Lebrikizumab Shows Prompt Clinical Response in Moderate to Severe Atopic Dermatitis

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Key clinical point: Lebrikizumab monotherapy rapidly and consistently reduced atopic dermatitis (AD) extent and severity in patients with moderate to severe AD across all Eczema Area and Severity Index (EASI) clinical signs and body regions.

Major finding: At week 16, lebrikizumab vs placebo led to greater improvements in EASI scores and clinical signs (both P < .001) across all body regions in ADvocate1 and ADvocate2, with improvements observed as early as week 2 for all signs except erythema on head/neck (P < .05) and lower extremity erythema, edema/papulation, and lichenification (all P < .001), which improved significantly only by week 4 in ADvocate2.

Study details: This post hoc analysis of ADvocate1 (n = 424) and ADvocate2 (n = 427) included adolescent and adult patients with moderate to severe AD who were randomly assigned to receive 250 mg lebrikizumab biweekly or placebo.

Disclosures: This study was funded by Dermira, Inc., a wholly owned subsidiary of Eli Lilly and Company. Several authors declared having various ties with Dermira, Eli Lilly, and others. Five authors declared being employees or stockholders of Eli Lilly.

Source: Simpson EL, de Bruin-Weller M, Hong HC, et al. Lebrikizumab provides rapid clinical responses across all Eczema Area and Severity Index body regions and clinical signs in adolescents and adults with moderate-to-severe atopic dermatitis. Dermatol Ther (Heidelb). 2024 (May 3). doi: 10.1007/s13555-024-01158-4 Source

 

 

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Key clinical point: Lebrikizumab monotherapy rapidly and consistently reduced atopic dermatitis (AD) extent and severity in patients with moderate to severe AD across all Eczema Area and Severity Index (EASI) clinical signs and body regions.

Major finding: At week 16, lebrikizumab vs placebo led to greater improvements in EASI scores and clinical signs (both P < .001) across all body regions in ADvocate1 and ADvocate2, with improvements observed as early as week 2 for all signs except erythema on head/neck (P < .05) and lower extremity erythema, edema/papulation, and lichenification (all P < .001), which improved significantly only by week 4 in ADvocate2.

Study details: This post hoc analysis of ADvocate1 (n = 424) and ADvocate2 (n = 427) included adolescent and adult patients with moderate to severe AD who were randomly assigned to receive 250 mg lebrikizumab biweekly or placebo.

Disclosures: This study was funded by Dermira, Inc., a wholly owned subsidiary of Eli Lilly and Company. Several authors declared having various ties with Dermira, Eli Lilly, and others. Five authors declared being employees or stockholders of Eli Lilly.

Source: Simpson EL, de Bruin-Weller M, Hong HC, et al. Lebrikizumab provides rapid clinical responses across all Eczema Area and Severity Index body regions and clinical signs in adolescents and adults with moderate-to-severe atopic dermatitis. Dermatol Ther (Heidelb). 2024 (May 3). doi: 10.1007/s13555-024-01158-4 Source

 

 

Key clinical point: Lebrikizumab monotherapy rapidly and consistently reduced atopic dermatitis (AD) extent and severity in patients with moderate to severe AD across all Eczema Area and Severity Index (EASI) clinical signs and body regions.

Major finding: At week 16, lebrikizumab vs placebo led to greater improvements in EASI scores and clinical signs (both P < .001) across all body regions in ADvocate1 and ADvocate2, with improvements observed as early as week 2 for all signs except erythema on head/neck (P < .05) and lower extremity erythema, edema/papulation, and lichenification (all P < .001), which improved significantly only by week 4 in ADvocate2.

Study details: This post hoc analysis of ADvocate1 (n = 424) and ADvocate2 (n = 427) included adolescent and adult patients with moderate to severe AD who were randomly assigned to receive 250 mg lebrikizumab biweekly or placebo.

Disclosures: This study was funded by Dermira, Inc., a wholly owned subsidiary of Eli Lilly and Company. Several authors declared having various ties with Dermira, Eli Lilly, and others. Five authors declared being employees or stockholders of Eli Lilly.

Source: Simpson EL, de Bruin-Weller M, Hong HC, et al. Lebrikizumab provides rapid clinical responses across all Eczema Area and Severity Index body regions and clinical signs in adolescents and adults with moderate-to-severe atopic dermatitis. Dermatol Ther (Heidelb). 2024 (May 3). doi: 10.1007/s13555-024-01158-4 Source

 

 

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Causal Relationship Exists Between Atopic Dermatitis and Brain Cancer

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Key clinical point: A causal relationship was observed between genetically related atopic dermatitis (AD) and brain cancer, delineating AD as a potential risk factor for brain cancer.

