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).
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).