Treatment Of ANCA-associated Vasculitis Research Articles

Update on treatment of ANCA-associated vasculitis

This article summarizes the current guidelines and recommendations published by the European Alliance of Associations for Rheumatology (EULAR), the Kidney Disease Improving Global Outcomes (KDIGO) and the American College of Rheumatology (ACR). In addition to glucocorticoids (GC), treatment with biologics is nowadays an established option to treat Anti-Neutrophil Cytoplasmic Antibody (ANCA)-associated vasculitis (AAV). Rituximab (RTX) is used for remission induction and maintenance in organ-threatening and non-organ-threatening granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). For eosinophilic GPA (EGPA) anti-interleukin 5 (IL5) strategies are an important component of treatment for remission induction and maintenance of refractory or relapsing non-organ-threatening diseases in conjunction with GC. The dosing of GC for remission induction in GPA and MPA is now lower than was previously used and additionally, avacopan is approved as anew GC-sparing medication for GPA and MPA over 52weeks. Conventional strategies, such as cyclophosphamide (CYC) are important for remission induction in severe or refractory organ-threatening disease for all AAVs. The use of methotrexate (MTX) and azathioprine (AZA) is becoming less prominent. The most important unanswered questions in the treatment of AAVs are with respect to the duration of remission maintenance treatment and the individualized treatment guidance based on biomarkers.

#1681 Efficacy and safety of combined treatment with rituximab and low doses of cyclophosphamide for ANCA associated renal vasculitis

Abstract Background and Aims Current guidelines recommend the use of rituximab (RTX) or cyclophosphamide (CP) as induction treatment for ANCA-associated vasculitis (AAV) with renal involvement. Some authors have described the combination of CP and RTX in the treatment of severe AAV, and recently a regimen of 6 cycles of low-dose CP combined with RTX has been used with good results. The aim our study was to compare the efficacy and safety of combined treatment with even lower doses of intravenous CP (2-3 cycles) and RTX, compared to standard treatment with RTX. Method We conducted a retrospective study that included 14 patients with histologically confirmed AAV, treated with an induction treatment scheme of corticosteroids, RTX and 2-3 cycles of intravenous CP. A case-control analysis was performed with 16 patients who received only corticosteroids and RTX in the same period, matched by propensity score for age, creatinine at presentation and histological parameters (sclerosed glomeruli, epithelial crescents and normal glomeruli). We compared renal and overall survival, and complications from immunosuppression in both groups. Results At presentation, patients treated with the combined regimen had a mean age of 67 ± 12.1 years, a mean glomerular filtration rate estimated by CKD-EPI of 19.8 ± 11.1 ml/min/1.73 m2, proteinuria of 1.6 (0.81- 1.84) g/24 hours and initial BVAS score of 18.5 ± 6.9. 78.6% of the patients were anti-MPO positive and 21.4% were anti-PR3 positive. According to Berden's classification, 85.7% had a mixed variant, 7.1% crescentic and 7.1% sclerotic, in the renal biopsy. The mean dose of CP was 1445 ± 384 mg, and of RTX was 2g. 28.6% required dialysis at presentation, of which 75% recovered kidney function. The duration of steroid treatment was 8 (4.6-16.9) months. Remission rate at 6 months was 71.4%, and after a median follow-up of 20 (15-35) months, 92.9% had remitted. During follow-up, 50% had serious infections; and at the end, 7.1% progressed to end-stage chronic kidney disease (ESKD). 21.4% of the patients included ended up dying. In comparison with the control group, patients who received the combined treatment had a higher remission rate (92.9% vs. 75%), a lower relapse rate (15.4% vs. 35.7%), lower progression to ESKD (7.1% vs. 20%) and lower mortality (21.4% vs 37.5%), with no differences for serious infections. Conclusion The association of low doses of cyclophosphamide to rituximab induction treatment could improve the prognosis in patients with severe ANCA-associated renal vasculitis.

