Failure to Achieve Target Drug Concentrations During Induction and Not HLA-DQA1∗05 Carriage Is Associated With Antidrug Antibody Formation in Patients With Inflammatory Bowel Disease

Proactive infliximab optimisation using a pharmacokinetic dashboard versus standard of care in patients with Crohn’s disease: study protocol for a randomised, controlled, multicentre, open-label study (the OPTIMIZE trial)

“…This therapeutic approach could also be applied in patients with increased IFX clearance, such as the paediatric IBD population and patients with ulcerative colitis, as well as in patients prone to develop ATI, such as those carrying the HLA-DQA1*05 allele 45–47. A post hoc analysis of a recent prospective study demonstrated that in an adult and paediatric cohort of patients with IBD optimised IFX monotherapy based on a PK dashboard-guided proactive TDM starting early during the induction phase the HLA-DQA1*05 risk variant carriage did not impact development of ATI nor drug durability 48…”

“… 45–47 A post hoc analysis of a recent prospective study demonstrated that in an adult and paediatric cohort of patients with IBD optimised IFX monotherapy based on a PK dashboard-guided proactive TDM starting early during the induction phase the HLA-DQA1*05 risk variant carriage did not impact development of ATI nor drug durability. 48 …”

Prognostication in inflammatory bowel disease

“…Most notably, the Personalizing Anti-TNF Therapy in CD (PANTS) consortium identified a variant, HLA-DQA1 * 05, associated with a significantly increased the risk of immunogenicity to anti-TNF (HR 1.90, 95% CI 1.60–2.25) in 1,240 biologic-naïve patients in the UK biobank ( 37 ). This has since been replicated in other cohorts, but the clinical action to take may be less straightforward as this risk variant did not confer risk for anti-drug antibody formation in two cohorts managed with proactively optimized infliximab monotherapy from induction ( 38 , 39 ); this signals that those with this risk variant could likely equally be treated with combination therapy or early proactively optimized monotherapy. Further study and collaboration across diverse populations are needed to continue to study the role of pharmacogenomics in the many new therapies currently available for IBD.…”

68 - Papel Del Hla Dqa1*05 en La Respuesta a Tratamiento Biológico Con Anti-TNF en Pacientes Con Enfermedad Inflamatoria Intestinal

“…Aquellos que presentasen la mutación pero no fuese posible asociar un inmunomodulador, advertían del alto riesgo de indicar terapia anti-TNF, en particular infliximab, por el alto riesgo de pérdida de respuesta secundaria. Por otro lado, sugerían que aquellos que no presentasen dicha mutación, independientemente del anti-TNF elegido, debería iniciarse en combinación con un inmunomodulador (20,21) Todos estos resultados, puestos en contexto y dada la elevada calidad del estudio, fueron considerados de gran valor por la comunidad científica, deseosa de encontrar factores predictores individuales de efectividad de algunas terapias biológicas. Determinar esta variante de HLA antes de iniciar un biológico, asociar o no terapia combinada con un inmunomodulador, e incluso elegir entre las opciones disponibles, se ha comenzado a implementar en algunos centros en su práctica clínica, asumiendo un mayor o menor riesgo individual de producción de anticuerpos contra el fármaco.…”

“…En un análisis post hoc del estudio PANTS, presentado durante el año 2021, no se encontraron diferencias estadísticamente significativas ni en el desarrollo de anticuerpos ni en la duración del tratamiento con infliximab entre aquellos que presentan la mutación y los que no lo hacían. Sugieren que los datos favorables previos se debían a un fallo del diseño del estudio, dando mayor relevancia a la influencia de los niveles séricos del fármaco durante la inducción y el desarrollo de inmunogenicidad (21,22).…”