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Background:
Our understanding of the genetic bases of predisposition to psoriasis is increasing exponentially due to the progresses of genetics. However, so far little is known about genetic predisposition in relation to the response to psoriasis treatments. Recent data identified genetic predictors for the clinical outcome of conventional treatments such as methotrexate, acitretin and vitamin D derivatives, but few studies are available on genetic predictors of response to biologics.We hypothesized that genetic variations associated with increased risk of developing psoriasis may also act as predictors for the biologic therapy outcome.
Objectives:
Aim of our study was to analyze the presence of three different psoriasis susceptibility genetic variations (HLA-Cw6; TNFAIP3 rs610604 polymorphism; LCE3B/3C genes deletion) in a cohort of patients affected by moderate to severe psoriasis under ustekinumab treatment. Our primary endpoint was to evaluate the association between PASI 75 response at week 12 and HLA-Cw6 status.
Methods:
Fifty-one patients were genotyped by standard methods and psoriasis severity (PASI score) was evaluated at day 0 and after 4, 12, 24 and 40 weeks of treatment.
Results:
We observed increased response to ustekinumab in Cw6POS patients (PASI75 at week 12 96.4% in Cw6POS vs 65.2% in Cw6NEG patients p=0.008). In addition we show that HLA-Cw6POS patients responded faster to ustekinumab, 89,3% of them reaching PASI 50 at week 4, after a single injection (versus 60,9% of HLACw6NEG patients). Superior response of HLA-Cw6POS patients was maintained throughout the study period, reaching the highest statistical significance for PASI 75 at week 28 (96.35% Cw6POS vs 72.7% Cw6NEG; odds ratio 9.8). Analysis of TNFAIP3 rs610604 polymorphism and LCE3B/3C genes deletion did not show any significant association with response to ustekinumab.
Conclusions:
Our observations underline the role of HLA-Cw6 not only as a psoriasis susceptibility gene, but also as a pharmacogenetic marker of response to ustekinumab in psoriasis.
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Our understanding of the genetic bases of predisposition to psoriasis is increasing exponentially due to the progresses of genetics. However, so far little is known about genetic predisposition in relation to the response to psoriasis treatments. Recent data identified genetic predictors for the clinical outcome of conventional treatments such as methotrexate, acitretin and vitamin D derivatives, but few studies are available on genetic predictors of response to biologics.We hypothesized that genetic variations associated with increased risk of developing psoriasis may also act as predictors for the biologic therapy outcome.
Objectives:
Aim of our study was to analyze the presence of three different psoriasis susceptibility genetic variations (HLA-Cw6; TNFAIP3 rs610604 polymorphism; LCE3B/3C genes deletion) in a cohort of patients affected by moderate to severe psoriasis under ustekinumab treatment. Our primary endpoint was to evaluate the association between PASI 75 response at week 12 and HLA-Cw6 status.
Methods:
Fifty-one patients were genotyped by standard methods and psoriasis severity (PASI score) was evaluated at day 0 and after 4, 12, 24 and 40 weeks of treatment.
Results:
We observed increased response to ustekinumab in Cw6POS patients (PASI75 at week 12 96.4% in Cw6POS vs 65.2% in Cw6NEG patients p=0.008). In addition we show that HLA-Cw6POS patients responded faster to ustekinumab, 89,3% of them reaching PASI 50 at week 4, after a single injection (versus 60,9% of HLACw6NEG patients). Superior response of HLA-Cw6POS patients was maintained throughout the study period, reaching the highest statistical significance for PASI 75 at week 28 (96.35% Cw6POS vs 72.7% Cw6NEG; odds ratio 9.8). Analysis of TNFAIP3 rs610604 polymorphism and LCE3B/3C genes deletion did not show any significant association with response to ustekinumab.
Conclusions:
Our observations underline the role of HLA-Cw6 not only as a psoriasis susceptibility gene, but also as a pharmacogenetic marker of response to ustekinumab in psoriasis.
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