Discontinuing infliximab results in significantly greater relapse at 48 weeks compared with continuing treatment among patients with ulcerative colitis in remission, according to a study in the Lancet Gastroenterology & Hepatology.
The open-label, randomized controlled HAYABUSA trial enrolled patients from 24 centers in Japan from June 16, 2014, to July 28, 2017. Participants were eligible if they had a definitive diagnosis of ulcerative colitis, had been in clinical remission with previous treatment of intravenous infliximab (5 mg/kg) every 8 weeks, and had started infliximab at least 14 weeks before enrollment. Remission rate (maintenance of Clinical Activity Index ≤4 without relapse) at week 48 after randomization was the primary end point.
A total of 95 patients who were confirmed to be in remission for more than 6 months were randomly assigned to either the infliximab-continued group (n=48) or the infliximab-discontinued group (n=47). The full analysis set for efficacy evaluation included 92 patients in either the infliximab-continued group (n=46; mean age, 46.1 [SD, 13.4] years; 52% male) or the infliximab-discontinued group (n=46; mean age, 41.1 [SD, 15.6] years; 67% male). The median duration of previous infliximab use was 166.1 weeks (interquartile range [IQR], 89.4-237.6 weeks).
In the full analysis set, 37 patients (80.4%; 95% CI, 66.1-90.6) in the infliximab-continued group and 25 patients (54.3%; 95% CI, 39.0-69.1) in the infliximab-discontinued group were in remission at week 48. The unadjusted between-group difference in remission rates was 26.1% (95% CI, 7.7-44.5; P =.0076).
Sensitivity analysis showed that the between-group difference in remission rates adjusted for use of immunomodulators and Mayo Endoscopic Subscore at randomization was 27.3% (95% CI, 8.0-44.1; P =.0059).
Overall, 8 of 48 patients (17%) in the infliximab-continued group and 6 of 47 patients (13%) in the infliximab-discontinued group reported 1 or more adverse events (between-group difference, 3.9%; 95% CI, −10.3 to 18.1; P =.59). An infusion reaction was reported in 1 patient and psoriatic skin lesions in 2 patients within the infliximab-continued group. No serious adverse events were observed in either group.
A total of 12 of 21 patients (57%) in the infliximab-discontinuation group who relapsed had re-treatment with infliximab, of whom 8 (66.7%; 95% CI, 34.9-90.1) achieved remission at week 8. No patients had an infusion reaction in the observation period after infliximab was reintroduced within 8 weeks.
The investigators noted some study limitations, including the possibility that it was underpowered to detect additional risk factors for relapse. Additionally, dose intensification of infliximab after secondary loss of response in the infliximab-continued group was not allowed, and the observation period was 1 year after randomization.
“Our findings provide an important insight for patients, clinicians, and payers about outcomes after discontinuation of maintenance anti–tumor necrosis factor agents,” stated the researchers. “Considering the high efficacy of the re-treatment with the same agent, discontinuation might not necessarily confer major adverse outcomes. Therefore, it might be worth discussing, with caution, the withdrawal of the treatment in patients at low risk of relapse.”
Disclosures: The study was sponsored by the Mitsubishi Tanabe Pharma Corporation. Some of the study authors declared affiliations with pharmaceutical companies. Please see the original reference for a full list of disclosures.
Kobayashi T, Motoya S, Nakamura S, et al. Discontinuation of infliximab in patients with ulcerative colitis in remission (HAYABUSA): a multicentre, open-label, randomised controlled trial. Lancet Gastroenterol Hepatol. Published online April 19, 2021. doi: 10.1016/S2468-1253(21)00062-5