Phase 3 Dupilumab Data Positive results were presented in a late-breaking news session from the phase 3 CAFÉ study of dupilumab (Dupixent) in adults with moderate to severe AD who are inadequately controlled with or intolerant to the broad immunosuppressant drug cyclosporine A (CSA), or when this treatment is medically inadvisable.1 Dupilumab is a human monoclonal antibody that is designed to simultaneously inhibit overactive signaling of IL-4 and IL-13 cytokines.
In the study, dupilumab with topical corticosteroids (TCS) significantly improved measures of overall disease severity, skin clearing, itching, and patient-reported quality of life measures. CSA is approved for the treatment of AD in most European countries and Japan; it is not approved in the United States for this use.
The study’s primary endpoint was the proportion of patients who achieved a 75% or greater improvement in the Eczema Area and Severity Index (EASI 75) score at 16 weeks from baseline. A total of 325 patients in Europe were randomized into 3 treatment arms in the 16-week study to either dupilumab 300 mg weekly with TCS, dupilumab 300 mg every 2 weeks with TCS, or placebo with TCS. A total of 59% of patients who received dupilumab weekly with TCS, and 63% of patients who received dupilumab every 2 weeks with TCS achieved EASI 75 compared with 30% of those patients who received placebo with TCS (P <.0001).
The mean percent change improvement in EASI from baseline at 16 weeks (a secondary endpoint) was 78% and 80% for patients who received dupilumab weekly or every 2 weeks with TCS, respectively, compared with 47% for those who received placebo plus TCS (P< .0001).
“In moderate-to-severe atopic dermatitis, some patients stop cyclosporine therapy due to intolerance or lack of efficacy, or are not candidates because of other medical conditions or contraindicated medications,” explained Marjolein De Bruin-Weller, MD, PhD, dermatologist with the National Expertise Center for Atopic Dermatitis, University Medical Center Utrecht in Utrecht, Netherlands. “In the CAFÉ study, dupilumab with topical corticosteroids significantly improved overall measures of disease severity including lesions, itch, quality of life measures, and symptoms of anxiety and depression in these patients. The safety profile in this study was consistent with 3 previous positive dupilumab phase 3 studies in moderate-to-severe atopic dermatitis.”
Other secondary endpoints of the study included measures of the impact of dupilumab on the persistent itch caused by the disease, quality of life measures, and symptoms of anxiety and depression. The results for these secondary endpoints at 16 weeks showed that the mean percent improvement from baseline in the intensity of patient-reported itch, as measured by the pruritus Numerical Rating Scale, was 52% and 54% in patients who received dupilumab weekly or every 2 weeks with TCS, respectively, compared with 25% for those who received placebo plus TCS (P <.0001).
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In addition, the proportion of patients with ≥4-point improvement from baseline in aspects of patient quality of life, as measured by the Dermatology Life Quality Index, was 78% and 88% in patients who received dupilumab weekly or every 2 weeks with TCS, respectively, compared with 44% of those who received placebo plus TCS (P< .0001). The proportion of patients with a ≥4-point improvement from baseline in the severity of their AD, as measured by the Patient Oriented Eczema Measure, was 76% and 83% in patients who received dupilumab weekly or every 2 weeks with TCS, respectively, compared with 42% for those who received placebo plus TCS (P <.0001).
The most common side effects include injection-site reactions; eye and eyelid inflammation, including redness, swelling and itching; and cold sores in mouth or on lips. No new adverse events were reported in the study. The proportion of patients reporting an adverse event was similar among the treatment arms. Conjunctivitis was more frequent in patients who received dupilumab with TCS, with 16% and 28% reported in patients who received dupilumab weekly or every 2 weeks with TCS, respectively, compared with 11% for patients who received placebo with TCS. Injection-site reactions were reported in 11% and 4% among patients who received dupilumab with TCS weekly or every 2 weeks, respectively, compared with 5% for patients who received placebo with TCS. Skin infections were reported in 4% and 2% among patients who received dupilumab weekly or every 2 weeks with TCS, respectively, compared with 8% for patients who received placebo with TCS.
