VEDOLIZUMAB THERAPY FOR VERY EARLY ONSET INFLAMMATORY BOWEL DISEASE

ABSTRACT

Background: Vedolizumab (VDZ) is effective in inducing and maintaining remission in patients with Inflammatory bowel disease (IBD), but limited data exists in the youngest patients diagnosed <6, known as very early onset (VEO)-IBD. We aimed to evaluate the efficacy and safety of VDZ in this cohort. Methods: This was a retrospective study of patients with VEO-IBD followed at the Children's Hospital of Philadelphia, treated with VDZ for >6 months. Data collected included demographics, disease characteristics, medications, hospitalizations, growth, surgeries, and labs. Disease activity was measured using the Pediatric Ulcerative Colitis Activity Index (PUCAI) and Pediatric Crohn Disease Activity Index (PCDAI) at baseline and 6 months. Primary outcome was clinical response defined as a decrease in PUCAI>20 or PCDAI>15 at 6 months. Secondary outcomes included improvement in growth, labs, steroid use and hospitalizations. Continuous variables were analyzed using the Friedman test followed by the Wilcoxon signed-rank test. Nominal data was analyzed using McNemar's test. Results: Thirty-three children with VEO-IBD, 66% male, treated with VDZ were included. Median age of diagnosis was 3.7 years (range 1.2-6 years), with a median baseline disease duration of 3 years (range 0.1-18.5 years). IBDU was classified in 61%, and CD in 39%. Disease location was 70% colonic, 27% ileocolonic and 3% small bowel. Seven patients had prior surgeries, including diverting ileostomies (n=6) and subtotal colectomy (n=1). Nineteen (58%) patients were biologic naïve. VDZ was used as combination therapy in 6 (18%) patients (methotrexate n=4, rapamycin n=1, tacrolimus n=1). Bridge therapy was initiated in 78% of patients, with steroids (n=8) and antibiotics (n=18). Clinical response at 6 months was achieved in 19 patients (58%) with improvement in median PUCAI from 25 to 5 (p<0.01) and median PCDAI from 18.75 to 5 (p<0.05). BMI for age Z-score improved from -0.325 to 0.65 (p<0.001). Steroids and antibiotics were tapered off in 6/8 (75%) and 14/18 (78%, p<0.001) respectively. Hospital length of stay decreased significantly during the 12 months after initiating VDZ compared to 3 months prior to initiation (p<0.05). 2 patients underwent surgery including a subtotal colectomy for colonic stricture and diverting ileostomy within 2 months of starting VDZ. Adverse effects included COVID-19 infection (n=2), influenza (n=2), upper respiratory infection (n=2), pneumonia (n=1), tracheitis (n= 1), cellulitis (n=1), molluscum (n=1), and pityriasis rosea (n=1). Conclusion: VDZ is effective at inducing clinical remission in a subset of children with VEO-IBD primarily with colonic disease. It has a favorable safety profile with minimal reported adverse events observed in this study. This study is limited by small sample size and retrospective design. Larger prospective studies are warranted.