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

NCT ID: NCT02304354

Last Updated: 2021-05-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-09
• Study Completion Date: 2019-12-18

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.

Detailed Description

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, (Edwards, Szczepanski et al. 2004; Cohen, Emery et al. 2006; Emery, Fleischmann et al. 2006) 25 to 50% of patients have an insufficient or absence of response to rituximab at week 24. In the pathogenesis of RA, B and T lymphocytes are tightly linked through the APC fonction and cytokines production of B lymphocytes. At present, a white blood cells count is recommended in routine every 3 months in patients receiving rituximab, since cases of neutropenia have been observed in approximately 8% of patients with lymphoma after treatment. In RA patients, B lymphocytes count before each rituximab course should be done to prevent opportunistic infections (Pham, Fautrel et al. 2008).

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 (Mélet, Mulleman et al. 2013). Moreover, few case reports of RA patients developing opportunist infections in conjunction with CD4+ T-lymphocyte depletion have been published (Teichmann, Woenckhaus et al. 2008; Clifford, Ances et al. 2011). 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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rituximab

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

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: 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.

Interventions

Rituximab

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.

Intervention Type: DRUG

Other Intervention Names

MabThera

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Tours

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Denis MULLEMAN, MD-PhD

Role: PRINCIPAL_INVESTIGATOR

CHRU de TOURS

Locations

Rhumatologie, CHRU de BREST

Brest, , France

Rhumatologie, CHD LA ROCHE SUR YON

La Roche-sur-Yon, , France

Rhumatologie, CHR du MANS

Le Mans, , France

Rhumatologie, CHRU de NANTES

Nantes, , France

Rhumatologie / IPROS, CHR d'ORLEANS

Orléans, , France

Rhumatologie, CHRU de POITIERS

Poitiers, , France

Rhumatologie, CHRU de ROUEN

Rouen, , France

Rhumatologie, CHRU de TOURS

Tours, , France

Countries

France

References

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.

Reference Type: BACKGROUND

PMID: 23918413 (View on PubMed)

Other Identifiers

2014-000859-91

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2014-R24

Identifier Type: OTHER

Identifier Source: secondary_id

140896A-32

Identifier Type: OTHER

Identifier Source: secondary_id

PHRI13-JM/LYRITUX

Identifier Type: -

Identifier Source: org_study_id