Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn’s Disease Patients: The SUSTAIN Study
Authors: Chaparro María , Baston-Rey Iria , Fernández-Salgado Estela , González García Javier , Ramos Laura , Diz-Lois Palomares María Teresa , Argüelles-Arias Federico , Iglesias Flores Eva , Cabello Mercedes , Rubio Iturria Saioa , Núñez Ortiz Andrea , Charro Mara , Ginard Daniel , Dueñas Sadornil Carmen , Merino Ochoa Olga , Busquets David , Iyo Eduardo , Gutiérrez Casbas Ana , Ramírez de la Piscina Patricia , Boscá-Watts Marta Maia , Arroyo Maite , García María José , Hinojosa Esther , Gordillo Jordi , Martínez Montiel Pilar , Velayos Jiménez Benito , Quílez Ivorra Cristina , Vázquez Morón Juan María , María Huguet José , González-Lama Yago , Muñagorri Santos Ana Isabel , Amo Víctor Manuel , Martín-Arranz María Dolores , Bermejo Fernando , Martínez Cadilla Jesús , Rubín de Célix Cristina , Fradejas Salazar Paola , San Román Antonio López , Jiménez Nuria , García López Santiago , Figuerola Anna , Jiménez Itxaso , Martínez Cerezo Francisco José , Taxonera Carlos , Varela Pilar , de Francisco Ruth , Monfort David , Molina Arriero Gema , Hernández Camba Alejandro , García-Alonso Francisco Javier , Van Domselaar Manuel , Pajares Villarroya Ramón , Núñez Alejandro , Rodríguez Moranta Francisco , Marín-Jiménez Ignacio , Robles Alonso Virginia , Martín Rodríguez María del Mar , Camo-Monterde Patricia , García Tercero Iván , Navarro Llavat Mercedes , Arias García Lara , Hervías Cruz Daniel , Sulleiro Sara , Novella Cynthia , Vispo Eugenia , Barreiro-de Acosta Manuel , Gisbert Javier P 
Published: February 2022

Abstract

Background
Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn’s disease (CD) patients in real-world clinical practice.

Methods
A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≥1 intravenous dose of ustekinumab for ≥6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety.

Results
A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≥3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≥1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required dose escalation or intensification; of these, 24.8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever).

Conclusions
Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice.