Improved Long-term Outcomes of Patients With Inflammatory Bowel Disease Receiving Proactive Compared With Reactive Monitoring of Serum Concentrations of Infliximab

Abstract

BACKGROUND & AIMS Monitoring serum concentrations of tumor necrosis factor antagonists in patients receiving these drugs as treatment for inflammatory bowel disease (IBD), also called therapeutic drug monitoring, is performed either after patient loss of response (reactive drug monitoring) or in patients in clinical remission whose drug has been titrated to a target concentration (proactive drug monitoring). We compared long-term outcomes of patients with IBD undergoing proactive vs reactive monitoring of serum concentrations of infliximab. METHODS We performed a multicenter, retrospective study of 264 consecutive patients with IBD (167 with Crohn’s disease) receiving infliximab maintenance therapy. The subjects received proactive (n = 130) or reactive (n = 134) drug monitoring, based on measurements of first infliximab concentration and antibodies to infliximab, from September 2006 to January 2015; they were followed through December 2015 (median time of 2.4 years). We analyzed time to treatment failure, first IBD-related surgery or hospitalization, serious infusion reaction, and detection of antibodies to infliximab. Treatment failure was defined as drug discontinuation for loss of response or serious adverse event, or need for surgery. RESULTS Multiple Cox regression analysis independently associated proactive drug monitoring, compared with reactive monitoring, with reduced risk for treatment failure (hazard ratio [HR], 0.16; 95% confidence interval [CI], 0.09–0.27; P < .001), IBD-related surgery (HR, 0.30; 95% CI, 0.11–0.80; P = .017), IBD-related hospitalization (HR, 0.16; 95% CI, 0.07–0.33; P < .001), antibodies to infliximab (HR, 0.25; 95% CI, 0.07–0.84; P = .025), and serious infusion reaction (HR, 0.17; 95% CI, 0.04–0.78; P = .023). CONCLUSIONS In a retrospective analysis of patients with IBD receiving proactive vs reactive monitoring of serum concentration of infliximab, proactive monitoring was associated with better clinical outcomes, including greater drug durability, less need for IBD-related surgery or hospitalization, and lower risk of antibodies to infliximab or serious infusion reactions.

Review article: consensus statements on therapeutic drug monitoring of anti‐tumour necrosis factor therapy in inflammatory bowel diseases

“…There was, however, potential for confounders in this study. Another retrospective observational study found significantly lower likelihood of treatment failure (HR 0.16, P < .001), hospitalisation (HR 0.16, P < .001), surgery (HR 0.30, P = .017), development of anti‐drug antibodies (HR 0.25, P = .025) and serious infusion reactions (HR 0.17, P = .023) with proactive vs reactive TDM‐guided infliximab dosing …”

Infliximab trough concentrations during maintenance therapy are associated with endoscopic and histologic healing in ulcerative colitis

“…Reactive therapeutic drug monitoring is emerging as the new standard‐of‐care for optimizing anti‐TNF therapy in inflammatory bowel disease (IBD) . Recent studies have demonstrated that proactive therapeutic drug monitoring of infliximab with drug titration to a therapeutic window is associated with favorable long‐term therapeutic outcomes in IBD and may be superior to reactive therapeutic drug monitoring . Moreover, many exposure‐response relationship studies have shown that higher serum anti‐TNF drug concentrations are associated with better clinical outcomes in IBD, suggesting that it is maybe time to go beyond from a ‘treat‐to‐target’ to a ‘treat‐to‐trough’ therapeutic approch .…”

Utilidad de la monitorización terapéutica de infliximab en el manejo de la enfermedad inflamatoria intestinal

“…En pacientes en tratamiento con IFX en esquema de mantención, dos estrategias han sido sugeridas en la práctica clínica 18,23, . Por una parte, la MTF ha sido planteada cuando los pacientes presentan evidencias de actividad inflamatoria, lo que permite definir la mejor estrategia terapéutica siendo esta decisión más costo efectiva que escalar de manera empírica 31,32 .…”

“…La monitorización terapéutica del fármaco (MTF), definida como la evaluación de la concentración de la droga y de los niveles de anticuerpos contra éste, ha demostrado ser más efectiva que el manejo estándar en términos de resultados clínicos y costo efectividad, logrando de esta manera una terapia personalizada [14][15][16][17][18][19][20][21][22][23] . Pese a estos resultados, no existen publicaciones nacionales que hayan evaluado la monitorización de IFX y ATI y su efecto en pacientes con EII.…”