Atopic Dermatitis

Key clinical point: Treatment of patients with atopic dermatitis (AD) with dupilumab is not associated with the development of primary or recurrent malignancy.

Major finding: Dupilumab-exposed and unexposed patients had comparable incidence rates of primary malignancies (adjusted hazard ratio [aHR], 1.010; P  =  .946), keratinocyte cancers (aHR, 0.994; P  =  .973), and recurrent cancers (aHR, 0.828; P  =  .758) per 1,000 person-years.

Study details: This single-center 5-year retrospective study included 9,707 patients with AD, of which 1,627 patients received dupilumab treatment.

Disclosures: This study did not receive any funding. Some authors declared serving as consultants for and/or receiving research funds from various organizations.

Source: Owji S et al. No association between dupilumab use and short-term cancer development in atopic dermatitis patients. J Allergy Clin Immunol Pract. 2022 (Dec 26). Doi: 10.1016/j.jaip.2022.12.018.

Key clinical point: Treatment of patients with atopic dermatitis (AD) with dupilumab is not associated with the development of primary or recurrent malignancy.

Major finding: Dupilumab-exposed and unexposed patients had comparable incidence rates of primary malignancies (adjusted hazard ratio [aHR], 1.010; P  =  .946), keratinocyte cancers (aHR, 0.994; P  =  .973), and recurrent cancers (aHR, 0.828; P  =  .758) per 1,000 person-years.

Study details: This single-center 5-year retrospective study included 9,707 patients with AD, of which 1,627 patients received dupilumab treatment.

Disclosures: This study did not receive any funding. Some authors declared serving as consultants for and/or receiving research funds from various organizations.

Source: Owji S et al. No association between dupilumab use and short-term cancer development in atopic dermatitis patients. J Allergy Clin Immunol Pract. 2022 (Dec 26). Doi: 10.1016/j.jaip.2022.12.018.

Key clinical point: Treatment of patients with atopic dermatitis (AD) with dupilumab is not associated with the development of primary or recurrent malignancy.

Major finding: Dupilumab-exposed and unexposed patients had comparable incidence rates of primary malignancies (adjusted hazard ratio [aHR], 1.010; P  =  .946), keratinocyte cancers (aHR, 0.994; P  =  .973), and recurrent cancers (aHR, 0.828; P  =  .758) per 1,000 person-years.

Study details: This single-center 5-year retrospective study included 9,707 patients with AD, of which 1,627 patients received dupilumab treatment.

Disclosures: This study did not receive any funding. Some authors declared serving as consultants for and/or receiving research funds from various organizations.

Source: Owji S et al. No association between dupilumab use and short-term cancer development in atopic dermatitis patients. J Allergy Clin Immunol Pract. 2022 (Dec 26). Doi: 10.1016/j.jaip.2022.12.018.

Key clinical point: Fatigue is a common symptom in children with atopic dermatitis (AD), particularly those with moderate-to-severe AD, and thus should be considered in clinical practice and trials.

Major finding: Most children had no (38.6%) or mild (32.1%) parent-proxy fatigue, but 27.2% had moderate fatigue and 2.0% had severe fatigue. Higher proportions of children with moderate-to-severe parent-proxy Patient-Reported Outcome Measurement Information System Pediatric fatigue scores were those with moderate (25.7%/1.4%) and severe (39.3%/5.4%) AD vs mild AD (18.0%/0.0%), as determined by Investigator’s Global Assessment, especially those with 5-6 (44.4%/0.0%) or 7 (44.2%/5.2%) nights of sleep disturbance from eczema.

Study details: This cross-sectional observational study included 248 children aged 0-17 years with AD.

Disclosures: This study was funded by the US National Institute of Arthritis and Musculoskeletal and Skin Diseases. The authors declared no conflicts of interest.

Source: Rangel SM et al. Prevalence and associations of fatigue in childhood atopic dermatitis: A cross-sectional study. J Eur Acad Dermatol Venereol. 2022 (Dec 21). Doi: 10.1111/jdv.18819

Key clinical point: Fatigue is a common symptom in children with atopic dermatitis (AD), particularly those with moderate-to-severe AD, and thus should be considered in clinical practice and trials.

Major finding: Most children had no (38.6%) or mild (32.1%) parent-proxy fatigue, but 27.2% had moderate fatigue and 2.0% had severe fatigue. Higher proportions of children with moderate-to-severe parent-proxy Patient-Reported Outcome Measurement Information System Pediatric fatigue scores were those with moderate (25.7%/1.4%) and severe (39.3%/5.4%) AD vs mild AD (18.0%/0.0%), as determined by Investigator’s Global Assessment, especially those with 5-6 (44.4%/0.0%) or 7 (44.2%/5.2%) nights of sleep disturbance from eczema.

Study details: This cross-sectional observational study included 248 children aged 0-17 years with AD.

Disclosures: This study was funded by the US National Institute of Arthritis and Musculoskeletal and Skin Diseases. The authors declared no conflicts of interest.

Source: Rangel SM et al. Prevalence and associations of fatigue in childhood atopic dermatitis: A cross-sectional study. J Eur Acad Dermatol Venereol. 2022 (Dec 21). Doi: 10.1111/jdv.18819

Key clinical point: Fatigue is a common symptom in children with atopic dermatitis (AD), particularly those with moderate-to-severe AD, and thus should be considered in clinical practice and trials.

Major finding: Most children had no (38.6%) or mild (32.1%) parent-proxy fatigue, but 27.2% had moderate fatigue and 2.0% had severe fatigue. Higher proportions of children with moderate-to-severe parent-proxy Patient-Reported Outcome Measurement Information System Pediatric fatigue scores were those with moderate (25.7%/1.4%) and severe (39.3%/5.4%) AD vs mild AD (18.0%/0.0%), as determined by Investigator’s Global Assessment, especially those with 5-6 (44.4%/0.0%) or 7 (44.2%/5.2%) nights of sleep disturbance from eczema.

Study details: This cross-sectional observational study included 248 children aged 0-17 years with AD.

Disclosures: This study was funded by the US National Institute of Arthritis and Musculoskeletal and Skin Diseases. The authors declared no conflicts of interest.

Source: Rangel SM et al. Prevalence and associations of fatigue in childhood atopic dermatitis: A cross-sectional study. J Eur Acad Dermatol Venereol. 2022 (Dec 21). Doi: 10.1111/jdv.18819

Key clinical point: Dupilumab maintained efficacy against moderate-to-severe atopic dermatitis (AD) with no new safety signals over 104 weeks; however, it was ineffective in treating head-and-neck AD.

Major finding: The median Eczema Area and Severity Index score decreased significantly from 18.0 at baseline to 2.0 at week 52 and 1.7 at week 104 (both P < .0001); 35% of patients reported an adverse event, with conjunctivitis being the most common (25%). Although the 104-week treatment persistence rate was 86%, the majority of patients still had AD in the head-and-neck area.

Study details: This real-world study included 347 adult patients with moderate-to-severe AD who received dupilumab and were registered in the prospective Severe and ChRonic Atopic dermatitis Treatment CoHort (SCRATCH) registry during 2017-2022.

Disclosures: The SCRATCH registry was supported by research grants from Sanofi-Genzyme and Pfizer. Some authors reported ties with various organizations, including Sanofi-Genzyme and Pfizer.

Source: Vittrup I et al. A nationwide 104 weeks real-world study of dupilumab in adults with atopic dermatitis: Ineffectiveness in head-and-neck dermatitis. J Eur Acad Dermatol Venereol. 2023 (Jan 6). Doi: 10.1111/jdv.18849

Key clinical point: Dupilumab maintained efficacy against moderate-to-severe atopic dermatitis (AD) with no new safety signals over 104 weeks; however, it was ineffective in treating head-and-neck AD.

