foods rich in phytochemicals. Consumption of phytochemical-rich foods has been associated with cardiovascular and metabolic diseases prevention in various populations. These foods include fruits, vegetables, whole grains, seeds, nuts, and legumes. The study included 265 adults age 20-50 who had a diagnosis of migraine. Participants were asked to fill out a questionnaire, which was used to evaluate their diet in the preceding year, and they were asked to complete a diary to track their migraine symptoms. The results showed an inverse relationship between DPI index and migraine frequency. Participants who had the highest DPI had the lowest migraine frequency.^[3] While the authors found the results to be statistically significant, they did not point to a cause and effect. Migraine-associated symptoms such as nausea can have an effect on dietary choices, so patients who experience migraine symptoms may avoid certain foods before, during, or after a migraine episode. They also may consistently avoid foods that they have experienced as migraine triggers.

Diet and lifestyle can have an effect on migraine frequency, severity, and overall migraine-associated quality of life. Beyond general recommendations, however, it is not yet well established which foods or supplements could potentially help alleviate migraines. Advice to maintain a healthy lifestyle is definitely worthwhile for migraine patients, but it is important to avoid conveying blame or stigma when it comes to communication about the effect of lifestyle on migraine. This is especially important for pediatric migraine patients because the stigma extends beyond children to parents and could potentially interfere with clear communication and adequate care.

Additional References

1. Gelfand AA, Irwin SL. Lifestyle advice for pediatric migraine: Blaming the patient, or evidence based? Semin Neurol. 2020;40:277-285. doi: 10.1055/s-0040-1708868 Source

2. National Institutes of Health. Office of Dietary Supplements. Omega-3 fatty acids. Updated February 15, 2023. Source

3. Hamedi-Shahraki S, Jowshan M-R, Zolghadrpour M-A, et al. Dietary phytochemical index is favorably associated with oxidative stress status and cardiovascular risk factors in adults with obesity. Sci Rep. 2023;13:7035. doi: 10.1038/s41598-023-34064-4 Source

Migraine and other headache types are common ailments, and there are many stereotypes and stigmas associated with these conditions. One of the prevailing beliefs about headaches and migraines is that they are linked with internalizing mental health conditions — anxiety and depression. These associations can affect pediatric migraine patients and their parents in complicated ways, potentially hindering adequate diagnosis and treatment. Results of a recent prospective study, published in the journal Headache, provided results that challenge the widespread belief that people who have migraines have a higher-than-average rate of internalizing mental health disorders. The authors provided a discussion and data to explain that their initial hypothesis of a relationship between migraine and mental health was disproven. The study included 123 participants age 8-18 years who had been previously diagnosed with migraine. The patients, who were seen in a pediatric neurology clinic, completed headache questionnaires and validated measures of anxiety and depressive symptoms. The final analysis showed no significant association between migraines or headaches with anxiety or depression.

Why does this matter? Stigma can prevent patients and parents from seeking care if parents feel that they will be judged as bad parents for contributing to their children's anxiety, depression, headaches, and migraines. In fact, beyond mental health stigma, children who have migraine can be blamed for having an unhealthy lifestyle.^[1] While advice to get enough sleep, eat healthy, and stay active is worthwhile, there can be an implication that pediatric migraine patients are causing their migraines by living an unhealthy lifestyle.^[1] Additionally, the implication that parents are not properly taking care of their children's health can inhibit an accurate symptom history. Releasing pediatric migraine patients and their parents from myths about migraines and headaches can be a beneficial component of doctor-patient communication regarding migraine care.

It is possible that dietary adjustments or supplements could help improve migraine frequency and severity. Maintaining a healthy diet is a frequent recommendation for people who have headaches, but it can be frustrating for patients to receive general recommendations to follow a healthy lifestyle. Specific direction regarding which foods to avoid and which foods to add to a diet can be helpful for patients as they try to navigate the challenge of adopting migraine-friendly lifestyle changes.

Eicosapentaenoic acid (EPA) is one of the omega-3 fatty acids. A recent study, with results published in Brain, Behavior, and Immunity, examined the effects of EPA on migraines. The 12-week randomized, double-blind, placebo-controlled trial included 70 participants who had been diagnosed with episodic migraine. Participants were randomly assigned to either EPA (2 g fish oil with 1.8 g of EPA/day) or placebo (2 g soybean oil/day). Migraine frequency and severity were assessed using standardized scales. According to the authors, the high-dose-EPA group had significantly reduced migraine frequency and severity, fewer number of days using acute treatment, reduced migraine-associated disability, improved anxiety and depression, and improved quality of life in comparison to the placebo group. The EPA group did not experience notable adverse events.To provide a sense of scale regarding dietary EPA, 3 oz of cooked wild salmon has 0.35 g of EPA, 3 oz of cooked shrimp has 0.2 g of EPA, and 3 oz of light canned tuna has 0.02 g of EPA.^[2] Thus, it's important to note that the amount of EPA used in this study was higher than what would be expected of dietary EPA.

An observational prospective study published in Scientific Reports examined the effects of dietary phytochemical index (DPI) on migraine. DPI is defined as the proportion of daily energy intake derived from foods rich in phytochemicals. Consumption of phytochemical-rich foods has been associated with cardiovascular and metabolic diseases prevention in various populations. These foods include fruits, vegetables, whole grains, seeds, nuts, and legumes. The study included 265 adults age 20-50 who had a diagnosis of migraine. Participants were asked to fill out a questionnaire, which was used to evaluate their diet in the preceding year, and they were asked to complete a diary to track their migraine symptoms. The results showed an inverse relationship between DPI index and migraine frequency. Participants who had the highest DPI had the lowest migraine frequency.^[3] While the authors found the results to be statistically significant, they did not point to a cause and effect. Migraine-associated symptoms such as nausea can have an effect on dietary choices, so patients who experience migraine symptoms may avoid certain foods before, during, or after a migraine episode. They also may consistently avoid foods that they have experienced as migraine triggers.

