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- Spotlight on risankizumab and its potential in the treatment of plaque psoriasis: evidence to datePublication . Machado, Á; Torres, T.Psoriasis is a common chronic immune-mediated skin disease, with systemic involvement and significant impact in patients' quality of life. Several highly specific treatments have been developed over the years, such as tumor necrosis factor-α inhibitors, a nonselective IL-23 inhibitor (ustekinumab), and most recently IL-17 inhibitors. Risankizumab is a monoclonal antibody which targets IL-23p19 without binding IL-12. This novel therapeutic approach is expected to have advantages over the recently approved anti-IL-17 agents, such as the avoidance of Candida infections and neutropenia. In addition, unlike ustekinumab, the selective inhibition of IL-23 may preserve IL-12-dependent functions such as protection against infections and tumor immune surveillance. Risankizumab showed an excellent efficacy when compared to placebo and ustekinumab, with higher Psoriasis Area Severity Index (PASI) 75, PASI 90, and PASI 100 rates, along with a convenient every 12-week maintenance dosing regimen. Overall, risankizumab was well tolerated and the most common adverse event was upper respiratory tract infection. In the near future, further data will be available not only in psoriasis but also in Crohn's disease and psoriatic arthritis fields. Head-to-head trials comparing risankizumab with other IL-23 inhibitors and with IL-17 inhibitors will be crucial to reveal the role of risankizumab in the treatment of psoriasis.
- Diagnosis, Screening and Treatment of Patients with Palmoplantar Pustulosis (PPP): A Review of Current Practices and RecommendationsPublication . Freitas, Egídio; Rodrigues, Maria Alexandra; T, TorresPalmoplantar pustulosis (PPP) is a rare, chronic, recurrent inflammatory disease that affects the palms and/or the soles with sterile, erupting pustules, which are debilitating and usually resistant to treatment. It has genetic, histopathologic and clinical features that are not present in psoriasis; thus, it can be classified as a variant of psoriasis or as a separate entity. Smoking and upper respiratory infections have been suggested as main triggers of PPP. PPP is a challenging disease to manage, and the treatment approach involves both topical and systemic therapies, as well as phototherapy and targeted molecules. No gold standard therapy has yet been identified, and none of the treatments are curative. In patients with mild disease, control may be achieved with on-demand occlusion of topical agents. In patients with moderate-to-severe PPP, phototherapy or a classical systemic agent (acitretin being the best treatment option, especially in combination with PUVA) may be effective. Refractory patients or those with contraindications to use these therapies may be good candidates for apremilast or biologic therapy, particularly anti-IL-17A and anti-IL-23 agents. Recent PPP trials are focusing on blockage of IL-36 or IL-1 pathways, which play an important role in innate immunity. Indeed, IL-36 isoforms have been strongly implicated in the pathogenesis of psoriasis. Therefore, blockage of the IL-36 pathway has become a new treatment target in PPP, and three studies are currently evaluating the use of monoclonal antibodies that block the IL-36 receptor in PPP: ANB019 and spesolimab (BI 655130). In this review, we explore the diagnosis, screening and treatment of patients with PPP.
- Guselkumab for the treatment of psoriasis - evidence to datePublication . Nogueira, Miguel; Torres, T.Psoriasis is a chronic, immune-mediated, inflammatory, and debilitating skin disease with significant impact on patients' quality of life. Its pathogenesis is complex and not yet fully understood. However, the IL-23/IL-17 axis is currently considered the main pathogenic pathway in psoriasis. Guselkumab is a fully human immunoglobulin G1 λ (IgG1λ) monoclonal antibody (mAb) that binds to the p19 subunit of IL-23. It is the first of its class, already approved by the US Food and Drug Administration (FDA), as well as the European Medicines Agency (EMA) for the treatment of adult patients with moderate-to-severe plaque psoriasis who are candidates for either systemic therapy or phototherapy. Several clinical trials have demonstrated potential benefits of guselkumab over other already approved immunomodulators in terms of safety and efficacy. The results of the head-to-head trial ECLIPSE were recently released and are addressed in this review. They contribute to the increasing confidence in guselkumab, demonstrating great potential for long-term treatment of psoriasis. However, further long-term data and additional comparative studies will be essential for positioning guselkumab in the therapeutic armamentarium for psoriasis.
