Undetectable anti-TNF drug levels in patients with long-term remission predict successful drug withdrawal

S. Ben-Horin*, Y. Chowers, B. Ungar, U. Kopylov, R. Loebstein, B. Weiss, R. Eliakim, E. Del Tedesco, S. Paul, X. Roblin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background Low drug levels are associated with emerging loss of response to anti-TNF. However, this may not be the case in patients with long-term remission. Aim To investigate the outcome of anti-TNF discontinuation in patients with long-term remission and incidental undetectable drug levels. Methods A retrospective cohort study examining the duration of relapse-free survival in IBD patients in remission who discontinued infliximab or adalimumab having undetectable drug levels. Results Forty eight patients who discontinued anti-TNF while in remission and had available drug levels were identified in two centres in France and Israel (infliximab-treated 35, adalimumab-13, Crohn's disease 30, ulcerative colitis 18, mean treatment duration of 22.7 ± 12.4 months). Endoscopy/MRE before stopping showed absence of active inflammation in 40/42 (95%) of evaluated patients, while inflammatory biomarkers (CRP and/or Calprotectin) were completely normal in only 31/48 (65%) of patients. During 12 months median follow-up, relapse occurred in 16/20 (80%) of patients who stopped anti-TNF while having measurable drug levels compared with 9/28 (32%) of patients who had undetectable drug levels (OR: 8.4, 95% CI: 2.2-32, P = 0.002). Relapse-free survival after anti-TNF cessation was significantly longer in patients with absent drug compared to those with detectable drug (P < 0.001, log rank test). On multivariate analysis, a patient's decision to stop therapy was weakly associated and abnormal inflammatory biomarkers and detectable drug levels were both strongly and independently associated with a higher risk of relapse after drug discontinuation. Conclusion Incidental finding of undetectable anti-TNF drug levels in patients with stable long-term deep remission may identify a subset of patients whose clinical remission is no longer dependent on anti-TNF treatment.

Original languageEnglish
Pages (from-to)356-364
Number of pages9
JournalAlimentary Pharmacology and Therapeutics
Volume42
Issue number3
DOIs
StatePublished - 1 Aug 2015

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