Diet and lifestyle can have an effect on migraine frequency, severity, and overall migraine-associated quality of life. Beyond general recommendations, however, it is not yet well established which foods or supplements could potentially help alleviate migraines. Advice to maintain a healthy lifestyle is definitely worthwhile for migraine patients, but it is important to avoid conveying blame or stigma when it comes to communication about the effect of lifestyle on migraine. This is especially important for pediatric migraine patients because the stigma extends beyond children to parents and could potentially interfere with clear communication and adequate care.

Additional References

1. Gelfand AA, Irwin SL. Lifestyle advice for pediatric migraine: Blaming the patient, or evidence based? Semin Neurol. 2020;40:277-285. doi: 10.1055/s-0040-1708868 Source

2. National Institutes of Health. Office of Dietary Supplements. Omega-3 fatty acids. Updated February 15, 2023. Source

3. Hamedi-Shahraki S, Jowshan M-R, Zolghadrpour M-A, et al. Dietary phytochemical index is favorably associated with oxidative stress status and cardiovascular risk factors in adults with obesity. Sci Rep. 2023;13:7035. doi: 10.1038/s41598-023-34064-4 Source

Bimekizumab is a novel biologic therapy that inhibits interleukin (IL)–17A and IL-17F and is efficacious in the treatment of psoriasis, PsA, and axial spondyloarthritis. In the absence of a formal head-to-head study, matching-adjusted indirect comparison is a method to evaluate comparative effectiveness. Warren and colleagues ran a study that included biological DMARD-naive patients and patients with inadequate response to tumor necrosis factor inhibitors (TNFi-IR) with PsA who received bimekizumab (160 mg every 4 weeks; 431 and 267 patients, respectively) and guselkumab (100 mg every 4 weeks or every 8 weeks; 495 and 189 patients, respectively). They demonstrate that in biological DMARD-naive patients, bimekizumab was associated with a greater likelihood of achieving ≥70% improvement in American College of Rheumatology (ACR) response and minimal disease activity outcome at week 52 compared with guselkumab. Similar outcomes were observed in the TNFi-IR subgroup. Thus, bimekizumab may be more effective than guselkumab in PsA. Formal head-to-head studies comparing bimekizumab vs guselkumab are required.

With the availability of multiple targeted therapies for PsA, choosing the most effective and safe drug for a patient is difficult, especially in the absence of many head-to-head clinical trials. To help address this problem, Lin and Ren conducted a network meta-analysis of head-to-head active comparison studies in PsA. They included 17 studies in their analysis and demonstrated that Janus kinase inhibitors had the highest probability of achieving ACR 20/50/70 response. Treatment with IL-17A inhibitors was more likely than TNFi therapy to lead to resolution of enthesitis and dactylitis and achieving combined ACR 50 and Psoriasis Area Severity Index 100 response. Patients receiving phosphodiesterase 4 inhibitors were least likely to have adverse events. They conclude that when both efficacy and safety are considered, IL-17A inhibitors may be the better agent for initial therapy for PsA. IL-17A inhibitors are indeed safe and efficacious in PsA; more direct head-to-head comparisons as well as strategy trials are required to determine choice of first and subsequent therapy in PsA.

Infections are the most important adverse effects of targeted therapies. The risk for infection in PsA in real-world settings is not well known. In a cohort study that included 12,071 patients with PsA from the French national health insurance database who were new users of targeted therapies (adalimumab, etanercept, golimumab, certolizumab pegol, infliximab, secukinumab, ixekizumab, ustekinumab, and tofacitinib), Bastard and colleagues demonstrated that the incidence of serious infections in users of targeted therapies was 17.0 per 1000 person-years. Compared with new users of adalimumab, the risk for serious infections was significantly lower in new users of etanercept (weighted hazard ratio [wHR] 0.72; 95% CI 0.53-0.97) and ustekinumab (wHR 0.57; 95% CI 0.35-0.93). Thus, the overall risk for serious infections is low, with etanercept and ustekinumab being safer treatment options than adalimumab.

Bimekizumab is a novel biologic therapy that inhibits interleukin (IL)–17A and IL-17F and is efficacious in the treatment of psoriasis, PsA, and axial spondyloarthritis. In the absence of a formal head-to-head study, matching-adjusted indirect comparison is a method to evaluate comparative effectiveness. Warren and colleagues ran a study that included biological DMARD-naive patients and patients with inadequate response to tumor necrosis factor inhibitors (TNFi-IR) with PsA who received bimekizumab (160 mg every 4 weeks; 431 and 267 patients, respectively) and guselkumab (100 mg every 4 weeks or every 8 weeks; 495 and 189 patients, respectively). They demonstrate that in biological DMARD-naive patients, bimekizumab was associated with a greater likelihood of achieving ≥70% improvement in American College of Rheumatology (ACR) response and minimal disease activity outcome at week 52 compared with guselkumab. Similar outcomes were observed in the TNFi-IR subgroup. Thus, bimekizumab may be more effective than guselkumab in PsA. Formal head-to-head studies comparing bimekizumab vs guselkumab are required.

With the availability of multiple targeted therapies for PsA, choosing the most effective and safe drug for a patient is difficult, especially in the absence of many head-to-head clinical trials. To help address this problem, Lin and Ren conducted a network meta-analysis of head-to-head active comparison studies in PsA. They included 17 studies in their analysis and demonstrated that Janus kinase inhibitors had the highest probability of achieving ACR 20/50/70 response. Treatment with IL-17A inhibitors was more likely than TNFi therapy to lead to resolution of enthesitis and dactylitis and achieving combined ACR 50 and Psoriasis Area Severity Index 100 response. Patients receiving phosphodiesterase 4 inhibitors were least likely to have adverse events. They conclude that when both efficacy and safety are considered, IL-17A inhibitors may be the better agent for initial therapy for PsA. IL-17A inhibitors are indeed safe and efficacious in PsA; more direct head-to-head comparisons as well as strategy trials are required to determine choice of first and subsequent therapy in PsA.

