Case report: Propylthiouracil-induced serious side effect: Perinuclear antineutrophil cytoplasmic antibody-associated vasculitis or IgA vasculitis?

INTRODUCTION: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare disease characterized by the inflammation and destruction of small blood vessels and circulating ANCAs. Drugs such as antithyroid drugs (ATDs), especially propylthiouracil (PTU), have been used for the production of ANCAs and cause the development of drug-induced AAV. The pathogenesis of this disease is unclear but could be related to the physiological processes affecting the degradation of neutrophil extracellular traps (NETs). At present, PTU is widely used in patients with Graves' disease (GD) who are preparing for pregnancy and whose condition has not been controlled. Once drug-induced AAV has occurred with important organ damage, considering NETs have a significant role in the immune system, whether the cessation of drugs could stop the progression of organ damage is unclear, and a consensus regarding standard treatment has not been established. PATIENT CONCERNS: In this case report, a female patient who planned pregnancy was hospitalized with multiple joint pain, impaired renal function, and hematuria. Immunofluorescence of the renal biopsy demonstrated spherical and diffuse mesangial distribution of IgA (3+). Autoimmune serology demonstrated positivity for autoantibodies against p-ANCA and an anti-MPO titer 74.72 RU/mL. DIAGNOSIS: She was diagnosed with PTU-induced p-ANCA-associated and IgA-associated vasculitis (IgAV). INTERVENTIONS: The patient accepted low doses of glucocorticoid, immunosuppressive therapy and RAI treatment. OUTCOMES: Both her kidney function and thyroid function remained were on the mend. CONCLUSION: The authors believe that this type of patient needs to fully consider their pregnancy preparation needs, suspend pregnancy when a small chance of GD remission is indicated, and avoid the use of drugs with reproductive toxicity and other serious adverse events. The multidisciplinary combination therapy of low-dose glucocorticoids and immunosuppressants combined with iodine radiotherapy is one reasonable scheme. At the same time, it is necessary to eliminate the organ damage caused by other reasons. This report provides a clinical treatment basis for patients with drug-induced vasculitis manifestations who cannot receive an accurate diagnosis.

ANCA-associated vasculitis presenting with isolated neurological manifestations in a patient with cocaine abuse: a case report and literature review.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of rare conditions predominantly affecting small vessels of skin, musculoskeletal, pulmonary, renal, and rarely central and peripheral nervous systems. Isolated neurological manifestations of AAV are uncommon and challenging to diagnose. Cocaine has been reported as a potential trigger for the development of AAV. There are only a few case reports of isolated neurological involvement in cocaine-induced AAV with poorly characterized histopathological features. We present a unique case of AAV with isolated neurological manifestations presenting with multiple cranial neuropathies, leptomeningeal enhancement on imaging and histopathologic evidence of small-vessel vasculitis in the leptomeninges and brain and extensive dural fibrosis in a patient with cocaine abuse. The patient's progressive neurological deficits were controlled after starting immunosuppression with rituximab and prednisone. We also reviewed the literature to provide the diagnostic overview of AAV and evaluate intervention options. To our knowledge, this is the first case of AAV with isolated neurological manifestations and histopathologic evidence of small-vessel vasculitis in a patient with cocaine abuse. Patients with multiple cranial neuropathies and meningeal involvement should be screened for AAV, especially if they have a history of cocaine abuse.

Comparison of agranulocytosis and anti-neutrophil cytoplasmic antibody-associated vasculitis caused by two antithyroid drugs: A pharmacovigilance study using the WHO international database.

