Landmark IBD trials · Summary of an original articleGastroenterology 2024;167:919–33

LIBERTY-CDCD · Biosimilars and dosing

Subcutaneous Infliximab (CT-P13 SC) as Maintenance Therapy for Inflammatory Bowel Disease: Two Randomized Phase 3 Trials (LIBERTY)

Hanauer SB, et al.

Gastroenterology 2024 · PMID 38788861 (PubMed, opens in a new tab) · doi 10.1053/j.gastro.2024.05.006 (full paper, opens in a new tab)

Figure 1. The two co-primary endpoints at week 54 in week-10 responders to IV infliximab induction, randomised to subcutaneous infliximab 120 mg every 2 weeks or placebo.

Data for this figure, percentage of patients
Endpoint	SC infliximab	Placebo	Difference
Clinical remission, Week 54 (primary endpoint)	62.3%	32.1%	P<0.0001
Endoscopic response, Week 54 (primary endpoint)	51.1%	17.9%	P<0.0001

Placebo here means stopping infliximab after IV induction; the trial does not compare subcutaneous with IV maintenance.

Source: Hanauer 2024, abstract (all-randomised population). The abstract gives percentages only, not counts.

Structured abstract

BackgroundInfliximab had been given only by intravenous infusion. A subcutaneous form promised steadier drug levels and home dosing, but it needed randomised evidence as maintenance therapy in Crohn's disease.

MethodsPhase 3, randomised (2:1), placebo-controlled, double-blind maintenance trial after open-label IV induction (published with the companion LIBERTY-UC trial). 396 patients. Primary endpoint: Co-primary at week 54: clinical remission and endoscopic response.

ResultsPrimary result. Clinical remission 62.3% vs 32.1% (P<0.0001); endoscopic response 51.1% vs 17.9% (P<0.0001).

Take-homeAfter IV infliximab induction, subcutaneous infliximab 120 mg every 2 weeks maintains remission and endoscopic response in Crohn's disease, an option for patients who prefer injections to infusions.

Table 1. Trial at a glance

Patients	396
Population	Moderately to severely active Crohn's disease with inadequate response or intolerance to corticosteroids and immunomodulators. 396 received open-label IV induction; clinical responders at week 10 were randomised.
Comparison	CT-P13 SC 120 mg every 2 weeks vs placebo from week 10 to week 54, after CT-P13 IV 5 mg/kg at weeks 0, 2 and 6
Drugs	infliximab (CT-P13 subcutaneous)
Classes	Anti-TNF
Published	Hanauer SB, et al. Gastroenterology 2024;167:919–33.

Key points

Key secondary endpoints were also significantly better with SC infliximab.
Well tolerated, with no new safety signals.
Companion LIBERTY-UC: week 54 clinical remission 43.2% vs 20.8% (P<0.0001).
A subcutaneous infliximab (Remsima SC) is marketed in Canada; check the current product monograph and drug-plan criteria for IBD use.

Limitations

Compared with placebo (infliximab withdrawal), not with IV infliximab maintenance.
Only week 10 responders were randomised.
Fixed 120 mg dose regardless of weight.
Sponsored by the manufacturer (Celltrion).

Commentary

LIBERTY-CD gives randomised evidence for switching from IV infusions to self-injected infliximab after induction. Subcutaneous dosing gives steadier drug levels than IV dosing, which may help patients who lose response late in the 8-week infusion cycle.

Journal club

PopulationModerately to severely active Crohn's disease with inadequate response or intolerance to corticosteroids and immunomodulators. 396 received open-label IV induction; clinical responders at week 10 were randomised.

InterventionCT-P13 SC 120 mg every 2 weeks

ComparisonPlacebo from week 10 to week 54, after CT-P13 IV 5 mg/kg at weeks 0, 2 and 6

Primary outcomeCo-primary at week 54: clinical remission and endoscopic response.

Design

Phase 3, randomised (2:1), placebo-controlled, double-blind maintenance trial after open-label IV induction (published with the companion LIBERTY-UC trial). 396 patients.

Primary result. Clinical remission 62.3% vs 32.1% (P<0.0001); endoscopic response 51.1% vs 17.9% (P<0.0001).

Validity and applicability

Compared with placebo (infliximab withdrawal), not with IV infliximab maintenance.
Only week 10 responders were randomised.
Fixed 120 mg dose regardless of weight.
Sponsored by the manufacturer (Celltrion).

Where it sits now

After IV infliximab induction, subcutaneous infliximab 120 mg every 2 weeks maintains remission and endoscopic response in Crohn's disease, an option for patients who prefer injections to infusions.

REScUE (2026): After secondary loss of response to ustekinumab, IV reinduction plus every-4-week dosing is no better than reinduction plus every-8-week dosing, and few patients regain remission either way.
SERENE-CD (2022): Extra-intensive adalimumab induction does not beat the standard 160/80 mg regimen, and proactive TDM-guided maintenance was no better than dosing adjusted to symptoms and CRP.
VISIBLE 2 (2022): After two IV doses, vedolizumab 108 mg SC every 2 weeks maintains remission in Crohn's disease better than placebo, so patients can switch to home injections.
PAILOT (2019): In children on adalimumab, proactive trough monitoring with dose adjustment to 5 µg/mL kept far more patients in steroid-free remission than reactive testing.

Questions for discussion

The comparator was withdrawal to placebo after induction. What question does that design answer, and what does it leave open?
How would you choose between IV and subcutaneous infliximab maintenance for a patient who loses response late in the 8-week infusion cycle?
A fixed 120 mg dose was used regardless of weight. Which patients might be underdosed?

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