Objective To assess the efficacy and safety of efalizumab in the treatment of psoriasis. Methods Randomized controlled trials (RCT) on efalizumab in the treatment of psoriasis were identified from The Cochrane Library ( issue 1, 2006) , specialized trials registered in Cochrane Skin Group (2006), MEDLINE (1966 - 2006) and EMBASE (1974 - 2006). The quality of the trials was assessed by two reviewers independently. RevMan 4.2.7 software provided by the Cochrane Collaboration was used for statistical analysis. Results Three RCTs involving 1 651 patients were included, all of which were of high methodological quality. All the patients were diagnosed as chronic moderate to severe plaque psoriasis with the age of 18-75 years. Meta-analysis indicated that at week 12, significantly more patients in both 1mg/kg/w and 2 mg/kg/w efalizumab subcutaneous groups achieved PASI50, PASI75, PASI90 improvement compared to the placebo group (Plt;0.0001), while there was no significant difference in PASI50, PASI75 and PASI90 responses between 1mg and 2mg efalizumab groups (P gt;0.05). No serious adverse effects were identified. Extended treatment for another 12w may contribute to further efficacy without increasing toxicty. Conclusions Efalizumab 12w therapy is safe and effective for treating adult patients with moderate to severe plaque psoriasis. More RCTs are required to assess the efficacy of the extended treatment.
Objective To investigate the associations of circulating inflammatory proteins and risk of psoriasis by using a two-sample Mendelian randomization (MR) approach. Methods Based on the genome-wide association study (GWAS) of inflammatory proteins and psoriasis, genetic variants associated with circulating inflammatory proteins were selected as instrumental variables (IVs), and genetic association data of psoriasis were extracted. The inverse-variance weighted method was used as the primary MR method, with statistical power analysis conducted to evaluate the test power. MR-Egger regression, weighted median, maximum likelihood, and MR Pleiotropy RESidual Sum and Outlier (PRESSO) tests were used to evaluate the influence of horizontal pleiotropy on the MR association estimates. Additionally, as sensitivity analysis, a GWAS of psoriasis from the FinnGen database was used as a replication dataset to evaluate the robustness of the results. Results A total of 558 single nucleotide polymorphisms associated with 74 inflammatory proteins were included. After False Discovery Rate (FDR) corrections, genetically predicted circulating levels of C-X-C motif chemokine ligand 9 (CXCL9) [odds ratio (OR)=1.76, 95% confidence interval (CI) (1.46, 2.11), P=2.31×10?9], C-C motif chemokine ligand 19 (CCL19) [OR=1.41, 95%CI (1.22, 1.62), P=2.97×10?6], and tumor necrosis factor-beta (TNFB) [OR=1.31, 95%CI (1.13, 1.52), P=3.56×10?4] were found to be significantly associated with an increased risk of psoriasis. Sensitivity analyses yielded similar results. Statistical power analysis indicated that the power to detect these associations was greater than 99%. Conclusion Genetically predicted circulating CXCL9, CCL19, and TNFB levels are positively associated with risk of psoriasis.
ObjectiveTo systematically review the long-term efficacy of biologics for moderate to severe plaque psoriasis. MethodsPubMed, EMbase, Web of Science and The Cochrane Library were electronically searched to collect randomized controlled trials (RCTs) on the long-term efficacy of approved biologics for moderate to severe plaque psoriasis from inception to May 2021. Two reviewers independently screened the literature, extracted data and assessed the risk of bias of the included studies; then, the network meta-analysis was performed by using Stata 16.0 software. ResultsA total of 26 RCTs were included. The results of network meta-analysis showed that among 11 biologics, the most effective biologics were risankizumab, followed by bimekizumab, brodalumab, guselkumab, and ixekizumab, and followed by secukinumab, adalimumab, ustekinumab, and etanercept was the last. ConclusionCurrent evidence shows that risankizumab is likely to be the best option for long-term treatment of moderate-to-severe plaque psoriasis. Due to the limited quality and quantity of the included studies, more high-quality studies are needed to verify the above conclusion.