Sequential medication options after TNFi failure in juvenile idiopathic arthritis

Trial of Sequential Medications AfteR TNFi Failure in Juvenile Idiopathic Arthritis

This test looks at whether switching to one of three non‑TNFi medicines or trying a different TNFi helps children aged 2–17 with polyarticular‑course JIA who didn't improve on their first TNFi.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 400 (estimated)
• Ages: 2 Years to 17 Years
• Sex: All
• Sponsor: Duke University (Academic / other)
• Drugs / interventions: adalimumab, tofacitinib
• Locations: 6 sites (San Francisco, California and 5 other locations)
• Trial ID: NCT06654882 on ClinicalTrials.gov

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.

Who should consider this trial

Good fit: Children aged 2 to <18 years with polyarticular‑course JIA, moderate-to-high disease activity (cJADAS10 >5), weight ≥10 kg, and inadequate response to an initial TNFi given for at least 3 months are ideal candidates.

Not a fit: Patients with systemic JIA, enthesitis‑related arthritis, active inflammatory bowel disease or psoriasis, recent active uveitis, sacroiliitis, active or incompletely treated tuberculosis, prior malignancy, or those who already respond to their initial TNFi are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the trial could help doctors choose the next best biologic or targeted drug more quickly for children who don't respond to their first TNFi, shortening time on ineffective therapy.

How similar studies have performed: While individual trials have shown that non‑TNFi agents can work after TNFi failure, using a SMART sequential design to identify optimal medication sequences in pediatric JIA is novel and largely untested.

Eligibility criteria

Inclusion Criteria:

* Polyarticular course JIA
* Moderate or high-disease activity (cJADAS10 \>5) despite treatment with an initial TNFi for ≥3 months
* Age ≥2 years and \<18 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 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 the opinion of the site investigator

Where this trial is running

San Francisco, California and 5 other locations

• 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)

Conditions Polyarticular Course Juvenile Idiopathic Arthritis; JIA; Rheumatology