Infections are the most important adverse effects of targeted therapies. The risk for infection in PsA in real-world settings is not well known. In a cohort study that included 12,071 patients with PsA from the French national health insurance database who were new users of targeted therapies (adalimumab, etanercept, golimumab, certolizumab pegol, infliximab, secukinumab, ixekizumab, ustekinumab, and tofacitinib), Bastard and colleagues demonstrated that the incidence of serious infections in users of targeted therapies was 17.0 per 1000 person-years. Compared with new users of adalimumab, the risk for serious infections was significantly lower in new users of etanercept (weighted hazard ratio [wHR] 0.72; 95% CI 0.53-0.97) and ustekinumab (wHR 0.57; 95% CI 0.35-0.93). Thus, the overall risk for serious infections is low, with etanercept and ustekinumab being safer treatment options than adalimumab.

Bimekizumab is a novel biologic therapy that inhibits interleukin (IL)–17A and IL-17F and is efficacious in the treatment of psoriasis, PsA, and axial spondyloarthritis. In the absence of a formal head-to-head study, matching-adjusted indirect comparison is a method to evaluate comparative effectiveness. Warren and colleagues ran a study that included biological DMARD-naive patients and patients with inadequate response to tumor necrosis factor inhibitors (TNFi-IR) with PsA who received bimekizumab (160 mg every 4 weeks; 431 and 267 patients, respectively) and guselkumab (100 mg every 4 weeks or every 8 weeks; 495 and 189 patients, respectively). They demonstrate that in biological DMARD-naive patients, bimekizumab was associated with a greater likelihood of achieving ≥70% improvement in American College of Rheumatology (ACR) response and minimal disease activity outcome at week 52 compared with guselkumab. Similar outcomes were observed in the TNFi-IR subgroup. Thus, bimekizumab may be more effective than guselkumab in PsA. Formal head-to-head studies comparing bimekizumab vs guselkumab are required.

With the availability of multiple targeted therapies for PsA, choosing the most effective and safe drug for a patient is difficult, especially in the absence of many head-to-head clinical trials. To help address this problem, Lin and Ren conducted a network meta-analysis of head-to-head active comparison studies in PsA. They included 17 studies in their analysis and demonstrated that Janus kinase inhibitors had the highest probability of achieving ACR 20/50/70 response. Treatment with IL-17A inhibitors was more likely than TNFi therapy to lead to resolution of enthesitis and dactylitis and achieving combined ACR 50 and Psoriasis Area Severity Index 100 response. Patients receiving phosphodiesterase 4 inhibitors were least likely to have adverse events. They conclude that when both efficacy and safety are considered, IL-17A inhibitors may be the better agent for initial therapy for PsA. IL-17A inhibitors are indeed safe and efficacious in PsA; more direct head-to-head comparisons as well as strategy trials are required to determine choice of first and subsequent therapy in PsA.

Infections are the most important adverse effects of targeted therapies. The risk for infection in PsA in real-world settings is not well known. In a cohort study that included 12,071 patients with PsA from the French national health insurance database who were new users of targeted therapies (adalimumab, etanercept, golimumab, certolizumab pegol, infliximab, secukinumab, ixekizumab, ustekinumab, and tofacitinib), Bastard and colleagues demonstrated that the incidence of serious infections in users of targeted therapies was 17.0 per 1000 person-years. Compared with new users of adalimumab, the risk for serious infections was significantly lower in new users of etanercept (weighted hazard ratio [wHR] 0.72; 95% CI 0.53-0.97) and ustekinumab (wHR 0.57; 95% CI 0.35-0.93). Thus, the overall risk for serious infections is low, with etanercept and ustekinumab being safer treatment options than adalimumab.

In "Atopic Dermatitis in Early Childhood and Risk of Inflammatory Bowel Disease: A Scandinavian Birth Cohort Study," Lerchova and colleagues found a statistically significant increased risk for inflammatory bowel disease (IBD) in children with atopic dermatitis. The study had a large patient population, giving it the power to identify very small differences. The researchers found increased risks for IBD, Crohn's disease, and ulcerative colitis (UC) in children with atopic dermatitis; UC had the greatest relative risk. But I don't think this risk was clinically meaningful. About 2 in every 1000 children with atopic dermatitis had UC, whereas about 1 in every 1000 children without atopic dermatitis had UC. Even if the increased absolute risk of 1 in 1000 children was due to atopic dermatitis and not to other factors, I don't think it justifies the authors' conclusion that "these findings might be useful in identifying at-risk individuals for IBD."

Sometimes reviewing articles makes me feel like a crotchety old man. A study by Guttman-Yassky and colleagues, "Targeting IL-13 With Tralokinumab Normalizes Type 2 Inflammation in Atopic Dermatitis Both Early and at 2 Years," didn't seem to test any specific hypothesis. The researchers just looked at a variety of inflammation markers in patients with atopic dermatitis treated with tralokinumab, an interleukin-13 (IL-13) antagonist. In these patients, as expected, the atopic dermatitis improved; so did the inflammatory markers. Did we learn anything clinically useful? I don't think so. We already know that IL-13 is important in atopic dermatitis because when we block IL-13, atopic dermatitis improves.

Vitamin D supplementation doesn't appear to improve atopic dermatitis, as reported by Borzutzky and colleagues in "Effect of Weekly Vitamin D Supplementation on the Severity of Atopic Dermatitis and Type 2 Immunity Biomarkers in Children: A Randomized Controlled Trial." A group of 101 children with atopic dermatitis were randomly assigned to receive oral vitamin D supplementation or placebo. The two groups improved to a similar extent. If you know me, you know I'm wondering whether they took the medication. It appears that they did, because at baseline most of the children were vitamin D deficient, and vitamin D levels improved greatly in the group treated with vitamin D but not in the placebo group.

Journals such as the Journal of the American Academy of Dermatology should require articles to report absolute risk. In "Risk of Lymphoma in Patients With Atopic Dermatitis: A Case-Control Study in the All of Us Database," Powers and colleagues tell us that atopic dermatitis is associated with a statistically significantly increased risk for lymphoma. This means that increased risk wasn't likely due to chance alone. The article says nothing, as far as I could tell, about how big the risk is. Does everyone get lymphoma? Or is it a one in a million risk? Without knowing the absolute risk, the relative risk doesn't tell us whether there is a clinically meaningful increased risk or not. I suspect the increased risk is small. If the incidence of lymphoma is about 2 in 10,000 and peripheral T-cell lymphomas (PTCL) account for 10% of those, even a fourfold increase in the risk for PTCL (the form of lymphoma with the highest relative risk) would not amount to much. 

