P0346THE EFFECTS OF RITUXIMAB MAINTENANCE THERAPY ON LUPUS NEPHRITIS

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Abstract Background and Aims Lupus Nephritis (LN) is the organ manifestation with the most severe prognosis in Systemic Lupus Erythematosus (SLE). Treatment options are limited due to partial efficacy, intolerance or side effects; moreover 10% of patients reach ESRD despite treatments. Rituximab (RTX) in LN is recommended as second line drug for induction of the remission after failure of Cyclophosphimide or Mycophenolate Mofetil. We have shown a role for RTX as maintenance therapy (RMT) in SLE however the effects of such approach on LN are still unclear. Aim of this study was a sub-analyses of a cohort of SLE patients treated with RTX focusing on the ones with active LN at the moment of the first RTX administration. Methods Patients with active LN at the time of the first RTX administration within a cohort of 147 patients with SLE were identified. Patients with SLE and a flare of LN were classified as treated with a “Single RTX course” (any RTX regimen administered within a single month) (SRC) or with RMT. Patients receiving at least three SRCs with the aim of relapse prevention and within 4 to 8 months between consecutive treatments, were classified as receiving RMT. LN activity was determined according to creatinine, proteinuria and haematuria; complete response (CR) was defined as a decrease of proteinuria to <0.5 g/day, normal creatinine and negative urinary sediment; partial response (PR) was defined as ≥50% improvement in creatinine and proteinuria, treatment failure (TF) was any other condition. A renal flare (RF) was defined as an increase of creatinine and/or proteinuria >30% or the detection of an active urinary sediment due, according to the treating physician, to active disease. Results 33 patients were identified; a renal biopsy had been performed in 76% with prevalence of class IV lupus nephritis in 16/33 (48%). Six months after RTX the rate of CR, PR and TF was respectively 36%, 27% and 36%; proteinuria and the prednisolone dose reduced significantly compared to baseline (respectively from a median of 2200 mg/day (IQR 499-5400) to 850 mg/day (IQR 400-1700) (p=0.005)) and from 25 mg (IQR 11-25) to 10 mg (IQR 6.125-15) (p<0.0001)). At univariate analyses the only factor associate to the risk of TF was a high number of immunosuppressive drugs employed before RTX (p=0.0077). Of the 33 patients, 11 received RMT with a median duration of 18 months (IQR 12,6-23,4) and a median RTX dose of 5 g (IQR 4-6). During the RMT 3 patients experienced a renal flare. The median follow-up after the last RTX administration within the SRC and the RMT groups was respectively 15 months (IQR 13,5-18,4) and 16 months (IQR 3,5-23). Comparing the RF free-survival of the two subgroups after the last RTX infusion, there was a trend towards a longer relapse free survival after the RMT (p=0.057) (figure, left panel). Of interest, the renal relapse free-survival of the 11 patients treated with RMT after the last RTX infusion was significantly longer compared to the one of the same group after the first RTX (p=0.0271) (figure, right panel). The incidence of SAEs per 100 patient years was 0.31 in the SRC group and 0.74 in the RMT group. Conclusion RTX is confirmed as an effective option for patients with LN. A RMT may have a role in improving LN disease control compared to a single RTX administration.