Top-Down versus Step-Up Therapy in Pediatric Patients with New Onset Crohnʼs Disease

Abstract

Purpose: Top-down (TD) therapy with tumor necrosis factor inhibitors early in disease course of adult Crohn's disease (CD) has been shown to result in decreased steroid dependence, hospitalization, complications, and disease activity compared to conventional step-up (SU) therapy. However, data regarding the efficacy of the TD approach in children are limited, due to concerns regarding potential side effects including lymphoma, and difficulty with insurance approval. The goal of this study was to begin to compare the outcome of TD versus SU therapy in our pediatric patients with new onset CD. Methods: We conducted a retrospective analysis of patients with CD seen in our practice using diagnostic codes 555.0,555.1, 555.2. Sixteen pediatric patients with new diagnosis CD identified as diagnosed within the last 1 year and with Crohn's disease activity index (CDAI) greater than 200 were included for study. Eleven had been treated with TD, 5 with SU therapy. Mean ages (SU 14.6years+/-2.4 and TD 14.27years+/-3.2, p=0.8435); gender (SU 63% male; TD 61% male), and CDAI were similar (SU 271+/-86 and TD 273+/-71, p=0.9743) in the two groups. Primary endpoints were remission at 4 and 52 weeks (CDAI less than 150), secondary endpoints were disease complication rate, hospitalization, and surgery. Two-tailed Fisher's exact test and unpaired t test were used to compare the two groups. Results: In the TD group 72% of patients achieved remission in 4 weeks as did 60% of the SU group (p=1.000). Mean CDAI was 116+/-42 for the TD patients, 173+/-68 for the SU patients at 4 weeks (p=0.0585). 100% of patients in the SU group versus 45% in the TD group developed complications of CD (p=0.0934). Also, 80% of patients in the SU group were hospitalized, only 45% in the TD group (p=0.3077). Surgical rates were 60% in the SU group, and 9% in the TD patients (p=0.0632). At 52 weeks CDAI was 82.9+/-29.3 for TD group, and 95.6+/-41.8 for the SU group (p=0.5274). One patient in the SU group was excluded from 52 week CDAI as he had undergone permanent colectomy/ileostomy and thus CDAI could not be calculated. Conclusion: Although not statistically significant, most likely due to small sample size, there is a clear trend suggesting the use of biologic agents early in disease course may reduce the risk of hospitalization, surgery and disease complications in children within the first year of their diagnosis of CD. Larger studies comparing safety and efficacy of TD versus SU treatment should be conducted in the pediatric age group. Disclosure: Dr Srivastava - Consultant Centocor Speaker's bureau.