Traidl and colleagues report in "Treatment of Moderate-to-Severe Atopic Dermatitis With Baricitinib: Results From an Interim Analysis of the TREATgermany Registry" that the Janus kinase inhibitor baricitinib makes atopic dermatitis better. 

In "Dupilumab Therapy for Atopic Dermatitis Is Associated With Increased Risk of Cutaneous T Cell Lymphoma," Hasan and colleagues report that "it requires 738 prescriptions of dupilumab to produce one case of CTCL [cutaneous T-cell lymphoma]." It seems that this finding could easily be due to 1 in 738 people with a rash thought to be severe atopic dermatitis needing dupilumab having CTCL, not atopic dermatitis, to begin with. If we were to wonder whether dupilumab causes CTCL, perhaps it would be better to study asthma patients treated with or without dupilumab.
 

In "Atopic Dermatitis in Early Childhood and Risk of Inflammatory Bowel Disease: A Scandinavian Birth Cohort Study," Lerchova and colleagues found a statistically significant increased risk for inflammatory bowel disease (IBD) in children with atopic dermatitis. The study had a large patient population, giving it the power to identify very small differences. The researchers found increased risks for IBD, Crohn's disease, and ulcerative colitis (UC) in children with atopic dermatitis; UC had the greatest relative risk. But I don't think this risk was clinically meaningful. About 2 in every 1000 children with atopic dermatitis had UC, whereas about 1 in every 1000 children without atopic dermatitis had UC. Even if the increased absolute risk of 1 in 1000 children was due to atopic dermatitis and not to other factors, I don't think it justifies the authors' conclusion that "these findings might be useful in identifying at-risk individuals for IBD."

Sometimes reviewing articles makes me feel like a crotchety old man. A study by Guttman-Yassky and colleagues, "Targeting IL-13 With Tralokinumab Normalizes Type 2 Inflammation in Atopic Dermatitis Both Early and at 2 Years," didn't seem to test any specific hypothesis. The researchers just looked at a variety of inflammation markers in patients with atopic dermatitis treated with tralokinumab, an interleukin-13 (IL-13) antagonist. In these patients, as expected, the atopic dermatitis improved; so did the inflammatory markers. Did we learn anything clinically useful? I don't think so. We already know that IL-13 is important in atopic dermatitis because when we block IL-13, atopic dermatitis improves.

Vitamin D supplementation doesn't appear to improve atopic dermatitis, as reported by Borzutzky and colleagues in "Effect of Weekly Vitamin D Supplementation on the Severity of Atopic Dermatitis and Type 2 Immunity Biomarkers in Children: A Randomized Controlled Trial." A group of 101 children with atopic dermatitis were randomly assigned to receive oral vitamin D supplementation or placebo. The two groups improved to a similar extent. If you know me, you know I'm wondering whether they took the medication. It appears that they did, because at baseline most of the children were vitamin D deficient, and vitamin D levels improved greatly in the group treated with vitamin D but not in the placebo group.

Journals such as the Journal of the American Academy of Dermatology should require articles to report absolute risk. In "Risk of Lymphoma in Patients With Atopic Dermatitis: A Case-Control Study in the All of Us Database," Powers and colleagues tell us that atopic dermatitis is associated with a statistically significantly increased risk for lymphoma. This means that increased risk wasn't likely due to chance alone. The article says nothing, as far as I could tell, about how big the risk is. Does everyone get lymphoma? Or is it a one in a million risk? Without knowing the absolute risk, the relative risk doesn't tell us whether there is a clinically meaningful increased risk or not. I suspect the increased risk is small. If the incidence of lymphoma is about 2 in 10,000 and peripheral T-cell lymphomas (PTCL) account for 10% of those, even a fourfold increase in the risk for PTCL (the form of lymphoma with the highest relative risk) would not amount to much. 

Traidl and colleagues report in "Treatment of Moderate-to-Severe Atopic Dermatitis With Baricitinib: Results From an Interim Analysis of the TREATgermany Registry" that the Janus kinase inhibitor baricitinib makes atopic dermatitis better. 

In "Dupilumab Therapy for Atopic Dermatitis Is Associated With Increased Risk of Cutaneous T Cell Lymphoma," Hasan and colleagues report that "it requires 738 prescriptions of dupilumab to produce one case of CTCL [cutaneous T-cell lymphoma]." It seems that this finding could easily be due to 1 in 738 people with a rash thought to be severe atopic dermatitis needing dupilumab having CTCL, not atopic dermatitis, to begin with. If we were to wonder whether dupilumab causes CTCL, perhaps it would be better to study asthma patients treated with or without dupilumab.
 

In "Atopic Dermatitis in Early Childhood and Risk of Inflammatory Bowel Disease: A Scandinavian Birth Cohort Study," Lerchova and colleagues found a statistically significant increased risk for inflammatory bowel disease (IBD) in children with atopic dermatitis. The study had a large patient population, giving it the power to identify very small differences. The researchers found increased risks for IBD, Crohn's disease, and ulcerative colitis (UC) in children with atopic dermatitis; UC had the greatest relative risk. But I don't think this risk was clinically meaningful. About 2 in every 1000 children with atopic dermatitis had UC, whereas about 1 in every 1000 children without atopic dermatitis had UC. Even if the increased absolute risk of 1 in 1000 children was due to atopic dermatitis and not to other factors, I don't think it justifies the authors' conclusion that "these findings might be useful in identifying at-risk individuals for IBD."

Sometimes reviewing articles makes me feel like a crotchety old man. A study by Guttman-Yassky and colleagues, "Targeting IL-13 With Tralokinumab Normalizes Type 2 Inflammation in Atopic Dermatitis Both Early and at 2 Years," didn't seem to test any specific hypothesis. The researchers just looked at a variety of inflammation markers in patients with atopic dermatitis treated with tralokinumab, an interleukin-13 (IL-13) antagonist. In these patients, as expected, the atopic dermatitis improved; so did the inflammatory markers. Did we learn anything clinically useful? I don't think so. We already know that IL-13 is important in atopic dermatitis because when we block IL-13, atopic dermatitis improves.