Clinical analysis of ear symptoms of 40 patients with ANCA-associated vasculitis

Objective:To analyze the clinical feature, diagnosis and treatment of Anca-associated vasculitis with ear symptoms. Methods:In this retrospective study, we summarized the clinical and laboratory examination, pure tone audiometry, aural immittance measurement, CT scan of temporal bone and treatment of 40 patients in the First Medical Center of the PLA General Hospital. Results:A total of 11 cases（27.5%） had the initial symptom in the ear. The most common symptoms were hearing loss, and the other symptoms included a sense of ear fullness, otorrhea and tinnitus. There were 35 cases with hearing loss: 19 cases with conductive hearing loss（47.5%）, 9 cases with sensorineural hearing loss（22.5%）, and 7 cases with mixed hearing loss（17.5%）. 5 cases had a sense of ear fullness or tinnitus, and the results of the hearing test were normal（12.5%）. All of the 40 patients had multi-system involvement, and respiratory system accounted for the most. All patients had a positive result of Anti-neutrophil cytoplasmic antibody（ANCA）. Treatment included systemic hormonal, immunosuppressive, or biologic therapy. There were 3 cases recovered（7.5%）, 22 cases with alleviated ear symptoms（55.0%）, 6 cases with recurrent hearing loss（15%） and 9 cases had no significant improvement（22.5%）. Conclusion:Conductive deafness（secretory otitis media） can be the first manifestation in the early stage of otitis media with AAV（OMAAV）, later it may turn to binaural mixed deafness. Otolaryngologists need to consider OMAAV diagnosis when diagnosing and treating patients with recurrent secretory otitis media. Multi-system symptom consultation and ANCA examination can help identify. Early systemic medication and the application of immunosuppressants or biological agents can help relieve the ear symptoms.

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis: A Glimpse into The Future

Background: A class of uncommon IgG4-related systemic diseases known as vasculitis caused by antineutrophil cytosolic antibodies (ANCA) is distinguished by the enlargement of small to large blood vessels. Objective: This review article offers an in-depth analysis of the most recent developments in ANCA-associated vasculitis, covering a range of topics from pathophysiology and diagnostics to treatment and long-term results. Methods: In this review we investigated the existing work on ANCA associated vasculitis by different sources such as Science Direct, Scopus, Pubmed, Web of Science, Google scholar and SciHub. Results: A number of diseases, including eosinophilic granulomatosis with polyangiitis (EGPA), microscopic polyangiitis (MPA), and granulomatosis with polyangiitis (GPA), can have significant morbidity and mortality if they are not appropriately diagnosed and treated. Understanding the pathophysiology, clinical presentation, and curative options for ANCA-associated vasculitis have advanced significantly during the past ten years. The development of specific immunosuppressive medications has been largely responsible for the remarkable evolution in recent years in the treatment of ANCA-associated vasculitis. Conclusion: This review article has provided a detailed examination of the therapy for AAV, alternatives available, including induction and maintenance regimens, as well as the accompanying advantages and disadvantages. Additionally, the growing importance of biologic drugs like rituximab was examined, emphasizing its potential as supplements or replacements for traditional medical treatments.

Invasive fungal infection in ANCA-associated vasculitis: Between the Devil and Deep blue sea. Case series and review of the literature.

Patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) are susceptible to opportunistic infections, including invasive fungal infections (IFI). This is due to many factors, including prolonged immunosuppressive therapy. The treatment of AAV with such IFIs is challenging. A descriptive analysis of 5 patients with AAV complicated by concomitant invasive fungal infections was performed. We also have done a comprehensive literature review of IFIs in AAV using PubMed and Google Scholar databases. All 5 patients initially received immunosuppressive medication but subsequently acquired IFI. One patient had sphenoid sinus involvement, and four had lung parenchymal involvement. Aspergillus infection was diagnosed in three patients, Cryptococcus infection in one patient and mixed infection with Aspergillus and Mucor infection in one patient. All our patients were on low doses of corticosteroids for several months to years or had received high-dose pulse steroids with cyclophosphamide in the last few weeks before being diagnosed with IFI. It was difficult to distinguish disease activity from IFI in all the cases. Two of the five patients died despite antifungal therapy. The literature review revealed a prevalence of IFIs ranging from 1 to 9.6% (excluding pneumocystis pneumonia). Aspergillosis was the predominant type of IFI, affecting 46 of 86 patients. Most of these patients (40/46) had pulmonary involvement. The prognosis for patients with IFI was consistently poor, as evidenced by 19 deaths out of 29 reported outcomes. Overall, IFIs have a poor prognosis in patients with AAV. Differentiating disease activity from IFI is difficult because of similar organ distribution, imaging lesions, and histopathological characteristics. A high suspicion index and good-quality microbiology are needed for early treatment and prevention of mortality.

