Psoriasis is a common disease, which has a considerable impact on the healthcare system. Therefore, appropriate use of therapeutic resources is very important. Management of psoriasis in daily clinical practice is highly variable because many issues are still debated and not definitely addressed by the evidence-based medicine. Moreover, the different availability and reimbursability of drugs in each country justifies national guidelines. Expert consensus can provide helpful guidelines for optimizing patient care. A total of 20 dermatologists from different areas of Italy and with large experience in the treatment of psoriasis agreed to participate in the guidelines expert panel who aimed to reach consensus on the factors influencing psoriasis severity, the indications for systemic treatments, the parameters to be considered in the choice of treatment, and the factors to be considered in the choice of biological treatment. The recommendations for the use, screening and monitoring of systemic therapies were based on the 2015 S3 European Dermatology Forum/European Academy of Dermatology and Venereology psoriasis guidelines. Recommendations on the treatment of psoriasis in special patient populations were also agreed. The final document was discussed in a meeting moderated by a facilitator with participation of the entire group and adopting a nominal group technique to reach consensus. A statement was regarded as consented when agreement was achieved by at least 75% of the voting experts according to the Delphi procedure.

Background: The anti-tumour necrosis factor (TNF)-α adalimumab is the only licenced biologic for moderate-to-severe hidradenitis suppurativa (HS). No predictors of response have been identified so far. Objective: To identify clinical parameters predicting response to adalimumab and confirm its efficacy/ safety. Methods: Data of 389 HS patients treated with adalimumab in 21 Italian centres were reviewed. Sex, ages at onset/diagnosis/baseline, body mass index, smoking, phenotypes, previous treatments, concomitant antibiotics , and "therapeutic delay", defined as the time from HS onset to adalimumab initiation, were assessed. Response to adalimumab and its impact on quality of life (QoL) were evaluated using "Hidradenitis Suppurativa Clinical Response" (HiSCR) and "Dermatology Life Quality Index" (DLQI)/"Visual Analogue Scale for pain" (VAS pain), respectively. Logistic regression analysis was performed. Results: The "therapeutic delay" correlated to lack of response to adalimumab at week 16 (OR,1.92 for therapeutic delay  10 years; 95% CI,1.28-2.89; P=0.0016). HiSCR was achieved in 43.7% and 53.9% patients at week 16 and 52, respectively. Significant reductions in both DLQI and VAS pain were found between week 16 versus baseline (p<0.0001 for both) and week 52 versus baseline (p<0.0001 for both). Previous immunosuppressants inversely correlated to HiSCR at week 52 [OR=1.74, 95% CI 1.04-2.91, p=0.0342]. Conclusion: Inverse correlation between therapeutic delay and clinical response was found, supporting early adalimumab use and providing evidence for a "window of opportunity" in HS. Adalimumab efficacy and safety were confirmed, along with patients' QoL improvement. Immunosuppressants could negatively influence response to adalimumab inducing a switch to non-TNFα-driven pathways.

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Background Chronic spontaneous urticaria (CSU) is defined as spontaneous occurrence of wheals and/or angioedema for ≥6 weeks. Omalizumab is a monoclonal anti-IgE antibody effective in refractory CSU, but its mechanism of action and markers predictive of response remain not completely defined.Objectives To correlate baseline levels of two proposed biomarkers, total IgE (bIgE) and D-dimer (bD-dimer), and clinical parameters to omalizumab response and to relapses after drug withdrawal.Methods In this retrospective Italian multicentre study, clinical data were collected in 470 CSU patients, and bIgE and bDdimer were measured in 340 and 342 patients, respectively. Disease activity was determined by Urticaria Activity Score 7 (UAS7) at week 1 and 12 after omalizumab starting. Relapses were evaluated during a 2-and 3-month interval after a first and a second course of treatment, respectively.Results bIgE correlated to a good response to omalizumab since levels were significantly higher in responders than nonresponders (P = 0.0002). Conversely, bD-dimer did not correlate to response. There was no correlation between both bIgE and D-dimer and either first or second relapse. Disease duration was significantly longer in patients who experienced either first or second relapse (P < 0.0001 and P = 0.0105, respectively), while baseline UAS7 correlated only to first relapse (P = 0.0023).Conclusions Our study confirms bIgE as a reliable biomarker predicting response to omalizumab in CSU, while it does not support the usefulness of bD-dimer unlike previous findings. CSU duration before omalizumab and baseline UAS7 may be clinical markers of relapse risk. JEADV 2019, 33, 918-924 Predictors of response to omalizumab and relapse in CSU Positivity for antithyroglobulin or antithyroperoxidase autoantibodies §, n (%) 106 (26.7) 15 (36.6) 0.1995 †IgE values missing for 130 patients. ‡D-dimer values missing for 128 patients. §Data missing for 32 patients. IQR: interquartile range; SD: standard deviation.

Psoriasis is a chronic inflammatory skin disease triggered by interplay between immune mediators from both innate and adaptive immune systems and skin tissue, in which the IL-23/IL-17 axis is critical. PI3Kδ and PI3Kγ play important roles in various immune cell functions. We found that mice lacking functional PI3Kδ or PI3Kγ are largely protected from imiquimod (IMQ)-induced psoriasis-like dermatitis, correlating with reduced IL-17 levels in the lesions, serum, and the draining lymph nodes. TCRγδ T cells were the major IL-17–producing population in the draining lymph nodes and were significantly diminished in IMQ-treated PI3Kδ knockin and PI3Kγ knockout mice. We also show that PI3Kδ and PI3Kγ inhibitors reduced IFN-γ production by human TCRγδ T cells and IL-17 and IFN-γ production by PBMCs from psoriatic or healthy donors. In addition, inhibition of PI3Kγ, but not PI3Kδ, blocked chemotaxis of CCR6+IL-17–producing cells from IMQ-treated mice or healthy human donors. Taken together, these data indicate that PI3Kδ and/or PI3Kγ inhibitors should be considered for treating IL-17–driven diseases, such as psoriasis.