Anti-TNF Withdrawal in Inflammatory Bowel Disease

Abstract

The introduction of the anti-tumor necrosis factorα agents (anti-TNFα) in clinical practice has greatly advanced the treatment of inflammatory bowel disease. The use of these medications results in durable remission in a subset of patients, preventing surgery and hospitalizations. However, there are some concerns about safety and costs associated with their long-term use. Therefore, anti-TNF withdrawal has emerged as an important consideration in clinical practice. Herein our goal was to discuss the available evidence about anti-TNFα discontinuation in IBD that could inform the clinician on the expected rates of relapse, the potential predictors of relapse, as well the response to re-treatment.

Anti-TNF Therapy in Crohn’s Disease

“…Anti-TNF treatment currently represents a central treatment modality in Crohn’s disease and can be improved by rapid dose escalation and the use of combination therapy [102]. However, two decades on from their introduction, questions still remain about their use including timing, dosing, monitoring and issues surrounding loss of response such as risk factors, biomarkers, mechanism and strategies for prevention and treatment [79].…”

“…In summary, anti-TNF introduction has led to major shifts in the therapeutic paradigm that evolved from slow symptomatic clinical remission towards rapid sustained and deep remission; short- and long-term clinical, and endoscopic endpoints can now be reached that were previously unachievable [ 89 , 92 ]. Anti-TNF treatment currently represents a central treatment modality in Crohn’s disease and can be improved by rapid dose escalation and the use of combination therapy [ 102 ]. However, two decades on from their introduction, questions still remain about their use including timing, dosing, monitoring and issues surrounding loss of response such as risk factors, biomarkers, mechanism and strategies for prevention and treatment [ 79 ].…”

“…Clinicians and patients are often faced with the question on whether it is possible to stop anti-TNF therapy once disease remission has been achieved. However, despite all the studies that have now addressed this issue in IBD, no conclusive strategy has yet emerged [ 102 ]. Data is inconclusive due to varying reported rates of relapse on stopping anti-TNF, and conclusions are difficult to draw from the studies due to disease phenotype heterogeneity, with variable definitions of clinical remission and variable duration of remission before drug withdrawal.…”

“…Relapse rates among those studies range from 21 to 56% at 12 months and from 47 to 64% at 24 month [ 104 , 105 , 106 , 107 , 108 , 109 ]. Further studies are still required in order to answer the question on whether maintaining the anti-TNF as opposed to reducing/discontinuing the drug is superior to maintain remission; as well as to define routine strategy in the future for long-term management of CD patients and to define the optimal withdrawal strategy [ 102 , 103 ]. Studies assessing withdrawal in circumstances such as early disease or in the context of monotherapy (as opposed to in combination with immunomodulator agent), and a large European trial (Biocycle Project) seeks to answer some of these questions [ 102 ].…”

A Review on the Use of Anti-TNF in Children and Adolescents with Inflammatory Bowel Disease

“…Amongst others, factors predictive of relapse in IBD are elevated inflammatory markers (e.g. elevated leukocyte count, elevated C-reactive protein, elevated faecal calprotectin) and absence of mucosal healing [97]. Although no official guidelines are available on the discontinuation of anti-TNF agents in paediatric IBD, according to the available literature it is suggested to evaluate all clinical parameters and perform an endoscopy to assess mucosal healing prior to withdrawal of anti-TNF therapy.…”