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Multicenter Study
. 2022 Apr 21;22(1):199.
doi: 10.1186/s12876-022-02280-3.

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

Rogério Serafim Parra  1 , Júlio Maria Fonseca Chebli  2 , Natália Sousa Freitas Queiroz  3 , Aderson Omar Mourão Cintra Damião  3 , Matheus Freitas Cardoso de Azevedo  3 , Liliana Andrade Chebli  2 , Erika Ruback Bertges  2 , Antonio José Tiburcio Alves Junior  4 , Orlando Ambrogini Junior  5 , Bianca Loyo Pona Schiavetti da Silva  6 , Marcio Lubini  7 , Mauro Bafutto  8 , Cristina Flores  9 , Eduardo Garcia Vilela  10 , Sandra Felice Boratto  11 , Newton Luiz Tricarico Gasparetti Junior  12 , Flavio Steinwurz  13 , Nayara Salgado Carvalho  13 , Omar Féres  14 , José Joaquim Ribeiro da Rocha  14
Affiliations
Multicenter Study

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

Rogério Serafim Parra et al. BMC Gastroenterol. .

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.

Keywords: Biological therapy; Crohn’s disease; Inflammatory bowel disease; Ustekinumab.

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Conflict of interest statement

Parra RS has received fees for serving as a speaker and/or an advisory board member for AbbVie, Ferring Pharmaceuticals, Janssen, and Takeda. Chebli JMF has received fees for serving as a speaker and/or an advisory board member for Abbott, AbbVie, Janssen, and Takeda. Queiroz NSF reports receiving consulting and lecture fees from Janssen, Takeda, and Abbvie. Damiao AOMC has received fees for serving as a speaker and/or an advisory board member for Takeda, Abbvie, Pfizer, Janssen, Ferring, and Natulab. Azevedo MFC reports receiving consulting fees from Janssen, lecture fees from Janssen, Takeda, and Abbvie, and travel grant support from Takeda, Janssen, and Abbvie. Chebli LA has received fees for serving as a speaker for Janssen and Takeda. Alves Jr AJT received fees for serving as a speaker and/or an advisory board member for Janssen, Takeda, Abbvie, Nestle and Apsen. Ambrogini Jr O has received fees for serving as a speaker and/or an advisory board member for Janssen, Abbvie, Takeda, and UCB. Da Silva BLPS has received fees for serving as a speaker for Pfizer, Abbvie, Janssen, and Takeda. Flores C has received fees for serving as a speaker for Janssen, Abbvie, UCB Biopharma, and Takeda. Steinwurz F is speaker/consultant/researcher for Abbvie, Amgen, Ferring, Janssen, Novartis, Pfizer, Sandoz, Takeda, and UCB biopharma. Bertges ER, Lubini M, Bafutto M, Vilela EG, Boratto SDF, Gasparetti Jr NLT, Salgado NC, Féres O, and Rocha JJR report no conflict of interest.

Figures

Fig. 1
Fig. 1
Flow chart of patients with CD using UST. CD Crohn’s disease, UST ustekinumab, IBD inflammatory bowel disease
Fig. 2
Fig. 2
Proportion of patients in clinical remission from weeks 8 to week 56 according to the NRI, LOCF and as-observed analysis. NRI nonresponder imputation, LOCF last observation carried forward
Fig. 3
Fig. 3
Proportion of patients under UST treatment with clinical response at week 8, biological response/remission up to week 16 and steroid-free remission at the end of follow-up. NRI nonresponder imputation, UST ustekinumab
Fig. 4
Fig. 4
Clinical remission and biological response/remission rates throughout the study comparing bio-naïve and bio-experienced CD patients treated with UST. NRI nonresponder imputation, CD Crohn’s disease, UST ustekinumab
Fig. 5
Fig. 5
Kaplan–Meier curve for persistence with UST for the whole cohort of patients with CD (A), bionaïve (blue line) and bioexperienced (green line) patients (B). CD Crohn’s disease, UST ustekinumab
See this image and copyright information in PMC

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