Major finding: The presence of AD led to an increased risk for brain cancer (odds ratio 1.0005; P = .0096); however, no significant causal association was observed on conducting reverse Mendelian randomization analysis.

Study details: This cohort study analyzed the data on AD-associated single nucleotide polymorphisms of patients with AD (n = 15,208) and control individuals without AD (n = 367,046) from the FinnGen database (10th release) and the summary data of patients with brain cancer (n = 606) and control individuals without cancer (n = 372,016) from the IEU Open GWAS database.

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

Source: Xin Y, Yuan T, Wang J. The causal relationship between atopic dermatitis and brain cancer: A bidirectional Mendelian randomization study. Skin Res Technol. 2024;30(4):e13715. doi: 10.1111/srt.13715 Source

 

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Key clinical point: A causal relationship was observed between genetically related atopic dermatitis (AD) and brain cancer, delineating AD as a potential risk factor for brain cancer.

Major finding: The presence of AD led to an increased risk for brain cancer (odds ratio 1.0005; P = .0096); however, no significant causal association was observed on conducting reverse Mendelian randomization analysis.

Study details: This cohort study analyzed the data on AD-associated single nucleotide polymorphisms of patients with AD (n = 15,208) and control individuals without AD (n = 367,046) from the FinnGen database (10th release) and the summary data of patients with brain cancer (n = 606) and control individuals without cancer (n = 372,016) from the IEU Open GWAS database.

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

Source: Xin Y, Yuan T, Wang J. The causal relationship between atopic dermatitis and brain cancer: A bidirectional Mendelian randomization study. Skin Res Technol. 2024;30(4):e13715. doi: 10.1111/srt.13715 Source

 

Key clinical point: A causal relationship was observed between genetically related atopic dermatitis (AD) and brain cancer, delineating AD as a potential risk factor for brain cancer.

Major finding: The presence of AD led to an increased risk for brain cancer (odds ratio 1.0005; P = .0096); however, no significant causal association was observed on conducting reverse Mendelian randomization analysis.

Study details: This cohort study analyzed the data on AD-associated single nucleotide polymorphisms of patients with AD (n = 15,208) and control individuals without AD (n = 367,046) from the FinnGen database (10th release) and the summary data of patients with brain cancer (n = 606) and control individuals without cancer (n = 372,016) from the IEU Open GWAS database.

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

Source: Xin Y, Yuan T, Wang J. The causal relationship between atopic dermatitis and brain cancer: A bidirectional Mendelian randomization study. Skin Res Technol. 2024;30(4):e13715. doi: 10.1111/srt.13715 Source

 

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Preventive Effect of Maternal Probiotic Supplementation in Atopic Dermatitis

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Key clinical point: Maternal probiotic supplementation was effective in preventing atopic dermatitis (AD) in children regardless of their filaggrin (FLG) gene mutation status.

Major finding: Heterozygous FLG mutations were observed in 7% of children. The risk for AD after maternal probiotic supplementation was similar between children who expressed a FLG mutation (risk ratio [RR] 0.6; 95% CI 0.1-4.1) and those having a wild-type FLG (RR 0.6; 95% CI 0.4-0.9).

Study details: This exploratory study included the data of 228 children from the Probiotic in the Prevention of Allergy among Children in Trondheim (ProPACT) study who did or did not have FLG mutations and whose mothers received probiotic or placebo milk from 36 weeks of gestation until 3 months post delivery while breastfeeding.

Disclosures: This study was funded by the Liaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology, and the Norwegian Research Council. The authors declared no conflicts of interest.

Source: Zakiudin DP, Thyssen JP, Zachariae C, Videm V, Øien T, Simpson MR. Filaggrin mutation status and prevention of atopic dermatitis with maternal probiotic supplementation. Acta Derm Venereol. 2024;104:adv24360 (Apr 24). doi: 10.2340/actadv.v104.24360  Source

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Key clinical point: Maternal probiotic supplementation was effective in preventing atopic dermatitis (AD) in children regardless of their filaggrin (FLG) gene mutation status.

Major finding: Heterozygous FLG mutations were observed in 7% of children. The risk for AD after maternal probiotic supplementation was similar between children who expressed a FLG mutation (risk ratio [RR] 0.6; 95% CI 0.1-4.1) and those having a wild-type FLG (RR 0.6; 95% CI 0.4-0.9).

Study details: This exploratory study included the data of 228 children from the Probiotic in the Prevention of Allergy among Children in Trondheim (ProPACT) study who did or did not have FLG mutations and whose mothers received probiotic or placebo milk from 36 weeks of gestation until 3 months post delivery while breastfeeding.

