Infliximab levels predict ASUC outcomes
Higher early clearance, especially by day 7, was strongly associated with nonresponse, treatment failure, and colectomy.
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12/26/2025
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by Doug Brunk
Early infliximab drug monitoring may predict short-term outcomes and identify acute severe ulcerative colitis (ASUC) patients who could benefit from intensified dosing, according to data from the multicenter PREDICT-UC study.
The goal of the PREDICT‑UC trial was to determine whether intensified or accelerated infliximab induction regimens are superior to standard infliximab induction for treating steroid‑refractory ASUC and to explore how infliximab drug levels and clearance relate to treatment response.
In a prospective observational study published in Gastroenterology, Australian researchers measured serum and fecal infliximab levels and modeled drug clearance during the first weeks of rescue therapy in 135 patients with steroid-refractory ASUC enrolled in PREDICT-UC. Nearly two-thirds of patients (63%) responded by day 7, but 27% experienced treatment failure by day 14 and 13% required colectomy within 3 months.
A key finding was the prognostic value of early serum infliximab exposure. Lower day 3 serum infliximab levels were associated with both day 14 treatment failure and subsequent colectomy. A day 3 level of 57.9 µg/mL or less identified patients at high risk for colectomy with 83.3% sensitivity, 67% specificity, and a negative predictive value of nearly 97%, suggesting early reassurance may be possible when levels are adequate, noted Christopher F.D. Li Wai Suen, MD, of the University of Melbourne, Department of Medicine, Australia, and colleagues.
Infliximab clearance emerged as another important determinant of outcome. Higher early clearance, especially by day 7, was strongly associated with nonresponse, treatment failure, and colectomy. Notably, patients with high clearance were more likely to respond to an initial 10 mg/kg dose than to standard 5 mg/kg dosing, and intensified induction appeared to mitigate colectomy risk in this subgroup.
Fecal infliximab levels correlated with inflammatory burden and endoscopic severity, supporting the concept of luminal drug loss in severe disease. Although management was not adjusted based on drug levels, the findings provide a rationale for early infliximab monitoring in ASUC.
“This study supports observational data indicating infliximab clearance to be a major determinant of outcomes in ASUC, and for the first time demonstrates that increased clearance may potentially be overcome by more intensive dosing,” the authors wrote.
Biological specimens for the current study were derived from a clinical trial that was supported by a Janssen-Cilag investigator-initiated study grant. Many of the authors reported financial relationships with pharmaceutical companies, including speaker/consulting fees and research funding.
Summary content
7 Key Takeaways
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Developed a paper-based colorimetric sensor array for chemical threat detection.
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Can detect 12 chemical agents, including industrial toxins.
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Production cost is under 20 cents per chip.
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Utilizes dye-loaded silica particles on self-adhesive paper.
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Provides rapid, simultaneous identification through image analysis.
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Inspired by the mammalian olfactory system for pattern recognition.
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Future developments include a machine learning-enabled reader device.
The guidelines emphasize four-hour gastric emptying studies over two-hour testing. How do you see this affecting diagnostic workflows in practice?
Dr. Staller: Moving to a four-hour solid-meal scintigraphy will actually simplify decision-making. The two-hour reads miss a meaningful proportion of delayed emptying; standardizing on four hours reduces false negatives and the “maybe gastroparesis” purgatory that leads to repeat testing. Practically, it means closer coordination with nuclear medicine (longer slots, consistent standardized meal), updating order sets to default to a four-hour protocol, and educating front-line teams so patients arrive appropriately prepped. The payoff is fewer equivocal studies and more confident treatment plans.
Metoclopramide and erythromycin are the only agents conditionally recommended for initial therapy. How does this align with what is being currently prescribed?
Dr. Staller: This largely mirrors real-world practice. Metoclopramide remains the only FDA-approved prokinetic for gastroparesis, and short “pulsed” erythromycin courses are familiar to many of us—recognizing tachyphylaxis limits durability. Our recommendation is “conditional” because the underlying evidence is modest and patient responses are heterogeneous, but it formalizes what many clinicians already do: start with metoclopramide (lowest effective dose, limited duration, counsel on neurologic adverse effects) and reserve erythromycin for targeted use (exacerbations, bridging).
Several agents, including domperidone and prucalopride, received recommendations against first-line use. How will that influence discussions with patients who ask about these therapies?
Dr. Staller: Two points I share with patients: evidence and access/safety. For domperidone, the data quality is mixed, and US access is through an FDA IND mechanism; you’re committing patients to EKG monitoring and a non-trivial administrative lift. For prucalopride, the gastroparesis-specific evidence isn’t strong enough yet to justify first-line use. So, our stance is not “never,” it’s just “not first.” If someone fails or cannot tolerate initial therapy, we can revisit these options through shared decision-making, setting expectations about benefit, monitoring, and off-label use. The guideline language helps clinicians have a transparent, evidence-based conversation at the first visit.
The guidelines suggest reserving procedures like G-POEM and gastric electrical stimulation for refractory cases. In your practice, how do you decide when a patient is “refractory” to medical therapy?
Dr. Staller: I define “refractory” with three anchors.
1. Adequate trials of foundational care: dietary optimization and glycemic control; an antiemetic; and at least one prokinetic at appropriate dose/duration (with intolerance documented if stopped early).
2. Persistent, function-limiting symptoms: ongoing nausea/vomiting, weight loss, dehydration, ER visits/hospitalizations, or malnutrition despite the above—ideally tracked with a validated instrument (e.g., GCSI) plus nutritional metrics.
3. Objective correlation: delayed emptying on a standardized 4-hour solid-meal study that aligns with the clinical picture (and medications that slow emptying addressed).
At that point, referral to a center with procedural expertise for G-POEM or consideration of gastric electrical stimulation becomes appropriate, with multidisciplinary evaluation (GI, nutrition, psychology, and, when needed, surgery).
What role do you see dietary modification and glycemic control playing alongside pharmacologic therapy in light of these recommendations?
Dr. Staller: They’re the bedrock. A small-particle, lower-fat, calorie-dense diet—often leaning on nutrient-rich liquids—can meaningfully reduce symptom burden. Partnering with dietitians early pays dividends. For diabetes, tighter glycemic control can improve gastric emptying and symptoms; I explicitly review medications that can slow emptying (e.g., opioids; consider timing/necessity of GLP-1 receptor agonists) and encourage continuous glucose monitor-informed adjustments. Pharmacotherapy sits on top of those pillars; without them, medications will likely underperform.
The guideline notes “considerable unmet need” in gastroparesis treatment. Where do you think future therapies or research are most urgently needed?
Dr. Staller: I see three major areas.
1. Truly durable prokinetics: agents that improve emptying and symptoms over months, with better safety than legacy options (e.g., next-gen motilin/ghrelin agonists, better-studied 5-HT4 strategies).
2. Endotyping and biomarkers: we need to stop treating all gastroparesis as one disease. Clinical, physiologic, and microbiome/omic signatures that predict who benefits from which therapy (drug vs G-POEM vs GES) would transform care.
3. Patient-centered trials: larger, longer RCTs that prioritize validated symptom and quality-of-life outcomes, include nutritional endpoints, and reflect real-world medication confounders.
Our guideline intentionally highlights these gaps to hopefully catalyze better trials and smarter referral pathways.
Dr. Staller is with the Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston.