Abrocitinib downregulates genes associated with atopic dermatitis pathology

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Key clinical point: Abrocitinib treatment over 12 weeks significantly decreased the cutaneous expression of selected genes involved in inflammation, epidermal hyperplasia, and T-helper (Th) 2 and Th22 immune responses in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: Compared with placebo, 12-week abrocitinib treatment led to a dose-dependent reduction in the cutaneous expression of genes involved in inflammation (MMP-12), epidermal hyperplasia (KRT16), Th2 (CCL17 and CCL18), and Th22 (S100A8, S100A9, and S100A12) responses (all P < .05).

Study details: Findings are from the phase 2a JADE MOA trial including patients with moderate-to-severe AD who were randomly assigned to receive 100 mg (n = 16) or 200 mg (n = 14) abrocitinib monotherapy or placebo (n = 16) daily for 12 weeks.

Disclosures: This study was sponsored by Pfizer Inc. Several authors declared being on the advisory board of; serving as consultants, advisors, or speakers for; or receiving honoraria or grants from Pfizer or others. Seven authors declared being current or former employees and shareholders of Pfizer.

Source: Guttman-Yassky E et al. Effect of abrocitinib on skin biomarkers in patients with moderate-to-severe atopic dermatitis. Allergy. 2023 (Dec 18). doi: 10.1111/all.15969

 

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Key clinical point: Abrocitinib treatment over 12 weeks significantly decreased the cutaneous expression of selected genes involved in inflammation, epidermal hyperplasia, and T-helper (Th) 2 and Th22 immune responses in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: Compared with placebo, 12-week abrocitinib treatment led to a dose-dependent reduction in the cutaneous expression of genes involved in inflammation (MMP-12), epidermal hyperplasia (KRT16), Th2 (CCL17 and CCL18), and Th22 (S100A8, S100A9, and S100A12) responses (all P < .05).

Study details: Findings are from the phase 2a JADE MOA trial including patients with moderate-to-severe AD who were randomly assigned to receive 100 mg (n = 16) or 200 mg (n = 14) abrocitinib monotherapy or placebo (n = 16) daily for 12 weeks.

Disclosures: This study was sponsored by Pfizer Inc. Several authors declared being on the advisory board of; serving as consultants, advisors, or speakers for; or receiving honoraria or grants from Pfizer or others. Seven authors declared being current or former employees and shareholders of Pfizer.

Source: Guttman-Yassky E et al. Effect of abrocitinib on skin biomarkers in patients with moderate-to-severe atopic dermatitis. Allergy. 2023 (Dec 18). doi: 10.1111/all.15969

 

Key clinical point: Abrocitinib treatment over 12 weeks significantly decreased the cutaneous expression of selected genes involved in inflammation, epidermal hyperplasia, and T-helper (Th) 2 and Th22 immune responses in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: Compared with placebo, 12-week abrocitinib treatment led to a dose-dependent reduction in the cutaneous expression of genes involved in inflammation (MMP-12), epidermal hyperplasia (KRT16), Th2 (CCL17 and CCL18), and Th22 (S100A8, S100A9, and S100A12) responses (all P < .05).

Study details: Findings are from the phase 2a JADE MOA trial including patients with moderate-to-severe AD who were randomly assigned to receive 100 mg (n = 16) or 200 mg (n = 14) abrocitinib monotherapy or placebo (n = 16) daily for 12 weeks.

Disclosures: This study was sponsored by Pfizer Inc. Several authors declared being on the advisory board of; serving as consultants, advisors, or speakers for; or receiving honoraria or grants from Pfizer or others. Seven authors declared being current or former employees and shareholders of Pfizer.

Source: Guttman-Yassky E et al. Effect of abrocitinib on skin biomarkers in patients with moderate-to-severe atopic dermatitis. Allergy. 2023 (Dec 18). doi: 10.1111/all.15969

 

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Rapid and sustained improvement in skin pain with abrocitinib in atopic dermatitis

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Key clinical point: Abrocitinib as monotherapy or in combination with topical therapy improves skin pain in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: Abrocitinib vs placebo led to a significantly greater dose-dependent least squares mean change in Pruritus and Symptoms Assessment for AD (PSAAD) skin pain score from baseline to as early as week 1 that were sustained through week 12 or 16 (nominal P < .05). A greater proportion of patients achieved a stringent threshold of skin pain improvement (PSAAD skin pain score < 2) with abrocitinib vs placebo (nominal P < .05).

Study details: This post hoc analysis of five phase 2/3 trials included 1822 patients with moderate-to-severe AD (age ≥ 12 years) treated with 100 mg or 200 mg abrocitinib as monotherapy or in combination with topical therapy or placebo for 12 or 16 weeks.

Disclosures: This study was funded by Pfizer Inc., USA. Six authors declared being employees and stockholders of Pfizer. The other authors declared receiving research or travel grants or having other ties with various sources, including Pfizer.

Source: Thyssen JP et al. Abrocitinib provides rapid and sustained improvement in skin pain and is associated with improved quality of life outcomes in adult and adolescent patients with moderate-to-severe atopic dermatitis. Dermatology. 2023 (Dec 11). doi: 10.1159/000535285

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Key clinical point: Abrocitinib as monotherapy or in combination with topical therapy improves skin pain in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: Abrocitinib vs placebo led to a significantly greater dose-dependent least squares mean change in Pruritus and Symptoms Assessment for AD (PSAAD) skin pain score from baseline to as early as week 1 that were sustained through week 12 or 16 (nominal P < .05). A greater proportion of patients achieved a stringent threshold of skin pain improvement (PSAAD skin pain score < 2) with abrocitinib vs placebo (nominal P < .05).

Study details: This post hoc analysis of five phase 2/3 trials included 1822 patients with moderate-to-severe AD (age ≥ 12 years) treated with 100 mg or 200 mg abrocitinib as monotherapy or in combination with topical therapy or placebo for 12 or 16 weeks.

Disclosures: This study was funded by Pfizer Inc., USA. Six authors declared being employees and stockholders of Pfizer. The other authors declared receiving research or travel grants or having other ties with various sources, including Pfizer.

Source: Thyssen JP et al. Abrocitinib provides rapid and sustained improvement in skin pain and is associated with improved quality of life outcomes in adult and adolescent patients with moderate-to-severe atopic dermatitis. Dermatology. 2023 (Dec 11). doi: 10.1159/000535285

Key clinical point: Abrocitinib as monotherapy or in combination with topical therapy improves skin pain in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: Abrocitinib vs placebo led to a significantly greater dose-dependent least squares mean change in Pruritus and Symptoms Assessment for AD (PSAAD) skin pain score from baseline to as early as week 1 that were sustained through week 12 or 16 (nominal P < .05). A greater proportion of patients achieved a stringent threshold of skin pain improvement (PSAAD skin pain score < 2) with abrocitinib vs placebo (nominal P < .05).

Study details: This post hoc analysis of five phase 2/3 trials included 1822 patients with moderate-to-severe AD (age ≥ 12 years) treated with 100 mg or 200 mg abrocitinib as monotherapy or in combination with topical therapy or placebo for 12 or 16 weeks.

Disclosures: This study was funded by Pfizer Inc., USA. Six authors declared being employees and stockholders of Pfizer. The other authors declared receiving research or travel grants or having other ties with various sources, including Pfizer.

Source: Thyssen JP et al. Abrocitinib provides rapid and sustained improvement in skin pain and is associated with improved quality of life outcomes in adult and adolescent patients with moderate-to-severe atopic dermatitis. Dermatology. 2023 (Dec 11). doi: 10.1159/000535285

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Allergic contact dermatitis a crucial comorbidity in atopic dermatitis

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Key clinical point: Allergic contact dermatitis (ACD) is an important comorbidity in patients with atopic dermatitis (AD) and leads to the maintenance and aggravation of their dermatosis, with a high frequency of ACD observed to textile dyes, isothiazolinones, and fragrances.

