Please select the eligibility criteria that correspond to the clinical trial below.
Title: A NORwegian Multicentre Randomised Controlled Trial Assessing the Effectiveness of Tailoring Infliximab Treatment by Therapeutic DRUg Monitoring - The NOR-DRUM Study
Brief Summary: Infliximab and other TNF-inhibitors have revolutionised the treatment of several immunological inflammatory diseases. Still, more than half of the patients either do not respond sufficiently to infliximab therapy or loose efficacy over time. The large individual variation in the serum drug concentrations on standard doses and the development of anti-drug antibodies are thought to be main reasons for these treatment failures. An individualised treatment strategy based on systematic assessments of serum drug concentrations, therapeutic drug monitoring, has been proposed as a clinical tool to optimise efficacy of infliximab treatment. Therapeutic drug monitoring seems reasonable both from a clinical and an economical point of view, but the effectiveness of this treatment strategy still remain to be shown. The NOR-DRUM study is planned as a national, randomised controlled multicentre trial in two parts aiming to assess the effectiveness of therapeutic drug monitoring in order to achieve remission in patients with immunological inflammatory diseases starting infliximab treatment (part A) and in order to maintain disease control in patients on maintenance infliximab treatment (part B). The results of the NOR-DRUM study will hopefully contribute to an implementation of a personalised medicine approach to treatment with infliximab and other biological drugs.


Options:
A: 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, or radiologic criteria. Participants with patchy colonic inflammation initially diagnosed as indeterminate colitis would meet inclusion criteria, if the investigator feels that the findings are consistent with CD or UC. Enrollment of participants 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 450 points for CD or a partial Mayo Score (PMS) \> 4 for UC (including a rectal bleeding subscore \[RBS\] ≥ 1), and at least 1 of the following:

   1. Elevated CRP (\> upper limit of normal)
   2. Elevated FC (\> 250 μg/g)
   3. SES-CD \> 6 (SES-CD \> 3 for isolated ileal disease) for CD only and a Mayo endoscopic subscore (MES) ≥ 2 for UC only.
4. Physician intends to prescribe IFX as part of the usual care of the subject.
5. No previous use of IFX prior to enrolment in the current study, unless the participant received 1 prior dose of IFX (within 2.5 weeks of enrolment) and met all eligibility criteria at the time of starting IFX and IFX was administered according to the requirements outlined in this protocol
6. Able to participate fully in all aspects of this clinical trial.
7. Written informed consent must be obtained and documented.

Exclusion Criteria:

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

   1. Abdominal or pelvic abscess, including perianal
   2. Presence of stoma, ileal pouch-anal anastomosis, or ostomy
   3. Isolated perianal disease
   4. Obstructive disease, such as obstructive stricture
   5. Short gut syndrome
   6. Toxic megacolon or any other complications that might require surgery, or any other manifestation that precludes or confounds the assessment of disease activity (CDAI or SES-CD for CD or PMS, PRO2, or MES for UC)
   7. Total colectomy.
2. History or current diagnosis of ulcerative proctitis (UC extending \< 15 cm from the anal verge), acute severe (fulminant) UC, hospitalised IV steroid-refractory UC, indeterminate colitis, microscopic colitis, ischemic colitis, colonic mucosal dysplasia, or untreated bile acid malabsorption.
3. Current bacterial or parasitic pathogenic enteric infection, according to SOC assessments, including: Clostridioides difficile; tuberculosis; known infection with hepatitis B or C virus; known infection with HIV; sepsis; abscesses. History of the following: opportunistic infection within 6 months prior to screening; any infection requiring antimicrobial therapy within 2 weeks prior to screening; more than 1 episode of herpes zoster or any episode of disseminated zoster; any other infection requiring hospitalization or intravenous antimicrobial therapy within 4 weeks prior to screening.
4. Has any malignancy or lymphoproliferative disorder other than nonmelanoma cutaneous malignancies or cervical carcinoma in situ that has been treated with no evidence of recurrence within the last 5 years.
5. Known primary or secondary immunodeficiency.
6. PNR to adalimumab, defined as no objective evidence of clinical benefit after 14 weeks of therapy.
7. Subjects with failure to a prior biologic, defined as PNR or SLR, will be excluded when a maximum of 40% of the planned enrollment (approximately 78 subjects) have failure to prior biologic exposure.
8. Concomitant use of oral corticosteroid therapy exceeding prednisone 40 mg/day, budesonide 9 mg/day, or equivalent, unless a tapering schedule is initiated with a plan to be off CS by Week 14
9. Presence of any medical condition or use of any medication that is a contraindication for IFX use, as outlined on the product label.
10. A concurrent clinically significant, serious, unstable, or uncontrolled underlying cardiovascular, pulmonary, hepatic, renal, GI, genitourinary, hematological, coagulation, immunological, endocrine/metabolic, or other medical disorder that, in the opinion of the investigator, might confound the study results, pose additional risk to the subject, or interfere with the subject's ability to participate fully in the study.
11. Pregnant or lactating women, to be excluded based on the physician's usual practice for determining pregnancy or lactation status.
12. Known intolerance or hypersensitivity to IFX or other murine proteins.
B: Inclusion Criteria:

* Male, or non-pregnant/non-lactating females, 18 or older
* Established Crohn's disease with active symptoms requiring prednisone therapy.
* Females of child-bearing potential must have a negative pregnancy test and must agree to use adequate contraception