Systematic literature review informing the 2022 update of the EULAR recommendations for the management of ANCA-associated vasculitis (AAV): part 1—treatment of granulomatosis with polyangiitis and microscopic polyangiitis

ObjectiveTo summarise and update evidence to inform the 2022 update of the EULAR recommendations for the management of antineutrophil cytoplasm antibody-associated vasculitis (AAV).MethodsA systematic literature review (SLR) was performed to...

#5835 A LOW DOSE GLUCOCORTICOID, LOW DOSE CYCLOPHOSPHAMIDE, RITUXIMAB TREATMENT PROTOCOL AS INDUCTION THERAPY IN ANCA ASSOCIATED VASCULITIS PATIENTS

Abstract Background and Aims There has been a considerable improvement in the survival of patients with ANCA associated vasculitis (AAV) since the introduction of immunosuppressive therapy. Nowadays early deaths are attributable to infection while cardiovascular disease, infection and malignancy are the most common causes in long term mortality in these patients. High-dose glucocorticoids and cyclophosphamide have numerous dose-dependent adverse effects and are associated with those events. The aim of this study is to investigate the efficacy and safety a low dose glucocorticoids, low dose cyclophosphamide, rituximab treatment protocol in AAV patients. Method This is a single-centre cohort study of patients on a combination of reduced-dose oral glucocorticoids, rituximab and low-dose pulsed intravenous cyclophosphamide followed by a maintenance regimen of rituximab and tapered steroid for the treatment of AAV (table). Data shown as median (IQR). Results Nine patients (3 women) aged 62.4 (55/67.8) years, with serum creatinine (sCre) 2.15 (1.8/2.5) mg/dL, eGFR CKD-EPI 28 (20/39) ml/min/1.73 m2, albuminuria 0.98 (0.57/1.45) gr/24 h and BVAS 14 at baseline were treated with the mentioned protocol. Seven patients had MPO and 2 had double MPO/PR3 positivity. Two were already on dialysis and 4 had pulmonary involvement. The median follow-up was 19 (12.5/39) months. One patient required the addition of plasma exchange and extended treatment due to aggressive disease and one was lost to follow-up after four months. The rest of the 7 patients were dialysis free with a sCre 2.15 (1.8/2.5) mg/dL, eGFR 28 (20/39) ml/min/1.73 m2 at the end of follow-up. Patient and renal survival were 88% and 100% respectively. 85.7% of patients achieved ANCA-negative status and all remained B cell deplete at 6 and 18 months. There were no major relapses, while two patients had infection related hospitalization. No unexpected side effects were observed during follow-up. Conclusion These findings confirm the literature that a combined regimen provides early disease control with low relapse rates, without significant adverse effects from immunosuppression. A regimen like this may provide the basis for further refinement of remission induction protocols in AAV, potentially allowing early withdrawal of corticosteroids.

New Insights into Pathogenesis and Treatment of ANCA-Associated Vasculitis: Autoantibodies and Beyond.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a group of rare systemic diseases affecting small-caliber vessels. The damage caused by AAV mainly involves the lung and kidneys. AAV includes three different types: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Although the different phenotypic forms of AAV share common features, recent studies have shown that there are significant differences in terms of pathogenetic mechanisms involving both the adaptive and innate immune systems. Advances in our understanding of pathogenesis have enabled the development of immuno-targeted therapies. This review illustrates the characteristics of the various forms of AAV and the new therapies available for this disease that can have lethal consequences if left untreated.

