Ixekizumab effective over long term for psoriasis

The interleukin-17A antagonist ixekizumab has shown sustained efficacy over 4 years of treatment in patients with moderate to severe plaque psoriasis, according to a study published in the Journal of the European Academy of Dermatology and Venereology.

The UNCOVER-3 trial was a double-blind, multicenter, phase 3 study in 1,346 individuals with moderate to severe psoriasis who were randomized to placebo, 80 mg of ixekizumab every 2 or 4 weeks, or 50 mg of etanercept twice weekly. At week 12, all patients were transferred to 80 mg of ixekizumab every 4 weeks for the long-term extension period, and after 60 weeks, some were dose adjusted to 80 mg every 2 weeks.

At week 204, 48.3% of the 385 patients who were receiving treatment either every 2 or 4 weeks achieved Psoriasis Area and Severity Index (PASI) 100 according to the modified nonresponder imputation method to summarize efficacy – in which patients who drop out of the study are counted as nonresponders – 66.4% achieved PASI 90 and 82.8% achieved PASI 75.

Using the as-observed method for assessing efficacy, 67.1% of patients achieved PASI 100, 87.8% achieved PASI 90, and 98.2% achieved PASI 75. Using the multiple-imputation method, those same figures were 52.7%, 73.3%, and 94.8% respectively.

They also saw consistently high response rates according to the static Physician’s Global Assessment (sPGA) score, which goes from 0 (clear) to 5 (severe disease). Using the as-observed, multiple imputation and modified nonresponder imputation methods, 68.9%, 54.6%, and 49.7% of patients respectively achieved a score of 0.

The study also saw complete resolution in 95.8% of patients with baseline palmoplantar involvement, 75.9% of those with baseline nail involvement, and 87.1% of those with scalp involvement, using the as-observed method.

“These results corroborate the results that were reported previously in patients with moderate to severe psoriasis,” wrote Mark G. Lebwohl, MD, professor and chair of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and coauthors. “Sustained high response was observed with all the efficacy parameters such as PASI 75, 90, 100, and sPGA (0) or (0, 1), regardless of the statistical analyses ... performed.”

The majority of adverse events were mild or moderate, but serious adverse events were seen in 18.1% of patients in the long-term extension and 9.4% of patients stopped taking the study drug because of adverse events.

The most frequently reported adverse events of special interest were infections, such as nasopharyngitis (28.5% of patients), upper respiratory tract infections (10.8%), and Candida infection (5.2%). However, clinically significant neutropenia only occurred in 0.7% of patients, and malignancies occurred in 2.2% of patients.

“These safety findings support the consistency in the safety profile of [ixekizumab] treatment with no new signals occurring even after the longer exposure,” the authors wrote.

The study was funded by Eli Lilly, which manufactures ixekizumab. Two authors were employees of Eli Lilly and own company stocks. The remaining three authors reported receiving research funding and consultancies from different pharmaceutical companies, including Eli Lilly.

SOURCE: Lebwohl MG et al. J Eur Acad Dermatol Venereol. 2019 Sep 3. doi: 10.1111/jdv.15921.

The interleukin-17A antagonist ixekizumab has shown sustained efficacy over 4 years of treatment in patients with moderate to severe plaque psoriasis, according to a study published in the Journal of the European Academy of Dermatology and Venereology.

The UNCOVER-3 trial was a double-blind, multicenter, phase 3 study in 1,346 individuals with moderate to severe psoriasis who were randomized to placebo, 80 mg of ixekizumab every 2 or 4 weeks, or 50 mg of etanercept twice weekly. At week 12, all patients were transferred to 80 mg of ixekizumab every 4 weeks for the long-term extension period, and after 60 weeks, some were dose adjusted to 80 mg every 2 weeks.

At week 204, 48.3% of the 385 patients who were receiving treatment either every 2 or 4 weeks achieved Psoriasis Area and Severity Index (PASI) 100 according to the modified nonresponder imputation method to summarize efficacy – in which patients who drop out of the study are counted as nonresponders – 66.4% achieved PASI 90 and 82.8% achieved PASI 75.

Using the as-observed method for assessing efficacy, 67.1% of patients achieved PASI 100, 87.8% achieved PASI 90, and 98.2% achieved PASI 75. Using the multiple-imputation method, those same figures were 52.7%, 73.3%, and 94.8% respectively.

They also saw consistently high response rates according to the static Physician’s Global Assessment (sPGA) score, which goes from 0 (clear) to 5 (severe disease). Using the as-observed, multiple imputation and modified nonresponder imputation methods, 68.9%, 54.6%, and 49.7% of patients respectively achieved a score of 0.