Major finding: Contact sensitization was significantly associated with facial involvement (P = .04) and a longer duration of AD (P = .005). The most frequent allergen was textile dye mix (24.70%) followed by nickel (20.21%), cobalt (12.70%), and methylchlorisothiazolinone+methylisothiazolinone (8.50%). The avoidance of relevant allergens led to a significant reduction in the Scoring of Atopic Dermatitis (SCORAD) scores at 6 months (P < .001).

Study details: This longitudinal prospective study included 93 patients with AD (age > 2 years) who were patch-tested with the 2019 European baseline series and the corticosteroid series, 60.2% of whom had positive patch test results.

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

Source: Trimeche K et al. Contact allergy in atopic dermatitis: A prospective study on prevalence, incriminated allergens and clinical insights. Contact Dermatitis. 2023 (Dec 27). doi: 10.1111/cod.14494

 

 

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Key clinical point: Allergic contact dermatitis (ACD) is an important comorbidity in patients with atopic dermatitis (AD) and leads to the maintenance and aggravation of their dermatosis, with a high frequency of ACD observed to textile dyes, isothiazolinones, and fragrances.

Major finding: Contact sensitization was significantly associated with facial involvement (P = .04) and a longer duration of AD (P = .005). The most frequent allergen was textile dye mix (24.70%) followed by nickel (20.21%), cobalt (12.70%), and methylchlorisothiazolinone+methylisothiazolinone (8.50%). The avoidance of relevant allergens led to a significant reduction in the Scoring of Atopic Dermatitis (SCORAD) scores at 6 months (P < .001).

Study details: This longitudinal prospective study included 93 patients with AD (age > 2 years) who were patch-tested with the 2019 European baseline series and the corticosteroid series, 60.2% of whom had positive patch test results.

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

Source: Trimeche K et al. Contact allergy in atopic dermatitis: A prospective study on prevalence, incriminated allergens and clinical insights. Contact Dermatitis. 2023 (Dec 27). doi: 10.1111/cod.14494

 

 

Key clinical point: Allergic contact dermatitis (ACD) is an important comorbidity in patients with atopic dermatitis (AD) and leads to the maintenance and aggravation of their dermatosis, with a high frequency of ACD observed to textile dyes, isothiazolinones, and fragrances.

Major finding: Contact sensitization was significantly associated with facial involvement (P = .04) and a longer duration of AD (P = .005). The most frequent allergen was textile dye mix (24.70%) followed by nickel (20.21%), cobalt (12.70%), and methylchlorisothiazolinone+methylisothiazolinone (8.50%). The avoidance of relevant allergens led to a significant reduction in the Scoring of Atopic Dermatitis (SCORAD) scores at 6 months (P < .001).

Study details: This longitudinal prospective study included 93 patients with AD (age > 2 years) who were patch-tested with the 2019 European baseline series and the corticosteroid series, 60.2% of whom had positive patch test results.

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

Source: Trimeche K et al. Contact allergy in atopic dermatitis: A prospective study on prevalence, incriminated allergens and clinical insights. Contact Dermatitis. 2023 (Dec 27). doi: 10.1111/cod.14494

 

 

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Aggregate response benefit in skin clearance and itch reduction favor upadacitinib over dupilumab in AD

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Key clinical point: The overall improvement in skin clearance and itch reduction suggested a preference for 30 mg upadacitinib over dupilumab and that for 15 mg or 30 mg upadacitinib over placebo in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: At week 24, the aggregate response benefit for skin clearance and itch, respectively, was 32.5% and 25.8% higher with 30 mg upadacitinib vs dupilumab. The benefit favored upadacitinib over dupilumab as early as week 4. Moreover, 15 and 30 mg upadacitinib showed similar benefits over placebo.

Study details: This post hoc analysis of the data from phase 3 studies (Heads Up, Measure Up 1, and Measure Up 2) included 2356 patients with moderate-to-severe AD who received upadacitinib, dupilumab, or placebo.

Disclosures: This study was sponsored by AbbVie. Five authors declared being employees of or owning stock or stock options in AbbVie. Several authors declared being consultants, speakers, or advisors of or having other ties with various sources, including AbbVie.

Source: Silverberg JI et al. Aggregate response benefit in skin clearance and itch reduction with upadacitinib or dupilumab in patients with moderate-to-severe atopic dermatitis. Dermatitis. 2023 (Dec 18). doi: 10.1089/derm.2023.0153

 

 

 

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Key clinical point: The overall improvement in skin clearance and itch reduction suggested a preference for 30 mg upadacitinib over dupilumab and that for 15 mg or 30 mg upadacitinib over placebo in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: At week 24, the aggregate response benefit for skin clearance and itch, respectively, was 32.5% and 25.8% higher with 30 mg upadacitinib vs dupilumab. The benefit favored upadacitinib over dupilumab as early as week 4. Moreover, 15 and 30 mg upadacitinib showed similar benefits over placebo.

Study details: This post hoc analysis of the data from phase 3 studies (Heads Up, Measure Up 1, and Measure Up 2) included 2356 patients with moderate-to-severe AD who received upadacitinib, dupilumab, or placebo.

Disclosures: This study was sponsored by AbbVie. Five authors declared being employees of or owning stock or stock options in AbbVie. Several authors declared being consultants, speakers, or advisors of or having other ties with various sources, including AbbVie.

Source: Silverberg JI et al. Aggregate response benefit in skin clearance and itch reduction with upadacitinib or dupilumab in patients with moderate-to-severe atopic dermatitis. Dermatitis. 2023 (Dec 18). doi: 10.1089/derm.2023.0153

 

 

 

Key clinical point: The overall improvement in skin clearance and itch reduction suggested a preference for 30 mg upadacitinib over dupilumab and that for 15 mg or 30 mg upadacitinib over placebo in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: At week 24, the aggregate response benefit for skin clearance and itch, respectively, was 32.5% and 25.8% higher with 30 mg upadacitinib vs dupilumab. The benefit favored upadacitinib over dupilumab as early as week 4. Moreover, 15 and 30 mg upadacitinib showed similar benefits over placebo.

Study details: This post hoc analysis of the data from phase 3 studies (Heads Up, Measure Up 1, and Measure Up 2) included 2356 patients with moderate-to-severe AD who received upadacitinib, dupilumab, or placebo.

Disclosures: This study was sponsored by AbbVie. Five authors declared being employees of or owning stock or stock options in AbbVie. Several authors declared being consultants, speakers, or advisors of or having other ties with various sources, including AbbVie.

Source: Silverberg JI et al. Aggregate response benefit in skin clearance and itch reduction with upadacitinib or dupilumab in patients with moderate-to-severe atopic dermatitis. Dermatitis. 2023 (Dec 18). doi: 10.1089/derm.2023.0153

 

 

 

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Rademikibart shows promise in moderate-to-severe atopic dermatitis

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Key clinical point: Rademikibart administered at 2-week (Q2W) and 4-week (Q4W) intervals was well-tolerated and effective in improving the overall symptoms in adults with moderate-to-severe atopic dermatitis (AD).

Major finding: At week 16, the least squares mean percent reductions in the Eczema Area Severity Index scores with 300 mg Q2W (−63.0%; P = .0007), 150 mg Q2W (−57.6%; P = .0067), and 300 mg Q4W (−63.5%; P = .0004) rademikibart were significantly higher than that with placebo (−39.7%). Treatment-emergent adverse event rates were similar with rademikibart (48.2%) and placebo (53.6%).

Study details: This phase 2 trial included 226 anti-interleukin (IL)-4Ra/IL-13 treatment-naive adults with moderate-to-severe AD who were randomly assigned (1:1:1:1) to receive rademikibart (300 mg Q2W, 150 mg Q2W, or 300 mg Q4W) or placebo for 16 weeks following a 600 mg loading dose of rademikibart or placebo, respectively, on day 1.

