P-138 Factors Predicting Treatment Response in Patients with Severe Inflammatory Bowel Disease Treated with Intravenous Immunoglobulin

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Abstract

Background:

Development of a secondary humoral immune deficiency has been postulated as one of the mechanisms leading to failure of conventional treatment in patients with severe IBD. IVIG has therefore been examined as a possible treatment option, and has demonstrated promise in the treatment of refractory disease. Our aim was to identify possible risk factors which can predict IVIG failures in the treatment of refractory IBD.

Methods:

In this historical cohort study, the study group included IBD patients with refractory disease admitted to our inpatient service with an exacerbation who were treated with at least one dose of IVIG (0.4 g/kg) from June 2010 to November 2014. Exclusion criteria included those with a known primary immunodeficiency disorder or HIV. Detailed clinical variables were recorded for subjects at the time of IVIG treatment, including basic demographics, disease type, duration of IBD, concomitant infections (Clostridium difficile [C.diff], cytomegalovirus [CMV]), other IBD-related treatments, prior bowel resection surgery, and basic laboratory testing. The primary outcome was defined as the duration of surgery-free survival following IVIG. Secondary outcomes included mortality, IBD-related hospitalization or emergency department visits, infusion reactions, post IVIG steroid use, and disease severity indices (Harvey-Bradshaw index [HBI], partial Mayo score, and modified pouchitis disease activity index [mPDAI]). The occurrences of these outcomes were measured through July 2016.

Results:

A total of 54 subjects (61% female, age 42 ± 16 yr, 23 with CD, 15 with UC, 16 with pouchitis) met inclusion criteria. Twenty-seven patients (50%) underwent surgery during the follow up period, with a mean surgery-free survival of 28.7 ± 3.7 months. On univariate analysis, subjects with C.diff infection had a 3-fold increased risk of bowel resection surgery following IVIG compared to those without (hazard ratio [HR] = 2.9, P = 0.023), and results remained consistent on multivariate analysis (hazard ratio [HR] = 3.0, P = 0.024). C.diff infection was also associated with increased risk of recurrent hospitalization (HR = 2.5, P = 0.038). Increased BMI (1 kg/m2 increments) was a risk factor for mortality following IVIG administration (HR = 1.08, P = 0.05). Mean times to recurrent IBD-related hospitalization and emergency department visits were 13.6 ± 2.3 and 38.8 ± 4.6 months, respectively. All disease severity scores were significantly improved following IVIG administration (HBI P = 0.007, partial Mayo score P = 0.002, mPDAI P = 0.008).

Conclusions:

Our study demonstrates that concomitant C.diff infection is a possible risk factor for the treatment failure of IVIG for medically refractory IBD, in terms of surgery-free survival as well as recurrent IBD-related hospitalization. Overall, IVIG also exhibited an improvement in disease severity scores for CD, UC, and pouchitis patients.

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