Dermatologists can better plan and manage systemic care for patients with psoriasis if they understand how to discern outcomes data related to approved biologics and are aware of the associated adverse events, according to April W. Armstrong, M.D., M.P.H., who directed the session “Common, Challenging and Controversial Short Topics in Patient Management,” at the 2018 American Academy of Dermatology annual meeting in San Diego.
“Psoriasis management has become increasingly complex because our patients not only have psoriasis but, oftentimes, they have a number of comorbidities that are associated with psoriasis,” says Dr. Armstrong, who is associate dean for clinical research at Keck School Medicine, University of Southern California, Los Angeles. “In addition to that, our treatment options have increased and, therefore, clinicians need to decide what treatments may be best for their psoriasis patients.”
There are four classes of biologics that have been approved by the U.S. Food and Drug Administration (FDA) to treat psoriasis:
Tumor necrosis factor (TNF) inhibitors;
IL-12/23 inhibitor ustekinumab (Stelara, Janssen);
IL-17 inhibitors, including secukinumab (Cosentyx, Novartis), ixekizumab (Taltz, Eli Lilly and Company), and brodalumab (Siliq, Valeant Pharmaceuticals); and
IL-23 inhibitor guselkumab (Tremfya, Janssen).
“One of the key issues with systemic medications in psoriasis is their ability to control the disease long-term,” she said.
However, determining long-term efficacy isn’t easy, yet. While there is long-term data for the oldest of the biologic options for psoriasis — TNF inhibitors — there isn’t similar long-term data for the newer IL-17 and IL-23 inhibitors.
From our cumulative experience with TNF inhibitors, we know that they work well initially, but a sizeable proportion will lose response later, she says. As more data becomes available on the newer biologics, we’ll better understand how these perform long-term.
While keeping up with the latest outcomes data can help dermatologists to better manage patient expectations, it can be challenging. Dermatologists should learn the differences in analytical methods.
“Long-term data [interpretation] depends on how the data is analyzed. The ability to discern the evidence and understand what analysis was used in the long-term data gives dermatologists greater ability to understand how the drugs will likely perform in their patient populations,” Dr. Armstrong says.
Different types of analyses yield very different numbers.
“For example, ‘as observed’ analyses tend to give a more optimistic estimate of how a drug does. Another analytical method, such as multiple imputation … tends to give a more conservative estimate,” she said.
ADVERSE EVENT MANAGEMENT
Newer biologics such as IL-17 inhibitors and IL-23 inhibitor generally have a reassuring safety profile; however, it’s important that dermatologists are able to manage adverse events when they occur, she says.
For example, inflammatory bowel diseases, such as Crohn’s disease or ulcerative colitis, have been reported to be associated with IL-17 inhibitors secukinumab (Cosentyx, Novartis), ixekizumab (Taltz, Eli Lilly and Company) and brodalumab (Siliq, Valeant Pharmaceuticals).
“Therefore, one might consider other types of biologics for patients with a personal history of inflammatory bowel diseases. Or, if clinicians feel that they want to still go ahead with the IL-17 inhibitor, they should make sure to inform the patient of the potential risk of exacerbation of inflammatory bowel diseases and be vigilant about monitoring symptoms of exacerbation,” Dr. Armstrong said.
Some biologics that have been approved to treat psoriasis are also approved by the U.S. Food and Drug Administration to treat inflammatory bowel disease. TNF-alpha blockers infliximab (Remicade, Janssen) and adalimumab (Humira, Abbvie) have been shown to effectively treat psoriasis, psoriatic arthritis, ulcerative colitis and Crohn's disease.
Baseline depression and suicidality are often elevated in patients with psoriasis. Among the IL-17 inhibitors, brodalumab has a black box warning for potential increased risk for suicidality.
“Therefore, providers should exercise caution when they prescribe brodalumab in those with increased risk factors for suicidality, such as a history of depression or other mental disorders,” Dr. Armstrong said.
Researchers have shown that people with psoriasis already have a significantly higher likelihood of suicidal ideation, suicide attempts, and completed suicides than people without psoriasis. In particular, younger patients and patients for whom psoriasis is more severe.
Dr. Armstrong is a consultant, advisor and speaker for AbbVie, Janssen, and Lilly; investigator and speaker for Eli Lilly and Company; advisor and investigator for Janssen-Ortho Inc.; consultant for Modernizing Medicine; advisor and investigator for Novartis Pharmaceuticals Corp.; advisor for Pfizer; investigator for Regeneron; and consultant for Sanofi and Science 37.
“S011 - Common, Challenging and Controversial Short Topics in Patient Management,” American Academy of Dermatology 2018 annual meeting. April W. Armstrong M.D., MPH, Friday, February 16, 3:25 p.m.