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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.

Phase 4
Conditions
Rheumatoid Arthritis
Interventions
Registration Number
NCT05153200
Lead Sponsor
Ottawa Hospital Research Institute
Brief Summary

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

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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
40
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Upadacitinib(Rinvoq)UpadacitinibUpadacitinib(Rinvoq) 15 mg po daily
Adalimumab(Idacio)Adalimumab-
Primary Outcome Measures
NameTimeMethod
Retention Rate6 months

Proportion of participants who complete the 6 months of follow-up

Recruitment Rate1 year

Number of participants recruited to study

Secondary Outcome Measures
NameTimeMethod
Change in C-Reactive Protein6 months
Change in Disease Activity Score (DAS)-28-ESR6 months
Change in DAS-28-CRP6 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 Widespread Pain Index (WPI)6 months

Score of 4 or more indicates widespread pain (no known MCID)

Change in 100 mm Pain visual analogue scale (VAS)6 months

"no pain" and "pain as bad as it can be" as anchors (MCID=11 mm)

Change in McGill Pain Questionnaire (MPQ)6 months

Detailed assessment of pain quantity, quality, and impact (MCID=5)

Change in OMERACT (Outcome Measures in Rheumatoid Arthritis in Clinical Trials) ultrasound task force Global Synovitis Score (GLOESS).6 months

US assessment of 32 joints assessing for Gray-scale synovitis and power-Doppler findings.

Change in Swollen Joint Count (44)6 months
Change in Tender Joint Count (44)6 months
Change in PainDETECT Questionnaire (PDQ)6 months

Nociceptive (PDQ\<13, unclear pain PDQ 14-18, neuropathic pain \>18)

ACR 50 response6 months
ACR 70 response6 months
Change in Erythrocyte Sedimentation Rate6 months
Change in Physician Global Assessment of Disease Severity6 months

VAS

Change in Patient Global Assessment of Disease Severity6 months

VAS

Change in Health Assessment Questionnaire6 months
American College of Rheumatology (ACR) 20 response6 months
Change in Short Form 36 (SF-36)6 months
Change in Patient Health Questionnaire (PHQ-9)6 months
Adverse Events6 months
Serious Adverse Events6 months
Drop-out due to Adverse Events6 months
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