Early biologic therapy induces larger effect than delayed treatment in Crohn’s disease

The benefit of biologic therapy versus placebo was similar for participants with short-term or long-term inflammatory bowel disease (IBD) in a recent systematic review. However, in participants with Crohn’s disease (CD), the absolute effects of both placebo and biologic therapies were larger in participants with short-term disease, implying that early treatment is important in these patients.

Prof. Shomron Ben-Horin (Tel-Aviv University, Israel) and colleagues conducted a systematic review to assess the treatment effect of biologic therapies in patients with short duration (≤18 months) and long duration (>18 months) IBD [1,2]. The study included 25 trials, investigating infliximab, adalimumab, certolizumab, golimumab, natalizumab, or vedolizumab with a total of 9,395 patients with IBD. The primary endpoint was the proportional benefit of biologic treatments compared with placebo with regard to the induction of remission^a.

The relative benefit of active treatment versus placebo was similar for participants with short-term CD (risk ratio 1.47; 95% CI 1.01–2.15) or long-term CD (risk ratio 1.43; 95% CI 1.19–1.72). In addition, no significant interaction effect was reported for treatment effect and disease duration (P=0.585). Similarly, for participants with ulcerative colitis (UC), the active-to-placebo treatment relative benefit was not significantly different between participants with short-term disease (risk ratio 1.82; 95% CI 1.12–2.97) or long-term disease (risk ratio 2.21; 95% CI 1.79–2.72). Notably, the absolute effects of both biologics and placebo were higher in participants with short-term CD compared with participants with long-term CD. In the UC population, this pattern was not observed (see Figure).

Figure: Absolute effects of biologics and placebo in IBD [1,2]



 

 

 

 

 

Reprinted from Shomron Ben-Horin et al. Gastroenterology. 2022;162(2):482-494. Doi: 10.1053/j.gastro.2021.10.037 under the terms of the Creative Commons Attribution 4.0 license.

Prof. Ben-Horin argued that the greater absolute benefits of both active therapy and placebo may be due to the greater plasticity of early CD. Another explanation may be that patients with early disease show a higher placebo response because they are more amenable to suggestions. However, further studies are warranted to investigate the explanations behind the observed larger absolute treatment effect in patients with early CD.

a. Induction of remissions for CD was defined as a Crohn’s Disease Activity Index <150 and for UC as a total Mayo score ≤2 with no individual subscore >1.

1. Ben-Horin S, et al. Efficacy of biologic drugs in short-duration versus long-duration Inflammatory Bowel Disease: A systematic review and an individual-patient data meta-analysis of randomized controlled trials. DOP62, ECCO 2022, 16–19 February.
2. Ben-Horin S, et al. Gastroenterology. 2022;162(2):482–494.

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Posted on 12 April, 20228 April, 2024