Abstract Background Vitamin D deficiency is highly prevalent among patients with inflammatory bowel disease (IBD) and may contribute to increased inflammatory activity and flare severity. However, its impact on clinical outcomes among IBD patients treated with adalimumab remains unclear. This study assessed whether low baseline vitamin D levels predict worse inflammatory markers and clinically significant outcomes following adalimumab initiation. Methods This retrospective cohort study utilized the TriNetX U.S. Collaborative Network. Adult patients (≥18 years) with Crohn’s disease or ulcerative colitis who received adalimumab between 2018–2024 were stratified by baseline vitamin D level: ≥20 ng/mL (Cohort 1) and 19 ng/mL (Cohort 2). Vitamin D levels were captured within 6 months before to 1 month after IBD diagnosis and prior to biologic exposure. Propensity score matching (1:1) produced 3,134 patients in each cohort, balanced across demographics, comorbidities, and inflammatory markers. Outcomes were evaluated over 365 days and included CRP elevation, steroid use, fecal calprotectin elevation, inpatient encounters, biologic escalation, hemoglobin drop, low albumin, gastrointestinal bleeding (GIB), abdominal pain/diarrhea, and fistula/abscess formation. Odds ratios (OR), risk ratios, and hazard ratios (HR) were reported. Results Vitamin D–deficient patients experienced significantly higher risks of multiple adverse outcomes compared with those with sufficient levels. Deficiency was associated with increased CRP elevation (22.7% vs 18.7%; OR 0.782, 95% CI 0.692–0.884; p 0.001), steroid use (40.9% vs 38.3%; OR 0.898, 95% CI 0.811–0.993; p = 0.036), inpatient encounters (20.0% vs 16.2%; OR 0.774, 95% CI 0.680–0.880; p 0.001), biologic escalation (11.7% vs 9.9%; OR 0.828, 95% CI 0.705–0.971; p = 0.020), hemoglobin drop (15.5% vs 11.1%; OR 0.681, 95% CI 0.587–0.789; p 0.001), and hypoalbuminemia (9.5% vs 7.5%; OR 0.765, 95% CI 0.640–0.915; p = 0.003). Survival analyses showed significantly reduced survival free of CRP elevation, steroid use, inpatient encounters, anemia, and hypoalbuminemia in the deficient cohort (all p 0.05). No significant differences were observed for fecal calprotectin elevation, GIB, or fistula/abscess outcomes. Conclusion Among IBD patients treated with adalimumab, baseline vitamin D deficiency (19 ng/mL) was associated with higher inflammation and increased risk of clinically significant flare outcomes, including hospitalization, anemia, hypoalbuminemia, and need for steroid therapy or additional biologic escalation. These findings suggest that vitamin D optimization may play an important role in improving outcomes for IBD patients initiating TNF-α inhibitor therapy. Conflict of interest: Dr. Johal, Jashanveer: No conflict of interest Patel, Om: No conflict of interest Hussein, Abdallah: No conflict of interest Al-Bataineh, Mahmoud: No conflict of interest Schneider, Yecheskel: No conflict of interest Hyman, Jason: No conflict of interest
Johal et al. (Thu,) studied this question.