Original article—alimentary tract
Low-Dose Maintenance Therapy With Infliximab Prevents Postsurgical Recurrence of Crohn's Disease

https://doi.org/10.1016/j.cgh.2010.01.016Get rights and content

Background & Aims

Infliximab might prevent postsurgical recurrence of Crohn's disease. However, it is unclear whether long-term therapy is necessary and whether alternative strategies could be applied to minimize potential side effects and reduce the costs of treatment.

Methods

We performed a prospective cohort study in 12 consecutive patients, treated immediately after surgery with maintenance infliximab (5 mg/kg), who did not have clinical or endoscopic evidence of disease recurrence after 24 months; they were followed up for an additional year. Infliximab treatment was then discontinued; patients with disease recurrence, based on endoscopy (Rutgeerts score, ≥2), were given lower doses of infliximab (starting with 1 mg/kg) to re-establish mucosal integrity. Surrogate markers of disease activity (fecal calprotectin [FC], C-reactive protein, and erythrocyte sedimentation rate) were assessed after each infliximab dose.

Results

None of the patients had clinical or endoscopic recurrence of Crohn's disease 3 years after surgery. However, discontinuation of infliximab caused endoscopic recurrence after 4 months in 10 of 12 patients (83%). All 10 patients then were treated again with infliximab, which, at a dose of 3 mg/kg every 8 weeks, restored and maintained mucosal integrity for 1 year. Among the surrogate markers, FC levels correlated with endoscopic scores (Wald test, P < .0001).

Conclusions

Long-term maintenance therapy with infliximab is required to maintain mucosal integrity in patients after surgery for Crohn's disease. However, a dose of 3 mg/kg (a 40% reduction from the standard dose) was sufficient to avoid disease recurrence, determined by endoscopy, in all patients at 1 year. FC levels correlate with mucosal status at different infliximab doses.

Section snippets

Patients and Methods

We enrolled in the current study a total of 12 consecutive patients treated postoperatively with infliximab and free of clinical and endoscopic recurrence at 2 years.3 The clinical features of all 12 patients are outlined in Table 1. Age ranged from 23 to 64 years (median, 38 y). Six of these patients had an ileocecal resection (during which a fistula tract was removed in 3 of the patients), 2 patients had a segmental ileal resection (the patients previously had been subjected to ileocecal

Results

A total of 12 patients treated immediately postoperatively with infliximab 5 mg/kg bw on a maintenance basis and free of clinical and endoscopic recurrence at 2 years were given infliximab for another year at the same dose and colonoscopy was performed immediately thereafter. None of the patients had mucosal or clinical recurrence as defined in the Patients and Methods section, and none of them reported serious side effects. We only recorded mild, single, short-lived, self-limiting episodes of

Discussion

Prevention of postsurgical recurrence of Crohn's disease is a fundamental task in the practical management of patients with this condition. Indeed, as of today, the large majority of affected individuals will undergo surgery within a few years of diagnosis.16 After surgery, the disease tends to occur in a similar fashion and usually within a short time. If left untreated, approximately 80% of patients will have an endoscopic recurrence within 1 year from surgery, and in a large majority of them

References (37)

  • S. Renna et al.

    Meta-analysis of the placebo rates of clinical relapse and severe endoscopic recurrence in postoperative Crohn's disease

    Gastroenterology

    (2008)
  • S. Onali et al.

    Frequency, pattern, and risk factors of postoperative recurrence of Crohn's disease after resection different from ileo-colonic

    J Gastrointest Surg

    (2009)
  • R.D. Cohen et al.

    Economics of the use of biologics in the treatment of inflammatory bowel disease

    Gastroenterol Clin North Am

    (2006)
  • J.D. Lewis et al.

    An evidence-based approach to studies of the natural history of gastrointestinal diseases: recurrence of symptomatic Crohn's disease after surgery

    Clin Gastroenterol Hepatol

    (2003)
  • D. Sorrentino et al.

    Prevention of postoperative recurrence of Crohn's disease by infliximab

    Eur J Gastroenterol Hepatol

    (2006)
  • D. Sorrentino et al.

    Infliximab and low dose methotrexate for prevention of postsurgical recurrence of ileocolonic Crohn's disease

    Arch Intern Med

    (2007)
  • M. Regueiro et al.

    Infliximab prevents Crohn's disease recurrence after ileal resection

    Gastroenterology

    (2009)
  • F. Baert et al.

    Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's disease

    N Engl J Med

    (2003)
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    This article has an accompanying continuing medical education activity on page e79. Learning Objectives—At the end of this activity, the learner should be able to understand the role of infliximab in the prevention of postsurgical Crohn's disease.

    Conflicts of interest The authors disclose the following: Dario Sorrentino has acted as a consultant and received fees from Schering-Plough, Centocor, and Abbott (study participants were informed about the potential conflicts of interest). The remaining authors disclose no conflicts.

    This study was not supported by the pharmaceutical industry.

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