Disclosures: This study was funded by Connect Biopharma. Ten authors declared being employees or shareholders of Connect Biopharma. The other authors declared being consultants of or having other ties with various sources, including Connect Biopharma.

Source: Silverberg JI et al. Efficacy and safety of rademikibart (CBP-201), a next-generation monoclonal antibody targeting IL-4Rα, in adults with moderate-to-severe atopic dermatitis: A phase 2 randomized trial (CBP-201-WW001). J Allergy Clin Immunol. 2023 (Dec 27). doi: 10.1016/j.jaci.2023.11.924

 

 

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Key clinical point: Rademikibart administered at 2-week (Q2W) and 4-week (Q4W) intervals was well-tolerated and effective in improving the overall symptoms in adults with moderate-to-severe atopic dermatitis (AD).

Major finding: At week 16, the least squares mean percent reductions in the Eczema Area Severity Index scores with 300 mg Q2W (−63.0%; P = .0007), 150 mg Q2W (−57.6%; P = .0067), and 300 mg Q4W (−63.5%; P = .0004) rademikibart were significantly higher than that with placebo (−39.7%). Treatment-emergent adverse event rates were similar with rademikibart (48.2%) and placebo (53.6%).

Study details: This phase 2 trial included 226 anti-interleukin (IL)-4Ra/IL-13 treatment-naive adults with moderate-to-severe AD who were randomly assigned (1:1:1:1) to receive rademikibart (300 mg Q2W, 150 mg Q2W, or 300 mg Q4W) or placebo for 16 weeks following a 600 mg loading dose of rademikibart or placebo, respectively, on day 1.

Disclosures: This study was funded by Connect Biopharma. Ten authors declared being employees or shareholders of Connect Biopharma. The other authors declared being consultants of or having other ties with various sources, including Connect Biopharma.

Source: Silverberg JI et al. Efficacy and safety of rademikibart (CBP-201), a next-generation monoclonal antibody targeting IL-4Rα, in adults with moderate-to-severe atopic dermatitis: A phase 2 randomized trial (CBP-201-WW001). J Allergy Clin Immunol. 2023 (Dec 27). doi: 10.1016/j.jaci.2023.11.924

 

 

Key clinical point: Rademikibart administered at 2-week (Q2W) and 4-week (Q4W) intervals was well-tolerated and effective in improving the overall symptoms in adults with moderate-to-severe atopic dermatitis (AD).

Major finding: At week 16, the least squares mean percent reductions in the Eczema Area Severity Index scores with 300 mg Q2W (−63.0%; P = .0007), 150 mg Q2W (−57.6%; P = .0067), and 300 mg Q4W (−63.5%; P = .0004) rademikibart were significantly higher than that with placebo (−39.7%). Treatment-emergent adverse event rates were similar with rademikibart (48.2%) and placebo (53.6%).

Study details: This phase 2 trial included 226 anti-interleukin (IL)-4Ra/IL-13 treatment-naive adults with moderate-to-severe AD who were randomly assigned (1:1:1:1) to receive rademikibart (300 mg Q2W, 150 mg Q2W, or 300 mg Q4W) or placebo for 16 weeks following a 600 mg loading dose of rademikibart or placebo, respectively, on day 1.

Disclosures: This study was funded by Connect Biopharma. Ten authors declared being employees or shareholders of Connect Biopharma. The other authors declared being consultants of or having other ties with various sources, including Connect Biopharma.

Source: Silverberg JI et al. Efficacy and safety of rademikibart (CBP-201), a next-generation monoclonal antibody targeting IL-4Rα, in adults with moderate-to-severe atopic dermatitis: A phase 2 randomized trial (CBP-201-WW001). J Allergy Clin Immunol. 2023 (Dec 27). doi: 10.1016/j.jaci.2023.11.924

 

 

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Interim analysis confirms the safety and efficacy of dupilumab in atopic dermatitis

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Key clinical point: Dupilumab led to a rapid improvement in disease control that was sustained through 2 years and showed an acceptable safety profile in adult and adolescent patients with moderate-to-severe atopic dermatitis (AD).

Major finding: Dupilumab led to an improvement in the mean Eczema Area and Severity Index score at 3 months (5.5) and 24 months (2.6) compared with baseline (16.1), with a mean absolute change from baseline to 24 months being −14.0. No new safety signals were observed.

Study details: Findings are from a 2-year interim analysis of real-world data from the PROSE registry study including 764 patients with moderate-to-severe AD (age ≥ 12 years) who initiated dupilumab.

Disclosures: The PROSE registry is sponsored by Sanofi and Regeneron Pharmaceuticals Inc. Three authors declared being employees of or holding stock or stock options in Sanofi or Regeneron. The other authors declared serving as consultants, investigators, or advisory board members for or receiving speaker or investigator fees from Sanofi, Regeneron, and others.

Source: Simpson EL et al. Real-world effectiveness of dupilumab in adult and adolescent patients with atopic dermatitis: 2-year Interim data from the PROSE registry. Dermatol Ther (Heidelb). 2024 (Jan 4). doi: 10.1007/s13555-023-01061-4

 

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Key clinical point: Dupilumab led to a rapid improvement in disease control that was sustained through 2 years and showed an acceptable safety profile in adult and adolescent patients with moderate-to-severe atopic dermatitis (AD).

Major finding: Dupilumab led to an improvement in the mean Eczema Area and Severity Index score at 3 months (5.5) and 24 months (2.6) compared with baseline (16.1), with a mean absolute change from baseline to 24 months being −14.0. No new safety signals were observed.

Study details: Findings are from a 2-year interim analysis of real-world data from the PROSE registry study including 764 patients with moderate-to-severe AD (age ≥ 12 years) who initiated dupilumab.

Disclosures: The PROSE registry is sponsored by Sanofi and Regeneron Pharmaceuticals Inc. Three authors declared being employees of or holding stock or stock options in Sanofi or Regeneron. The other authors declared serving as consultants, investigators, or advisory board members for or receiving speaker or investigator fees from Sanofi, Regeneron, and others.

Source: Simpson EL et al. Real-world effectiveness of dupilumab in adult and adolescent patients with atopic dermatitis: 2-year Interim data from the PROSE registry. Dermatol Ther (Heidelb). 2024 (Jan 4). doi: 10.1007/s13555-023-01061-4

 

Key clinical point: Dupilumab led to a rapid improvement in disease control that was sustained through 2 years and showed an acceptable safety profile in adult and adolescent patients with moderate-to-severe atopic dermatitis (AD).

Major finding: Dupilumab led to an improvement in the mean Eczema Area and Severity Index score at 3 months (5.5) and 24 months (2.6) compared with baseline (16.1), with a mean absolute change from baseline to 24 months being −14.0. No new safety signals were observed.

Study details: Findings are from a 2-year interim analysis of real-world data from the PROSE registry study including 764 patients with moderate-to-severe AD (age ≥ 12 years) who initiated dupilumab.

Disclosures: The PROSE registry is sponsored by Sanofi and Regeneron Pharmaceuticals Inc. Three authors declared being employees of or holding stock or stock options in Sanofi or Regeneron. The other authors declared serving as consultants, investigators, or advisory board members for or receiving speaker or investigator fees from Sanofi, Regeneron, and others.

Source: Simpson EL et al. Real-world effectiveness of dupilumab in adult and adolescent patients with atopic dermatitis: 2-year Interim data from the PROSE registry. Dermatol Ther (Heidelb). 2024 (Jan 4). doi: 10.1007/s13555-023-01061-4

 

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Atopic dermatitis not linked with increased venous thromboembolism risk

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Key clinical point: Atopic dermatitis (AD) is associated with a lower risk for venous thromboembolism (VTE) than several rheumatologic and gastrointestinal immune-mediated inflammatory diseases (IMID).

