Considerations, challenges and future of anti-TNF therapy in treating inflammatory bowel disease

Abstract

Anti-TNF therapy remains the cornerstone in the treatment of IBD. When initiating long-term therapy, safety and cost issues are of great importance. The therapeutic armamentarium in the treatment of IBD is rapidly growing. Therefore, the challenge is to optimize the use and refine the exact position of anti-TNF therapy in the near future, with personalized medicine as the ultimate goal.

Next generation of small molecules in inflammatory bowel disease

“…Furthermore, a significant proportion of patients (between 13% and 25% per year)19–21 may develop a loss of response to anti-TNF agents over time (ie, secondary non-response) 20 21. This loss of response may be due to pharmacodynamic, pharmacokinetic and/or immunogenic factors 22. Combination therapy is the best way to prevent the formation of antibodies,23 which are known to decrease efficacy and increase the risk of infusion reactions 24.…”

Loss of Response to Vedolizumab and Ability of Dose Intensification to Restore Response in Patients With Crohn’s Disease or Ulcerative Colitis: A Systematic Review and Meta-analysis

“…1 Anti-TNF agents have a well-established efficacy for the use as maintenance therapy in both Crohn's disease (CD) and ulcerative colitis (UC); however, a proportion of patients lose response over time. 2 The annual risk for loss of response in CD was estimated to be 13% per patientyear for infliximab 3 and 20.3% per patient-year for adalimumab. 4 In the majority of IBD patients, dose intensification proved to be an efficacious way to recapture response.…”

“…All monoclonal agents have the potential for immunogenicity, 8 but low rates of anti-drug antibody formation were reported in the phase 3 trials with vedolizumab. 2 Nevertheless, patients who have initially responded to vedolizumab therapy might subsequently lose response and experience flares of symptoms during maintenance treatment with the drug. This scenario poses important challenges to practicing clinicians, as different therapeutic approaches should then be considered: vedolizumab dose intensification, switch to other drugs, or surgical interventions.…”

The RAGE signaling pathway is involved in intestinal inflammation and represents a promising therapeutic target for Inflammatory Bowel Diseases

“…In the last 2 decades, a shift toward a pathway-based approach occurred, targeting immunomodulatory molecules with known physiopathological implications 4,5 . Despite the advent of anti-TNF which has constituted a major breakthrough for patients, many patients remain refractory to treatment or lose response over time 6 . New therapeutics in IBD should not only lead to clinical improvement but more importantly to deep remission which will prevent long-term sequelae.…”