Fistula formation is everyday in p...

Fistula formation is everyday in patients with Crohn's disease. Fecal drainage from fistulas is a distressing symptom. Surgical diversion of the colon to a stoma many times leads to fistula closure, if it be not that this invasive option also generates substantial patient distress. Tumor necrosis factor inhibitors, similar as infliximab, have been used with a certain success in patients with inflammatory bowel disease. Sands and colleagues investigated the use of infliximab for closure of fistula tracts in patients with Crohn's disease.

This multinational trial was underwritten on Centocor, the manufacturer of infliximab. Eligible patients were adults with at least united perianal or enterocutaneous fistula that had been draining for at least three month Initial enrollment included 306 patients who were given intravenous infusions of infliximab in a dosage of 5 mg by kg at weeks zero, 2 and 6 Use of other standard medications for Crohn's disease, as it is as 5-aminosalicylates, oral steroids, or azathioprine, continued during the trial.

Adverse conclusions withdrawn consent, lack of efficacy, or noncompliance l to exclusion of 24 patients after the initial induction phase. The remaining 282 participants were re-evaluated at weeks 10 and 14 and those who maintained a reduction of at least 50 percent in the number of draining fistulas at the two visits were classified as responder (195 patients, 69 percent) Responder were randomized to maintenance therapy with infliximab or placebo each eight weeks until 54 weeks of follow-up Los of reply during maintenance treatment was defined as reappearance of a draining fistula, ne for an additional treatment or change to other disease-related medications, ne for surgical treatment related to Crohn's disease, or perceived lack of efficacy.

The time to los of rejoinder during maintenance therapy was significantly longer in patients randomized to infliximab (40 weeks) than in patients receiving placebo (14 weeks). At 54 weeks of follow-up a entire response (no draining fistulas) was sustained more frequently in those still receiving infliximab (36 percent) than in those assigned to placebo (19 percent) Multivariate analysis did not identify any patient characteristics that predicted a sustained rejoinder in patients randomized to infliximab maintenance therapy.

Patients without an initial answer to infliximab also were studied to behold if further active treatment would eventually increase reply rates. No significant improvement occurr with postponeed infliximab treatment, compared with placebo, in initial nonresponders.

Antibody formation to inf liximab occurr in 32 percent of patients forward active treatment. Presence of antibodies did not decrease the efficacy of infliximab, on the other hand it did increase the likelihood of an infusion reaction. Patients who also were taking oral steroids and immunomodulators were les likely to bring to maturity antibodies to infliximab. Only united infusion reaction was considered serious. couple opportunistic infections occurred in patients receiving active treatment (i.e., cytomegalovirus infection and cutaneous nocardia infection).

The authors gather that more than one half of patients with Crohn's disease and draining fistulas rejoin to initial treatment with infliximab, and that maintenance therapy each eight weeks over one year approximately doubles the likelihood of maintaining fistula closure

BILL ZEPF MD

Sands BE, et al. Infliximab maintenance therapy for fistulizing Crohn's disease. N Engl J M February 26 2004;350:876-85

COPYRIGHT 2004 American Academy of Family Physicians

COPYRIGHT 2004 Gale Group