Major finding: The median Eczema Area and Severity Index score decreased significantly from 18.0 at baseline to 2.0 at week 52 and 1.7 at week 104 (both P < .0001); 35% of patients reported an adverse event, with conjunctivitis being the most common (25%). Although the 104-week treatment persistence rate was 86%, the majority of patients still had AD in the head-and-neck area.

Study details: This real-world study included 347 adult patients with moderate-to-severe AD who received dupilumab and were registered in the prospective Severe and ChRonic Atopic dermatitis Treatment CoHort (SCRATCH) registry during 2017-2022.

Disclosures: The SCRATCH registry was supported by research grants from Sanofi-Genzyme and Pfizer. Some authors reported ties with various organizations, including Sanofi-Genzyme and Pfizer.

Source: Vittrup I et al. A nationwide 104 weeks real-world study of dupilumab in adults with atopic dermatitis: Ineffectiveness in head-and-neck dermatitis. J Eur Acad Dermatol Venereol. 2023 (Jan 6). Doi: 10.1111/jdv.18849

Key clinical point: Dupilumab maintained efficacy against moderate-to-severe atopic dermatitis (AD) with no new safety signals over 104 weeks; however, it was ineffective in treating head-and-neck AD.

Major finding: The median Eczema Area and Severity Index score decreased significantly from 18.0 at baseline to 2.0 at week 52 and 1.7 at week 104 (both P < .0001); 35% of patients reported an adverse event, with conjunctivitis being the most common (25%). Although the 104-week treatment persistence rate was 86%, the majority of patients still had AD in the head-and-neck area.

Study details: This real-world study included 347 adult patients with moderate-to-severe AD who received dupilumab and were registered in the prospective Severe and ChRonic Atopic dermatitis Treatment CoHort (SCRATCH) registry during 2017-2022.

Disclosures: The SCRATCH registry was supported by research grants from Sanofi-Genzyme and Pfizer. Some authors reported ties with various organizations, including Sanofi-Genzyme and Pfizer.

Source: Vittrup I et al. A nationwide 104 weeks real-world study of dupilumab in adults with atopic dermatitis: Ineffectiveness in head-and-neck dermatitis. J Eur Acad Dermatol Venereol. 2023 (Jan 6). Doi: 10.1111/jdv.18849

Key clinical point: Upadacitinib is effective and safe for the treatment of patients with difficult-to-treat moderate-to-severe atopic dermatitis (AD).

Major finding: At week 16, the percentages of patients achieving the Eczema Area and Severity Index (EASI) 50, EASI 75, EASI 90, and EASI 100 were 94.29%, 91.43%, 74.29%, and 60.0%, respectively; 91.43% of patients achieved a ≥4-point decrease in itch-numerical rating scale score. No severe adverse events were reported.

Study details: This single-center retrospective real-life study included 38 patients aged ≥12 years with moderate-to-severe AD and inadequate response, intolerance, or contraindications to cyclosporine or dupilumab who had received upadacitinib (15/30 mg daily) for ≥8 weeks; 35 patients received the treatment for 16 weeks.

Disclosures: This study was supported by grants from Fondazione Roma, Italian Ministry of Health (Rome, Italy), “Ricerca Finalizzata” project. Some authors reported ties with various organizations.

Source: Gargiulo L et al. Real-life effectiveness and safety of upadacitinib in adults and adolescents with moderate-to-severe atopic dermatitis: A single-center 16-week study. Dermatol Ther (Heidelb). 2023 (Jan 9). Doi: 10.1007/s13555-022-00882-z

Key clinical point: Upadacitinib is effective and safe for the treatment of patients with difficult-to-treat moderate-to-severe atopic dermatitis (AD).

Major finding: At week 16, the percentages of patients achieving the Eczema Area and Severity Index (EASI) 50, EASI 75, EASI 90, and EASI 100 were 94.29%, 91.43%, 74.29%, and 60.0%, respectively; 91.43% of patients achieved a ≥4-point decrease in itch-numerical rating scale score. No severe adverse events were reported.

Study details: This single-center retrospective real-life study included 38 patients aged ≥12 years with moderate-to-severe AD and inadequate response, intolerance, or contraindications to cyclosporine or dupilumab who had received upadacitinib (15/30 mg daily) for ≥8 weeks; 35 patients received the treatment for 16 weeks.

Disclosures: This study was supported by grants from Fondazione Roma, Italian Ministry of Health (Rome, Italy), “Ricerca Finalizzata” project. Some authors reported ties with various organizations.

Source: Gargiulo L et al. Real-life effectiveness and safety of upadacitinib in adults and adolescents with moderate-to-severe atopic dermatitis: A single-center 16-week study. Dermatol Ther (Heidelb). 2023 (Jan 9). Doi: 10.1007/s13555-022-00882-z

Key clinical point: Upadacitinib is effective and safe for the treatment of patients with difficult-to-treat moderate-to-severe atopic dermatitis (AD).

Major finding: At week 16, the percentages of patients achieving the Eczema Area and Severity Index (EASI) 50, EASI 75, EASI 90, and EASI 100 were 94.29%, 91.43%, 74.29%, and 60.0%, respectively; 91.43% of patients achieved a ≥4-point decrease in itch-numerical rating scale score. No severe adverse events were reported.

Study details: This single-center retrospective real-life study included 38 patients aged ≥12 years with moderate-to-severe AD and inadequate response, intolerance, or contraindications to cyclosporine or dupilumab who had received upadacitinib (15/30 mg daily) for ≥8 weeks; 35 patients received the treatment for 16 weeks.

Disclosures: This study was supported by grants from Fondazione Roma, Italian Ministry of Health (Rome, Italy), “Ricerca Finalizzata” project. Some authors reported ties with various organizations.

Source: Gargiulo L et al. Real-life effectiveness and safety of upadacitinib in adults and adolescents with moderate-to-severe atopic dermatitis: A single-center 16-week study. Dermatol Ther (Heidelb). 2023 (Jan 9). Doi: 10.1007/s13555-022-00882-z

Key clinical point: The safety profile of baricitinib in patients with moderate-to-severe atopic dermatitis (AD) was similar to that reported in earlier analyses; major adverse cardiovascular event (MACE), pulmonary embolism (PE), and malignancy were within the background range.

Major finding: The adjusted incidence rate/100 patient-years at risk for any infection was 67.2 and that for herpes simplex, herpes zoster, opportunistic infections, serious adverse events, MACE, PE, and 14 malignancies excluding nonmelanoma skin cancer was 6.7, 2.8, 0.3, 5.2, 0.15, 0.06, and 0.3, respectively.

Study details: This updated integrated analysis of eight clinical trials included 2636 patients with moderate-to-severe AD treated with ≥1 baricitinib dose (1/2/4 mg) through 3.9 years (4628.4 patient-years of exposure).

Disclosures: Baricitinib is developed by Eli Lilly and Company, under license from Incyte Corporation. Some authors reported ties with various organizations, including Eli Lilly. Five authors declared being employees and stockholders of Eli Lilly.

Source: Bieber T et al. Safety of baricitinib for the treatment of atopic dermatitis over a median of 1.6 years and up to 3.9 years of treatment: An updated integrated analysis of eight clinical trials. J Dermatolog Treat. 2022 (Dec 22). Doi: 10.1080/09546634.2022.2161812

Key clinical point: The safety profile of baricitinib in patients with moderate-to-severe atopic dermatitis (AD) was similar to that reported in earlier analyses; major adverse cardiovascular event (MACE), pulmonary embolism (PE), and malignancy were within the background range.

Major finding: The adjusted incidence rate/100 patient-years at risk for any infection was 67.2 and that for herpes simplex, herpes zoster, opportunistic infections, serious adverse events, MACE, PE, and 14 malignancies excluding nonmelanoma skin cancer was 6.7, 2.8, 0.3, 5.2, 0.15, 0.06, and 0.3, respectively.