Phase 2 Results on Baricitinib
New safety and efficacy data also were released at the EADV Congress from a phase 2 study of the once-daily oral Janus kinase inhibitor baricitinib in people with moderate to severe AD. The results showed that baricitinib in combination with a mid-potency TCS significantly improved the signs and symptoms of AD compared with TCS alone.2
After 16 weeks of treatment, 61% of patients treated with baricitinib 4 mg in combination with TCS (n=38) achieved a 50% or greater reduction in their overall disease severity as measured by the EASI 50 compared with 37% of patients treated with TCS monotherapy (n=49) (P<.05). Among patients treated with baricitinib 2 mg in combination with TCS (n=37), 57% achieved EASI 50, although these results were not statistically different compared with treatment with TCS alone (P=.065). At 4 weeks, 68% of patients treated with baricitinib 4 mg in combination with TCS and 62% of patients treated with baricitinib 2 mg in combination with TCS achieved EASI 50 compared with 16% of patients treated with TCS monotherapy (P<.001).
“Importantly, in this study, patients had to fail 4 weeks of supervised therapy with a mid-potency topical corticosteroid before randomization, selecting for a difficult to treat patient population,” said Emma Guttman-Yassky, MD, PhD, Sol and Clara Kest professor of dermatology, vice chair department of dermatology, director of the Center for Excellence in Eczema, and director of the Laboratory of Inflammatory Skin Diseases in the department of dermatology, Icahn School of Medicine at Mount Sinai Medical Center in New York, NY.
“These new results suggest that baricitinib may have the potential to become an oral treatment option for patients suffering from atopic dermatitis who are unable to achieve adequate control with TCS,” she said.
During the treatment period, treatment-emergent adverse events occurred in 49% of patients treated with TCS, 46% and 71% of the baricitinib 2 mg and 4 mg in combination with TCS groups, respectively. The most common treatment-emergent adverse events in the baricitinib 4 mg in combination with TCS group were upper respiratory tract infections, nasopharyngitis, headache, and increases in asymptomatic laboratory changes, namely increases in creatine phosphokinase.
References
1. de Bruin-Weller M, et al. Dupilumab in adult patients with atopic dermatitis and history of inadequate response, intolerance to, or medically inadvisable for cyclosporine A: a placebo-controlled, randomized phase 3 clinical trial (Liberty AD CAFÉ). Presented at: The European Academy of Dermatology and Venereology Congress 2017; September 13-17, 2017; Geneva, Switzerland.
2. Guttman-Yassky E. Baricitinib in patients with moderate-to-severe atopic dermatitis: A phase 2 parallel, double-blinded, randomized, placebo-controlled, multiple dose study. Presented at: The European Academy of Dermatology and Venereology Congress 2017; September 13-17, 2017; Geneva, Switzerland. Abstract FC04.01.
Phase 3 Dupilumab Data
Positive results were presented in a late-breaking news session from the phase 3 CAFÉ study of dupilumab (Dupixent) in adults with moderate to severe AD who are inadequately controlled with or intolerant to the broad immunosuppressant drug cyclosporine A (CSA), or when this treatment is medically inadvisable.1 Dupilumab is a human monoclonal antibody that is designed to simultaneously inhibit overactive signaling of IL-4 and IL-13 cytokines.
In the study, dupilumab with topical corticosteroids (TCS) significantly improved measures of overall disease severity, skin clearing, itching, and patient-reported quality of life measures. CSA is approved for the treatment of AD in most European countries and Japan; it is not approved in the United States for this use.
The study’s primary endpoint was the proportion of patients who achieved a 75% or greater improvement in the Eczema Area and Severity Index (EASI 75) score at 16 weeks from baseline. A total of 325 patients in Europe were randomized into 3 treatment arms in the 16-week study to either dupilumab 300 mg weekly with TCS, dupilumab 300 mg every 2 weeks with TCS, or placebo with TCS. A total of 59% of patients who received dupilumab weekly with TCS, and 63% of patients who received dupilumab every 2 weeks with TCS achieved EASI 75 compared with 30% of those patients who received placebo with TCS (P <.0001).
