Efficacy and Safety of Two Treatment Algorithms in Adults With Moderate to Severe Crohn's Disease
Condition: Crohn's Disease
MeSH terms: Crohn Disease
Intervention: Adalimumab; Prednisone; Azathioprine
Intervention description: If adalimumab was initiated, it was administered subcutaneously as a 160 mg induction dose the first week, followed by 80 mg 2 weeks later, followed by 40 mg every other week as a maintenance dose. The dose of adalimumab was increased from 40 mg eow to 40 mg every week in participants with an inadequate response and de-escalated to 40 mg eow in participants who met success criteria.; The suggested regimen for participants initiating prednisone consisted of a maximum dose of prednisone 40 mg/day for 2 weeks, followed by a fixed taper for 6 weeks.; Participants with normal thiopurine methyltransferase (TPMT) enzyme activity could receive oral azathioprine 2.5 mg/kg/day. In participants with intermediate TPMT enzyme activity azathioprine was initiated at a dose of 1.25 mg/kg/day. The dose of azathioprine was adjusted according to abnormalities of white blood cell (WBC) count, platelet count, liver function tests (LFTs; i.e. alanine transaminase [ALT], aspartate transaminase [AST], alkaline phosphatase), lipase, blood urea nitrogen (BUN), and serum creatinine.
Intervention MeSH terms: Prednisone; Adalimumab; Azathioprine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 252.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The primary objective of this study was to demonstrate that tight control of disease
      activity, using stringent criteria based on Crohn's disease activity Index (CDAI), biomarkers
      (high sensitivity C-reactive protein [hs-CRP] and fecal calprotectin), and corticosteroid
      use, improves the rate of mucosal healing 48 weeks after randomization compared with
      management using less stringent criteria based only on CDAI and corticosteroid use.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of ileal, colonic (including rectal), or ileocolonic Crohn's disease (CD)
             confirmed using imaging technology or endoscopy not more than 6 years prior to
             Baseline.

          -  CDAI score of greater than or equal to 220 and less than or equal to 450 at the
             Baseline visit in participants not receiving prednisone or equivalent at Baseline.
             CDAI score of greater than or equal to 200 and less than or equal to 450 at the
             Baseline visit if the participant is receiving prednisone less than or equal to 20 mg
             or equivalent for at least 7 days before Baseline. CDAI score of greater than 150 and
             less than or equal to 450 at the Baseline visit if the participant is receiving
             prednisone higher than 20 mg or equivalent for greater than or equal to 7 days before
             Baseline

          -  Participant or his/her legal representative have voluntarily signed and dated an
             informed consent approved by and compliant with the requirements of this study
             protocol which has been approved by an Institutional Review Board (IRB)/Independent
             Ethics Committee (IEC).

          -  Adequate cardiac, renal and hepatic function as determined by the Principal
             Investigator and demonstrated by Screening laboratory evaluations, questionnaires and
             physical examination results that do not indicate an abnormal clinical condition which
             would place the participant at undue risk and thus preclude participation in the
             study.

          -  Participant must be able to self-inject and orally administer study medication or have
             a designee or Healthcare Professional who can assist

        Exclusion Criteria:

          -  Previous or current biologic use for Crohn's disease or participation in a biologic
             study

          -  Previous or current use of immunomodulators (e.g., methotrexate, azathioprine,
             6-mercaptopurine, JAK inhibitor, alpha-integrin) for Crohn's disease or participation
             in a Crohn's disease study with immunomodulator(s). Current use of immunomodulators
             for non-Crohn's disease at Baseline.

          -  Greater than two previous courses of corticosteroid (systemic corticosteroid) or
             budesonide) for Crohn's Disease. A course is defined as 1) total duration for burst
             and taper ≥ 4 weeks and 2) prednisone or equivalent ≥ 40 mg (or budesonide ≥ 9 mg) for
             at least 2 weeks.

          -  Participants with a poorly controlled medical condition such as: uncontrolled diabetes
             with documented history of recurrent infections, unstable ischemic heart disease,
             moderate to severe congestive heart failure (New York Heart Association [NYHA] class
             III or IV), recent cerebrovascular accident and any other condition which, in the
             opinion of the Investigator or the sponsor, would put the participant at risk by
             participation in the protocol

          -  Participants with positive C. difficile stool assay at Screening.