Rheumatoid Arthritis (RA)
Conditions
Keywords
pharmacological biomarker, rituximab, retreatment, low dose
Brief summary
Evaluation of the prediction of clinical response to rituximab at a dose of 1000 mg once using a pharmacological model including several pharmacokinetic and pharmacodynamic parameters.
Detailed description
Rituximab is an anti-CD20 monoclonal antibody which is effective in RA. The dose indicated in the marketing authorisation is 1000 mg twice per cycle. However, rituximab is associated with adverse events, and more specifically the risk of infection, which seems to be dose-dependent. The dose of 1000 mg once a cycle has been evaluated and is non-inferior for maintenance treatment. Lower doses than 1000 mg once could also be sufficient, but there is a lack of predictive criteria to guide clinicians in their search for the minimal effective dose for a given patient. In our center, a PK-PD model including several parameters (body surface area, serum IgG concentration, residual rituximab concentrations and CD4+ T-cell count) has enabled to quantify part of the concentration-effect relationship of rituximab in this indication and at standard dose (1000 mg twice at 15-day intervals). On the basis of this model, a model for predicting clinical response has been developed.with reliable prediction of clinical response. The aim of this study is to apply this model to patients receiving low-dose rituximab (1000 mg once per cycle) and to evaluate the prediction of clinical response to low-dose rituximab using this model. Correlation and coefficient of determination between DAS28-CRP observed 6 months after a second low-dose cycle and DAS-28 predicted by a PK-PD model taking into account gender, body surface area, IgG concentration, rituximab concentration and CD4 T-cell count.
Interventions
None listed
Sponsors
University Hospital, Tours
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
. Age ≥ 18 years * Diagnosis of rheumatoid arthritis meeting ACR/EULAR 2010 criteria. * Candidates for a Low Dose regimen: on standard dose rituximab and with a good clinical response according to the referring rheumatologist. No maximum duration of use of standard-dose rituximab has been defined. * In the case of co-prescription of csDMARDs (Methotrexate, Leflunomide, Salazopyrine, Plaquenil), the dose must have been stable for 3 months. * If corticosteroids are co-prescribed, the dose should be ≤ 10 mg/d and stable for 3 months.
Exclusion criteria
* Other associated targeted disease-modifying therapy * Sjögren's syndrome or other associated inflammatory rheumatism * Fibromyalgia or other pathology having an impact on the assessment of disease activity * Any active haematological disease affecting lymphocytes (chronic lymphocytic leukaemia, Hodgkin's and non-Hodgkin's lymphomas, lymphoplasmacytic lymphoma, T lymphoma). * Opposition to data processing * No inclusion of persons covered by articles L. 1121-5 to L. 1121-8 and L. 1122-1-2 of the Public Health Code (e.g. minors, protected adults, etc.).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Observed Disease Activity Score(DAS) 28-CRP | 6 months after a second low-dose cycle | DAS28-CRP measured by the clinician 6 months after the second cycle of rituximab |
| Calculated DAS28-CRP | 6 months after a second low-dose cycle | DAS28-CRP calculated 6 months after the second cycle of rituximab by a PK-PD model, taking into account gender, body surface area in m2, IgG concentration, rituximab concentration and CD4+ T-cell count |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prevalence observed DAS28-CRP | 3 months and 6 months of the first and second cycle of low-dose rituximab | * Percentage of patients with a DAS28-CRP \< 3.2 at 3 months and 6 months of the first and second cycle of low-dose rituximab * Percentage of patients with a DAS28-CRP \<2.6 at 3 months and 6 months of the first and second cycle of low-dose rituximab |
| Description of events | From enrolment to 12 months | Description of moderate and severe infectious events. Description of adverse events occurring during infusions |
| prevalence calculated DAS28-CRP | 6 months of the second cycle of low-dose rituximab | * percentage of patients with a predicted DAS 28 CRP \< 3.2 at 6 months of the second cycle of low-dose rituximab * percentage of patients with a predicted DAS 28 CRP \< 2.6 at 6 months of the second cycle of low-dose rituximab |
| CD4 T cell count | 6 months of a second cycle of low dose rituximab. | T cell count (\< 500/mm3) |
| immunoglobulin G level | 6 months of a second cycle of low dose rituximab. | immunoglobulin G level (\< 6 g/L) |
Countries
France
Contacts
CONTACTSimon BRUNET
Outcome results
None listed