Maintenance treatment with infliximab beyond 1 year after ileocolonic resection for Crohn’s disease was associated with reduced recurrence in a prospective, open-label long-term follow-up study.
Subjects were randomized in a prior study to receive infliximab for 1 year after ileocolonic resection performed between 2004 and 2007. At 1 year, the patients – who were blinded as to whether they had received placebo or infliximab – underwent ileocolonoscopy, were informed of the endoscopic findings, and were offered open-label infliximab every 8 weeks or other treatment.
Source: American Gastroenterological Association
Of 11 patients who had been receiving infliximab during the first year after surgery, 8 elected to stop infliximab, and all 8 experienced endoscopic recurrences at a mean of 18.2 months, including 5 who underwent re-resection. Of the three who continued on infliximab, one experienced endoscopic recurrence at the end of the first year, but stayed on treatment for control of arthritis symptoms and has not had Crohn’s disease symptoms, and two continued infliximab for the duration of long-term follow-up and remained in remission, Dr. Miguel Regueiro of the University of Pittsburgh Medical Center and his colleagues reported in the September issue of Clinical Gastroenterology and Hepatology (2014 [doi:10.1016/j.cgh.2013.12.035]).
Of 13 patients who received placebo during the first year after resection, 12 elected to initiate infliximab at 1-year follow-up, and 7 of those responded with endoscopic remission. The remaining five required another surgical resection. The patient who did not initiate infliximab ultimately progressed and underwent re-resection, the investigators said.
Overall, the time to first endoscopic recurrence was longer among those originally assigned to infliximab than among those who received placebo (1,231 days vs. 460 days). Additionally, 77.8% of colonoscopies performed on patients who received infliximab identified disease in remission, compared with only 6.1% of colonoscopies performed in patients not receiving biologic therapy.
"This analysis reflects the intermittent nature of use of infliximab and strong temporal relationship between exposure to infliximab and the probability of being in disease remission. To illustrate, compared with those not on biologic therapy, the adjusted rate ratio of patients being in remission while on infliximab was 13.47," they explained.
Also, while the rate of re-resectional surgery was similar among patients who originally received placebo and those who originally received infliximab, the time to repeat surgery was longer for those who originally received infliximab (1,798 vs. 1,058 days), and four of the five infliximab-treated patients who underwent reoperation during long-term follow-up did so after discontinuing infliximab after the initial 12 months, four of six of those without reoperation remained on infliximab for all or nearly all of the follow-up period, and five of seven patients who initially received placebo and who did not undergo reoperation received infliximab for most of the post 1-year follow-up period.
"Among patients on infliximab therapy for at least 60% of the full study period, and irrespective of initial random assignment, the rate of surgical re-resection was significantly lower, compared with those with less frequent use of infliximab (20.0% vs. 64.3%)," the investigators wrote.
The study is limited by several factors, including the small sample size and open-label design, and the fact that stopping and starting therapy was allowed at the discretion of the patient’s physician, with no restrictions placed on the use of concomitant medications.
The findings suggest, however, that patients at high risk for postoperative Crohn’s disease recurrence may benefit from long-term anti-TNF maintenance, the investigators concluded, noting that "results from postoperative anti-TNF studies with larger sample size and randomization to immediate ‘top down’ treatment vs. waiting for endoscopic recurrence are anticipated," they said.
Dr. Regueiro reported serving as a consultant for AbbVie, Janssen, Shire, Takeda, and UCB.