Benefits, safety of dupilumab-steroid combination in adults with AD sustained

Dupilumab significantly improved symptoms when used in conjunction with topical steroids over one year in a phase III randomized trial of adults with moderate to severe atopic dermatitis (AD) conducted at 161 centers in 14 countries.

The study is “the first large, randomized, double-blinded placebo-controlled study of long-term systemic treatment in patients with moderate-to-severe atopic dermatitis,” wrote Andrew Blauvelt, MD, president of the Oregon Medical Research Center, Portland, and his coauthors. “These results validate the fundamental role for interleukin 4 and interleukin 13 in the pathogenesis of atopic dermatitis,” they added. The findings were published online (Lancet. 2017 May 4. doi: 10.1016/S0140-6736[17]31191-1).

Dupilumab (Dupixent), a monoclonal antibody that inhibits signaling of both interleukin-4 and interleukin-13, was approved by the Food and Drug Administration in March for treating moderate-to-severe AD in adults.

In the study, known as LIBERTY AD CHRONOS, 740 patients were enrolled and 1-year data were available for 270 adults who received 300 mg of dupilumab once a week plus topical corticosteroids, 89 patients who received 300 mg of dupilumab every two weeks plus topical corticosteroids, and 264 patients who received a placebo plus topical corticosteroids. The two efficacy endpoints were the percent of patients with Investigator’s Global Assessment (IGA) of 0/1 and a 2-point or higher improvement from baseline and a 75% improvement from baseline on the Eczema Area and Severity Index.

At week 16, significantly more patients who received dupilumab plus topical corticosteroids achieved IGA 0/1 (39% of weekly dupilumab plus topical corticosteroids and 39% of those who received dupilumab every 2 weeks plus topical corticosteroids), compared with 12% of placebo/corticosteroid patients. The percentages of patients in each group who met the EASI-75 endpoint were 64%, 69%, and 23%, respectively (P less than .0001).

“The improvement was sustained over the 52-week treatment period,” and the combination therapy was also associated with improvements in “several other measures of clinical signs and symptoms of atopic dermatitis including pruritus, as well as symptoms of anxiety and depression and health-related quality of life, over the 52-week treatment period,” they wrote.

Adverse events were similar among the groups, with 83%, 88%, and 84% of patients in the weekly dupilumab, biweekly dupilumab, and placebo groups, respectively, reporting at least one adverse event. Nonherpetic skin infections were less common among dupilumab patients than among placebo patients, but conjunctivitis was more common among those on dupilumab (14%-19% vs. 8%). “Dupilumab might be the first targeted immune biologic that is neither immunosuppressive nor associated with increased risk of infection but, rather, restorative of barrier and immune function,” the researchers noted.

The results were limited by several factors including the challenges of determining how much topical medication was actually used by patients across multiple study sites, they wrote. However, the data suggest that “the emerging benefit-to-risk profile in this 52-week study supports the role of dupilumab as a primary targeted biologic therapy for up to 1 year in patients with moderate-to-severe atopic dermatitis who are not controlled with topical medications alone,” they said.

The study was funded by Sanofi and Regeneron Pharmaceuticals. Dr. Blauvelt and coauthors disclosed relationships with companies including Sanofi and Regeneron. Several authors were employees of the two companies.

Dupilumab significantly improved symptoms when used in conjunction with topical steroids over one year in a phase III randomized trial of adults with moderate to severe atopic dermatitis (AD) conducted at 161 centers in 14 countries.

The study is “the first large, randomized, double-blinded placebo-controlled study of long-term systemic treatment in patients with moderate-to-severe atopic dermatitis,” wrote Andrew Blauvelt, MD, president of the Oregon Medical Research Center, Portland, and his coauthors. “These results validate the fundamental role for interleukin 4 and interleukin 13 in the pathogenesis of atopic dermatitis,” they added. The findings were published online (Lancet. 2017 May 4. doi: 10.1016/S0140-6736[17]31191-1).

Dupilumab (Dupixent), a monoclonal antibody that inhibits signaling of both interleukin-4 and interleukin-13, was approved by the Food and Drug Administration in March for treating moderate-to-severe AD in adults.

In the study, known as LIBERTY AD CHRONOS, 740 patients were enrolled and 1-year data were available for 270 adults who received 300 mg of dupilumab once a week plus topical corticosteroids, 89 patients who received 300 mg of dupilumab every two weeks plus topical corticosteroids, and 264 patients who received a placebo plus topical corticosteroids. The two efficacy endpoints were the percent of patients with Investigator’s Global Assessment (IGA) of 0/1 and a 2-point or higher improvement from baseline and a 75% improvement from baseline on the Eczema Area and Severity Index.

