Use of systemic therapies for treatment of psoriasis in patients with a history of treated solid tumours
Today's report also covers long-term treatment with brodalumab, IL-17 vs. IL-23 inhibitors in pustular psoriasis, and more (1,600 words, 7 minutes, 30 seconds)
The Vender on Psoriasis e-newsletter is supported by an unrestricted grant from Sun Pharma Canada
Good morning and welcome to the seventh issue of Special Reports: Skin Spectrum Weekly presents “Vender on Psoriasis.” This series is based on Dr. Vender’s popular column appearing in each edition of The Chronicle of Skin & Allergy, which offers expert commentary and opinions on current clinical developments in PsO. We’d love to get your feedback and suggestions and invite you to be in touch. Please write to us at health@chronicle.org
Use of Systemic Therapies for Treatment of Psoriasis in Patients with a History of Treated Solid Tumours
Do systemic agents for psoriasis increase the risk of malignancy or malignancy recurrence in patients with a history of treated solid tumours (TSTs)?
Led by Canadian researchers, this study in Dermatol Ther (Heidelb) (2023; 13:867–889) was designed to provide a structured framework to discuss the risks and benefits of systemic psoriasis therapy in these patients with TST.
The expert multidisciplinary panel of dermatologists and oncologists analyzed five indirect indicators of iatrogenic immunosuppression in patients with TSTs, including overall survival, rates of malignancies and infections associated with psoriasis and systemic psoriasis therapies, common disease biochemical pathways, and solid organ transplant outcomes.
Based on their review, the authors drew inference-based conclusions and assigned a level of support for each statement. They found that patients with TSTs and a favourable cancer prognosis had similar outcomes to non-TST patients when treated with systemic psoriasis therapies. However, for patients with TSTs and a poor cancer prognosis, the potential benefits of treating psoriasis may outweigh the theoretical risks.
Although mortality and incidence rates of many solid tumours are on the decline, the researchers noted patients with TSTs face challenges related to delayed cancer treatment toxicities, secondary cancers, and comorbidities associated with common risk factors.
Clinicians expressed concerns about the immunosuppressive nature of systemic psoriasis therapies in patients with past or active malignancy. The study stressed the importance of understanding the cancer prognosis before considering new psoriasis therapies for patients with TSTs. The paper underscored the need for personalized psoriasis treatment decisions based on an understanding of cancer prognosis and informed discussions between healthcare professionals and patients.
Comment: The most important aspect of this paper is having frank and open discussions with the patient and their oncologist. One must be very sensitive to the wishes of the patient and their prognosis. If palliative, and the goal is to make the patient more comfortable, that may require clear skin. Breast cancer is probably the most common solid tumour malignancy encountered and each case must be considered differently. A multidisciplinary approach is the most prudent.
Effectiveness of Long-Term Treatment with Brodalumab on Anxiety or Depressive Symptoms in Japanese Patients with Psoriasis: The ProLOGUE Study
A prospective study called ProLOGUE was conducted in Japan to evaluate the effectiveness of brodalumab on anxiety and depressive symptoms in Japanese patients with psoriasis. The study included 73 patients, predominantly male with a median age of 54 years with plaque psoriasis and had not responded adequately to other therapies.
The results showed the proportion of patients without anxiety symptoms significantly increased from baseline (72.6%) to weeks 12 (88.9%, p=0.008) and 48 (87.7%, p=0.02). However, the proportion of patients without depressive symptoms did not change significantly. The scores on the Generalized Anxiety Disorder-7 and Patient Health Questionnaire-8 significantly decreased after treatment, indicating a reduction in anxiety and depressive symptoms.
The results showed the proportion of patients without anxiety symptoms significantly increased from baseline (72.6%) to weeks 12 (88.9%, p=0.008) and 48 (87.7%, p=0.02). However, the proportion of patients without depressive symptoms did not change significantly. The scores on the Generalized Anxiety Disorder-7 and Patient Health Questionnaire-8 significantly decreased after treatment, indicating a reduction in anxiety and depressive symptoms.
At week 12, the researchers observed that patients with baseline depressive symptoms had more impaired health-related quality of life compared to those without depressive symptoms. However, this impairment generally resolved by week 48.
