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

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.

Transmural healing and MRI healing are associated with lower risk of bowel damage progression than endoscopic mucosal healing in Crohn's disease.

BACKGROUND: Endoscopic mucosal healing is the current therapeutic target in Crohn's disease. However, transmural healing could lead to better outcomes. AIMS: To assess whether transmural healing or magnetic resonance imaging (MRI) healing are better therapeutic targets than endoscopic mucosal healing to predict long-term improved outcome in Crohn's disease METHODS: From our MRI database, we retrospectively identified all Crohn's disease patients who had MRI and colonoscopy within a 3-month interval (median interval = 17.5 days). Four groups were considered: endoscopic mucosal healing (no ulceration or aphthoid erosion), MRI healing (no MRI signs of inflammation and no complication), transmural healing (combination of endoscopic and MRI healing) or no healing. Outcomes were time to surgery, bowel damage progression, hospitalisation, major outcomes (one of the three previous endpoints) and Crohn's disease-related drug discontinuation. Results were expressed in multivariable analyses adjusted on potential confounders (hazard ratio (HR) [95% confidence interval]). RESULTS: Among 154 patients with Crohn's disease, 51.9% (80/154), 10.4% (16/154), 19.5% (30/154) and 18.2% (28/154) achieved no healing, endoscopic mucosal healing, MRI healing and transmural healing, respectively. Transmural healing (HR = 0.05 [0.00-0.40], P = 0.002) and MRI healing (HR = 0.09 [0.00-0.47], P = 0.005) were associated with lower risk of bowel damage progression than endoscopic mucosal healing. In addition, achieving transmural healing or MRI healing reduced the risk of experiencing major outcomes compared to endoscopic mucosal healing (HR = 0.28 [0.00-0.74], P = 0.01). Patients with transmural healing also had a decreased risk of relapse-related drug discontinuation (HR = 0.35 [0.13-0.95], P = 0.039) compared to those with endoscopic mucosal healing. CONCLUSION: Transmural healing and MRI healing are associated with lower risk of bowel damage progression than endoscopic mucosal healing and could be considered as better therapeutic targets in Crohn's disease.

Combined evaluation of biomarkers as predictor of maintained remission in Crohn's disease.

BACKGROUND: The individual performances and the complementarity of Crohn's disease (CD) activity index (CDAI), C-reactive protein (CRP) and faecal calprotectin (Fcal) to monitor patients with CD remain poorly investigated in the era of "tight control" and "treat to target" strategies. AIM: To assess CDAI, CRP and Fcal variation, alone or combined, after 12 wk (W12) of anti-tumor necrosis factor (TNF) therapy to predict corticosteroids-free remission (CFREM = CDAI < 150, CRP < 2.9 mg/L and Fcal < 250 µg/g with no therapeutic intensification and no surgery) at W52. METHODS: CD adult patients needing anti-TNF therapy with CDAI > 150 and either CRP > 2.9 mg/L or Fcal > 250 µg/g were prospectively enrolled. RESULTS: Among the 40 included patients, 13 patients (32.5%) achieved CFREM at W52. In univariable analysis, CDAI < 150 at W12 (P = 0.012), CRP level < 2.9 mg/L at W12 (P = 0.001) and Fcal improvement at W12 (Fcal < 300 µg/g; or, for patients with initial Fcal < 300 µg/g, at least 50% decrease of Fcal or normalization of Fcal (< 100 µg/g) (P = 0.001) were predictive of CFREM at W52. Combined endpoint (CDAI < 150 and CRP ≤ 2.9 mg/L and FCal improvement) at W12 was the best predictor of CFREM at W52 with positive predictive value = 100.0% (100.0-100.0) and negative predictive value = 87.1% (75.3-98.9). In multivariable analysis, Fcal improvement at W12 [odd ratio (OR) = 45.1 (2.96-687.9); P = 0.03] was a better predictor of CFREM at W52 than CDAI < 150 [OR = 9.3 (0.36-237.1); P = 0.145] and CRP < 2.9 mg/L (0.77-278.0; P = 0.073). CONCLUSION: The combined monitoring of CDAI, CRP and Fcal after anti-TNF induction therapy is able to predict favorable outcome within one year in patients with CD.