Alterations in the innate and adaptive immunity underpin psoriasis pathophysiology, with the Th17 cells subset now recognised 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 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 β‐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 (NAFLD), closely related to metabolic syndrome, but also in other mentioned cardio‐metabolic disorders, a predominance of IL‐23 and other related pro‐inflammatory 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.

Generalized pustular psoriasis (GPP) is a rare, chronic, and severe inflammatory skin disorder characterized by sudden eruption of sterile pustules, often accompanied by systemic inflammation. GPP flares can be life-threatening if untreated, owing to potential serious complications such as sepsis and cardiovascular failure. Diagnosis and clinical measurement of disease severity in GPP are often difficult. Lack of standardized criteria in the international guidelines and the heterogeneity of cutaneous and extracutaneous symptoms make the diagnosis of GPP difficult. Clinical criteria for description and diagnosis of pustular conditions, including GPP, are variable and there is no specific agreement on commonly sustained concepts. Differentiation of GPP from other similar conditions/diseases is important and requires careful assessments. The evidence that supports current topical or systemic therapies is largely based on case reports and small studies. Some biologic agents that target key cytokines involved in the activation of inflammatory pathways have been used as treatments for GPP. Recently, spesolimab, an IL-36R antagonist, has been approved in the USA and Japan for the treatment of GPP flares in adults, but there are no currently approved treatments for GPP in Europe. The IL-36 pathway has recently emerged as a central axis driving the pathogenic inflammatory mechanisms of GPP. Biologic agents that inhibit the IL-36 pathway have shown efficacy and safety in patients with GPP, addressing a generally considered unmet medical need.

Background: The efficacy and safety of secukinumab in patients with plaque psoriasis (PsO) has been demonstrated in randomized clinical trials (RCTs). However, data regarding its efficacy and safety in real-life settings are scarce. Objectives: To evaluate the efficacy and safety of secukinumab in clinical practice in patients with PsO attending 10 dermatology centres in Spain. Methods: Data from 136 patients consecutively treated with secukinumab for at least 52 weeks were collected in a retrospective observational study. Results: After 52 weeks of treatment, 69% and 46% of patients achieved a PASI-75, PASI-90, respectively. PASI-score ≤ 5 was achieved in 83% of patients, PASI-score ≤ 3 in 73% and PASI-score ≤ 1 in 47%. Response rates were found significantly lower in patients with obesity and non-naïve to biologics (p< 0.05). The most common adverse event (AE) was candidiasis (5/136). Thirty-six patients (26.5%) discontinued treatment by week 52 due to lack or loss of response (n = 29), AEs (n = 2) or other causes (n = 5). Conclusion: These findings complement the efficacy and safety profiles of secukinumab in PsO outlined in RCTs. The effectiveness in clinical practice may be lower in patients whit a BMI ≥ 30 and those previously treated with other biologic agents.

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.