Effectiveness of ustekinumab in patients with refractory Crohn’s disease: a multicentre real-life study in Italy

Abstract

Background: The effectiveness of ustekinumab in patients with refractory Crohn’s disease (CD) has been investigated in several real-world studies. However, very few data concerning the real-life experience in Italy have been reported. Therefore, this study assessed the effectiveness of ustekinumab in a large cohort of Italian patients with refractory CD. Methods: All patients who had started on ustekinumab after failure of or intolerance to antitumour necrosis factor-α (TNF-α) treatment at five tertiary centres between November 2018 and February 2020 were retrospectively enrolled. The coprimary outcome was corticosteroid-free clinical remission, defined as a Harvey–Bradshaw Index (HBI) score of ⩽4, at weeks 26 and 52. The secondary outcomes were changes in the HBI and C-reactive protein (CRP) values at weeks 8, 26, and 52 from baseline and the normalization of CRP in patients with initially abnormal values. Results: Totally, 140 patients who had previously received at least one anti-TNF-α agent were enrolled; 40.0% received two anti-TNF-α agents and 20.0% received vedolizumab. At baseline, 108 patients (77.1%) had HBI scores of >4; of these, 56.5% and 58.3% achieved corticosteroid-free clinical remission at weeks 26 and 52, respectively. Significant decreases in HBI and CRP values were observed at weeks 8, 26, and 52 in the entire study cohort (all p < 0.0001). The CRP values were normalized in 34.9%, 37.8%, and 49.3% of the patients by weeks 8, 26, and 52, respectively. The baseline HBI score of ⩾8 was a negative predictor of corticosteroid-free clinical remission at week 52 (odds ratio: 0.21, 95% confidence interval: 0.08–0.56, p = 0.002). The probability of remaining on ustekinumab after 52 weeks was 92.1%. Eleven (7.9%) patients discontinued ustekinumab (three for adverse events). Conclusion: Our study findings confirm the effectiveness and safety of ustekinumab in patients with CD after failure of or intolerance to anti-TNF-α therapy.

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 , ...…”

Effectiveness and safety of ustekinumab in bio-naïve Crohn’s disease patients: a multicentre observational retrospective study

“…In these refractory population, rates of clinical remission after 1 year range from 39% to 64%. 9,11,14,18,19 In a Spanish study by Iborra et al , 14 from ENEIDA registry, a total of 463 patients were included, 96.5% of them had received prior biological therapy. At week 52, 64.4% had clinical remission; however, when analysing rates of clinical remission according to the number of previous anti-TNF agents, a trend towards better results in bio-naïve patients ( n = 18) was observed.…”

“…However, the vast majority of patients included in these cohorts had previously failed one or several biologicals. 8–19…”

“…However, the vast majority of patients included in these cohorts had previously failed one or several biologicals. [8][9][10][11][12][13][14][15][16][17][18][19] It is important to continue to collect real-life data not only in bio-failure but also in bio-naïve patients, to compare response rate and safety in these two populations and to look for predictive factors of response.…”

Characteristics of Facilities With Early and Rapid Ustekinumab Adoption for Patients With Inflammatory Bowel Disease

“…Drug development is critical to advancing IBD care, but its impact is limited without successful dissemination (11)(12)(13). We examined ustekinumab adoption, exemplifying the uptake of novel biologic prescribing.…”