Study details: This updated integrated analysis of eight clinical trials included 2636 patients with moderate-to-severe AD treated with ≥1 baricitinib dose (1/2/4 mg) through 3.9 years (4628.4 patient-years of exposure).

Disclosures: Baricitinib is developed by Eli Lilly and Company, under license from Incyte Corporation. Some authors reported ties with various organizations, including Eli Lilly. Five authors declared being employees and stockholders of Eli Lilly.

Source: Bieber T et al. Safety of baricitinib for the treatment of atopic dermatitis over a median of 1.6 years and up to 3.9 years of treatment: An updated integrated analysis of eight clinical trials. J Dermatolog Treat. 2022 (Dec 22). Doi: 10.1080/09546634.2022.2161812

Key clinical point: The safety profile of baricitinib in patients with moderate-to-severe atopic dermatitis (AD) was similar to that reported in earlier analyses; major adverse cardiovascular event (MACE), pulmonary embolism (PE), and malignancy were within the background range.

Major finding: The adjusted incidence rate/100 patient-years at risk for any infection was 67.2 and that for herpes simplex, herpes zoster, opportunistic infections, serious adverse events, MACE, PE, and 14 malignancies excluding nonmelanoma skin cancer was 6.7, 2.8, 0.3, 5.2, 0.15, 0.06, and 0.3, respectively.

Study details: This updated integrated analysis of eight clinical trials included 2636 patients with moderate-to-severe AD treated with ≥1 baricitinib dose (1/2/4 mg) through 3.9 years (4628.4 patient-years of exposure).

Disclosures: Baricitinib is developed by Eli Lilly and Company, under license from Incyte Corporation. Some authors reported ties with various organizations, including Eli Lilly. Five authors declared being employees and stockholders of Eli Lilly.

Source: Bieber T et al. Safety of baricitinib for the treatment of atopic dermatitis over a median of 1.6 years and up to 3.9 years of treatment: An updated integrated analysis of eight clinical trials. J Dermatolog Treat. 2022 (Dec 22). Doi: 10.1080/09546634.2022.2161812

Key clinical point: Over 68-week continuous treatment, 4 mg and 2 mg baricitinib plus topical corticosteroids (TCS) showed clinically meaningful efficacy in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: The proportions of patients with a validated Investigator’s Global Assessment for AD score of 0/1 at weeks 32/68 in the 4 mg baricitinib intent-to-treat, 4 mg baricitinib responder or partial responder (RPR), and 2 mg baricitinib RPR cohorts were 21.6%/23.5%, 31.7%/34.9%, and 45.3%/30.2%, respectively; Eczema Area and Severity Index 75 response rates were 46.1%/43.1%, 57.1%/49.2%, and 69.8%/58.5%, respectively.

Study details: This ongoing extension study of BREEZE-AD7 (BREEZE-AD3) included 292 patients with moderate-to-severe AD, of which RPR receiving 2 mg baricitinib +TCS/4 mg baricitinib + TCS continued their original treatment, nonresponders receiving 2 mg baricitinib were reassigned to receive 2 mg or 4 mg baricitinib, and nonresponders receiving 4 mg baricitinib continued their treatment.

Disclosures: This study was funded by Eli Lilly and Company, under license from Incyte Corporation. Some authors reported ties with various organizations, including Eli Lilly. Four authors declared being employees and stockholders of Eli Lilly.

Source: Silverberg JI et al. Long-term efficacy (up to 68 weeks) of baricitinib in combination with topical corticosteroids in adult patients with moderate-to-severe atopic dermatitis: Analysis of treatment responders, partial responders and nonresponders originating from study BREEZE-AD7. J Eur Acad Dermatol Venereol. 2023 (Dec 14, 2022). Doi: 10.1111/jdv.18816

Key clinical point: Over 68-week continuous treatment, 4 mg and 2 mg baricitinib plus topical corticosteroids (TCS) showed clinically meaningful efficacy in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: The proportions of patients with a validated Investigator’s Global Assessment for AD score of 0/1 at weeks 32/68 in the 4 mg baricitinib intent-to-treat, 4 mg baricitinib responder or partial responder (RPR), and 2 mg baricitinib RPR cohorts were 21.6%/23.5%, 31.7%/34.9%, and 45.3%/30.2%, respectively; Eczema Area and Severity Index 75 response rates were 46.1%/43.1%, 57.1%/49.2%, and 69.8%/58.5%, respectively.

Study details: This ongoing extension study of BREEZE-AD7 (BREEZE-AD3) included 292 patients with moderate-to-severe AD, of which RPR receiving 2 mg baricitinib +TCS/4 mg baricitinib + TCS continued their original treatment, nonresponders receiving 2 mg baricitinib were reassigned to receive 2 mg or 4 mg baricitinib, and nonresponders receiving 4 mg baricitinib continued their treatment.

Disclosures: This study was funded by Eli Lilly and Company, under license from Incyte Corporation. Some authors reported ties with various organizations, including Eli Lilly. Four authors declared being employees and stockholders of Eli Lilly.

Source: Silverberg JI et al. Long-term efficacy (up to 68 weeks) of baricitinib in combination with topical corticosteroids in adult patients with moderate-to-severe atopic dermatitis: Analysis of treatment responders, partial responders and nonresponders originating from study BREEZE-AD7. J Eur Acad Dermatol Venereol. 2023 (Dec 14, 2022). Doi: 10.1111/jdv.18816

Key clinical point: Over 68-week continuous treatment, 4 mg and 2 mg baricitinib plus topical corticosteroids (TCS) showed clinically meaningful efficacy in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: The proportions of patients with a validated Investigator’s Global Assessment for AD score of 0/1 at weeks 32/68 in the 4 mg baricitinib intent-to-treat, 4 mg baricitinib responder or partial responder (RPR), and 2 mg baricitinib RPR cohorts were 21.6%/23.5%, 31.7%/34.9%, and 45.3%/30.2%, respectively; Eczema Area and Severity Index 75 response rates were 46.1%/43.1%, 57.1%/49.2%, and 69.8%/58.5%, respectively.

Study details: This ongoing extension study of BREEZE-AD7 (BREEZE-AD3) included 292 patients with moderate-to-severe AD, of which RPR receiving 2 mg baricitinib +TCS/4 mg baricitinib + TCS continued their original treatment, nonresponders receiving 2 mg baricitinib were reassigned to receive 2 mg or 4 mg baricitinib, and nonresponders receiving 4 mg baricitinib continued their treatment.

Disclosures: This study was funded by Eli Lilly and Company, under license from Incyte Corporation. Some authors reported ties with various organizations, including Eli Lilly. Four authors declared being employees and stockholders of Eli Lilly.

Source: Silverberg JI et al. Long-term efficacy (up to 68 weeks) of baricitinib in combination with topical corticosteroids in adult patients with moderate-to-severe atopic dermatitis: Analysis of treatment responders, partial responders and nonresponders originating from study BREEZE-AD7. J Eur Acad Dermatol Venereol. 2023 (Dec 14, 2022). Doi: 10.1111/jdv.18816

Key clinical point: Patients with moderate-to-severe atopic dermatitis (AD) experienced a significantly greater reduction in itch as early as 4 days after treatment with 200 mg abrocitinib compared with dupilumab and placebo.

Major finding: At day 4 after treatment, a significantly higher proportion of patients achieved a ≥4-point improvement in Peak Pruritus Numerical Rating Scale score in the 200 mg abrocitinib group (18.6%) than in the placebo (6.0%; P < .003) and dupilumab (5.6%; P < .001) groups.

Study details: This post hoc analysis of JADE COMPARE included 837 adult patients with moderate-to-severe AD who were randomly assigned to receive oral abrocitinib (200 or 100 mg), subcutaneous dupilumab (300 mg), or placebo with medicated topical therapy for 16 weeks.

