LAUSR

Etanercept has greatly improved management considerably. However, the efficacy and safety of combination therapy with methotrexate and the mechanism of action are not known. We aimed to describe the use of combined therapy of etanercept and methotrexate against moderate-to-severe plaque psoriasis in a Chinese population. We also wished to study the changes in expression of pro-inflammatory factors in peripheral blood mononuclear cells (PBMCs) and serum after the treatment to ascertain the mechanism of action. Thirty patients with moderate-to-severe plaque psoriasis were assigned into a monotherapy group and combination group randomly and equally. All patients received etanercept (50 mg, s.c., weekly), whereas patients in the combination group also received oral methotrexate (7.5-15 mg, p.o., weekly). Serum levels of interleukin (IL)-17A, IL-23, tumor necrosis factor (TNF)-α and their mRNA expressions in PBMCs were measured by ELISA and qRT-PCR. In the monotherapy group, Psoriasis Area and Severity Index (PASI) 50/75/90 responses were achieved by 86.7/66.7/40% after 24 weeks of treatment whereas, in the combination group, they were achieved by 93.3/80/60%, respectively. Although the overall prevalence of adverse effects (AEs) was higher in the combination group (60%) than in the monotherapy group (33.3%), the AEs were mild to moderate. The serum levels of IL-17A, IL-23, TNF-α, IL-33 and their mRNA expression in the PBMCs of the two groups were significantly higher than those of healthy controls (P < 0.05). Compared with the monotherapy group, serum levels of IL-17A, IL-23, TNF-α and their mRNA expression in PBMCs were decreased significantly in the combination group (P < 0.05). These data suggest that the efficacy of etanercept could be improved upon combination with methotrexate in the treatment of moderate-to-severe plaque psoriasis without increasing the risk of serious AEs. The mechanism of action might be associated with down-regulation of IL-17A, IL-23, and TNF-α.