Paolo Dapavo

Blockade of Phosphatidylinositol 3-Kinase (PI3K)δ or PI3Kγ Reduces IL-17 and Ameliorates Imiquimod-Induced Psoriasis-like Dermatitis

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.

PACE study: real-life Psoriasis Area and Severity Index (PASI) 100 response with biological agents in moderate-severe psoriasis

Abstract Background: Few studies have compared the use of different biologics in a real-life setting in plaque psoriasis patients. Objective: To compare the efficacy of biologics in psoriasis/psoriatic arthritis patients. Methods: Patients treated with adalimumab, etanercept and ustekinumab for at least 16 weeks were included. Achievement of Psoriasis Area Severity Index (PASI), PASI 90/100 response and time taken to achieve PASI 90/100 response were measured. Logistic regression was used to evaluate the effect of psoriasis localization on achievement of PASI 100 response. Results: Two hundred and fifty five patients were included. No difference was observed in PASI 90 response between etanercept and ustekinumab (65.5 vs. 55.4%), while adalimumab-treated patients had a higher response versusustekinumab (71.6 vs. 55.4%, p = .02). More patients achieved complete remission (PASI 100 response) with adalimumab versus etanercept (65.7 vs. 23%, p < .001) or ustekinumab (65.7 vs. 44.6%, p = .003). Adalimumab-treated patients achieving PASI 90 responded more quickly (by three and six months) versus ustekinumab or etanercept. PASI100 response was achieved in ∼43% of adalimumab and ustekinumab treated-patients by three months versus etanercept (14.3%), increasing to 92.5, 85.4 and 35.7%, respectively by six months. PASI100 response was associated with psoriasis nail involvement or genital psoriasis. Conclusion: In the real-life setting, adalimumab was the most effective biological agent for the treatment of plaque psoriasis.