Serum levels of infliximab and adalimumab are associated with deep remission in inflammatory bowel disease
Por:
Pascual-Marmaneu, O, Belles-Medall, M, Ferrando-Piqueres, R, Almela-Notari, P, Mendoza-Aguilera, M and Alvarez-Martin, T
Publicada:
1 sep 2021
Resumen:
Objective: Deep remission defined by clinical-biomarker remission and mucosal healing has emerged as a new therapeutic target in inflammatory bowel disease. The aim of this study was to define an optimal cut- off concentration for infliximab and adalimumab during maintenance therapy associated with deep remission. The secondary objective, was to evaluate the influence of variables on anti tumor necrosis factor-alpha concentrations and deep remission.
Method: Retrospective study including 120 and 122 patients inflammatory bowel disease diagnosed who received maintenance therapy with infliximab and adalimumab. Biomarker remission was considered by C-reactive protein < 5 mg/L and fecal calprotectin < 100 mu g/g. Crohn's disease clinical remission was defined by a Harvey Bradshaw score < 5 and mucosal healing by a simple endoscopic score for Crohn's disease< 3. In ulcerative colitis, it was defined as a Mayo total score < 3 and Mayo endoscopic subscore < 2. Receiver operating characteristic test was performed to determine drug concentration thresholds associated with deep remission. Anti tumor necrosis factor- alpha concentrations were classified into quartiles. X-2 and Kruskal-Wallis test were used to compare discrete and continuous variables between quartile groups. Multivariate logistic regression was performed to identify patient characteristics andserological facto C-reactive protein rs associated with deep remission.
Results: Anti tumor necrosis factor-alpha concentrations were higher inpatients with deep remission, in infliximab (4.4, interquartile range: 3.3-6.5 vs 2.3, interquartile range: 1.1-4.2 mu g/mL, P < 0.005) and adalimumab (6.3, interquartile range: 4.2-8.2 vs 3.9, interquartile range: 2.4-5.5 mu g/mL,P < 0.005). A Receiver operating characteristic test identified a concentration threshold of 3.1 mu g/mL in infliximab (area under the Receiver operating characteristic test curve, 0.72) and 6.3 mu g/mL in adalimumab (area underreceiver operating characteristic test curve, 0.75) associated with deep remission. Factors associated with the highest quartiles of serum infliximab concentration were: elevated body mass index, absence of previous inflammatory bowel disease-surgery, C-reactive protein < 5 mg/L, and fecal calprotectin < 100 mu g/g. In adalimumab, higher quartiles were related to concomitant immunosuppressants, low body mass index, absence of previous inflammatory bowel disease-surgery, and C-reactive protein < 5 mg/L and fecal calprotectin < 100 mu g/g. Multivariate regression identified fecal calprotectin < 100 mu g/g, C-reactive protein < 5 mg/L, infliximab >= 3.1 mu g/mL and adalimumab concentrations >= 6.3 mu g/mL as factors significantly associated with deep remission.
Conclusions: Trough infliximab and adalimumab concentrations, C-reactive protein < 5 mg/L and fecal calprotectin < 100 mu g/g are associated with deep remission during maintenance therapy. Cutoff point of 3.1 and 6.3 g/mL for inflixi-mab and adalimumab respectively, were identified as deep remission predictors.
Filiaciones:
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Univ Castellon, Gen Hosp, Serv Farm Hosp, Castellon de La Plana, Spain
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Univ Castellon, Gen Hosp, Serv Farm Hosp, Castellon de La Plana, Spain
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Univ Castellon, Gen Hosp, Serv Farm Hosp, Castellon de La Plana, Spain
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Univ Castellon, Gen Hosp, Serv Aparato Digestivo, Castellon de La Plana, Spain
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Univ Castellon, Gen Hosp, Serv Farm Hosp, Castellon de La Plana, Spain
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Univ Castellon, Gen Hosp, Serv Farm Hosp, Castellon de La Plana, Spain
Open Access
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