Disclosures: This study was funded by the Liaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology, and the Norwegian Research Council. The authors declared no conflicts of interest.

Source: Zakiudin DP, Thyssen JP, Zachariae C, Videm V, Øien T, Simpson MR. Filaggrin mutation status and prevention of atopic dermatitis with maternal probiotic supplementation. Acta Derm Venereol. 2024;104:adv24360 (Apr 24). doi: 10.2340/actadv.v104.24360  Source

Key clinical point: Maternal probiotic supplementation was effective in preventing atopic dermatitis (AD) in children regardless of their filaggrin (FLG) gene mutation status.

Major finding: Heterozygous FLG mutations were observed in 7% of children. The risk for AD after maternal probiotic supplementation was similar between children who expressed a FLG mutation (risk ratio [RR] 0.6; 95% CI 0.1-4.1) and those having a wild-type FLG (RR 0.6; 95% CI 0.4-0.9).

Study details: This exploratory study included the data of 228 children from the Probiotic in the Prevention of Allergy among Children in Trondheim (ProPACT) study who did or did not have FLG mutations and whose mothers received probiotic or placebo milk from 36 weeks of gestation until 3 months post delivery while breastfeeding.

Disclosures: This study was funded by the Liaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology, and the Norwegian Research Council. The authors declared no conflicts of interest.

Source: Zakiudin DP, Thyssen JP, Zachariae C, Videm V, Øien T, Simpson MR. Filaggrin mutation status and prevention of atopic dermatitis with maternal probiotic supplementation. Acta Derm Venereol. 2024;104:adv24360 (Apr 24). doi: 10.2340/actadv.v104.24360  Source

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Pharmacological Interventions in Atopic Dermatitis Reduce Anxiety and Depression

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Key clinical point: Pharmacological interventions aimed at reducing disease severity in patients with moderate to severe atopic dermatitis (AD) are also effective for improving anxiety and depression.

Major finding: Pharmacologic interventions for AD led to significant improvements in anxiety levels (standardized mean difference [SMD] −0.29; 95% CI −0.49 to −0.09) and depression severity (SMD −0.27; 95% CI −0.45 to −0.08) and an overall significant improvement in Hospital Anxiety and Depression scale scores (SMD −0.50; 95% CI −0.064 to −0.35).

Study details: This meta-analysis of seven phase 2b or 3 randomized controlled trials included 4723 patients with AD who were treated with either abrocitinib, baricitinib, dupilumab, tralokinumab, or placebo.

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

Source: Hartono SP, Chatrath S, Aktas ON, et al. Interventions for anxiety and depression in patients with atopic dermatitis: A systematic review and meta-analysis. Sci Rep. 2024;14:8844 (Apr 17). Source

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Key clinical point: Pharmacological interventions aimed at reducing disease severity in patients with moderate to severe atopic dermatitis (AD) are also effective for improving anxiety and depression.

Major finding: Pharmacologic interventions for AD led to significant improvements in anxiety levels (standardized mean difference [SMD] −0.29; 95% CI −0.49 to −0.09) and depression severity (SMD −0.27; 95% CI −0.45 to −0.08) and an overall significant improvement in Hospital Anxiety and Depression scale scores (SMD −0.50; 95% CI −0.064 to −0.35).

Study details: This meta-analysis of seven phase 2b or 3 randomized controlled trials included 4723 patients with AD who were treated with either abrocitinib, baricitinib, dupilumab, tralokinumab, or placebo.

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

Source: Hartono SP, Chatrath S, Aktas ON, et al. Interventions for anxiety and depression in patients with atopic dermatitis: A systematic review and meta-analysis. Sci Rep. 2024;14:8844 (Apr 17). Source

Key clinical point: Pharmacological interventions aimed at reducing disease severity in patients with moderate to severe atopic dermatitis (AD) are also effective for improving anxiety and depression.

Major finding: Pharmacologic interventions for AD led to significant improvements in anxiety levels (standardized mean difference [SMD] −0.29; 95% CI −0.49 to −0.09) and depression severity (SMD −0.27; 95% CI −0.45 to −0.08) and an overall significant improvement in Hospital Anxiety and Depression scale scores (SMD −0.50; 95% CI −0.064 to −0.35).

Study details: This meta-analysis of seven phase 2b or 3 randomized controlled trials included 4723 patients with AD who were treated with either abrocitinib, baricitinib, dupilumab, tralokinumab, or placebo.

