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Background: The complement system has been recently proposed to play an important role in the pathogenesis of ANCA-associated vasculitis (AAV). This study evaluated the value of serum and kidney deposited C3 in predicting renal outcomes in AAV. Methods: This was a retrospective study of 47 patients with AAV, who were categorized according to their serum C3 levels as hypo-or normo-complementemic and to those with positive or negative kidney biopsy immunofluorescence (IF) for C3. Baseline characteristics as well as progression to end-stage renal disease (ESRD) between the 2 groups were compared. Results: In total, 23% (11/47) were hypo-complementemic; these patients were older (74 vs. 65 years, p ¼ 0.013), had higher creatinine levels (4.9 vs. 2.2 mg/dL, p ¼ 0.006), were more often hemodialysis dependent (64% vs. 19%, p ¼ 0.009) and progressed more often to ESRD (55% vs. 11%, p ¼ 0.01) compared to normo-complementemic patients (n ¼ 36). On multivariate analysis, serum creatinine at diagnosis (HR ¼ 16.8, 95%CI: 1.354-208.62, p ¼ 0.028) and low serum C3 (HR ¼ 2.492; 95% CI: 1.537-11.567; p ¼ 0.044) were independent predictors for ESRD. Among 25 patients with an available kidney biopsy, 56% had C3 deposition by IF and displayed more often a mixed histological pattern (72% vs. 27%, p ¼ 0.033), low serum C3 levels (42% vs. 18%, p < 0.001) and serious infections during follow-up (57% vs. 18%, p ¼ 0.047) compared to those with negative (n ¼ 11) IF staining. Conclusion: Almost one of four patients with AAV has low C3 levels at diagnosis which is associated with more severe renal disease and worse renal outcomes (ESRD). This should be taken into account in therapeutic and monitoring strategies.

Background Serious infections (SI) are common in patients with ANCA-associated vasculitides (AAV) like granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Real-life data regarding their incidence and predisposing factors—after the introduction of B cell depleting agents—are limited while data quantifying the risk per treatment modality and year of the disease are missing. Here, we aim to describe in details the incidence and the risk factors for SI in a contemporary AAV cohort. Methods Multicenter, observational, retrospective study of AAV patients followed in three tertiary referral centers. Results We included 162 patients with GPA (63%) and MPA (37%), males 51.9%, mean age 60.9 years, ΑΝCA+ 86%, and generalized disease 80%. During follow-up (891.2 patient-years, mean 5.4 years), 67 SI were recorded in 50 patients at an incidence rate of 7.5 per 100 patient-years. The SI incidence rate was higher during induction with cyclophosphamide (CYC) compared to rituximab (RTX, 19.3 vs. 11.3 per 100 patient-years, respectively) while it was lower and comparable between RTX and other regimens (5.52 vs. 4.54 per 100 patient-years, respectively) in the maintenance phase. By multivariate analysis, plasmapheresis (PLEX) and/or dialysis was a strong predictor for an SI during the 1st year after diagnosis (OR = 3.16, 95% CI 1.001–9.96) and throughout the follow-up period (OR = 5.21, 95% CI 1.93–14.07). In contrast, a higher baseline BVAS (OR = 1.11, 95% CI 1.01–1.21) was associated with SI only during the 1st year. Conclusions In this real-life study of patients with AAV, the SI incidence was higher during CYC compared to RTX induction while there was no difference between RTX and other agents used for maintenance therapy. Higher disease activity at baseline and need for PLEX and/or dialysis were independent factors associated with an SI.