Major finding: Patients with AD vs AD-matched control individuals did not have a higher risk for VTE (adjusted hazard ratio [aHR] 0.96; 95% CI 0.90-1.02). Compared with patients having AD, those with Crohn’s disease (aHR 1.71; 95% CI 1.47-1.99), rheumatoid arthritis (aHR 1.57; 95% CI 1.43-1.72), ulcerative colitis (aHR 1.84; 95% CI 1.63-2.09), and ankylosing spondylitis (aHR 1.45; 95% CI 1.03-2.03) had higher risks for VTE.

Study details: This retrospective observational cohort study analyzed 2,061,222 adult patients with IMID, including 1,098,633 patients with AD who were matched with 1,098,633 control individuals without IMID.

Disclosures: This study was funded by AbbVie Inc. JF Merola declared being a consultant or investigator for AbbVie and others. The other authors declared being current or former employees of or owning stocks or stock options in AbbVie.

Source: Merola JF et al. Venous thromboembolism risk is lower in patients with atopic dermatitis than other immune-mediated inflammatory diseases: A retrospective, observational, comparative cohort study using US claims data. J Am Acad Dermatol. 2023 (Dec 23). doi: 10.1016/j.jaad.2023.12.027

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Key clinical point: Atopic dermatitis (AD) is associated with a lower risk for venous thromboembolism (VTE) than several rheumatologic and gastrointestinal immune-mediated inflammatory diseases (IMID).

Major finding: Patients with AD vs AD-matched control individuals did not have a higher risk for VTE (adjusted hazard ratio [aHR] 0.96; 95% CI 0.90-1.02). Compared with patients having AD, those with Crohn’s disease (aHR 1.71; 95% CI 1.47-1.99), rheumatoid arthritis (aHR 1.57; 95% CI 1.43-1.72), ulcerative colitis (aHR 1.84; 95% CI 1.63-2.09), and ankylosing spondylitis (aHR 1.45; 95% CI 1.03-2.03) had higher risks for VTE.

Study details: This retrospective observational cohort study analyzed 2,061,222 adult patients with IMID, including 1,098,633 patients with AD who were matched with 1,098,633 control individuals without IMID.

Disclosures: This study was funded by AbbVie Inc. JF Merola declared being a consultant or investigator for AbbVie and others. The other authors declared being current or former employees of or owning stocks or stock options in AbbVie.

Source: Merola JF et al. Venous thromboembolism risk is lower in patients with atopic dermatitis than other immune-mediated inflammatory diseases: A retrospective, observational, comparative cohort study using US claims data. J Am Acad Dermatol. 2023 (Dec 23). doi: 10.1016/j.jaad.2023.12.027

Key clinical point: Atopic dermatitis (AD) is associated with a lower risk for venous thromboembolism (VTE) than several rheumatologic and gastrointestinal immune-mediated inflammatory diseases (IMID).

Major finding: Patients with AD vs AD-matched control individuals did not have a higher risk for VTE (adjusted hazard ratio [aHR] 0.96; 95% CI 0.90-1.02). Compared with patients having AD, those with Crohn’s disease (aHR 1.71; 95% CI 1.47-1.99), rheumatoid arthritis (aHR 1.57; 95% CI 1.43-1.72), ulcerative colitis (aHR 1.84; 95% CI 1.63-2.09), and ankylosing spondylitis (aHR 1.45; 95% CI 1.03-2.03) had higher risks for VTE.

Study details: This retrospective observational cohort study analyzed 2,061,222 adult patients with IMID, including 1,098,633 patients with AD who were matched with 1,098,633 control individuals without IMID.

Disclosures: This study was funded by AbbVie Inc. JF Merola declared being a consultant or investigator for AbbVie and others. The other authors declared being current or former employees of or owning stocks or stock options in AbbVie.

Source: Merola JF et al. Venous thromboembolism risk is lower in patients with atopic dermatitis than other immune-mediated inflammatory diseases: A retrospective, observational, comparative cohort study using US claims data. J Am Acad Dermatol. 2023 (Dec 23). doi: 10.1016/j.jaad.2023.12.027

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Atopic dermatitis not linked with increased venous thromboembolism risk

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Key clinical point: Atopic dermatitis (AD) is associated with a lower risk for venous thromboembolism (VTE) than several rheumatologic and gastrointestinal immune-mediated inflammatory diseases (IMID).

Major finding: Patients with AD vs AD-matched control individuals did not have a higher risk for VTE (adjusted hazard ratio [aHR] 0.96; 95% CI 0.90-1.02). Compared with patients having AD, those with Crohn’s disease (aHR 1.71; 95% CI 1.47-1.99), rheumatoid arthritis (aHR 1.57; 95% CI 1.43-1.72), ulcerative colitis (aHR 1.84; 95% CI 1.63-2.09), and ankylosing spondylitis (aHR 1.45; 95% CI 1.03-2.03) had higher risks for VTE.

Study details: This retrospective observational cohort study analyzed 2,061,222 adult patients with IMID, including 1,098,633 patients with AD who were matched with 1,098,633 control individuals without IMID.

Disclosures: This study was funded by AbbVie Inc. JF Merola declared being a consultant or investigator for AbbVie and others. The other authors declared being current or former employees of or owning stocks or stock options in AbbVie.

Source: Merola JF et al. Venous thromboembolism risk is lower in patients with atopic dermatitis than other immune-mediated inflammatory diseases: A retrospective, observational, comparative cohort study using US claims data. J Am Acad Dermatol. 2023 (Dec 23). doi: 10.1016/j.jaad.2023.12.027

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Key clinical point: Atopic dermatitis (AD) is associated with a lower risk for venous thromboembolism (VTE) than several rheumatologic and gastrointestinal immune-mediated inflammatory diseases (IMID).

Major finding: Patients with AD vs AD-matched control individuals did not have a higher risk for VTE (adjusted hazard ratio [aHR] 0.96; 95% CI 0.90-1.02). Compared with patients having AD, those with Crohn’s disease (aHR 1.71; 95% CI 1.47-1.99), rheumatoid arthritis (aHR 1.57; 95% CI 1.43-1.72), ulcerative colitis (aHR 1.84; 95% CI 1.63-2.09), and ankylosing spondylitis (aHR 1.45; 95% CI 1.03-2.03) had higher risks for VTE.

Study details: This retrospective observational cohort study analyzed 2,061,222 adult patients with IMID, including 1,098,633 patients with AD who were matched with 1,098,633 control individuals without IMID.

Disclosures: This study was funded by AbbVie Inc. JF Merola declared being a consultant or investigator for AbbVie and others. The other authors declared being current or former employees of or owning stocks or stock options in AbbVie.

Source: Merola JF et al. Venous thromboembolism risk is lower in patients with atopic dermatitis than other immune-mediated inflammatory diseases: A retrospective, observational, comparative cohort study using US claims data. J Am Acad Dermatol. 2023 (Dec 23). doi: 10.1016/j.jaad.2023.12.027

Key clinical point: Atopic dermatitis (AD) is associated with a lower risk for venous thromboembolism (VTE) than several rheumatologic and gastrointestinal immune-mediated inflammatory diseases (IMID).

Major finding: Patients with AD vs AD-matched control individuals did not have a higher risk for VTE (adjusted hazard ratio [aHR] 0.96; 95% CI 0.90-1.02). Compared with patients having AD, those with Crohn’s disease (aHR 1.71; 95% CI 1.47-1.99), rheumatoid arthritis (aHR 1.57; 95% CI 1.43-1.72), ulcerative colitis (aHR 1.84; 95% CI 1.63-2.09), and ankylosing spondylitis (aHR 1.45; 95% CI 1.03-2.03) had higher risks for VTE.

