Efficacy and Safety of Top-down Therapy in Pediatric Crohn's Disease

Summary

Crohn's disease (CD) is an incurable debilitating disorder affecting an increasing number of children. The etiology remains elusive, but a genetically determined aberrant immune response against microbiota appears to be responsible. TNFα plays a pivotal role in the cytokine cascade of the inflammatory process and mediates multiple processes central to the pathogenesis of CD. The natural history of pediatric CD is characterized by recurrent flare-ups that severely impair patients growth, pubertal development and nutritional status. Epidemiological observations have shown that the course of CD, despite conventional treatment, inevitably progresses to the development of severe complications and surgery. Infliximab is the most widely used biological agent in moderate-to-severe pediatric CD. At present biologics are used after the failure of conventional drugs (step-up approach) and represent the peak of the CD therapeutic pyramid. The early use of biologics (top-down approach) has been demonstrated to be effective in adults with CD. The project aims at evaluating if a top-down approach may achieve mucosal healing before irreversible tissue damage present in late CD and thus alter the natural course of the disease, compared to the conventional approach. The study can also add information about the safety of infliximab used as first-line therapy and may add data on the benefit and costs of a reversal of the traditional therapeutic pyramid in pediatric CD, guiding the clinician in deciding in whom, when and how to introduce early aggressive treatment in daily practice.

Conditions

• Pediatric Crohn's Disease

Interventions

DRUG

Top-down

Patients randomized to top-down arm will receive an induction regimen of three consecutive i.v. infusions of infliximab (Remicade, 5 mg/kg) at weeks 0, 2, and 6 plus AZA (2 mg/Kg per os/day). Patients who will not respond to the induction regimen at week 8 will receive no further treatment with infliximab. Disease recurrences will be treated with infliximab (reduction of the interval between two doses). At 12 months pazients will discontinue azathioprine and continue infliximab (5mg/kg every 8 weeks). During the trial, other drugs will be not allowed, including immunosuppressive agents, other biological agents or steroids.

DRUG

Step-up

Patients randomized on Step-up arm will receive methylprednisolone (1 mg/Kg/day per os. for 2 weeks then tapering of 5 mg/week then stop) plus azathioprine (2 mg/Kg/die per os/day).Disease recurrences under azathioprine will be treated with steroid courses (methylprednisolone 1-2 mg/Kg/day per os. for 2 weeks then tapering of 5 mg/week then stop). During the trial, other drugs will be not allowed, including immunosuppressive agents, other biological agents or steroids.

Sponsors & Collaborators

• University of Roma La Sapienza

  lead OTHER

Principal Investigators

• Marina Aloi, Investigator · University of Roma La Sapienza

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

6 Years

Max Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-12-31

Primary Completion

2014-01-31

Completion

2015-12-31

Countries

• Italy

Study Locations