Relationship Between T LYmphocytes Depletion and Clinical Response to RITUXimab in Rheumatoid Arthritis (LYRITUX)

NCT02304354 | Completed Phase 3

• 4 other identifiers: PHRI13-JM/LYRITUX2014-000859-912014-R24140896A-32
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 8

Brief Summary

Rituximab, an anti CD-20 monoclonal antibody targeting B lymphocytes is prescribed in rheumatoid arthritis (RA) patients refractory to TNF alpha antagonists. According to previous studies, 25 to 50% of patients have an insufficient or absence of response to rituximab at week 24. In a recent retrospective study, a CD4+ T-lymphocytes depletion was observed after a first course of rituximab in RA patients. The absolute CD4+ number at week 12 was 37% (±33) of the baseline value, leading to \< 200 cells/µL in 5% of patients. Interestingly the absence of CD4+ T-lymphocytes depletion was observed in clinical non-responders, suggesting the involvement of T-lymphocytes in the mechanism of action of rituximab. So far no prospective study have supported the usefulness of lymphocyte phenotyping, in particular T-lymphocytes, to monitor rituximab-treated RA patients.

Conditions

Rheumatoid Arthritis

Keywords

rheumatoid arthritis; T lymphocytes; rituximab

Outcome Measures

Primary Outcomes (2)

• DAS28

  Disease Activity Score on 28 joints (DAS28) is a composite score that comprise tender joints count, swollen joints count, patient's disease activity on visual analog scale and erythrocyte sedimentation rate. DAS28 will be measured at baseline, week 2, week 4, week 16 and at the end of the study (i.e. between week 24 and week 48).

  up week 48

• T-lymphocyte count

  T-lymphocyte count will be measured at baseline, week 2, week 4, week 16 and at the end of the study (i.e. between week 24 and week 48).

  up to week 48

Secondary Outcomes (8)

• C reactive Protein (CRP)

  Baseline up to 48 weeks

• Immunoglobulines G

  Baseline up to 48 weeks

• Cytokine profile

  Baseline up to 48 weeks

• Occurrence of infections

  Baseline up to 48 weeks

• Pharmacokinetics (Systemic Clearance and central volume of distribution)

  Baseline up to 48 weeks

Study Arms (1)

Rituximab

EXPERIMENTAL

two intravenous infusions of 1000 mg with a two-week interval between them

Drug: Rituximab

Interventions

Rituximab DRUG

For rheumatoid arthritis, MabThera is given as two intravenous infusions of 1000 mg with a two-week interval between them. Patients usually respond to treatment within 16 to 24 weeks of initial treatment. After 24 weeks, treatment can be repeated depending on the patient's response.

Also known as: MabThera

Rituximab

Eligibility Criteria

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

You may qualify if:

• RA according to the American College of Rheumatology (ACR) criteria
• Treatment with adalimumab in accordance to the SPC
• Disease modifying anti rheumatic drugs (DMARDs) stable 4 weeks before enrollment and during 16 weeks.
• Signed consent

You may not qualify if:

• No anti TNF-alpha failure or contraindication
• Previous adalimumab treatment
• Contraindication to adalimumab, methylprednisolone or methotrexate (when used in combination with adalimumab)
• methotrexate-naive patient
• Any hematologic disease affecting the lymphocytes (in particular lymphomas)
• Any osteo-articular disease which could interfere with the interpretation of the influence of the rituximab on RA

Sponsors & Collaborators

• University Hospital, Tours: lead

Study Sites (8)

Rhumatologie, CHRU de BREST

Brest, 29609, France

Location

Rhumatologie, CHD LA ROCHE SUR YON

La Roche-sur-Yon, 85925, France

Location

Rhumatologie, CHR du MANS

Le Mans, 72037, France

Location

Rhumatologie, CHRU de NANTES

Nantes, 44093, France

Location

Rhumatologie / IPROS, CHR d'ORLEANS

Orléans, 45000, France

Location

Rhumatologie, CHRU de POITIERS

Poitiers, 86021, France

Location

Rhumatologie, CHRU de ROUEN

Rouen, 76031, France

Location

Rhumatologie, CHRU de TOURS

Tours, 37044, France

Location

Related Publications (1)

• Melet J, Mulleman D, Goupille P, Ribourtout B, Watier H, Thibault G. Rituximab-induced T cell depletion in patients with rheumatoid arthritis: association with clinical response. Arthritis Rheum. 2013 Nov;65(11):2783-90. doi: 10.1002/art.38107.

  PMID: 23918413 BACKGROUND

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

• Denis MULLEMAN, MD-PhD

  CHRU de TOURS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2014
• First Posted: December 1, 2014
• Study Start: March 9, 2015
• Primary Completion: April 9, 2019
• Study Completion: December 18, 2019
• Last Updated: May 6, 2021

Record last verified: 2021-05

Locations

FR (8)