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New agents for treating psoriasis have shown great promise in terms of efficacy, but assurances of safety await further data from larger studies.
Thus far, phase II data show impressive efficacy and no worrisome safety signals for the anti-interleukin-17 agents AMG 827 and secukinumab and the small molecules apremilast and tofacitinib. However, the studies have been too small and of insufficient duration to definitively rule out cardiovascular, infectious, and cancer risks, said Dr. Kenneth B. Gordon at the Las Vegas Dermatology Seminar, sponsored by Skin Disease Education Foundation (SDEF).
"It is my hope that these drugs are going to be fantastic. We just have to maintain a level of concern and vigilance for both biologics and small molecules ... We just desperately need large trials," said Dr. Gordon, head of the division of dermatology at NorthShore University HealthSystem, Chicago.
The discovery of IL-17 as a key player in psoriatic plaque formation has led to a new understanding of psoriasis pathophysiology and has become a new target for drug development. However, experience with one agent that blocks IL-12/23 – which induces activated IL-17 – gives pause.
Briakinumab, an extremely effective anti-psoriatic agent that blocks IL 12/23, was withdrawn from development after phase III studies showed a signal – albeit statistically insignificant – for serious infections including cellulitis and pneumonia, MACE events (cardiac arrest, myocardial infarction, and stroke), and malignancies (nonmelanoma skin cancer and squamous cell carcinoma of the lung and nasopharynx).
The absolute MACE event numbers were small, but were counter to what would be expected from a systemic anti-inflammatory agent, which should reduce cardiovascular disease, Dr. Craig L. Leonardi, a clinical professor of dermatology at St. Louis University, said in a separate presentation.
According to Dr. Gordon, "It’s really an exciting time for new psoriatic therapies based on a better understanding of psoriasis pathophysiology. However, we are less excited about phase II data because of what happened to briakinumab in phase III."
It will be essential to determine the etiology of the adverse effects, he said. "If the effects are not related to how well the agent controls psoriasis but to mechanisms like IL-12 blockade that may not have relevance to IL-17, they may not show up [with the new agents in development]. That’s what the phase II studies suggest, but it’s too early to really make a final statement," Dr. Gordon said in an interview.
Source: .skinandallergynews.com
Thus far, phase II data show impressive efficacy and no worrisome safety signals for the anti-interleukin-17 agents AMG 827 and secukinumab and the small molecules apremilast and tofacitinib. However, the studies have been too small and of insufficient duration to definitively rule out cardiovascular, infectious, and cancer risks, said Dr. Kenneth B. Gordon at the Las Vegas Dermatology Seminar, sponsored by Skin Disease Education Foundation (SDEF).
"It is my hope that these drugs are going to be fantastic. We just have to maintain a level of concern and vigilance for both biologics and small molecules ... We just desperately need large trials," said Dr. Gordon, head of the division of dermatology at NorthShore University HealthSystem, Chicago.
The discovery of IL-17 as a key player in psoriatic plaque formation has led to a new understanding of psoriasis pathophysiology and has become a new target for drug development. However, experience with one agent that blocks IL-12/23 – which induces activated IL-17 – gives pause.
Briakinumab, an extremely effective anti-psoriatic agent that blocks IL 12/23, was withdrawn from development after phase III studies showed a signal – albeit statistically insignificant – for serious infections including cellulitis and pneumonia, MACE events (cardiac arrest, myocardial infarction, and stroke), and malignancies (nonmelanoma skin cancer and squamous cell carcinoma of the lung and nasopharynx).
The absolute MACE event numbers were small, but were counter to what would be expected from a systemic anti-inflammatory agent, which should reduce cardiovascular disease, Dr. Craig L. Leonardi, a clinical professor of dermatology at St. Louis University, said in a separate presentation.
According to Dr. Gordon, "It’s really an exciting time for new psoriatic therapies based on a better understanding of psoriasis pathophysiology. However, we are less excited about phase II data because of what happened to briakinumab in phase III."
It will be essential to determine the etiology of the adverse effects, he said. "If the effects are not related to how well the agent controls psoriasis but to mechanisms like IL-12 blockade that may not have relevance to IL-17, they may not show up [with the new agents in development]. That’s what the phase II studies suggest, but it’s too early to really make a final statement," Dr. Gordon said in an interview.
Source: .skinandallergynews.com