P437 Risk of immunomediated adverse events or secondary loss of response to infliximab in elderly patients with inflammatory bowel disease: a cohort study of the ENEIDA registry

Calafat, Margalida; Mañosa, Míriam; Panés, J; Nos, Pilar; Iglesias, Eva; Vera, Isabel; López-Sanromán, Antonio; Guardiola, Jordi; Taxonera, Carlos; Mínguez, Miguel; Martin, M; Castro, Luísa; Riestra, Sabino; Rivero, Miguel; García‐Planella, Esther; Calvet, Xavier; García-López, Santiago; Andreu, M.; Gomollón, Fernando; Barrio, Jesús; Esteve, M.; Rodríguez, A; Gisbert, J.P.; Gutiérrez, Alejandro García; Hinojosa, Joaquín; Argüelles, F; Busquets, David; Bujanda, Luís; Lazaro, J. L.; Sicilia, B; Merino, Olga; Martínez, Patricia; Bermejo, Fernando; Lorente, Rufo; Barreiro-de-Acosta, Manuel; Rodríguez, Carlos; Fe, Mireia Morgades de la; Piqueras, Marta; Romero, Pilar; Rodríguez, Esther; Roncero, Óscar; Llaó, Jordina; Alcaín, G; Riera, Joan; Sierra, Mónica S.; Salazar, L I Fdez.; Navarro, Mercè; Montoro, Miguel; Muñoz, Carmen; Lucendo, Alfredo J.; Domselaar, Manuel Van; Moraleja, Irene; Huguet, J M; Ramos, Lídia Roque; Ramírez, Pablo; Almeda, P; Pajares, Ramón; Khorrami, Sam; Madrigal, R; Sesé, E; Trapero, A M; Legido, Jesús; Abad, Águeda; Cañete, Fiorella; Cabré, E.; Domènech, Eugeni

doi:10.1093/ecco-jcc/jjy222.561

Cited by 3 publications

(3 citation statements)

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“…Biologics are an effective and safe treatment for moderate‐to‐severe CD. However, there is a high proportion of primary LOR, and patients who initially respond to biologics may lose response to the biologics over time 10,12 . It would be of great value to identify associated factors for LOR.…”

Section: Discussionmentioning

confidence: 99%

“…Identifying the associated factors that can predict responses to therapies is important when making personalized medicine decisions 2 . Several risk factors for LOR have also been reported 8,12,13 such as treatment duration and disease activity after induction. Nevertheless, in clinical practice, predicting which patients will respond to biologic therapy remains challenging.…”

Section: Introductionmentioning

confidence: 99%

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Sarcopenia assessed by computed tomography or magnetic resonance imaging is associated with the loss of response to biologic therapies in adult patients with Crohn's disease

Liu,

Tang,

Lin

et al. 2023

Clinical Translational Sci

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Sarcopenia occurs in patients with Crohn's disease (CD). However, the association between sarcopenia and loss of response (LOR) to biologic agents remains unclear. This study explored such association in CD patients. This retrospective study included 94 CD patients who received biologic therapy. The skeletal muscle cross‐sectional area at the third lumbar was assessed by computed tomography or magnetic resonance imaging for sarcopenia evaluation. An LOR was defined by fecal calprotectin (FC) < 250 μg/g or > 50% reduction from baseline levels or other factors, such as the used agent being replaced by other biologic agents. The association between sarcopenia and LOR was assessed by logistic regression analysis. LOR was observed in 54 patients (57.4%). The prevalence of sarcopenia in LOR group was higher than that in response group (70.4% vs 40.0%, p = 0.003). Sarcopenia (odds ratio (OR) = 3.89, 95% confidence interval (CI): 1.31‐11.54), Montreal L1 type (OR = 0.20, 95% CI: 0.06‐0.60), perianal lesions (OR = 4.08, 95% CI: 1.31‐12.70) and monocytes percentage (OR = 1.27, 95% CI: 1.02‐1.57) at baseline were independent associated factors for LOR. Sarcopenia was also associated with LOR in patients who received infliximab (OR = 3.31, 95% CI: 1.11‐9.87). Montreal L1 type, perianal lesions and monocyte percentage (model one), and with additional consideration of sarcopenia (model two) were developed to predict LOR. Model two showed better performance than model one (area under the curve, 0.82 vs 0.75). Sarcopenia was associated with the LOR to biological agents or infliximab in adult patients with CD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sarcopenia assessed by computed tomography or magnetic resonance imaging is associated with the loss of response to biologic therapies in adult patients with Crohn's disease

Liu,

Tang,

Lin

et al. 2023

Clinical Translational Sci

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“…Despite the introduction of newer anti-TNF and more gutspeci c biologics, IFX remains widely prescribed due to its extensive safety pro le and long history of use in clinical practice [4]. However, 10-46% of IBD patients on anti-TNF treatment experience a loss of response (LOR) in the rst year of therapy [5]. LOR induces inescapable discontinuation of IFX treatment and complications leading to surgeries.…”

