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• W2238184577 abstract "To the Editor: Genetic factors have been well studied in genomewide association studies: interleukin 23 receptor, interleukin 12B, and HLA-C*06 of the major histocompatibility complex have been strongly linked with psoriasis.1Prieto-Pérez R. Cabaleiro T. Daudén E. Ochoa D. Roman M. Abad-Santos F. Genetics of psoriasis and pharmacogenetics of biological drugs.Autoimmune Dis. 2013; 2013: 613086Google Scholar Current knowledge on pharmacogenomics and the resulting impact on psoriasis treatment have important limitations, including small patient numbers and a lack of analyses.2Tejasvi T. Stuart P.E. Chandran V. et al.TNFAIP3 gene polymorphisms are associated with response to TNF blockade in psoriasis.J Invest Dermatol. 2012; 132: 593-600Abstract Full Text Full Text PDF PubMed Scopus (139) Google Scholar, 3Vasilopoulos Y. Manolika M. Zafiriou E. et al.Pharmacogenetic analysis of TNF, TNFRSF1A, and TNFRSF1B gene polymorphisms and prediction of response to anti-TNF therapy in psoriasis patients in the Greek population.Mol Diagn Ther. 2012; 16: 29-34Crossref PubMed Google Scholar, 4Schmitt-Egenolf M. Eiermann T.H. Boehncke W.H. Ständer M. Sterry W. Familial juvenile onset psoriasis is associated with the human leukocyte antigen (HLA) class I side of the extended haplotype Cw6-B57-DRB1*0701-DQA1*0201 DQB1*0303: a population- and family-based study.J Invest Dermatol. 1996; 106: 711-714Abstract Full Text PDF PubMed Scopus (116) Google Scholar, 5Talamonti M. Botti E. Galluzzo M. et al.Pharmacogenetics of psoriasis: HLA-Cw6 but not LCE3B/3C deletion nor TNFAIP3 polymorphism predisposes to clinical response to interleukin 12/23 blocker ustekinumab.Br J Dermatol. 2013; 169: 458-463Crossref PubMed Scopus (121) Google Scholar In this retrospective study, we reviewed data from 134 patients with psoriasis (83 male and 51 female) who started ustekinumab treatment in our psoriasis unit to confirm the role of HLA-C*06 as a pharmacogenetic marker of response to treatment. The patients received ustekinumab (45 mg in patients ≤100 kg and 90 mg in patients >100 kg), at weeks 0 and 4, and every 12 weeks thereafter. Venous blood for genotyping was collected in EDTA tubes and stored at −70°C. DNA was extracted from whole blood using DNeasy blood and tissue kits (Qiagen Inc, Hilden, Germany). The HLA-C*06 allele was detected as previously described.5Talamonti M. Botti E. Galluzzo M. et al.Pharmacogenetics of psoriasis: HLA-Cw6 but not LCE3B/3C deletion nor TNFAIP3 polymorphism predisposes to clinical response to interleukin 12/23 blocker ustekinumab.Br J Dermatol. 2013; 169: 458-463Crossref PubMed Scopus (121) Google Scholar We evaluated psoriasis severity by Psoriasis Area and Severity Index (PASI) score at baseline and at follow-up visits in weeks 4, 12, 28, 52, 76, 104, and 156 (year 3). Efficacy data were analyzed by intent to treat/last observation carried forward analysis. A χ2 test was performed to compare the clinical response with categorical data. Meta-analysis was performed using software (STATA 11.2, Statacorp LP Inc, College Station, TX). At baseline, the mean PASI score was 16.6 (range 8-59) and the mean disease duration was 22.9 years (range 2-65). In all, 73 patients were HLA-C*06-positive (C*06POS) and 61 patients were HLA-C*06-negative (C*06NEG) (Table I).Table IDemographic data for each genotype at baselineDemographic dataC*06POSC*06NEGPatients7361Male/female39/3444/17Age, y†Mean and SD.44.0 ± 13.450.2 ± 12.3Range20-7527-79Age of disease onset, y†Mean and SD.20.8 ± 12.327.2 ± 14.4Range0-600-62BMI kg/m2 (range)25.9 ± 4.4 (18.7-40)27.3 ± 4.9 (19.6-42.7)Duration of psoriasis, y†Mean and SD.23.0 ± 11.222.8 ± 12.1Range2-482-65PASI score at baseline†Mean and SD.16.0 ± 7.217.1 ± 9.2Range8-36.68-59Previous biological agents40 (54.8%)38 (62.3%)BMI, Body mass index; C*06NEG, HLA-C*06-negative; C*06POS, HLA-C*06-positive; PASI, Psoriasis Area and Severity Index.