The HLA-DQA1*05 genotype does not influence the clinical response to ustekinumab and vedolizumab.

BACKGROUND: the success of strategies with earlier anti-TNF drugs for the treatment of inflammatory bowel disease (IBD) have been shadowed by the development of anti-drug antibodies that reduce their effectiveness. The HLA-DQA1*05 allele has been shown to increase the risk of immunogenicity to anti-TNF drugs by approximately two-fold. The negative impact of this allele has not been fully investigated for newer biotherapies. OBJECTIVE: whether the presence of the HLA-DQA1*05 allele is associated with a reduction of response to ustekinumab and vedolizumab was investigated. MATERIAL AND METHODS: the impact of HLA-DQA1*05 on disease activity in 93 patients with IBD, treated with ustekinumab (n = 39) or vedolizumab (n = 54) was investigated in a retrospective cohort study. Treatment response and remission was assessed at 6 and 12 months for ustekinumab, and up to 18 and 24 months for vedolizumab, using Harvey-Bradshaw index (Crohn's disease) and Mayo score (ulcerative colitis). RESULTS: the HLA-DQA1*05 allele was found in 35.9 % and 38.9 % of patients treated with ustekinumab and vedolizumab, respectively. Clinical response was not affected by the presence of the HLA-DQA1*05 allele for both treatment groups. CONCLUSIONS: in contrast to anti-TNF drugs, HLA-DQA1*05 presence does not correlate with the decreased response to ustekinumab or vedolizumab.

The HLA-DQA1*05 genotype does not influence the clinical response to ustekinumab and vedolizumab

Background: the success of strategies with earlier anti-TNF drugs for the treatment of inflammatory bowel disease (IBD) have been shadowed by the development of anti-drug antibodies that reduce their effectiveness. The HLA-DQA1*05 allele has been shown to increase the risk of immunogenicity to anti-TNF drugs by approximately two-fold. The negative impact of this allele has not been fully investigated for newer biotherapies. Objective: whether the presence of the HLA-DQA1*05 allele is associated with a reduction of response to ustekinumab and vedolizumab was investigated. Material and methods: the impact of HLA-DQA1*05 on disease activity in 93 patients with IBD, treated with ustekinumab (n = 39) or vedolizumab (n = 54) was investigated in a retrospective cohort study. Treatment response and remission was assessed at 6 and 12 months for ustekinumab, and up to 18 and 24 months for vedolizumab, using Harvey-Bradshaw index (Crohn’s disease) and Mayo score (ulcerative colitis). Results: the HLA-DQA1*05 allele was found in 35.9 % and 38.9 % of patients treated with ustekinumab and vedolizumab, respectively. Clinical response was not affected by the presence of the HLA-DQA1*05 allele for both treatment groups. Conclusions: in contrast to anti-TNF drugs, HLA-DQA1*05 presence does not correlate with the decreased response to ustekinumab or vedolizumab (AU)

Ustekinumab en la enfermedad de Crohn: resultados en la vida real y posibles factores de respuesta / Ustekinumab in Crohn's disease: real-world outcomes and predictors of response

Antecedentes: ustekinumab es un anticuerpo monoclonal que inhibe las interleucinas IL-12 e IL-23, y está aprobado para el tratamiento de la enfermedad de Crohn (EC) y, más recientemente, también de la colitis ulcerosa (CU). El objetivo de este estudio fue evaluar la eficacia y seguridad de ustekinumab, así como identificar posibles factores predictivos de respuesta en un entorno de la vida real.Métodos: se realizó un estudio observacional, retrospectivo y multicéntrico en 4 hospitales de Andalucía. Se incluyeron pacientes adultos con diagnóstico confirmado de EC tratados con ustekinumab entre 2017 y 2019. Se analizó la respuesta clínica a los 3, 6 y 12 meses de tratamiento. La actividad clínica de la enfermedad se evaluó con el índice de Harvey-Bradshaw (HBI) y el índice de actividad de la enfermedad de Crohn (CDAI); La respuesta bioquímica se evaluó con parámetros de laboratorio como CRP y ESR. Se analizó la supervivencia al fármaco ustekinumab a un año.Resultados: Se analizaron un total de 98 pacientes (edad media, 43 años; el 52 % eran hombres); El 56 % había fracasado con ≥ 2 terapias biológicas previas. A los 3 meses, el 69 % de los pacientes estaban en respuesta y el 40,8 % en remisión. A los 6 meses, el 56 % estaba en remisión clínica. A los 12 meses, el 73,7 % estaba en respuesta clínica y el 60,5 % en remisión. La remisión sin corticosteroides fue del 32,4 %, 44 % y 47,4 % a los 3, 6 y 12 meses, respectivamente. La supervivencia acumulada tras un año de tratamiento con ustekinumab fue del 85,3 %. Los parámetros bioquímicos como CRP y ESR mostraron una disminución estadísticamente significativa entre los niveles de referencia y de control a los 3, 6 y 12 meses. Un HBI más bajo al inicio y el sexo femenino fueron predictores de remisión clínica libre de corticosteroides en un análisis univariante. (AU)

Ustekinumab in Crohn's disease: real-world outcomes and predictors of response.

BACKGROUND: ustekinumab is a monoclonal antibody that inhibits interleukins IL-12 and IL-23, and is approved for the treatment of Crohn's disease (CD) and, more recently, also ulcerative colitis (UC). The aim of this study was to evaluate the effectiveness and safety of ustekinumab, as well as to identify possible predictive factors of response in a real-life setting. METHODS: an observational, retrospective, multicenter study was carried out in 4 hospitals in Andalusia. Adult patients with a confirmed diagnosis of CD treated with ustekinumab from 2017 to 2019 were included. Clinical response was analyzed at 3, 6 and 12 months of treatment. Clinical disease activity was assessed with the Harvey-Bradshaw index (HBI) and the Crohn's Disease Activity Index (CDAI); biochemical response was assessed with lab parameters such as CRP and ESR. One-year ustekinumab drug-survival was analyzed. RESULTS: a total of 98 patients were analyzed (mean age, 43 years; 52 % were male); 56 % had failed with ≥ 2 previous biologicals therapies. At 3 months, 69 % of the patients were in response and 40.8 % in remission. At 6 months, 56 % were in clinical remission. At 12 months, 73.7 % were in clinical response and 60.5 % in remission. Corticosteroid-free remission was 32.4 %, 44 %, and 47.4 % at 3, 6, and 12 months, respectively. Cumulative survival after one year of treatment with ustekinumab was 85.3 %. Biochemical parameters such as CRP and ESR showed a statistically significant decrease between baseline and control levels at 3, 6, and 12 months. A lower HBI at baseline and female sex were predictors of corticosteroid-free clinical remission in a univariate analysis. In the multivariate analysis no variables were found as predictors of corticosteroid-free clinical remission. CONCLUSION: ustekinumab therapy is safe and useful, inducing clinical response in more than 50 % of patients, including patients who failed with other biological therapies.