Key takeaways:
- Restarting subcutaneous infliximab 240 mg after at least a 16-week drug holiday recaptured response by 8 ± 2 weeks with sustained benefits.
- This was also effective among anti-drug antibody-positive patients.
CHICAGO — Restarting subcutaneous infliximab 240 mg after treatment interruption of at least 16 weeks was able to recapture response early, with sustained biochemical and endoscopic improvements over time, according to a presenter here.
Data presented at Digestive Disease Week showed that early clinical responses were observed as early as 8 ± 2 weeks after reintroduction of 240 mg subcutaneous infliximab (Zymfentra, Celltrion).
“Historically, patients may have discontinued IV infliximab for a multitude of reasons, such as insurance, tolerance, anti-drug antibodies or pharmacokinetic reasons,” Marla C. Dubinsky, MD, codirector of the Susan and Leonard Feinstein Inflammatory Bowel Disease Clinical Center at Mount Sinai, told Healio. “However, despite cycling through multiple other therapies, patients still report that they did the best when they were on IV infliximab.
“We are concerned that after a drug holiday, particularly if longer than 6 months, patients are at high risk of developing anti-drug antibodies, which can be associated with significant infusion reactions, especially on the second reinduction dose,” she added. “What these data suggest is that perhaps the key to avoiding this clinical scenario is to go straight to subcutaneous infliximab at 240 mg.”
To assess the efficacy and safety of restarting subcutaneous infliximab, Dubinsky and colleagues analyzed patient data from the LIBERTY-CD and LIBERTY-UC trials, specifically that of patients who had improved on IV infliximab, were then switched to placebo and later reinitiated treatment after a 16-week drug holiday when their disease worsened.
Patients who had responded to IV infliximab were later assigned at week 10 to either subcutaneous infliximab 120 mg or placebo every other week through week 54. Dose escalation to subcutaneous infliximab 240 mg from week 22 through week 102 was permitted either at the physician’s discretion or if the patients lost response.
The researchers aligned all data to the time patients reinitiated subcutaneous infliximab, tracking clinical, biochemical and endoscopic endpoints throughout treatment, as well as treatment persistence and treatment-emergent adverse events. They also performed multivariable regression analyses to determine which patients from the placebo groups —51 with Crohn’s disease and 77 with ulcerative colitis — were most likely to benefit when restarting subcutaneous infliximab.
After a median interval of 16 weeks between the final IV infliximab induction and starting subcutaneous infliximab, Dubinsky and colleagues reported that early clinical responses were observed by 8±2 weeks for both patients with CD and UC and maintained throughout the study.
“Starting subcutaneous infliximab 240 mg after at least a 16-week interruption was associated with early recapture of clinical response and meaningful rates of biochemical and endoscopic improvement through longer follow-up, without new safety signals identified after restart,” Dubinsky told Healio.
The researchers observed that by the end of the study, 61.1% of patients with CD and 65.2% with UC had attained fecal calprotectin remission, with endoscopic response/improvement among 64% and 68.8%, respectively. Treatment persistence was 72.3% for patients with CD and 61.9% for UC. Although serum infliximab levels were notably increased when reinitiating subcutaneous infliximab vs. preinitiation trough levels, they remained stable through week 102.
This treatment persistence “was observed even among patients who were anti-drug antibody (ADA)-positive prior to restarting subcutaneous infliximab,” Dubinsky noted. More than two-thirds (68.2%) of patients with ADA-positive CD and 61.9% with ADA-positive UC remained on therapy vs. 83.6% and 50% of ADA-negative patients, respectively.
“This is an important real-world nuance, since immunogenicity is often the central concern when patients return after a drug holiday,” she said. “[This] is clinically meaningful because it pushes back on an overly binary mindset that ‘antibodies automatically mean you can’t restart.’”
The researchers reported that, for patients with CD, achieving clinical remission at week 10 and maintaining infliximab levels of 20 g/mL or higher at 16 weeks were associated with clinical remission at 24 ± 2 weeks after starting subcutaneous infliximab.
For UC, a lower partial Mayo score at week 10, lower C-reactive protein at treatment initiation and infliximab levels of at least 22 g/mL at 8 weeks were linked to partial clinical remission at 40 ± 2 weeks after beginning subcutaneous infliximab.
“Drug holidays happen, and when patients flare, restarting infliximab can be a reasonable strategy for selected patients, but it must be done so thoughtfully,” Dubinsky told Healio. “Despite a honeymoon period off the drug, patients were able to resume therapy, given at 240 mg and not 120 mg, and recapture response without worrying about infusion reactions thought to be the rate-limiting step of reintroduction of infliximab after a drug holiday.
“This could be practice changing,” she added.
For more information:
Marla C. Dubinsky, MD, can be reached at gastroenterology@healio.com.
Sources/Disclosures
Source:
Dubinsky MC, et al. Recapturing disease control with subcutaneous infliximab after a drug holiday following intravenous infliximab induction: A post hoc analysis of LIBERTY-CD and -UC studies. Presented at: Digestive Disease Week; May 2-5, 2026; Chicago.
Disclosures:
Dubinsky reports employment with Trellus Health and consulting roles with AbbVie, Abivax, AstraZeneca, Boehringer Ingelheim, Celltrion, Genentech, Janssen, Johnson & Johnson, Merck, Pfizer, Prometheus Labs, Sanofi, Spyre Therapeutics and Takeda Pharmaceuticals. Please see the study for all other authors’ relevant financial disclosures.
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