Screening for Flare After b/tsDMARD Discontinuation in Rheumatoid Arthritis

Screening for Flare After Discontinuation of Biological/Targeted Synthetic Disease Modifying Anti-rheumatic Drug (b/tsDMARD) in Rheumatoid Arthritis

To evaluate whether stringent follow-up consisting of combined laboratory and ultrasound surveillance is superior to clinical monitoring alone to maintain clinical remission in rheumatoid arthritis.

Study Overview

• Status: Not yet recruiting
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Other: Discontinuation of biological/targeted synthetic disease modifying anti-rheumatic drug (b/tsDMARD)

Detailed Description

Randomized, controlled, parallel-group, multi-centre study in which patients with rheumatoid arthritis treated with biological/targeted synthetic disease modifying antirheumatic drug (b/tsDMARD) in mono- or combination therapy with conventional synthetic disease modifying antirheumatic drug (csDMARD) in a stable dosage and interval for ≥6 months with low disease activity or remission will receive an power Doppler musculoskeletal ultrasound examination (PDUS) and monitoring of C-reactive protein (CRP) levels at baseline and several timepoints within a 24 month study period (primary endpoint) and within a 48 month long-term extension. At baseline, b/tsDMARD medication will be withdrawn in all patients, who will be randomized in a 1:1 ratio in an "Assisted monitoring" (arm A) or a "Clinical monitoring" (arm B) arm respectively. Further stratification for remission vs. low disease activity and mono- vs combination therapy will be implemented in the randomisation process. In arm A, CRP and PDUS information will be made available to the clinical assessors who, at each time-point will use this information along with that from clinical examination, to identify patients experiencing recurrence of inflammation which will then be counted as subclinical flare according to predefined criteria. In arm B the results of CRP and PDUS will be recorded but will not be made available to the clinical assessor who will have to identify clinical flares according to predefined criteria based on information from the clinical examination only.

• Study Type: Interventional
• Enrollment (Anticipated): 85
• Phase: Not Applicable

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:

Patients with rheumatoid arthritis classified by the American College of Rheumatology/European League Against Rheumatism classification criteria

• biological disease-modifying anti-rheumatic drug (bDMARD) or targeted synthetic disease-modifying anti-rheumatic drug (tsDMARD) treatment in monotherapy or in combination therapy with conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) in a stable dosage and interval for ≥6 months. Previous extension of bDMARD or tsDMARD interval will also be accepted. bDMARDs and tsDMARDs will include all currently available originator and biosimilar compounds, with the exception of rituximab and its biosimilar compounds
• No swollen joint by 28-joint count at baseline, and screening
• C-reactive protein of ≤0.5mg/dL at baseline AND history of C-reactive protein >0,5mg/dl related to rheumatoid arthritis activity
• Clinical disease activity index ≤10
• Shared decision between patient and physician to attempt b/tsDMARD withdrawal
• Willing and able to understand and follow the study procedures
• Written informed consent
• Female and male subjects aged ≥ 18 years

Exclusion Criteria:

• History of or current extra-articular manifestation of rheumatoid arthritis, with exception of rheumatoid nodules
• Systemic glucocorticoid treatment in the past 3 months
• Intraarticular injection with glucocorticoids in the past 1 month
• Joint replacement surgery other than total knee or hip arthroplasty or complete joint destruction
• Power Doppler signal ≥2 in any assessed joint and/or tendon at screening or baseline

