Analysis Of Influencing Factors Of The Therapeutic Effect Of Yisaipu On Moderate And Severe Plaque Psoriasis

Objectives:Psoriasis is an immune-mediated chronic inflammatory skin disease.Yisaipu,as a TNF-?inhibitor,can effectively control the disease clinically,but it still cannot reach a good effect.We are going to analyze factors influencing the efficacy of general treatment for moderate to severe plaque psoriasis,so that we can know how to improve and predict the efficacy of drugs and better apply Yisaipu in clinical practice.Methods:Clinical data of a total of 209 patients with moderate to severe plaque psoriasis were collected from eight research centers nationwide from August 2014 to October2016 in a clinical trial of"Yisaipu combined with methotrexate for psoriasis".The factors influencing the efficacy of Yisaipu were analyzed in three parts.1)Drug combination as a relatively large influencing factor,taking methotrexate as an example to analyze the efficacy and safety of Yisaipu combined with methotrexate in the treatment of moderate to severe plaque psoriasis.The main evaluation index is the proportion of patients who reached PASI75 at week 24.The secondary evaluation indicators include PASI50,PASI90,PGA,Pt GA,and DLQI scores;2)To investigate whether age,gender,BMI,PASI score at baseline,smoking and drinking history,and other clinical characteristics affect the efficacy of Yisaipu in the treatment of psoriasis through univariate analysis and multivariate logistic regression analysis;3)Study the genetic polymorphisms related to the efficacy response of Yisaipu through genome-wide association analysis.Results:At 24 weeks,the number of patients who achieved PASI75 in the Yisaipu combined with methotrexate group was significantly higher than that of the Yisaipu group alone?81%vs 60,p<0.001?.The same results were also seen at 12 weeks?61%vs 45%,p<0.001?.With the efficacy endpoints of PASI50 and PASI90,the efficacy of the two-agent group was higher than that of the single-agent group.The improvement of PGA,Pt GA,and DLQI scores of the two-agent group was also better than that of the single-agent group.2)The results of multivariate logistic regression analysis showed that methotrexate?0R=3.889,P<0.01?,PASI score at baseline?OR=0.963,P<0.05?,and BMI?OR=3.106,P<0.01?is related to the final effect.3)The Meta-GWAS analysis of 3478293 overlapped SNPs revealed significant association at 137 SNPs within 7 loci with a p value of the top most significant SNP less than 10^-5.These seven loci are RN7SKP91,NPAS2,IQGAP2,IRF1-AS1,PWRN4,KRT35 and CTSZ,respectively.Conclusions:1)The combination therapy of Yplus MTX was an effective therapy for moderate-to-severe plaque psoriasis with an acceptable safety and tolerability profile,indicating that it was feasible and well tolerated for patients.2)Baseline PASI,and BMI can predict the efficacy of Yisaipu in patients.The efficacy of Yisaipu in patients with low baseline BMI,and higher PASI may be better.The PASI absolute value score is also important in clinical practice.3)Using a meta-analysis of two independent GWAS,seven genomic regions demonstrated significant associations with etanercept biosimilar treatment response.