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Journal of the American Society of Nephrology ; 32:508, 2021.
Article in English | EMBASE | ID: covidwho-1490081


Background: Induction therapy for severe ANCA-associated vasculitis (AAV) combines glucocorticoids (GC) with either rituximab (RTX) or cyclophosphamide (CYC). The coronavirus 2019 disease (COVID-19) pandemic has increased concern around using aggressive immunosuppression;whether this concern has impacted AAV management is unknown. Here, we report treatment regimens and outcomes of patients with active AAV receiving induction immunosuppression during the first wave of the pandemic. Methods: We retrospectively studied AAV patients with new or relapsing disease receiving remission induction therapy during the first wave of the COVID-19 pandemic across sites in the US, UK and Europe. Primary outcome was achievement of complete remission at 6 months. Results: Of 191 patients with a mean age of 65 years old, 52% were female and a majority (89%) were Caucasian. Standard induction was deployed across all sites. Out of the US, UK, and European patient populations, the US used higher GC pulses leading to a higher average cumulative GC dose for remission induction (4153 mg, 2174 mg, 3408 mg, respectively, p<0.001) and had the highest proportion of patients given RTX induction therapy (64%;p=0.005). Complete remission was achieved in 90% of patients. Improvement in kidney function at 6 months was similar with all treatment regimens (6 ml/min2 increase, p=0.68). Sixteen patients were diagnosed with COVID-19 and had similar exposures to CYC and RTX. There were no differences in remission rates, ESKD or death when stratified by induction therapy type. Conclusions: Induction immunotherapy practices differ across the world, but specialists continued their standard management during the COVID-19 pandemic. AAV outcomes or rates of COVID-19 infection were not influenced by different induction regimens.

Journal of the American Society of Nephrology ; 32:100, 2021.
Article in English | EMBASE | ID: covidwho-1489752


Background: The development of efficacious vaccines against COVID-19 is an overarching achievement of modern medicine. This efficacy, however, may not be achieved in patients on immunosuppression. We looked to ascertain humoral response and tolerability of these vaccines in patients with ANCA associated vasculitis(AAV) treated with B-cell depleting agents Methods: AAV patients who completed 2 doses of BNT162b2 or mRNA-1273 or a dose of JNJ-78436735, subsequently screened for spike protein antibody against SARSCoV-2 were included in the study. Clinical details, demographics and immunosuppression regimes were ascertained, with primary outcome being humoral response to SARSCoV-2.Statistics included Fischer's exact test and Wilcoxon rank sum test. Results: Forty-eight patients with a mean age of 67y(35% female) completed vaccine series with BNT161b2(n=19), mRNA-1273(n=25) and JNJ-78436735(n=4). Vaccine associated side effects occurred in 27% of patients after 1st dose, with 39% after the 2nd dose. Spike protein antibody was tested at a median of 31 days after vaccination-30(61%) patients had demonstrable antibody. All patients (n=44) other than 4 post-transplant patients, were treated with Rituximab-only 17/44(39%) developed an antibody response. In the setting of rituximab treatment, absence of seroconversion post vaccination was associated with vaccine type, duration elapsed since last rituximab dose (figure 1), low IgM level and absence of B-cell reconstitution (all stastically significant). Two patients without serologic response had severe COVID-19 infection Conclusions: This data demonstrates that majority of patients treated with rituximab lack demonstrable serologic response, with risk of severe COVID-19 infections despite vaccination. Confirmation of B-cell reconstitution before vaccination may have a bearing on serological conversion. It is imperative that authorities consider these factors while designing vaccination schedules and provide recommendations for booster doses in this vulnerable population.