At week 16, significantly more patients who received dupilumab plus topical corticosteroids achieved IGA 0/1 (39% of weekly dupilumab plus topical corticosteroids and 39% of those who received dupilumab every 2 weeks plus topical corticosteroids), compared with 12% of placebo/corticosteroid patients. The percentages of patients in each group who met the EASI-75 endpoint were 64%, 69%, and 23%, respectively (P less than .0001).

“The improvement was sustained over the 52-week treatment period,” and the combination therapy was also associated with improvements in “several other measures of clinical signs and symptoms of atopic dermatitis including pruritus, as well as symptoms of anxiety and depression and health-related quality of life, over the 52-week treatment period,” they wrote.

Adverse events were similar among the groups, with 83%, 88%, and 84% of patients in the weekly dupilumab, biweekly dupilumab, and placebo groups, respectively, reporting at least one adverse event. Nonherpetic skin infections were less common among dupilumab patients than among placebo patients, but conjunctivitis was more common among those on dupilumab (14%-19% vs. 8%). “Dupilumab might be the first targeted immune biologic that is neither immunosuppressive nor associated with increased risk of infection but, rather, restorative of barrier and immune function,” the researchers noted.

The results were limited by several factors including the challenges of determining how much topical medication was actually used by patients across multiple study sites, they wrote. However, the data suggest that “the emerging benefit-to-risk profile in this 52-week study supports the role of dupilumab as a primary targeted biologic therapy for up to 1 year in patients with moderate-to-severe atopic dermatitis who are not controlled with topical medications alone,” they said.

The study was funded by Sanofi and Regeneron Pharmaceuticals. Dr. Blauvelt and coauthors disclosed relationships with companies including Sanofi and Regeneron. Several authors were employees of the two companies.

Dupilumab significantly improved symptoms when used in conjunction with topical steroids over one year in a phase III randomized trial of adults with moderate to severe atopic dermatitis (AD) conducted at 161 centers in 14 countries.

The study is “the first large, randomized, double-blinded placebo-controlled study of long-term systemic treatment in patients with moderate-to-severe atopic dermatitis,” wrote Andrew Blauvelt, MD, president of the Oregon Medical Research Center, Portland, and his coauthors. “These results validate the fundamental role for interleukin 4 and interleukin 13 in the pathogenesis of atopic dermatitis,” they added. The findings were published online (Lancet. 2017 May 4. doi: 10.1016/S0140-6736[17]31191-1).

Dupilumab (Dupixent), a monoclonal antibody that inhibits signaling of both interleukin-4 and interleukin-13, was approved by the Food and Drug Administration in March for treating moderate-to-severe AD in adults.

In the study, known as LIBERTY AD CHRONOS, 740 patients were enrolled and 1-year data were available for 270 adults who received 300 mg of dupilumab once a week plus topical corticosteroids, 89 patients who received 300 mg of dupilumab every two weeks plus topical corticosteroids, and 264 patients who received a placebo plus topical corticosteroids. The two efficacy endpoints were the percent of patients with Investigator’s Global Assessment (IGA) of 0/1 and a 2-point or higher improvement from baseline and a 75% improvement from baseline on the Eczema Area and Severity Index.

At week 16, significantly more patients who received dupilumab plus topical corticosteroids achieved IGA 0/1 (39% of weekly dupilumab plus topical corticosteroids and 39% of those who received dupilumab every 2 weeks plus topical corticosteroids), compared with 12% of placebo/corticosteroid patients. The percentages of patients in each group who met the EASI-75 endpoint were 64%, 69%, and 23%, respectively (P less than .0001).

“The improvement was sustained over the 52-week treatment period,” and the combination therapy was also associated with improvements in “several other measures of clinical signs and symptoms of atopic dermatitis including pruritus, as well as symptoms of anxiety and depression and health-related quality of life, over the 52-week treatment period,” they wrote.

Adverse events were similar among the groups, with 83%, 88%, and 84% of patients in the weekly dupilumab, biweekly dupilumab, and placebo groups, respectively, reporting at least one adverse event. Nonherpetic skin infections were less common among dupilumab patients than among placebo patients, but conjunctivitis was more common among those on dupilumab (14%-19% vs. 8%). “Dupilumab might be the first targeted immune biologic that is neither immunosuppressive nor associated with increased risk of infection but, rather, restorative of barrier and immune function,” the researchers noted.

The results were limited by several factors including the challenges of determining how much topical medication was actually used by patients across multiple study sites, they wrote. However, the data suggest that “the emerging benefit-to-risk profile in this 52-week study supports the role of dupilumab as a primary targeted biologic therapy for up to 1 year in patients with moderate-to-severe atopic dermatitis who are not controlled with topical medications alone,” they said.

The study was funded by Sanofi and Regeneron Pharmaceuticals. Dr. Blauvelt and coauthors disclosed relationships with companies including Sanofi and Regeneron. Several authors were employees of the two companies.