A study published in the New England Journal of Medicine demonstrates the safety and efficacy of Remicade (infliximab) in maintaining fistula closure when administered every eight weeks in patients with fistulizing Crohn’s disease (CD). Nearly twice as many patients who received Remicade as a maintenance therapy every eight weeks had complete and durable fistula closure compared with patients who received placebo maintenance in the 54-week ACCENT II study (36 per cent vs.19 per cent, respectively), the largest clinical trial of fistulizing Crohn’s disease ever conducted. As many as 43 per cent of the estimated half-million Americans with Crohn’s disease have fistulas associated with their disease — openings that burrow through the bowel wall into nearby organs or through the surface of the skin that can lead to infections, scarring and a severe negative impact on quality of life.

Crohn’s disease is a chronic inflammatory bowel disorder that commonly affects the lower part of the small intestine and the large intestine and typically begins in late childhood or early adulthood. The disease causes inflammation of the gastrointestinal tract, typically resulting in symptoms such as diarrhea, fever, abdominal pain and weight loss. More than 500,000 Americans suffer from this gastrointestinal disorder.

“These findings are of major importance to physicians treating patients with fistulizing Crohn’s disease,” said Bruce Sands, Massachusetts General Hospital, and lead study author. “This treatment fills a significant unmet medical need for these patients by potentially reducing the need for hospitalizations and surgeries.”

All patients in the study received an induction regimen of Remicade at weeks 0, 2 and 6. Patients who were classified as responders at week 14 were then randomized to receive either maintenance doses of placebo or Remicade (5 mg/kg) at week 14 and every eight weeks thereafter. Patients in both treatment groups also continued to be treated with the standard Crohn’s disease therapies they had been receiving, including conventional immunomodulators (6-MP, azathioprine and methotrexate), corticosteroids and 5-ASA drugs.

“Results like these have never been seen before and are exciting for physicians and patients who struggle with managing fistulizing Crohn’s,” said Jerome Boscia, vice president, Clinical Research & Development, Centocor. “Again, these data demonstrate that Remicade offers significant relief for a wide range of patients, even those with the most severe disease.”

Remicade was approved in 1998 by the US Food and Drug Administration (FDA) as a short-term treatment for reducing the signs and symptoms of moderate-to-severe Crohn’s disease and as a short-term treatment for reducing the number of draining enterocutaneous fistulas. The indications were expanded in 2002 to include inducing and maintaining clinical remission in patients with moderate-to-severe Crohn’s disease. In January of last year, the FDA granted a priority review of a supplemental Biologics License Application (sBLA) based on 54-week data from the ACCENT II trial. A priority review is ordinarily granted if a particular treatment presents a potential significant therapeutic advance over existing therapies. In April, the FDA expanded the approved use of Remicade to include reducing the number of draining enterocutaneous and rectovaginal fistulas and for maintaining fistula closure in patients with fistulizing Crohn’s disease based on these data. Remicade is the worldwide market share leader among anti-TNF therapies and is the only biologic drug indicated for the treatment of both Crohn’s disease and rheumatoid arthritis (RA), and, in the European Union, for ankylosing spondilitis (AS).

The ACCENT II study evaluated the effectiveness of maintenance therapy with Remicade in sustaining fistula closure in patients suffering from one or more fistulas for at least three months immediately preceding screening and who responded to induction therapy with Remicade. The primary efficacy endpoint was defined as the time from randomization until loss of response.

All patients received induction therapy of 5 mg/kg of Remicade at week 0, 2 and 6. Of the 282 patients who completed the study through week 14, 69 per cent had closure of at least 50 per cent of draining fistulas that was sustained over one month. These patients were classified as responders and were then randomized to receive either placebo (99 patients) or 5 mg/kg of Remicade (96 patients) every eight weeks through week 46.

According to researchers, results show that at week 54, 36 per cent of patients taking Remicade had complete absence of draining fistulas vs. 19 per cent of patients receiving placebo (p=0.009). Time to loss of response was significantly longer for patients who received maintenance therapy with Remicade (greater than 40 weeks vs. 14 weeks for placebo, p<0.001).

The most frequently reported adverse events were consistent with those associated with previous studies in Crohn’s disease. The most commonly reported serious adverse event in this study was the worsening of Crohn’s disease, which occurred in six per cent of all randomized patients.