354. Safety proile of repeat rituximab treatment in ANCA associated vasculitis: a 10-year single centre study
Creators: name: Pek Ghe Tan1
Publisher: name: Zenodo
Year: 2022
Subjects: Vasculitis
ANCA
Abstracts
Giant Cell Arthritis
MPA
GPA
EGPA
Takayasu
IgA vasculitis

description: <strong>Background:</strong> Rituximab is a proven effective induction and remission-maintenance treatment in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Hypogammaglobulinemia, infection, and late-onset neutropenia (LON) have been identified as potential adverse events. We conducted a retrospective study to examine the long-term safety ile of repeated rituximab treatment in AAV. <strong>Methods:</strong> All patients with AAV treated with rituximab between 1<sup>st</sup> January 2008 and 31<sup>st</sup> December 2018 were identified through local dispensary database. Patients were stratified into low (LD) (4g), medium (MD) (&gt;4g to 8g) and high (HD) (&gt;8g) dose groups according to the cumulative rituximab dose received until 1<sup>st</sup> October 2019. Baseline characteristics and adverse events including death, opportunistic and serious infections (defined as infections required hospitalization or intravenous antimicrobial), neutropenia (neutrophil count 1.5x10<sup>9</sup>/L), hypogammaglobulinemia (IgG level5.0), and malignancy diagnosed post-rituximab treatment were examined and compared between the groups. <strong>Results: </strong>364 patients (49% male, mean age of 56) received rituximab for AAV treatment. 49% (n=175) had repeated rituximab with 275 treatment courses for relapsing disease and 251 for remission maintenance. 262 (72%), 70 (19%) and 32 (9%) patients were in LD, MD and HD groups, respectively. The median rituximab dose for each group was 2g, 6g and 12g (p&lt;0.001). LD group were older (LD:58-years, MD:50-years, HD:43-years, p&lt;0.001), more likely to have kidney impairment (eGFR&lt;60) (LD:66.4%, MD:38.6%, HD:21.9%, p&lt;0.001) and renal-limited AAV disease compared to MD and HD groups (LD:18%, MD:2.9%, HD:0 p&lt;0.05). Conversely, more ear-nose-throat/ocular limited (40.6% and 12.6%; p&lt;0.05) and PR3-ANCA positive disease (62.5% vs 39.7%, p&lt;0.05) in HD compared to LD group. The median duration of follow up after first rituximab was 47 (IQR:67.2) months. Outcomes (Table1): LD group recorded the highest serious infection rates (LD:14.3/100-Patient-Years (100-PY), MD:8.6/100-PY, HD: 9.2/100-PY, p=0.006). Pneumonia was the leading cause. Herpesvirus (e.g.Herpes Zoster/Herpes Simplex) reactivations were the commonest opportunistic infections across three groups. Hypogammaglobulinemia incidence was comparable across groups (LD:3.2/100-PY, MD:1.9/100-PY, HD:2.9/100-PY). Age (61 vs 55-years-old, p&lt;0.01), concurrent cyclophosphamide (81% vs 54%, p&lt;0.01) and kidney impairment (75% vs 54%, p&lt;0.01) were risk factors for hypogammaglobulinemia. Neutropenic incidence was higher in LD group (LD:10.1/100-PY, MD:3.0/100-PY, HD:6.8/100-PY, p=0.01). 127/134 neutropenic events were related to concomitant immunosuppressants or illnesses. 5 (LD:3 and HD:2) met definition of rituximab-related-LON. There was no difference in malignancy rate between groups (LD:1.4/100-PY, MD:2.6/100-PY, HD:0.7/100-PY, p=0.13). The commonest reported new cancers were skin (48%) and breast cancer (14.8%). 58 patients died with comparable mortality rate between LD and MD group (82% survival at 30-month after last rituximab). Conversely, there were no deaths in HD group. Infection was the major cause of death (41.4%). <strong>Conclusions:</strong> In this single-centre AAV cohort, repeated rituximab treatment was more common in younger patients and those with ENT involvement. We did not observe an increased incidence of adverse events with increasing cumulative rituximab exposure. This likely reflects both underlying disease features and physician bias in patient selection for repeat treatment. Our data suggests that in selected patients, extended periods of rituximab treatment might be safe. <strong>Disclosures:</strong> none