Pediatric Crohn's Disease AdalImumab Level-based Optimization Treatment (PAILOT) Trial
Condition: Crohn's Disease
MeSH terms: Crohn Disease
Study type: Interventional
Phase: Phase 4

Summary: 
      Objectives: To examine the effect of drug level-based personalized treatment of adalimumab in
      children with Crohn's disease. Design: A prospective, randomized, open label study. Setting:
      Pediatric gastroenterology centers. Participants: Children 6 year to 17 years who are
      diagnosed with CD and are planned to receive adalimumab treatment. Main outcome measures:
      Pediatric Crohn's Activity Index (PCDAI) at 48 and 72 weeks. Secondary outcome measures:
      Corticosteroids free remission rates and on adalimumab at 48 and 72 weeks. The effect of
      routine adalimumab drug monitoring-based treatment on trough levels and anti-adalimumab
      antibodies during therapy.
    

Detailed description: 
      The efficacy of adalimumab in inducing and maintaining remission in both adults and children
      with moderate-to-severe Crohn's Disease has been demonstrated in multiple clinical trials.
      Despite efforts to optimize treatment, approximately 40% of patients who initially respond to
      anti-TNF ultimately lose response. Measurement of adalimumab (ADA) drug levels and antibodies
      to adalimumab (ATAs) in patients has been shown to assist decision making in patients who
      have lost response during the course of treatment. This approach is based on the observations
      showing that higher ADA concentrations are associated with higher treatment efficacy and that
      loss of response is primarily attributed to either undetectable drug levels or to the
      presence of high titers of ATAs. Existing data is mostly based on retrospective cohort
      studies, nevertheless, the concept of routine therapeutic drug monitoring in-order to improve
      efficacy is still evolving. Recently, preliminary results of the Trough level Adapted
      infliXImab Treatment (TAXIT) study, performed in adult IBD patients, have failed to
      demonstrate superiority of level-based treatment over clinically-based treatment regarding
      rates of response over time. Nevertheless, it is premature to conclude that patients do not
      benefit from a tailored approach as the reported abstract did not stratify patients according
      to type of disease (CD vs. ulcerative colitis) and as some significant advantages such as
      reduced rate of antibodies and reduction of CRP were described in the level-based arm.
      Anti-TNF treatment in pediatric patients may differ from adults due to a higher risk for
      developing the rare hepatosplenic T cell lymphomas (HSCTL) in young males treated with
      combination therapy including thiopurines and anti-TNF agents. Concomitant therapy (using
      immunomodulators, mainly azathioprine) which has demonstrated superiority over mono-therapy
      has become a standard of care in moderate to severe CD in adults. In-view of the concerns of
      pediatric gastroenterologist from concomitant therapy-induced adverse events the option to
      improve efficacy of mono-therapy by guiding it according to drug monitoring is further
      appealing. Therefore, our aim is to assess the efficacy of routine therapeutic drug
      monitoring based treatment in pediatric CD patients in a prospective randomized control
      trial. We hope that this study will further contribute to the understanding of the potential
      benefits of therapeutic drug monitoring based management in pediatric patients treated with
      anti-TNF agents.Hypothesis:

      We hypothesize that by routine measuring of ADA trough levels and ATAs titers we will achieve
      higher and stable trough levels resulting in greater corticosteroid free remission rates and
      decreased LOR rates. We assume that this will be associated with lower frequencies of ATAs.
      We further assume that the intervention will reduce the need for alteration of treatment
      schemes by adding immunomodulators or by switching treatment within class or out of class.

      Objectives:

      This is ADA therapy optimization study in patients starting or receiving ADA due to active
      disease.

        1. Primary Efficacy Objective: To evaluate the effect of routine ADA drug monitoring-based
           treatment, in comparison to clinically-based monitoring on disease activity.

        2. Secondary Objective: To evaluate the effect of routine ADA drug monitoring-based
           treatment on trough levels and ATAs during therapy.
    

Intervention name(s): Adalimumab
Intervention type(s): Drug
Intervention description(s): Eligible patients are those who are planned to start Adalimumab (ADA). Patients will be randomized at the first screening visits to either group 1 (interventional) or group 2 (clinical). Eligible patients, will start induction treatment (weeks 0,2) with ADA (> 40kg 160/80/40 mg every 2 weeks or < 40 kg 100/50/25 mg for m2 body surface area every 2 weeks). Interventions will start from the 4th injection for responding patients only (based on levels taken prior to the third injection). Responding patients will continue to the maintenance phase in which they will receive ADA every 2 weeks, either 40 mg or 25 mg/m2. At screening, and every 2 months all patients will be examined and have height, weight, PCDAI performed as well as comprehensive laboratory examinations.
Other intervention name(s): Humira
Intervention MeSH terms: Adalimumab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment