Alimentary Tract
Infliximab as a bridge to remission maintained by antimetabolite therapy in Crohn's disease: A retrospective study

https://doi.org/10.1016/j.dld.2014.04.012Get rights and content

Abstract

Background

Infliximab withdrawal in patients with Crohn's disease on concomitant antimetabolite therapy is considered to be superior if obtained after a maintenance therapy period compared to induction alone.

Methods

We retrospectively analyzed the outcome of Crohn's disease patients treated with infliximab and an antimetabolite after infliximab was withdrawn using induction alone or induction plus at least 1-year of maintenance therapy. The time to relapse was analyzed using univariate and multivariate analyses. The model was adjusted according to the period of infliximab withdrawal.

Results

A total of 92 patients were included, 54 in the induction alone group. The patient characteristics were identical in the two groups except for the period of infliximab withdrawal. After a median follow-up period of 47.1 (interquartile range = 4.4–110.2) months, 66 patients (72%) experienced a relapse. After a year-adjustment, no significant difference was observed between the two groups. Based on year-adjusted multivariate analysis, the risk factors for relapse were active smoking, previous antimetabolite failure, and perianal disease. After relapse, 53 patients (80%) were retreated with infliximab. After infliximab retreatment, clinical remission was observed in 47 patients (89%) at weeks 8–10.

Conclusion

In Crohn's disease patients, the probability of relapse on antimetabolite therapy after infliximab withdrawal was not superior after a 1-year scheduled maintenance therapy as compared with an induction alone.

Introduction

The advent of anti-tumour necrosis factor (TNF) agents has established new goals for the management of Crohn's disease (CD). In addition to controlling disease activity, anti-TNF therapy reduces the need for hospitalization and surgery while also improving patient quality of life [1], [2], [3], [4], [5]. However, the economic burden of long-term anti-TNF therapy and the desire of patients to discontinue medication support a strategy of drug withdrawal. If and when a patient should cease infliximab treatment for CD remains a debated issue. A study from the Groupe d’Etude Thérapeutique des Affections Inflammatoires du tube Digestif (GETAID) has evaluated the outcome of patients treated with azathioprine and induction therapy with infliximab [6]. In this study, 113 CD steroid-dependent patients were randomized to receive either infliximab at week 0, 2 and 6, or placebo. The rate of steroid-free remission was significantly higher in the infliximab group than in the placebo group at weeks 12, 24 and 52 (75%, 57% and 38%, respectively) but decreased over time. Patients who had reached steroid-free remission at the end of the study were further evaluated for up to 4 years, and the data demonstrated that infliximab was no longer superior to placebo [7].

Recently, Louis et al. prospectively evaluated the outcome of CD patients using combined therapy after infliximab was discontinued in patients with prolonged remission longer than 6 months [8]. After one year, the rate of relapse was 43.9% (±5.0). An analysis of the clinical and biological markers defined a group with a low risk of relapse. The authors concluded that Crohn's disease patients in stable remission treated with combined therapy consisting of infliximab and an antimetabolite could safely withdraw from infliximab. Re-treatment with infliximab was effective and well tolerated in patients who experienced a relapse. In the absence of any controlled study, further data are warranted.

The aim of this study was to compare the outcome of CD patients in stable remission treated with combined therapy consisting of infliximab and then an antimetabolite after infliximab was discontinued, after induction therapy alone or induction plus at least one year of scheduled maintenance therapy.

Section snippets

Patients

We retrospectively reviewed consecutive case records of all adult CD patients referred to Henri Mondor university hospital in Paris, France from January 2000 to June 2012. Patients were recruited from our personal database and/or a standardized hospital inpatient dataset. The patients eligible for this study were at least 17 years of age and had received combined infliximab and antimetabolite treatment for active CD. All patients had discontinued infliximab treatment but maintained

Patient characteristics

Ninety-two patients (57 females; median age at inclusion 32.6 [IQR = 23.9–44.4] years) fulfilled the inclusion criteria. Table 1 shows the patient demographic and CD characteristics. All patients were treated with stables doses of antimetabolite therapy for a median duration of 11.0 months (range, 93.6–25.0). Fifty-four patients were included in the induction group, and 38 patients were in the maintenance group. The median follow-up period was 47.1 months (range, 4.4–110.2) for the overall

Discussion

Our study reports the clinical outcomes in 92 patients with CD in stable steroid-free remission on combined therapy after infliximab was discontinued but antimetabolite treatment was maintained. To our knowledge, this is the largest collection of CD patients evaluated at a single centre comparing infliximab withdrawal after induction therapy alone and after at least 1-year scheduled maintenance therapy. In our cohort, the 1- and 2-year treatment-free remission rates were 70% and 52%. There was

Conflict of interest

AA has received payment for lectures from Biocodex and MSD and travel accommodation from Abbvie, MSD and Biocodex. None of the remaining authors have any potential conflicts to disclose about the present study.

References (22)

  • J. Satsangi et al.

    The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications

    Gut

    (2006)
  • Cited by (31)

    • De-escalation of immunomodulator and biological therapy in inflammatory bowel disease

      2020, The Lancet Gastroenterology and Hepatology
      Citation Excerpt :

      Conversely, the risks of both infection and malignancy increase with thiopurine and anti-TNF treatment if the patient is older than 65 years, favouring discontinuation in older patients.10 Extensive disease is an important risk factor for Crohn's disease, which has also been proposed for ulcerative colitis; additional adverse clinical features of Crohn's disease include smoking, perianal or colonic disease, and stricturing disease.30,47,51,55,60 Discontinuation of biological therapy in perianal disease is associated with particularly high relapse rates, and continuation of therapy is strongly favoured in this group.61,62

    • Outcomes 7 Years After Infliximab Withdrawal for Patients With Crohn's Disease in Sustained Remission

      2018, Clinical Gastroenterology and Hepatology
      Citation Excerpt :

      A Danish retrospective observational study reported a low rate of remission (12%) at 10 years after the last IFX infusion.14 A French retrospective cohort comparing the outcome of CD patients after IFX withdrawal using induction alone or induction plus at least 1 year of maintenance therapy found that 72% of patients relapsed after a median follow-up period of 47 months in both groups.16 A retrospective study from Leuven, Belgium, reported the lowest rates of CD relapse after IFX discontinuation while in clinical remission with 96%, 93%, and 52% without clinical relapse after 1, 2, and 10 years, respectively.17

    • Proposal for an anti-TNF-exit strategy based on trough serum level

      2017, Biologicals
      Citation Excerpt :

      The most difficult decision was, to define which further factor might have a predictive value for a relapse-free revival and should be part of the algorithm-criteria. To this regard, the existing data are rare and partially contradictory [20–25]. We consciously chose a small number of criteria, expecting the best empirical value in recent literature.

    View all citing articles on Scopus
    View full text