BACKGROUND: Methimazole (MMI) and propylthiouracil (PTU) are commonly used for patients with thyrotoxicosis. Agranulocytosis and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is associated with high morbidity and mortality, requiring appropriate interventions. In this study, we compared adverse drug effects associated with MMI and PTU using a real-world large pharmacovigilance database. METHODS: We searched all Individual Case Safety Reports reported to be associated with MMI and PTU, from VigiBase between 1967 and June 2, 2021. We conducted disproportionality analysis (case/non-case analysis) to analyze the difference in reported adverse drug reactions (ADRs) between antithyroid drugs (case) and the entire database (non-cases). We further analyzed information for the cases of agranulocytosis and AAV. RESULTS: Among 11 632 cases of ADRs reported after MMI intake, agranulocytosis occurred in 1633 cases and AAV occurred in 41 cases. For 5055 cases of ADRs reported after PTU intake, agranulocytosis occurred in 459 cases and AAV occurred in 110 cases. Agranulocytosis occurred after a median of 28 days after PTU intake and 33 days after MMI intake. More than 95% of the agranulocytosis cases were classified as serious, but most of them (65.1% for PTU and 70.4% for MMI) were reported to have recovered after dechallenge actions; mostly drug withdrawal. AAV occurred after a median of 668 days after PTU intake, and 1162 days after MMI intake. CONCLUSIONS: This is a pharmacoepidemiological study investigating agranulocytosis and AAV caused by MMI and PTU. Through this research, we could provide more specific insights into a safe prescription of antithyroid drugs in a real-world setting.

A projected cost-utility analysis of avacopan for the treatment of antineutrophil cytoplasmic antibody-associated vasculitis in Spain.

BACKGROUND: Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) are rare autoimmune diseases characterized by inflammation of blood vessels. This study aimed to assess the cost-utility of avacopan in combination with rituximab (RTX) or cyclophosphamide (CYC) compared with glucocorticoids (GC) for the treatment of severe, active AAV in Spain. METHODS: A 9-state Markov model was designed to reflect the induction of remission and sustained remission of AAV over a lifetime horizon. Clinical data and utility values were mainly obtained from the ADVOCATE trial, and costs (€ 2022) were sourced from national databases. Quality-adjusted life years (QALYs), and incremental cost-utility ratio (ICUR) were evaluated. An annual discount rate of 3% was applied. Sensitivity analyses were performed to examine the robustness of the results. RESULTS: Avacopan yielded an increase in effectiveness (6.52 vs. 6.17 QALYs) and costs (€16,009) compared to GC, resulting in an ICUR of €45,638 per additional QALY gained. Avacopan was associated with a lower incidence of end-stage renal disease (ESRD), relapse and hospitalization-related adverse events. Sensitivity analyses suggested that the model outputs were robust and that the progression to ESRD was a driver of ICUR. CONCLUSIONS: Avacopan is a cost-effective option for patients with severe, active AAV compared to GC in Spain.

First reported case of ANCA-associated vasculitis induced by oxaliplatin, capecitabine, and trastuzumab.

A 68-year-old male, who was undergoing XELOX plus trastuzumab therapy for gastric cancer, developed proteinuria, hematuria, and progressive increase in creatinine after 3 months. Subsequently, the patient also experienced hemoptysis, nasal bleeding. Chest CT examination shown pulmonary hemorrhage. The MRI of the nasopharynx ruled out nasopharyngeal cancer recurrence. The MPO and PR3 were elevated, and renal biopsy confirmed ANCA-related vasculitis, which affected the lungs, kidneys, and nasopharynx. Based on the review of the patient''s medical history and medication, it is believed that ANCA-related vasculitis was caused by XELOX plus trastuzumab chemotherapy, but it is difficult to confirm which specific drug caused it. After stopping XELOX plus trastuzumab chemotherapy, glucocorticoids and cyclophosphamide was given, the patient''s pulmonary hemorrhage and nasal bleeding stopped, and the lung lesions were absorbed. The renal function also improved. The patient later experienced pulmonary infection again, and tNGS indicated Legionella pneumophila and pulmonary tuberculosis infection. Despite anti-infection treatment, steroid dose was rapidly reduced. Ultimately, the patient gave up on treatment and eventually died.

Late Onset of Rivaroxaban-Associated Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis.