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

Source: Hartono SP, Chatrath S, Aktas ON, et al. Interventions for anxiety and depression in patients with atopic dermatitis: A systematic review and meta-analysis. Sci Rep. 2024;14:8844 (Apr 17). Source

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Comparable Efficacy of Tralokinumab and Dupilumab in Moderate to Severe Atopic Dermatitis

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Key clinical point: When combined with topical corticosteroids (TCS), tralokinumab and dupilumab demonstrate similar efficacy in the treatment of patients with moderate to severe atopic dermatitis (AD) at 32 weeks of therapy.

Major finding: At week 32, tralokinumab and dupilumab treatment, both in combination with TCS, led to a similar proportion of patients achieving an Investigator's Global Assessment score of 0 or 1 (49.9% vs 39.3%; P = .95) or 75% improvement in the Eczema Area Severity Index scores (71.5% vs 71.9%; P = .95).

Study details: This unanchored matching-adjusted indirect comparison study analyzed the individual patient data of adults with moderate to severe AD (sample size 123.4) treated with tralokinumab plus TCS in ECZTRA 3, which were matched with the aggregate data of 106 patients treated with dupilumab plus TCS in the LIBERTY AD CHRONOS trial.

Disclosures: This study was funded by LEO Pharma. Four authors declared being employees of LEO Pharma. The other authors declared receiving consultancy or speaker honoraria from or having other ties with various sources, including LEO Pharma.

Source: Torres T, Sohrt Petersen A, Ivens U, et al. Matching-adjusted indirect comparison of the efficacy at week 32 of tralokinumab and dupilumab in the treatment of moderate-to-severe atopic dermatitis. Dermatol Ther (Heidelb). 2024;14:983-992 (Apr 13). doi: 10.1007/s13555-024-01143-x Source

 

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Key clinical point: When combined with topical corticosteroids (TCS), tralokinumab and dupilumab demonstrate similar efficacy in the treatment of patients with moderate to severe atopic dermatitis (AD) at 32 weeks of therapy.

Major finding: At week 32, tralokinumab and dupilumab treatment, both in combination with TCS, led to a similar proportion of patients achieving an Investigator's Global Assessment score of 0 or 1 (49.9% vs 39.3%; P = .95) or 75% improvement in the Eczema Area Severity Index scores (71.5% vs 71.9%; P = .95).

Study details: This unanchored matching-adjusted indirect comparison study analyzed the individual patient data of adults with moderate to severe AD (sample size 123.4) treated with tralokinumab plus TCS in ECZTRA 3, which were matched with the aggregate data of 106 patients treated with dupilumab plus TCS in the LIBERTY AD CHRONOS trial.

Disclosures: This study was funded by LEO Pharma. Four authors declared being employees of LEO Pharma. The other authors declared receiving consultancy or speaker honoraria from or having other ties with various sources, including LEO Pharma.

Source: Torres T, Sohrt Petersen A, Ivens U, et al. Matching-adjusted indirect comparison of the efficacy at week 32 of tralokinumab and dupilumab in the treatment of moderate-to-severe atopic dermatitis. Dermatol Ther (Heidelb). 2024;14:983-992 (Apr 13). doi: 10.1007/s13555-024-01143-x Source

 

Key clinical point: When combined with topical corticosteroids (TCS), tralokinumab and dupilumab demonstrate similar efficacy in the treatment of patients with moderate to severe atopic dermatitis (AD) at 32 weeks of therapy.

Major finding: At week 32, tralokinumab and dupilumab treatment, both in combination with TCS, led to a similar proportion of patients achieving an Investigator's Global Assessment score of 0 or 1 (49.9% vs 39.3%; P = .95) or 75% improvement in the Eczema Area Severity Index scores (71.5% vs 71.9%; P = .95).

Study details: This unanchored matching-adjusted indirect comparison study analyzed the individual patient data of adults with moderate to severe AD (sample size 123.4) treated with tralokinumab plus TCS in ECZTRA 3, which were matched with the aggregate data of 106 patients treated with dupilumab plus TCS in the LIBERTY AD CHRONOS trial.

Disclosures: This study was funded by LEO Pharma. Four authors declared being employees of LEO Pharma. The other authors declared receiving consultancy or speaker honoraria from or having other ties with various sources, including LEO Pharma.

Source: Torres T, Sohrt Petersen A, Ivens U, et al. Matching-adjusted indirect comparison of the efficacy at week 32 of tralokinumab and dupilumab in the treatment of moderate-to-severe atopic dermatitis. Dermatol Ther (Heidelb). 2024;14:983-992 (Apr 13). doi: 10.1007/s13555-024-01143-x Source

 

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Topical Ruxolitinib Provides Long-Term Disease Control in Adolescents With Atopic Dermatitis

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Key clinical point: Topical 1.5% ruxolitinib was effective and well-tolerated and offered long-term disease control with as-needed use in adolescents with atopic dermatitis (AD).