Vitamin D supplementation doesn't appear to improve atopic dermatitis, as reported by Borzutzky and colleagues in "Effect of Weekly Vitamin D Supplementation on the Severity of Atopic Dermatitis and Type 2 Immunity Biomarkers in Children: A Randomized Controlled Trial." A group of 101 children with atopic dermatitis were randomly assigned to receive oral vitamin D supplementation or placebo. The two groups improved to a similar extent. If you know me, you know I'm wondering whether they took the medication. It appears that they did, because at baseline most of the children were vitamin D deficient, and vitamin D levels improved greatly in the group treated with vitamin D but not in the placebo group.

Journals such as the Journal of the American Academy of Dermatology should require articles to report absolute risk. In "Risk of Lymphoma in Patients With Atopic Dermatitis: A Case-Control Study in the All of Us Database," Powers and colleagues tell us that atopic dermatitis is associated with a statistically significantly increased risk for lymphoma. This means that increased risk wasn't likely due to chance alone. The article says nothing, as far as I could tell, about how big the risk is. Does everyone get lymphoma? Or is it a one in a million risk? Without knowing the absolute risk, the relative risk doesn't tell us whether there is a clinically meaningful increased risk or not. I suspect the increased risk is small. If the incidence of lymphoma is about 2 in 10,000 and peripheral T-cell lymphomas (PTCL) account for 10% of those, even a fourfold increase in the risk for PTCL (the form of lymphoma with the highest relative risk) would not amount to much. 

Traidl and colleagues report in "Treatment of Moderate-to-Severe Atopic Dermatitis With Baricitinib: Results From an Interim Analysis of the TREATgermany Registry" that the Janus kinase inhibitor baricitinib makes atopic dermatitis better. 

In "Dupilumab Therapy for Atopic Dermatitis Is Associated With Increased Risk of Cutaneous T Cell Lymphoma," Hasan and colleagues report that "it requires 738 prescriptions of dupilumab to produce one case of CTCL [cutaneous T-cell lymphoma]." It seems that this finding could easily be due to 1 in 738 people with a rash thought to be severe atopic dermatitis needing dupilumab having CTCL, not atopic dermatitis, to begin with. If we were to wonder whether dupilumab causes CTCL, perhaps it would be better to study asthma patients treated with or without dupilumab.
 

Key clinical point: Specific behavioral patterns of attention-deficit/hyperactivity disorder, such as impulsivity and hyperactivity, were associated with the development of prurigo nodularis (PN) in children with atopic dermatitis (AD), regardless of AD severity.

Major finding: Among children with AD, the impulsivity/hyperactivity score was significantly higher in those with vs without PN (5.5 ± 4.2 vs 2.9 ± 2.9; P = .038); no significant differences were observed in Eczema Area Severity Index scores, itch numeric rating scale scores, or other AD outcomes in children with vs without PN (P > .05).

Study details: This cross-sectional study included 39 children with AD who did (n = 21) or did not (n = 18) have PN.

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

Source: Kim Y, Lee J, Shin K, et al. Association between prurigo nodularis and behavioural patterns of attention-deficit/hyperactivity disorder in children with atopic dermatitis: A cross-sectional study. J Eur Acad Dermatol Venereol. 2024(Mar 27). doi: 10.1111/jdv.19967  Source

Key clinical point: Specific behavioral patterns of attention-deficit/hyperactivity disorder, such as impulsivity and hyperactivity, were associated with the development of prurigo nodularis (PN) in children with atopic dermatitis (AD), regardless of AD severity.

Major finding: Among children with AD, the impulsivity/hyperactivity score was significantly higher in those with vs without PN (5.5 ± 4.2 vs 2.9 ± 2.9; P = .038); no significant differences were observed in Eczema Area Severity Index scores, itch numeric rating scale scores, or other AD outcomes in children with vs without PN (P > .05).

Study details: This cross-sectional study included 39 children with AD who did (n = 21) or did not (n = 18) have PN.

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

Source: Kim Y, Lee J, Shin K, et al. Association between prurigo nodularis and behavioural patterns of attention-deficit/hyperactivity disorder in children with atopic dermatitis: A cross-sectional study. J Eur Acad Dermatol Venereol. 2024(Mar 27). doi: 10.1111/jdv.19967  Source

Key clinical point: Specific behavioral patterns of attention-deficit/hyperactivity disorder, such as impulsivity and hyperactivity, were associated with the development of prurigo nodularis (PN) in children with atopic dermatitis (AD), regardless of AD severity.

Major finding: Among children with AD, the impulsivity/hyperactivity score was significantly higher in those with vs without PN (5.5 ± 4.2 vs 2.9 ± 2.9; P = .038); no significant differences were observed in Eczema Area Severity Index scores, itch numeric rating scale scores, or other AD outcomes in children with vs without PN (P > .05).

Study details: This cross-sectional study included 39 children with AD who did (n = 21) or did not (n = 18) have PN.

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

Source: Kim Y, Lee J, Shin K, et al. Association between prurigo nodularis and behavioural patterns of attention-deficit/hyperactivity disorder in children with atopic dermatitis: A cross-sectional study. J Eur Acad Dermatol Venereol. 2024(Mar 27). doi: 10.1111/jdv.19967  Source

Key clinical point: Upadacitinib treatment rapidly and sustainably improved multiple patient-reported outcomes, including itch, in adults and adolescents with moderate to severe atopic dermatitis (AD).

Major finding: At week 1, more than 10% and 15% of patients receiving 15 and 30 mg upadacitinib, respectively, experienced improvements in itch; thereafter, response rates increased steadily and sustainably through week 52. Similar improvements were observed for pain and other skin symptoms.

