Abstract Background Vitamin D deficiency is common among patients with inflammatory bowel disease (IBD) and has been associated with increased inflammatory activity. However, its impact on flare severity and clinical significant outcomes among IBD patients receiving infliximab remains unclear. This study evaluated whether low baseline vitamin D levels predict worse disease activity and adverse clinical outcomes in this population. Methods A retrospective cohort study was conducted using the TriNetX U.S. Collaborative Network. Adult IBD patients (≥18 years) treated with infliximab between 2018–2024 were stratified by baseline vitamin D level: ≥20 ng/mL (Cohort 1) vs 19 ng/mL (Cohort 2). Baseline vitamin D was measured within 6 months prior to 1 month after IBD diagnosis, and levels were required prior to biologic exposure. Propensity score matching (1:1) yielded 3,537 patients per cohort with balanced demographic and clinical characteristics. Outcomes assessed within 365 days after index infliximab exposure included CRP elevation, steroid use, fecal calprotectin elevation, inpatient encounters, biologic escalation, hemoglobin drop, hypoalbuminemia, gastrointestinal bleeding (GIB), abdominal pain/diarrhea, and fistula/abscess formation. Analysis were reported using odds ratios (ORs), hazard ratios (HRs), and log-rank statistics. Results Vitamin D–deficient patients demonstrated significantly higher risks of several adverse clinical outcomes. Compared with patients with vitamin D ≥ 20 ng/mL, those with vitamin D 19 ng/mL had increased risks of inpatient encounters (21.8% vs 18.9%; OR 0.834, 95% CI 0.742–0.936; p = 0.002), hemoglobin drop (19.0% vs 14.8%; OR 0.740, 95% CI 0.653–0.839; p 0.001), and low albumin (13.7% vs 10.7%; OR 0.751, 95% CI 0.651–0.867; p 0.001). Kaplan-Meier curves indicated significantly reduced survival free of CRP elevation (p = 0.010), steroid use (p = 0.011), inpatient encounters (p = 0.001), anemia (p 0.001), and hypoalbuminemia (p 0.001) in the vitamin D–deficient cohort. No statistically significant differences were found for fecal calprotectin elevation, biologic escalation, GIB, abdominal pain/diarrhea, or fistula/abscess formation. Conclusion Among IBD patients treated with infliximab, baseline vitamin D deficiency (19 ng/mL) was associated with higher inflammatory activity and increased risk of clinically significant flare outcomes, including hospitalization, anemia, and hypoproteinemia. This highlight the potential role of vitamin D optimization as part of a proactive disease-management strategy for initiating biologic therapy. Conflict of interest: Dr. Patel, Om: No conflict of interest Johal, Jashanveer: No conflict of interest Al-Bataineh, Mahmoud: No conflict of interest Hussein, Abdallah: No conflict of interest Schneider, Yecheskel: No conflict of interest Hyman, Jason:
Patel et al. (Thu,) studied this question.