Top-down versus step-up treatment in newly diagnosed crohn's disease: No difference in long-term outcome

Background: Early combined immunosuppression ('top-down' (TD)) is more effective than conventional management ('step-up' (SU)) for induction of remission and reduction of corticosteroid use in patients recently diagnosed with Crohn's disease (CD). However, it remains unknown whether short-term benefits are sustained long-term and thus the natural history of CD can be altered. Therefore, we aimed to investigate the long-term effects of TD (induction IFX and maintenance azathioprine (AZA)) vs. conventional SU treatment in CD. Methods: Long-term follow-up data was retrospectively collected from patients who participated in a randomized controlled trial evaluating TD vs. SU in patients with newly diagnosed Crohn's disease (1). Data collection was performed in 12 of the 18 participating centers. For 16 semesters following the original trial follow-up, the following was abstracted from patients' medical records: clinical disease activity by global assessment, medication use, hospitalization, surgery, and the occurrence of new fistulas and significant flares. Comparisons were done by intention-to-treat analysis. Time to event data was evaluated using the Kaplan-Meier and log-rank test. To compare the proportions of time in remission, Fisher's exact test was used. Algorithm failure was considered any of the following: surgery, start of adalimumab, ciclosporin or experimental therapy. Results: 112 patients (SU n=57) were included in the analysis, of whom 83.5% was in clinical remission during ≥50% of semesters. At the start of follow-up, 81.6% (57.1% AZA, 24.5% methotrexate (MTX)) vs. 66.7% (54.2% AZA, 12.5% MTX) of patients used an immunomodulator, and 20.4% vs. 16.7% received IFX in TD and SU, respectively. No difference in the proportion of semesters that patients were in clinical remission during follow-up was found between TD and SU (66.6% vs. 68.3%; p=0.52). Mean time to first hospitalization was 13.9 vs. 13.1 semesters (p=0.46), mean time to first new fistula was 15.1 vs. 14.5 semesters (p=0.53) and mean time to algorithm failure was 11.7 vs. 10.5 semesters (p=0.27). The median time to Crohnrelated surgery was similar in both groups (15.0 vs. 14.1; p=0.28). A trend towards a difference between TD and SU was observed for time to significant flare (median time 6 vs. 8 semesters; p=0.09). Conclusion: No difference in long-term outcome was found between top-down versus step-up treatment algorithms for newly diagnosed Crohn's disease. A potential explanation may be that top-down induction was restricted to only 3 IFX infusions. Furthermore, an early start of immunomodulation and/or IFX in the SU group, could have lead to a reduced contrast between patient groups. (1) D'Haens, GR et al. Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial. (Figure Presented).