The purpose of this phase 4 pilot study is to assess 1-year recruitment, and 6-month retention rates for participants with rheumatoid arthritis (RA) recruited to this study. Secondarily, we aim to study the difference in multifaceted pain scoring and Musculoskeletal Ultrasound (MSK-US)-detected synovitis between those treated with Upadacitinib vs Adalimumab.

This is a 26-week phase 4 randomized, single-blind, parallel-group, active treatment-controlled pilot/feasibility study designed to primary assess recruitment and retention rates and to secondarily assess the efficacy of Upadacitinib vs Adalimumab in controlling multiple measures of pain and MSK-US-detected synovitis in those with Active Rheumatoid Arthritis.

Participants with active RA despite combination conventional synthetic Disease Modifying Antirheumatic Drugs (csDMARD), alternative biologic DMARD (bDMARD), or alternative targeted synthetic DMARD (tsDMARD) will be randomized in a 1:1 ratio to:

• Upadacitinib(Rinvoq) 15 mg orally (po) daily or
• Comparison Group: Adalimumab(Idacio) 40 mg subcutaneously (sc) every other week Baseline methotrexate may be continued if patient is receiving at time of study enrollment.

At 1 year after study initiation, recruitment rate over the first year will be measured and rate of 6-month participant retention will also be measured.

At baseline, 1 month, 3 months, and 6 months after initiation of study drug, disease activity, pain, MSK-US synovitis, and other patient important outcomes will be collected.

The study will be completed after 6-months of follow-up.

Inclusion Criteria:

• Diagnosis of RA based on ACR/EULAR 2020 Classification Criteria
• Moderate-to-high disease activity according to clinical disease activity indices
• Referred to the biologics clinic (The Ottawa Hospital Arthritis Centre) by their primary rheumatologist who practices within the division following decision to escalate to, or switch between, advanced therapy.

Exclusion Criteria:

• Any contraindication to initiation of either Upadacitinib or Adalimumab
• Unable to come to follow-up at 1, 3, and 6 months
• Current or planned (within 6 months) pregnancy or breastfeeding
• Inability to give informed consent
• Inability to communicate verbal or written responses to pain questionnaires
• Intraarticular steroid injections if done within 30 days of first visit
• Initiation of study intervention prior to baseline assessment
• Previous use of either study drug

MSK-US assessors will be blinded to treatment allocation, pain scores, and disease activity measures.