Disclosures: This study was funded by Pfizer Inc. Some authors reported ties with various organizations, including Pfizer. Six authors declared being current or former employees and shareholders of Pfizer.

Source: Ständer S et al. Early itch response with abrocitinib is associated with later efficacy outcomes in patients with moderate-to-severe atopic dermatitis: Subgroup analysis of the randomized phase III JADE COMPARE trial. Am J Clin Dermatol. 2022 (Dec 13). Doi: 10.1007/s40257-022-00738-4

Key clinical point: Patients with moderate-to-severe atopic dermatitis (AD) experienced a significantly greater reduction in itch as early as 4 days after treatment with 200 mg abrocitinib compared with dupilumab and placebo.

Major finding: At day 4 after treatment, a significantly higher proportion of patients achieved a ≥4-point improvement in Peak Pruritus Numerical Rating Scale score in the 200 mg abrocitinib group (18.6%) than in the placebo (6.0%; P < .003) and dupilumab (5.6%; P < .001) groups.

Study details: This post hoc analysis of JADE COMPARE included 837 adult patients with moderate-to-severe AD who were randomly assigned to receive oral abrocitinib (200 or 100 mg), subcutaneous dupilumab (300 mg), or placebo with medicated topical therapy for 16 weeks.

Disclosures: This study was funded by Pfizer Inc. Some authors reported ties with various organizations, including Pfizer. Six authors declared being current or former employees and shareholders of Pfizer.

Source: Ständer S et al. Early itch response with abrocitinib is associated with later efficacy outcomes in patients with moderate-to-severe atopic dermatitis: Subgroup analysis of the randomized phase III JADE COMPARE trial. Am J Clin Dermatol. 2022 (Dec 13). Doi: 10.1007/s40257-022-00738-4

Key clinical point: Patients with moderate-to-severe atopic dermatitis (AD) experienced a significantly greater reduction in itch as early as 4 days after treatment with 200 mg abrocitinib compared with dupilumab and placebo.

Major finding: At day 4 after treatment, a significantly higher proportion of patients achieved a ≥4-point improvement in Peak Pruritus Numerical Rating Scale score in the 200 mg abrocitinib group (18.6%) than in the placebo (6.0%; P < .003) and dupilumab (5.6%; P < .001) groups.

Study details: This post hoc analysis of JADE COMPARE included 837 adult patients with moderate-to-severe AD who were randomly assigned to receive oral abrocitinib (200 or 100 mg), subcutaneous dupilumab (300 mg), or placebo with medicated topical therapy for 16 weeks.

Disclosures: This study was funded by Pfizer Inc. Some authors reported ties with various organizations, including Pfizer. Six authors declared being current or former employees and shareholders of Pfizer.

Source: Ständer S et al. Early itch response with abrocitinib is associated with later efficacy outcomes in patients with moderate-to-severe atopic dermatitis: Subgroup analysis of the randomized phase III JADE COMPARE trial. Am J Clin Dermatol. 2022 (Dec 13). Doi: 10.1007/s40257-022-00738-4

Key clinical point: Compared with topical corticosteroids (TCS) alone, lebrikizumab+TCS significantly improved outcomes in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: At week 16, a significantly higher proportion of patients in the lebrikizumab+TCS vs placebo+TCS group achieved an Investigator’s Global Assessment score of 0 or 1 (41.2% vs 22.1%; P  =  .01) and a 75% improvement in the Eczema Area and Severity Index (69.5% vs 42.2%; P < .001). The frequencies of patient-reported serious adverse events (AE) were similar in both groups (<2%); most treatment-emergent AE were of mild or moderate severity.

Study details: Findings are from a multicenter phase 3 study, ADhere, including 211 patients aged ≥ 12 years with moderate-to-severe AD who were randomly assigned to receive lebrikizumab+TCS (n = 145) or placebo+TCS (n = 66).

Disclosures: This study was sponsored by Dermira, Inc; a wholly-owned subsidiary of Eli Lilly and Company. Some authors reported ties with various organizations, including Eli Lilly. Six authors declared being employees or stockholders of Eli Lilly.

Source: Simpson EL et al for the ADhere Investigators. Efficacy and safety of lebrikizumab in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis: A randomized clinical trial (ADhere). JAMA Dermatol. 2023 (Jan 11). Doi: 10.1001/jamadermatol.2022.5534

Key clinical point: Compared with topical corticosteroids (TCS) alone, lebrikizumab+TCS significantly improved outcomes in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: At week 16, a significantly higher proportion of patients in the lebrikizumab+TCS vs placebo+TCS group achieved an Investigator’s Global Assessment score of 0 or 1 (41.2% vs 22.1%; P  =  .01) and a 75% improvement in the Eczema Area and Severity Index (69.5% vs 42.2%; P < .001). The frequencies of patient-reported serious adverse events (AE) were similar in both groups (<2%); most treatment-emergent AE were of mild or moderate severity.

Study details: Findings are from a multicenter phase 3 study, ADhere, including 211 patients aged ≥ 12 years with moderate-to-severe AD who were randomly assigned to receive lebrikizumab+TCS (n = 145) or placebo+TCS (n = 66).

Disclosures: This study was sponsored by Dermira, Inc; a wholly-owned subsidiary of Eli Lilly and Company. Some authors reported ties with various organizations, including Eli Lilly. Six authors declared being employees or stockholders of Eli Lilly.

Source: Simpson EL et al for the ADhere Investigators. Efficacy and safety of lebrikizumab in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis: A randomized clinical trial (ADhere). JAMA Dermatol. 2023 (Jan 11). Doi: 10.1001/jamadermatol.2022.5534

Key clinical point: Compared with topical corticosteroids (TCS) alone, lebrikizumab+TCS significantly improved outcomes in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: At week 16, a significantly higher proportion of patients in the lebrikizumab+TCS vs placebo+TCS group achieved an Investigator’s Global Assessment score of 0 or 1 (41.2% vs 22.1%; P  =  .01) and a 75% improvement in the Eczema Area and Severity Index (69.5% vs 42.2%; P < .001). The frequencies of patient-reported serious adverse events (AE) were similar in both groups (<2%); most treatment-emergent AE were of mild or moderate severity.

Study details: Findings are from a multicenter phase 3 study, ADhere, including 211 patients aged ≥ 12 years with moderate-to-severe AD who were randomly assigned to receive lebrikizumab+TCS (n = 145) or placebo+TCS (n = 66).

Disclosures: This study was sponsored by Dermira, Inc; a wholly-owned subsidiary of Eli Lilly and Company. Some authors reported ties with various organizations, including Eli Lilly. Six authors declared being employees or stockholders of Eli Lilly.

Source: Simpson EL et al for the ADhere Investigators. Efficacy and safety of lebrikizumab in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis: A randomized clinical trial (ADhere). JAMA Dermatol. 2023 (Jan 11). Doi: 10.1001/jamadermatol.2022.5534

Pediatric patients with atopic dermatitis (AD) are more likely to experience symptoms at classical sites such as the knees and have more associated and severe signs of AD, while older adults tend to present with less flexural eczema and the fewest associated signs.

Those are key findings from a study conducted at a single academic medical center, which aimed to identify the age-related clinical phenotypes of AD.

LucaLorenzelli/Thinkstock

“Previous studies have found differences in the clinical characteristics of AD depending on age of AD onset, ethnic background, and AD severity,” senior author Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research in the department of dermatology at George Washington University, Washington, and his coauthor wrote in the study, which was published online in JAAD International. “However, none have prospectively compared the clinical characteristics and associated signs by age group. Improved understanding of the clinical phenotypes of AD may help guide choice of treatment and improve health outcomes,” they added.

