Inflammatory bowel disease (IBD) affects at least 1.3% of the U.S. population and is associated with significant morbidity. The development of monoclonal antibodies against tumor necrosis factor-alpha (TNF-a) revolutionized the management of IBD. Among these agents, infliximab, an anti-TNF-a chimeric monoclonal IgG1 antibody, is one of the preferred treatment options. However, about one-half of patients who achieve clinical remission with infliximab relapse within 1 year of discontinuation.
A meta-analysis and systematic review was conducted to evaluate the efficacy and safety of infliximab retreatment in patients with IBD who initially responded to infliximab but relapsed after it was discontinued.
MEDLINE, Embase, CINAHL, and SCOPUS electronic databases were searched from their inceptions through August 15, 2020, for prospective or retrospective controlled or uncontrolled studies involving patients diagnosed with IBD who restarted infliximab treatment after discontinuation of initial therapy and who had no history of any other biological agent.
The outcome of interest was the proportion of patients who experienced either induction of remission (i.e., clinical, biochemical or endoscopic remission), maintenance of remission, or infusion-related reactions. Nonhuman studies, those only available as abstracts or posters, cases reports, reviews, meta-analyses, letters, editorials, or ongoing studies, were excluded.
Nine studies involving 428 patients were included in the meta-analysis, five involving Crohn's disease (CD), one involving ulcerative colitis (UC), and three involving both CD and UC. These patients had reinitiated infliximab treatment within 4 to 26.7 months following discontinuation of therapy. All of these studies were nonrandomized, single-arm, observational trials. Most patients received a dose of infliximab of 5 mg/kg, with fewer than 3% receiving 7.5 or 10 mg/kg IV at Weeks 0, 2, and 6. Between 61% and 100% of patients received concomitant immunomodulator therapy during infliximab discontinuation and retreatment. Only three studies reported on infliximab-positive antibodies.
Eight of the studies (n = 358) reported on clinical remission following infliximab retreatment in patients with IBD. The pooled remission rate after infliximab retreatment was 85% for induction treatment (i.e., administered for at least 3 months) and 73% for maintenance treatment (i.e., treated for at least 1 year). The remission induction rate for patients with IBD who restarted infliximab after a minimum drug holiday of 16 weeks or more was 84%. The remission reduction rates were similar between the different subtypes of IBD.
Regarding infusion-related reactions, seven studies (n = 368 patients) reported on this outcome. Nine percent of patients with IBD experienced an infusion reaction. The use of immunomodulators did not affect the occurrence of infusion reactions. Severe infusion reactions requiring discontinuation of the infusion due to dyspnea or hypotension were reported in five studies and ranged from 0% to 12.5%.
The authors concluded that the studies were of moderate quality, with the risk of bias varying among the papers.
Pharmacists can utilize this information to encourage patients to discuss possible retreatment with their providers if they had been responding to infliximab for IBD but discontinued therapy for non-life-threatening reasons.
The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.
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