Long-term effectiveness and safety of ustekinumab in bio-naïve and bio-experienced anti-tumor necrosis factor patients with Crohn’s disease: a real-world multicenter Brazilian study

Abstract

Background The effectiveness of ustekinumab (UST) in the treatment of Crohn’s disease (CD) has been demonstrated in the pivotal Phase 3 UNITI 1 and 2 and IM-UNITI studies in both anti-TNF-naïve and anti-TNF-exposed patients. Given the selective nature of pivotal trial designs, real-world effectiveness and safety studies are warranted. We report our experience with UST treatment in a large, real-world multicenter cohort of Brazilian patients with CD. Methods We performed a retrospective multicenter study including patients with CD, predominantly biologically refractory CD, who received UST. The primary endpoint was the proportion of patients in clinical remission at weeks 8, 24 and 56. Possible predictors of clinical and biological response/remission and safety outcomes were also assessed. Results Overall, 245 CD (mean age 39.9 [15–87]) patients were enrolled. Most patients (86.5%) had been previously exposed to biologics. According to nonresponder imputation analysis, the proportions of patients in clinical remission at weeks 8, 24 and 56 were 41.0% (n = 98/239), 64.0% (n = 153/239) and 39.3% (n = 94/239), respectively. A biological response was achieved in 55.4% of patients at week 8, and 59.3% were in steroid-free remission at the end of follow-up. No significant differences in either clinical or biological remission were noted between bio-naïve and bio-experienced patients. Forty-eight patients (19.6%) presented 60 adverse events during the follow-up, of which 8 (13.3%) were considered serious adverse events (3.2% of 245 patients). Overall, a proximal disease location, younger age, perianal involvement, and smoking were associated with lower rates of clinical remission over time. Conclusions UST therapy was effective and safe in the long term in this large real-life cohort of Brazilian patients with refractory CD, regardless of previous exposure to other biological agents.

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.…”

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

“…Three real-world studies have reported effectiveness specifically in bio-naïve patients treated with ustekinumab. A study from Brazil by Parra et al 21 reported effectiveness of ustekinumab in 245 patients, most (86.5%) had been previously exposed to biologicals and 33 were bio-naïve. The proportion of bio-naïve patients in clinical remission at weeks 8, 24 and 56 were 36.4%, 54.5% and 39.4%, respectively.…”

Access to High-Cost Biological Agents: Perceptions of Brazilian Patients with Inflammatory Bowel Diseases

“…In CD, the PCDT does not offer any biologic other than anti-TNF drugs. Despite being approved in Brazil, new biologics such as ustekinumab and vedolizumab are not available for these patients [ 28 , 29 ]. Thus, there are no other options for treatment with biologics for patients with primary nonresponse to anti-TNF drugs or with contraindications for anti-TNF use, such as neoplasms, tuberculosis, and congestive heart failure.…”