This article was selected to provide additional insights into the relationship between psoriasis and the use of immune checkpoint inhibitors (ICIs) in cancer treatment.
Immunotherapy with ICIs has revolutionized cancer treatment, particularly in advanced stages1. Survival improvement varies depending on the tumor type, disease stage, and individual response to treatment, but the progress has been remarkable.
Just over 15 years ago, before immunotherapy, the five-year survival rate for patients with metastatic melanoma was around 5-10%2. Recent studies have demonstrated a 52% survival rate at ten years3. Similarly, significant improvements have been observed in non-small cell lung cancer1, small cell lung cancer4, metastatic renal cancer5, and advanced bladder cancer6.
However, ICI use is associated with immune-mediated adverse effects affecting multiple organs and systems, including cutaneous manifestations such as vitiligo and psoriasis7, 8. While the association between ICIs and psoriasis is already recognized, gaps remain in understanding the underlying pathophysiological mechanisms, the actual frequency of these events, and the best management strategies for oncology patients who develop or experience worsening of the condition.
This article presents a national cohort study designed as a target trial emulation. Using data from the Taiwan National Health Insurance and the Taiwan Cancer Registry, the study investigated the association between ICI use and the risk of psoriasis development in cancer patients.
With an aging population and rising cancer incidence, along with the success of immunotherapy in previously untreatable malignancies, the use of ICIs is expected to increase. As dermatologists, it is crucial that we better understand these risks to identify and manage affected patients accurately. A thorough evaluation of cutaneous adverse effects associated with immunotherapy is essential to minimize negative outcomes and improve patients’ quality of life.
This study evaluated the association between the use of immune checkpoint inhibitors (ICIs) in oncology patients and the development of psoriasis, clearly demonstrating a positive correlation. Using data from the population-based registry of the Taiwan National Health Insurance system, a nationwide cohort study was conducted, including all patients diagnosed with clinical stage III or IV cancer or metastatic cancer (ICD-10 codes C77-C79) who received antineoplastic treatment between January 1, 2019, and June 30, 20219.
Oncologic treatments were categorized into conventional chemotherapy, including alkylating agents, antimetabolites, plant alkaloids, cytotoxic antibiotics, and other antineoplastic agents; protein kinase inhibitors; monoclonal antibodies; and ICI-based immunotherapy, specifically PD-1 and PD-L1 inhibitors, as Taiwan’s healthcare system does not cover CTLA-4 inhibitors. The first three groups were classified as non-ICI users, while the fourth group was categorized as ICI users.
Patients with a prior history of psoriasis were excluded to avoid counting disease exacerbations, ensuring a more accurate correlation between ICI use and the risk of developing new-onset psoriasis. The primary endpoint was the incidence of psoriasis, defined as the presence of at least one diagnosis (ICD-10 code L40) during the follow-up period. Each patient was monitored until the occurrence of one of the following events: psoriasis diagnosis, death, or December 31, 2021 (the last date in the study database), whichever occurred first.
Over a follow-up period totaling 197,107 person-years, 295 patients (0.2%) were diagnosed with psoriasis. The incidence rates were 5.76 cases per 1,000 person-years among ICI users and 1.44 cases per 1,000 person-years among non-ICI users.
In the initial analysis, a Cox proportional hazards regression model demonstrated an adjusted hazard ratio (HR) of 3.52 for psoriasis in ICI users compared to non-users after controlling for demographic characteristics, comorbidities, and outpatient visits. Following the application of inverse probability of treatment weighting (IPTW), the IPTW-adjusted HR for psoriasis in ICI users versus non-users was 3.31.
ICI users exhibited a significantly higher risk of developing psoriasis across all follow-up periods, with the greatest risk observed during the first 180 days of follow-up.
The risk of psoriasis was statistically significant among ICI users over the age of 66 [HR:7.87(4.02−15.42)] compared to those under 66 [HR:1.32(0.45−3.81)]. Additionally, male patients undergoing ICI therapy had a significantly higher risk [HR:3.58(1.88−6.82)].
ICIs were associated with a significantly increased risk of psoriasis compared to other oncologic therapies, including conventional chemotherapy (IPTW−adjusted SHR: 2.69), monoclonal antibodies (IPTW−adjusted SHR: 2.31), and protease inhibitors (IPTW−adjusted SHR: 2.34).
No statistically significant differences were observed in the number of outpatient or dermatologic visits between ICI users and non-users.
It remains unclear whether ICI use induces a psoriasiform reaction or true psoriasis. However, these reactions appear to resemble chronic psoriasis more closely than the paradoxical psoriasiform reactions induced by anti-TNF therapy10. Differentiating between true psoriasis and an ICI-induced reaction may be challenging, but this distinction is likely of limited clinical relevance.
