Adalimumab Treatment For Plaque Psoriasis:Study Of Efficacy And Patient's Vitamin D Status

Psoriasis is a common T lymphocyte mediated,multiple gene related inflammatory dermatologic disease,manifesting with scaling red plaques.As more and more progress is made on immunologic mechanisms of psoriasis,arise many kinds of biological agents targeting different sites.TNF-? inhibitors,mainly exert anti-inflammatory ability by inhibiting TNF-?,which plays an important role in the chronic inflammation.It's efficacious in autoimmune diseases like psoriasis,RA and inflammatory bowel disease etc.Adalimumab,first came into the market on January,2003,USA.It's efficacious,response fast and safe,now is widely used in European countries and the USA.However,we have not seen reports about its use in China.Vitamin D not only participate in the metabolism of calcium and phosphate,but also play a role in the synthesis and decomposition of bones,furthermore,it decreases risks of many chronic disease like autoimmune disease,infectious disease,cardiovascular disease,colorectal carcinoma,breast cancer and prostate cancer,etc.Moreover,vitamin D is an immunomodulator,which has therapeutic values for inflammatory diseases mediated by Th1 cells,such as psoriasis,DM and Crohn's disease.Lots of researches reveal that vitamin D deficiency is common in patients with psoriasis,and 25(OH)D status is negatively related with PASI.Ala-Houhala et al.treated 12 psoriatic patients with orally cholecalciferol,and NB-UVB,then they found that compare to only taking cholecalciferol,NB-UVB could significantly increase serum 25(OH)D level.Which implies that NB-UVB may possibly improve psoriasis by increasing serum 25(OH)D level.Peterson et al.found that serum TNF-? is negatively related with vitamin D level.Then,we made a hypothesis that serum vitamin D level may be altered after Adalimumab therapy.The objects of our research are patients with moderate to severe psoriasis.We record their PASI,PGA,DLQI and serum 25(OH)D level before and after Adalimumab treatment,compare those data to evaluate the efficacy of Adalimumab and whether vitamin D status would change after Adalimumab treatment.At the same time,by high-throughput SNP sequencing technique,we examined the SNPs of VDR gene locus Cdx2 of two groups of patients who were divided by whether they've achieved PASI75 after 12 weeks' treatment.And the allelic frequencies and genotypic frequencies between the two groups were compared by ?2 test.Thus,to offer possible new theoretical basis for psoriasis.Part1.Adalimumab therapy for moderate to severe plaque psoriasis: Observation of efficacy.[Objective] To observe the efficacy of a group of moderate to severe plaque type psoriatic patients treated by adalimumab.[Methods] 42 patients,who were clinically diagnosed as moderate to severe psoriasis,and did not improve by usual psoriatic treatment,were given adalimumab subcutaneously,80 mg at week0,then 40 mg every other week.Totally 12 weeks.Change of PASI,PGA and DLQI scores were recorded.[Results] Subtotal of 41 patients completed the treatment.At week 12,there are 32 patients(78.0%)had PASI75(greater than or equal to 75% improvement in Psoriasis Area and Severity Index(PASI)score)response,while 9 patients(22.0%)did not.Scores of PASI,PGA and DLQI were significantly lower than week 0(P<0.001).No severe adverse event happened during the entire experiment.[Conclusion] Adalimumab is efficacious and well-tolerated in the treatment of chronic plaque psoriasis.Part2.Adalimumab therapy for moderate to severe plaque psoriasis: Observation of serum vitamin D status.[Objective] To observe whether serum vitamin D status would change after the patients were treated by adalimumab.[Methods] At week0 and week12,samples(2 ml)of venous blood were collected from each participant in tubes,centrifuged,then stored in-70? liquid nitrogen.Using high performance liquid chromatography-tandem massspectrometry(HPLC-MS/MS)to determine serum 25(OH)D level(normal:0.1-100.0 ng/mL;insufficiency: 20.1-30.0ng/m L;deficiency:?20ng/m L;over dose: ?100ng/m L).[Results] Serum 25(OH)D level was significantly higher in week 12 compared to week 0(P<0.001).[Conclusion] After 12-week treatment,serum 25(OH)D level was significantly higher than baseline,which implies there could be some connections between adalimumab and vitamin D level.More trials needed to be done to explore its mechanism.Part3.The Association between Vitamin D Receptor Gene Cdx2 Polymorphism and Response to Adalimumab Treatment[Objective]To study the association between vitamin D receptor gene Cdx2 polymorphism and response to Adalimumab treatment of plaque psoriasis,in order to predict the outcomes of biologics in treating psoriasis.[Methods] By high-throughput SNP sequencing technique,we examined the SNPs of VDR gene locus Cdx2 of two groups of patients who were divided by whether they've achieved PASI75 after 12 weeks' treatment.And the allelic frequencies and genotypic frequencies between the two groups were compared by?2 test.[Results] The allelic frequencies and genotypic frequencies of VDR gene locus Cdx2 between the two groups had no statistical significance(P>0.05).[Conclusion]There is no association between vitamin D receptor gene Cdx2 polymorphism and response to Adalimumab treatment of plaque psoriasis.