Loss of RESponse to Ustekinumab Treated by Dose Escalation

Inclusion Criteria

• •1. ≥18 years
• •2. Diagnosis of Crohn's disease by endoscopic and/or radiologic examination.
• •3. Patient currently treated with ustekinumab, independent of previous biological exposure.
• •4. Patients treated with maintenance dose of ustekinumab subcutaneous 90 mg every 8 weeks
• •5. Documented primary response at any time point after induction (week 16) and during maintenance defined as a clinical response (physician discretion) AND confirmed by either any of the following:
• •a. if biomarker elevated at start of ustekinumab (C-reactive protein\>5 mg/l or fecal calprotectin \>250µg/g): i. decrease of C-reactive protein by 50 % or more compared to baseline( prior to ustekinumab induction) ii. C-reactive protein \<5 mg/l iii. decrease of fecal calprotectin by 50 % or more compared to baseline( prior to ustekinumab induction) iv. fecal calprotectin\<250µg/g b. Documented mucosal healing (simple endoscopic score for Crohn's disease (SES-CD)\<3)
• •6. Documented loss of response after induction (\> week 16) assessed by the physician as Moderate to severe active Crohn's disease, defined as Patient Reported Outcome-2 (Abdominal Pain \> 1 AND Stool Frequency \> 3) AND C-reactive protein and/or fecal calprotectin increased by 25 % or more compared to the lowest value under ustekinumab treatment (C-reactive protein\>5 mg/L and/or fecal calprotectin\>250µg/g).
• •7. Presence of mucosal ulcers in at least one segment of the ileum or colon and a simple endoscopic score for Crohn's disease (SES-CD) ≥6 (for patients with isolated ileitis ≥4), as assessed by ileocolonoscopy
• •8. Adequate contraception in female of reproductive age
• •9. Have the capacity to understand and sign an informed consent form.
• •10. Be able to adhere to the study visit schedule and other protocol requirements.