Long-term ulcerative colitis study shows Remicade responders maintained improvement

Findings presented at Digestive Disease Week 2007 (DDW), from long-term extensions of the ACT trials (Active Ulcerative Colitis 1 & 2) show that subjects with moderately to severely active ulcerative colitis (UC) who had responded to REMICADE (infliximab) in the blinded phase of the trials maintained improvement in their clinical symptoms for up to two years.

The ACT extension trials were conducted in both the United States and Europe, under co-principle investigators William Sandborn, M.D. of the Mayo Clinic and Walter Reinisch, M.D., of the University Hospital Vienna, Austria. The data show that for patients who completed follow-up through week 56 of the extension trials, 92 percent reported mild or no disease activity, as measured by the Physician's Global Assessment (PGA). For patients followed through week 104, 97 percent reported mild or no disease activity.

At week 0 of the ACT extension trials, 76 percent of 229 responder patients enrolled had mild or no disease activity, as indicated by a PGA score of 0 or 1, and 41 percent had no disease activity (PGA score of 0). At week 56, 92 percent of those patients remaining in the extension trials (n=181) had mild or no disease activity, and 61 percent had no disease activity. At week 104, 97 percent of those patients remaining in the extension trials (n=97) had mild or no disease activity, and 75 percent had no disease activity.

"The data demonstrate the sustained efficacy of REMICADE for many patients with UC," said co-principle investigator Walter Reinisch, M.D., of the University Hospital Vienna, Austria. "Because UC is a chronic condition, many patients live with cycles of recurring flares. This can greatly hinder a person's social and professional life. The availability of therapies that quickly reduce symptoms and maintain response and remission long term is a significant benefit to patients."

Separate data also presented at DDW today show the significant impact of UC on patients' productivity, employment and social activities. A survey of 1,000 patients who rated their UC symptoms on a scale of 1 to 5, with 5 being very severe, showed that patients with more severe disease reported greater disability, significantly more days missed from work and significantly more days of reduced productivity, compared with patients with less severe disease (P < 0.01). In fact, 19 percent of patients with the most severe disease were on long- or short-term medical leave from work, compared with less than seven percent of patients whose disease was less severe (P < 0.01). Of patients who were employed, those with the most severe disease missed an average of 19 days of work in the past year, compared with one day for those with the mildest disease (P < 0.01). Furthermore, even when at work, patients who rated their disease as more severe reported being less productive on more than 30 days in the past year, underscoring the negative impact of UC on patients' ability to function in the workplace.

"Many patients with ulcerative colitis report experiencing extremely bothersome symptoms, that affect many areas of their lives, including their ability to maintain full-time employment and make and keep social engagements," said Richard J. Geswell, President, Crohn's & Colitis Foundation of America. "Since patients with more severe symptoms experience more difficulties than those with milder disease, a treatment that rapidly reduces UC symptoms and keeps disease activity at bay over time may reduce the impact of the disease on patients' work status and productivity."

About the ACT Long-Term Extension Patients with moderate to severe UC, defined as a baseline Mayo score ¡Ý 6 and ¡Ü 12, who were unresponsive to or intolerant to at least one standard therapy, including corticosteroids, immunosuppressants or 5ASAs, were enrolled in ACT 1 (n=364) or ACT 2 (n=364). The 728 patients were randomized to receive REMICADE 5 mg/kg, REMICADE 10 mg/kg or placebo at weeks 0, 2, 6 and every subsequent 8 weeks through week 22 (ACT 2) or week 46 (ACT 1). Patients were allowed to continue to receive conventional therapy.

Patients who had benefited from treatment with REMICADE and, in the investigators opinion, could enroll in the extension trials; 118 patients entered the ACT 1 extension and 111 patients entered the ACT 2 extension. During the extension, patients continued to receive REMICADE 5 mg/kg or REMICADE 10 mg/kg every 8 weeks. Patients in the extension trials were assessed using the PGA, which is 1 of 4 measures of disease activity included in the Mayo score. Of these 229 patients who entered the extension, 181 have been followed through one year, and 92 have completed two years. Patients who had responded to placebo also enrolled in the extension to maintain the blind and continued to receive placebo every 8 weeks, but were discontinued upon unblinding.

Over the course of the extension trials subjects were allowed to adjust corticosteroid use as required. When corticosteroid use during the extension in all participants (which included subjects previously on corticosteroids and those that had not used corticosteroids) was examined, a smaller proportion of the subjects who had completed follow-up through Weeks 56 and 104 were using corticosteroids. At weeks 8, 56 and 104 of the ACT extension trials, 80 percent, 88 percent and 98 percent of patients, respectively, were corticosteroid-free.

Overall, side effects were generally well tolerated with less than five percent of patients discontinuing therapy due to an adverse event (AE). As previously reported, other notable serious adverse events (SAEs) included: prostate cancer, breast cancer, pneumonia, sarcoidosis, abscess and a death following Histoplasmosis pneumonia.

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