Tapering of Rituximab Based on Interval Prolongation Compared to Disease Activity-guided Dose Reduction in Patients With Rheumatoid Arthritis (RITUXERA)

Tapering of Rituximab Based on Interval Prolongation Compared to Disease Activity-guided Dose Reduction in Patients With Rheumatoid Arthritis: The RITUXERA Trial

The goal of this open label multicenter randomized controlled pragmatic superiority trial is to investigate the optimal treatment/tapering strategy with rituximab for patients with rheumatoid arthritis.

The main questions it aims to answer are:

• What is the optimal treatment/tapering strategy for rituximab in patients with rheumatoid arthritis in terms of reducing patient reported disease impact?
• What is the optimal treatment/tapering strategy for rituximab in patients with rheumatoid arthritis in terms of therapeutic efficacy?

Participants will be randomized to one of two study arms:

• Tapering based on disease-activity guided dose reduction (experimental arm)
• Tapering based on interval prolongation (active comparator arm)

Study Overview

• Status: Recruiting
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Rituximab

• Study Type: Interventional
• Enrollment (Estimated): 134
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Patrick Verschueren, MD, PhD; Phone Number: +32 016342541; Email: patrick.verschueren@uzleuven.be
• Study Contact Backup: Name: Johan Joly, MSc; Phone Number: +32 016340258; Email: johan.joly@uzleuven.be

Study Locations

• Belgium
  • Brussel, Belgium, 1000
    • Not yet recruiting
    • Cliniques Universitaires Saint-Luc Bruxelles
    • Contact: Patrick Durez, MD, PhD
  • Antwerpen
    • Merksem, Antwerpen, Belgium, 2170
      • Not yet recruiting
      • ZNA Jan Palfijn
      • Contact: Alla Ishchenko, MD
  • Limburg
    • Genk, Limburg, Belgium, 3600
      • Recruiting
      • Reumacentrum Genk
      • Contact: Philip Remans, MD, PhD
    • Genk, Limburg, Belgium, 3600
      • Recruiting
      • ReumaClinic Genk
      • Contact: Johan Vanhoof, MD
  • Oost-Vlaanderen
    • Aalst, Oost-Vlaanderen, Belgium, 9300
      • Recruiting
      • OLV Aalst
      • Contact: Tom Zwaenepoel, MD
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • Recruiting
      • RZ Heilig Hart
      • Contact: Veerle Taelman, MD
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • Recruiting
      • University Hospitals Leuven (UZ Leuven)
      • Contact: Patrick Verschueren, MD, PhD
      • Contact: Johan Joly, MSc
      • Sub-Investigator: Elias De Meyst, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Able and willing to give written informed consent and participate in the study before any study procedure.
• Age ≥ 18 years.
• Understanding and able to write in Dutch or French.
• Diagnosis of rheumatoid arthritis according to the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Classification Criteria for rheumatoid arthritis.
• Previous response to rituximab, defined as a minimum of one successful rituximab cycle (= a moderate/good EULAR response 16 weeks after the first administration of rituximab).
• Current treatment with rituximab.
• Need for a subsequent rituximab cycle according to the Belgian reimbursement criteria for the use of rituximab in rheumatoid arthritis (DAS28 score ≥3.2).
• Stable dose of methotrexate or other conventional synthetic disease-modifying antirheumatic drugs (DMARDs) 4 weeks prior to baseline.

Exclusion Criteria:

• Current treatment with another biological DMARD than rituximab.
• Current treatment with a targeted synthetic DMARD.
• Pregnancy or pregnancy wish.
• Presence of an absolute contraindication to treatment with rituximab, according to the label of rituximab and according to medical judgement.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tapering of rituximab based on disease activity guided dose reduction; Treatment with rituximab every 6 months (24 weeks) with dosing based on disease activity, measured by the DAS28-CRP. DAS28-CRP ≤ 3.2: dose reduction according to the following sequence: 1 x 1000 mg IV (maximum), 1 x 500 mg IV, 1 x 200 mg IV (minimum). DAS28-CRP > 3.2: administration of previously effective dose.	Drug: Rituximab; IV rituximab; Other Names: MabThera; Ruxience; Truxima; Rixathon
Active Comparator: Tapering of rituximab based on interval prolongation; Treatment with fixed dose of rituximab (1 x 1000 mg IV) if DAS28-CRP ≥ 3.2 AND interval of at least 6 months (24 weeks) since previous administration of rituximab.	Drug: Rituximab; IV rituximab; Other Names: MabThera; Ruxience; Truxima; Rixathon

