RESUMEN
Objective: We investigated relapse rates after anti-tumor necrosis factor (anti-TNF) withdrawal in inflammatory bowel disease (IBD) patients, response to restart of anti-TNF treatment and predictors for relapse. Methods: IBD patients in remission receiving infliximab or adalimumab treatment for ≥1 year who discontinued treatment were included. Relapse rates and predictors for relapse were studied using survival and Cox regression analysis. Results: In total, 101 patients were included (77 CD, 24 UC). A total of 56 patients (55%) experienced a relapse (CD 38, UC 18) with a median time to relapse of 32 and 18 months in CD and UC, respectively. Of patients that were retreated with the same anti-TNF agent, 84% responded. A trough serum concentration ≥2 µg/ml within 1 year prior to anti-TNF discontinuation was associated with a higher relapse rate in CD patients (HR 2.89; p = .018), which was more evident in patients requiring retreatment with biologicals, bowel-related surgery or experimental medication (HR: 4.18; p = .009). A young age (<17 years) at diagnosis was associated with a higher relapse rate (HR: 2.29; p = .040) and fecal calprotectin levels <25 µg/g with a lower relapse rate in CD patients (HR: 0.34; p = .041). Relapse rates, requiring treatment with biologicals or experimental medication, was lower in UC patients who continued immunosuppressive treatment (HR: 0.26; p = .042). Conclusions: Approximately 55% of patients relapsed after anti-TNF withdrawal with a median time to relapse of 32 and 18 months in CD and UC, respectively. Retreatment with the same anti-TNF was successful in 84% of patients.
Asunto(s)
Adalimumab , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Infliximab , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab/administración & dosificación , Adulto , Estudios de Cohortes , Heces/química , Femenino , Humanos , Infliximab/administración & dosificación , Estimación de Kaplan-Meier , Complejo de Antígeno L1 de Leucocito/análisis , Masculino , Persona de Mediana Edad , Análisis Multivariante , Países Bajos , Modelos de Riesgos Proporcionales , Recurrencia , Inducción de Remisión , Factores de TiempoRESUMEN
BACKGROUND: Several factors influencing the pharmacokinetics of infliximab (IFX) in inflammatory bowel disease (IBD) have been identified. We studied the impact of patient, disease, and treatment characteristics on clearance and immunogenicity of IFX in a real-world patient-with-IBD cohort. METHODS: Serum concentrations of IFX and antibodies to IFX (ATIs) were measured in patients with IBD at a single center using an enzyme-linked immunosorbent assay and radioimmunoassay. Patient, disease, and treatment characteristics were retrospectively collected along with laboratory values. Pharmacokinetics and ATI titer were analyzed simultaneously by nonlinear mixed-effects modeling. RESULTS: Nine hundred ninety-seven IFX concentrations and 756 ATI measurements from 332 patients with IBD (253 Crohn's disease and 79 ulcerative colitis) were included. Mean (SD) IFX dose was 5.47 ± 1.33 mg/kg. ATIs were detected in 75/332 (23%) patients; insufficient exposure below an IFX trough level of 3 µg/mL was the most predictive factor of developing ATI and resulted in a 4-fold increased risk of ATI development. ATI titer was a better predictor of IFX clearance than ATI as a dichotomous parameter. ATI titers >30 AU/mL were consistently associated with undetectable IFX concentrations. IFX clearance was affected by body weight (40-149 kg) ranging from 0.27 to 0.53 L/d, serum albumin (2-5.4 g/dL) from 0.93 to 0.24 L/d, and titers of ATIs (0-53,000 AU/mL) from 0.36 L/d to 15.93 L/d (P < 0.001). Previously biologic-treated patients exhibited a higher clearance of IFX. CONCLUSIONS: IFX exposure below 3 µg/mL increases risk of ATIs. Identification of influential pharmacokinetics and ATI factors improves prediction of IFX levels, potentially allowing individualized dosing and cost reduction.
Asunto(s)
Anticuerpos Monoclonales/farmacocinética , Monitoreo de Drogas , Fármacos Gastrointestinales/farmacocinética , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Infliximab/farmacocinética , Adulto , Anticuerpos Monoclonales/sangre , Anticuerpos Monoclonales/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/sangre , Enfermedades Inflamatorias del Intestino/inmunología , Infliximab/sangre , Infliximab/inmunología , Masculino , Tasa de Depuración Metabólica/inmunología , Persona de Mediana Edad , Estudios Retrospectivos , Albúmina Sérica/efectos de los fármacosRESUMEN
OBJECTIVE: Infliximab maintenance treatment for Crohn's disease (CD) consists of intravenous infusions that are usually given at 6-8-week intervals. We aimed to evaluate whether home-based infliximab infusions could offer a useful and safe alternative for the management of CD patients. METHODS: Adult CD patients receiving infliximab maintenance treatment at the Academic Medical Center in Amsterdam were invited to receive their infusions at home for the duration of 1 year. Patients had to be in clinical remission and should have had no adverse events during previous infusions. Patient satisfaction and experience were studied. Costs were analyzed and compared with hospital-based infliximab infusions. RESULTS: Twenty-nine patients were invited, of whom 13 (45%) wanted to participate. Of the participants, 54% were female, and the median age was 33 years. In total, 59 infliximab infusions were administered at home at a median dose of 360 mg. The median rating of patient satisfaction was 8 on a scale from 1 to 10 for both home and hospital treatment settings. An important observation was that patients' willingness to participate would have been 70% if the possibility of receiving infusions at home outside office hours had been offered. Costs of infliximab infusions at home were 229 per infusion compared with 284 at the infusion clinic (excluding drug costs). CONCLUSION: Home-based infliximab infusions were associated with a cost saving of 55 per infusion. Most participants were satisfied and would recommend home-based infusions to others. Infliximab treatment at home might be recommended as routine care for CD patients.