Stable incidence but increase in prevalence of ANCA-associated vasculitis in southern Sweden: a 23-year study

ObjectiveTo update the epidemiology of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) in a defined geographical area of southern Sweden.MethodsThe study area comprised 14 municipalities with a combined adult population (≥18 years)...

Recommendations on the diagnosis and treatment of anti-neutrophil cytoplasmic antibody associated vasculitis in China

Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) is a group of systemic small vasculitis characterized by ANCA positive in serum. Three diseases are included in this group of diseases: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). In China, standardized diagnosis and treatment of AAV is still lacking. Based on the evidence and guidelines from China and abroad, the Chinese Rheumatology Association formulated the standardization of diagnosis and treatment of ANCA associated vasculitis. The purpose is to standardize the diagnosis of AAV and disease activity assessment, and recommend the treatment strategies.

Challenges of Diagnosis and Treatment of ANCA Associated Vasculitis in COVID-19 Pandemic - A Case Report

As COVID-19 pandemic is spreading worldwide with high infectivity rates of various strains, it is also challenging our healthcare system with its respiratory complications, and limited availability of healthcare providers. On the other hand, a huge vaccination program against COVID-19 is being conducted throughout the world. This viral infection and vaccination program has also brought into account the controversies of some neurological and autoimmune complications. Although the exact mechanism of these complications is still unknown, some autoimmune mechanisms have been predicted. These complications may further challenge the management of this novel viral infection. One of the rare complications of COVID-19 infection and its vaccination is de novo development or flare of ANCA-associated vasculitis, which has also been found in many recent case reports.

FC057: Incidence of Infections in the Avacopan Group Versus Prednisone Group in Anca-Associated Vasculitis, Results from the Phase 3 Advocate Study

Abstract BACKGROUND AND AIMS Standard therapy for ANCA-associated vasculitis (AAV) includes glucocorticoids (GC), which are associated with increased infections. Avacopan is an orally administered selective inhibitor of the C5a receptor recently approved for treatment of AAV. The phase 3 ADVOCATE study tested daily avacopan as a substitute for a standard, scheduled, daily oral GC tapered regimen (all with standard background therapy), resulting in a 63% mean reduction in overall GC load for the avacopan group. At week 26, the avacopan group achieved a comparable remission rate to prednisone (72.3% versus 70.1%) and superior sustained remission at Week 52 (65.7% versus 54.9%; one-sided P = 0.0066) (1). The present analysis compared infections in avacopan and prednisone groups in the ADVOCATE trial. METHOD ADVOCATE, a phase 3, randomized, double-blind, controlled trial in 330 patients, evaluated the efficacy and safety of avacopan. AAV patients (new onset or relapsing disease) were randomized to receive avacopan 30 mg twice daily, or a standard 20-week oral prednisone taper, plus matching placebos. Both groups had background therapy of either cyclophosphamide (followed by azathioprine) or rituximab, and additional GC exposure from premedication for rituximab, from taper of pre-randomization GC, and as required per investigator judgment. Patients were on blinded study drug for 52 weeks. Infections occurring from first dose of blinded study drug through day 56 after last dose were analyzed. RESULTS Total mean GC use during the first 26 weeks of the study was 1073 mg with avacopan and 3193 mg with prednisone groups, and in the last 26 weeks, 296 and 489 mg, respectively. Infections were higher in the prednisone group than with avacopan: 291 events (prednisone) versus 233 (avacopan), with a 75.6% incidence (124/164) with prednisone versus 68.1% (113/166) with avacopan (Table 1). During the prednisone taper period (first 20 weeks), infection incidence was 54.9% in prednisone group versus 49.4% for avacopan, and after the first 20 weeks 52.4% in prednisone group versus 44.0% avacopan. Fewer patients in the avacopan group experienced serious AEs of infection (13.3%/25 events) versus prednisone group (15.2%/31 events); also serious opportunistic infections (3.6% versus 6.7%), life-threatening AEs of infection (0.6% versus 1.2%), and infections resulting in death (0.6% versus 1.2%) were fewer with avacopan (Table 1). No Neisseria meningitidis infections occurred in any patient in the trial. CONCLUSION In the ADVOCATE trial, the mean dose of GCs from all sources was 63% lower in the avacopan group than the prednisone group (1349 versus 3655 total mg, respectively). The avacopan group had a numerically lower incidence of infections, including serious, life-threatening, fatal and serious opportunistic infections compared with the prednisone group.