Along with coauthor Sheena Chatrath, a dermatology research fellow in the department, Dr. Silverberg prospectively reviewed self-reported questionnaires that were completed by 380 patients prior to their visit at GWU’s eczema clinic between 2013 and 2019. Questions included age of AD onset, sociodemographics, Visual Analog Scale (VAS) itch and sleep for Scoring AD, and Numeric Rating Scale (NRS) for skin pain and itch. The researchers used the Eczema Area Severity Index to assess AD severity and a dermatologist conducted full body skin exams, noting the distribution of AD involvement as well as associated signs.

Of the 380 patients, 6.1% were younger than aged 18 years, 46.3% were young adults aged 18-39 years, and 47.6% were older adults 40 years of age and older.

Compared with pediatric patients, both young and older adults were less likely to experience AD on the ankles (adjusted odds ratio [aOR], 0.41 and 0.43, respectively), moderate to severe AD lesions on flexures (aOR, 0.47 and 0.30), pityriasis alba (aOR, 0.24 and 0.07), oozing lesions (aOR, 0.44 and 0.35), and moderate to severe excoriations (aOR, 0.49 and 0.44).

In children, severe itch was more common, reported in 47.1%, compared with 43.4% of the young adults and 38.6% of the older adults, and itch was less severe among the young and older adults. “Interestingly, despite increased itch in pediatric patients, we found no difference in the severity of skin pain across all age groups,” the researchers wrote. “Moreover, pediatric patients reported skin pain less often than adult patients. This may be due to age-related differences of pain perception.”

In other findings, compared with pediatric patients, young adults were more likely to experience AD around the eyes (aOR, 2.92), while older adults were less likely to experience AD on elbows (aOR, 0.34), nipples (aOR, 0.40), knees (aOR, 0.27), and less likely to have keratosis pilaris (aOR, 0.38), and lichenification (aOR, 0.47).

Dr. Silverberg and Ms. Chatrath used latent class analysis to identify four classes for distribution of AD lesions. In this model, class 1 had low probabilities of AD involvement at all sites examined and class 2 had low probabilities of scalp, face, and foot involvement, and intermediate probability of all other AD sites. Class 3 had low probabilities of hand and foot involvement, high probability of facial erythema, and intermediate probability of all other AD signs, while class 4 had intermediate probability of postauricular and foot involvement, and high probability of all other AD sites examined.

“Pediatric patients were most commonly in class 4 (33.3%), followed by class 1 and 2 (26.7%), and least commonly in class 3 (13.3%),” the authors wrote. “In young adults, class 4 and 1 were most common (32.4% and 29.4%), followed by class 2 (27.9%), and least commonly class 3 (10.3%). In older adults, class 1 was most common (40.3%), followed by class 4 (23.6%), and least commonly classes 2 and 3 (18.1%).”

The researchers also used latent class analysis to identify four classes for the signs and symptoms of AD. In this model, class 1 had zero-low probability of all AD signs and class 2 had low probability of all AD signs. Class 3 had high probability of oozing lesions and low probability of all other signs, while class 4 had high probability of xerosis, intermediate probability of ichthyosis and palmar hyperlinearity, and low probability of all other AD signs.

In all three groups, the most common class was class 1 (85.6% of older adults, 81.8% of younger adults, and 82.6% of pediatric patients). Among the pediatric patients, they wrote, “class 3 was the second most common (8.7%), followed by class 2 and 4 (4.4%).” Among the young adults, 9.7% were in class 2, 5.7% were in class 4, and 2.8% were in class 3; and among the older adults, 8.3% were in class 4, 4.4% were in class 2, and 1.67% were in class 3.

Zelma Chiesa Fuxench, MD, of the department of dermatology at the University of Pennsylvania, Philadelphia, who was asked to comment on the study, said that while AD is traditionally largely thought of as a disease of children primarily involving the flexural areas, “this study provides additional evidence to support that AD is more than just a disease of childhood with a fixed clinical presentation, but is a heterogeneous disease whose clinical presentation varies across different population groups.”

Pediatric patients with atopic dermatitis (AD) are more likely to experience symptoms at classical sites such as the knees and have more associated and severe signs of AD, while older adults tend to present with less flexural eczema and the fewest associated signs.

Those are key findings from a study conducted at a single academic medical center, which aimed to identify the age-related clinical phenotypes of AD.

LucaLorenzelli/Thinkstock

“Previous studies have found differences in the clinical characteristics of AD depending on age of AD onset, ethnic background, and AD severity,” senior author Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research in the department of dermatology at George Washington University, Washington, and his coauthor wrote in the study, which was published online in JAAD International. “However, none have prospectively compared the clinical characteristics and associated signs by age group. Improved understanding of the clinical phenotypes of AD may help guide choice of treatment and improve health outcomes,” they added.

Along with coauthor Sheena Chatrath, a dermatology research fellow in the department, Dr. Silverberg prospectively reviewed self-reported questionnaires that were completed by 380 patients prior to their visit at GWU’s eczema clinic between 2013 and 2019. Questions included age of AD onset, sociodemographics, Visual Analog Scale (VAS) itch and sleep for Scoring AD, and Numeric Rating Scale (NRS) for skin pain and itch. The researchers used the Eczema Area Severity Index to assess AD severity and a dermatologist conducted full body skin exams, noting the distribution of AD involvement as well as associated signs.

Of the 380 patients, 6.1% were younger than aged 18 years, 46.3% were young adults aged 18-39 years, and 47.6% were older adults 40 years of age and older.

Compared with pediatric patients, both young and older adults were less likely to experience AD on the ankles (adjusted odds ratio [aOR], 0.41 and 0.43, respectively), moderate to severe AD lesions on flexures (aOR, 0.47 and 0.30), pityriasis alba (aOR, 0.24 and 0.07), oozing lesions (aOR, 0.44 and 0.35), and moderate to severe excoriations (aOR, 0.49 and 0.44).

In children, severe itch was more common, reported in 47.1%, compared with 43.4% of the young adults and 38.6% of the older adults, and itch was less severe among the young and older adults. “Interestingly, despite increased itch in pediatric patients, we found no difference in the severity of skin pain across all age groups,” the researchers wrote. “Moreover, pediatric patients reported skin pain less often than adult patients. This may be due to age-related differences of pain perception.”

In other findings, compared with pediatric patients, young adults were more likely to experience AD around the eyes (aOR, 2.92), while older adults were less likely to experience AD on elbows (aOR, 0.34), nipples (aOR, 0.40), knees (aOR, 0.27), and less likely to have keratosis pilaris (aOR, 0.38), and lichenification (aOR, 0.47).

Dr. Silverberg and Ms. Chatrath used latent class analysis to identify four classes for distribution of AD lesions. In this model, class 1 had low probabilities of AD involvement at all sites examined and class 2 had low probabilities of scalp, face, and foot involvement, and intermediate probability of all other AD sites. Class 3 had low probabilities of hand and foot involvement, high probability of facial erythema, and intermediate probability of all other AD signs, while class 4 had intermediate probability of postauricular and foot involvement, and high probability of all other AD sites examined.

“Pediatric patients were most commonly in class 4 (33.3%), followed by class 1 and 2 (26.7%), and least commonly in class 3 (13.3%),” the authors wrote. “In young adults, class 4 and 1 were most common (32.4% and 29.4%), followed by class 2 (27.9%), and least commonly class 3 (10.3%). In older adults, class 1 was most common (40.3%), followed by class 4 (23.6%), and least commonly classes 2 and 3 (18.1%).”

The researchers also used latent class analysis to identify four classes for the signs and symptoms of AD. In this model, class 1 had zero-low probability of all AD signs and class 2 had low probability of all AD signs. Class 3 had high probability of oozing lesions and low probability of all other signs, while class 4 had high probability of xerosis, intermediate probability of ichthyosis and palmar hyperlinearity, and low probability of all other AD signs.

In all three groups, the most common class was class 1 (85.6% of older adults, 81.8% of younger adults, and 82.6% of pediatric patients). Among the pediatric patients, they wrote, “class 3 was the second most common (8.7%), followed by class 2 and 4 (4.4%).” Among the young adults, 9.7% were in class 2, 5.7% were in class 4, and 2.8% were in class 3; and among the older adults, 8.3% were in class 4, 4.4% were in class 2, and 1.67% were in class 3.

