Overview

This study aims to compare the effectiveness of a conventional therapeutic regimen, based on treatment escalation (step-up strategy) and driven by the treat-to-target approach, with that of an early aggressive intervention based on the initial start of a combination of conventional and biological DMARDs (step-down strategy).

Eligibility

Inclusion Criteria

Each patient must meet all the following criteria in order to be enrolled in the trial:

        I. Newly-diagnosed and synthetic or biologic DMARD-naïve children (only treatment with 1
        NSAID is allowed and no corticosteroid joint injections prior to randomization ) with a JIA
        classified according to the following ILAR categories:
        i. Oligoarthritis ii. Rheumatoid factor negative polyarthritis
        II. Active arthritis
        III. Onset of JIA symptoms no more than 6 months before randomization
        IV. Age 2 to 17 years at enrolment.
        V. Female of child-bearing potential must have a negative pregnancy test at the beginning
        of the trial. If sexually active, they must agree to use highly effective contraceptive
        measures, throughout study participation, and must have no intention of conceiving during
        the course of the study. Post-pubertal males must have no plans to father a child during
        the study and agree to use highly effective contraceptive measures if sexually active.
        VI. Ability to comply with the entire study procedures, ability to communicate meaningfully
        with the investigational staff, competence to give written informed consent; to be applied
        to the parents and/or patients, as appropriate
        VII. Duly executed, written, informed consent/assent obtained from the parents/patient.
        Exclusion criteria
        I. Classification in one of the following JIA categories: systemic arthritis, RF-positive
        polyarthritis, psoriatic arthritis, enthesitis-related arthritis, undifferentiated
        arthritis
        II. Patients who need systemic treatment for uveitis
        III. Tuberculosis related issues: patients are excluded from the study if they have:
          1. Active TB or a history of incompletely treated TB
          2. PPD or QuantiFERON-TB positive patients (with no active disease) unless it is
             documented by a specialist that the patient has been adequately treated for TB and can
             start treatment with a biologic agent, based on the medical judgment of the study
             investigator and / or an infectious disease specialist.
          3. Suspected extrapulmonary TB infection
          4. Patients at high risk of contracting TB, such as close contact with individual with
             active or latent TB
        IV. Previous treatment with any synthetic or biologic DMARD
        V. Any live attenuated vaccine within 4 weeks prior to the baseline visit, such as
        varicella-zoster, oral polio, measles, mumps or rubella vaccines and throughout the study.
        Killed or inactive vaccine may be permitted based on the investigator's judgment
        VI. Prior or current history of malignancy or any other significant concomitant illness(es)
        as per the treating physician evaluation
        VII. Any of the following laboratory abnormalities based on the most recent laboratory
        results:
          1. White blood cell (WBC) count <3.50 x 103/mm3 (SI units: <3.50 x 109/L) and neutrophils
             < 1x109/L;
          2. Hemoglobin < 8.5 g/dL (SI units: <85 g/L);
          3. Platelet Count < 125,0000/mm3 or ≥1,000,000/mm3 (SI units: <125 x 109/L or ≥1,000 x
             109/L
          4. Aspartate aminotransaminase (AST) or alanine aminotransaminase (ALT) ≥ 2.0 x upper
             limit of normal (ULN).