Study details: This retrospective observational cohort study analyzed 2,061,222 adult patients with IMID, including 1,098,633 patients with AD who were matched with 1,098,633 control individuals without IMID.

Disclosures: This study was funded by AbbVie Inc. JF Merola declared being a consultant or investigator for AbbVie and others. The other authors declared being current or former employees of or owning stocks or stock options in AbbVie.

Source: Merola JF et al. Venous thromboembolism risk is lower in patients with atopic dermatitis than other immune-mediated inflammatory diseases: A retrospective, observational, comparative cohort study using US claims data. J Am Acad Dermatol. 2023 (Dec 23). doi: 10.1016/j.jaad.2023.12.027

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Commentary: Fertility Concerns and Treatment-Related QOL After Breast Cancer, January 2024

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

Erin Roesch, MD
Future fertility is an important consideration for many young women diagnosed with breast cancer, and oncofertility counseling in women with a germline BRCA mutation can carry additional complexities. Examples include concern regarding transmission of the pathogenic gene to offspring, the effect of the deficient gene itself on ovarian function, and the recommendation to pursue risk-reducing bilateral salpingo-oophorectomy at a young age. The safety of pregnancy after breast cancer diagnosis has been demonstrated in several prior studies,1 but data in BRCA carriers have been limited to date. A retrospective cohort study conducted at 78 worldwide centers, including 4732 BRCA carriers diagnosed with breast cancer at age ≤ 40 years, investigated the incidence of pregnancy and maternal and fetal outcomes among these women (Lambertini et al). A total of 659 women had at least one pregnancy each after breast cancer; the cumulative incidence of pregnancy at 10 years was 22% (95% CI 21%-24%), and median time from breast cancer diagnosis to conception was 3.5 years (interquartile range 2.2-5.3 years). There was no significant difference in disease-free survival between those with or without pregnancy after breast cancer (adjusted hazard ratio 0.99; 95% CI 0.81-1.20, P = .90). Continued oncofertility research efforts are essential as the treatment landscape for early-stage breast cancer continues to evolve. Long-term follow-up of the POSITIVE trial included a small group of BRCA carriers and has shown reassuring results regarding interruption of endocrine therapy during attempts at conceiving.2

Young women diagnosed with breast cancer have been shown to experience higher rates of symptoms that may adversely affect quality of life (QOL), including depression, weight gain, vasomotor symptoms, and sexual dysfunction; they may also have a harder time managing these issues.3 Chemotherapy-related amenorrhea (CRA) is one of the side effects of breast cancer treatment that can affect premenopausal women, and is associated with both patient- (age, body mass index) and treatment-related (regimen, duration) factors.4 A study analyzing data derived from the prospective, longitudinal Cancer Toxicities Study included 1636 premenopausal women ≤ 50 years of age with stage I-III breast cancer treated with chemotherapy but not receiving ovarian suppression (Kabirian et al). A total of 83.0% of women reported CRA at year 1, 72.5% at year 2, and 66.1% at year 4. A higher likelihood of CRA was observed for women of older age vs those age 18-34 years (adjusted odds ratio [aOR] for 35-39 years 1.84; 40-44 years 5.90; and ≥ 45 years 21.29; P < .001 for all), those who received adjuvant tamoxifen (aOR 1.97; P < .001), and those who had hot flashes at baseline (aOR 1.83; P = .01). In the QOL analysis, 57.1% reported no recovery of menses. Persistent CRA was associated with worse insomnia, more systemic therapy–related adverse effects, and worse sexual functioning. These findings highlight the importance of identifying and discussing CRA with our patients, as this can have both physical and psychological effects in the survivorship setting.

The phase 3 KEYNOTE-522 trial has established immunotherapy plus an anthracycline-based chemotherapy backbone for the treatment of stage II-III triple-negative breast cancer (TNBC), with improvements in pathologic complete response (pCR) rates and survival outcomes.5 This regimen can present tolerance issues in clinical practice, and rare risks for cardiotoxicity and secondary hematologic malignancies are also relevant to consider. Furthermore, some patients may not be candidates for anthracycline-based treatment due to prior receipt of a drug in this class or cardiac comorbidities. De-escalation strategies are desired to lessen toxicity and maintain (or improve) outcomes. An open-label phase 2 trial (NeoPACT) investigated the efficacy of neoadjuvant carboplatin (AUC 6), docetaxel (75 mg/m2), and pembrolizumab (200 mg) every 21 days for six cycles among 115 patients with stage I-III TNBC (Sharma et al). The overall pCR and residual cancer burden (RCB 0+1) rates were 58% (95% CI 48%-67%) and 69% (95% CI 60%-78%), respectively. Estimated 3-year event-free survival was 86% (95% CI 77%-95%) in all patients, 98% in those with a pCR, and 68% in those with residual disease. This study also demonstrated a positive association of immune biomarkers and pathologic response. The most common grade ≥ 3 treatment-related adverse events were diarrhea (4.3%), anemia (3.5%), and peripheral sensory neuropathy (2.6%). The phase 3 SCARLET (Shorter Anthracycline-Free Chemoimmunotherapy Adapted to Pathologic Response in Early TNBC) trial is comparing the NeoPACT regimen with the standard KEYNOTE-522 regimen in early-stage TNBC and will be critical to further defining this treatment space.6 Presently, considering the described efficacy outcomes with the NeoPACT regimen, this regimen would be very reasonable to consider in patients who are not candidates for an anthracycline. Future prospective evaluation of immune biomarkers and additional predictors of response will also be valuable to further individualize treatment for our patients.

Additional References

  1. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: A systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.21.00535
  2. Partridge AH, Niman SM, Ruggeri M, et al, for the International Breast Cancer Study Group and POSITIVE Trial Collaborators. Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med. 2023;388:1645-1656. doi: 10.1056/NEJMoa2212856
  3. Howard-Anderson J, Ganz PA, Bower JE, Stanton AL. Quality of life, fertility concerns, and behavioral health outcomes in younger breast cancer survivors: A systematic review. J Natl Cancer Inst. 2012;104:386-405. doi: 10.1093/jnci/djr541
  4. Turnbull AK, Patel S, Martinez-Perez C, et al. Risk of chemotherapy-related amenorrhoea (CRA) in premenopausal women undergoing chemotherapy for early stage breast cancer. Breast Cancer Res Treat. 2021;186:237-245. doi: 10.1007/s10549-020-05951-5
  5. Schmid P, Cortes J, Dent R, et al; KEYNOTE-522 Investigators. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med. 2022;386:556-567. doi: 10.1056/NEJMoa2112651
  6. US National Cancer Institute, Cancer Therapy Evaluation Program. Shorter anthracycline-free chemoimmunotherapy adapted to pathological response in early TNBC (SCARLET); SWOG S2212. Source
Author and Disclosure Information

Erin Roesch, MD Assistant Professor, Department of Medicine, Cleveland Clinic Lerner College of Medicine; Assocaite Staff Physician, Hematology and Oncology, Cancer Institute, 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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Erin Roesch, MD Assistant Professor, Department of Medicine, Cleveland Clinic Lerner College of Medicine; Assocaite Staff Physician, Hematology and Oncology, Cancer Institute, 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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Erin Roesch, MD Assistant Professor, Department of Medicine, Cleveland Clinic Lerner College of Medicine; Assocaite Staff Physician, Hematology and Oncology, Cancer Institute, 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
Future fertility is an important consideration for many young women diagnosed with breast cancer, and oncofertility counseling in women with a germline BRCA mutation can carry additional complexities. Examples include concern regarding transmission of the pathogenic gene to offspring, the effect of the deficient gene itself on ovarian function, and the recommendation to pursue risk-reducing bilateral salpingo-oophorectomy at a young age. The safety of pregnancy after breast cancer diagnosis has been demonstrated in several prior studies,1 but data in BRCA carriers have been limited to date. A retrospective cohort study conducted at 78 worldwide centers, including 4732 BRCA carriers diagnosed with breast cancer at age ≤ 40 years, investigated the incidence of pregnancy and maternal and fetal outcomes among these women (Lambertini et al). A total of 659 women had at least one pregnancy each after breast cancer; the cumulative incidence of pregnancy at 10 years was 22% (95% CI 21%-24%), and median time from breast cancer diagnosis to conception was 3.5 years (interquartile range 2.2-5.3 years). There was no significant difference in disease-free survival between those with or without pregnancy after breast cancer (adjusted hazard ratio 0.99; 95% CI 0.81-1.20, P = .90). Continued oncofertility research efforts are essential as the treatment landscape for early-stage breast cancer continues to evolve. Long-term follow-up of the POSITIVE trial included a small group of BRCA carriers and has shown reassuring results regarding interruption of endocrine therapy during attempts at conceiving.2