Major finding: At week 8, a substantially higher number of patients receiving 1.5% ruxolitinib vs vehicle achieved an Investigator's Global Assessment (IGA) score of 0 or 1 with ≥2 grade improvement from baseline (50.6% vs 14.0%) and ≥75% improvement in the Eczema Area and Severity Index score (60.9% vs 34.9%), with sustained or increased proportion of patients achieving an IGA score of 0 or 1 during the long-term safety (LTS) period. No serious adverse events were reported.

Study details: This study used pooled data from two phase 3 trials (TRuE-AD1 and TRuE-AD2) and included 137 adolescents (age, 12-17 years) with AD who were randomly assigned to receive 0.75% or 1.5% ruxolitinib cream or vehicle twice daily for 8 weeks, followed by an LTS period lasting up to 52 weeks.

Disclosures: This study was funded by Incyte Corporation. Four authors declared being employees or shareholders of Incyte Corporation. Several authors declared ties with various sources, including Incyte Corporation.

Source: Eichenfield LF, Simpson EL, Papp K, et al. Efficacy, safety, and long-term disease control of ruxolitinib cream among adolescents with atopic dermatitis: Pooled results from two randomized phase 3 studies. Am J Clin Dermatol. 2024 (May 2). doi:  10.1007/s40257-024-00855-2 Source

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Key clinical point: Topical 1.5% ruxolitinib was effective and well-tolerated and offered long-term disease control with as-needed use in adolescents with atopic dermatitis (AD).

Major finding: At week 8, a substantially higher number of patients receiving 1.5% ruxolitinib vs vehicle achieved an Investigator's Global Assessment (IGA) score of 0 or 1 with ≥2 grade improvement from baseline (50.6% vs 14.0%) and ≥75% improvement in the Eczema Area and Severity Index score (60.9% vs 34.9%), with sustained or increased proportion of patients achieving an IGA score of 0 or 1 during the long-term safety (LTS) period. No serious adverse events were reported.

Study details: This study used pooled data from two phase 3 trials (TRuE-AD1 and TRuE-AD2) and included 137 adolescents (age, 12-17 years) with AD who were randomly assigned to receive 0.75% or 1.5% ruxolitinib cream or vehicle twice daily for 8 weeks, followed by an LTS period lasting up to 52 weeks.

Disclosures: This study was funded by Incyte Corporation. Four authors declared being employees or shareholders of Incyte Corporation. Several authors declared ties with various sources, including Incyte Corporation.

Source: Eichenfield LF, Simpson EL, Papp K, et al. Efficacy, safety, and long-term disease control of ruxolitinib cream among adolescents with atopic dermatitis: Pooled results from two randomized phase 3 studies. Am J Clin Dermatol. 2024 (May 2). doi:  10.1007/s40257-024-00855-2 Source

Key clinical point: Topical 1.5% ruxolitinib was effective and well-tolerated and offered long-term disease control with as-needed use in adolescents with atopic dermatitis (AD).

Major finding: At week 8, a substantially higher number of patients receiving 1.5% ruxolitinib vs vehicle achieved an Investigator's Global Assessment (IGA) score of 0 or 1 with ≥2 grade improvement from baseline (50.6% vs 14.0%) and ≥75% improvement in the Eczema Area and Severity Index score (60.9% vs 34.9%), with sustained or increased proportion of patients achieving an IGA score of 0 or 1 during the long-term safety (LTS) period. No serious adverse events were reported.

Study details: This study used pooled data from two phase 3 trials (TRuE-AD1 and TRuE-AD2) and included 137 adolescents (age, 12-17 years) with AD who were randomly assigned to receive 0.75% or 1.5% ruxolitinib cream or vehicle twice daily for 8 weeks, followed by an LTS period lasting up to 52 weeks.

Disclosures: This study was funded by Incyte Corporation. Four authors declared being employees or shareholders of Incyte Corporation. Several authors declared ties with various sources, including Incyte Corporation.

Source: Eichenfield LF, Simpson EL, Papp K, et al. Efficacy, safety, and long-term disease control of ruxolitinib cream among adolescents with atopic dermatitis: Pooled results from two randomized phase 3 studies. Am J Clin Dermatol. 2024 (May 2). doi:  10.1007/s40257-024-00855-2 Source

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Obesity Associated With Disease Severity in Moderate to Severe Atopic Dermatitis

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Key clinical point: Obesity is significantly associated with patient- and physician-assessed measures of atopic dermatitis (AD) disease severity.

