BERLIN — Treatment with adalimumab led to significantly more remissions than did placebo in patients with moderately to severely active Crohn's disease who had failed treatment with infliximab, in a study with 325 patients.
The safety and efficacy of adalimumab, a fully human antibody to tumor necrosis factor-α (TNF-α), was proven in the “first placebo-controlled study of an anti-TNF agent following failure to respond to another anti-TNF agent,” Dr. Paul Rutgeerts said at the 14th United European Gastroenterology Week.
“It's very important. We were waiting for this result,” commented Dr. Marc Lemann, a gastroenterologist at Saint-Louis Hospital in Paris. The finding shows that there's no cross-drug interference between the two anti-TNF antibodies, he said.
The Gauging Adalimumab Effectiveness in Infliximab Nonresponders (GAIN) study enrolled patients with a Crohn's disease activity index (CDAI) of 220–450. All of the patients had been previously treated with infliximab (Remicade) but had been off that drug for at least 8 weeks, either because of loss of response or because they developed intolerance. The patients could be taking other medications, such as a steroid or immunosuppressant.
The 159 patients randomized to adalimumab received a self-administered, 160-mg subcutaneous injection at week 0, and an 80-mg dose at week 2. The 166 patients in the control arm received placebo injections. The average age was about 38, and the average CDAI was 313. About 40% were on steroid treatment.
The study was sponsored by Abbott Laboratories, which markets adalimumab (Humira). Adalimumab is licensed in the United States for ttreating rheumatoid arthritis and psoriatic arthritis. Abbott has applied to the Food and Drug Administration to market the drug for treating moderately to severely active Crohn's disease. Results from the GAIN study form part of the application. Dr. Rutgeerts has received grants and honoraria from Abbott, and he is a consultant to the company.
The primary end point was the percentage of patients in remission, defined as a CDAI of less than 150 when evaluated 4 weeks after the first dose. That rate was 21% in the patients treated with adalimumab and 7% in the placebo group, a statistically significant difference, reported Dr. Rutgeerts, professor of medicine and chief of the inflammatory bowel disease unit at the University of Leuven in Belgium.
Adalimumab was also significantly better than placebo at producing clinical responses, rated by either the CR-70 score (the percentage of patients whose CDAI score fell by at least 70 points) or the CR-100 score (the percentage whose scores dropped by at least 100 points). (See box.)
Responses to adalimumab started early. Although few patients had a remission 1 week after receiving their first dose, 35% had a CR-70 after 1 week (compared with a 21% rate in the placebo group).
Adalimumab had roughly the same efficacy regardless of patients' prior experience with infliximab. The remission rate was 16%–22% in patients who had lost their initial response to infliximab, became intolerant of infliximab, or both, Dr. Rutgeerts said at the meeting.
Adalimumab was well tolerated and was associated with fewer serious adverse events than was placebo. Its overall adverse effect profile was similar to what was seen in earlier, rheumatoid arthritis trials.
ELSEVIER GLOBAL MEDICAL NEWS