Ustekinumab for the Treatment of Refractory Crohn's Disease: The Spanish Experience in a Large Multicentre Open-label Cohort.
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.



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.



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.



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.
*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.
Sam
S
Khorrami
Daniel
D
Ginard
Ignacio
I
Marín-Jiménez
María
M
Chaparro
Mónica
M
Sierra
Mariam
M
Aguas
Beatriz
B
Sicilia
Valle
V
García-Sánchez
Cristina
C
Suarez
Albert
A
Villoria
Carlos
C
Taxonera
Antonio
A
Velasco-Guardado
Javier
J
Martínez-González
Javier P
JP
Gisbert
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003424:Crohn Disease / Q000150:complications / Q000188:drug therapy*; D017577:Cutaneous Fistula / Q000188:drug therapy* / Q000209:etiology; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D012003:Rectal Fistula / Q000188:drug therapy* / Q000209:etiology; D019233:Retreatment; D012189:Retrospective Studies; D013030:Spain; D000069549:Ustekinumab / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D000069549:Ustekinumab