ORLANDO – Risk-based drug treatment with colonoscopy at 6 months – and treatment step-up for recurrence – was significantly more effective in preventing postoperative recurrence of Crohn’s disease, compared with standard drug therapy alone, based on data from the POCER (Post-Operative Crohn’s Endoscopic Recurrence) study.
At an 18-month follow-up colonoscopy, 49% of patients randomized to a risk-based intervention had endoscopic recurrence, compared with 67% of those in a standard drug therapy arm, Dr. Peter De Cruz reported during a late-breaking abstract session at the annual Digestive Disease Week.
Researchers compared the two recurrence-prevention strategies in 174 subjects who were stratified as high risk or low risk based on smoking status, presence of perforating disease, and previous surgeries. The participants were randomized 2:1 to either active care or standard drug therapy. Approximately one-third of patients in the active care arm showed signs of early recurrence at a 6-month colonoscopy and thus received step-up treatment.
Complete mucosal normality was observed in 22% of those in the risk-based treatment arm, compared with 8% in the standard therapy arm; no significant differences were noted with respect to severe endoscopic recurrence or clinical recurrence, said Dr. De Cruz of St. Vincent’s Hospital, Melbourne, Australia.
Patients in the multicenter POCER study were adults undergoing intestinal resection of all macroscopic disease. The treatment arms were similar in terms of demographics, disease characteristics, and prior drug therapy. Of 122 patients in the risk-based treatment arm, 101 were high-risk, and 21 were low-risk. Of 52 patients in the standard drug therapy arm, 44 were high-risk, and 8 were low-risk.
All patients were treated beginning postoperatively with 3 months of 400 mg metronidazole twice daily. High-risk patients also received 2 mg/kg of azathioprine daily, or 1.5 mg/kg of 6 mercaptopurine. Those intolerant of thiopurine were treated with adalimumab induction, followed by 40 mg every 2 weeks. Low-risk patients received no additional treatment following the 3 months of metronidazole.
For recurrence at 6 months, low-risk patients were stepped up to thiopurine; high-risk patients on thiopurine were stepped up to 40 mg adalimumab every 2 weeks, and high-risk patients on adalimumab every 2 weeks stepped up to weekly adalimumab.
The endoscopic remission rate at 18 months was 25% for the low-risk patients who stepped up to thiopurine 41% for high-risk patients who stepped up to thiopurine, and 50% for those who stepped up to weekly adalimumab.
Overall, 39% of patients who stepped up at 6 months were in remission at 1 year. Notably, 31% of the low-risk patients with endoscopic remission at the 6-month colonoscopy, 46% of the high-risk patients on thiopurine, and 41% of the high-risk patients on adalimumab with endoscopic remission at 6 months had endoscopic recurrence 1 year later.
"We can’t afford to relax," Dr. De Cruz said regarding those patients with remission 6 months postoperatively.
This study also allowed for comparison of the efficacy of adalimumab and thiopurine given immediately postoperatively in the high-risk patients. At 6 months, adalimumab was associated with a nearly 80% endoscopic remission rate, compared with 55% for thiopurine, Dr. De Cruz noted.
At 18 months, there was no significant difference in the recurrence rates between patients treated with adalimumab immediately postoperatively and those stepped up to adalimumab in combination with thiopurine. There was, however, a trend toward reduced recurrence rates among those on immediate postoperative adalimumab.
A multivariate analysis showed that active smoking was significantly associated with an increased endoscopic recurrence rate at 18 months, whereas the intervention of endoscopy at 6 months was significantly associated with a reduced recurrence risk at 18 months.
Most prior studies of postoperative recurrence prevention in Crohn’s surgery patients have focused on drug therapy compared with placebo; few have focused on risk-based strategies, Dr. De Cruz noted.
The findings indicate that step-up therapy based on endoscopy is a viable postoperative strategy in patients at high risk of recurrence, he said. No unexpected serious adverse events occurred in this study.
Dr. De Cruz warned, however, that remission at 6 months is no guarantee of remission 1 year later.
"Intensifying treatment at 6 months brings about 40% of patients with recurrence into remission, and we found that a small group of patients had recurrent disease despite endoscopic monitoring and intense treatment," he said.
Dr. De Cruz reported having no disclosures. Several study coauthors disclosed relationships with multiple pharmaceutical companies.