The proposed pathophysiological mechanism is highly plausible, as ICIs block inhibitory pathways such as PD-1/PD-L1 and CTLA-4, which cancer cells use to evade immune surveillance. This blockade leads to T-cell reactivation, enhancing immune activity and potentially triggering inflammation and autoimmunity, which may manifest as psoriasis11, 12.
Managing this condition is particularly challenging, as immune activation plays a crucial role in tumor control8. Treating ICI-induced psoriasis may reduce immune activity, potentially compromising tumor suppression. Although this risk has been documented in a case of pembrolizumab-induced psoriasis, in which treatment with secukinumab led to disease progression13, there are reports where oncologic progression was not observed. Cases of psoriasis and psoriatic arthritis induced by ICIs and treated with apremilast, secukinumab, ixekizumab, guselkumab, and risankizumab have been successfully managed while maintaining oncologic control14-16.
Additionally, there are recommendations that ICI-induced psoriasis should be treated according to its severity, which may include topical treatments, non-biologic systemic therapies, and biologic agents17.
The authors clearly demonstrated that ICI use is significantly associated with the development of psoriasis compared to other oncologic treatments, particularly among older men. A key strength of this study is its use of a large-scale national database, further enhanced by a well-defined target trial emulation framework.
The authors highlight a strong association between ICI use and an increased risk of new-onset psoriasis, as they excluded patients with a prior psoriasis diagnosis. However, given the study’s database-based nature, pre-existing psoriasis cases may not have been properly coded. The absence of a diagnostic code does not necessarily indicate the absence of disease. Mild or localized forms, particularly those affecting the nails or the intergluteal fold, are common and often go undiagnosed as psoriasis.
Additionally, the study does not account for factors such as family history of psoriasis, genetic predisposition, lifestyle, body mass index, and environmental exposures, all of which may influence psoriasis incidence.
While including ICD codes for psoriatic arthritis could have introduced potential confounding, their analysis might have provided a more comprehensive understanding of the association between ICIs and psoriatic spectrum diseases18.
A better understanding of the risks associated with psoriasis or psoriasiform reactions due to ICI use is essential. However, the treatment of metastatic cancer remains the priority. As dermatologists, we must be prepared to recognize and manage these manifestations, ensuring patients’ quality of life while allowing them to continue oncologic therapies that offer significant survival benefits.
Immune Checkpoint Inhibitors Significantly Raise Psoriasis Risk: National Cohort Study Findings
Leandro Linhares Leite, MD, MSc
Hospital de Clínicas de Porto Alegre
Porto Alegre, Brazil
IPC Councilor
PUBLICATIONS
Psoriasis Risk With Immune Checkpoint Inhibitors. To SY, Lee CH, Chen YH, Hsu CL, Yang HW, Jiang YS, et al. JAMA Dermatol. 2025;161(1):31-8.
Why This Article Was Chosen
This article was selected to provide additional insights into the relationship between psoriasis and the use of immune checkpoint inhibitors (ICIs) in cancer treatment.
Immunotherapy with ICIs has revolutionized cancer treatment, particularly in advanced stages1. Survival improvement varies depending on the tumor type, disease stage, and individual response to treatment, but the progress has been remarkable.
Just over 15 years ago, before immunotherapy, the five-year survival rate for patients with metastatic melanoma was around 5-10%2. Recent studies have demonstrated a 52% survival rate at ten years3. Similarly, significant improvements have been observed in non-small cell lung cancer1, small cell lung cancer4, metastatic renal cancer5, and advanced bladder cancer6.
However, ICI use is associated with immune-mediated adverse effects affecting multiple organs and systems, including cutaneous manifestations such as vitiligo and psoriasis7, 8. While the association between ICIs and psoriasis is already recognized, gaps remain in understanding the underlying pathophysiological mechanisms, the actual frequency of these events, and the best management strategies for oncology patients who develop or experience worsening of the condition.
This article presents a national cohort study designed as a target trial emulation. Using data from the Taiwan National Health Insurance and the Taiwan Cancer Registry, the study investigated the association between ICI use and the risk of psoriasis development in cancer patients.
With an aging population and rising cancer incidence, along with the success of immunotherapy in previously untreatable malignancies, the use of ICIs is expected to increase. As dermatologists, it is crucial that we better understand these risks to identify and manage affected patients accurately. A thorough evaluation of cutaneous adverse effects associated with immunotherapy is essential to minimize negative outcomes and improve patients’ quality of life.
Commentary
This study evaluated the association between the use of immune checkpoint inhibitors (ICIs) in oncology patients and the development of psoriasis, clearly demonstrating a positive correlation. Using data from the population-based registry of the Taiwan National Health Insurance system, a nationwide cohort study was conducted, including all patients diagnosed with clinical stage III or IV cancer or metastatic cancer (ICD-10 codes C77-C79) who received antineoplastic treatment between January 1, 2019, and June 30, 20219.