Zelma Chiesa Fuxench, MD, of the department of dermatology at the University of Pennsylvania, Philadelphia, who was asked to comment on the study, said that while AD is traditionally largely thought of as a disease of children primarily involving the flexural areas, “this study provides additional evidence to support that AD is more than just a disease of childhood with a fixed clinical presentation, but is a heterogeneous disease whose clinical presentation varies across different population groups.”

Pediatric patients with atopic dermatitis (AD) are more likely to experience symptoms at classical sites such as the knees and have more associated and severe signs of AD, while older adults tend to present with less flexural eczema and the fewest associated signs.

Those are key findings from a study conducted at a single academic medical center, which aimed to identify the age-related clinical phenotypes of AD.

LucaLorenzelli/Thinkstock

“Previous studies have found differences in the clinical characteristics of AD depending on age of AD onset, ethnic background, and AD severity,” senior author Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research in the department of dermatology at George Washington University, Washington, and his coauthor wrote in the study, which was published online in JAAD International. “However, none have prospectively compared the clinical characteristics and associated signs by age group. Improved understanding of the clinical phenotypes of AD may help guide choice of treatment and improve health outcomes,” they added.

Along with coauthor Sheena Chatrath, a dermatology research fellow in the department, Dr. Silverberg prospectively reviewed self-reported questionnaires that were completed by 380 patients prior to their visit at GWU’s eczema clinic between 2013 and 2019. Questions included age of AD onset, sociodemographics, Visual Analog Scale (VAS) itch and sleep for Scoring AD, and Numeric Rating Scale (NRS) for skin pain and itch. The researchers used the Eczema Area Severity Index to assess AD severity and a dermatologist conducted full body skin exams, noting the distribution of AD involvement as well as associated signs.

Of the 380 patients, 6.1% were younger than aged 18 years, 46.3% were young adults aged 18-39 years, and 47.6% were older adults 40 years of age and older.

Compared with pediatric patients, both young and older adults were less likely to experience AD on the ankles (adjusted odds ratio [aOR], 0.41 and 0.43, respectively), moderate to severe AD lesions on flexures (aOR, 0.47 and 0.30), pityriasis alba (aOR, 0.24 and 0.07), oozing lesions (aOR, 0.44 and 0.35), and moderate to severe excoriations (aOR, 0.49 and 0.44).

In children, severe itch was more common, reported in 47.1%, compared with 43.4% of the young adults and 38.6% of the older adults, and itch was less severe among the young and older adults. “Interestingly, despite increased itch in pediatric patients, we found no difference in the severity of skin pain across all age groups,” the researchers wrote. “Moreover, pediatric patients reported skin pain less often than adult patients. This may be due to age-related differences of pain perception.”

In other findings, compared with pediatric patients, young adults were more likely to experience AD around the eyes (aOR, 2.92), while older adults were less likely to experience AD on elbows (aOR, 0.34), nipples (aOR, 0.40), knees (aOR, 0.27), and less likely to have keratosis pilaris (aOR, 0.38), and lichenification (aOR, 0.47).

Dr. Silverberg and Ms. Chatrath used latent class analysis to identify four classes for distribution of AD lesions. In this model, class 1 had low probabilities of AD involvement at all sites examined and class 2 had low probabilities of scalp, face, and foot involvement, and intermediate probability of all other AD sites. Class 3 had low probabilities of hand and foot involvement, high probability of facial erythema, and intermediate probability of all other AD signs, while class 4 had intermediate probability of postauricular and foot involvement, and high probability of all other AD sites examined.

“Pediatric patients were most commonly in class 4 (33.3%), followed by class 1 and 2 (26.7%), and least commonly in class 3 (13.3%),” the authors wrote. “In young adults, class 4 and 1 were most common (32.4% and 29.4%), followed by class 2 (27.9%), and least commonly class 3 (10.3%). In older adults, class 1 was most common (40.3%), followed by class 4 (23.6%), and least commonly classes 2 and 3 (18.1%).”

The researchers also used latent class analysis to identify four classes for the signs and symptoms of AD. In this model, class 1 had zero-low probability of all AD signs and class 2 had low probability of all AD signs. Class 3 had high probability of oozing lesions and low probability of all other signs, while class 4 had high probability of xerosis, intermediate probability of ichthyosis and palmar hyperlinearity, and low probability of all other AD signs.

In all three groups, the most common class was class 1 (85.6% of older adults, 81.8% of younger adults, and 82.6% of pediatric patients). Among the pediatric patients, they wrote, “class 3 was the second most common (8.7%), followed by class 2 and 4 (4.4%).” Among the young adults, 9.7% were in class 2, 5.7% were in class 4, and 2.8% were in class 3; and among the older adults, 8.3% were in class 4, 4.4% were in class 2, and 1.67% were in class 3.

Zelma Chiesa Fuxench, MD, of the department of dermatology at the University of Pennsylvania, Philadelphia, who was asked to comment on the study, said that while AD is traditionally largely thought of as a disease of children primarily involving the flexural areas, “this study provides additional evidence to support that AD is more than just a disease of childhood with a fixed clinical presentation, but is a heterogeneous disease whose clinical presentation varies across different population groups.”

Adult and adolescent patients with moderate to severe atopic dermatitis (AD) showed significant improvements with the addition of lebrikizumab to topical corticosteroid (TCS) therapy, compared with TCS plus placebo, according to results of the 16-week phase 3 ADhere trial.

“Lebrikizumab, a monoclonal antibody inhibiting interleukin-13, combined with TCS was associated with reduced overall disease severity of moderate to severe AD in adolescents and adults, and had a safety profile consistent with previous lebrikizumab AD studies,” noted lead author Eric L. Simpson, MD, professor of dermatology at Oregon Health & Science University, Portland, and coauthors in their article on the study, which was published in JAMA Dermatology.

The double-blind trial, conducted at 54 sites across Germany, Poland, Canada, and the United States, included 211 patients, mean age 37.2 years, of whom 48.8% were female and roughly 22% were adolescents. Almost 15% were Asian, and about 13% were Black.

At baseline, participants had a score of 16 or higher on the Eczema Area and Severity Index (EASI), a score of 3 or higher on the Investigator’s Global Assessment (IGA) scale, AD covering a body surface area of 10% or greater, and a history of inadequate response to treatment with topical medications.

After a minimum 1-week washout period from topical and systemic therapy, participants were randomized in a 2:1 ratio to receive lebrikizumab plus TCS (n = 145) or placebo plus TCS (n = 66) for 16 weeks.

Lebrikizumab or placebo was administered by subcutaneous injection every 2 weeks; the loading and week-2 doses of lebrikizumab were 500 mg, followed by 250 mg thereafter. All patients were instructed to use low- to mid-potency TCS at their own discretion. Study sites provided a mid-potency TCS (triamcinolone acetonide 0.1% cream) and a low-potency TCS (hydrocortisone 1% cream), with topical calcineurin inhibitors permitted for sensitive skin areas.

Primary outcomes at 16 weeks included a 2-point or more reduction in IGA score from baseline and EASI-75 response. Patients in the lebrikizumab arm had superior responses on both of these outcomes, with statistical significance achieved as early as week 8 and week 4, respectively, and maintained through week 16. Specifically, 41.2% of those treated with lebrikizumab had an IGA reduction of 2 points or more, compared with 22.1% of those receiving placebo plus TCS (P = .01), and the proportion of patients achieving EASI-75 responses was 69.5% vs. 42.2%, respectively (P < .001).