Major finding: Increased body mass index (BMI) values were associated with higher disease severity as assessed by objective Scoring AD (adjusted β 1.24; P = .013) and patient-oriented eczema measure (adjusted β 1.09; P = .038) scores.

Study details: This study based on data from the prospective observational TREATgermany registry included 1416 patients with moderate to severe AD who were either underweight (BMI < 18.5 kg/m2; n = 33), normal weight or overweight (nonobese; BMI ≥ 18.5 and < 30 kg/m2; n = 1149), or obese (BMI ≥ 30 kg/m2; n = 234).

Disclosures: The TREATgermany registry is supported by AbbVie Deutschland GmbH & Co. KG, Galderma SA, LEO Pharma GmbH, Lilly Deutschland GmbH, Pfizer Inc., and Sanofi. Eight authors declared serving as consultants or lecturers for or receiving research grants, personal fees, or lecture or consulting honoraria from various sources, including some of the supporters of TREATgermany.

Source: Traidl S, Hollstein MM, Kroeger N, et al, and The TREATgermany Study Group. Obesity is linked to disease severity in moderate to severe atopic dermatitis—Data from the prospective observational TREATgermany registry. J Eur Acad Dermatol Venereol. 2024 (Apr 25). doi:  10.1111/jdv.20042 Source

 

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Key clinical point: Obesity is significantly associated with patient- and physician-assessed measures of atopic dermatitis (AD) disease severity.

Major finding: Increased body mass index (BMI) values were associated with higher disease severity as assessed by objective Scoring AD (adjusted β 1.24; P = .013) and patient-oriented eczema measure (adjusted β 1.09; P = .038) scores.

Study details: This study based on data from the prospective observational TREATgermany registry included 1416 patients with moderate to severe AD who were either underweight (BMI < 18.5 kg/m2; n = 33), normal weight or overweight (nonobese; BMI ≥ 18.5 and < 30 kg/m2; n = 1149), or obese (BMI ≥ 30 kg/m2; n = 234).

Disclosures: The TREATgermany registry is supported by AbbVie Deutschland GmbH & Co. KG, Galderma SA, LEO Pharma GmbH, Lilly Deutschland GmbH, Pfizer Inc., and Sanofi. Eight authors declared serving as consultants or lecturers for or receiving research grants, personal fees, or lecture or consulting honoraria from various sources, including some of the supporters of TREATgermany.

Source: Traidl S, Hollstein MM, Kroeger N, et al, and The TREATgermany Study Group. Obesity is linked to disease severity in moderate to severe atopic dermatitis—Data from the prospective observational TREATgermany registry. J Eur Acad Dermatol Venereol. 2024 (Apr 25). doi:  10.1111/jdv.20042 Source

 

Key clinical point: Obesity is significantly associated with patient- and physician-assessed measures of atopic dermatitis (AD) disease severity.

Major finding: Increased body mass index (BMI) values were associated with higher disease severity as assessed by objective Scoring AD (adjusted β 1.24; P = .013) and patient-oriented eczema measure (adjusted β 1.09; P = .038) scores.

Study details: This study based on data from the prospective observational TREATgermany registry included 1416 patients with moderate to severe AD who were either underweight (BMI < 18.5 kg/m2; n = 33), normal weight or overweight (nonobese; BMI ≥ 18.5 and < 30 kg/m2; n = 1149), or obese (BMI ≥ 30 kg/m2; n = 234).

Disclosures: The TREATgermany registry is supported by AbbVie Deutschland GmbH & Co. KG, Galderma SA, LEO Pharma GmbH, Lilly Deutschland GmbH, Pfizer Inc., and Sanofi. Eight authors declared serving as consultants or lecturers for or receiving research grants, personal fees, or lecture or consulting honoraria from various sources, including some of the supporters of TREATgermany.

Source: Traidl S, Hollstein MM, Kroeger N, et al, and The TREATgermany Study Group. Obesity is linked to disease severity in moderate to severe atopic dermatitis—Data from the prospective observational TREATgermany registry. J Eur Acad Dermatol Venereol. 2024 (Apr 25). doi:  10.1111/jdv.20042 Source

 

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Antibiotics in Early Infancy Disrupt Gut Microbiome and Increase Risk for Atopic Dermatitis

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Key clinical point: Antibiotic use early in life, especially within one year of age, disrupts the gut microbiome and increases the risk for atopic dermatitis (AD) at 5 years of age.