Study details: This pooled analysis included 1609 adults and adolescents with moderate to severe AD from the phase 3 Measure Up 1 and Measure Up 2 studies who had received upadacitinib (15 mg n = 557; 30 mg n = 567) or placebo (followed by upadacitinib 15 or 30 mg after 16 weeks; n = 485).

Disclosures: This study was funded by AbbVie, Inc. Eight authors declared being employees of or holding stock or stock options in AbbVie. The other authors declared serving as speakers for, receiving consulting fees, or having other ties with various sources, including AbbVie.

Source: Silverberg JI, Gooderham MJ, Paller AS, et al. Early and sustained improvements in symptoms and quality of life with upadacitinib in adults and adolescents with moderate-to-severe atopic dermatitis: 52-week results from two phase III randomized clinical trials (Measure Up 1 and Measure Up 2). Am J Clin Dermatol. 2024 (Mar 25). doi: 10.1007/s40257-024-00853-4 Source

Key clinical point: Upadacitinib treatment rapidly and sustainably improved multiple patient-reported outcomes, including itch, in adults and adolescents with moderate to severe atopic dermatitis (AD).

Major finding: At week 1, more than 10% and 15% of patients receiving 15 and 30 mg upadacitinib, respectively, experienced improvements in itch; thereafter, response rates increased steadily and sustainably through week 52. Similar improvements were observed for pain and other skin symptoms.

Study details: This pooled analysis included 1609 adults and adolescents with moderate to severe AD from the phase 3 Measure Up 1 and Measure Up 2 studies who had received upadacitinib (15 mg n = 557; 30 mg n = 567) or placebo (followed by upadacitinib 15 or 30 mg after 16 weeks; n = 485).

Disclosures: This study was funded by AbbVie, Inc. Eight authors declared being employees of or holding stock or stock options in AbbVie. The other authors declared serving as speakers for, receiving consulting fees, or having other ties with various sources, including AbbVie.

Source: Silverberg JI, Gooderham MJ, Paller AS, et al. Early and sustained improvements in symptoms and quality of life with upadacitinib in adults and adolescents with moderate-to-severe atopic dermatitis: 52-week results from two phase III randomized clinical trials (Measure Up 1 and Measure Up 2). Am J Clin Dermatol. 2024 (Mar 25). doi: 10.1007/s40257-024-00853-4 Source

Key clinical point: Upadacitinib treatment rapidly and sustainably improved multiple patient-reported outcomes, including itch, in adults and adolescents with moderate to severe atopic dermatitis (AD).

Major finding: At week 1, more than 10% and 15% of patients receiving 15 and 30 mg upadacitinib, respectively, experienced improvements in itch; thereafter, response rates increased steadily and sustainably through week 52. Similar improvements were observed for pain and other skin symptoms.

Study details: This pooled analysis included 1609 adults and adolescents with moderate to severe AD from the phase 3 Measure Up 1 and Measure Up 2 studies who had received upadacitinib (15 mg n = 557; 30 mg n = 567) or placebo (followed by upadacitinib 15 or 30 mg after 16 weeks; n = 485).

Disclosures: This study was funded by AbbVie, Inc. Eight authors declared being employees of or holding stock or stock options in AbbVie. The other authors declared serving as speakers for, receiving consulting fees, or having other ties with various sources, including AbbVie.

Source: Silverberg JI, Gooderham MJ, Paller AS, et al. Early and sustained improvements in symptoms and quality of life with upadacitinib in adults and adolescents with moderate-to-severe atopic dermatitis: 52-week results from two phase III randomized clinical trials (Measure Up 1 and Measure Up 2). Am J Clin Dermatol. 2024 (Mar 25). doi: 10.1007/s40257-024-00853-4 Source

Key clinical point: Patients with atopic dermatitis (AD) treated with dupilumab have an increased risk for cutaneous T-cell lymphoma (CTCL) compared with those not treated with dupilumab.

Major finding: Patients with AD who did vs did not receive dupilumab had a significantly higher risk of developing CTCL (odds ratio [OR] 4.1003; 95% CI 2.055-8.192). The risk for CTCL persisted in those with no prior exposure to disease-modifying antirheumatic drugs (OR 3.202; 95% CI 1.573-6.514).

Study details: This retrospective cohort study included patients with AD who did (n = 22,888) or did not (n = 22,871) receive dupilumab treatment and did not have a preexisting diagnosis for CTCL, Hodgkin lymphoma, non-Hodgkin lymphoma, nonfollicular lymphoma, leukemia, malignant melanoma, squamous cell carcinoma, or basal cell carcinoma.

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

Source: Hasan I, Parsons L, Duran S, Zinn Z. Dupilumab therapy for atopic dermatitis is associated with increased risk of cutaneous T cell lymphoma: A retrospective cohort study. J Am Acad Dermatol. 2024 (Apr 6). doi: 10.1016/j.jaad.2024.03.039 Source

Key clinical point: Patients with atopic dermatitis (AD) treated with dupilumab have an increased risk for cutaneous T-cell lymphoma (CTCL) compared with those not treated with dupilumab.

Major finding: Patients with AD who did vs did not receive dupilumab had a significantly higher risk of developing CTCL (odds ratio [OR] 4.1003; 95% CI 2.055-8.192). The risk for CTCL persisted in those with no prior exposure to disease-modifying antirheumatic drugs (OR 3.202; 95% CI 1.573-6.514).

Study details: This retrospective cohort study included patients with AD who did (n = 22,888) or did not (n = 22,871) receive dupilumab treatment and did not have a preexisting diagnosis for CTCL, Hodgkin lymphoma, non-Hodgkin lymphoma, nonfollicular lymphoma, leukemia, malignant melanoma, squamous cell carcinoma, or basal cell carcinoma.

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

Source: Hasan I, Parsons L, Duran S, Zinn Z. Dupilumab therapy for atopic dermatitis is associated with increased risk of cutaneous T cell lymphoma: A retrospective cohort study. J Am Acad Dermatol. 2024 (Apr 6). doi: 10.1016/j.jaad.2024.03.039 Source

Key clinical point: Patients with atopic dermatitis (AD) treated with dupilumab have an increased risk for cutaneous T-cell lymphoma (CTCL) compared with those not treated with dupilumab.