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Assisted monitoring; In the Assisted monitoring arm, C-reactive protein and musculoskeletal ultrasound information will be made available to the clinical assessors who, at each time-point will use this information, along with information from the clinical examination, to identify patients experiencing recurrence of inflammation which will then be counted as subclinical flare according to predefined criteria.	Other: Discontinuation of biological/targeted synthetic disease modifying anti-rheumatic drug (b/tsDMARD); The biological/targeted synthetic disease modifying anti-rheumatic drug will be discontinued in both arms at baseline; Other Names: b/tsDMARD: Adalimumab, Infliximab, Golimumab, Certolizumab pegol, Tocilizumab, Sarilumab, Etanercept, Anakinra, Filgotinib, Updacitinib, Tofacitinib, Baricitinib
Other: Clinical monitoring; In the Clinical monitoring arm, the results of C-reactive protein and musculoskeletal ultrasound information will be recorded but will not be made available to the clinical assessor who at each time-point will make the decision on whether the patient is experiencing or has experienced a clinical flare according to predefined criteria based on information from the clinical examination.	Other: Discontinuation of biological/targeted synthetic disease modifying anti-rheumatic drug (b/tsDMARD); The biological/targeted synthetic disease modifying anti-rheumatic drug will be discontinued in both arms at baseline; Other Names: b/tsDMARD: Adalimumab, Infliximab, Golimumab, Certolizumab pegol, Tocilizumab, Sarilumab, Etanercept, Anakinra, Filgotinib, Updacitinib, Tofacitinib, Baricitinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects without a clinical flare until week 24	Proportion of subjects without a clinical flare	week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects without a clinical flare	Proportion of subjects without a clinical flare	week 48
Time to clinical flare (days)	Time to clinical flare (days)	study period
28 swollen joint count	28 swollen joint count, scale 0 (best) - 28 (worse)	week 24
28 tender joint count	28 tender joint count, scale 0 (best) - 28 (worse)	week 24
Proportion of subjects with a clinical flare in the assisted monitoring arm vs. clinical monitoring arm, the latter stratified according to b/tsDMARD reinitiation	Proportion of subjects with a clinical flare in the assisted monitoring arm vs. clinical monitoring arm, the latter stratified according to b/tsDMARD reinitiation	week 24
Proportion of patients in low disease activity or remission based on simplified disease activity index	Proportion of patients in low disease activity or remission based on simplified disease activity index	week 24
Proportion of patients in low disease activity or remission based on simplified disease activity index	Proportion of patients in low disease activity or remission based on simplified disease activity index	week 48
Patient's global assessment	Patient's global assessment, scale 0 (best) - 100 (worst)	week 24
Evaluator's global assessment	Evaluator's global assessment, scale 0 (best) - 100 (worst)	week 24
C-reactive protein	C-reactive protein, scale 0 (best) - infinite (worst)	week 24
Radiographic progression	change in Sharp Van der Heijde score, scale 0 (best) - 488 (worse)	at week 48 weeks from baseline
Health Assessment Questionnaire Disability Index	Health Assessment Questionnaire Disability Index, scale 0 (best) - 3.0 (worse)	week 24
World Health Organization Quality of Life Questionnaire	World Health Organization Quality of Life Questionnaire, scale 0 (worse) - 100 (best)	week 24
Morning stiffness	Morning joint stiffness, (minutes), scale 0 (best) - infinite (worst)	week 24
Fatigue	Fatigue, visual analogue scale, scale 0 (worse) - 100 (best)	week 24

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Collaborators: Medical University of Graz; Medical University Innsbruck; Hospital Hietzing; Krankenhaus Bruneck

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2022
• Primary Completion (Anticipated): September 1, 2024
• Study Completion (Anticipated): September 1, 2024

Study Registration Dates

• First Submitted: November 2, 2021
• First Submitted That Met QC Criteria: November 12, 2021
• First Posted (Actual): November 15, 2021

Study Record Updates

• Last Update Posted (Actual): November 15, 2021
• Last Update Submitted That Met QC Criteria: November 12, 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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Dermatologic Agents; Protein Kinase Inhibitors; Tumor Necrosis Factor Inhibitors; Etanercept; Adalimumab; Infliximab; Golimumab; Certolizumab Pegol; Tofacitinib; Antirheumatic Agents
• Other Study ID Numbers: 1389/2020

Drug and device information, study documents

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