Section: Introductionmentioning

confidence: 99%

HLA-DQA1*05 and upstream variants of PPARGC1B are associated with infliximab persistence in Japanese Crohn’s disease patients

et al. 2023

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Recently, the HLA-DQA1*05 (rs2097432) genetic variation has been reported to be linked to early In iximab (IFX) treatment failure in the Caucasian Crohn's disease (CD) population, but that evidence is scarce in the Asian population. This study aimed to investigate the relationship between rs2097432 and the cumulative discontinuation-free time of IFX (IFX persistence) in 189 Japanese IFX-naiveCD patients. We also performed a genome-wide association study (GWAS) to discover novel genetic predictors for IFX persistence. The rs2097432 signi cantly increased the risk of early discontinuation of IFX even after being adjusted by other clinical parameters [Hazard ratio (HR) = 2.13 and P-value = 0.038]. In GWAS, one locus tagged by rs73277969, located upstream of PPARGC1B, reached genome-wide signi cance (HR = 6.04 and P-value = 7.93E-9). We con rmed the robust association of rs2097432 with IFX persistence regardless of the population. A novel genetic factor for IFX persistence was also identi ed using GWAS.In addition, unbiased genome-wide association research (GWAS) has revealed relationships between genetic backgrounds and clinical response to several drugs, such as rs2097432. Recent pharmacogenomics research in Asian patients with IBD showed a link between a genetic polymorphism of the Nudix hydrolase 15 (NUDT15) and the severe adverse effect of thiopurines [16]. Before these ndings, NUDT15's role in thiopurine metabolism was unknown, suggesting the usefulness of the unbiased approaches in this eld. Performing GWAS to identify novel predictors for IFX failure in Japanese patients, which has never been found before, is also an urgent issue.This study primarily aimed to explore the association between rs2097432 and cumulative IFX discontinuationfree rates in Japanese patients with CD. Furthermore, we conducted an unbiased genome-wide survival analysis to identify the novel genetic factors associated with cumulative IFX discontinuation-free rates. Materials And Methods Study designThis was a single-center retrospective, observational cohort study. The study protocol was reviewed and approved by the Tohoku University Hospital Ethics Committee (2020-1-608). All the patients provided written informed consent. The research followed the Japanese Ministry of Health, Labor, and Welfare ethical guidelines for medical and health studies in humans. SubjectsFrom August 2002 to December 2020, we enrolled consecutive, self-reported Japanese CD patients who had a history of treatment with IFX (Remicade®, Mitsubishi-Tanabe Pharma, Tokyo, Japan) at Tohoku University Hospital. We excluded patients who did not receive the scheduled maintenance treatment within 8 weeks due to either primary non-response or intolerance to the agents. Primary non-response was de ned as a case where IFX was stopped in the induction phase ( rst three administrations) due to a lack of or unsatisfactory agent response. Intolerance was de ned as a case where IFX was stopped because of an adverse event.CD was diagnosed based on endoscopic, radiological, and/or his...

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HLA-DQA1*05 and upstream variants of PPARGC1B are associated with infliximab persistence in Japanese Crohn’s disease patients

Naito

Shimoda²,

Kakuta

et al. 2023

Preprint

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Recently, the HLA-DQA1*05 (rs2097432) genetic variation has been reported to be linked to early Infliximab (IFX) treatment failure in the Caucasian Crohn’s disease (CD) population, but that evidence is scarce in the Asian population. This study aimed to investigate the relationship between rs2097432 and the cumulative discontinuation-free time of IFX (IFX persistence) in 189 Japanese IFX-naiveCD patients. We also performed a genome-wide association study (GWAS) to discover novel genetic predictors for IFX persistence. The rs2097432 significantly increased the risk of early discontinuation of IFX even after being adjusted by other clinical parameters [Hazard ratio (HR) = 2.13 and P-value = 0.038]. In GWAS, one locus tagged by rs73277969, located upstream of PPARGC1B, reached genome-wide significance (HR = 6.04 and P-value = 7.93E-9). We confirmed the robust association of rs2097432 with IFX persistence regardless of the population. A novel genetic factor for IFX persistence was also identified using GWAS.

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P437 Risk of immunomediated adverse events or secondary loss of response to infliximab in elderly patients with inflammatory bowel disease: a cohort study of the ENEIDA registry

Cited by 3 publications

References 0 publications

Sarcopenia assessed by computed tomography or magnetic resonance imaging is associated with the loss of response to biologic therapies in adult patients with Crohn's disease

Sarcopenia assessed by computed tomography or magnetic resonance imaging is associated with the loss of response to biologic therapies in adult patients with Crohn's disease

HLA-DQA1*05 and upstream variants of PPARGC1B are associated with infliximab persistence in Japanese Crohn’s disease patients

HLA-DQA1*05 and upstream variants of PPARGC1B are associated with infliximab persistence in Japanese Crohn’s disease patients

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