The researchers note that treatment with brodalumab led to a reduction in self-assessed anxiety and depressive symptoms in Japanese patients with psoriasis. While anxiety symptoms improved significantly, depressive symptoms did not completely resolve with brodalumab treatment. They conclude that patients with psoriasis and depressive symptoms may require long-term treatment to effectively address their mental health needs.
Comment: Psychiatric comorbidities are common with psoriatic disease. Depression and anxiety compounds other comorbidities by isolating the patient and reducing their chances of socializing, exercising, and eating well. This may compound obesity, hyperlipidemia and could lead to cardiovascular comorbidities. Clearing the skin with safe and effective biologics such as brodalumab improves a patient’s quality of life. The sooner in the psoriatic journey the patient is treated the more likely improvement in depression and anxiety will occur. However, some patients do need continuous psychiatric monitoring as the burden of psoriasis still remains in their mind despite disappearing from the skin.
Interleukin-17 vs. Interleukin-23 Inhibitors in Pustular and Erythrodermic Psoriasis: A Retrospective, Multicentre Cohort Study
Pustular and erythrodermic psoriasis are rare and challenging conditions to treat. Recent research has demonstrated the high effectiveness of interleukin (IL)-17 inhibitors in managing these forms of psoriasis. However, the potential of IL-23 inhibitors in treating these same conditions remains largely unknown. This multicentre retrospective study published in the Journal of Clinical Medicine (2023; 12(4):1662) compared the safety, effectiveness, and drug survival of IL-17 and IL-23 inhibitors among patients affected by these rare psoriasis variants.
The study involved 27 patients with erythrodermic psoriasis and 59 patients with pustular psoriasis, including 36 with generalized pustular psoriasis and 23 with palmoplantar pustular psoriasis. These patients received treatment with either an IL-17 or IL-23 inhibitor. The effectiveness of the two drug classes was evaluated using the Psoriasis Area Severity Index (PASI) and the Investigator Global Assessment, which were measured at different time points.
The findings indicated a consistent trend toward a higher rate of PASI 100 responses in patients treated with IL-17 inhibitors compared to those treated with IL-23 inhibitors. Similar trends were observed in other efficacy outcomes. In the cohort of patients with erythrodermic psoriasis, no significant difference in efficacy was observed between the two drug classes at any of the time points. However, among patients with pustular psoriasis, IL-17 inhibitors resulted in significantly higher PASI 90 and PASI 100 response rates at week 12 (IL-23: 19% vs. IL-17: 54%, and IL-23: 6% vs. IL-17: 40%, respectively). Moreover, the percentage of responders to IL-17 inhibition was significantly higher at week 24 (IL-23: 25% vs. IL-17: 74%).
This study suggests that both IL-17 and IL-23 inhibitors are effective in treating pustular and erythrodermic psoriasis. However, IL-17 inhibitors appear to exhibit greater efficacy in managing pustular psoriasis compared to IL-23 inhibitors. Further research is warranted to gain a more comprehensive understanding of the therapeutic potential of IL-23 inhibitors in these rare psoriasis variants.
Comment: Pustular and erythrodermic psoriasis are often excluded from clinical trials, making it difficult to determine which medications may be beneficial for these difficult to treat diseases. Pustular psoriasis can be classified into palmo-plantar pustular and generalized pustular psoriasis. Palmo-plantar pustular psoriasis is extremely difficult to treat and therefore any attempt or any improvement with any medication such as those above is beneficial. However, generalized pustular psoriasis has a new medication called spesolimab—an IL-36 R inhibitor recently approved in North America to treat this difficult disease. One must also be careful with erythrodermic psoriasis because this may mimic Sezary syndrome associated with cutaneous. T cell lymphoma, and so biopsies should be performed.
If you find the contents of this newsletter interesting, please check out the Vender on Psoriasis podcast. It’s available at Apple iTunes, Stitcher, Spotify, or wherever you get your podcasts.
Dr. Ron Vender is a Hamilton-based certified dermatologist with 31 years of clinical practice experience and over 100 clinical trials in psoriasis. He is founder and director of Venderm Innovations in Psoriasis, a centre of excellence for Psoriasis offering a comprehensive management solution for individuals with psoriasis.
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