Long-term drug survival of risankizumab in psoriasis: insights from a real-life multicenter study on hard-to-treat areas.

Psoriasis, a chronic inflammatory condition, often presents challenges in treatment, particularly in areas such as nails, palms/soles, scalp/face, and genitalia. Monoclonal antibodies (mAb) like risankizumab targeting interleukin-23 (IL-23) have emerged as promising treatments, yet data on long-term efficacy remain limited. This multicenter retrospective study aimed to evaluate the drug survival at 12 and 36 months of 191 psoriasis patients treated with risankizumab, focusing on critical areas. Patients, previously unresponsive to first-line therapies, were treated according to Italian Guidelines. Survival analysis revealed a 97.6% one-year and 95% three-year drug survival rate. Secondary ineffectiveness was the primary reason for discontinuation, particularly in palmoplantar involvement cases. Factors such as BMI, gender, age, disease duration, baseline severity, and previous biologic exposure did not significantly impact drug survival, except for palmoplantar psoriasis (HR 4.72). Risankizumab demonstrated prolonged response with low treatment switch requirements, especially notable in challenging areas. Understanding such factors can aid in optimizing therapeutic approaches for improved patient care and long-term outcomes in managing psoriasis. Further research is warranted to refine treatment strategies in difficult-to-treat areas.

Line-field confocal optical coherence tomography: New insights for psoriasis treatment monitoring.

BACKGROUND: Line-field confocal optical coherence tomography (LC-OCT) is a new, valid means for a rapid and non-invasive in vivo examination of the epidermis and upper dermis, allowing digital interpretation and measurement of high-resolution images on a cellular level. Given these properties, it may represent a valid tool for monitoring psoriasis during treatment, allowing a new method to set a precise objective severity of the disease. OBJECTIVES: We aimed to investigate the potentialities of LC-OCT in the non-invasive monitoring of microscopical changes associated with moderate-severe plaque psoriasis (PP) during the treatment with the most common biological drugs. MATERIALS AND METHODS: We performed LC-OCT imaging of PP lesions from 17 patients before and after 8 weeks of treatment. The clinical severity of the single lesions was evaluated using a lesion score (LS), designed considering three parameters: erythema, desquamation and infiltration. LC-OCT images were segmented by artificial intelligence and evaluated based on three microscopic criteria: the thickness of the stratum corneum, the thickness of the living epidermis and the undulation of the dermo-epidermal junction. RESULTS: Line-field confocal optical coherence tomography digital analysis allowed recognition and quantification of the three microscopic criteria, showing a reduction of all these during the follow-up. Furthermore, a high correlation between change in LS and the thickness of the stratum corneum and the thickness of the living epidermis was found. CONCLUSION: Line-field confocal optical coherence tomography can non-invasively monitor the response of PP to different treatments. Morphometric changes occurring in the psoriatic lesion during the 8-week treatment period were identified by in vivo LC-OCT and measured by using artificial intelligence. Although future studies are required, based on these preliminary results, LC-OCT may represent a valid potential tool for precise monitoring of therapeutic response.

Ocular hypertension management in long-term treatments with intravitreal dexamethasone implants: a 3-year experience.

PURPOSE: A commonly recognized complication of intravitreal steroids is ocular hypertension (OHT).The aim of this study was to investigate the effectiveness of pharmacotherapy in controlling this side effect, even in patients receiving sequential injections. METHODS: A total of 146 injections were performed on 78 patients over 3 years. 78 eyes were treated with 1 injection, 44 eyes were treated with 2 injections; 24 eyes were treated with 3 injections. The intravitreal corticosteroid used in this observational study is 0.7mg dexamethasone, commercially known as 0.7mg Ozurdex®. RESULTS: Following the first injection, mean intraocular pressure (IOP) increased by 1,90 mmHg. Following the second injection, mean IOP increased by 0.23 mmHg. Following the third injection, there was no statistically significant change. Patients with IOP >= 21mmHg (7% of all participants) were started on topical pressure-lowering medications. CONCLUSIONS: Intravitreal dexamethasone implants increased IOP of variable degrees in different patients. However, secondary OHT was effectively controlled with pharmacotherapy alone. This allowed for continuation of dexamethasone therapy.

Loss of tumor progression locus 2 (tpl2) enhances tumorigenesis and inflammation in two-stage skin carcinogenesis.

Tumor progression locus 2 (Tpl2) is a serine/threonine kinase in the mitogen-activated protein kinase signal transduction cascade known to regulate inflammatory pathways. Previously identified as an oncogene, its mutation or overexpression is reported in a variety of human cancers. To address its role in skin carcinogenesis, Tpl2(-/-) or wild-type (WT) C57BL/6 mice were subjected to a two-stage dimethylbenzanthracene/12-O-tetradecanoylphorbol-13-acetate (TPA) mouse skin carcinogenesis model. Tpl2(-/-) mice developed a significantly higher incidence of tumors (80%) than WT mice (17%), as well as a reduced tumor latency and a significantly higher number of total tumors (113 vs 6). Moreover, Tpl2(-/-) mice treated with TPA experienced significantly higher nuclear factor kappaB (NF-κB) activation, edema, infiltrating neutrophils and production of proinflammatory cytokines than did WT mice. We investigated the role of the p38, JNK, MEK and NF-κB signaling pathways both in vitro and in vivo in WT and Tpl2(-/-) mice by using inhibitors for each of these pathways. We confirmed that the proinflammatory effect in Tpl2(-/-) mice was due to heightened activity of the NF-κB pathway. These studies indicate that Tpl2 may serve more as a tumor suppressor than as an oncogene in chemically induced skin carcinogenesis, with its absence contributing to both tumorigenesis and inflammation.