番茄社区

PD-1 and PD-L1 immune checkpoint inhibitors (ICIs) for treating advanced cancer were associated with an increased risk of new-onset psoriasis, a large observational study from Taiwan found.

In an as-started analysis, the risk for psoriasis among patients with stage III/IV cancers was two- to three-fold higher among ICI users when compared against controls who received chemotherapy or targeted agents (5.76 vs 1.44 cases per 1,000 person-years, respectively):

• HR 3.31 (95% CI 1.93-5.68) with adjusted inverse probability of treatment weighting (IPTW)
• Subdistribution HR 2.43 (95% CI 1.41-4.20) with adjusted IPTW

Findings from the nationwide cohort were consistent in on-treatment analyses (16.13 vs 2.35 per 1,000 person-years) and across all follow-up intervals and all sensitivity analyses, reported Li-Ting Kao, PhD, of National Defense Medical Center in Taipei City, Taiwan, and colleagues.

"Although this adverse effect is relatively uncommon, it is important for medical professionals, clinicians, and caregivers to be aware of this potential risk to improve skin health and ensure optimal cancer care," the group concluded in .

This study provides robust evidence of a significantly elevated risk of new-onset psoriasis specifically in ICI users across a large cancer patient cohort, commented Shoshana Marmon, MD, PhD, of New York Medical College in Valhalla.

"Oncologists should monitor for early signs of psoriasis after starting ICIs, educate patients to report skin changes promptly, and collaborate with dermatologists on how to best manage psoriasis without disrupting cancer treatment," Marmon told 番茄社区.

The mechanism behind an ICI-psoriasis link is unknown, Kao and colleagues noted.

However, "ICIs block inhibitory pathways, such as PD-1/PD-L1 and CTLA-4, which cancer cells use to evade the immune system, thereby leading to the reactivation of T cells," they wrote. "This may enhance immune activity and can quickly lead to inflammation and autoimmunity, manifesting as psoriasis."

Notably, the researchers reported that the excess risk of psoriasis was highest within the first 180 days of ICI use, with a subdistribution HR of 7.69 (95% CI 3.98-14.85) in the IPTW adjusted as-treated analysis, which was meant to mimic an intent-to-treat analysis.

The findings confirm what is seen in clinical practice, observed Steven Daveluy, MD, of Wayne State Dermatology in Dearborn, Michigan.

"One of the interesting aspects of immune-related [adverse events] is their ability to present just about any time during treatment or even after treatment is completed," said Daveluy, who was not involved with the study. "The authors confirmed this finding in psoriasis, noting it could show up anywhere between 2 and 150 weeks of treatment, with a median of 4 weeks."

As for managing incident psoriasis that requires more than topical agents, Daveluy said biologics can help gain control of the chronic skin condition while keeping patients on cancer treatment. He usually opts for an interleukin (IL)-17 inhibitor first.

"There is evidence that cancers utilize the IL-17 pathway for growth and angiogenesis," Daveluy said. "IL-17 inhibitors are under study to investigate their potential benefits as part of a cancer treatment regimen." IL-23 inhibitors also appear safe in cancer patients, but more data would help to confirm that, he added.

For their study, Kao and co-authors relied on data from the Taiwan National Health Insurance database -- which captures more than 99% of residents -- and the Taiwan Cancer Registry.

They found records of 135,230 stage III/IV cancer patients (mean 63 years, 45% female) who received antineoplastic medications from January 2019 to June 2021, including 3,188 patients eligible for the ICI group. Over an average follow-up of about 18 months (197,107 person-years), psoriasis was diagnosed in 295 patients (0.2%).

In the absence of randomization, the researchers used the IPTW approach to balance baseline variables between ICI and non-ICI groups. Among the ICI group, most users took the agents as monotherapy (74%), with the remaining on ICI therapy in combination with targeted therapies or cytotoxic therapies.

Subgroup analyses showed potentially higher risks for psoriasis among ICI users who were over age 65 or men, but this was not supported by subsequent statistical testing. There were no significant differences between ICI users and non-ICI users in rates of outpatient or dermatology visits per month.

Kao and colleagues acknowledged study limitations, including the lack of details on psoriasis severity and missing patient variables (e.g., lifestyle, genetic factors, body mass index, and environmental exposures) that may be related to psoriasis. Additionally, Taiwan's insurance database did not cover CTLA-4 inhibitors, which limits the generalizability of results beyond PD-1 and PD-L1 inhibitors.

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