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.

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Upadacitinib; Drug: 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.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Elliot P Hepworth, MD; Phone Number: 81571 613-738-8400; Email: elhepworth@toh.ca
• Study Contact Backup: Name: Sibel Z Aydin, MD; Phone Number: 81840 (613) 738-8400; Email: saydin@toh.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Upadacitinib(Rinvoq); Upadacitinib(Rinvoq) 15 mg po daily	Drug: Upadacitinib; 15 mg po daily; Other Names: Rinvoq
Active Comparator: Adalimumab(Idacio)	Drug: Adalimumab; 40 mg sc every other week; Other Names: Idacio

What is the study measuring?

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
Adverse Events		6 months
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
Serious Adverse Events		6 months
Drop-out due to Adverse Events		6 months

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute
• Collaborators: The Ottawa Hospital; University of Ottawa

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2022
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): June 1, 2023

Study Registration Dates

• First Submitted: November 29, 2021
• First Submitted That Met QC Criteria: November 29, 2021
• First Posted (Actual): December 10, 2021

Study Record Updates

• Last Update Posted (Actual): December 10, 2021
• Last Update Submitted That Met QC Criteria: November 29, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Synovitis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Protein Kinase Inhibitors; Janus Kinase Inhibitors; Adalimumab; Upadacitinib
• Other Study ID Numbers: 20210654-01H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No