The mean percent change improvement in EASI from baseline at 16 weeks (a secondary endpoint) was 78% and 80% for patients who received dupilumab weekly or every 2 weeks with TCS, respectively, compared with 47% for those who received placebo plus TCS (P< .0001).
“In moderate-to-severe atopic dermatitis, some patients stop cyclosporine therapy due to intolerance or lack of efficacy, or are not candidates because of other medical conditions or contraindicated medications,” explained Marjolein De Bruin-Weller, MD, PhD, dermatologist with the National Expertise Center for Atopic Dermatitis, University Medical Center Utrecht in Utrecht, Netherlands. “In the CAFÉ study, dupilumab with topical corticosteroids significantly improved overall measures of disease severity including lesions, itch, quality of life measures, and symptoms of anxiety and depression in these patients. The safety profile in this study was consistent with 3 previous positive dupilumab phase 3 studies in moderate-to-severe atopic dermatitis.”
Other secondary endpoints of the study included measures of the impact of dupilumab on the persistent itch caused by the disease, quality of life measures, and symptoms of anxiety and depression. The results for these secondary endpoints at 16 weeks showed that the mean percent improvement from baseline in the intensity of patient-reported itch, as measured by the pruritus Numerical Rating Scale, was 52% and 54% in patients who received dupilumab weekly or every 2 weeks with TCS, respectively, compared with 25% for those who received placebo plus TCS (P <.0001).
Article continues on page 2
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In addition, the proportion of patients with ≥4-point improvement from baseline in aspects of patient quality of life, as measured by the Dermatology Life Quality Index, was 78% and 88% in patients who received dupilumab weekly or every 2 weeks with TCS, respectively, compared with 44% of those who received placebo plus TCS (P< .0001). The proportion of patients with a ≥4-point improvement from baseline in the severity of their AD, as measured by the Patient Oriented Eczema Measure, was 76% and 83% in patients who received dupilumab weekly or every 2 weeks with TCS, respectively, compared with 42% for those who received placebo plus TCS (P <.0001).
The most common side effects include injection-site reactions; eye and eyelid inflammation, including redness, swelling and itching; and cold sores in mouth or on lips. No new adverse events were reported in the study. The proportion of patients reporting an adverse event was similar among the treatment arms. Conjunctivitis was more frequent in patients who received dupilumab with TCS, with 16% and 28% reported in patients who received dupilumab weekly or every 2 weeks with TCS, respectively, compared with 11% for patients who received placebo with TCS. Injection-site reactions were reported in 11% and 4% among patients who received dupilumab with TCS weekly or every 2 weeks, respectively, compared with 5% for patients who received placebo with TCS. Skin infections were reported in 4% and 2% among patients who received dupilumab weekly or every 2 weeks with TCS, respectively, compared with 8% for patients who received placebo with TCS.
Phase 2 Results on Baricitinib
New safety and efficacy data also were released at the EADV Congress from a phase 2 study of the once-daily oral Janus kinase inhibitor baricitinib in people with moderate to severe AD. The results showed that baricitinib in combination with a mid-potency TCS significantly improved the signs and symptoms of AD compared with TCS alone.2
After 16 weeks of treatment, 61% of patients treated with baricitinib 4 mg in combination with TCS (n=38) achieved a 50% or greater reduction in their overall disease severity as measured by the EASI 50 compared with 37% of patients treated with TCS monotherapy (n=49) (P<.05). Among patients treated with baricitinib 2 mg in combination with TCS (n=37), 57% achieved EASI 50, although these results were not statistically different compared with treatment with TCS alone (P=.065). At 4 weeks, 68% of patients treated with baricitinib 4 mg in combination with TCS and 62% of patients treated with baricitinib 2 mg in combination with TCS achieved EASI 50 compared with 16% of patients treated with TCS monotherapy (P<.001).
“Importantly, in this study, patients had to fail 4 weeks of supervised therapy with a mid-potency topical corticosteroid before randomization, selecting for a difficult to treat patient population,” said Emma Guttman-Yassky, MD, PhD, Sol and Clara Kest professor of dermatology, vice chair department of dermatology, director of the Center for Excellence in Eczema, and director of the Laboratory of Inflammatory Skin Diseases in the department of dermatology, Icahn School of Medicine at Mount Sinai Medical Center in New York, NY.
