Subcutaneous Infliximab Recaptures Disease Control After Treatment Interruption in IBD

Treatment interruptions with anti-TNFs are common in clinical practice, driven by loss of response, safety concerns, pregnancy, or patient preference. Historically, reintroducing the drug intravenously has carried meaningful risk.

However, new post hoc data from the phase 3 LIBERTY trials suggest that subcutaneous (SC) infliximab may offer a safer, more durable path back to disease control for patients with Crohn's disease (CD) or ulcerative colitis (UC) following a drug holiday. The analysis was presented by Marla Dubinsky, MD, a gastroenterologist and professor of medicine at the Icahn School of Medicine at Mount Sinai, at Digestive Disease Week (DDW) 2026 in Chicago, IL.

"Historically, about 50% of patients are off anti-TNF therapy over the first 2 to 3 years," Dubinsky told HCPLive. "Before we understood drug levels and antibodies, we just waited for people to lose response and then moved on."Before we understood drug levels, safety, antibodies, there were quite a number of patients who were stopping it, predominantly for loss of response, with a large number of them associated with anti drug antibodies because they were not proactively optimized. We just waited for people to lose response, got a drug level and said ‘You've now got antibodies, I have to move on.’”

Study Design and Population

The LIBERTY-CD and LIBERTY-UC trials randomly assigned patients who responded to IV infliximab induction to either SC infliximab 120 mg or placebo every other week through week 54. Patients in the placebo arm who experienced disease recurrence after a minimum 16-week drug holiday were eligible to receive SC infliximab 240 mg, double the approved maintenance dose, as a form of reintroduction.

The present post hoc analysis evaluated 51 CD and 77 UC patients from the placebo arms, assessing clinical, biochemical, endoscopic, and pharmacokinetic outcomes through week 102.

Efficacy and Pharmacokinetic Outcomes

Early clinical responses emerged within 8 weeks of SC infliximab initiation and were sustained throughout the study period, with partial clinical response rates of 92.3% in CD and 96.6% in UC at treatment end. Fecal calprotectin remission was achieved in 61.1% of CD patients and 65.2% of UC patients, with endoscopic response rates of 64.0% and 68.8%, respectively. Additionally, treatment persistence through week 102 was 72.3% in CD and 61.9% in UC.

Dubinsky highlighted the parallel between clinical recapture and pharmacokinetic recovery as a key finding. Serum infliximab levels rose markedly after SC reintroduction and remained stable, a pattern that tracked directly with clinical response.

“You see this parallel where you get this recapturing in 8 weeks, and when you look at the trough level, you then see you've recaptured the trough level that you stay at throughout that period of you now being in the 240 arm,” she said. “I think the fact that you see that association of the PK coming back after no drug level, or a honeymoon during that period, and you see that clinical response parallel the recapture of the trough level, or that consistent, sustained drug level that we're used to, really tells you that you recapture because you're able to bring back the drug concentration that's associated with response.”

The Immunogenicity Advantage

Dubinsky additionally highlighted immunogenicity findings as among the most clinically significant data from her research. Reintroduction of IV infliximab after a drug holiday carries well-documented risk of infusion reactions, driven by a surge in anti-drug antibodies (ADAs) upon re-exposure. SC reintroduction appeared to sidestep this problem. Despite high ADA rates at the time of SC reintroduction, antibody status had minimal impact on outcomes, with approximately three quarters of patients maintaining treatment persistence regardless of ADA status.

Dubinsky noted that SC infliximab 240 mg is not currently FDA-approved for this indication in the US, but expressed hope that publication of these data would support conversations with payers and health authorities about its clinical utility.

Editor's note: Dubinsky reports relevant disclosures with AbbVie, Abivax, Astra Zeneca, BMS, Celltrion, Eli Lilly, Janssen, Johnson and Johnson, Merck, Pfizer, Prometheus Labs, Roche, Sanofi, Spyre, Takeda, and others.

References

1. Dubinsky MC, Sands BE, Abraham BP, 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 (DDW) 2026; Chicago, IL; May 2–5, 2026.

2. Rubin DT. Restarting Biologic Agents After a Drug Holiday. Gastroenterol Hepatol (N Y). 2019;15(11):612-615.