NEW YORK (Reuters Health) – A study from Japan has found increased rates of relapse of ulcerative colitis (UC) when patients on long-term infliximab therapy go off the drug.

Long-term use of infliximab, an anti-TNF agent, might lead to an increased risk of malignancy or infection. As the number of patients receiving maintenance treatment with infliximab is increasing, “questions have arisen regarding whether infliximab could be discontinued in some patients,” the study team notes in a report in The Lancet Gastroenterology and Hepatology.

In the open-label, randomized HAYABUSA study, funded in part by the Mitsubishi Tanabe Pharma Corporation, researchers compared the outcomes of 92 patients with UC on maintenance infliximab therapy and in remission; half continued on infliximab and half discontinued the drug.

At 48 weeks, 37 (80%) patients in the infliximab-continued group were still in remission compared with only 25 (54%) patients in the infliximab-discontinued group (P=0.0076). No serious adverse events were reported in either group.

Twelve of 21 (57%) relapsed patients in the infliximab-discontinued group restarted the drug and eight (67%) of these patients achieved remission within eight weeks.

“Maintenance of remission was significantly more common in patients who continued infliximab than in those who discontinued. Discontinuing infliximab should therefore be discussed with caution, taking both risk of relapse and efficacy of re-treatment into account,” Dr. Taku Kobayashi of Kitasato University Kitasato Institute Hospital in Tokyo and colleagues advise in their paper.

In a linked comment, Dr. Bella Ungar of Tel Aviv University in Israel says this study contributes considerably to the knowledge base on withdrawal of anti-TNF therapy.

Dr. Ungar points out that all patients with UC in the study who stopped therapy were on long-standing infliximab therapy and in clinical and endoscopic remission or had mild endoscopic activity at the start of the study. Despite this, substantially more patients relapsed in the discontinuation group.

“Contrary to several previous studies, concomitant immunomodulatory therapy before withdrawal had no effect on the recurrence rate. Previous studies have shown that immunomodulator monotherapy after withdrawal decreases rates of recurrence, but this effect was not examined in the current study,” Dr. Ungar notes.

“With regard to infliximab trough concentrations before withdrawal, although not associated with recurrence rate, the median concentration in the total cohort was 5 ug/mL. Perhaps higher concentrations at the time of withdrawal would have reduced recurrence rates. Furthermore, no longitudinal trough concentration measurement was undertaken,” Dr. Ungar writes.

“Infliximab was the first biologic treatment in all participants who were randomly assigned, which reinforces the homogeneity of the study groups. Additional studies are needed to determine whether previous biologic therapy failure predicts detrimental outcomes upon withdrawal. Finally, the finding that histological index (especially given that it was established blinded to clinical and endoscopic data) was more predictive of relapse, compared with endoscopic score, is remarkable and suggests that anti- TNF therapy withdrawal should be attempted not only in deep remission, but also in histological remission,” Dr. Ungar suggests.

Several authors have financial relationships with Mitsubishi Tanabe Pharma Corporation.

SOURCE: https://bit.ly/3aEGwMo and https://bit.ly/3gHDtXU The Lancet Gastroenterology and Hepatology, online April 19, 2021.

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