Rituximab Treatment in Nephrotic Syndrome ESPN 2009.

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Rituximab Treatment in Nephrotic Syndrome ESPN 2009

Rituximab Chimeric anti-CD20 monoclonal antibody Reduction in B cell proliferation Rx of lymphoma First used in NS patients with ITP or lymphoma NS only a T-cell disease?? Only 73 cases published

French Rituximab study Objectives: To achieve sustained remission in severe SD-NS and avoid toxicity of other steroid-sparing agents To induce remission in SR or cyclosporin-resistant NS patients 100 children 75 analysed 41 > 18 mths follow-up

Rituximab 1-4 injections of 375mg/m² All achieved complete B cell depletion

Duration of Remission Dependent on B cell depletion duration Independent of associated immunosuppression after Ritux (none, MMF, Tac, CyA, Pred)

Long term efficacy 39 patients Mean follow-up 26 mo (18-48) 11 (28%) – No relapse 23 relapsed on reappearance of CD20 cells Most did not relapse after 2 nd injection

Adults with SD NS 9 adults Long term remission: 1/3 remain well 2/3 relapsed, but needed less IS

Rituximab in SR NS Ritux given in nephrotic state Associated IS B-cell depletion not always achieved even after 4 courses Efficacy better in 2° SR, rather than 1°SR NS.

Rituximab: Side effects 1/3 patients experienced Minor Hypotension (7), fever, rash (6) Delayed Severe: 1 death (pulmonary fibrosis) Transient neutropenia (2) Infection (3) Papilloedema (1) Connective tissue disease (1)

Rituximab – Long term rx Number of reinjections? Risk of progressive multifocal leucoencephalopathy (PML)?

Rituximab – conclusions Mechanism of action speculative Immediate effect Better if used in remission Relapses can occur during B cell depletion and at reappearance of B cells Relapses not correlated to B cell count Late effects unclear B cell role in idiopathic NS?