Oncologic treatments were categorized into conventional chemotherapy, including alkylating agents, antimetabolites, plant alkaloids, cytotoxic antibiotics, and other antineoplastic agents; protein kinase inhibitors; monoclonal antibodies; and ICI-based immunotherapy, specifically PD-1 and PD-L1 inhibitors, as Taiwan’s healthcare system does not cover CTLA-4 inhibitors. The first three groups were classified as non-ICI users, while the fourth group was categorized as ICI users.
Patients with a prior history of psoriasis were excluded to avoid counting disease exacerbations, ensuring a more accurate correlation between ICI use and the risk of developing new-onset psoriasis. The primary endpoint was the incidence of psoriasis, defined as the presence of at least one diagnosis (ICD-10 code L40) during the follow-up period. Each patient was monitored until the occurrence of one of the following events: psoriasis diagnosis, death, or December 31, 2021 (the last date in the study database), whichever occurred first.
Over a follow-up period totaling 197,107 person-years, 295 patients (0.2%) were diagnosed with psoriasis. The incidence rates were 5.76 cases per 1,000 person-years among ICI users and 1.44 cases per 1,000 person-years among non-ICI users.
In the initial analysis, a Cox proportional hazards regression model demonstrated an adjusted hazard ratio (HR) of 3.52 for psoriasis in ICI users compared to non-users after controlling for demographic characteristics, comorbidities, and outpatient visits. Following the application of inverse probability of treatment weighting (IPTW), the IPTW-adjusted HR for psoriasis in ICI users versus non-users was 3.31.
ICI users exhibited a significantly higher risk of developing psoriasis across all follow-up periods, with the greatest risk observed during the first 180 days of follow-up.
The risk of psoriasis was statistically significant among ICI users over the age of 66 [HR:7.87(4.02−15.42)] compared to those under 66 [HR:1.32(0.45−3.81)]. Additionally, male patients undergoing ICI therapy had a significantly higher risk [HR:3.58(1.88−6.82)].
ICIs were associated with a significantly increased risk of psoriasis compared to other oncologic therapies, including conventional chemotherapy (IPTW−adjusted SHR: 2.69), monoclonal antibodies (IPTW−adjusted SHR: 2.31), and protease inhibitors (IPTW−adjusted SHR: 2.34).
No statistically significant differences were observed in the number of outpatient or dermatologic visits between ICI users and non-users.
It remains unclear whether ICI use induces a psoriasiform reaction or true psoriasis. However, these reactions appear to resemble chronic psoriasis more closely than the paradoxical psoriasiform reactions induced by anti-TNF therapy10. Differentiating between true psoriasis and an ICI-induced reaction may be challenging, but this distinction is likely of limited clinical relevance.
The proposed pathophysiological mechanism is highly plausible, as ICIs block inhibitory pathways such as PD-1/PD-L1 and CTLA-4, which cancer cells use to evade immune surveillance. This blockade leads to T-cell reactivation, enhancing immune activity and potentially triggering inflammation and autoimmunity, which may manifest as psoriasis11, 12.
Managing this condition is particularly challenging, as immune activation plays a crucial role in tumor control8. Treating ICI-induced psoriasis may reduce immune activity, potentially compromising tumor suppression. Although this risk has been documented in a case of pembrolizumab-induced psoriasis, in which treatment with secukinumab led to disease progression13, there are reports where oncologic progression was not observed. Cases of psoriasis and psoriatic arthritis induced by ICIs and treated with apremilast, secukinumab, ixekizumab, guselkumab, and risankizumab have been successfully managed while maintaining oncologic control14-16.
Additionally, there are recommendations that ICI-induced psoriasis should be treated according to its severity, which may include topical treatments, non-biologic systemic therapies, and biologic agents17.
The authors clearly demonstrated that ICI use is significantly associated with the development of psoriasis compared to other oncologic treatments, particularly among older men. A key strength of this study is its use of a large-scale national database, further enhanced by a well-defined target trial emulation framework.
The authors highlight a strong association between ICI use and an increased risk of new-onset psoriasis, as they excluded patients with a prior psoriasis diagnosis. However, given the study’s database-based nature, pre-existing psoriasis cases may not have been properly coded. The absence of a diagnostic code does not necessarily indicate the absence of disease. Mild or localized forms, particularly those affecting the nails or the intergluteal fold, are common and often go undiagnosed as psoriasis.
Additionally, the study does not account for factors such as family history of psoriasis, genetic predisposition, lifestyle, body mass index, and environmental exposures, all of which may influence psoriasis incidence.
While including ICD codes for psoriatic arthritis could have introduced potential confounding, their analysis might have provided a more comprehensive understanding of the association between ICIs and psoriatic spectrum diseases18.
A better understanding of the risks associated with psoriasis or psoriasiform reactions due to ICI use is essential. However, the treatment of metastatic cancer remains the priority. As dermatologists, we must be prepared to recognize and manage these manifestations, ensuring patients’ quality of life while allowing them to continue oncologic therapies that offer significant survival benefits.
References
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