† Mean and SD. Open table in a new tab BMI, Body mass index; C*06NEG, HLA-C*06-negative; C*06POS, HLA-C*06-positive; PASI, Psoriasis Area and Severity Index. When considering the response to treatment, we found a striking difference in the rate of response to ustekinumab between patients who were C*06POS and C*06NEG (Fig 1). At week 12, 82.9% of patients who were C*06POS had reached at least 75% reduction in the PASI score (PASI75), whereas 54.2% of patients who were C*06NEG had done so (odds ratio [OR] 4.1, P = .001). At week 52, a significantly higher percentage of the C*06POS group showed a PASI75 response (83.9% vs 58.2%, OR 3.7, P = .003). A similar trend was observed in the second and third year of treatment. We also investigated the relationship between HLA-C*06 and the response to ustekinumab treatment in 56 patients who were anti–tumor necrosis factor therapy-naïve (33 C*06POS and 23 C*06NEG) (Table II). At week 12, 93.3% of the C*06POS group achieved PASI75, compared with 47.6% of the C*06NEG group (OR 15.4, P = .001). At week 52, a significantly higher percentage of the C*06POS group showed a PASI75 response (91.3% vs 61.1%, OR 6.7, P = .03) (Fig 2). A multivariate logistic regression analysis was performed to rule out potential confounders (ie, sex, age, age of disease onset, body mass index, or baseline PASI scores). The results confirmed a strong association only with C*06POS status and response to treatment.Table IIDemographic data for each genotype of the group naïve to biological therapies (age and duration in years)Demographic dataC*06POSC*06NEGPatients3323Male/female17/1618/5Age, y†Mean and SD.46.3 ± 14.548.5 ± 12Range22-7527-70BMI kg/m2 (range)26.4 ± 4.2 (21.3-34.4)26.0 ± 4.2 (20.5-32.2)Age of disease onset, y†Mean and SD.19.1 ± 13.230.8 ± 18.8Range0-590-62Duration of psoriasis, y†Mean and SD.26.5 ± 4.218.7 ± 11.3Range6-482-47PASI score at baseline†Mean and SD.17.8 ± 815.8 ± 6.6Range8-36.68.4-32BMI, Body mass index; C*06NEG, HLA-C*06-negative; C*06POS, HLA-C*06-positive; PASI, Psoriasis Area and Severity Index.† Mean and SD. Open table in a new tab Fig 2Clinical response to ustekinumab between weeks (W) 4 and 52, in group naïve to biological therapies stratified for the presence of HLA-C*06. Proportion of patients achieving 75% reduction in the Psoriasis Area and Severity Index score (PASI 75). #P < .05. C*06NEG, HLA-C*06 negative; C*06POS, HLA-C*06 positive.View Large Image Figure ViewerDownload Hi-res image Download (PPT) BMI, Body mass index; C*06NEG, HLA-C*06-negative; C*06POS, HLA-C*06-positive; PASI, Psoriasis Area and Severity Index. Previously we found that patients who are C*06POS have a significantly higher response rate to ustekinumab therapy. We now provide further evidence that genetic polymorphisms can be used to predict response to biologic therapy in patients with psoriasis." @default.
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• W2238184577 title "HLA-C*06 and response to ustekinumab in Caucasian patients with psoriasis: Outcome and long-term follow-up" @default.
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