Major finding: Children who received antibiotics during the first year of life vs later were significantly more likely to develop AD at 5 years of age (adjusted odds ratio [aOR] 1.81; P < .001), with an increased number of antibiotic courses leading to a dose-response-like increased risk for AD (1 course: aOR 1.67; P = .0044; ≥ 2 courses: aOR 2.16; P = .0030).

Study details: This study analyzed the clinical data for AD diagnosis at age 5 years of 2484 children from the prospective, general population CHILD birth cohort, which enrolled pregnant women and infants with no congenital abnormalities born at ≥ 34 weeks of gestation.

Disclosures: The CHILD Study is funded by the Canadian Institutes of Health Research, the Allergy, Genes, and Environment Network of Centres of Excellence, Debbie and Don Morrison, and others. The authors declared no conflicts of interest.

Source: Hoskinson C, Medeleanu MV, Reyna ME, et al. Antibiotics within first year are linked to infant gut microbiome disruption and elevated atopic dermatitis risk. J Allergy Clin Immunol. 2024 (Apr 24). doi: 10.1016/j.jaci.2024.03.025 Source

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Key clinical point: Antibiotic use early in life, especially within one year of age, disrupts the gut microbiome and increases the risk for atopic dermatitis (AD) at 5 years of age.

Major finding: Children who received antibiotics during the first year of life vs later were significantly more likely to develop AD at 5 years of age (adjusted odds ratio [aOR] 1.81; P < .001), with an increased number of antibiotic courses leading to a dose-response-like increased risk for AD (1 course: aOR 1.67; P = .0044; ≥ 2 courses: aOR 2.16; P = .0030).

Study details: This study analyzed the clinical data for AD diagnosis at age 5 years of 2484 children from the prospective, general population CHILD birth cohort, which enrolled pregnant women and infants with no congenital abnormalities born at ≥ 34 weeks of gestation.

Disclosures: The CHILD Study is funded by the Canadian Institutes of Health Research, the Allergy, Genes, and Environment Network of Centres of Excellence, Debbie and Don Morrison, and others. The authors declared no conflicts of interest.

Source: Hoskinson C, Medeleanu MV, Reyna ME, et al. Antibiotics within first year are linked to infant gut microbiome disruption and elevated atopic dermatitis risk. J Allergy Clin Immunol. 2024 (Apr 24). doi: 10.1016/j.jaci.2024.03.025 Source

Key clinical point: Antibiotic use early in life, especially within one year of age, disrupts the gut microbiome and increases the risk for atopic dermatitis (AD) at 5 years of age.

Major finding: Children who received antibiotics during the first year of life vs later were significantly more likely to develop AD at 5 years of age (adjusted odds ratio [aOR] 1.81; P < .001), with an increased number of antibiotic courses leading to a dose-response-like increased risk for AD (1 course: aOR 1.67; P = .0044; ≥ 2 courses: aOR 2.16; P = .0030).

Study details: This study analyzed the clinical data for AD diagnosis at age 5 years of 2484 children from the prospective, general population CHILD birth cohort, which enrolled pregnant women and infants with no congenital abnormalities born at ≥ 34 weeks of gestation.

Disclosures: The CHILD Study is funded by the Canadian Institutes of Health Research, the Allergy, Genes, and Environment Network of Centres of Excellence, Debbie and Don Morrison, and others. The authors declared no conflicts of interest.

Source: Hoskinson C, Medeleanu MV, Reyna ME, et al. Antibiotics within first year are linked to infant gut microbiome disruption and elevated atopic dermatitis risk. J Allergy Clin Immunol. 2024 (Apr 24). doi: 10.1016/j.jaci.2024.03.025 Source

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Commentary: Evaluating Recent BC Treatment Trials, May 2024

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Dr. Roesch scans the journals, so you don't have to!

Erin Roesch, MD
Support for de-escalation of axillary surgery for select patients, specifically those with cT1-2, node-negative breast cancer and a positive sentinel lymph node (SLN) biopsy, has been demonstrated in prior studies, including the ACOSOG Z0011 and AMAROS trials.[1,2] Both of these trials showed no benefit of completion axillary-node dissection (ALND) after 10 years of follow-up for these patients, and higher rates of lymphedema for ALND were observed in AMAROS. The phase 3 noninferiority SENOMAC trial aimed to validate findings from prior studies and to include groups of patients that were underrepresented (patients undergoing mastectomy, SLN with extracapsular extension, T3 tumors, and males). A total of 2540 patients with cT1-3cN0 primary breast cancer and one to two SLN macrometastases were randomly assigned to SLNB or completion ALND. The majority of patients received radiation, including nodal target volumes, as well as adjuvant systemic therapy. The estimated 5-year recurrence-free survival after SLNB only was noninferior to that seen with complete ALND (89.7%, 95% CI 87.5%-91.9%; vs 88.7%, 95% CI 86.3%-91.1%) with a hazard ratio for recurrence or death of 0.89, which was significantly (P < .001) below the noninferiority margin. These results add to the growing body of data indicating that certain patient populations can be spared more aggressive axillary surgery while maintaining excellent survival outcomes and reducing side effects.

