Systematic review with meta-analysis:Time to diagnosis and the impact of delayed diagnosis on clinical outcomes in inflammatory bowel disease

Background: The impact of diagnostic delay on the clinical course of inflammatory bowel disease (IBD) remains uncertain. Aim: To perform a systematic review of time to diagnosis and the impact of delayed diagnosis on clinical outcomes in Crohn's disease (CD) and ulcerative colitis (UC). Methods: We searched EMBASE and Medline from inception to 30th November 2022 for studies reporting diagnostic interval, from symptom onset to IBD diagnosis. We calculated the median, interquartile range (IQR) and pooled weighted median, of median diagnostic intervals of eligible studies. We defined delayed diagnosis as individuals above the 75th centile of longest time to diagnosis in each study. Using random effects meta-analysis, we pooled odds ratios (ORs) with 95% confidence intervals (CI) for studies reporting clinical outcomes, according to delayed diagnosis. Results: One hundred and one studies representing 112,194 patients with IBD (CD = 59,359; UC = 52,835) met inclusion criteria. The median of median times to diagnosis was 8.0 (IQR: 5.0–15.2) and 3.7 months (IQR: 2.0–6.7) in CD and UC, respectively. In high-income countries, this was 6.2 (IQR: 5.0–12.3) and 3.2 months (IQR: 2.2–5.3), compared with 11.7 (IQR: 8.3–18.0) and 7.8 months (IQR: 5.2–21.8) in low-middle-income, countries, for CD and UC respectively. The pooled weighted median was 7.0 (95% CI: 3.0–26.4) and 4.6 (95% CI: 1.0–96.0) months, for CD and UC respectively. Eleven studies, representing 6164 patients (CD = 4858; UC = 1306), were included in the meta-analysis that examined the impact of diagnostic delay on clinical outcomes. In CD, delayed diagnosis was associated with higher odds of stricturing (OR = 1.88; CI: 1.35–2.62), penetrating disease (OR = 1.64; CI: 1.21–2.20) and intestinal surgery (OR = 2.24; CI: 1.57–3.19). In UC, delayed diagnosis was associated with higher odds of colectomy (OR = 4.13; CI: 1.04–16.40). Conclusion: Delayed diagnosis is associated with disease progression in CD, and intestinal surgery in both CD and UC. Strategies are needed to achieve earlier diagnosis of IBD.