“These new results suggest that baricitinib may have the potential to become an oral treatment option for patients suffering from atopic dermatitis who are unable to achieve adequate control with TCS,” she said.
During the treatment period, treatment-emergent adverse events occurred in 49% of patients treated with TCS, 46% and 71% of the baricitinib 2 mg and 4 mg in combination with TCS groups, respectively. The most common treatment-emergent adverse events in the baricitinib 4 mg in combination with TCS group were upper respiratory tract infections, nasopharyngitis, headache, and increases in asymptomatic laboratory changes, namely increases in creatine phosphokinase.
References
1. de Bruin-Weller M, et al. Dupilumab in adult patients with atopic dermatitis and history of inadequate response, intolerance to, or medically inadvisable for cyclosporine A: a placebo-controlled, randomized phase 3 clinical trial (Liberty AD CAFÉ). Presented at: The European Academy of Dermatology and Venereology Congress 2017; September 13-17, 2017; Geneva, Switzerland.
2. Guttman-Yassky E. Baricitinib in patients with moderate-to-severe atopic dermatitis: A phase 2 parallel, double-blinded, randomized, placebo-controlled, multiple dose study. Presented at: The European Academy of Dermatology and Venereology Congress 2017; September 13-17, 2017; Geneva, Switzerland. Abstract FC04.01.
Phase 3 Dupilumab Data
Positive results were presented in a late-breaking news session from the phase 3 CAFÉ study of dupilumab (Dupixent) in adults with moderate to severe AD who are inadequately controlled with or intolerant to the broad immunosuppressant drug cyclosporine A (CSA), or when this treatment is medically inadvisable.1 Dupilumab is a human monoclonal antibody that is designed to simultaneously inhibit overactive signaling of IL-4 and IL-13 cytokines.
In the study, dupilumab with topical corticosteroids (TCS) significantly improved measures of overall disease severity, skin clearing, itching, and patient-reported quality of life measures. CSA is approved for the treatment of AD in most European countries and Japan; it is not approved in the United States for this use.
The study’s primary endpoint was the proportion of patients who achieved a 75% or greater improvement in the Eczema Area and Severity Index (EASI 75) score at 16 weeks from baseline. A total of 325 patients in Europe were randomized into 3 treatment arms in the 16-week study to either dupilumab 300 mg weekly with TCS, dupilumab 300 mg every 2 weeks with TCS, or placebo with TCS. A total of 59% of patients who received dupilumab weekly with TCS, and 63% of patients who received dupilumab every 2 weeks with TCS achieved EASI 75 compared with 30% of those patients who received placebo with TCS (P <.0001).
The mean percent change improvement in EASI from baseline at 16 weeks (a secondary endpoint) was 78% and 80% for patients who received dupilumab weekly or every 2 weeks with TCS, respectively, compared with 47% for those who received placebo plus TCS (P< .0001).
“In moderate-to-severe atopic dermatitis, some patients stop cyclosporine therapy due to intolerance or lack of efficacy, or are not candidates because of other medical conditions or contraindicated medications,” explained Marjolein De Bruin-Weller, MD, PhD, dermatologist with the National Expertise Center for Atopic Dermatitis, University Medical Center Utrecht in Utrecht, Netherlands. “In the CAFÉ study, dupilumab with topical corticosteroids significantly improved overall measures of disease severity including lesions, itch, quality of life measures, and symptoms of anxiety and depression in these patients. The safety profile in this study was consistent with 3 previous positive dupilumab phase 3 studies in moderate-to-severe atopic dermatitis.”
Other secondary endpoints of the study included measures of the impact of dupilumab on the persistent itch caused by the disease, quality of life measures, and symptoms of anxiety and depression. The results for these secondary endpoints at 16 weeks showed that the mean percent improvement from baseline in the intensity of patient-reported itch, as measured by the pruritus Numerical Rating Scale, was 52% and 54% in patients who received dupilumab weekly or every 2 weeks with TCS, respectively, compared with 25% for those who received placebo plus TCS (P <.0001).
