Lymphatic transport was previously examined by these investigators using Near InfraRed Indocyanine Green fluorescence imaging (NIR-ICG) of the upper extremities. They established reliable and reproducible methodologies in RA patients. The purpose of this phase 2 pilot is to study RA disease progression and effectiveness as well as the mechanism of action of clinical interventions using established NIR-ICG methodologies in previous studies.

In preclinical studies, these investigators demonstrated that amelioration of tumor necrosis factor (TNF)-induced arthritis with anti-TNF, but not methotrexate (MTX) therapy, correlates with normalization of ICG clearance and popliteal lymph node (PLN) contractions. In RA patients during hand flare, it was found that ICG clearance from the web spaces, and numbers of ICG+ lymphatic basilic vessels of RA hands, are significantly decreased vs. healthy controls. Based on these observations, two important questions warrant testing to assess the clinical utility of NIR-ICG biomarkers in RA hands: Does amelioration of active synovitis pre and post treatment) correlate with: 1) increased ICG clearance (primary outcome) and/or 2) recovery of basilic ICG+ vessels (secondary outcome)? To formally address these questions, a clinical pilot will be conducted of early RA patients with symptomatic disease in their hand(s), who will undergo NIR-ICG imaging at baseline, 16-weeks, and 1-year post anti-TNF therapy, and examine if NIR-ICG outcome measures predict and correlate with clinical response.

Inclusion Criteria:

Early RA

• Ability to provide written informed consent
• Subjects must be 18 years old or older
• RA subjects must fulfill 2010 American College of Rheumatology (ACR) criteria with a DAS28-C-Reactive Protein (CRP) >3.5
• Must have 1 year or less of disease
• Must be MTX inadequate responder (DAS28-CRP >2.6 at 4 months of therapy) OR experience a flare on MTX (self-reported and score of >25 on the Outcome Measures in Rheumatology (OMERACT) Flare questionnaire AND are starting an anti-TNF therapy.
• Must have active synovitis in one or both hands confirmed by ultrasound

Established RA

• Ability to provide written informed consent
• Subjects must be 18 years of age or older
• RA subjects must fulfill 2010 ACR criteria with a DAS-CRP >3.5
• Must have at least 10 years of disease
• Must have active synovitis in one or both hands confirmed by ultrasound
• Must be on a stable dose of DMARD (MTX, leflunomide, azulfidine, hydroxychloroquine), Janus Kinase (JAK) inhibitor or biologic agent for 8 weeks

Exclusion Criteria: All PATIENTS

• Active systemic disorders or inflammatory conditions other than RA, (i.e., chronic infections with hepatitis B, hepatitis C or HIV) that would confound the study results.
• Known sensitivity to iodine because of residual iodide in Indocyanine Green
• Pregnant women should not participate; pregnancy tests will not be performed
• Inability to donate blood due to poor venous access