Efficacy And Safety Of Ustekinumab In Patients With Plaque Psoriasis:a Meta-analysis

Background:Psoriasis is a common, chronic relapsing/remitting immune-mediated skin disease characterized by red, scaly patches, papules, and plaques. The skin lesions seen in psoriasis may vary in severity from minor localized patches to complete body coverage.There are four main types of psoriasis:plaque, guttate, pustular and erythrodermic.Plaque psoriasis is the most common form.The causes of psoriasis are not fully understood. It is generally considered a genetic disease thought to be triggered or influenced by environmental factors. Because of renal, hepatic, pulmonary toxicity and limited efficacy, the long-term use of traditional systemic therapies is frequently unacceptable.Recently,researchers have focused on the genetic and immunologic features of psoriasis.Ustekinumab, a fully human monoclonal antibody directed against the shared p40subunit of interleukin (IL)-12and IL-23, was demonstrated to be highly efficacious and generally well tolerated in treating patients with moderate to severe psoriasis.Theoretical risks of pharmacologic blockade of IL-12and IL-23include susceptibility to infection and malignancy. In this article, we collected the past published related research results at home and abroad, conducted a systematic review of all randomized controlled trials (RCTs) to evaluate the efficacy and safety of ustekinumab for patients with plaque psoriasis.Objectives:To systematically review the efficacy and safety of ustekinumab on these conditions in patients with plaque psoriasis.Methods:The PubMed,Google Scholar, EMBASE, Cochrane Library were searched using the open strings "IL-12and IL-23and psoriasis","ABT-874and psoriasis","IL-12/23monoclonal antibody","IL-12/23antibody","CNTO-1275".Searches were updated to December2013.Reference lists of prior reviews, systematic reviews and trials were also checked.Inclusion criteria:randomized controlled trial, RCT; plaque psoriasis; Ustekinumab-placebo-controlled treatment; The proportion of patients with at least50%,75%,90%improvement in the psoriasis area and severity index (PASI50, PASI75,PASI90);The proportion of patients with PGA clear; The proportion of patients with DLQI of0or1.Satistical analyses were performed using the Stata(version12.0).Heterogeneity was examined by Q test,12statistic inspection levelα=0.05.If heterogeneity was low, a fixed-effects model was used for analysis, otherwise a random-effects model was used.In addition to95%confidence intervals (CIs), relative risks (RRs) were respectively used. Differences are statistically significant (P<0.05).Publication bias was assessed by Begg’s funnel plot and Egger’test.Results:The literature search identified5randomized controlled trials (RCTs) met the inclusion criteria and were included in the meta-analysis.A total of2466cases were included.Meta-analysis results suggested that Ustekinumab was superior to placebo for moderate to plaque psoriasis, Ustekinumab45mg groups and90mg groups both improve PASI. There was no significant difference between the two groups of Ustekinumab to get PASI90.There was no significant difierence in the improvement of the life quality.But Ustekinumab90mg groups have a better curative effect than45mg groups at PASI50and PASI75. The most common adverse events were upper respiratory tract infection, nasopharyngitis, headache, there were no significant diferences between Ustekinumab and placebo, the two groups of Ustekinumab had no significant diferences too. No significant publication bias was detected among the included studies.Conclusion:This systematic review shows using Ustekinumab was safe and effective for patients with plaque psoriasis.