BackgroundRituximab (RTX) is a novel, recently approved therapeutic agent for the treatment of active ANCA-associated vasculitis (AAV, Granulomatosis with polyangiitis-GPA, Microscopic polyangiitis-MPA) with limited data available from daily clinical practice.ObjectivesTo study the efficacy and safety of RTX in patients with AAV in real life settings.MethodsRetrospective study of all patients with active AAV treated with RTX in our tertiary center between 2010 and 2015.Results16 patients with active AAV were included (GPA n=12, MPA n=4); 50% females with a mean age of 61.8±13.9 years and median disease duration of 33.5 months. The majority of patients had generalized disease (88%) and the most commonly involved organs were lungs (75%), kidney (63%), joints (50%) and ENT (31%). The patients were followed for a mean period of 21.5±16.1 months. Eleven (68%) patients were treated with RTX due to resistant or relapsing disease and 5 (32%) received RTX as initial treatment. Seven patients received 1 cycle, one patient 2 cycles and 8 patients received ≥3 cycles of RTX (1 gm x 2, 15 days apart). Among patients who received ≥1 cycle of RTX (n=9), 6 received RTX on a regular basis (every 6 months) and 3 at relapse. During treatment, a statistically significant improvement in disease activity was observed (BVAS/WG before RTX was 4.8 and decreased to 0.9 and 0.8 at 6 and 12 months, p=0.001 and 0.003 respectively). At 6 months, 87% of patients (13/15) responded to therapy (6 showed complete and 7 partial response). Additionally, one patient who had not responded at 6 months demonstrated complete response at 9 months. Among the 13 responders, 6 (46%) relapsed during follow up. The majority of relapses were minor (5/6, 83%) and occurred mainly in patients not receiving RTX in a regular basis (4/6, 67%). One patient with GPA and fulminant pulmonary-renal syndrome died from septic shock one month after RTX administration (6%). No other serious infections or allergic reactions were noticed during the follow up period.ConclusionsThese real life data confirm the excellent efficacy and safety of RTX in patients with active newly diagnosed or relapsing AAV.AcknowledgementsThis work was supported in part by research grants from the Special Account for Research Grants (S.A.R.G.), National and Kapodistrian University of Athens, Athens, Greece.Disclosure of InterestNone declared

Background and Aims The role of plasmapheresis in the overall and renal survival of patients with ANCA-associated vasculitis (AAV) has not been fully elucidated. The aim of this study is to address whether plasmapheresis is associated with improvement in renal function and survival at 12 months in patients with severe manifestations of AAV and to record the indications, adverse events and treatment characteristics. Method Retrospective, descriptive study of 28 patients with AAV diagnosed over the last five years in a tertiary center. Patients were included if they had received therapeutic plasmapheresis adjunctive to conventional therapy (steroids and immunosuppressants) for the first episode of AAV or in relapse. Results 12 patients (75% male) were enrolled with average age at diagnosis 78.5±6.14 years. The patients were followed for a median period of 20 months. In 75% of the patients MPO-ANCA was positive, in 17% ANCA negative and in 8% double positive anti-GBM/ANCA. On admission, all patients had abnormal renal function with average serum creatinine 5mg/dl±2.12 and the majority of patients (9/12) were dialysis dependent. Indications for plasmapheresis were: alveolar hemorrhage in 33%, renal impairment in 25% and combination of the two above in 42%. 11 patients received plasmapheresis for the first episode of AAV and 1 patient for relapse. Plasmapheresis was performed using filtration and fresh frozen plasma as replacement fluid. The mean number of plasmapheresis treatment was 8 (range 1 to 19 days) and the average internal time between admission and first plasmapheresis treatment was 3 days. One patient had a severe allergic reaction resulting in early discontinuation and no episodes of severe infection or death were recorded during plasmapheresis. As far as treatment all patients received concomitant immunosuppressive therapy with cyclophosphamide (CYC) and corticosteroids while Rituximab (RTX) was added in 3 patients (3/12). Alveolar hemorrhage was resolved in all patients (100%). After one year, 75% of the patients had renal recovery (cre=5mg/dl±2.12 vs cre=2.6mg/dl±1.6, p=0.06) and 67% of the patients who required hemodialysis at the time of diagnosis, during the first year became independent of dialysis (75% vs 33%, p=0.5). Finally, survival at the end of the first year was 83% with cancer and ischaemic heart disease being the cause of death. Conclusion Plasmapheresis is quite often used in daily clinical practice with remarkable results in dialysis independence and survival, without serious complications. The actual role of plasmapheresis in ANCA-vasculitis therapeutic algorithm will be determined shortly with the expected results of a randomized multicenter study.