Although anti-thyroid drugs (ATDs) are the most common cause of drug-associated anti-neutrophil cytoplasmic antibody (ANCA) vasculitis (AAV), many other classes of drugs can lead to drug-associated AAV. We present a unique case of rivaroxaban-associated AAV. A 76-year-old female with a past medical history of atrial fibrillation on rivaroxaban presented with fatigue, bilateral lower extremity purpura, and hemoptysis to an outside hospital. Investigations revealed a positive cytoplasmic-ANCA (c-ANCA) titer of 1:320 and a positive anti-myeloperoxidase (anti-MPO), and negative perinuclear-ANCA (p-ANCA) and anti-proteinase 3 (anti-PR3). In addition, chest imaging demonstrated bilateral ground-glass opacities which raised suspicion for diffuse alveolar hemorrhage (DAH). A lung biopsy revealed acute and ongoing DAH with focally active capillaritis and characteristic pathological findings, which strongly suggested that was likely secondary to rivaroxaban. Rivaroxaban was discontinued, and the patient received pulses of intravenous glucocorticosteroids and rituximab. Her symptoms improved. She continued immunosuppressive therapy with rituximab for 2 years. She presented to our hospital for a second opinion regarding the discontinuation of rituximab, and we decided to discontinue rituximab. After discontinuation, the patient remained stable after 1.5 years of follow-up and did not have any relapses. This is a unique case of rivaroxaban-associated AAV. Clinicians should consider drug-associated AAV in all patients who present with an atypical clinical presentation and/or pathological findings of AAV. Given the broad and rapidly increasing use of novel anticoagulants, it is important to raise awareness of this potential complication. Prompt discontinuation of the drug and initiation of immunosuppressant treatment in severe cases may be lifesaving.

Diagnostic dilemma: drug-induced vasculitis versus systemic vasculitis.

Drug-induced vasculitis can rarely cause inflammation and necrosis of blood vessel walls of both kidney and lung tissue. Diagnosis is challenging because of the lack of difference between systemic and drug-induced vasculitis in clinical presentation, immunological workup and pathological findings. Tissue biopsy guides diagnosis and treatment. Pathological findings must be correlated with clinical information to arrive at a presumed diagnosis of drug-induced vasculitis. We present a patient with hydralazine-induced antineutrophil cytoplasmic antibodies-positive vasculitis with a pulmonary-renal syndrome manifesting as pauci-immune glomerulonephritis and alveolar haemorrhage.

Overlapping drug-induced vasculitis, ANCA-associated vasculitis, and lupus nephritis caused by low-dose hydralazine.

INTRODUCTION: We present a case of drug-induced vasculitis secondary to low-dose hydralazine with overlapping features of antineutrophil cytoplasmic antibody-associated vasculitis and drug-induced lupus nephritis. CASE PRESENTATION: A 52-year-old Hispanic woman with a medical history of resistant hypertension treated with hydralazine 10 mg twice daily for 1 year presented with generalized weakness, dizziness, nausea, vomiting, and gross hematuria. There was fever, tachycardia, leukocytosis, lactic acidosis, hyperkalemia, renal failure, and anemia. Chest computed tomography and bronchoscopy revealed a left lower lobe infiltrate and diffuse alveolar hemorrhage. Serologic testing was positive for anti-double-stranded DNA, anti-Smith, lupus anticoagulant, anti-histone, anti-cardiolipin IgM antibodies, and antineutrophil cytoplasmic antibodies (myeloperoxidase and proteinase 3). A kidney biopsy revealed crescentic glomerulonephritis with an overlapping finding of membranous nephropathy. Broad-spectrum antibiotics, immunosuppressants, corticosteroids, and plasmapheresis were initiated. The patient survived but required continuous hemodialysis. CONCLUSIONS: Although a few cases of simultaneous antibody-associated vasculitis and drug-induced lupus nephritis secondary to hydralazine use have been reported, this case is singular. Similar findings were previously reported with doses of 50-100 mg two to three times daily over 1-5 years. In our patient, a dose of only 10 mg twice daily for a year caused a severe disease presentation. This brings to light the combination of different vasculitides that can coexist and the potentially life-threatening adverse effects of low-dose hydralazine that should be kept in mind.