Young women diagnosed with breast cancer have been shown to experience higher rates of symptoms that may adversely affect quality of life (QOL), including depression, weight gain, vasomotor symptoms, and sexual dysfunction; they may also have a harder time managing these issues.3 Chemotherapy-related amenorrhea (CRA) is one of the side effects of breast cancer treatment that can affect premenopausal women, and is associated with both patient- (age, body mass index) and treatment-related (regimen, duration) factors.4 A study analyzing data derived from the prospective, longitudinal Cancer Toxicities Study included 1636 premenopausal women ≤ 50 years of age with stage I-III breast cancer treated with chemotherapy but not receiving ovarian suppression (Kabirian et al). A total of 83.0% of women reported CRA at year 1, 72.5% at year 2, and 66.1% at year 4. A higher likelihood of CRA was observed for women of older age vs those age 18-34 years (adjusted odds ratio [aOR] for 35-39 years 1.84; 40-44 years 5.90; and ≥ 45 years 21.29; P < .001 for all), those who received adjuvant tamoxifen (aOR 1.97; P < .001), and those who had hot flashes at baseline (aOR 1.83; P = .01). In the QOL analysis, 57.1% reported no recovery of menses. Persistent CRA was associated with worse insomnia, more systemic therapy–related adverse effects, and worse sexual functioning. These findings highlight the importance of identifying and discussing CRA with our patients, as this can have both physical and psychological effects in the survivorship setting.

The phase 3 KEYNOTE-522 trial has established immunotherapy plus an anthracycline-based chemotherapy backbone for the treatment of stage II-III triple-negative breast cancer (TNBC), with improvements in pathologic complete response (pCR) rates and survival outcomes.5 This regimen can present tolerance issues in clinical practice, and rare risks for cardiotoxicity and secondary hematologic malignancies are also relevant to consider. Furthermore, some patients may not be candidates for anthracycline-based treatment due to prior receipt of a drug in this class or cardiac comorbidities. De-escalation strategies are desired to lessen toxicity and maintain (or improve) outcomes. An open-label phase 2 trial (NeoPACT) investigated the efficacy of neoadjuvant carboplatin (AUC 6), docetaxel (75 mg/m2), and pembrolizumab (200 mg) every 21 days for six cycles among 115 patients with stage I-III TNBC (Sharma et al). The overall pCR and residual cancer burden (RCB 0+1) rates were 58% (95% CI 48%-67%) and 69% (95% CI 60%-78%), respectively. Estimated 3-year event-free survival was 86% (95% CI 77%-95%) in all patients, 98% in those with a pCR, and 68% in those with residual disease. This study also demonstrated a positive association of immune biomarkers and pathologic response. The most common grade ≥ 3 treatment-related adverse events were diarrhea (4.3%), anemia (3.5%), and peripheral sensory neuropathy (2.6%). The phase 3 SCARLET (Shorter Anthracycline-Free Chemoimmunotherapy Adapted to Pathologic Response in Early TNBC) trial is comparing the NeoPACT regimen with the standard KEYNOTE-522 regimen in early-stage TNBC and will be critical to further defining this treatment space.6 Presently, considering the described efficacy outcomes with the NeoPACT regimen, this regimen would be very reasonable to consider in patients who are not candidates for an anthracycline. Future prospective evaluation of immune biomarkers and additional predictors of response will also be valuable to further individualize treatment for our patients.

Additional References

  1. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: A systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.21.00535
  2. Partridge AH, Niman SM, Ruggeri M, et al, for the International Breast Cancer Study Group and POSITIVE Trial Collaborators. Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med. 2023;388:1645-1656. doi: 10.1056/NEJMoa2212856
  3. Howard-Anderson J, Ganz PA, Bower JE, Stanton AL. Quality of life, fertility concerns, and behavioral health outcomes in younger breast cancer survivors: A systematic review. J Natl Cancer Inst. 2012;104:386-405. doi: 10.1093/jnci/djr541
  4. Turnbull AK, Patel S, Martinez-Perez C, et al. Risk of chemotherapy-related amenorrhoea (CRA) in premenopausal women undergoing chemotherapy for early stage breast cancer. Breast Cancer Res Treat. 2021;186:237-245. doi: 10.1007/s10549-020-05951-5
  5. Schmid P, Cortes J, Dent R, et al; KEYNOTE-522 Investigators. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med. 2022;386:556-567. doi: 10.1056/NEJMoa2112651
  6. US National Cancer Institute, Cancer Therapy Evaluation Program. Shorter anthracycline-free chemoimmunotherapy adapted to pathological response in early TNBC (SCARLET); SWOG S2212. Source

Erin Roesch, MD
Future fertility is an important consideration for many young women diagnosed with breast cancer, and oncofertility counseling in women with a germline BRCA mutation can carry additional complexities. Examples include concern regarding transmission of the pathogenic gene to offspring, the effect of the deficient gene itself on ovarian function, and the recommendation to pursue risk-reducing bilateral salpingo-oophorectomy at a young age. The safety of pregnancy after breast cancer diagnosis has been demonstrated in several prior studies,1 but data in BRCA carriers have been limited to date. A retrospective cohort study conducted at 78 worldwide centers, including 4732 BRCA carriers diagnosed with breast cancer at age ≤ 40 years, investigated the incidence of pregnancy and maternal and fetal outcomes among these women (Lambertini et al). A total of 659 women had at least one pregnancy each after breast cancer; the cumulative incidence of pregnancy at 10 years was 22% (95% CI 21%-24%), and median time from breast cancer diagnosis to conception was 3.5 years (interquartile range 2.2-5.3 years). There was no significant difference in disease-free survival between those with or without pregnancy after breast cancer (adjusted hazard ratio 0.99; 95% CI 0.81-1.20, P = .90). Continued oncofertility research efforts are essential as the treatment landscape for early-stage breast cancer continues to evolve. Long-term follow-up of the POSITIVE trial included a small group of BRCA carriers and has shown reassuring results regarding interruption of endocrine therapy during attempts at conceiving.2

Young women diagnosed with breast cancer have been shown to experience higher rates of symptoms that may adversely affect quality of life (QOL), including depression, weight gain, vasomotor symptoms, and sexual dysfunction; they may also have a harder time managing these issues.3 Chemotherapy-related amenorrhea (CRA) is one of the side effects of breast cancer treatment that can affect premenopausal women, and is associated with both patient- (age, body mass index) and treatment-related (regimen, duration) factors.4 A study analyzing data derived from the prospective, longitudinal Cancer Toxicities Study included 1636 premenopausal women ≤ 50 years of age with stage I-III breast cancer treated with chemotherapy but not receiving ovarian suppression (Kabirian et al). A total of 83.0% of women reported CRA at year 1, 72.5% at year 2, and 66.1% at year 4. A higher likelihood of CRA was observed for women of older age vs those age 18-34 years (adjusted odds ratio [aOR] for 35-39 years 1.84; 40-44 years 5.90; and ≥ 45 years 21.29; P < .001 for all), those who received adjuvant tamoxifen (aOR 1.97; P < .001), and those who had hot flashes at baseline (aOR 1.83; P = .01). In the QOL analysis, 57.1% reported no recovery of menses. Persistent CRA was associated with worse insomnia, more systemic therapy–related adverse effects, and worse sexual functioning. These findings highlight the importance of identifying and discussing CRA with our patients, as this can have both physical and psychological effects in the survivorship setting.

