Switching patients with inflammatory bowel disease (IBD) in stable remission from intravenous (IV) to subcutaneous (SC) infliximab significantly reduced treatment failure at 48 weeks compared with continued IV therapy, according to results of a multicenter randomized controlled trial presented at Digestive Disease Week® (DDW) 2026.
In the Subcutaneous Infliximab Switch Study (SISS), treatment failure occurred in 15 of 103 patients (14.6%) who switched to SC infliximab compared with 40 of 101 patients (39.6%) who continued IV therapy — an absolute risk reduction of 25 percentage points (95% CI, 13.3-36.8%, P <.001). The trial enrolled 204 patients, including 130 with Crohn's disease (CD) and 74 with ulcerative colitis (UC).
Infliximab remains a cornerstone of IBD therapy with more than 25 years of post-marketing efficacy and safety data, but its long-term effectiveness is limited by loss of response over time, drug immunogenicity, and the practical burden of IV infusions, lead investigator John Chetwood, MBBS, FRACP, told GI & Hepatology News. Indirect evidence had suggested SC infliximab might offer efficacy advantages and lower immunogenicity than the IV formulation, but head-to-head randomized data have been lacking.
“The subcutaneous formulation of infliximab is therefore attractive to many, for both convenience and healthcare economic reasons,” Dr. Chetwood said. “It was therefore important to determine definitively how effective SC infliximab is in relation to IV.”
Methods
The investigators conducted a prospective, multicenter, open-label basket trial that enrolled adults with CD or UC who had been in steroid-free clinical and biochemical remission for at least 3 months while receiving IV infliximab. Participants — including those on doses up to 10 mg/kg every 8 weeks — were randomized 1:1, stratified by disease type, to continue IV infliximab or switch to SC infliximab.
The primary endpoint was treatment failure at week 48, a composite endpoint that included clinical relapse, discontinuation due to adverse events, therapeutic drug level failure, or patient withdrawal. Median age was 37 years, and 43% of participants were female.
Results
In the CD subgroup, switching significantly reduced treatment failure (13.6% vs 42.2%; absolute risk reduction [ARR], 28.6%; 95% CI, 13.9-43.2; P = .001).
In the UC subgroup, a numerical reduction was observed but did not reach statistical significance (16.2% vs 35.1%; ARR, 18.9%; 95% CI, -0.5- 38.4; P = .062). The benefit was concentrated among patients receiving standard-dose 5 mg/kg every 8 weeks (P < .001) and was not observed in those on dose-escalated regimens (P = .23). Anti-drug antibodies developed in three patients, all in the IV group. Adverse and serious adverse event rates were similar between arms.
On multivariate analysis, SC therapy was independently associated with maintenance of remission (hazard ratio [HR], 0.30; 95% CI, 0.17 – 0.55; P < .001), along with prior corticosteroid exposure (HR, 0.51; 95% CI, 0.30 – 0.86; P = .013 ), with a trend noted for lower baseline white blood cell count (HR, 1.14; 95% CI, 1.00 – 1.32; P = .055). Prior advanced therapy exposure, baseline escalated infliximab dosing, immunomodulator use, age, and sex were not independently associated with outcome.
“The efficacy differences were striking, showing SC infliximab was associated with greater corticosteroid-free remission to 48 weeks of follow up,” Dr. Chetwood said.
He noted that patients on IV therapy also had numerically more frequent undetectable serum drug levels — with or without anti-drug antibodies — and a greater need for elective dose escalation, though those differences did not reach statistical significance. Subgroup analyses also favored SC infliximab among patients with a body mass index of 30 or higher and among those receiving immunomodulator co-therapy at baseline.
“Our work suggests that SC infliximab is the preferred method of administration for maintenance therapy, particularly for patients on standard dosing (5 mg/kg 8-weekly),” Dr. Chetwood said. “This aligns with existing observational studies and network meta-analyses suggesting SC infliximab is more efficacious than IV infliximab.”
The findings carry a clear caveat for patients already on intensified IV regimens. “We did not detect a difference in the subgroup of patients on escalated IV dosing prior to switching to SC,” Dr. Chetwood said.
Limitations
The trial was open-label. The UC subgroup, while showing numerical benefit, did not statistical significance independently (though showed benefit in per protocol analysis), and the findings may not extend to patients already on dose-escalated IV infliximab, in whom no efficacy advantage from switching was observed.
Chetwood reported speaker fees from Dr. Falk Pharma, Novartis, Takeda, Johnson & Johnson, and Eli Lilly. Celltrion provided an unrestricted travel grant to support his attendance at DDW and an unrestricted grant supporting the study; the sponsor had no role in study design, conduct, analysis, or manuscript preparation.
DDW® is AGA's annual meeting, jointly sponsored by AGA, AASLD, ASGE, and SSAT. Learn more atddw.org.