Risk-Benefit Favorable for New Oral Psoriasis Tx

SAN ANTONIO — A novel oral therapy with broad anti-inflammatory activity is showing promise for the treatment of moderate to severe plaque psoriasis, according to phase II study data presented at the annual meeting of the American Academy of Dermatology.

Apremilast (CC-10004, Celgene Corp.) is a phosphodiesterase type 4 inhibitor that has potent anti-inflammatory activity believed to result in part from inhibition of tumor necrosis factor-α and other proinflammatory mediators, including interleukin-2, interferon-α, leukotrienes, and nitric oxide synthase, Dr. Kim Papp of Probity Medical Research Inc., Waterloo, Ont., explained during a poster discussion session.

A group of 260 patients was enrolled in the randomized, controlled, 12-week trial, which compared once- and twice-daily 20-mg dosages of Apremilast with placebo. The study was supported by Celgene.

At week 12 of treatment, a significantly higher proportion of patients in the twice-daily treatment group achieved Psoriasis Activity and Severity Index-75 (PASI-75) scores, compared with the other groups (24% in the twice-daily treatment group versus 10% in the once-daily treatment and placebo groups). Similarly, PASI-50 scores were achieved by 57% of those in the twice-daily treatment group, 28% in the once-daily group, and 23% in the placebo group.

PASI-90 scores were achieved by 14% of patients in the twice-daily group, by 2% in the once-daily group, and by 6% in the placebo group, Dr. Papp said.

As for Dermatology Life Quality Index scores, the mean changes from baseline were 7 points among those treated twice daily, 5 points among those treated once daily, and 3 points among given placebo, he noted.

Patients in the treatment groups continued to show improvement over time, with the greatest mean percent reduction in PASI scores demonstrated at the final assessment at 12 weeks, he said.

Adverse events in the study were generally mild and were similar in all three groups. Fifty-four percent in the twice-daily treatment group, 68% in the once-daily group, and 60% in the placebo group reported at least one adverse event. Headache and nasopharyngitis were the most common adverse events in all three groups, followed by diarrhea, pruritus, fatigue, aggravated psoriasis, and nausea.

The participants in this phase II study were at least 18 years old, had a diagnosis of moderate to severe plaque psoriasis for at least 6 months prior to enrollment (but were otherwise in good health), had PASI scores of at least 10 and body surface area involvement of at least 10%, and were candidates for photo- or systemic therapy.

The findings demonstrate a favorable risk-benefit profile for Apremilast, Dr. Papp said.

"Current therapies are limited by toxicities or by lack of efficacy," he said, noting that very few available treatments are effective across the spectrum of psoriatic disease.

"We continue to seek novel and safe therapies for chronic plaque psoriasis … and this is the first [phosphodiesterase type 4 inhibitor] that has shown itself to be well tolerated, safe, and effective," he said.

SAN ANTONIO — A novel oral therapy with broad anti-inflammatory activity is showing promise for the treatment of moderate to severe plaque psoriasis, according to phase II study data presented at the annual meeting of the American Academy of Dermatology.

Apremilast (CC-10004, Celgene Corp.) is a phosphodiesterase type 4 inhibitor that has potent anti-inflammatory activity believed to result in part from inhibition of tumor necrosis factor-α and other proinflammatory mediators, including interleukin-2, interferon-α, leukotrienes, and nitric oxide synthase, Dr. Kim Papp of Probity Medical Research Inc., Waterloo, Ont., explained during a poster discussion session.

A group of 260 patients was enrolled in the randomized, controlled, 12-week trial, which compared once- and twice-daily 20-mg dosages of Apremilast with placebo. The study was supported by Celgene.

At week 12 of treatment, a significantly higher proportion of patients in the twice-daily treatment group achieved Psoriasis Activity and Severity Index-75 (PASI-75) scores, compared with the other groups (24% in the twice-daily treatment group versus 10% in the once-daily treatment and placebo groups). Similarly, PASI-50 scores were achieved by 57% of those in the twice-daily treatment group, 28% in the once-daily group, and 23% in the placebo group.

PASI-90 scores were achieved by 14% of patients in the twice-daily group, by 2% in the once-daily group, and by 6% in the placebo group, Dr. Papp said.