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of disease impact in both study arms, measured using the Rheumatoid Arthritis Impact of Disease (RAID) questionnaire	RAID questionnaire score range: 0 - 10, with higher scores indicating worse status.	Over 2 years (104 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of disease activity in both study arms, measured using the Disease Activity Score in 28 joints - C-reactive protein (DAS28-CRP)	Main secondary outcome. DAS28-CRP range: 0 - ..., with higher values indicating higher disease activity.	Over 2 years (104 weeks)
Comparison of disease activity in both study arms, measured using the Simplified Disease Activity Index (SDAI)	SDAI range: 0 - ..., with higher values indicating higher disease activity.	Over 2 years (104 weeks)
Comparison of cumulative dose of rituximab in both study arms		Over 2 years (104 weeks)
Comparison of cumulative dose of glucocorticoids in both study arms		Over 2 years (104 weeks)
Proportion of patients in both study arms achieving a good or moderate European League Against Rheumatism (EULAR) treatment response after administration of rituximab, over a period of 2 years (104 weeks)	A good EULAR response is defined as a decrease in Disease Activity Score in 28 joints - C-reactive protein (DAS28-CRP) > 1.2 and a present DAS-CRP ≤ 3.2. A moderate EULAR response is defined as a decrease in DAS28-CRP > 0.6 to ≤ 1.2 and a present DAS28-CRP ≤ 5.1, or a decrease in DAS28-CRP > 1.2 and a present DAS28-CRP > 3.2. Treatment responses will be evaluated 12 weeks after every administration of rituximab.	Over 2 years (104 weeks)
Comparison of loss of disease control in both study arms	Loss of disease control is defined as achieving a Disease Activity Score in 28 joints - C-reactive protein (DAS28-CRP) > 3.2 with previous DAS28-CRP ≤ 3.2.	Over 2 years (104 weeks)
Comparison of rituximab drug retention rate in both study arms	Defined as the percentage of patients remaining on treatment with rituximab over time.	Over 2 years (104 weeks)
Proportion of patients tapering rituximab below 1000 mg in the experimental arm		Over 2 years (104 weeks)
Mean/median interval between rituximab administrations in the active comparator group		Over 2 years (104 weeks)
Comparison of serious adverse events/reactions rates in both study arms.	An adverse event or adverse reaction is considered serious if it leads to inpatient hospitalization or prolongation of existing hospitalization, if it results in persistent or significant disability or incapacity, if it results in a life-threatening experience (meaning that the subject was at risk of death), or if it results in death.	Over 2 years (104 weeks)
Comparison of serious infections rate in both study arms.	An infection is considered serious if it leads to inpatient hospitalization or prolongation of existing hospitalization, if it results in persistent or significant disability or incapacity, if it results in a life-threatening experience (meaning that the subject was at risk of death), or if it results in death.	Over 2 years (104 weeks)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of functional status in both study arms, measured using the Health Assessment Questionnaire - Disability Index (HAQ-DI)	HAQ-DI score range: 0 - 3, with higher scores indicating worse functional status.	Over 2 years (104 weeks)
Self-efficacy in both study arms, measured using the Arthritis Self-Efficacy Scale (ASES)	ASES score range: 11 - 110, with higher scores indicating higher perceived self-efficacy.	Over 2 years (104 weeks)
Pain in both study arms, measured using a Visual Analogue Scale (VAS) completed by the patient	VAS pain range: 0 - 100, with higher values indicating higher pain	Over 2 years (104 weeks)
Fatigue in both study arms, measured using a Visual Analogue Scale (VAS) completed by the patient	VAS fatigue range: 0 - 100, with higher values indicating more fatigue.	Over 2 years (104 weeks)
Patient global assessment (PGA) of disease in both study arms, measured using a Visual Analogue Scale (VAS) completed by the patient	VAS PGA range: 0 - 100, with higher values indicating worse disease.	Over 2 years (104 weeks)
Cluster of Differentiation (CD) 19+ and Memory B cell counts in both study arms	Determined at baseline, before administration of rituximab and at year 2 (104 weeks) in both study arms.	Over 2 years (104 weeks)
Immunoglobulin (Ig) counts (IgG, IgA and IgM) in both study arms	Determined at baseline, before administration of rituximab and at year 2 (104 weeks) in both study arms.	Over 2 years (104 weeks)
Health utility index in both study arms, calculated using the summary index score of the EuroQol - 5 dimensions (EQ-5D) questionnaire	Summary index score range: less than 0 (health state worse than dead, 0 being the value of a health state equivalent to death) to 1 (full health).	Over 2 years (104 weeks)
Professional and vocational participation in both study arms, calculated using the Work Productivity and Activity Impairment questionnaire: General Health (WPAI:GH)	The WPAI:GH calculates the percent work time missed due to health (range 0-100, higher numbers indicating more missed work time), the percent impairment while working due to health (range 0-100, higher numbers indicating higher impairment), the percent overall work impairment due to health (range 0-100, higher numbers indicating higher impairment), and the percent activity impairment due to health (range 0-100, higher numbers indicating higher impairment).	Over 2 years (104 weeks)

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Collaborators: Fonds voor Wetenschappelijk Reumaonderzoek (FWRO)
• Investigators: Principal Investigator: Patrick Verschueren, MD, PhD, University Hospitals Leuven/KU Leuven

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: July 19, 2023
• First Submitted That Met QC Criteria: August 17, 2023
• First Posted (Actual): August 21, 2023

Study Record Updates

• Last Update Posted (Actual): May 31, 2025
• Last Update Submitted That Met QC Criteria: May 26, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Rituximab; Rheumatoid arthritis; Tapering; Disease impact
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Arthritis; Arthritis, Rheumatoid; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Rituximab
• Other Study ID Numbers: S67309

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
• product manufactured in and exported from the U.S.: No