HLA-C*06:02 genotype is a predictive biomarker of biologic treatment response in psoriasis.
J Allergy Clin Immunol
; 143(6): 2120-2130, 2019 06.
Article
en En
| MEDLINE
| ID: mdl-30578879
ABSTRACT
BACKGROUND:
Biologic therapies can be highly effective for the treatment of severe psoriasis, but response for individual patients can vary according to drug. Predictive biomarkers to guide treatment selection could improve patient outcomes and treatment cost-effectiveness.OBJECTIVE:
We sought to test whether HLA-C*0602, the primary genetic susceptibility allele for psoriasis, predisposes patients to respond differently to the 2 most commonly prescribed biologics for psoriasis adalimumab (anti-TNF-α) and ustekinumab (anti-IL-12/23).METHODS:
This study uses a national psoriasis registry that includes longitudinal treatment and response observations and detailed clinical data. HLA alleles were imputed from genome-wide genotype data for 1326 patients for whom 90% reduction in Psoriasis Area and Severity Index score (PASI90) response status was observed after 3, 6, or 12 months of treatment. We developed regression models of PASI90 response, examining the interaction between HLA-C*0602 and drug type (adalimumab or ustekinumab) while accounting for potentially confounding clinical variables.RESULTS:
HLA-C*0602-negative patients were significantly more likely to respond to adalimumab than ustekinumab at all time points (most strongly at 6 months odds ratio [OR], 2.95; P = 5.85 × 10-7), and the difference was greater in HLA-C*0602-negative patients with psoriatic arthritis (OR, 5.98; P = 6.89 × 10-5). Biologic-naive patients who were HLA-C*0602 positive and psoriatic arthritis negative demonstrated significantly poorer response to adalimumab at 12 months (OR, 0.31; P = 3.42 × 10-4). Results from HLA-wide analyses were consistent with HLA-C*0602 itself being the primary effect allele. We found no evidence for genetic interaction between HLA-C*0602 and ERAP1.CONCLUSION:
This large observational study suggests that reference to HLA-C*0602 status could offer substantial clinical benefit when selecting treatments for severe psoriasis.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Psoriasis
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Terapia Biológica
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Antígenos HLA-C
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Biomarcadores Farmacológicos
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Adalimumab
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Ustekinumab
/
Genotipo
Tipo de estudio:
Diagnostic_studies
/
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Idioma:
En
Revista:
J Allergy Clin Immunol
Año:
2019
Tipo del documento:
Article
País de afiliación:
Reino Unido