Proactive Infliximab Optimization Using a Pharmacokinetic Dashboard Versus Standard of Care in Patients with Inflammatory Bowel Disease: the OPTIMIZE Trial

Inclusion Criteria:

1. Males or nonpregnant, nonlactating females aged 16 to 80 years inclusive.

2. Diagnosis of IBD prior to screening using standard endoscopic, histologic, orradiologic criteria. Participants with patchy colonic inflammation initiallydiagnosed as indeterminate colitis would meet inclusion criteria, if theinvestigator feels that the findings are consistent with CD or UC. Enrollment ofparticipants with UC will be capped at 49% of the planned study population (maximum 61 participants).

3. Moderately to severely active IBD, defined by a total CDAI score between 220 and 450points for CD or a partial Mayo Score (PMS) > 4 for UC (including a rectal bleedingsubscore [RBS] ≥ 1), and at least 1 of the following:

4. Elevated CRP (> upper limit of normal)

5. Elevated FC (> 250 μg/g)

6. SES-CD > 6 (SES-CD > 3 for isolated ileal disease) for CD only and a Mayoendoscopic subscore (MES) ≥ 2 for UC only.

7. Physician intends to prescribe IFX as part of the usual care of the subject.

8. No previous use of IFX prior to enrolment in the current study, unless theparticipant received 1 prior dose of IFX (within 2.5 weeks of enrolment) and met alleligibility criteria at the time of starting IFX and IFX was administered accordingto the requirements outlined in this protocol

9. Able to participate fully in all aspects of this clinical trial.

10. Written informed consent must be obtained and documented.

Exclusion Criteria:

1. Participants with any of the following IBD-related complications:

2. Abdominal or pelvic abscess, including perianal

3. Presence of stoma, ileal pouch-anal anastomosis, or ostomy

4. Isolated perianal disease

5. Obstructive disease, such as obstructive stricture

6. Short gut syndrome

7. Toxic megacolon or any other complications that might require surgery, or anyother manifestation that precludes or confounds the assessment of diseaseactivity (CDAI or SES-CD for CD or PMS, PRO2, or MES for UC)

8. Total colectomy.

9. History or current diagnosis of ulcerative proctitis (UC extending < 15 cm from theanal verge), acute severe (fulminant) UC, hospitalised IV steroid-refractory UC,indeterminate colitis, microscopic colitis, ischemic colitis, colonic mucosaldysplasia, or untreated bile acid malabsorption.

10. Current bacterial or parasitic pathogenic enteric infection, according to SOCassessments, including: Clostridioides difficile; tuberculosis; known infection withhepatitis B or C virus; known infection with HIV; sepsis; abscesses. History of thefollowing: opportunistic infection within 6 months prior to screening; any infectionrequiring antimicrobial therapy within 2 weeks prior to screening; more than 1episode of herpes zoster or any episode of disseminated zoster; any other infectionrequiring hospitalization or intravenous antimicrobial therapy within 4 weeks priorto screening.

11. Has any malignancy or lymphoproliferative disorder other than nonmelanoma cutaneousmalignancies or cervical carcinoma in situ that has been treated with no evidence ofrecurrence within the last 5 years.

12. Known primary or secondary immunodeficiency.

13. PNR to adalimumab, defined as no objective evidence of clinical benefit after 14weeks of therapy.

14. Subjects with failure to a prior biologic, defined as PNR or SLR, will be excludedwhen a maximum of 40% of the planned enrollment (approximately 78 subjects) havefailure to prior biologic exposure.

15. Concomitant use of oral corticosteroid therapy exceeding prednisone 40 mg/day,budesonide 9 mg/day, or equivalent, unless a tapering schedule is initiated with aplan to be off CS by Week 14

16. Presence of any medical condition or use of any medication that is acontraindication for IFX use, as outlined on the product label.

17. A concurrent clinically significant, serious, unstable, or uncontrolled underlyingcardiovascular, pulmonary, hepatic, renal, GI, genitourinary, hematological,coagulation, immunological, endocrine/metabolic, or other medical disorder that, inthe opinion of the investigator, might confound the study results, pose additionalrisk to the subject, or interfere with the subject's ability to participate fully inthe study.

18. Pregnant or lactating women, to be excluded based on the physician's usual practicefor determining pregnancy or lactation status.

19. Known intolerance or hypersensitivity to IFX or other murine proteins.