The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD With the European Crohn's and Colitis Organization: When to Start, When to Stop, Which Drug to Choose, and How to Predict Response?

Abstract

The advent of biological therapy has revolutionized inflammatory bowel disease (IBD) care. Nonetheless, not all patients require biological therapy. Selection of patients depends on clinical characteristics, previous response to other medical therapy, and comorbid conditions. Availability, reimbursement guidelines, and patient preferences guide the choice of first-line biological therapy for luminal Crohn's disease (CD). Infliximab (IFX) has the most extensive clinical trial data, but other biological agents (adalimumab (ADA), certolizumab pegol (CZP), and natalizumab (NAT)) appear to have similar benefits in CD. Steroid-refractory, steroid-dependent, or complex fistulizing CD are indications for starting biological therapy, after surgical drainage of any sepsis. For fistulizing CD, the efficacy of IFX for inducing fistula closure is best documented. Unique risks of NAT account for its labeling as a second-line biological agent in some countries. Patients who respond to induction therapy benefit from systematic re-treatment. The combination of IFX with azathioprine is better than monotherapy for induction of remission and mucosal healing up to 1 year in patients who are naïve to both agents. Whether this applies to other agents remains unknown. IFX is also effective for treatment-refractory, moderate, or severely active ulcerative colitis. Patients who have a diminished or loss of response to anti-tumor necrosis factor (TNF) therapy may respond to dose adjustment of the same agent or switching to another agent. Careful consideration should be given to the reasons for loss of response. There are insufficient data to make recommendations on when to stop anti-TNF therapy. Preliminary evidence suggests that a substantial proportion of patients in clinical remission for >1 year, without signs of active inflammation can remain in remission after stopping treatment.

Rol de infliximab en enfermedad inflamatoria intestinal: Experiencia local

“…La indicación principal es refractariedad a las terapias convencionales 9,[12][13][14] . En nuestro estudio esta causa fue 48%, seguido por compromiso perianal en EC (36%).…”

“…En pacientes jóvenes en terapia asociada a inmunosupresores aumenta el riesgo de linfoma hepatoesplénico de células T 12 . Además, estudios han señalado mayor riesgo de infecciones oportunistas 2,12,13 , micóticas y de reactivación de tuberculosis 2,8,41 , principalmente con su uso asociado a esteroides e inmunomoduladores 8,14,41 . En nuestro estudio sólo tres pacientes presentaron infecciones, las cuales no fueron graves ni motivaron la suspensión de la terapia.…”

“…Diferentes estudios han demostrado la eficacia de la terapia con infliximab tanto en EC como en CU, logrando cumplir los objetivos del tratamiento en estas patologías 1,3,4,10,[12][13][14]15 . Infliximab está indicado en pacientes con corticodependencia, refractariedad a corticoides e inmunomoduladores, fístula perianal y manifestaciones extraintestinales asociadas a EII 9,[12][13][14]16 .…”

“…Infliximab está indicado en pacientes con corticodependencia, refractariedad a corticoides e inmunomoduladores, fístula perianal y manifestaciones extraintestinales asociadas a EII 9,[12][13][14]16 . No obstante, aún existe una subutilización de esta terapia por temor a los eventos adversos asociados a su uso y por los costos del tratamiento 2,17 .…”

Therapeutic Drug Monitoring in Inflammatory Bowel Disease

“…Several factors have been demonstrated to be associated with a primary loss of response to anti-TNF in IBD, including longer (>2 years) disease duration, extensive small bowel disease in CD, smoking and normal C-reactive protein (CRP) on initiation of treatment [7,8]. Polymorphisms in the apoptosis-related genes such as FAS-L and Caspase 9, as well as in the IBD5 locus, were also associated with an increased risk of primary LOR in CD [8,9].…”