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.

Ottawa Hospital Research Institute40 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Conditions

Interventions

UpadacitinibDRUG

15 mg po daily

AdalimumabDRUG

40 mg sc every other week

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Recruitment Rate

Number of participants recruited to study

Time frame: 1 year

Retention Rate

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

Time frame: 6 months

Secondary Outcomes

Change in 100 mm Pain visual analogue scale (VAS)

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

Time frame: 6 months

Change in McGill Pain Questionnaire (MPQ)

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

Time frame: 6 months

Change in Widespread Pain Index (WPI)

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

Time frame: 6 months

Change in PainDETECT Questionnaire (PDQ)

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

Time frame: 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.

Time frame: 6 months

Change in Swollen Joint Count (44)

Time frame: 6 months

Change in Tender Joint Count (44)

Time frame: 6 months

Change in Physician Global Assessment of Disease Severity

VAS

Time frame: 6 months

Change in Patient Global Assessment of Disease Severity

VAS

Time frame: 6 months

Change in Health Assessment Questionnaire

Time frame: 6 months

American College of Rheumatology (ACR) 20 response

Time frame: 6 months

ACR 50 response

Time frame: 6 months

ACR 70 response

Time frame: 6 months

Change in Erythrocyte Sedimentation Rate

Time frame: 6 months

Change in C-Reactive Protein

Time frame: 6 months

Change in Disease Activity Score (DAS)-28-ESR

Time frame: 6 months

Change in DAS-28-CRP

Time frame: 6 Months

Change in Clinical Disease Activity Index (CDAI)

Time frame: 6 months

Change in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT)

Time frame: 6 months

Change in Insomnia Severity Index (ISI)

Time frame: 6 months

Change in Short Form 36 (SF-36)

Time frame: 6 months

Change in Patient Health Questionnaire (PHQ-9)

Time frame: 6 months

Adverse Events

Time frame: 6 months

Serious Adverse Events

Time frame: 6 months

Drop-out due to Adverse Events

Time frame: 6 months

Central Contacts

Elliot P Hepworth, MD

CONTACT

613-738-8400 elhepworth@toh.ca

Sibel Z Aydin, MD

CONTACT

(613) 738-8400 saydin@toh.ca

Data from ClinicalTrials.gov

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