The study also saw complete resolution in 95.8% of patients with baseline palmoplantar involvement, 75.9% of those with baseline nail involvement, and 87.1% of those with scalp involvement, using the as-observed method.

“These results corroborate the results that were reported previously in patients with moderate to severe psoriasis,” wrote Mark G. Lebwohl, MD, professor and chair of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and coauthors. “Sustained high response was observed with all the efficacy parameters such as PASI 75, 90, 100, and sPGA (0) or (0, 1), regardless of the statistical analyses ... performed.”

The majority of adverse events were mild or moderate, but serious adverse events were seen in 18.1% of patients in the long-term extension and 9.4% of patients stopped taking the study drug because of adverse events.

The most frequently reported adverse events of special interest were infections, such as nasopharyngitis (28.5% of patients), upper respiratory tract infections (10.8%), and Candida infection (5.2%). However, clinically significant neutropenia only occurred in 0.7% of patients, and malignancies occurred in 2.2% of patients.

“These safety findings support the consistency in the safety profile of [ixekizumab] treatment with no new signals occurring even after the longer exposure,” the authors wrote.

The study was funded by Eli Lilly, which manufactures ixekizumab. Two authors were employees of Eli Lilly and own company stocks. The remaining three authors reported receiving research funding and consultancies from different pharmaceutical companies, including Eli Lilly.

SOURCE: Lebwohl MG et al. J Eur Acad Dermatol Venereol. 2019 Sep 3. doi: 10.1111/jdv.15921.

The interleukin-17A antagonist ixekizumab has shown sustained efficacy over 4 years of treatment in patients with moderate to severe plaque psoriasis, according to a study published in the Journal of the European Academy of Dermatology and Venereology.

The UNCOVER-3 trial was a double-blind, multicenter, phase 3 study in 1,346 individuals with moderate to severe psoriasis who were randomized to placebo, 80 mg of ixekizumab every 2 or 4 weeks, or 50 mg of etanercept twice weekly. At week 12, all patients were transferred to 80 mg of ixekizumab every 4 weeks for the long-term extension period, and after 60 weeks, some were dose adjusted to 80 mg every 2 weeks.

At week 204, 48.3% of the 385 patients who were receiving treatment either every 2 or 4 weeks achieved Psoriasis Area and Severity Index (PASI) 100 according to the modified nonresponder imputation method to summarize efficacy – in which patients who drop out of the study are counted as nonresponders – 66.4% achieved PASI 90 and 82.8% achieved PASI 75.

Using the as-observed method for assessing efficacy, 67.1% of patients achieved PASI 100, 87.8% achieved PASI 90, and 98.2% achieved PASI 75. Using the multiple-imputation method, those same figures were 52.7%, 73.3%, and 94.8% respectively.

They also saw consistently high response rates according to the static Physician’s Global Assessment (sPGA) score, which goes from 0 (clear) to 5 (severe disease). Using the as-observed, multiple imputation and modified nonresponder imputation methods, 68.9%, 54.6%, and 49.7% of patients respectively achieved a score of 0.

The study also saw complete resolution in 95.8% of patients with baseline palmoplantar involvement, 75.9% of those with baseline nail involvement, and 87.1% of those with scalp involvement, using the as-observed method.

“These results corroborate the results that were reported previously in patients with moderate to severe psoriasis,” wrote Mark G. Lebwohl, MD, professor and chair of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and coauthors. “Sustained high response was observed with all the efficacy parameters such as PASI 75, 90, 100, and sPGA (0) or (0, 1), regardless of the statistical analyses ... performed.”

The majority of adverse events were mild or moderate, but serious adverse events were seen in 18.1% of patients in the long-term extension and 9.4% of patients stopped taking the study drug because of adverse events.

The most frequently reported adverse events of special interest were infections, such as nasopharyngitis (28.5% of patients), upper respiratory tract infections (10.8%), and Candida infection (5.2%). However, clinically significant neutropenia only occurred in 0.7% of patients, and malignancies occurred in 2.2% of patients.

“These safety findings support the consistency in the safety profile of [ixekizumab] treatment with no new signals occurring even after the longer exposure,” the authors wrote.

The study was funded by Eli Lilly, which manufactures ixekizumab. Two authors were employees of Eli Lilly and own company stocks. The remaining three authors reported receiving research funding and consultancies from different pharmaceutical companies, including Eli Lilly.

SOURCE: Lebwohl MG et al. J Eur Acad Dermatol Venereol. 2019 Sep 3. doi: 10.1111/jdv.15921.