Psoriasis is a chronic inflammatory disease with an established genetic background. The HLA-Cw*06 allele and different polymorphisms in genes involved in inflammatory responses and keratinocyte proliferation have been associated with the development of the disease. Despite the effectiveness and safety of psoriasis treatment, a significant percentage of patients still do not achieve adequate disease control. Pharmacogenetic and pharmacogenomic studies on how genetic variations affect drug efficacy and toxicity could provide important clues in this respect. This comprehensive review assessed the available evidence for the role that those different genetic variations may play in the response to psoriasis treatment. One hundred fourteen articles were included in this qualitative synthesis. VDR gene polymorphisms may influence the response to topical vitamin D analogs and phototherapy. Variations affecting the ABC transporter seem to play a role in methotrexate and cyclosporine outcomes. Several single-nucleotide polymorphisms affecting different genes are involved with anti-TNF-α response modulation (TNF-α, TNFRSF1A, TNFRSF1B, TNFAIP3, FCGR2A, FCGR3A, IL-17F, IL-17R, and IL-23R, among others) with conflicting results. HLA-Cw*06 has been the most extensively studied allele, although it has only been robustly related to the response to ustekinumab. However, further research is needed to firmly establish the usefulness of these genetic biomarkers in clinical practice.
7 March 2024 in Journal of Investigative Dermatology
Despite significant advances in psoriasis treatment, off-label dosing studies of psoriasis biologic therapies are limited. In this retrospective case series, medical records from 28 patients with moderate-to-severe psoriasis treated with bimekizumab during 64-week period from May 2023 to October 2024 at the Psoriasis Unit of the Grupo Jaen (Madrid, Spain), were evaluated. Patients were managed with an off-label, as-needed, dosing strategy, with all patients initially receiving two 320 mg doses of bimekizumab at Weeks 0 and 4; subsequent doses were administered only if a given patient dropped below a PASI90 response. Primary outcome was the percentage of patients that achieved and maintained optimal skin control over time, defined as achieving a PASI90 response. Twenty-seven out of the 28 patients achieved a PASI90 response after the first two bimekizumab doses, and all maintained PASI90 responses with as-needed dosing over time. One patient achieved PASI90 after a single dose of bimekizumab, and voluntarily decided not to receive a second dose. No adverse events were observed. Larger prospective studies comparing efficacy and safety of this off-label, as needed, bimekizumab dosing regimen with standard on-label dosing are necessary to corroborate these findings.
Background: Psoriasis is an inflammatory disease primarily treated through molecular-targeted therapies. However, emerging evidence suggests that dietary interventions may also play a role in managing inflammation associated with this condition. The Mediterranean diet (MedDiet), prevalent in southern European countries, has been widely recognized for its ability to reduce cardiovascular mortality, largely due to its anti-inflammatory properties. This anti-inflammatory potential has prompted interest in exploring the MedDiet’s role in immune-mediated diseases, including psoriasis. Observational studies have indicated potential benefits, such as reductions in the Psoriasis Area and Severity Index. However, there is a need for well-designed clinical trials to address the methodological limitations of these studies and to establish specific dietary recommendations for psoriasis. Objective: This study aims to evaluate the impact of an intensive dietary intervention based on the MedDiet in patients with psoriasis. The study will assess the effects of this intervention on skin involvement, metabolic parameters, and inflammatory cytokines. In addition, the emotional well-being and quality of life of participants will be evaluated using validated questionnaires. A methodological analysis will also be conducted to enhance the design of future large-scale clinical trials. Methods: An open-label, single-blinded (evaluator) randomized controlled trial was designed to assess the impact of a high-intensity MedDiet intervention in patients with mild-to-moderate psoriasis. A total of 38 patients will be randomly assigned into 2 groups—an intervention group receiving the MedDiet intervention and a control group receiving standard care. The intervention group will participate in dietary education sessions aimed at adopting the MedDiet over 4 months, with monthly monitoring by experienced nutritionists. Participants will receive 500 mL of extra virgin olive oil per week, along with informative materials, recipes, and weekly menus. In contrast, the control group will receive standard low-fat diet recommendations without nutritionist monitoring. All participants will undergo a baseline visit, a 2-month follow-up visit, and a final visit at 4 months. Blood tests will be conducted at the beginning and end of the study. This study protocol was approved by the Institutional Review Board of the Hospital Ramón y Cajal (Madrid) in July 2023. Results: Enrollment concluded in October 2024, with data collection set to finish by February 2025. The findings will be presented at national and international conferences and published in peer-reviewed journals. Conclusions: This protocol outlines the design of a clinical trial that implements the MedDiet in patients with psoriasis to evaluate its benefits on skin involvement, systemic inflammation, and quality of life. Trial Registration: ClinicalTrials.gov NCT06257641; https://clinicaltrials.gov/study/NCT06257641 International Registered Report Identifier (IRRID): DERR1-10.2196/64277