Early Changes in Pain, Disease Activity, and Ultrasound Evidence of Inflammatory Synovitis in Patients Receiving JAK-inhibitor vs. TNF-inhibitor Therapy for Active Rheumatoid Arthritis: A Feasibility Study.

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Early Changes in Pain, Disease Activity, and Ultrasound Evidence of Inflammatory Synovitis in Patients Receiving JAK-inhibitor vs. TNF-inhibitor Therapy for Active Rheumatoid Arthritis: A Feasibility Study.

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Upadacitinib
* Drug: Adalimumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Upadacitinib(Rinvoq)<br>Upadacitinib(Rinvoq) 15 mg po daily | Drug: Upadacitinib<br>* 15 mg po daily<br>* Other names: Rinvoq;|
| Active Comparator: Adalimumab(Idacio)<br> | Drug: Adalimumab<br>* 40 mg sc every other week<br>* Other names: Idacio;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recruitment Rate | Number of participants recruited to study | 1 year | 
| Retention Rate | Proportion of participants who complete the 6 months of follow-up | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 100 mm Pain visual analogue scale (VAS) | no pain and pain as bad as it can be as anchors (MCID=11 mm) | 6 months | 
| Change in McGill Pain Questionnaire (MPQ) | Detailed assessment of pain quantity, quality, and impact (MCID=5) | 6 months | 
| Change in Widespread Pain Index (WPI) | Score of 4 or more indicates widespread pain (no known MCID) | 6 months | 
| Change in PainDETECT Questionnaire (PDQ) | Nociceptive (PDQ<13, unclear pain PDQ 14-18, neuropathic pain >18) | 6 months | 
| Change in OMERACT (Outcome Measures in Rheumatoid Arthritis in Clinical Trials) ultrasound task force Global Synovitis Score (GLOESS). | US assessment of 32 joints assessing for Gray-scale synovitis and power-Doppler findings. | 6 months | 
| Change in Swollen Joint Count (44) |  | 6 months | 
| Change in Tender Joint Count (44) |  | 6 months | 
| Change in Physician Global Assessment of Disease Severity | VAS | 6 months | 
| Change in Patient Global Assessment of Disease Severity | VAS | 6 months | 
| Change in Health Assessment Questionnaire |  | 6 months | 
| American College of Rheumatology (ACR) 20 response |  | 6 months | 
| ACR 50 response |  | 6 months | 
| ACR 70 response |  | 6 months | 
| Change in Erythrocyte Sedimentation Rate |  | 6 months | 
| Change in C-Reactive Protein |  | 6 months | 
| Change in Disease Activity Score (DAS)-28-ESR |  | 6 months | 
| Change in DAS-28-CRP |  | 6 Months | 
| Change in Clinical Disease Activity Index (CDAI) |  | 6 months | 
| Change in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT) |  | 6 months | 
| Change in Insomnia Severity Index (ISI) |  | 6 months | 
| Change in Short Form 36 (SF-36) |  | 6 months | 
| Change in Patient Health Questionnaire (PHQ-9) |  | 6 months | 
| Adverse Events |  | 6 months | 
| Serious Adverse Events |  | 6 months | 
| Drop-out due to Adverse Events |  | 6 months |