- Update on Atopic DermatitisPublication . Torres, T.; Ferreira, E.; Gonçalo, M.; Mendes-Bastos, P.; Selores, M.; Filipe, P.With an increasing prevalence during the past decades, atopic dermatitis has become a global health issue. A literature search following a targeted approach was undertaken to perform this non-systematic review, which intends to provide an overview of the epidemiology, pathophysiology, clinical features, comorbidities, and current therapies for the treatment of atopic dermatitis. In sum, this is a heterogeneous skin disorder associated with variable morphology, distribution, and disease course. Although not completely understood, its pathogenesis is complex and seems to result from a combination of genetic and environmental factors that induce skin barrier dysfunction, cutaneous and systemic immune dysregulation, skin microbiota dysbiosis, and a strong genetic influence. Diagnosis is based on specific criteria that consider patient and family history and clinical manifestations. Overall disease severity must be determined by evaluating both objective signs and subjective symptoms. Therapeutic goals require a multistep approach, focusing on reducing pruritus and establishing disease control. Patients should be advised on basic skin care and avoidance of triggers. Topical anti-inflammatory agents should be considered in disease flares or chronic/recurrent lesions. In case of inadequate response, phototherapy, systemic immunosuppressants and, more recently, dupilumab, should be added. Nevertheless, the treatment of moderate-to-severe atopic dermatitis remains challenging and novel, efficacious, safe and targeted treatments are urgently needed. In conclusion, although the last few years have seen important improvement in the understanding of the disease, future research in atopic dermatitis will continue exploring gene-environment interactions and how it affects pathophysiology, disease severity, and treatment outcomes.
- Conjunctivitis in patients with atopic dermatitis treated with dupilumabPublication . Ferreira, Sandra; Torres, TiagoAtopic dermatitis (AD) is a common, chronic, inflammatory skin disorder with high physical and emotional burden. Robust evidence suggests that interleukin (IL)-4 and IL-13 are key cytokines in the immunopathogenesis of AD. New emerging agents include dupilumab, a fully human monoclonal antibody directed against the IL-4 receptor a subunit that blocks both IL-4 and IL-13 signaling and has shown significant efficacy in patients with moderate-to-severe AD. Dupilumab is approved for the treatment of moderate-to-severe AD, moderate-to-severe eosinophilic or oral corticosteroid-dependent asthma, and chronic rhinosinusitis with nasal polyps. Data from phase phase 2 and 3 studies have revealed that dupilumab generally has a low rate of adverse events, although an increased incidence of mild-to-moderate conjunctivitis has been reported for dupilumab compared with placebo. The present paper reviews the data of dupilumab-associated conjunctivitis and risk factors in adults with moderate-to-severe AD and other atopic diseases in dupilumab clinical trials and addresses the characteristics and treatment options available for this clinically highly relevant condition. Additionally, it presents data from ten studies in the real-life setting with dupilumab. Dupilumab-associated conjunctivitis incidence is higher in AD, although most cases are mild-to-moderate and have good response to topical treatment, with no need to suspend dupilumab therapy
- The successful treatment with ixekizumab in a multi-failure psoriasis patientPublication . Azevedo, A.; Torres, T.We report a patient with severe psoriasis who failed to respond to phototherapy, conventional systemic treatment and four biologic agents (etanercept, ustekinumab, adalimumab and secukinumab). Combination of a higher-dose secukinumab regimen with phototherapy had no success. Remarkably, ixekizumab, an IL-17A inhibitor, provided almost complete psoriasis clearance after 24 weeks of treatment. The reason for the success of ixekizumab after the failure to respond to a biologic with same mechanism of action is still unknown. Interestingly, failure of secukinumab does not preclude future therapeutic success with a second IL-17A-inhibitor.
- The Changing Landscape of Atopic Dermatitis - Focusing on JAK InhibitorsPublication . Rodrigues, M.A.; Torres, Tiago
- Neurofibromatose Tipo 1: Envolvimento Cutâneo ExuberantePublication . Ferreira, Sandra; Selores, Manuela; Torres, Tiago
- Ustekinumab in Real-Life Practice: Experience in 116 Patients with Moderate-To-Severe PsoriasisPublication . Raposo, I.; Bettencourt, A.; Leite, L.; Selores, M.; T, TorresUstekinumab is a monoclonal antibody directed against the p40 subunit common to both IL-12 and IL-23 cytokines. Although the evidence of ustekinumab efficacy and safety in clinical trials is extensively recognized, data on its use in clinical practice is limited. Our objective is to report on the real-life experience of two Portuguese dermatology departments with ustekinumab in patients with moderate to severe psoriasis, and to identify the clinical characteristics associated with a weaker clinical response.
- Psoriasis, biologic therapy, and the pandemic of the 21st centuryPublication . Nogueira, Miguel; Vender, Ron; Torres, TiagoThe pandemic known as coronavirus disease-19 (COVID-19) has quickly spread worldwide, with a significant impact on lives all over the world. The complexity related to the new coronavirus and the clinical syndrome it causes is not yet fully understood. The impact of COVID-19 on patients with psoriasis under biologic agents is continuously being observed in this rapidly changing pandemic. A case-by-case evaluation must be made by dermatologists, and the final decision should be discussed and decided by both the patient and the specialist. Observations reveal that immunosuppressive therapy may have a role in the treatment of this virus, placing emphasis on the scenario of safety through maintenance of therapy with biologic agents, especially when there are no signs or symptoms related to the infection or contact with an infected patient.