Comparison between Rituximab and Cyclophosphamide in Treatment of ANCA-Associated Vasculitis on Remission Induction: A Meta-Analysis

Objectives: Currently, immunosuppressants including cyclophosphamide and azathioprine are the main treatment options for anti-neutrophil associated vasculitis. However, since cyclophosphamide may cause serious adverse reactions, it is necessary to explore for a new drug, and rituximab is one option with less adverse reaction. There are a few studies on rituximab versus cyclophosphamide in the treatment of antineutrophil associated vasculitis. The meta-analysis is carried out to evaluate the efficacy of rituximab, compared with cyclophosphamide, as a remission induction therapy in AAV. Methods: Firstly we searched a Chinese database (CNKI, Wanfang) and English databases (Pubmed, Cochrane Library, Embase) according to inclusion criteria and exclusion criteria before October, 2021. Then Revman5.4 and Stata were used for data analysis which was then integrated by fixed effects or random effects. Results: After browsing the full texts, we finally included 7 eligible articles, involving 737 patients in total. With Revman5.4 software, we could draw the following conclusions: 6-month complete response rate (Chi²=0.46, df=1 P=0.50 I²=0%), 12-month complete response rate (Chi²=0.31 df=1 P=0.58 I²=0%), 18-month complete response rate (Chi²=0.18 df=1 P=0.67 I²=0%). Adverse event (Chi²=3.15 df=4 P=0.53 I²=0%), respectively for reached primary endpoint, failed primary endpoint in contrast. The result showed (Chi²=3.29 df=3 P=0.35 I²=9%, Chi²=1.72 df=2 P=0.42 I²=0%), 6-momth relapse, 12-momth relapse, 18-month relapse (Chi²=0.22 df=1 P=0.64 I²=0%, Chi²=0.04 df=2 P=0.98 I²=0%, Chi²=0.13 df=1 P=0.72 I²=0%), GPA 0f 6-month (Chi²=0.47 df=1 P=0.50 I²=0%), MPA of 6-month (Chi²=1.52 df=1 P=0.22 I²=34%). The above data are statistically significant. Conclusion: Based on the above data, we can conclude that compared with cyclophosphamide, rituximab can play a certain role in the treatment of ANCA disease, improve the complete response rate, reduce the rate of adverse reactions and recurrence, and is expected to replace cyclophosphamide as a first-line drug in clinical practice.

Comparison between Rituximab and Cyclophosphamide in Treatment of ANCA-Associated Vasculitis on Remission Induction: A Meta-Analysis

Objectives: Currently, immunosuppressants including cyclophosphamide and azathioprine are the main treatment options for anti-neutrophil associated vasculitis. However, since cyclophosphamide may cause serious adverse reactions, it is necessary to explore for a new drug, and rituximab is one option with less adverse reaction. There are a few studies on rituximab versus cyclophosphamide in the treatment of antineutrophil associated vasculitis. The meta-analysis is carried out to evaluate the efficacy of rituximab, compared with cyclophosphamide, as a remission induction therapy in AAV. Methods: Firstly we searched a Chinese database (CNKI, Wanfang) and English databases (Pubmed, Cochrane Library, Embase) according to inclusion criteria and exclusion criteria before October, 2021. Then Revman5.4 and Stata were used for data analysis which was then integrated by fixed effects or random effects. Results: After browsing the full texts, we finally included 7 eligible articles, involving 737 patients in total. With Revman5.4 software, we could draw the following conclusions: 6-month complete response rate (Chi²=0.46, df=1 P=0.50 I²=0%), 12-month complete response rate (Chi²=0.31 df=1 P=0.58 I²=0%), 18-month complete response rate (Chi²=0.18 df=1 P=0.67 I²=0%). Adverse event (Chi²=3.15 df=4 P=0.53 I²=0%), respectively for reached primary endpoint, failed primary endpoint in contrast. The result showed (Chi²=3.29 df=3 P=0.35 I²=9%, Chi²=1.72 df=2 P=0.42 I²=0%), 6-momth relapse, 12-momth relapse, 18-month relapse (Chi²=0.22 df=1 P=0.64 I²=0%, Chi²=0.04 df=2 P=0.98 I²=0%, Chi²=0.13 df=1 P=0.72 I²=0%), GPA 0f 6-month (Chi²=0.47 df=1 P=0.50 I²=0%), MPA of 6-month (Chi²=1.52 df=1 P=0.22 I²=34%). The above data are statistically significant. Conclusion: Based on the above data, we can conclude that compared with cyclophosphamide, rituximab can play a certain role in the treatment of ANCA disease, improve the complete response rate, reduce the rate of adverse reactions and recurrence, and is expected to replace cyclophosphamide as a first-line drug in clinical practice.