Major finding: Patients with AD who did vs did not receive dupilumab had a significantly higher risk of developing CTCL (odds ratio [OR] 4.1003; 95% CI 2.055-8.192). The risk for CTCL persisted in those with no prior exposure to disease-modifying antirheumatic drugs (OR 3.202; 95% CI 1.573-6.514).

Study details: This retrospective cohort study included patients with AD who did (n = 22,888) or did not (n = 22,871) receive dupilumab treatment and did not have a preexisting diagnosis for CTCL, Hodgkin lymphoma, non-Hodgkin lymphoma, nonfollicular lymphoma, leukemia, malignant melanoma, squamous cell carcinoma, or basal cell carcinoma.

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

Source: Hasan I, Parsons L, Duran S, Zinn Z. Dupilumab therapy for atopic dermatitis is associated with increased risk of cutaneous T cell lymphoma: A retrospective cohort study. J Am Acad Dermatol. 2024 (Apr 6). doi: 10.1016/j.jaad.2024.03.039 Source

Key clinical point: Established and new atopic dermatitis (AD)-associated filaggrin loss-of-function variants are associated with increased risks for clinical AD outcomes and disruption of skin barrier integrity in lesional and nonlesional skin of children with AD.

Major finding: Twenty variants were identified, including one novel variant. The presence of one or more variants was associated with a higher risk for moderate or severe AD vs mild AD (odds ratio 2.00; corrected P = .0394), a higher Scoring AD score (corrected P = .0394), and transepidermal water loss in both lesional (P = .018) and nonlesional (P = .015) skin.

Study details: This study included 438 children with AD (age ≤ 2 years; gestation period ≥ 36 weeks) from the early-life Mechanisms of Progression of Atopic Dermatitis to Asthma in Children cohort without a comorbid lung condition or dependence on immunosuppression or oral steroids for a condition except asthma.

Disclosures: This study was funded by the US National Institutes of Health. Matthew S. Hestand declared being an employee and shareholder of Pacific Biosciences. The other authors declared no conflicts of interest.

Source: Virolainen SJ, Satish L, Biagini JM, et al. Filaggrin loss-of-function variants are associated with atopic dermatitis phenotypes in a diverse, early life prospective cohort. JCI Insight. 2024 (Apr 2). doi: 10.1172/jci.insight.178258 Source

Key clinical point: Established and new atopic dermatitis (AD)-associated filaggrin loss-of-function variants are associated with increased risks for clinical AD outcomes and disruption of skin barrier integrity in lesional and nonlesional skin of children with AD.

Major finding: Twenty variants were identified, including one novel variant. The presence of one or more variants was associated with a higher risk for moderate or severe AD vs mild AD (odds ratio 2.00; corrected P = .0394), a higher Scoring AD score (corrected P = .0394), and transepidermal water loss in both lesional (P = .018) and nonlesional (P = .015) skin.

Study details: This study included 438 children with AD (age ≤ 2 years; gestation period ≥ 36 weeks) from the early-life Mechanisms of Progression of Atopic Dermatitis to Asthma in Children cohort without a comorbid lung condition or dependence on immunosuppression or oral steroids for a condition except asthma.

Disclosures: This study was funded by the US National Institutes of Health. Matthew S. Hestand declared being an employee and shareholder of Pacific Biosciences. The other authors declared no conflicts of interest.

Source: Virolainen SJ, Satish L, Biagini JM, et al. Filaggrin loss-of-function variants are associated with atopic dermatitis phenotypes in a diverse, early life prospective cohort. JCI Insight. 2024 (Apr 2). doi: 10.1172/jci.insight.178258 Source

Key clinical point: Established and new atopic dermatitis (AD)-associated filaggrin loss-of-function variants are associated with increased risks for clinical AD outcomes and disruption of skin barrier integrity in lesional and nonlesional skin of children with AD.

Major finding: Twenty variants were identified, including one novel variant. The presence of one or more variants was associated with a higher risk for moderate or severe AD vs mild AD (odds ratio 2.00; corrected P = .0394), a higher Scoring AD score (corrected P = .0394), and transepidermal water loss in both lesional (P = .018) and nonlesional (P = .015) skin.

Study details: This study included 438 children with AD (age ≤ 2 years; gestation period ≥ 36 weeks) from the early-life Mechanisms of Progression of Atopic Dermatitis to Asthma in Children cohort without a comorbid lung condition or dependence on immunosuppression or oral steroids for a condition except asthma.

Disclosures: This study was funded by the US National Institutes of Health. Matthew S. Hestand declared being an employee and shareholder of Pacific Biosciences. The other authors declared no conflicts of interest.

Source: Virolainen SJ, Satish L, Biagini JM, et al. Filaggrin loss-of-function variants are associated with atopic dermatitis phenotypes in a diverse, early life prospective cohort. JCI Insight. 2024 (Apr 2). doi: 10.1172/jci.insight.178258 Source

Key clinical point: Baricitinib treatment was effective and well-tolerated in patients with moderate to severe atopic dermatitis (AD) who were followed-up for 3 months in real-world settings.

Major finding: Baricitinib led to a significant reduction in the Eczema Area Severity Index (21.5 ± 13.2 vs 9.3 ± 9.0) and objective Scoring AD (45.9 ± 12.3 vs 28.2 ± 15.5) scores at 3 months vs start visit (both P < .001). The treatment discontinuation rate was 16.7%, with two patients discontinuing baricitinib due to adverse events.

Study details: This was an interim analysis of the TREATgermany registry that included 81 adult patients with moderate to severe AD who received baricitinib and concomitant topical treatment, of whom 49 had initiated baricitinib at a registry visit; 26 of these did not switch from a previous systemic drug and had their first follow-up visit at 3 months.

Disclosures: TREATgermany is supported by AbbVie Deutschland GmbH & Co. KG, Galderma S.A., and others. Six authors declared serving as consultants, lecturers, etc., for or having other ties with various organizations, including the sponsors of TREATgermany. The other authors declared no conflicts of interest.