Avacopan for the Treatment of Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis.

OBJECTIVE: To review the safety and efficacy of avacopan for the treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. DATA SOURCES: A systematic review of the literature was performed using the terms avacopan OR tavneos OR CCX168 OR ANCA-associated vasculitis in PubMed and Google Scholar. Articles between January 2016 and January 2023 were considered for inclusion. Bibliographies and ClinicalTrials.gov were also searched for completion. STUDY SELECTION AND DATA EXTRACTION: Relative English language and human studies related to pharmacology, clinical trials, and safety were included. DATA SYNTHESIS: The 52-week ADVOCATE and 12-week CLEAR clinical trials evaluated the safety and efficacy of avacopan. The remission rate was 65.7% and 54.9% in the avacopan and placebo group, respectively, in the ADVOCATE trial. The Birmingham Vasculitis Activity Score improved by ≥50% in 86.4% of avacopan treated patients and 70% of prednisone treated patients in the CLEAR trial. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON WITH EXISTING DRUGS: Glucocorticoids in combination with cyclophosphamide, azathioprine, and/or rituximab have been a mainstay of ANCA-associated vasculitis treatment. However, short- and long-term medication-related adverse effects risk negative outcomes for patients. Avacopan may provide equivalent to better treatment with fewer side effects due to a reduction, if not elimination, of glucocorticoids. CONCLUSIONS: Avacopan used in isolation or combination is safe and effective for ANCA-associated vasculitis.

Human leukocyte antigen association with azathioprine-induced drug hypersensitivity reactions in patients with anti-neutrophil cytoplasmic antibody associated vasculitis.

Azathioprine (AZA) drug hypersensitivity reaction (DHR) is an uncommon yet potentially lethal condition that often goes unrecognised in patients with anti-Neutrophil Cytoplasmic Antibody (ANCA) associated vasculitis (AAV). We conducted a retrospective review of AAV patients on AZA maintenance therapy (N = 35). Participants were categorised into those who had experienced AZA-DHR (N = 15) and those who were AZA-tolerant (N = 20). Human leukocyte antigen (HLA) typing was performed in both groups. The primary endpoint was identification of a HLA gene association with AZA-DHR in the context of AAV. HLA-C*06:02, was solely expressed in AZA-DHR patients (33.3 %), whilst no patient who tolerated AZA carried this allele (0.0 %). This yielded a positive predictive value of 100 % for HLA-C*06:02 in predicting AZA-DHR in AAV patients, negative predictive value of 66.7 %, sensitivity of 33.3 % and specificity of 100 %. HLA-C*06:02 may predict the development of AZA-DHR in patients with AAV and inform safer therapeutic choice.

A Cavitary Lesion in a Patient with Antineutrophilic Cytoplasmic Antibody (ANCA) Associated Vasculitis: A Case Report and Review of the Literature.

Patients with antineutrophilic cytoplasmic antibody (ANCA) associated vasculitis who were on immunosuppressive therapy with corticosteroids may be susceptible to cavitary lesions.1 Only a few cases have been reported in the literature to date. Immunosuppression was shown to improve prognosis in patients with vasculitis. However, adverse therapy events and the risk of opportunistic infections become a major cause of morbidity and mortality in this specific patient population. We present a case of a 75-year-old female who was diagnosed and treated in our hospital for ANCA-associated vasculitis and returned within a few weeks of medical therapy and was found to have developed cavitation concerning for worsening vasculitis or an opportunistic fungal infection or combination of both. Given the risk of severe complications from opportunistic fungal infections, close monitoring and prophylactic antifungal therapy should be considered. Further studies are needed to evaluate the benefit of prophylaxis in this patient population.

Tocilizumab Attenuates Anti-neutrophil Cytoplasmic Antibody-associated Nephritis Occurring during Abatacept and Adalimumab Therapy for Rheumatoid Arthritis.

