Comparison of short‐ and long‐term effectiveness between ustekinumab and vedolizumab in patients with Crohn's disease refractory to anti‐tumour necrosis factor therapy

Abstract

Summary Background The best option between vedolizumab and ustekinumab after anti‐tumour necrosis factor (TNF) failure remains unclear in Crohn's disease. Aims To compare the short‐ and long‐term effectiveness of vedolizumab and ustekinumab in Crohn's disease patients with prior anti‐TNF exposure. Methods All Crohn's disease patients treated with ustekinumab or vedolizumab after exposure to at least one anti‐TNF agent were included from two referral centres. Primary endpoint was corticosteroid‐free clinical remission defined as Crohn's disease activity index <150 at week 54. Deep remission (corticosteroid‐free clinical remission and faecal calprotectin <100 µg/g) was assessed at week 14. Propensity‐matched analyses were applied to make the two groups comparable. Results Overall, 312 patients (ustekinumab = 224 and vedolizumab = 88) were included. After propensity score analysis, ustekinumab was more effective to achieve corticosteroid‐free clinical remission at week 54 (49.3% vs 41.2%, P = 0.04) and deep remission at Week 14 (25.9% vs 3.8%, P = 0.02) than vedolizumab. The rate of primary nonresponders (6.7% vs 14.8%, P = 0.034) and the long‐term risk of drug discontinuation due to therapeutic failure (HR = 1.53 [1.04‐2.07], P = 0.029) were lower in patients treated with ustekinumab compared with vedolizumab. Predictors of ustekinumab failure were complicated phenotype (odds ratio [OR] = 2.35 [1.31‐4.22]; P = 0.004) and anti‐TNF primary non‐response (OR = 2.55 [1.27‐5.12]; P = 0.008). We did not find any predictor of corticosteroid‐free clinical remission in patients treated with vedolizumab. Vedolizumab was less effective than ustekinumab in patients >35 years old (OR = 0.41 [0.19‐0.87]), with noncomplicated phenotype (OR=0.42 [0.18‐0.96]), no prior bowel resection (OR = 0.49 [0.24‐0.96]), and no steroids at baseline (OR=0.47 [0.23‐0.97]). Conclusion Ustekinumab was more effective to achieve early and long‐term effectiveness than vedolizumab in Crohn's disease patients who previously failed response to anti‐TNF agents.

A propensity score‐matched, real‐world comparison of ustekinumab vs vedolizumab as a second‐line treatment for Crohn’s disease. The Cross Pennine study II

“…We found ustekinumab to be superior in inducing remission, while no difference was noticed between ustekinumab and vedolizumab at 52 weeks. This finding is in contrast with three previously published propensity score‐matched analyses including 45 (Liverpool study), 24 85 and 224 (two French studies), 26 , 41 and 107 (Dutch study) 25 ustekinumab‐treated CD patients, respectively, in which they found (although with some important differences), ustekinumab to be superior in maintaining remission at 1‐year follow‐up. There might be a number of reasons for this apparent discrepancy, and one reason is that propensity score‐matched analysis may underperform when the number of included patients is low, increasing the risk of overfitting.…”

Real-World Evidence of the Effectiveness and Safety of Ustekinumab for the Treatment of Crohn’s Disease: Systematic Review and Meta-Analysis of Observational Studies

“…A total of 63 studies (including 8529 patients) met the inclusion criteria and were finally included in the systematic review and meta-analysis ( Figure 1 ) [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , ...…”

“…Predictors of response were reported in 37 studies (59%). The most frequent predictors of poor clinical response were previous biologic exposure (anti-TNF and/or vedolizumab) [ 26 , 39 , 40 , 44 , 47 , 51 , 65 , 72 , 74 ], stricturing disease [ 19 , 20 , 39 , 44 , 65 ], penetrating disease [ 27 , 39 , 44 , 51 , 65 ], and high Harvey-Bradshaw index (HBI) at first dose [ 19 , 20 , 51 , 72 , 73 , 75 ]. Concomitant corticosteroids, extraintestinal manifestations, male sex, old age, smoking, and low body mass index were also reported in some studies.…”

Primary Failure to an Anti-TNF Agent in Inflammatory Bowel Disease: Switch (to a Second Anti-TNF Agent) or Swap (for Another Mechanism of Action)?

“…Manlay et al [94] compared the short-and long-term effectiveness of vedolizumab and ustekinumab in CD patients with prior anti-TNF exposure. After propensity score analysis (ensuring that prior primary anti-TNF non-response was similar for both groups), ustekinumab was more effective than vedolizumab to achieve corticosteroid-free clinical remission at Week 54 (49% vs. 41%) and deep remission at Week 14 (26% vs. 3.8%).…”