RESUMEN
Detecting the association of genetic variants to the response of biological therapy represents an important advance in developing a personalized therapy. The aim of this work was to study the association of polymorphisms with an optimal response to tildrakizumab in patients with psoriasis in a real-life clinical practice. Ninety patients with plaque psoriasis recruited from-Spanish hospitals receiving tildrakizumab for at least 24 weeks were genotyped for 180 polymorphisms. Optimal response to tildrakizumab was evaluated by absolute PASI ≤1 at 6 and 12 months. Polymorphisms corrected for weight and disease duration with an FDR <0.15 were included in a multiple regression model. Sixty three percent of patients achieved an absolute PASI ≤1 at 6 months, while 71% did so after 12 months. Disease duration (>27 years) and weight (>76 kg) were associated with treatment response; after correcting by these factors, no association (FDR >0.15) was found for any polymorphism and response to tildrakizumab at 6 months. The analysis at 12 months identified the genotype GG for rs610604 (TNFAIP3), CT for rs9373839 (ATG5), and delCTGT/delCTGT for rs72167053 (PDE4D) as risk factors to not achieve an optimal response (PASI ≤1), while CT for rs708567 (IL17RC) was protective, independently of weight and disease duration (FDR <0.15). The final multivariable model at 12 months showed an AUC of 0.90 (95% CI 0.82 to -0.98). We identified a set of polymorphisms that could be helpful to identify psoriatic patients with an optimal response to tildrakizumab at 12 months in real-world practice conditions.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Psoriasis , Humanos , Psoriasis/tratamiento farmacológico , Psoriasis/genética , Femenino , Masculino , Persona de Mediana Edad , Anticuerpos Monoclonales Humanizados/uso terapéutico , Adulto , Polimorfismo de Nucleótido Simple , Resultado del Tratamiento , Genotipo , Anciano , Polimorfismo GenéticoRESUMEN
BACKGROUND: Prediction of the response to a biological treatment in psoriasis patients would allow efficient treatment allocation. OBJECTIVE: To identify polymorphisms associated with secukinumab response in psoriasis patients in a daily practice setting. METHODS: We studied 180 SNPs in patients with moderate-to-severe plaque psoriasis recruited from 15 Spanish hospitals. Treatment effectiveness was evaluated by absolute PASI ≤3 and ≤1 at 6 and 12 months. Individuals were genotyped using a custom Taqman array. Multiple logistic regression models were generated. Sensitivity, specificity and area under the curve (AUC) were analysed. RESULTS: A total of 173 patients were studied at 6 months, (67% achieved absolute PASI ≤ 3 and 65% PASI ≤ 1) and 162 at 12 months (75% achieved absolute PASI ≤ 3 and 64% PASI ≤ 1). Multivariable analysis showed the association of different sets of SNPs with the response to secukinumab. The model of absolute PASI≤3 at 6 months showed best values of sensitivity and specificity. Four SNPs were associated with the capability of achieving absolute PASI ≤ 3 at 6 months. rs1801274 (FCGR2A), rs2431697 (miR-146a) and rs10484554 (HLCw6) were identified as risk factors for failure to achieve absolute PASI≤3, while rs1051738 (PDE4A) was protective. AUC including these genotypes, weight of patients and history of biological therapy was 0.88 (95% CI 0.83-0.94), with a sensitivity of 48.6% and specificity of 95.7% to discriminate between both phenotypes. CONCLUSION: We have identified a series of polymorphisms associated with the response to secukinumab capable of predicting the potential response/non-response to this drug in patients with plaque psoriasis.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Polimorfismo de Nucleótido Simple , Psoriasis , Humanos , Psoriasis/tratamiento farmacológico , Psoriasis/genética , Femenino , Masculino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Persona de Mediana Edad , Adulto , Fármacos Dermatológicos/uso terapéutico , MicroARNs/genética , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
There is a lack of studies assessing whether wide excision surgery in hidradenitis suppurativa affected areas is useful for the global control of the hidradenitis suppurativa. We aimed to find whether surgery results were a better global control on the disease activity in both, the area where the surgery is performed and distant areas. We evaluated the disease course of 17 patients with hidradenitis suppurativa who underwent wide excision of complex fistula tracts between October 2018 and January 2022 at the Hospital Universitario de la Princesa, Madrid. We found that wide excision of complex fistulas produces an overall positive effect on the inflammatory activity in hidradenitis suppurativa that may be important to achieve an adequate control of the disease (AU)
No existen estudios que se centren en la utilidad del tratamiento con cirugía amplia para el control global de la hidradenitis supurativa. En el presente estudio hemos evaluado el curso de la enfermedad de 17 pacientes con hidradenitis supurativa a los que se les realizó extirpación de trayectos fistulosos mediante cirugía amplia entre octubre de 2018 y enero de 2022 en el Hospital Universitario de La Princesa. Encontramos como resultado que el tratamiento mediante cirugía amplia produce un beneficio global en la actividad inflamatoria de la enfermedad y puede ser importante para el control de la hidradenitis supurativa (AU)
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Hidradenitis Supurativa/cirugía , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
No existen estudios que se centren en la utilidad del tratamiento con cirugía amplia para el control global de la hidradenitis supurativa. En el presente estudio hemos evaluado el curso de la enfermedad de 17 pacientes con hidradenitis supurativa a los que se les realizó extirpación de trayectos fistulosos mediante cirugía amplia entre octubre de 2018 y enero de 2022 en el Hospital Universitario de La Princesa. Encontramos como resultado que el tratamiento mediante cirugía amplia produce un beneficio global en la actividad inflamatoria de la enfermedad y puede ser importante para el control de la hidradenitis supurativa (AU)
There is a lack of studies assessing whether wide excision surgery in hidradenitis suppurativa affected areas is useful for the global control of the hidradenitis suppurativa. We aimed to find whether surgery results were a better global control on the disease activity in both, the area where the surgery is performed and distant areas. We evaluated the disease course of 17 patients with hidradenitis suppurativa who underwent wide excision of complex fistula tracts between October 2018 and January 2022 at the Hospital Universitario de la Princesa, Madrid. We found that wide excision of complex fistulas produces an overall positive effect on the inflammatory activity in hidradenitis suppurativa that may be important to achieve an adequate control of the disease (AU)
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Hidradenitis Supurativa/cirugía , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
There is a lack of studies assessing whether wide excision surgery in hidradenitis suppurativa affected areas is useful for the global control of the hidradenitis suppurativa. We aimed to find whether surgery results were a better global control on the disease activity in both, the area where the surgery is performed and distant areas. We evaluated the disease course of 17 patients with hidradenitis suppurativa who underwent wide excision of complex fistula tracts between October 2018 and January 2022 at the Hospital Universitario de la Princesa, Madrid. We found that wide excision of complex fistulas produces an overall positive effect on the inflammatory activity in hidradenitis suppurativa that may be important to achieve an adequate control of the disease.