We encountered an 86-year-old Japanese woman who presented with proteinuria (0.4 g/day) and hematuria (red blood cell sediment >100/high-power field), a decreased renal function (serum creatinine, 1.51 mg/dL), and elevated myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) levels (231 IU/mL) during treatment of rheumatoid arthritis with abatacept (a cytotoxic T-lymphocyte-associated antigen 4 agent) and adalimumab (a tumor necrosis factor-α agent). A kidney biopsy showed pauci-immune necrotizing glomerulonephritis, and ANCA-associated vasculitis was diagnosed. Treatment with tocilizumab (an interleukin 6 receptor antibody) monotherapy resulted in the improvement of renal findings and normalization of rheumatoid arthritis disease activity and serum ANCA levels. Tocilizumab can also suppress ANCA-associated vasculitis.

Predictors of hypogammaglobulinemia in ANCA-associated vasculitis after a rituximab-based induction: a multicentre study.

OBJECTIVES: Rituximab has become the cornerstone of induction treatment in ANCA-associated vasculitis (AAV). B-cell depletion may increase the risk of hypogammaglobulinemia, potentially leading to severe infections. This study aims to assess factors associated with hypogammaglobulinemia in AAV patients treated with rituximab. METHODS: This retrospective cohort study included AAV patients treated with rituximab induction in 14 European centres. Severe adverse events (SAEs) were defined as episodes requiring hospitalization or intravenous antibiotics, malignancies, or death. Linear and logistic regression were used to identify predictors of IgG levels and of the risk of hypogammaglobulinemia, defined as IgG ≤7 g/l at 6 months. RESULTS: The study included 227 patients. IgG levels at 6 months were lower than baseline (P < 0.001). Patients requiring intravenous antibiotics during the first 6 months had lower IgG levels at 6 months (P = 0.004). Age [ß (95% CI): -0.23 (-0.38, -0.08) per 10 years, P = 0.003], oral glucocorticoid dose at induction [ß (95% CI): -0.37 (-0.51, -0.24) per sqrt-transformed mg prednisone, P < 0.001] and concomitant use of intravenous glucocorticoid pulses [ß (95% CI): -0.88 (-1.73, -0.02), P = 0.044] were associated with IgG levels at 6 months. Hypogammaglobulinemia was identified in 97 (42.7%) patients. In multivariable logistic regression, factors associated with the risk of hypogammaglobulinemia were age [OR (95% CI): 1.46 (1.15, 1.86) per 10 years, P = 0.002] and oral glucocorticoid dose at induction [OR (95% CI): 1.52 (1.23, 1.89) per 10 mg prednisone, P < 0.001]. CONCLUSIONS: In AAV patients treated with rituximab, hypogammaglobulinemia at 6 months after induction is common, and lower IgG levels are associated with serious infections. The risk of hypogammaglobulinemia in these patients increases with age and higher glucocorticoid doses.

Hypertrophic Pachymeningitis Associated with Myeloperoxidase-anti-neutrophil Cytoplasmic Antibodies Induced by Propylthiouracil.

A 71-year-old man with hyperthyroidism complained of headache lasting two months. He had been using propylthiouracil (PTU) for 14 years. Treatment intensification did not improve the symptoms. Blood tests detected a positive myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA). Diffuse dural thickening was identified by magnetic resonance imaging. The patient was diagnosed with hypertrophic pachymeningitis (HP) due to ANCA-associated vasculitis (AAV). He received methylprednisolone pulse therapy followed by prednisolone and methotrexate, which improved his headache. PTU-induced AAV-related HP is a rare and indiscernible disease. Therefore, the possibility of the disease should be proactively considered when a PTU user experiences refractory headaches.

Favourable outcome of acute hepatitis E infection in patients with ANCA-associated vasculitis.