Patients treated with lebrikizumab also showed statistically significant improvements, compared with TCS alone in all key secondary endpoints, “including skin clearance, improvement in itch, itch interference on sleep, and enhanced QoL [quality of life],” noted the authors. “This study captured the clinical benefit of lebrikizumab through the combined end point of physician-assessed clinical sign of skin clearance (EASI-75) and patient-reported outcome of improvement in itch (Pruritus NRS).”

The percentage of patients who achieved the combined endpoint was more than double for the lebrikizumab plus TCS group vs. the group on TCS alone, indicating that patients treated with lebrikizumab plus TCS “were more likely to experience improvement in skin symptoms and itch,” the investigators added.

The authors noted that most treatment-emergent adverse events “were nonserious, mild, or moderate in severity, and did not lead to study discontinuation.” These included conjunctivitis (4.8%), headache (4.8%), hypertension (2.8%), injection-site reactions (2.8%), and herpes infection (3.4%) – all of which occurred in 1.5% or less of patients in the placebo group.

“The higher incidence of conjunctivitis has also been reported in other biologics inhibiting IL [interleukin]–13 and/or IL-4 signaling, as well as lebrikizumab monotherapy studies,” they noted. The 4.8% rate of conjunctivitis reported in the combination study, they added, is “compared with 7.5% frequency in 16-week data from the lebrikizumab monotherapy studies. Although the mechanism remains unclear, it has been reported that conjunctival goblet cell scarcity due to IL-13 and IL-4 inhibition, and subsequent effects on the homeostasis of the conjunctival mucosal surface, results in ocular AEs [adverse events].”

“This truly is a time of great hope and promise for our patients with AD,” commented Zelma Chiesa Fuxench, MD, who was not involved in the study. “The advent of newer, targeted therapeutic agents for AD continues to revolutionize the treatment experience for our patients, offering the possibility of greater AD disease control with a favorable risk profile and less need for blood work monitoring compared to traditional systemic agents.”

On the basis of the study results, Dr. Chiesa Fuxench, of the department of dermatology at the University of Pennsylvania, Philadelphia, said in an interview that “lebrikizumab represents an additional option in the treatment armamentarium for providers who care for patients with AD.” She added that, “while head-to-head trials comparing lebrikizumab to dupilumab, the first FDA-approved biologic for AD, would be beneficial, to the best of my knowledge this data is currently lacking. However, based on the results of this study, we would expect lebrikizumab to work at least similarly to dupilumab, based on the reported improvements in IGA and EASI score.”

Additionally, lebrikizumab showed a favorable safety profile, “with most treatment-emergent adverse effects reported as nonserious and not leading to drug discontinuation,” she said. “Of interest to clinicians may be the reported rates of conjunctivitis in this study. Rates of conjunctivitis for lebrikizumab appear to be lower than those reported in the LIBERTY AD CHRONOS study for dupilumab – a finding that merits further scrutiny in my opinion, as this one of the most frequent treatment-emergent adverse events that I encounter in my clinical practice.”

The study was funded by Dermira, a subsidiary of Eli Lilly. Dr. Simpson reported personal fees and grants from multiple sources, including Dermira and Eli Lilly, the companies developing lebrikizumab. Several authors were employees of Eli Lilly. Dr. Fuxench disclosed serving as a consultant for the Asthma and Allergy Foundation of America, National Eczema Association, Pfizer, AbbVie, and Incyte, for which she has received honoraria for AD-related work. She is the recipient of research grants through Regeneron, Sanofi, Tioga, Vanda, Menlo Therapeutics, Leo Pharma, and Eli Lilly for work related to AD as well as honoraria for continuing medical education work related to AD sponsored through educational grants from Regeneron/Sanofi and Pfizer.

A version of this article first appeared on Medscape.com.

Adult and adolescent patients with moderate to severe atopic dermatitis (AD) showed significant improvements with the addition of lebrikizumab to topical corticosteroid (TCS) therapy, compared with TCS plus placebo, according to results of the 16-week phase 3 ADhere trial.

“Lebrikizumab, a monoclonal antibody inhibiting interleukin-13, combined with TCS was associated with reduced overall disease severity of moderate to severe AD in adolescents and adults, and had a safety profile consistent with previous lebrikizumab AD studies,” noted lead author Eric L. Simpson, MD, professor of dermatology at Oregon Health & Science University, Portland, and coauthors in their article on the study, which was published in JAMA Dermatology.

The double-blind trial, conducted at 54 sites across Germany, Poland, Canada, and the United States, included 211 patients, mean age 37.2 years, of whom 48.8% were female and roughly 22% were adolescents. Almost 15% were Asian, and about 13% were Black.

At baseline, participants had a score of 16 or higher on the Eczema Area and Severity Index (EASI), a score of 3 or higher on the Investigator’s Global Assessment (IGA) scale, AD covering a body surface area of 10% or greater, and a history of inadequate response to treatment with topical medications.

After a minimum 1-week washout period from topical and systemic therapy, participants were randomized in a 2:1 ratio to receive lebrikizumab plus TCS (n = 145) or placebo plus TCS (n = 66) for 16 weeks.

Lebrikizumab or placebo was administered by subcutaneous injection every 2 weeks; the loading and week-2 doses of lebrikizumab were 500 mg, followed by 250 mg thereafter. All patients were instructed to use low- to mid-potency TCS at their own discretion. Study sites provided a mid-potency TCS (triamcinolone acetonide 0.1% cream) and a low-potency TCS (hydrocortisone 1% cream), with topical calcineurin inhibitors permitted for sensitive skin areas.

Primary outcomes at 16 weeks included a 2-point or more reduction in IGA score from baseline and EASI-75 response. Patients in the lebrikizumab arm had superior responses on both of these outcomes, with statistical significance achieved as early as week 8 and week 4, respectively, and maintained through week 16. Specifically, 41.2% of those treated with lebrikizumab had an IGA reduction of 2 points or more, compared with 22.1% of those receiving placebo plus TCS (P = .01), and the proportion of patients achieving EASI-75 responses was 69.5% vs. 42.2%, respectively (P < .001).

Patients treated with lebrikizumab also showed statistically significant improvements, compared with TCS alone in all key secondary endpoints, “including skin clearance, improvement in itch, itch interference on sleep, and enhanced QoL [quality of life],” noted the authors. “This study captured the clinical benefit of lebrikizumab through the combined end point of physician-assessed clinical sign of skin clearance (EASI-75) and patient-reported outcome of improvement in itch (Pruritus NRS).”

The percentage of patients who achieved the combined endpoint was more than double for the lebrikizumab plus TCS group vs. the group on TCS alone, indicating that patients treated with lebrikizumab plus TCS “were more likely to experience improvement in skin symptoms and itch,” the investigators added.

The authors noted that most treatment-emergent adverse events “were nonserious, mild, or moderate in severity, and did not lead to study discontinuation.” These included conjunctivitis (4.8%), headache (4.8%), hypertension (2.8%), injection-site reactions (2.8%), and herpes infection (3.4%) – all of which occurred in 1.5% or less of patients in the placebo group.

“The higher incidence of conjunctivitis has also been reported in other biologics inhibiting IL [interleukin]–13 and/or IL-4 signaling, as well as lebrikizumab monotherapy studies,” they noted. The 4.8% rate of conjunctivitis reported in the combination study, they added, is “compared with 7.5% frequency in 16-week data from the lebrikizumab monotherapy studies. Although the mechanism remains unclear, it has been reported that conjunctival goblet cell scarcity due to IL-13 and IL-4 inhibition, and subsequent effects on the homeostasis of the conjunctival mucosal surface, results in ocular AEs [adverse events].”

“This truly is a time of great hope and promise for our patients with AD,” commented Zelma Chiesa Fuxench, MD, who was not involved in the study. “The advent of newer, targeted therapeutic agents for AD continues to revolutionize the treatment experience for our patients, offering the possibility of greater AD disease control with a favorable risk profile and less need for blood work monitoring compared to traditional systemic agents.”