Source: Traidl S, Heinrich L, Siegels D, et al, and the TREATgermany study group. Treatment of moderate-to-severe atopic dermatitis with baricitinib: Results from an interim analysis of the TREATgermany registry. J Eur Acad Dermatol Venereol. 2024 (Mar 28). doi: 10.1111/jdv.19979 Source

Key clinical point: Baricitinib treatment was effective and well-tolerated in patients with moderate to severe atopic dermatitis (AD) who were followed-up for 3 months in real-world settings.

Major finding: Baricitinib led to a significant reduction in the Eczema Area Severity Index (21.5 ± 13.2 vs 9.3 ± 9.0) and objective Scoring AD (45.9 ± 12.3 vs 28.2 ± 15.5) scores at 3 months vs start visit (both P < .001). The treatment discontinuation rate was 16.7%, with two patients discontinuing baricitinib due to adverse events.

Study details: This was an interim analysis of the TREATgermany registry that included 81 adult patients with moderate to severe AD who received baricitinib and concomitant topical treatment, of whom 49 had initiated baricitinib at a registry visit; 26 of these did not switch from a previous systemic drug and had their first follow-up visit at 3 months.

Disclosures: TREATgermany is supported by AbbVie Deutschland GmbH & Co. KG, Galderma S.A., and others. Six authors declared serving as consultants, lecturers, etc., for or having other ties with various organizations, including the sponsors of TREATgermany. The other authors declared no conflicts of interest.

Source: Traidl S, Heinrich L, Siegels D, et al, and the TREATgermany study group. Treatment of moderate-to-severe atopic dermatitis with baricitinib: Results from an interim analysis of the TREATgermany registry. J Eur Acad Dermatol Venereol. 2024 (Mar 28). doi: 10.1111/jdv.19979 Source

Key clinical point: Baricitinib treatment was effective and well-tolerated in patients with moderate to severe atopic dermatitis (AD) who were followed-up for 3 months in real-world settings.

Major finding: Baricitinib led to a significant reduction in the Eczema Area Severity Index (21.5 ± 13.2 vs 9.3 ± 9.0) and objective Scoring AD (45.9 ± 12.3 vs 28.2 ± 15.5) scores at 3 months vs start visit (both P < .001). The treatment discontinuation rate was 16.7%, with two patients discontinuing baricitinib due to adverse events.

Study details: This was an interim analysis of the TREATgermany registry that included 81 adult patients with moderate to severe AD who received baricitinib and concomitant topical treatment, of whom 49 had initiated baricitinib at a registry visit; 26 of these did not switch from a previous systemic drug and had their first follow-up visit at 3 months.

Disclosures: TREATgermany is supported by AbbVie Deutschland GmbH & Co. KG, Galderma S.A., and others. Six authors declared serving as consultants, lecturers, etc., for or having other ties with various organizations, including the sponsors of TREATgermany. The other authors declared no conflicts of interest.

Source: Traidl S, Heinrich L, Siegels D, et al, and the TREATgermany study group. Treatment of moderate-to-severe atopic dermatitis with baricitinib: Results from an interim analysis of the TREATgermany registry. J Eur Acad Dermatol Venereol. 2024 (Mar 28). doi: 10.1111/jdv.19979 Source

Key clinical point: Patients with atopic dermatitis (AD) have a significantly increased risk of developing lymphoma.

Major finding: Patients with AD vs control individuals showed a significantly increased likelihood of developing noncutaneous T-cell lymphoma (odds ratio [OR] 2.52; 95% CI 1.37-4.62), with similar outcomes for the peripheral T-cell lymphoma subtype (OR 4.00; 95% CI 1.50-10.66).

Study details: Findings are from a nested case-control study including 6425 adult patients with AD and 25,700 matched control individuals without AD from electronic health records.

Disclosures: This study did not receive any funding. Benjamin Ungar reported being an employee of Mount Sinai and receiving research funds from and serving as a consultant for various organizations.

Source: Powers CM, Piontkowski AJ, Orloff J, et al. Risk of lymphoma in patients with atopic dermatitis: A case-control study in the All of Us database. J Am Acad Dermatol. 2024 (Apr 4). doi: 10.1016/j.jaad.2024.03.038 Source

Key clinical point: Patients with atopic dermatitis (AD) have a significantly increased risk of developing lymphoma.

Major finding: Patients with AD vs control individuals showed a significantly increased likelihood of developing noncutaneous T-cell lymphoma (odds ratio [OR] 2.52; 95% CI 1.37-4.62), with similar outcomes for the peripheral T-cell lymphoma subtype (OR 4.00; 95% CI 1.50-10.66).

Study details: Findings are from a nested case-control study including 6425 adult patients with AD and 25,700 matched control individuals without AD from electronic health records.

Disclosures: This study did not receive any funding. Benjamin Ungar reported being an employee of Mount Sinai and receiving research funds from and serving as a consultant for various organizations.

Source: Powers CM, Piontkowski AJ, Orloff J, et al. Risk of lymphoma in patients with atopic dermatitis: A case-control study in the All of Us database. J Am Acad Dermatol. 2024 (Apr 4). doi: 10.1016/j.jaad.2024.03.038 Source

Key clinical point: Patients with atopic dermatitis (AD) have a significantly increased risk of developing lymphoma.

Major finding: Patients with AD vs control individuals showed a significantly increased likelihood of developing noncutaneous T-cell lymphoma (odds ratio [OR] 2.52; 95% CI 1.37-4.62), with similar outcomes for the peripheral T-cell lymphoma subtype (OR 4.00; 95% CI 1.50-10.66).

Study details: Findings are from a nested case-control study including 6425 adult patients with AD and 25,700 matched control individuals without AD from electronic health records.

Disclosures: This study did not receive any funding. Benjamin Ungar reported being an employee of Mount Sinai and receiving research funds from and serving as a consultant for various organizations.

Source: Powers CM, Piontkowski AJ, Orloff J, et al. Risk of lymphoma in patients with atopic dermatitis: A case-control study in the All of Us database. J Am Acad Dermatol. 2024 (Apr 4). doi: 10.1016/j.jaad.2024.03.038 Source