Pharmacokinetic Study of Rituximab Induction Regimen in ANCA-associated Vasculitis

Study Overview
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Brief Summary
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The aim of the investigators' study is to evaluate whether monitoring serum rituximab levels could be an interesting tool in the follow-up of ANCA-associated vasculitis patients. All consecutive patients, hospitalized for a new diagnosis of ANCA-associated vasculitis or the relapse of a known ANCA-associated vasculitis, in which the decision to start an induction regimen with rituximab has been taken, will be included. Serum rituximab levels (along with serum anti-rituximab antibodies levels) will be determined (at M+1 and M+3) and the correlation with clinical outcome at M+6 will be analyzed.

Official Title
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Pharmacokinetic Study of Rituximab Induction Regimen in ANCA-associated Vasculitis : a Predictive Factor of Clinical Outcome? (MONITUX)

Conditions
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Granulomatosis, Wegener's, Microscopic Polyangiitis

Intervention / Treatment
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* Other: blood specimen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years Granulomatosis with polyangiitis or microscopic polyangiitis (according to Chapel Hill criterions), with or without detectable ANCA Decision taken to start an induction regimen with rituximab Informed and having signed the study consent form If of child-bearing potential, female patients will have use an effective method of contraception during RTX (rituximab) treatment and in the 12 months following RTX treatment stop no-breast-feeding during RTX treatment and in the 12 months following RTX treatment stop Exclusion Criteria: Other primary or secondary systemic vasculitis Incapacity or refusal to sign the informed consent form Incapacity or refusal to adhere to treatment or perform the follow-up examinations required by the study Allergy, documented hypersensitivity or contraindication to the medications used in the present study (corticosteroids, rituximab) severe active infection Patient with severe heart failure (stage NYHA IV) or any other unstable heart disease Pregnancy, except for cases where the expected benefit oj treatment seems to surpass the potential risks Patients with active hepatitis B Any live vaccine within four weeks prior to the first infusion of RTX

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Rituximab<br>a classical induction regimen with rituximab (decision taken before inclusion), implying an infusion of 375mg/m² per week, for 4 consecutive weeks (from week -3 until week 0) with blood specimen. | Other: blood specimen<br>* blood specimen for serum rituximab level and serum anti-rituximab level at M1 and M3 after stop of induction rituximab treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum rituximab levels | rituximab level comparison between number of non-responders and number of responders after rituximab induction regimen. The number of non-responders is defined by a Birmingham Vascularitis Activity score > 0, 6 months after stop of induction regimen | 1 month after stop of rituximab induction regimen | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum rituximab levels | rituximab level comparison between number of non-responders and number of responders after rituximab induction regimen. The number of non-responders is defined by a Birmingham Vascularitis Activity score > 0 six months after stop of induction regimen | 3 months after stop of rituximab induction regimen | 
| serum rituximab levels | rituximab level comparison between number of non-responders and number of responders after rituximab induction regimen. The number of non-responders is defined by a Birmingham Vascularitis Activity score > 0 six months after stop of induction regimen | 6 months after stop of rituximab induction regimen | 
| serum anti-rituximab antibodies | serum anti-rituximab antibodies level comparison between number of non-responders and number of responders after rituximab induction regimen. The number of non-responders is defined by a Birmingham Vascularitis Activity score > 0 six months after stop of induction regimen | 1 month after stop of rituximab induction regimen | 
| serum anti-rituximab antibodies | serum anti-rituximab antibodies level comparison between number of non-responders and number of responders after rituximab induction regimen. The number of non-responders is defined by a Birmingham Vascularitis Activity score > 0 six months after stop of induction regimen | 3 months after stop of rituximab induction regimen | 
| serum anti-rituximab antibodies | serum anti-rituximab antibodies level comparison between number of non-responders and number of responders after rituximab induction regimen. The number of non-responders is defined by a Birmingham Vascularitis Activity score > 0 six months after stop of induction regimen | 6 months after stop of rituximab induction regimen | 
| Serum B lymphocytes (CD19+ cells) levels | Serum B lymphocytes (CD19+ cells) levels comparison between number of non-responders and number of responders after rituximab induction regimen. The number of non-responders is defined by a Birmingham Vascularitis Activity score > 0 six months after stop of induction regimen | 1 month after stop of rituximab induction regimen | 
| Serum B lymphocytes (CD19+ cells) levels | Serum B lymphocytes (CD19+ cells) levels comparison between number of non-responders and number of responders after rituximab induction regimen. The number of non-responders is defined by a Birmingham Vascularitis Activity score > 0 six months after stop of induction regimen | 3 months after stop of rituximab induction regimen | 
| Serum B lymphocytes (CD19+ cells) levels | Serum B lymphocytes (CD19+ cells) levels comparison between number of non-responders and number of responders after rituximab induction regimen. The number of non-responders is defined by a Birmingham Vascularitis Activity score > 0 six months after stop of induction regimen | 6 months after stop of rituximab induction regimen | 
| patient number with adverse event | frequency and nature of rituximab-attributed adverse events | from start of induction rituximab regimen until six monthes after stop of induction regimen |