CHICAGO – A randomized, multicenter open-label trial found that cyclosporine was not more effective than infliximab in patients with acute, severe ulcerative colitis refractory to intravenous steroids, according to Dr. David Laharie.
Acute severe ulcerative colitis (UC) occurs in about 25% of patients with UC, and while intravenous corticosteroids are the primary therapy, 40% of patients are refractory to them. After steroid failure, only two medical options are available to avoid colectomy: cyclosporine and infliximab.
"However, there has been no randomized clinical trial comparing the two," said Dr. Laharie of Centre Hospitalier Universitaire in Bordeaux, France. He presented the findings of a multicenter, randomized open-label study comparing cyclosporine with infliximab in severe acute UC refractory to intravenous steroids. This study found cyclosporine to be no more effective than infliximab in this population, he said at the annual Digestive Disease Week.
Patients with steroid-refractory acute severe UC were randomized to cyclosporine (55 patients) or infliximab (56 patients). The researchers sought to determine whether treatment failure was less frequent with cyclosporine than with infliximab.
Adults were randomized if they were having a severe acute flare of UC (Lichtiger score greater than 10) and were refractory to intravenous steroid therapy (greater than or equal to 0.8 mg/kg per day of methylprednisone or equivalent) for at least 5 days. They had to be naive to the two treatment drugs and could not be under treatment with azathioprine/6-mercaptopurine unless therapy had been initiated fewer than 4 weeks before randomization.
The two groups were treated for up to 98 days, and the trial’s primary end point was treatment failure, defined as an absence of early clinical response, relapse after day 7, colectomy, absence of remission off steroids at the trial’s end, a severe adverse event, or death. Secondary end points included the Lichtiger score from day 0 to day 7, the percentage of patients showing clinical response at day 7, endoscopic response and colectomy at day 98, and the number of severe adverse events.
Approximately half the patients in both groups were female, with a median age of approximately 37 years, and had UC for at least 1 year. More than 90% of patients in both groups were naive to azathioprine. Lichtiger scores in both groups were 11 and over, and Mayo scores ranged from less than or equal to 0 to 12.
For the primary end point of treatment failure, 60% failed in the cyclosporine arm versus 54% in the infliximab arm, a nonsignificant difference.
The response rate at day 7 was 85.4% in the cyclosporine arm versus 85.7% in the infliximab arm, also not a significant difference. Response was defined as a Lichtiger score less than 10, and a decrease of at least 3 points compared with baseline.
The Lichtiger score from day 0 to day 6 showed that the median time to clinical response was 4 days (interquartile range [IQR], 3-6) with infliximab, versus 5 days (IQR, 4-7) for cyclosporine, a significant difference (P = .046).
At day 98, signs of mucosal healing were found in 52% of patients in the cyclosporine group and 53% of patients in the infliximab group. Healing was defined as having a Mayo endoscopic subscore of 0-1.
The colectomy rates were 18% in the cyclosporine arm and 21% in the infliximab arm. Severe adverse events affected 15% (8 patients) in the cyclosporine group and 25% (14 patients) in the infliximab group. Three patients developed cytomegalovirus colitis and two developed septicemia.
"In acute severe ulcerative colitis refractory to intravenous steroids, cyclosporine was not more effective than infliximab," said Dr. Laharie. "The short-term response was achieved with both drugs in more than 80% of patients within 1 week. Three-month colectomy rates were similar (18% with cyclosporine versus 21% with infliximab). And in this severe population, both drugs were well tolerated," he said.
Dr. Laharie disclosed financial relationships with Schering-Plough and Abbott Laboratories (royalty, speaking, and teaching), and with Norgine (consulting fee and board membership). The study received support from the Association François Aupetit, the Société Nationale Française de Gastro-Entérologie, and the International Organization for the Study of Inflammatory Bowel Disease, and was sponsored by Groupe d’Etude Thérapeutique des Affections Inflammatoires du Tube Digestif.