COPENHAGEN — Regular treatment with adalimumab maintained remission in patients with Crohn's disease during a year of follow-up, in a controlled study with 55 patients.
A larger study that's powered to definitively assess the long-term efficacy of adalimumab is in progress, William J. Sandborn, M.D., said at the 13th United European Gastroenterology Week.
Adalimumab is a fully humanized, anti-tumor necrosis factor monoclonal antibody that's administered by subcutaneous injection. It's currently approved in the United States for treating rheumatoid arthritis and psoriatic arthritis, and is marketed as Humira by Abbott Laboratories, which is sponsoring development of the drug for Crohn's disease. Dr. Sandborn is a consultant to Abbott and several other companies.
Assessment of adalimumab's ability to maintain remission in patients with moderately to severely active Crohn's disease began with a study of 299 patients who received two doses of the drug to induce remission, defined as a Crohn's Disease Activity Index score of less than 150.
After induction efficacy was assessed 2 weeks following the second dose, patients were given the option of receiving two more doses on an open-label basis.
Fifty-five patients were in clinical remission at both the start and end of the 4-week open-label phase, and these patients were then rerandomized for the long-term maintenance phase.
Another 221 patients who were not in remission after both the induction phase and the open-label phase were continued on long-term, open-label treatment.
In the randomized group, 18 patients received 40 mg of adalimumab once a week for 1 year. Nineteen patients received the same dose every other week, and 18 patients received placebo.
After a year, remission continued in 83% of patients on the weekly dose, compared with 44% of those on placebo, a statistically significant difference. Remission was maintained in 74% of patients who received the drug every other week, which was not significantly different from placebo.
The failure to reach statistical significance was probably due to the small number of patients in the study, said Dr. Sandborn, a professor of medicine at the Mayo Medical School, Rochester, Minn.
Serious adverse events occurred in two patients in the placebo group, in one patient who got adalimumab every other week, and in no patients who got the drug weekly.
Antiadalimumab antibodies were found in one patient in the placebo group and one in the group that received adalimumab every other week. Injection-site reactions occurred in three patients, one of whom was in the placebo group. No patient in the study had an opportunistic infection.
Among the 221 patients who received long-term treatment with adalimumab on an open-label basis, 131 (59%) remained on the drug after 1 year. Seventy of these patients were receiving one dose of adalimumab every 2 weeks, and 60 patients were receiving it weekly.
Of the patients who entered the open-label phase, 43% were in remission after a year of treatment, Dr. Sandborn said in a separate report at the meeting.
Serious adverse events occurred in 17% of patients, including 5% who had an infection while receiving treatment. Antibodies to the drug were measured in six patients.
The first phase of this study showed that adalimumab was more effective than placebo for inducing an initial remission. The 299 patients enrolled in the induction phase were randomized to receive 160 mg, 80 mg, 40 mg, or placebo as their initial dose. For their second induction dose, these groups received 80 mg, 40 mg, 20 mg, or placebo, respectively.
Two weeks after the second dose, 36% of patients in the highest-dose group were in remission, compared with 24% in the 80 mg/40 mg group and 12% in the placebo group.
The remission rate in the highest-dose group (160 mg followed by 80 mg) was significantly higher than that in the placebo group. The response rate in the 80 mg/40 mg group just missed statistical significance, compared with the control group (P = .06).