LIBERTY: Prior Anti-Drug Antibodies Did Not Blunt SC Infliximab After Drug Holiday

Most patients with Crohn disease (CD) or ulcerative colitis (UC) who restarted infliximab as subcutaneous (SC) infliximab 240 mg after an interruption in intravenous (IV) therapy had detectable anti-drug antibodies (ADAs). Even so, clinical outcomes were generally similar regardless of prior ADA status, according to a post hoc analysis of the phase 3 LIBERTY-CD and LIBERTY-UC trials presented at the American College of Gastroenterology (ACG) 2026 Annual Scientific Meeting in Nashville, Tennessee.1

ADAs can compromise IV infliximab reinitiation after a drug holiday, and therapeutic drug monitoring is recommended before restarting IV therapy. Data on SC infliximab initiation after a drug holiday are limited, particularly regarding prior ADA status, according to investigators led by Marla Dubinsky, MD, of the Icahn School of Medicine at Mount Sinai.1 The SC formulation, infliximab-dyyb (Zymfentra), received US Food and Drug Administration approval in October 2023 for maintenance treatment of UC and CD following IV induction.3

Which Patients Restarted Infliximab After a Drug Holiday in LIBERTY?

In LIBERTY, patients received open-label IV infliximab 5 mg/kg at weeks 0, 2, and 6, and week 10 responders were randomized to SC infliximab 120 mg or placebo every 2 weeks. From week 22 through week 102, patients could escalate to SC infliximab 240 mg every 2 weeks for loss of response or at physician discretion.1,2

This analysis focused on 51 patients with CD and 77 with UC in the placebo arm who later initiated SC infliximab 240 mg. Prior ADA positivity was defined as ADA detection at least once between week 10 and SC initiation, using a drug-tolerant electrochemiluminescence assay.1

Overall, 72.5% (37/51) of patients with CD and 92.2% (71/77) with UC were ADA positive before SC initiation. The median interval from the last IV infusion to SC initiation was 16 weeks in all subgroups.1

ADA-positive patients were less likely to be receiving immunomodulators than ADA-negative patients (CD, 16.2% vs 50.0%; UC, 18.3% vs 50.0%). Among patients with CD, ADA-positive patients also had higher median baseline Crohn’s Disease Activity Index scores (318.1 vs 273.1) and C-reactive protein (CRP) levels (10.4 vs 3.6 mg/L).1

Did Prior ADAs Affect Response to SC Infliximab 240 mg?

Clinical response emerged by 8 ± 2 weeks after SC initiation and was sustained through 78 to 80 weeks in both diseases. In CD, clinical remission and response rates at the final assessment were 86.7% (13/15) and 93.3% (14/15) among ADA-positive patients vs 81.8% (9/11) and 90.9% (10/11) among ADA-negative patients.1

In UC, partial clinical remission and response rates were 69.2% (18/26) and 96.2% (25/26) among ADA-positive patients vs 100% (3/3) for both end points among ADA-negative patients. Clinical remission and response by modified Mayo score were 62.1% (18/29) and 79.3% (23/29) vs 66.7% (2/3) and 100% (3/3), respectively.1

Median CRP levels fell by the first assessment at 8 ± 2 weeks, and median fecal calprotectin levels fell by the first measurement at 32 ± 2 weeks. Both reductions were maintained through 78 to 80 weeks regardless of prior ADA status.1

What Happened to Infliximab Levels and ADAs on SC Therapy?

Serum infliximab concentrations rose substantially after SC infliximab 240 mg initiation in both ADA subgroups and converged over time.¹ Among patients with pre-existing ADAs, ADA positivity declined during SC treatment, reaching 66.7% in CD and 65.5% in UC at the last assessment, 78 to 80 weeks after initiation. De novo ADA development was uncommon among patients without prior ADAs.1

The investigators concluded pre-existing ADAs did not appear to compromise outcomes after SC infliximab initiation following a drug holiday, and noted the decline in ADA positivity warrants further mechanistic study.1

References

1. Dubinsky MC, Sands BE, Abraham BP, et al. Impact of prior anti-drug antibody status on clinical outcomes following subcutaneous infliximab initiation after intravenous infliximab interruption: a post hoc analysis of LIBERTY-CD and -UC studies. Presented at: American College of Gastroenterology 2026 Annual Scientific Meeting; October 9-14, 2026; Nashville, TN.

2. Hanauer SB, Sands BE, Schreiber S, et al. Subcutaneous infliximab (CT-P13 SC) as maintenance therapy for inflammatory bowel disease: two randomized phase 3 trials (LIBERTY). Gastroenterology. 2024;167(5):919-933. doi:10.1053/j.gastro.2024.05.006

3. Campbell P. FDA approves first subcutaneous infliximab for maintenance therapy in UC and Crohn disease. HCPLive. Accessed October 13, 2026. https://www.hcplive.com/view/fda-approves-first-subcutaneous-infliximab-for-maintenance-therapy-in-uc-and-crohn-disease