Clinical trial NCT06003283: Tapering of Rituximab Based on Interval Prolongation Compared to Disease Activity-guided Dose Reduction in Patients With Rheumatoid Arthritis
Official title: Tapering of Rituximab Based on Interval Prolongation Compared to Disease Activity-guided Dose Reduction in Patients With Rheumatoid Arthritis: The RITUXERA Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid arthritis
Rituximab
Tapering
Disease impact
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
Collaborators: name: Fonds voor Wetenschappelijk Reumaonderzoek (FWRO)
First posted: 2023-08-21
Enrollment: 134
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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)


Eligibility criteria: 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.

Primary outcomes:
measure: Comparison of disease impact in both study arms, measured using the Rheumatoid Arthritis Impact of Disease (RAID) questionnaire
timeFrame: Over 2 years (104 weeks)
Secondary outcomes:
measure: Comparison of disease activity in both study arms, measured using the Disease Activity Score in 28 joints - C-reactive protein (DAS28-CRP)
timeFrame: Over 2 years (104 weeks)
measure: Comparison of disease activity in both study arms, measured using the Simplified Disease Activity Index (SDAI)
timeFrame: Over 2 years (104 weeks)
measure: Comparison of cumulative dose of rituximab in both study arms
timeFrame: Over 2 years (104 weeks)
measure: Comparison of cumulative dose of glucocorticoids in both study arms
timeFrame: Over 2 years (104 weeks)
measure: 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)
timeFrame: Over 2 years (104 weeks)
measure: Comparison of loss of disease control in both study arms
timeFrame: Over 2 years (104 weeks)
measure: Comparison of rituximab drug retention rate in both study arms
timeFrame: Over 2 years (104 weeks)
measure: Proportion of patients tapering rituximab below 1000 mg in the experimental arm
timeFrame: Over 2 years (104 weeks)
measure: Mean/median interval between rituximab administrations in the active comparator group
timeFrame: Over 2 years (104 weeks)
measure: Comparison of serious adverse events/reactions rates in both study arms.
timeFrame: Over 2 years (104 weeks)
measure: Comparison of serious infections rate in both study arms.
timeFrame: Over 2 years (104 weeks)
Other outcomes:
measure: Comparison of functional status in both study arms, measured using the Health Assessment Questionnaire - Disability Index (HAQ-DI)
timeFrame: Over 2 years (104 weeks)
measure: Self-efficacy in both study arms, measured using the Arthritis Self-Efficacy Scale (ASES)
timeFrame: Over 2 years (104 weeks)
measure: Pain in both study arms, measured using a Visual Analogue Scale (VAS) completed by the patient
timeFrame: Over 2 years (104 weeks)
measure: Fatigue in both study arms, measured using a Visual Analogue Scale (VAS) completed by the patient
timeFrame: Over 2 years (104 weeks)
measure: Patient global assessment (PGA) of disease in both study arms, measured using a Visual Analogue Scale (VAS) completed by the patient
timeFrame: Over 2 years (104 weeks)
measure: Cluster of Differentiation (CD) 19+ and Memory B cell counts in both study arms
timeFrame: Over 2 years (104 weeks)
measure: Immunoglobulin (Ig) counts (IgG, IgA and IgM) in both study arms
timeFrame: Over 2 years (104 weeks)
measure: Professional and vocational participation in both study arms, calculated using the Work Productivity and Activity Impairment questionnaire: General Health (WPAI:GH)
timeFrame: Over 2 years (104 weeks)
measure: Health utility index in both study arms, calculated using the summary index score of the EuroQol - 5 dimensions (EQ-5D) questionnaire
timeFrame: Over 2 years (104 weeks)
Locations:
city: Merksem
country: Belgium
facility: ZNA Jan Palfijn
state: Antwerpen
city: Genk
country: Belgium
facility: Reumacentrum Genk
state: Limburg
city: Genk
country: Belgium
facility: ReumaClinic Genk
state: Limburg
city: Aalst
country: Belgium
facility: OLV Aalst
state: Oost-Vlaanderen
city: Leuven
country: Belgium
facility: RZ Heilig Hart
state: Vlaams-Brabant
city: Leuven
country: Belgium
facility: University Hospitals Leuven (UZ Leuven)
state: Vlaams-Brabant
city: Brussel
country: Belgium
facility: Cliniques Universitaires Saint-Luc Bruxelles
Study officials:
affiliation: University Hospitals Leuven/KU Leuven
name: Patrick Verschueren, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: