ESPN 50th Annual Meeting

ESPN 2017


 
Tocilizumab (anti-IL6 receptor) as a potential treatment for Idiopathic nephrotic Syndrome
MARIE MAGNAVACCA 1 CLAIRE DOSSIER 1 VéRONIQUE BAUDOUIN 1 THERESA KWON 1 JULIEN HOGAN 1 GEORGES DESCHENES 1

1- HôPITAL ROBERT-DEBRE
 
Introduction:

 B cell depletion is a recognized treatment of steroid dependant(SDNS) and steroid resistant nephrotic syndrome(SRNS). Interleukine-6(IL-6) is  an attractive target as it promotes B-cell differenciation into antibody-forming plasma cells. We report a pilot series of SRNS and SDNS patients treated with tocilizumab(TCZ), a monoclonal anti IL6-receptor antibody, with Intraveinous Immunoglobulins(IVIg).

Material and methods:

17 patients received an initial treatment combining IVIg(2g/kg) at day 0 and 30 and TCZ(8mg/kg, or 12mg/kg if weight <35kg) at day 15 and 45 followed by TCZ once a month in patients in complete remission(A) or twice a month if proteinuria persisted(B).  Anticalcineurin inhibitors were discontinued 3 months after remission. Treatment objective was a sustained remission after anticalcineurin inhibitors withdrawal and/or after end of the protocol.

Results:

Five SDNS and 12 SRNS were included. Among SRNS, five had tacrolimus-dependant remission and 7 multidrug resistance. All patients but the two youngest had previously received rituximab. Eight patients received schedule (A): tacrolimus was successfully discontinued in 4/6 patients initially under tacrolimus. Sustained remission was observed in three patients, with a follow up after M6 TCZ of 15 months, 2 and 1 months. Nine patients received schedule (B): remission of proteinuria was obtained in 4/9 patients in association with tacrolimus. Tacrolimus was successfully discontinued in one patient. 3 patients are still under TCZ and tacrolimus for longer than 6 months. Immunophenotyping showed no reduction in memory B cell subsets while under TCZ. Reversible leuconeutropenia occurred in 2/17 patients.

Conclusions:

Targeting IL-6 has been modestly efficient in this small pilot series. Effect of IL-6 inhibition on B cells subsets is inconclusive but most patients had received rituximab in the previous months. Longer follow-up is required to assess if it is a valuable treatment option to be discussed in severe NS or as an alternative to B cell depletion.