Article continues on page 2
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In addition, the proportion of patients with ≥4-point improvement from baseline in aspects of patient quality of life, as measured by the Dermatology Life Quality Index, was 78% and 88% in patients who received dupilumab weekly or every 2 weeks with TCS, respectively, compared with 44% of those who received placebo plus TCS (P< .0001). The proportion of patients with a ≥4-point improvement from baseline in the severity of their AD, as measured by the Patient Oriented Eczema Measure, was 76% and 83% in patients who received dupilumab weekly or every 2 weeks with TCS, respectively, compared with 42% for those who received placebo plus TCS (P <.0001).
The most common side effects include injection-site reactions; eye and eyelid inflammation, including redness, swelling and itching; and cold sores in mouth or on lips. No new adverse events were reported in the study. The proportion of patients reporting an adverse event was similar among the treatment arms. Conjunctivitis was more frequent in patients who received dupilumab with TCS, with 16% and 28% reported in patients who received dupilumab weekly or every 2 weeks with TCS, respectively, compared with 11% for patients who received placebo with TCS. Injection-site reactions were reported in 11% and 4% among patients who received dupilumab with TCS weekly or every 2 weeks, respectively, compared with 5% for patients who received placebo with TCS. Skin infections were reported in 4% and 2% among patients who received dupilumab weekly or every 2 weeks with TCS, respectively, compared with 8% for patients who received placebo with TCS.
Phase 2 Results on Baricitinib
New safety and efficacy data also were released at the EADV Congress from a phase 2 study of the once-daily oral Janus kinase inhibitor baricitinib in people with moderate to severe AD. The results showed that baricitinib in combination with a mid-potency TCS significantly improved the signs and symptoms of AD compared with TCS alone.2
After 16 weeks of treatment, 61% of patients treated with baricitinib 4 mg in combination with TCS (n=38) achieved a 50% or greater reduction in their overall disease severity as measured by the EASI 50 compared with 37% of patients treated with TCS monotherapy (n=49) (P<.05). Among patients treated with baricitinib 2 mg in combination with TCS (n=37), 57% achieved EASI 50, although these results were not statistically different compared with treatment with TCS alone (P=.065). At 4 weeks, 68% of patients treated with baricitinib 4 mg in combination with TCS and 62% of patients treated with baricitinib 2 mg in combination with TCS achieved EASI 50 compared with 16% of patients treated with TCS monotherapy (P<.001).
“Importantly, in this study, patients had to fail 4 weeks of supervised therapy with a mid-potency topical corticosteroid before randomization, selecting for a difficult to treat patient population,” said Emma Guttman-Yassky, MD, PhD, Sol and Clara Kest professor of dermatology, vice chair department of dermatology, director of the Center for Excellence in Eczema, and director of the Laboratory of Inflammatory Skin Diseases in the department of dermatology, Icahn School of Medicine at Mount Sinai Medical Center in New York, NY.
“These new results suggest that baricitinib may have the potential to become an oral treatment option for patients suffering from atopic dermatitis who are unable to achieve adequate control with TCS,” she said.
During the treatment period, treatment-emergent adverse events occurred in 49% of patients treated with TCS, 46% and 71% of the baricitinib 2 mg and 4 mg in combination with TCS groups, respectively. The most common treatment-emergent adverse events in the baricitinib 4 mg in combination with TCS group were upper respiratory tract infections, nasopharyngitis, headache, and increases in asymptomatic laboratory changes, namely increases in creatine phosphokinase.
References
1. de Bruin-Weller M, et al. Dupilumab in adult patients with atopic dermatitis and history of inadequate response, intolerance to, or medically inadvisable for cyclosporine A: a placebo-controlled, randomized phase 3 clinical trial (Liberty AD CAFÉ). Presented at: The European Academy of Dermatology and Venereology Congress 2017; September 13-17, 2017; Geneva, Switzerland.
2. Guttman-Yassky E. Baricitinib in patients with moderate-to-severe atopic dermatitis: A phase 2 parallel, double-blinded, randomized, placebo-controlled, multiple dose study. Presented at: The European Academy of Dermatology and Venereology Congress 2017; September 13-17, 2017; Geneva, Switzerland. Abstract FC04.01.