The phase 3 KEYNOTE-522 trial has established immunotherapy plus an anthracycline-based chemotherapy backbone for the treatment of stage II-III triple-negative breast cancer (TNBC), with improvements in pathologic complete response (pCR) rates and survival outcomes.5 This regimen can present tolerance issues in clinical practice, and rare risks for cardiotoxicity and secondary hematologic malignancies are also relevant to consider. Furthermore, some patients may not be candidates for anthracycline-based treatment due to prior receipt of a drug in this class or cardiac comorbidities. De-escalation strategies are desired to lessen toxicity and maintain (or improve) outcomes. An open-label phase 2 trial (NeoPACT) investigated the efficacy of neoadjuvant carboplatin (AUC 6), docetaxel (75 mg/m2), and pembrolizumab (200 mg) every 21 days for six cycles among 115 patients with stage I-III TNBC (Sharma et al). The overall pCR and residual cancer burden (RCB 0+1) rates were 58% (95% CI 48%-67%) and 69% (95% CI 60%-78%), respectively. Estimated 3-year event-free survival was 86% (95% CI 77%-95%) in all patients, 98% in those with a pCR, and 68% in those with residual disease. This study also demonstrated a positive association of immune biomarkers and pathologic response. The most common grade ≥ 3 treatment-related adverse events were diarrhea (4.3%), anemia (3.5%), and peripheral sensory neuropathy (2.6%). The phase 3 SCARLET (Shorter Anthracycline-Free Chemoimmunotherapy Adapted to Pathologic Response in Early TNBC) trial is comparing the NeoPACT regimen with the standard KEYNOTE-522 regimen in early-stage TNBC and will be critical to further defining this treatment space.6 Presently, considering the described efficacy outcomes with the NeoPACT regimen, this regimen would be very reasonable to consider in patients who are not candidates for an anthracycline. Future prospective evaluation of immune biomarkers and additional predictors of response will also be valuable to further individualize treatment for our patients.

Additional References

  1. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: A systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.21.00535
  2. Partridge AH, Niman SM, Ruggeri M, et al, for the International Breast Cancer Study Group and POSITIVE Trial Collaborators. Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med. 2023;388:1645-1656. doi: 10.1056/NEJMoa2212856
  3. Howard-Anderson J, Ganz PA, Bower JE, Stanton AL. Quality of life, fertility concerns, and behavioral health outcomes in younger breast cancer survivors: A systematic review. J Natl Cancer Inst. 2012;104:386-405. doi: 10.1093/jnci/djr541
  4. Turnbull AK, Patel S, Martinez-Perez C, et al. Risk of chemotherapy-related amenorrhoea (CRA) in premenopausal women undergoing chemotherapy for early stage breast cancer. Breast Cancer Res Treat. 2021;186:237-245. doi: 10.1007/s10549-020-05951-5
  5. Schmid P, Cortes J, Dent R, et al; KEYNOTE-522 Investigators. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med. 2022;386:556-567. doi: 10.1056/NEJMoa2112651
  6. US National Cancer Institute, Cancer Therapy Evaluation Program. Shorter anthracycline-free chemoimmunotherapy adapted to pathological response in early TNBC (SCARLET); SWOG S2212. Source
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Commentary: Variations in DMARD Effectiveness and Enthesitis Treatment in PsA, January 2024

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

Vinod Chandran, MBBS, MD, DM, PhD
Interest is growing in understanding sex differences in psoriatic arthritis (PsA), especially in regard to disease manifestations and treatment response. A recent meta-analysis highlighted differential response to treatment in male vs female patients with PsA. Eder and colleagues conducted a meta-analysis of 54 randomized controlled trials that included 22,621 patients with PsA who received targeted advanced therapies (biological disease-modifying antirheumatic drugs [bDMARD] and targeted synthetic DMARD [tsDMARD]) or placebo. When considering bDMARD, they found that the odds of achieving ≥ 20% improvement in American College of Rheumatology score was significantly higher in men compared with women, with the difference being more pronounced in the case of all bDMARD, including tumor necrosis factor (TNF) inhibitors, interleukin (IL)-17 inhibitors, IL-23 inhibitors, and IL-12 and IL-23 inhibitors. Surprisingly, no such difference was found with tsDMARD (JAK inhibitors). Another retrospective observational study, from 13 European registries, analyzed treatment response and retention rates in 7679 and 17,842 PsA patients who received their first TNF inhibitor, respectively. Hellamand and colleagues found that, at 6 months, women were 17% less likely than men to achieve low disease activity according to Disease Activity Score-28 C-reactive protein measurements. Women had less TNF inhibitor treatment retention rates at all time points compared with men. These studies highlight the sex differences in response to bDMARD and the intriguing possibility that such differences might not be present with JAK inhibitors. If confirmed in future prospective interventional and observational studies, treatment strategies would need to be tailored to the sex of the patient, and the underlying mechanisms will need to be explored.

 

Treatment of enthesitis can be challenging. Head-to-head clinical trials using clinical enthesitis indices have indicated that TNF inhibitors and IL-17 inhibitors have similar efficacy in treating enthesitis. However, clinically determined enthesitis may not be true inflammatory enthesitis. Ultrasonography-confirmed enthesitis probably reflects true enthesitis. Therefore, Elliot and colleagues conducted an observational study that compared the change in MAdrid Sonographic Enthesitis Index (MASEI) at 16 weeks of treatment with either TNF inhibitors or secukinumab. They observed that the mean reduction in MASEI that assesses both active and chronic entheseal disease was not significantly different with TNF inhibitors vs secukinumab treatment. However, TNF inhibitors were significantly more effective than secukinumab when only active entheseal lesions were considered. Thus, TNF inhibitors may be more effective for active enthesitis; randomized trials using ultrasonographic enthesitis indices comparing the two treatments are required.

 

Serum drug levels have previously been shown to be associated with response to bDMARD therapy, but use of drug-level measurement is not routine in rheumatology practice. Moreover, trough levels are emphasized and may not often be feasible to obtain. Curry and colleagues investigated the relationship between serum non-trough drug levels (SDL) and treatment response at 3 months in patients with PsA who initiated treatment with adalimumab (n = 104) or etanercept (n = 97). They demonstrated that patients with higher etanercept SDL or higher adalimumab SDL were significantly more likely to be responders. A non-trough etanercept SDL of 2.0 µg/mL and adalimumab SDL of 3.6 µg/mL could differentiate between responders and nonresponders with ~50% specificity and > 60% sensitivity. However, the area under the receiver operating characteristic curves were only about 65%; thus, the ability of SDL to discriminate between responders and nonresponders is low.