Exclusion Criteria:

* Intolerance or hypersensitivity to infliximab, methotrexate, prednisone and or known allergy to murine proteins or other chimeric proteins
* Are pregnant, nursing, or planning pregnancy (both men and women) during or in the 6 months after the study
* In the 2 months prior to screening, have had a serious infection, or have been hospitalized for and/or treated with intravenous (IV) antibiotics for infection. In the 6 months prior to screening, have had an opportunistic infection.
* After screening, need to continue non-study medical therapy for CD
* In the 8 weeks prior to screening, have received any of the following: systemic steroid therapy, azathioprine, 6-mercaptopurine, cyclosporine, probiotic products, or omega-3 fatty acids
* Have received any of the following: biologics in the last 6 months; methotrexate in the last year; and/or ever received infliximab.
* Have any of the following: biopsy-proven cirrhosis, clinically important lung disease, pre-existing demyelinating disorder, systemic lupus erythematosus, congestive heart failure, diabetes mellitus (insulin dependent), increased risk for steroid-related side effects, body weight 40% higher than standard, human immunodeficiency virus and/or hepatitis B or hepatitis C
* Have any of the following: an active draining fistula as the primary manifestation of CD; documented short bowel syndrome; a stoma; or severe, and/or fixed symptomatic stenosis of the intestine.
* Have had any of the following: clinically important bowel obstruction in the last 3 months; a bowel resection in the last 3 months; and/or other intra-abdominal surgery within 6 months.
* Clinically significant impairment in cardiac, liver or renal function; central nervous system (CNS), pulmonary, hematological, immunological, vascular and gastrointestinal disease in addition to CD; current malignancy or malignancy within 5 years prior to screening.
C: Inclusion Criteria:

NOR-DRUM A

1. A clinical diagnosis of one of the following; rheumatoid arthritis, spondyloarthritis (including ankylosing spondylitis), psoriatic arthritis\*, ulcerative colitis, Crohn's disease or chronic plaque psoriasis
2. Male or non-pregnant female
3. ≥18 and \< 75 years of age at screening
4. A clinical indication to start INX
5. Subject not in remission according to diagnosis-specific disease activity scores
6. Subject capable of understanding and signing an informed consent form

   * Patients with psoriatic arthritis with predominantly axial manifestations should be included and assessed as spondyloarthritis

NOR-DRUM B

1. A clinical diagnosis of one of the following; rheumatoid arthritis, spondyloarthritis (including ankylosing spondylitis), psoriatic arthritis\*, ulcerative colitis, Crohn's disease or chronic plaque psoriasis
2. Male or non-pregnant female
3. ≥18 and \< 75 years of age at screening
4. On maintenance therapy with infliximab for a minimum of 30 weeks and a maximum of 3 years
5. A clinical indication for further infliximab treatment
6. Subject capable of understanding and signing an informed consent form

   * Patients with psoriatic arthritis and predominantly axial manifestations should be included and assessed as spondyloarthritis

Exclusion Criteria:

NOR-DRUM A

1. Major co-morbidities, such as previous malignancies within the last 5 years, severe diabetes mellitus, severe infections (including HIV), uncontrollable hypertension, severe cardiovascular disease (NYHA class 3 or 4), severe respiratory diseases, demyelinating disease, significant chronic widespread pain syndrome, laboratory abnormalities or significant renal or hepatic disease and/or other diseases or conditions where treatment with infliximab is either found contra-indicated by the clinician or which make adherence to the protocol difficult
2. A positive screening for TB and hepatitis
3. Inadequate birth control, pregnancy or subject considering becoming pregnant during the study period
4. Psychiatric or mental disorders, alcohol abuse or other substance abuse, language barriers or other factors which makes adherence to the study protocol difficult
5. Prior use of infliximab within the last 6 months

NOR-DRUM B

1. Major co-morbidities, such as previous malignancies within the last 5 years, severe diabetes mellitus, severe infections, uncontrollable hypertension, severe cardiovascular disease (NYHA class 3 or 4), severe respiratory diseases, demyelinating disease, significant chronic widespread pain syndrome, laboratory abnormalities or significant renal or hepatic disease and/or other diseases or conditions where treatment with infliximab is either found contra-indicated by the clinician or which make adherence to the protocol difficult
2. Inadequate birth control, pregnancy or subject considering becoming pregnant during the study period
3. Psychiatric or mental disorders, alcohol abuse or other substance abuse, language barriers or other factors which makes adherence to the study protocol difficult
D: Inclusion Criteria:

* age 16 - 75 years
* diagnosis of Crohn's disease within the past 4 years
* no previous treatment with corticosteroids, antimetabolites, or biologic agents.
* Active Crohn's disease, defined by a Crohn's Disease Activity Index (CDAI)20 score of greater than 200 points for a minimum of 2 weeks prior to randomization.

Exclusion Criteria:

* immediate need for surgery
* symptomatic stenosis or ileal/colonic strictures with prestenotic dilatation;
* signs, symptoms or laboratory tests indicating severe, medical disease;
* documented chronic infection
* a positive stool culture for pathogens
* a positive tuberculin test or a chest radiograph consistent with tuberculosis.
* malignancy
* allergy to murine proteins
* pregnancy
* substance abuse

Answer: C