41 Serious Infections and Associated Risk Factors in Patients Receiving Infliximab and Immunotherapies for Children With Inflammatory Bowel Disease: Develop Registry Data

Abstract

all pts with PSC-IBD who underwent LT for non-cholangiocarcinoma indications at Mayo Clinic, Rochester from 1998-2008, with follow-up through 2012. Information on course of pre-transplant IBD, de novo IBD and colectomy was extracted. Progression of IBD was defined as need for escalation of medical therapy, as compared to pre-LT course. Risk factors for progression of IBD were identified using multivariate Cox proportional hazard analysis. Results: One hundred one pts with PSC underwent LT (mean age, 48 yrs; 62 males). Median follow-up (IQR) was 8.4 years (5.5-10.7). Of these, 80 pts had associated IBD (74 pts with ulcerative colitis, 6 pts with Crohn's disease). Twenty-five pts underwent colectomy prior to LT (18 for medically-refractory IBD, 7 for colorectal neoplasia). Further analysis was restricted to 55 pts with PSC-IBD with intact colon at time of LT. Pre-LT, 32 pts had quiescent IBD requiring no therapy and 21 were maintained on 5-ASA. Post-LT, despite transplant-related immunosuppression, 26/55 (47.3%) required escalation of therapy, whereas 28/55 had a stable course (50.9%) and 1 patient (1.8%) improved (Table). One, 5and 10-year risk of progression of IBD was 10.9%, 36.4% and 45.4%, respectively. Thirteen pts underwent colectomy after LT (5 for medically-refractory IBD, 8 for colorectal neoplasia), with 1-, 5and 10-year risk of colectomy being 1.8%, 16.4% and 21.8%. On multivariate Cox proportional hazard analysis, use of tacrolimus (hazard ratio, 5.6; 95% CI, 1.1-103.4) was associated with progression of IBD, whereas recurrence of PSC (HR, 0.2; 95% CI, 0.1-0.6) was protective against progression of IBD. There was no association between progression of IBD and transplant(CMV infection/mismatch), immunosuppression-(use of mycophenolate, azathioprine or prolonged prednisone use), or IBD-related factors (pretransplant IBD activity, empirical initiation of 5-aminosalicylates within 4 months of LT). Eleven pts developed de novo IBD after LT, with 1-, 5and 10-year risk (among PSC pts without IBD after LT) being 4.8%, 38.1% and 47.6%. No specific transplant or immunosuppression-related risk factor was identified, including CMV infection. Conclusion: The cumulative probability of IBD flare requiring escalation of therapy after LT for PSC is 45% at 10 years, despite immunosuppression for LT. Recurrent PSC was associated with mild course of IBD after LT, similar to the observation that advanced PSC requiring LT is associated with a mild course of IBD pre-transplant.