On the basis of the study results, Dr. Chiesa Fuxench, of the department of dermatology at the University of Pennsylvania, Philadelphia, said in an interview that “lebrikizumab represents an additional option in the treatment armamentarium for providers who care for patients with AD.” She added that, “while head-to-head trials comparing lebrikizumab to dupilumab, the first FDA-approved biologic for AD, would be beneficial, to the best of my knowledge this data is currently lacking. However, based on the results of this study, we would expect lebrikizumab to work at least similarly to dupilumab, based on the reported improvements in IGA and EASI score.”

Additionally, lebrikizumab showed a favorable safety profile, “with most treatment-emergent adverse effects reported as nonserious and not leading to drug discontinuation,” she said. “Of interest to clinicians may be the reported rates of conjunctivitis in this study. Rates of conjunctivitis for lebrikizumab appear to be lower than those reported in the LIBERTY AD CHRONOS study for dupilumab – a finding that merits further scrutiny in my opinion, as this one of the most frequent treatment-emergent adverse events that I encounter in my clinical practice.”

The study was funded by Dermira, a subsidiary of Eli Lilly. Dr. Simpson reported personal fees and grants from multiple sources, including Dermira and Eli Lilly, the companies developing lebrikizumab. Several authors were employees of Eli Lilly. Dr. Fuxench disclosed serving as a consultant for the Asthma and Allergy Foundation of America, National Eczema Association, Pfizer, AbbVie, and Incyte, for which she has received honoraria for AD-related work. She is the recipient of research grants through Regeneron, Sanofi, Tioga, Vanda, Menlo Therapeutics, Leo Pharma, and Eli Lilly for work related to AD as well as honoraria for continuing medical education work related to AD sponsored through educational grants from Regeneron/Sanofi and Pfizer.

A version of this article first appeared on Medscape.com.

Adult and adolescent patients with moderate to severe atopic dermatitis (AD) showed significant improvements with the addition of lebrikizumab to topical corticosteroid (TCS) therapy, compared with TCS plus placebo, according to results of the 16-week phase 3 ADhere trial.

“Lebrikizumab, a monoclonal antibody inhibiting interleukin-13, combined with TCS was associated with reduced overall disease severity of moderate to severe AD in adolescents and adults, and had a safety profile consistent with previous lebrikizumab AD studies,” noted lead author Eric L. Simpson, MD, professor of dermatology at Oregon Health & Science University, Portland, and coauthors in their article on the study, which was published in JAMA Dermatology.

The double-blind trial, conducted at 54 sites across Germany, Poland, Canada, and the United States, included 211 patients, mean age 37.2 years, of whom 48.8% were female and roughly 22% were adolescents. Almost 15% were Asian, and about 13% were Black.

At baseline, participants had a score of 16 or higher on the Eczema Area and Severity Index (EASI), a score of 3 or higher on the Investigator’s Global Assessment (IGA) scale, AD covering a body surface area of 10% or greater, and a history of inadequate response to treatment with topical medications.

After a minimum 1-week washout period from topical and systemic therapy, participants were randomized in a 2:1 ratio to receive lebrikizumab plus TCS (n = 145) or placebo plus TCS (n = 66) for 16 weeks.

Lebrikizumab or placebo was administered by subcutaneous injection every 2 weeks; the loading and week-2 doses of lebrikizumab were 500 mg, followed by 250 mg thereafter. All patients were instructed to use low- to mid-potency TCS at their own discretion. Study sites provided a mid-potency TCS (triamcinolone acetonide 0.1% cream) and a low-potency TCS (hydrocortisone 1% cream), with topical calcineurin inhibitors permitted for sensitive skin areas.

Primary outcomes at 16 weeks included a 2-point or more reduction in IGA score from baseline and EASI-75 response. Patients in the lebrikizumab arm had superior responses on both of these outcomes, with statistical significance achieved as early as week 8 and week 4, respectively, and maintained through week 16. Specifically, 41.2% of those treated with lebrikizumab had an IGA reduction of 2 points or more, compared with 22.1% of those receiving placebo plus TCS (P = .01), and the proportion of patients achieving EASI-75 responses was 69.5% vs. 42.2%, respectively (P < .001).

Patients treated with lebrikizumab also showed statistically significant improvements, compared with TCS alone in all key secondary endpoints, “including skin clearance, improvement in itch, itch interference on sleep, and enhanced QoL [quality of life],” noted the authors. “This study captured the clinical benefit of lebrikizumab through the combined end point of physician-assessed clinical sign of skin clearance (EASI-75) and patient-reported outcome of improvement in itch (Pruritus NRS).”

The percentage of patients who achieved the combined endpoint was more than double for the lebrikizumab plus TCS group vs. the group on TCS alone, indicating that patients treated with lebrikizumab plus TCS “were more likely to experience improvement in skin symptoms and itch,” the investigators added.

The authors noted that most treatment-emergent adverse events “were nonserious, mild, or moderate in severity, and did not lead to study discontinuation.” These included conjunctivitis (4.8%), headache (4.8%), hypertension (2.8%), injection-site reactions (2.8%), and herpes infection (3.4%) – all of which occurred in 1.5% or less of patients in the placebo group.

“The higher incidence of conjunctivitis has also been reported in other biologics inhibiting IL [interleukin]–13 and/or IL-4 signaling, as well as lebrikizumab monotherapy studies,” they noted. The 4.8% rate of conjunctivitis reported in the combination study, they added, is “compared with 7.5% frequency in 16-week data from the lebrikizumab monotherapy studies. Although the mechanism remains unclear, it has been reported that conjunctival goblet cell scarcity due to IL-13 and IL-4 inhibition, and subsequent effects on the homeostasis of the conjunctival mucosal surface, results in ocular AEs [adverse events].”

“This truly is a time of great hope and promise for our patients with AD,” commented Zelma Chiesa Fuxench, MD, who was not involved in the study. “The advent of newer, targeted therapeutic agents for AD continues to revolutionize the treatment experience for our patients, offering the possibility of greater AD disease control with a favorable risk profile and less need for blood work monitoring compared to traditional systemic agents.”

On the basis of the study results, Dr. Chiesa Fuxench, of the department of dermatology at the University of Pennsylvania, Philadelphia, said in an interview that “lebrikizumab represents an additional option in the treatment armamentarium for providers who care for patients with AD.” She added that, “while head-to-head trials comparing lebrikizumab to dupilumab, the first FDA-approved biologic for AD, would be beneficial, to the best of my knowledge this data is currently lacking. However, based on the results of this study, we would expect lebrikizumab to work at least similarly to dupilumab, based on the reported improvements in IGA and EASI score.”

Additionally, lebrikizumab showed a favorable safety profile, “with most treatment-emergent adverse effects reported as nonserious and not leading to drug discontinuation,” she said. “Of interest to clinicians may be the reported rates of conjunctivitis in this study. Rates of conjunctivitis for lebrikizumab appear to be lower than those reported in the LIBERTY AD CHRONOS study for dupilumab – a finding that merits further scrutiny in my opinion, as this one of the most frequent treatment-emergent adverse events that I encounter in my clinical practice.”

The study was funded by Dermira, a subsidiary of Eli Lilly. Dr. Simpson reported personal fees and grants from multiple sources, including Dermira and Eli Lilly, the companies developing lebrikizumab. Several authors were employees of Eli Lilly. Dr. Fuxench disclosed serving as a consultant for the Asthma and Allergy Foundation of America, National Eczema Association, Pfizer, AbbVie, and Incyte, for which she has received honoraria for AD-related work. She is the recipient of research grants through Regeneron, Sanofi, Tioga, Vanda, Menlo Therapeutics, Leo Pharma, and Eli Lilly for work related to AD as well as honoraria for continuing medical education work related to AD sponsored through educational grants from Regeneron/Sanofi and Pfizer.

A version of this article first appeared on Medscape.com.