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. Exclusion Criteria: 1. Ongoing treatment with 1. other concomitant biological (vedolizumab, anti-TNF) 2. Steroids \>20 mg prednisolone or equivalent at baseline (budesonide \>6 mg) 3. Patient already receiving ustekinumab every 4 weeks 2. Women that are pregnant, nursing, or planning pregnancy 3. Have screening laboratory test results within the following parameters: 1. Haemoglobin \< 8.5 g/dL 2. Platelets \< 100,000 /mm3 3. Serum creatinine ≥ 1.7 mg/dL 4. aspartate aminotransferase and alanine aminotransferase \> 3 times the upper limit of normal range 5. Direct (conjugated) bilirubin ≥ 3.0 mg/dL. 4. Have current signs or symptoms of infection confirmed by positive stool or blood testing (including gastrointestinal pathogens, tuberculosis, human immunodeficiency virus, hepatitis B, hepatitis C). 5. Patients with a positive stool sample for gastrointestinal pathogen including Clostridium difficile. 6. Evidence of current or previous clinically significant disease, medical condition other than Crohn's Disease, finding of the medical examination, or laboratory value at the screening visit outside the reference range that is of clinical relevance, that in the opinion of the Investigator, would compromise the safety of the patient or the quality of the data. 7. Patients with an ileostomy 8. Patients that received an intravenous re-induction with ustekinumab within the 6 months prior to baseline. 9. Patients with an impassable stenosis even after attempt of endoscopic balloon dilation. 10. Patients with an abscess