Sam Khorrami1, Daniel Ginard, Ignacio Marín-Jiménez, María Chaparro, Mónica Sierra, Mariam Aguas, Beatriz Sicilia, Valle García-Sánchez, Cristina Suarez, Albert Villoria, Carlos Taxonera, Antonio Velasco-Guardado, Javier Martínez-González, Javier P Gisbert. 1. *Servicio de Aparato Digestivo, Hospital Universitario Son Espases, Instituto de Investigación Sanitaria de Palma (IdISPa), Palma de Mallorca, Spain; †Servicio de Aparato Digestivo, Hospital Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; ‡Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain; §Servicio de Aparato Digestivo, Complejo Hospitalario de León, León, Spain; ‖Servicio de Aparato Digestivo, Hospital Universitario y Politécnico La Fe, CIBERehd, Valencia, Spain; ¶Servicio de Aparato Digestivo, Complejo Asistencial Universitario de Burgos, Burgos, Spain; **Servicio de Aparato Digestivo, Hospital Universitario Reina Sofía, IMIBIC, Córdoba, Spain; ††Servicio de Aparato Digestivo, Hospital Universitario Puerta de Hierro, Madrid, Spain; ‡‡Servicio de Aparato Digestivo, Corporació Sanitària Universitària Parc Taulí, CIBERehd, Instituto de Salud Carlos III, Sabadell, Spain; §§Servicio de Aparato Digestivo, Hospital Clínico San Carlos, Instituto de Investigación del Hospital Clínico San Carlos (IdISSC), Madrid, Spain; ‖‖Servicio de Aparato Digestivo, Hospital Universitario de Salamanca, Salamanca, Spain; and ¶¶Servicio de Aparato Digestivo, Hospital Universitario Ramón y Cajal, Madrid, Spain.
Abstract
BACKGROUND: Ustekinumab is a fully human monoclonal antibody against IL-12/23. Ustekinumab induced clinical response and maintained higher rate of response than placebo in patients with Crohn's disease (CD). This study aims to assess the effectiveness and safety of ustekinumab in refractory patients with CD in real-life practice. METHODS: Consecutive patients with CD who were treated with subcutaneous ustekinumab between March 2010 and December 2014 were retrospectively included in a multicenter open-label study. Clinical response was defined by Harvey-Bradshaw index score and assessed after the loading doses, 6, 12 months, and last follow-up. RESULTS: One hundred sixteen patients were included, with a median follow-up of 10 months (interquartile range: 5-21). Clinical response after loading ustekinumab was achieved in 97/116 (84%) patients. The clinical benefit at 6, 12 months, and at the end of the follow-up was 76%, 64%, and 58%, respectively. Dose escalation was effective in 8 of 11 (73%) patients. Perianal disease also improved in 11 of 18 (61%) patients with active perianal fistulae. The initial response to ustekinumab and previous use of more than 2 immunosuppressant drugs were associated with a clinical response to ustekinumab maintenance therapy. In contrast, previous bowel resection predicted a long-term failure with ustekinumab. Adverse events were reported in 11 (9.5%) patients, but none required ustekinumab withdrawal. CONCLUSIONS: Subcutaneous ustekinumab is effective and safe in a high proportion of patients with CD that were resistant to conventional immunosuppressant and antitumor necrosis factor drugs.
BACKGROUND:Ustekinumab is a fully human monoclonal antibody against IL-12/23. Ustekinumab induced clinical response and maintained higher rate of response than placebo in patients with Crohn's disease (CD). This study aims to assess the effectiveness and safety of ustekinumab in refractory patients with CD in real-life practice. METHODS: Consecutive patients with CD who were treated with subcutaneous ustekinumab between March 2010 and December 2014 were retrospectively included in a multicenter open-label study. Clinical response was defined by Harvey-Bradshaw index score and assessed after the loading doses, 6, 12 months, and last follow-up. RESULTS: One hundred sixteen patients were included, with a median follow-up of 10 months (interquartile range: 5-21). Clinical response after loading ustekinumab was achieved in 97/116 (84%) patients. The clinical benefit at 6, 12 months, and at the end of the follow-up was 76%, 64%, and 58%, respectively. Dose escalation was effective in 8 of 11 (73%) patients. Perianal disease also improved in 11 of 18 (61%) patients with active perianal fistulae. The initial response to ustekinumab and previous use of more than 2 immunosuppressant drugs were associated with a clinical response to ustekinumab maintenance therapy. In contrast, previous bowel resection predicted a long-term failure with ustekinumab. Adverse events were reported in 11 (9.5%) patients, but none required ustekinumab withdrawal. CONCLUSIONS: Subcutaneous ustekinumab is effective and safe in a high proportion of patients with CD that were resistant to conventional immunosuppressant and antitumor necrosis factor drugs.
Authors: Christopher Andrew Lamb; Nicholas A Kennedy; Tim Raine; Philip Anthony Hendy; Philip J Smith; Jimmy K Limdi; Bu'Hussain Hayee; Miranda C E Lomer; Gareth C Parkes; Christian Selinger; Kevin J Barrett; R Justin Davies; Cathy Bennett; Stuart Gittens; Malcolm G Dunlop; Omar Faiz; Aileen Fraser; Vikki Garrick; Paul D Johnston; Miles Parkes; Jeremy Sanderson; Helen Terry; Daniel R Gaya; Tariq H Iqbal; Stuart A Taylor; Melissa Smith; Matthew Brookes; Richard Hansen; A Barney Hawthorne Journal: Gut Date: 2019-09-27 Impact factor: 23.059
Authors: Remo Panaccione; A Hillary Steinhart; Brian Bressler; Reena Khanna; John K Marshall; Laura Targownik; Waqqas Afif; Alain Bitton; Mark Borgaonkar; Usha Chauhan; Brendan Halloran; Jennifer Jones; Erin Kennedy; Grigorios I Leontiadis; Edward V Loftus; Jonathan Meddings; Paul Moayyedi; Sanjay Murthy; Sophie Plamondon; Greg Rosenfeld; David Schwartz; Cynthia H Seow; Chadwick Williams; Charles N Bernstein Journal: J Can Assoc Gastroenterol Date: 2018-07-10
Authors: Jacob E Ollech; Inessa Normatov; Noam Peleg; Jingzhou Wang; Shivani A Patel; Victoria Rai; Yangtian Yi; Jorie Singer; Sushila R Dalal; Atsushi Sakuraba; Russell D Cohen; David T Rubin; Joel Pekow Journal: Clin Gastroenterol Hepatol Date: 2020-02-26 Impact factor: 11.382
Authors: A Hillary Steinhart; Remo Panaccione; Laura Targownik; Brian Bressler; Reena Khanna; John K Marshall; Waqqas Afif; Charles N Bernstein; Alain Bitton; Mark Borgaonkar; Usha Chauhan; Brendan Halloran; Jennifer Jones; Erin Kennedy; Grigorios I Leontiadis; Edward V Loftus; Jonathan Meddings; Paul Moayyedi; Sanjay Murthy; Sophie Plamondon; Greg Rosenfeld; David Schwartz; Cynthia H Seow; Chadwick Williams Journal: J Can Assoc Gastroenterol Date: 2018-09-14