Report from IIS Award Winner 2020: Myrthe Jongsma

In this study newly diagnosed and therapy-naïve children with moderate-to-severe luminal CD were randomised to compare top-down infliximab treatment, consisting of five infusions of infliximab, with the conventional step-up strategy, consisting of 6 weeks of exclusive enteral nutrition or 10 weeks of oral prednisolone. Both strategies were combined with azathioprine, which was continued after the remission induction treatment was stopped.

Our results demonstrate that top-down infliximab treatment resulted in significantly higher (19/46, 41%) sustained clinical remission rates than step-up treatment (6/48, 12%), without the need for additional CD-related therapy or surgery within 52 weeks after the start of therapy (p=0.002). Moreover, the height for age standard deviation score decreased in significantly more step-up treated patients (30/47, 64%) than top-down treated patients (18/48, 37%) during the first year, suggesting that conventional step-up treatment provides less adequate disease control (p=0.01).

In addition to the assessment of clinical outcomes, endoscopic findings after induction treatment were reported in 59% of the patients, showing a significantly higher mucosal healing rate in top-down (16/27, 59%) than in step-up (5/30, 17%) treated patients at 10 weeks (p=0.001). Median SES-CD score at 10 weeks was 3 (IQR 0–5) in top-down treated patients compared with 9 (IQR 3–19) in step-up treated patients (p=0.005). Also, all inflammatory markers, such as C-reactive protein, erythrocyte sedimentation rate, leucocyte count and faecal calprotectin, were significantly lower in the top-down treated patients after 10 weeks. In total, 95 adverse events were reported in 22/50 (44%) top-down treated patients and in 28/47 (60%) step-up treated patients (p=0.125).

This study clearly establishes the value of early infliximab in the treatment of children with CD and provides unequivocal evidence that primary infliximab treatment is more effective in achieving sustained clinical remission than the conventional step-up strategy in children with moderate-to-severe CD. In clinical practice, infliximab therapy usually is not stopped after five infusions, and whether early cessation is advisable may be open to debate; in this context, the risk of immunogenicity associated with infliximab should be taken into account. We found that, if indicated, infliximab could be safely restarted in patients in our cohort. Five-year follow-up will be essential to compare long-term outcomes, and translational analysis of this study is ongoing with a view to further personalising treatment. Considering the negative impact on growth and development of an ineffective treatment strategy for chronically ill children and adolescents, an optimally effective therapy from diagnosis onwards in these patients is pivotal. Our findings support the use of primary infliximab therapy in children with newly diagnosed moderate-to-severe CD.

References

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