Factors contributing to anti-TNF loss of response in CD

Apr 28, 2015 - E-Mentoring in IBD | Volume 08 • 2015

Issue 08

Clinical Question

Are there modifiable factors associated with loss of response to the anti-TNFs infliximab (IFX) and adalimumab (ADA) in patients with Crohn’s disease (CD)?

Editor’s Bottom Line

Stopping azathioprine combination therapy in the first six months of anti-TNF therapy and smoking led to premature loss of response in more than 2/3 of patients.

Editorial Note

This study highlights the importance of the first few months of anti-TNF therapy in determining success or failure. Combination therapy and a short course of corticosteroids at induction ensures anti-TNF success.

Smoking frequently leads to anti-TNF failure. We all need to ensure we have solid anti-smoking programs for our IBD patients.


Viazis N, Koukouratos T, Anastasiou J, et al. Azathioprine discontinuation earlier than 6 months in Crohn’s disease patients started on anti-TNF therapy is associated with loss of response and the need for anti-TNF dose escalation. Eur J Gastroenterol Hepatol. 2015 Apr;27(4):436–41.


Consecutive patients with active CD, who received IFX or ADA standard induction and maintenance treatment were enrolled in the study. Patients also received concomitant azathioprine treatment (2.0-2.5 mg/kg). Endoscopy was performed at baseline, 1 year, and 2 years following anti-TNF initiation. Primary non-responders were excluded from the follow-up. Loss of response was defined as: (1) reappearance of symptoms and increased CRP at any time after 14 weeks of combination anti-TNF therapy; or (2) endoscopic evidence of active disease at 1 or 2 years. In case of secondary loss of response, IFX was doubled then the interval shortened to every 6 or 4 weeks while ADA was administered every week. De-escalation occurred after 1 year if the patient remained in remission.

Of 161 patients, 132 had a primary response to the anti-TNFs (IFX: 77; ADA: 55). A total of 22 patients discontinued azathioprine before the 6-month milestone because of side effects.

Patients who stopped azathioprine before 6 months had a loss of response rate of 14/22 (64%) whereas those who completed 6 months of azathioprine combination therapy had a loss of response rate of 17/110 (16%) (P=0.0001).

Loss of response occurred in 26/35 (74.3%) smokers and 5/97 (5.2%) non-smokers (P<0.0001).

In those patients with loss of response, dose-escalation led to clinical remission in 80% of patients of which 64% were then successfully de-escalated after 1 year.


Study Design: Prospective observational cohort study
Funding: None reported
Allocation: n/a
Setting: Two tertiary referral hospitals in Athens, Greece
Level of Evidence: 2b (Oxford Levels of Evidence)

The summary and conclusion in this issue of E-mentoring in IBD pertains to the manuscript(s) being reviewed, and should be considered in the context of what is already known surrounding the topic and incorporated into practice as deemed appropriate by the individual learner.