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
Author and Disclosure Information

Erin E. Roesch, MD, Associate Staff, Department of Medical Oncology, Cleveland Clinic, Cleveland, Ohio
Erin E. Roesch, MD, has disclosed the following relevant financial relationships:
Serve(d) as a speaker or a member of a speakers bureau for: Puma Biotechnology

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Author and Disclosure Information

Erin E. Roesch, MD, Associate Staff, Department of Medical Oncology, Cleveland Clinic, Cleveland, Ohio
Erin E. Roesch, MD, has disclosed the following relevant financial relationships:
Serve(d) as a speaker or a member of a speakers bureau for: Puma Biotechnology

Author and Disclosure Information

Erin E. Roesch, MD, Associate Staff, Department of Medical Oncology, Cleveland Clinic, Cleveland, Ohio
Erin E. Roesch, MD, has disclosed the following relevant financial relationships:
Serve(d) as a speaker or a member of a speakers bureau for: Puma Biotechnology

Dr. Roesch scans the journals, so you don't have to!
Dr. Roesch scans the journals, so you don't have to!

Erin Roesch, MD
Support for de-escalation of axillary surgery for select patients, specifically those with cT1-2, node-negative breast cancer and a positive sentinel lymph node (SLN) biopsy, has been demonstrated in prior studies, including the ACOSOG Z0011 and AMAROS trials.[1,2] Both of these trials showed no benefit of completion axillary-node dissection (ALND) after 10 years of follow-up for these patients, and higher rates of lymphedema for ALND were observed in AMAROS. The phase 3 noninferiority SENOMAC trial aimed to validate findings from prior studies and to include groups of patients that were underrepresented (patients undergoing mastectomy, SLN with extracapsular extension, T3 tumors, and males). A total of 2540 patients with cT1-3cN0 primary breast cancer and one to two SLN macrometastases were randomly assigned to SLNB or completion ALND. The majority of patients received radiation, including nodal target volumes, as well as adjuvant systemic therapy. The estimated 5-year recurrence-free survival after SLNB only was noninferior to that seen with complete ALND (89.7%, 95% CI 87.5%-91.9%; vs 88.7%, 95% CI 86.3%-91.1%) with a hazard ratio for recurrence or death of 0.89, which was significantly (P < .001) below the noninferiority margin. These results add to the growing body of data indicating that certain patient populations can be spared more aggressive axillary surgery while maintaining excellent survival outcomes and reducing side effects.

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

Erin Roesch, MD
Support for de-escalation of axillary surgery for select patients, specifically those with cT1-2, node-negative breast cancer and a positive sentinel lymph node (SLN) biopsy, has been demonstrated in prior studies, including the ACOSOG Z0011 and AMAROS trials.[1,2] Both of these trials showed no benefit of completion axillary-node dissection (ALND) after 10 years of follow-up for these patients, and higher rates of lymphedema for ALND were observed in AMAROS. The phase 3 noninferiority SENOMAC trial aimed to validate findings from prior studies and to include groups of patients that were underrepresented (patients undergoing mastectomy, SLN with extracapsular extension, T3 tumors, and males). A total of 2540 patients with cT1-3cN0 primary breast cancer and one to two SLN macrometastases were randomly assigned to SLNB or completion ALND. The majority of patients received radiation, including nodal target volumes, as well as adjuvant systemic therapy. The estimated 5-year recurrence-free survival after SLNB only was noninferior to that seen with complete ALND (89.7%, 95% CI 87.5%-91.9%; vs 88.7%, 95% CI 86.3%-91.1%) with a hazard ratio for recurrence or death of 0.89, which was significantly (P < .001) below the noninferiority margin. These results add to the growing body of data indicating that certain patient populations can be spared more aggressive axillary surgery while maintaining excellent survival outcomes and reducing side effects.

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
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Commentary: Diet and Lifestyle in Migraine, May 2024

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Dr Moawad scans the journals so you don't have to!

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

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Case Western Reserve School of Medicine
Cleveland, OH

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Dr Moawad scans the journals so you don't have to!
Dr Moawad scans the journals so you don't have to!

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

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