As for Dermatology Life Quality Index scores, the mean changes from baseline were 7 points among those treated twice daily, 5 points among those treated once daily, and 3 points among given placebo, he noted.

Patients in the treatment groups continued to show improvement over time, with the greatest mean percent reduction in PASI scores demonstrated at the final assessment at 12 weeks, he said.

Adverse events in the study were generally mild and were similar in all three groups. Fifty-four percent in the twice-daily treatment group, 68% in the once-daily group, and 60% in the placebo group reported at least one adverse event. Headache and nasopharyngitis were the most common adverse events in all three groups, followed by diarrhea, pruritus, fatigue, aggravated psoriasis, and nausea.

The participants in this phase II study were at least 18 years old, had a diagnosis of moderate to severe plaque psoriasis for at least 6 months prior to enrollment (but were otherwise in good health), had PASI scores of at least 10 and body surface area involvement of at least 10%, and were candidates for photo- or systemic therapy.

The findings demonstrate a favorable risk-benefit profile for Apremilast, Dr. Papp said.

"Current therapies are limited by toxicities or by lack of efficacy," he said, noting that very few available treatments are effective across the spectrum of psoriatic disease.

"We continue to seek novel and safe therapies for chronic plaque psoriasis … and this is the first [phosphodiesterase type 4 inhibitor] that has shown itself to be well tolerated, safe, and effective," he said.

SAN ANTONIO — A novel oral therapy with broad anti-inflammatory activity is showing promise for the treatment of moderate to severe plaque psoriasis, according to phase II study data presented at the annual meeting of the American Academy of Dermatology.

Apremilast (CC-10004, Celgene Corp.) is a phosphodiesterase type 4 inhibitor that has potent anti-inflammatory activity believed to result in part from inhibition of tumor necrosis factor-α and other proinflammatory mediators, including interleukin-2, interferon-α, leukotrienes, and nitric oxide synthase, Dr. Kim Papp of Probity Medical Research Inc., Waterloo, Ont., explained during a poster discussion session.

A group of 260 patients was enrolled in the randomized, controlled, 12-week trial, which compared once- and twice-daily 20-mg dosages of Apremilast with placebo. The study was supported by Celgene.

At week 12 of treatment, a significantly higher proportion of patients in the twice-daily treatment group achieved Psoriasis Activity and Severity Index-75 (PASI-75) scores, compared with the other groups (24% in the twice-daily treatment group versus 10% in the once-daily treatment and placebo groups). Similarly, PASI-50 scores were achieved by 57% of those in the twice-daily treatment group, 28% in the once-daily group, and 23% in the placebo group.

PASI-90 scores were achieved by 14% of patients in the twice-daily group, by 2% in the once-daily group, and by 6% in the placebo group, Dr. Papp said.

As for Dermatology Life Quality Index scores, the mean changes from baseline were 7 points among those treated twice daily, 5 points among those treated once daily, and 3 points among given placebo, he noted.

Patients in the treatment groups continued to show improvement over time, with the greatest mean percent reduction in PASI scores demonstrated at the final assessment at 12 weeks, he said.

Adverse events in the study were generally mild and were similar in all three groups. Fifty-four percent in the twice-daily treatment group, 68% in the once-daily group, and 60% in the placebo group reported at least one adverse event. Headache and nasopharyngitis were the most common adverse events in all three groups, followed by diarrhea, pruritus, fatigue, aggravated psoriasis, and nausea.

The participants in this phase II study were at least 18 years old, had a diagnosis of moderate to severe plaque psoriasis for at least 6 months prior to enrollment (but were otherwise in good health), had PASI scores of at least 10 and body surface area involvement of at least 10%, and were candidates for photo- or systemic therapy.

The findings demonstrate a favorable risk-benefit profile for Apremilast, Dr. Papp said.

"Current therapies are limited by toxicities or by lack of efficacy," he said, noting that very few available treatments are effective across the spectrum of psoriatic disease.

"We continue to seek novel and safe therapies for chronic plaque psoriasis … and this is the first [phosphodiesterase type 4 inhibitor] that has shown itself to be well tolerated, safe, and effective," he said.