Is There a Place for Complement Inhibition with Monoclonal Anti-C5a Antibody Vilobelimab in the Treatment of Patients with ANCA-associated Vasculitis?

Recent studies have implicated the complement system in the pathogenesis of antineutrophil cytoplasmic antibody-associated vasculitis (AAV), prompting the development of novel therapeutic agents to target the complement system accordingly. The pivotal role of complement component C5a, in particular, has been the subject of a number of phase II and phase III clinical trials. Indeed, the US Food and Drug Administration has already approved avacopan, an oral C5a receptor inhibitor, as an adjunct for the treatment of active severe AAV, based on its favourable safety profile and non-inferiority to glucocorticoids (GCs) (at Week 26). The novel monoclonal anti-C5a antibody vilobelimab has also been studied in a phase II trial in patients with AAV (IXchange; ClinicalTrials.gov Identifier: NCT03895801). The results appear promising; in addition to decreased GC toxicity index, a smaller number of treatment-emergent adverse events have been observed in vilobelimab-treated patients. However, the study was not powered statistically to compare the efficacy of vilobelimab to standard GC treatment. This editorial summarizes the study findings and outlines potential future directions.

47-Year-Old Woman With Bilateral Flank Pain

47-Year-Old Woman With Bilateral Flank Pain

Application of the ANCA Renal Risk Score in the United States: A Single-Center Experience

Application of the ANCA Renal Risk Score in the United States: A Single-Center Experience

POS1201 Incidence and outcome of COVID-19 in ANCA-associated vasculitis: impact of COVID-19 in patients undergoing rituximab for maintenance

