Early IBD care tied to better CD outcomes
Review synthesizes data linking diagnostic delay to complications and supports early biologic therapy in Crohn’s disease.
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02/24/2026
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by Doug Brunk
Delays in diagnosing and properly treating inflammatory bowel disease (IBD), especially Crohn’s disease (CD), are linked to worse health outcomes. A comprehensive review found that starting advanced therapy early in Crohn’s disease helps more patients achieve remission and lowers the need for surgery.
For the review, published in the Journal of Crohn’s and Colitis, British investigators summarized evidence on diagnostic delay and early intervention in CD and ulcerative colitis (UC), highlighting marked differences in disease trajectory and treatment response.
Diagnostic delay common, clinically relevant
Across cohorts cited in the review, median diagnostic delays for CD ranged from 5 months in France to 9 months in Switzerland, with longer delays reported in US studies. In lower- and middle-income countries, median delay was 8 months for CD and 3 months for UC. Laboratory abnormalities may precede diagnosis by up to 8 years in CD and 3 years in UC.
A pooled analysis of 8 studies found that patients with CD whose diagnosis fell above the 75th percentile for delay had an 88% higher odds of stricturing disease and a 65% higher odds of penetrating complications. Delayed diagnosis was also associated with a 2-fold increased risk of intestinal surgery. In UC, data were less consistent, although one meta-analysis reported a pooled odds ratio (OR) of 4.13 for colectomy in adults with delayed diagnosis.
Evidence from the review suggests that risk factors for delayed diagnosis in CD include ileal involvement and being younger than 40 years old. In a retrospective study of 28, 092 patients, female sex, Black or Asian race/ethnicity, obesity, smoking, socioeconomic deprivation, loperamide prescription, and preexisting anxiety or depression were associated with time to diagnosis exceeding 12 months.
A prospective study that evaluated fecal calprotectin (FCAL) testing in primary care demonstrated high negative predictive value (98%-99%) for excluding IBD, although positive predictive value ranged from 27% to 50%. In a separate, small validation study, combining FCAL with the International Organization for Inflammatory Bowel Disease Red Flags Index increased sensitivity from 50% to 100% and positive predictive value from 59% to 72% in a validation study.
Early ‘top-down’ therapy benefits in Crohn’s disease
Evidence supporting early biologic therapy is strongest in CD. In the CALM randomized controlled trial of patients with disease duration ≤1 year, 46% of patients in a tight-control arm achieved mucosal healing (Crohn’s Disease Endoscopic Index of Severity <4 without deep ulcers) at 48 weeks.
Meta-analyses cited in the review further demonstrated benefit from early anti–tumor necrosis factor (anti-TNF) therapy. Initiation within 3 years of diagnosis was associated with reduced abdominal surgery (relative risk [RR], 0.43) and disease progression (RR, 0.51). Another pooled analysis found early biologic use (≤2 years from diagnosis) doubled the odds of clinical remission (OR, 2.1).
More recent data suggest benefit from even earlier treatment. In a retrospective cohort, starting biologic therapy within 12 months of diagnosis was associated with higher transmural healing (adjusted OR, 2.82; 95% CI, 1.13-7.06) and reduced bowel damage progression (adjusted hazard ratio [aHR], 0.28) and CD-related surgery (aHR, 0.21).
The PROFILE trial randomized patients a median of 12 days after diagnosis to “top-down” infliximab plus immunomodulator vs accelerated step-up therapy. Sustained steroid- and surgery-free remission differed by 64% between groups, with 67% of the top-down group achieving ulcer-free endoscopic remission at week 48 and a 10-fold reduction in urgent abdominal surgery.
Limited evidence for early advanced therapy in UC
In contrast, starting advanced therapy early has not consistently shown clear benefits for people with UC. An individual participant data meta-analysis found no increase in remission rates among patients with shorter disease duration at treatment initiation. Population-based studies reported no difference in hospitalization or colectomy rates between early and late anti-TNF initiation. Similarly, early (≤30 days) vs delayed vedolizumab showed no difference in nonresponse at 6 or 12 months.
The researchers attribute these differences to pathophysiology: transmural inflammation in CD predisposes to cumulative structural damage, while UC inflammation is mucosal and often controllable with mesalazine or thiopurines.
“To provide the best possible clinical outcomes for patients living with IBD, we feel the global IBD community should focus effort and resources on early recognition, early diagnosis, and early initiation of appropriate, effective therapy,” they concluded.
Summary content
7 Key Takeaways
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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.