Alterations in the innate and adaptive immunity underpin psoriasis pathophysiology, with the Th17 cells subset now recognized as the fundamental cells in the key controlling pathway involved in its pathogenesis. Since psoriasis is a systemic disease with important comorbidity, further knowledge on the interleukin (IL)-23/Th17 axis led to the hypothesis that there may be shared pathogenic pathways between primary skin disease and comorbidity. Psoriasis has been identified as a risk factor for cardiovascular and metabolic disease, and increasing evidence gives support to this epidemiological observation from the clinical-pathologically field. As an example, increased levels of IL-23 and IL-23R have been found in human atherosclerotic plaque, and levels correlated with symptom duration and mortality. Also, upregulation of IL-23/IL-17 seems to play an important role in both myocardial damage and stroke, with interesting reports on deleterious effect neutralization after administration of related anti-bodies in both associated conditions. In diabetic patients, increased levels of IL-23/IL-17 have also been observed and available data support a synergistic role of IL-23/IL-17 in b-cells damage. In obesity, signs of an expansion of Th17 subset in adipose tissue have been reported, as well as elevated concentrations of IL-23 in obese patients. In non-alcoholic fatty liver disease, closely related to metabolic syndrome, but also in other mentioned cardiometabolic disorders, a predominance of IL-23 and other related proinflammatory factors has been identified as participating in their pathogenesis. Thus, the involvement of the IL-23/Th17 axis in these shared psoriasis-cardiometabolic pathogenic mechanisms is reviewed and discussed in the light of the existing preclinical and clinical evidence, including that from comorbid psoriasis patients.
The advances in psoriasis management currently allow achieving a good control of the disease. In particular, with the latest developed molecules, available evidence suggests that it is possible to pose an ambitious therapeutic goal, such as a Dermatology Life Quality Index 0/1, a Physician Global Assessment 0/1, or a Psoriasis Area and Severity Index 90/100 response. However, patients often fail to achieve the complete clearance of their cutaneous lesions or the improvement of disease factors that impair their quality of life. To optimize the treatment of psoriasis, it is not enough to define precisely the therapeutic objective, but also to adapt the therapeutic strategy to make the necessary modifications in case of not achieving it at the time point (at the end of the induction phase, or every 3-6 months) to be agreed with the patient (the so-called treat-to-target approach). In the present report, based on the Delphi methodology, 11 dermatologists from the Spanish Psoriasis Group addressed key issues that could be involved in the achievement and maintenance of the therapeutic goals of patients with moderate to severe psoriasis. The document provides 27 consensus statements intended to support clinical decision-making by healthcare professionals for patients who might be candidates to receive biologic therapy.
Biologic drugs have revolutionized the treatment of moderate to severe psoriasis in recent years because of their high efficacy and low risk of toxicity. However, even within the group of biologic therapies, there are differences related to the different mechanisms of action. Areas covered: We review the main adverse events associated with the biologic agents currently available for the treatment of psoriasis and the new inhibitors targeting the p19 subunit of interleukin (IL) 23 and the IL-17A receptor. This review covers injection site reactions, infections, cardiovascular events, demyelinating disorders, tumours, class effects secondary adverse events, immunogenicity, safety in pregnancy and vaccines efficacy. Expert commentary: More than a decade after the first approval of biologic drugs for use in psoriasis, the good safety profile of these drugs is one of the main justifications and incentives for their long-term use. The emergence of new pharmacological groups has made it possible to avoid some of the class effects of first-generation biologic agents and the new therapies appear to pose less risk of reactivation of latent infections, such as hepatitis B virus and tuberculosis. However, they are associated with new adverse effects related to their mechanism of action, including candidiasis and the risk of exacerbation or onset of inflammatory bowel disease.
Background:The 29th EADV Virtual Congress took place between the 29th-31st of October 2020. On October 29th, there was a Session on systemic treatment in which Professors Ulrich Mrowietz and Mar Llamas-Velasco presented the latest research on the efficacy of dimethyl fumarate (DMF) treatment for moderate-to-severe plaque psoriasis (BRIDGE and DIMESKIN 1 studies, respectively). The accepted DMF abstract from Professor Matthias Augustin, on the SKILL study, is also presented here. Results: Data from either prospective interventional (BRIDGE) or non-interventional (DIMESKIN 1, SKILL) studies among patients with moderate-to-severe psoriasis showed that DMF provides a positive efficacy profile in all four body regions included in the Psoriasis Area and Severity Index assessment (head and neck, trunk, upper and lower extremities) and a particularly interesting profile (strong efficacy) in the head and neck region. These findings may be of special interest to patients with scalp psoriasis who have been using topical therapies for a long time. Patient-reported outcomes (quality of life, pruritus) also improved during the 24 weeks of DMF treatment. The safety profile of DMF was similar to the previously described with fumaric acid esters. Conclusions: In summary, these results confirm the favorable efficacy and safety profile of DMF in longterm treatment.
Background and ObjectiveMulti-criteria decision analysis (MCDA) is a tool that systematically considers multiple factors relevant to health decision-making. The aim of this study was to use an MCDA to assess the value of dupilumab for severe atopic dermatitis compared with secukinumab for moderate to severe plaque psoriasis in Spain.MethodFollowing the EVIDEM (Evidence and Value: Impact on DEcision Making) methodology, the estimated value of both interventions was obtained by means of an additive linear model that combined the individual weighting (between 1 and 5) of each criterion with the individual scoring of each intervention in each criterion. Dupilumab was evaluated against placebo, while secukinumab was evaluated against placebo, etanercept and ustekinumab. A retest was performed to assess the reproducibility of weights, scores and value estimates.ResultsThe overall MCDA value estimate for dupilumab versus placebo was 0.51 ± 0.14. This value was higher than those obtained for secukinumab: 0.48 ± 0.15 versus placebo, 0.45 ± 0.15 versus etanercept and 0.39 ± 0.18 versus ustekinumab. The highest-value contribution was reported by the patients’ group, followed by the clinical professionals and the decision makers. A fundamental element that explained the difference in the scoring between pathologies was the availability of therapeutic alternatives. The retest confirmed the consistency and replicability of the analysis.ConclusionsUnder this methodology, and assuming similar economic costs per patient for both treatments, the results indicated that the overall value estimated of dupilumab for severe atopic dermatitis was similar to, or slightly higher than, that of secukinumab for moderate to severe plaque psoriasis.Electronic supplementary materialThe online version of this article (10.1007/s40259-018-0284-3) contains supplementary material, which is available to authorized users.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.