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The administration of intravenous immunoglobulin (IVIG) has demonstrated promise in the treatment of medically refractory inflammatory bowel diseases (IBD). We aimed to identify factors associated with IVIG failures in the treatment of refractory IBD.Our historical cohort included patients with refractory IBD admitted to our inpatient service with an exacerbation and treated with at least 1 dose of IVIG (0.4 g/kg). Detailed clinical variables were recorded for subjects. Examined outcomes included changes in disease-specific severity indices, the duration of surgery-free survival after IVIG, infusion reactions, subsequent IBD-related emergency department visits, hospital readmissions, and mortality.Fifty-four subjects with refractory IBD (61% female, age 42 ± 16 yrs, 23 with Crohn's disease, 15 with ulcerative colitis, 16 with pouchitis) met the inclusion criteria. All disease severity scores were significantly improved after IVIG administration (Harvey–Bradshaw index P = 0.007, partial Mayo score P = 0.002, modified Pouchitis Disease Activity Index P = 0.008). Twenty-seven patients (50%) underwent surgery, with a mean surgery-free survival of 28.7 ± 3.7 months. In univariable analysis, patients with Clostridium difficile infection (CDI) had a 3-fold increased risk of bowel resection surgery after IVIG compared with those without (hazard ratio = 2.9, 95% confidence interval, 1.2–7.4; P = 0.023), and in subsequent multivariable analysis, CDI remained significant (hazard ratio = 3.0, 95% confidence interval, 1.2–7.6; P = 0.024). CDI was also associated with increased risk of hospital readmission (hazard ratio = 2.5, 95% confidence interval, 1.05–5.9; P = 0.038).Our study demonstrates that IVIG is beneficial in patients with medically refractory IBD, and that concomitant CDI is a risk factor for the treatment failure of IVIG for refractory disease.