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

NCT06003283 | Recruiting Phase 4

• 1 other identifier: S67309
• Study Type: interventional
• Target: 134
• Locations: 1 country
• Sites: 7

Brief Summary

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)

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid arthritis; Rituximab; Tapering; Disease impact

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Comparison of disease activity in both study arms, measured using the Disease Activity Score in 28 joints - C-reactive protein (DAS28-CRP)

  Over 2 years (104 weeks)

• Comparison of disease activity in both study arms, measured using the Simplified Disease Activity Index (SDAI)

  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)

  Over 2 years (104 weeks)

Other Outcomes (9)

• Comparison of functional status in both study arms, measured using the Health Assessment Questionnaire - Disability Index (HAQ-DI)

  Over 2 years (104 weeks)

• Self-efficacy in both study arms, measured using the Arthritis Self-Efficacy Scale (ASES)

  Over 2 years (104 weeks)

• Pain in both study arms, measured using a Visual Analogue Scale (VAS) completed by the patient

  Over 2 years (104 weeks)

Study Arms (2)

Tapering of rituximab based on disease activity guided dose reduction

EXPERIMENTAL

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

Tapering of rituximab based on interval prolongation

ACTIVE COMPARATOR

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

Interventions

Rituximab DRUG

IV rituximab

Also known as: MabThera, Truxima, Ruxience, Rixathon

Tapering of rituximab based on disease activity guided dose reduction; Tapering of rituximab based on interval prolongation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead
• Fonds voor Wetenschappelijk Reumaonderzoek (FWRO): collaborator

Study Sites (7)

ZNA Jan Palfijn

Merksem, Antwerpen, 2170, Belgium

NOT YET RECRUITING

Cliniques Universitaires Saint-Luc Bruxelles

Brussels, Brussels Capital, 1000, Belgium

NOT YET RECRUITING

Reumacentrum Genk

Genk, Limburg, 3600, Belgium

RECRUITING

ReumaClinic Genk

Genk, Limburg, 3600, Belgium

RECRUITING

OLV Aalst

Aalst, Oost-Vlaanderen, 9300, Belgium

RECRUITING

RZ Heilig Hart

Leuven, Vlaams-Brabant, 3000, Belgium

RECRUITING

University Hospitals Leuven (UZ Leuven)

Leuven, Vlaams-Brabant, 3000, Belgium

RECRUITING

Related Publications (1)

• De Meyst E, Bertrand D, Joly J, Doumen M, Marchal A, Thelissen M, Neerinckx B, Westhovens R, Verschueren P. Treat-to-target fixed dose rituximab retreatment versus fixed interval retreatment with disease activity-guided rituximab dose optimisation for patients with rheumatoid arthritis: study protocol for a multicentre randomised controlled superiority trial focusing on long-term disease impact (RITUXERA). Trials. 2024 Oct 15;25(1):681. doi: 10.1186/s13063-024-08542-7.

  PMID: 39407334 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Patrick Verschueren, MD, PhD

  University Hospitals Leuven/KU Leuven

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Patrick Verschueren, MD, PhD

CONTACT

016342541; patrick.verschueren@uzleuven.be

Johan Joly, MSc

CONTACT

016340258; johan.joly@uzleuven.be

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open label multicenter pragmatic randomized controlled superiority trial. Patients will be 1:1 randomized to either the experimental arm or the active comparator arm. Study visits are scheduled every 12 weeks (3 months). Recruitment period: 1 year. Trial duration: 2 years.

Study Record Dates

• First Submitted: July 19, 2023
• First Posted: August 21, 2023
• Study Start: January 9, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: May 31, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

BE (7)