Sequential medication options after TNFi failure in juvenile idiopathic arthritis

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

SMART-JIA is an open-label, randomized, multicenter trial that compares a second TNFi (active control) to each of three non‑TNFi medications (an IL-6 inhibitor, a JAK inhibitor, or abatacept) in children with polyarticular‑course JIA who did not respond adequately to an initial TNFi. The study uses a sequential multiple assignment randomized trial (SMART) design with two randomization stages: the first compares each non‑TNFi to a second TNFi, and the second rerandomizes patients who do not respond to their assigned therapy to identify optimal next-step sequencing. Treatments are given by usual routes (subcutaneous injections for most biologics; oral dosing for JAK inhibitors) and the trial is pragmatic and international in scope. The goal is to identify effective medication sequences and inform individualized treatment strategies for children who fail initial TNFi therapy.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* Polyarticular course JIA
* Moderate or high-disease activity (cJADAS10 \>5) despite treatment with an initial TNFi for ≥2 months
* Age ≥2 years and \<21 years and weight ≥ 10kg
* No systemic glucocorticoids or systemic glucocorticoids at a stable dose of ≤0.2 mg/kg/day (maximum 10 mg/day) for ≥2 weeks prior to baseline visit
* Documented informed consent/assent obtained from the parent/caregiver/patient

Exclusion Criteria:

* Systemic JIA
* Enthesitis-related arthritis/juvenile spondyloarthritis (2001 International League of Associations for Rheumatology \[ILAR\] criteria)30
* History of or currently active inflammatory bowel disease
* History of or currently active psoriasis
* Active uveitis within 3 months of the baseline visit
* History of or currently active sacroiliitis
* History of or current malignancy
* Active tuberculosis (TB) or a history of incompletely treated TB; Purified Protein derivative (PPD) or QuantiFERON-TB positive patients (without active TB) unless it is documented that the patient has been adequately treated for TB and can start treatment with a biologic agent, based on the medical judgment of the site investigator and/or an infectious disease specialist; suspected extrapulmonary TB infection; or at high risk of contracting TB, such as close contact with individual with active or latent TB
* Prior treatment with more than one TNFi molecule; exposure to more than one biosimilar of the same TNFi molecule is allowed
* Prior treatment with non-TNFi bDMARDs and/or any JAKi
* Aspartate aminotransferase (AST) or alanine transaminase (ALT) ≥3 × upper limit of normal (ULN) for age and sex
* Serum creatinine \>1.5 × ULN for age and sex
* Platelet count \<150 × 103/μL (\<150,000/mm3)
* Hemoglobin \<7.0 g/dL (\<4.3 mmol/L)
* White blood cell (WBC) count \<3,000/mm3 (\<3.0 × 109/L)
* Neutrophil count \<1,500/mm3 (\<1.5 × 109/L)
* Any active acute, subacute, chronic, or recurrent bacterial, viral, or systemic fungal infection or any major episode of infection requiring hospitalization or treatment during screening or treatment with IV antibiotics completed within 4 weeks of the screening visit or oral antibiotics completed within 2 weeks of the screening visit
* Any live attenuated vaccine, such as varicella-zoster, oral polio, measles, mumps or rubella vaccines, within 4 weeks prior to the baseline visit.
* Any medical history that may be considered a contraindication/safety concern with the use of adalimumab, etanercept, tofacitinib, ABA, or an IL-6 inhibitor or their biosimilars. In particular, subjects at known high risk for venous thromboembolism will be excluded, including recent heart failure or prior myocardial infarction, known inherited thrombotic risk factors, history of venous thromboembolism (deep venous thrombosis or pulmonary embolism, undergoing major surgery, or are chronically immobilized).
* Pregnant or breastfeeding
* Sexually active females of childbearing potential who refuse to use at least one required contraception method (See Contraception paragraph 8.9 for definition of childbearing potential and details).
* History of hypersensitivity or allergic reaction to any study drug or any of its excipients (inactive ingredients).

Where it's running

• University of California San Francisco Pediatric Rheumatology
  San Francisco, California, United States Recruiting
• University of Florida
  Gainesville, Florida, United States Recruiting
• Hackensack Meridian Health - Joseph M. Sanzari Children's Hospital
  Hackensack, New Jersey, United States Recruiting
• Nationwide Children's Hospital
  Columbus, Ohio, United States Recruiting
• Asklepios Children's Hospital
  Sankt Augustin, North Rhine-Westphalia, Germany Recruiting
• IRCCS Giannina Gaslini Institute
  Genoa, Liguria, Italy Recruiting

Study contacts

• Study coordinator: Laura E Schanberg (Contact PI)
• Email: laura.schanberg@duke.edu
• Phone: 919-373-3863

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.