Background:COVID-19 is an emerging infectious disease caused by SARS-CoV-2. Risk factors for the worst outcome in COVID-19 are pre-existing pulmonary and cardiovascular disease, while the impact of chronic immunosuppression has not yet completely been clarified (1).Currently, there is no clinical evidence that chronically immunosuppressed rheumatic patients under biologic agent or a small molecule may have a higher risk of COVID-19 or a worse prognosis(2). However, the anti-CD20 antibody monoclonal rituximab may contribute to severe consequences, inhibiting the humoral response to SARS-CoV-2 and capacity to produce efficient antibodies against it (3,4). Rituximab is widely use in the treatment of ANCA-associated vasculitis (AAV). Nowadays, the incidence and impact of COVID-19 in AAV-patients are still unknown and, in particular, in AAV-patients who have been exposed to rituximab since the outbreak (5).Objectives:Herein we evaluate the incidence and outcome of SARS-CoV-2 infection in our cohort of AAV-patients who had at least one visit in the year 2020.Methods:We collected clinical data of 100 AAV-patients who had at least one visit in our Centre from February 2020 to December 2020, and we described cases of COVID-19 infection among them. The COVID-19 was proved by detection of SARS-CoV-2 RNA in nose-pharyngeal swabs. In case of infection, anti-SARS-CoV-2 IgM or IgG production was then investigated.Results:Among 100 patients (53 females; 47 males) regularly followed, the median age was 65, and the mean (SD) duration of disease was 8.8 (6.8) years. The most frequent diagnosis was granulomatosis with polyangiitis (GPA) (56%), followed by granulomatosis eosinophilic with polyangiitis (EGPA) (31%), and microscopic polyangiitis (MPA) (13%). The mean (SD) BVASv3 at the onset of disease was 12.6 (5.6). More than half of the patients (59%) have had lung and/or ENT involvement at the onset of disease. Overall, 84% of our patients received immunosuppressive agents and 45% also received glucocorticoids (GC). Rituximab was administered in 15% of patients during the pandemic. COVID-19 was diagnosed in 2 cases (2%). Both patients have received rituximab as maintenance: the last rituximab infusion was on November 9, 2020 for patient 1 (female, 73 years old, GPA ANCA-PR3+) and was on August 17, 2020 for patient 2 (female, 74 years old, MPA ANCA-MPO+). Both patients had a BVAS 0 and negative ANCA antibodies at the time of the first positive nose-pharyngeal swab RT-PCR test, on December 24 and on November 25, respectively. Both patients were B-cell depleted and IgG levels were 455 mg/dL and 866 mg/dL, respectively. While patient 1 died due to critically ill COVID-19 pneumonia 25 days after the COVID-19 disease onset, patient 2 remained asymptomatic with nose-pharyngeal swab still positive on day 56 after the first detection. Anti-SARS-CoV-2 IgM or IgG antibodies above the cut-off (cut-off value 10 AU/mL) were absent in patient 1, while in patient 2 a low level of anti-SARS-CoV-2 IgG (39 AU/mL, cut-off value 10 AU/mL) was documented.Conclusion:Prevalence of COVID-19 in AAV seems lower than in general population (prevalence of 29582/466700, 6.3%, in the same geographical area). Rituximab compromises the B-cells function and can lead to humoral immunodeficiency, causing the inability to produce anti-SARS-CoV-2 IgG antibodies. The timing of the last rituximab infusion and the levels of IgG can greatly affect the outcome. Patients who underwent anti-CD20 therapy are at higher risk of severe outcome in case of infection (3), and require prioritization for SARS-CoV-2 vaccination.

Update in the Management of ANCA-Associated Vasculitis: Recent Developments and Future Perspectives.

Significant progress has been made in the treatment of ANCA-associated vasculitides (AAV), notably in granulomatosis with polyangiitis and microscopic polyangiitis. Over the past few years, many innovative studies have changed the way we now induce and maintain remission in AAV; achieving remission while limiting treatment toxicity is the key. This article provides an in-depth, up-to-date summary of recent trials and suggests treatment algorithms for induction and maintenance of remission based on the latest guidelines. Future possible therapies in AAV will also be discussed.

Topic modeling to characterize the natural history of ANCA-Associated vasculitis from clinical notes: A proof of concept study

ObjectivesClinical notes from electronic health records (EHR) are important to characterize the natural history, comorbidities, and complications of ANCA-associated vasculitis (AAV) because these details may not be captured by claims and structured data. However, labor-intensive chart review is often required to extract information from notes. We hypothesized that machine learning can automatically discover clinically-relevant themes across longitudinal notes to study AAV. MethodsThis retrospective study included prevalent PR3- or MPO-ANCA+ AAV cases managed within the Mass General Brigham integrated health care system with providers’ notes available between March 1, 1990 and August 23, 2018. We generated clinically-relevant topics mentioned in notes using latent Dirichlet allocation-based topic modeling and conducted trend analyses of those topics over the 2 years prior to and 5 years after the initiation of AAV-specific treatment. ResultsThe study cohort included 660 patients with AAV. We generated 90 topics using 113,048 available notes. Topics were related to the AAV diagnosis, treatment, symptoms and manifestations (e.g., glomerulonephritis), and complications (e.g., end-stage renal disease, infection). AAV-related symptoms and psychiatric symptoms were mentioned months before treatment initiation. Topics related to pulmonary and renal diseases, diabetes, and infections were common during the disease course but followed distinct temporal patterns. ConclusionsAutomated topic modeling can be used to discover clinically-relevant themes and temporal patterns related to the diagnosis, treatment, comorbidities, and complications of AAV from EHR notes. Future research might compare the temporal patterns in a non-AAV cohort and leverage clinical notes to identify possible AAV cases prospectively.