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Vinod Chandran MBBS, MD, DM, PhD, FRCPC

Staff Physician, Department of Medicine/Rheumatology, University Health Network, Toronto, ON, Canada

Vinod Chandran, MBBS, MD, DM, PhD, has disclosed the following relevant financial relationships: Member of the board of directors of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). Received research grant from: Amgen; AbbVie; Bristol-Myers Squibb; Eli Lilly. Received income in an amount equal to or greater than $250 from: Amgen; AbbVie; Bristol-Myers Squibb; Eli Lilly; Janssen; Novartis; UCB.
Spousal employment: AstraZeneca

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Vinod Chandran MBBS, MD, DM, PhD, FRCPC

Staff Physician, Department of Medicine/Rheumatology, University Health Network, Toronto, ON, Canada

Vinod Chandran, MBBS, MD, DM, PhD, has disclosed the following relevant financial relationships: Member of the board of directors of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). Received research grant from: Amgen; AbbVie; Bristol-Myers Squibb; Eli Lilly. Received income in an amount equal to or greater than $250 from: Amgen; AbbVie; Bristol-Myers Squibb; Eli Lilly; Janssen; Novartis; UCB.
Spousal employment: AstraZeneca

Author and Disclosure Information

Vinod Chandran MBBS, MD, DM, PhD, FRCPC

Staff Physician, Department of Medicine/Rheumatology, University Health Network, Toronto, ON, Canada

Vinod Chandran, MBBS, MD, DM, PhD, has disclosed the following relevant financial relationships: Member of the board of directors of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). Received research grant from: Amgen; AbbVie; Bristol-Myers Squibb; Eli Lilly. Received income in an amount equal to or greater than $250 from: Amgen; AbbVie; Bristol-Myers Squibb; Eli Lilly; Janssen; Novartis; UCB.
Spousal employment: AstraZeneca

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

Vinod Chandran, MBBS, MD, DM, PhD
Interest is growing in understanding sex differences in psoriatic arthritis (PsA), especially in regard to disease manifestations and treatment response. A recent meta-analysis highlighted differential response to treatment in male vs female patients with PsA. Eder and colleagues conducted a meta-analysis of 54 randomized controlled trials that included 22,621 patients with PsA who received targeted advanced therapies (biological disease-modifying antirheumatic drugs [bDMARD] and targeted synthetic DMARD [tsDMARD]) or placebo. When considering bDMARD, they found that the odds of achieving ≥ 20% improvement in American College of Rheumatology score was significantly higher in men compared with women, with the difference being more pronounced in the case of all bDMARD, including tumor necrosis factor (TNF) inhibitors, interleukin (IL)-17 inhibitors, IL-23 inhibitors, and IL-12 and IL-23 inhibitors. Surprisingly, no such difference was found with tsDMARD (JAK inhibitors). Another retrospective observational study, from 13 European registries, analyzed treatment response and retention rates in 7679 and 17,842 PsA patients who received their first TNF inhibitor, respectively. Hellamand and colleagues found that, at 6 months, women were 17% less likely than men to achieve low disease activity according to Disease Activity Score-28 C-reactive protein measurements. Women had less TNF inhibitor treatment retention rates at all time points compared with men. These studies highlight the sex differences in response to bDMARD and the intriguing possibility that such differences might not be present with JAK inhibitors. If confirmed in future prospective interventional and observational studies, treatment strategies would need to be tailored to the sex of the patient, and the underlying mechanisms will need to be explored.

 

Treatment of enthesitis can be challenging. Head-to-head clinical trials using clinical enthesitis indices have indicated that TNF inhibitors and IL-17 inhibitors have similar efficacy in treating enthesitis. However, clinically determined enthesitis may not be true inflammatory enthesitis. Ultrasonography-confirmed enthesitis probably reflects true enthesitis. Therefore, Elliot and colleagues conducted an observational study that compared the change in MAdrid Sonographic Enthesitis Index (MASEI) at 16 weeks of treatment with either TNF inhibitors or secukinumab. They observed that the mean reduction in MASEI that assesses both active and chronic entheseal disease was not significantly different with TNF inhibitors vs secukinumab treatment. However, TNF inhibitors were significantly more effective than secukinumab when only active entheseal lesions were considered. Thus, TNF inhibitors may be more effective for active enthesitis; randomized trials using ultrasonographic enthesitis indices comparing the two treatments are required.

 

Serum drug levels have previously been shown to be associated with response to bDMARD therapy, but use of drug-level measurement is not routine in rheumatology practice. Moreover, trough levels are emphasized and may not often be feasible to obtain. Curry and colleagues investigated the relationship between serum non-trough drug levels (SDL) and treatment response at 3 months in patients with PsA who initiated treatment with adalimumab (n = 104) or etanercept (n = 97). They demonstrated that patients with higher etanercept SDL or higher adalimumab SDL were significantly more likely to be responders. A non-trough etanercept SDL of 2.0 µg/mL and adalimumab SDL of 3.6 µg/mL could differentiate between responders and nonresponders with ~50% specificity and > 60% sensitivity. However, the area under the receiver operating characteristic curves were only about 65%; thus, the ability of SDL to discriminate between responders and nonresponders is low.

Vinod Chandran, MBBS, MD, DM, PhD
Interest is growing in understanding sex differences in psoriatic arthritis (PsA), especially in regard to disease manifestations and treatment response. A recent meta-analysis highlighted differential response to treatment in male vs female patients with PsA. Eder and colleagues conducted a meta-analysis of 54 randomized controlled trials that included 22,621 patients with PsA who received targeted advanced therapies (biological disease-modifying antirheumatic drugs [bDMARD] and targeted synthetic DMARD [tsDMARD]) or placebo. When considering bDMARD, they found that the odds of achieving ≥ 20% improvement in American College of Rheumatology score was significantly higher in men compared with women, with the difference being more pronounced in the case of all bDMARD, including tumor necrosis factor (TNF) inhibitors, interleukin (IL)-17 inhibitors, IL-23 inhibitors, and IL-12 and IL-23 inhibitors. Surprisingly, no such difference was found with tsDMARD (JAK inhibitors). Another retrospective observational study, from 13 European registries, analyzed treatment response and retention rates in 7679 and 17,842 PsA patients who received their first TNF inhibitor, respectively. Hellamand and colleagues found that, at 6 months, women were 17% less likely than men to achieve low disease activity according to Disease Activity Score-28 C-reactive protein measurements. Women had less TNF inhibitor treatment retention rates at all time points compared with men. These studies highlight the sex differences in response to bDMARD and the intriguing possibility that such differences might not be present with JAK inhibitors. If confirmed in future prospective interventional and observational studies, treatment strategies would need to be tailored to the sex of the patient, and the underlying mechanisms will need to be explored.

 

Treatment of enthesitis can be challenging. Head-to-head clinical trials using clinical enthesitis indices have indicated that TNF inhibitors and IL-17 inhibitors have similar efficacy in treating enthesitis. However, clinically determined enthesitis may not be true inflammatory enthesitis. Ultrasonography-confirmed enthesitis probably reflects true enthesitis. Therefore, Elliot and colleagues conducted an observational study that compared the change in MAdrid Sonographic Enthesitis Index (MASEI) at 16 weeks of treatment with either TNF inhibitors or secukinumab. They observed that the mean reduction in MASEI that assesses both active and chronic entheseal disease was not significantly different with TNF inhibitors vs secukinumab treatment. However, TNF inhibitors were significantly more effective than secukinumab when only active entheseal lesions were considered. Thus, TNF inhibitors may be more effective for active enthesitis; randomized trials using ultrasonographic enthesitis indices comparing the two treatments are required.

 

Serum drug levels have previously been shown to be associated with response to bDMARD therapy, but use of drug-level measurement is not routine in rheumatology practice. Moreover, trough levels are emphasized and may not often be feasible to obtain. Curry and colleagues investigated the relationship between serum non-trough drug levels (SDL) and treatment response at 3 months in patients with PsA who initiated treatment with adalimumab (n = 104) or etanercept (n = 97). They demonstrated that patients with higher etanercept SDL or higher adalimumab SDL were significantly more likely to be responders. A non-trough etanercept SDL of 2.0 µg/mL and adalimumab SDL of 3.6 µg/mL could differentiate between responders and nonresponders with ~50% specificity and > 60% sensitivity. However, the area under the receiver operating characteristic curves were only about 65%; thus, the ability of SDL to discriminate between responders and nonresponders is low.

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Clinical Edge Journal Scan: Psoriatic Arthritis January 2024
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