Review article: applying pharmacokinetics to optimise dosing of anti‐TNF biologics in acute severe ulcerative colitis

Abstract

Background Acute severe ulcerative colitis (ASUC), the most aggressive presentation ulcerative colitis (UC), occurs in 15 percent of adults and children with UC. First line therapy with intravenous corticosteroids is ineffective in half of adults and one third of children. Therapeutic monoclonal antibodies against TNF (anti-TNF therapy) are emerging as a common treatment for ASUC due to their similar efficacy to calcineurin inhibitors and more favorable adverse effect profile. Aim To comprehensively review the evidence for anti-TNF therapy for ASUC in children and adults with regard to outcomes and pharmacokinetics. Methods PubMed and recent conference proceedings were searched using the terms “ulcerative colitis”, “acute severe ulcerative colitis”, “anti-TNF”, “pharmacokinetics”, and the generic names of specific anti-TNF agents. Results Outcomes after anti-TNF therapy for ASUC remain suboptimal with aboutone half of children and adults undergoing colectomy. While several randomized controlled trials have demonstrated the efficacy of anti-TNF therapy for ambulatory patients with moderate to severely active UC, patients in these studies were less ill than those with ASUC. Patients with ASUC may exhibit more rapid clearance of anti-TNF biologics due pharmacokinetic mechanisms influenced by disease severity. Conclusions Conventional weight-based dosing effective in patients with moderately to severely active UC, may not be equally effective in those with ASUC. Personalized anti-TNF dosing strategies that integratepatient factors and early measures of pharmacokinetics and response hold promise for ensuring sustained drug exposure and maximizing early mucosal healing in patients with ASUC.

Predicting durable response or resistance to antitumor necrosis factor therapy in inflammatory bowel disease

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Terapia de inducción acelerada con infliximab en paciente con colitis ulcerosa grave refractaria a corticoides. Caso clínico

“…Por ello, es importante considerar la presencia de factores que pueden modificar la farmacocinética de infliximab y con ello los niveles plasmáticos y tisulares del fármaco [17][18][19] . Niveles elevados de TNF-α a nivel plasmático y tisular, PCR elevada, hipoalbuminemia y un índice de masa corporal elevado, pueden aumentar el clearence de infliximab afectando de esta manera su efectividad.…”

Update on anti-tumor necrosis factor agents and other new drugs for inflammatory bowel disease

“…171 A 2015 survey of the The association of anti-TNF therapy with postoperative complications and infections is controversial. The literature comprises mostly single center retrospective studies with conflicting results.…”