Systematic review: efficacy of escalated maintenance anti‐tumour necrosis factor therapy in Crohn's disease

Abstract

Summary Background Loss of response to anti‐TNF agents is a common clinical problem. Dose escalation may be effective for reestablishing clinical response in Crohn's disease (CD). Aims To perform a systematic review assessing the efficacy of escalated maintenance anti‐TNF therapy in CD. Methods EMBASE, MEDLINE, Web of Science, and CENTRAL databases were searched for English language publications through to April 25, 2021. Full‐text articles evaluating escalated maintenance treatment (infliximab or adalimumab) in adult CD patients were included. Results A total of 4733 records were identified, and 68 articles met eligibility criteria. Rates of clinical response (33%‐100%) and remission (15%‐83%) after empiric dose escalation for loss of response to standard anti‐TNF therapy were high but varied across studies. Dose intensification strategies (doubling the dose versus shortening the therapeutic interval) were similarly efficacious. Dose‐escalated patients tended to have higher serum drug levels compared to those on standard dosing. An exposure‐response relationship following dose escalation was found in a number of observational studies. Randomised controlled trials comparing therapeutic drug monitoring (TDM) to empiric treatment intensification have failed to reach their primary end‐points. Strategies including Bayesian dashboard‐dosing and early treatment escalation targeting biomarker normalisation were found to be associated with improved long‐term outcomes. Conclusions Empiric escalation of maintenance anti‐TNF therapy can recapture clinical response in a majority of patients with secondary loss of response to standard maintenance doses. Proactive optimisation of maintenance dosing might prolong time to loss of response in some patients.

Controversies in the management of anti-TNF therapy in patients with Crohn’s disease: a Delphi consensus

“…Delphi participants agreed that in the case of loss of response to anti-TNF therapy due to immunogenicity, assessing whether immunogenicity was preventable appears to be vital in order to improve CD management. In patients with secondary loss of response due to immunogenicity, a great variability in the rates of clinical response (33–100%) and remission (15–83%) was found upon empirical anti-TNF dose intensification 73. Small observational studies have reported reductions in antibody levels and increases in drug trough levels resulting in clinical responses upon adding an IMM drug 26 74–79.…”

High Adalimumab Dose at Beginning Maintenance Therapy in Crohn’s disease Patients

“…In iximab and adalimumab have been approved in mainland China for the treatment of CD, the recommended maintenance dose for adalimumab is 40 mg every other week (14). However, some CD patients do not achieve a clinical response to the standard dose of adalimumab, with the primary and secondary non-response rates for 10-30% and 23-46%, respectively (15). The results of our study suggest that both standard and high doses of adalimumab are effective in inducing clinical remission in patients with Crohn's disease, with no signi cant different in clinical remission rates (78.0% vs 73.8% P = 0.674) or time to treatment failure (HR0.6,95%CI [0.27,1.36], P = 0.225) between the two regimens in in iximab-naïve CD patients.…”

Long-term clinical and real-world experience with Crohn’s disease treated with anti-tumor necrosis factor-α antibodies

“…The reasons for this are difficult to explain. The clinical response and clinical remission rates were, respectively, 34% to 90% and 26% to 81% after dose escalation of IFX and 33% to 100% and 15% to 83% after dose escalation of ADA [ 23 ]. In patients with secondary LOR to ADA, administering ADA at an escalated dose of 80 mg every 2 weeks or at a dose of 40 mg every week was effective, but 56.8% of patients experienced tertiary LOR [ 24 ].…”

“…The clinical response and clinical remission rates were, respectively, 34% to 90% and 26% to 81% after dose escalation of IFX and 33% to 100% and 15% to 83% after dose escalation of ADA. 23 In patients with secondary LOR to ADA, administering ADA at an escalated dose of 80 mg every 2 weeks or at a dose of 40 mg every week was effective, but 56.8% of patients experienced tertiary LOR. 24 In recent years, the importance of the treat-to-target strategy www.irjournal.org has been emphasized to improve the long-term prognosis of inflammatory bowel disease.…”