BACKGROUND: Hepatitis E virus (HEV) infection is a frequent cause of acute viral hepatitis. Immunocompromised patients are at increased risk for viral infection and chronic courses of hepatitis. Whether patients with autoimmune diseases are at risk of developing clinically relevant hepatitis or even chronic liver disease after HEV infection is discussed controversially. ANCA-associated vasculitis is a rare autoimmune disease with potentially life-threatening organ involvement, thus requiring intensive immunosuppression with glucocorticoids, cyclophosphamide, or rituximab. As there are no reports available on the infection with HEV in patients with ANCA-associated vasculitis, clinical decision making in such cases is based on experiences from other disease entities. Therefore, in this study we analyzed the course of liver disease and the therapeutic management of autoimmune vasculitis in a retrospective cohort of five patients with ANCA-associated vasculitis and acute hepatitis E. RESULTS: Four patients were on immunosuppressive maintenance therapy and one patient was on remission induction therapy with cyclophosphamide and high dose glucocorticoids. All patients had at least one potentially hepatotoxic co-medication at the time of hepatitis. Hepatitis-associated clinical symptoms were recorded in four of five patients. The course of hepatitis was characterized by strongly elevated transaminases, a temporary liver failure was observed in one case. The management of hepatitis E included cessation of the immunosuppressants in all patients, whereas oral glucocorticoids were not discontinued. Under this regime, all patients cleared the virus without additional anti-viral treatment. Liver enzymes normalized one month after they peaked. In the follow-up period of at least 1.5 years (range 1.5-12 years), no chronic liver disease was observed, although one patient died of cholangiocarcinoma with liver metastases some years after HEV infection. Vasculitis was not active in our patient cohort at the time of HEV infection. However, inflammatory flares occured in three of five patients after discontinuation of the immunosuppressive therapy. Immunosuppressants were paused for a median time of 4 weeks and after their resumption vasculitic disease activity was controlled in all patients. CONCLUSIONS: Acute HEV infection in patients with ANCA-associated vasculitis shows a favorable outcome of liver disease but bears the risk of inflammatory flares due to cessation of immunosuppression.

Steroid Sparing Therapies for Antineutrophil Cytoplasmic Autoantibodies Associated Vasculitis.

Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis comprises a rare entity of disorders that affects primarily small and medium-sized blood vessels. Since first documented in 1897, we have come a long way trying to understand the pathogenesis and finding an optimal treatment regimen. The pathogenesis of ANCA vasculitis is not well understood and despite many advances in treatment, the morbidity and mortality remains high. Over the last decade, there have been many advancements toward elucidating the pathogenesis, optimizing current therapies, and discovering new medicines. Presently, one trend is aimed at minimizing the adverse effects of glucocorticoids by reducing their use without sacrificing efficacy and safety. A new medicine targeting the alternative complement system has emerged and intends to replace glucocorticoids. Here, we review three articles that describe these new trends in the management of ANCA vasculitis.

Antineutrophil Cytoplasmic Antibody-associated Vasculitis after COVID-19 Vaccination with Pfizer-BioNTech.

The extent of rare side effects of mRNA vaccines for coronavirus disease 2019 (COVID-19) remains unclear. Several cases of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) following COVID-19 vaccination have been reported. We herein report a 72-year-old man who presented with a fever after receiving the second dose of the Pfizer-BioNTech COVID-19 vaccine. He was diagnosed with acute kidney injury due to myeloperoxidase-ANCA-associated vasculitis and was treated with intermittent hemodialysis, high-dose prednisolone, and intravenous rituximab. His general symptoms and renal impairment subsequently improved. When systemic symptoms are prolonged or renal abnormalities appear after COVID-19 vaccination, the possibility of AAV should be considered.

Evaluation of Rituximab for Induction and Maintenance Therapy in Patients 75 Years and Older With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Importance: Older patients are underrepresented in studies of rituximab for the treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Little is known about outcomes and adverse events associated with the use of rituximab therapy among patients 75 years and older with ANCA-associated vasculitis. Objective: To examine outcomes and adverse events associated with the use of rituximab therapy in patients 75 years and older with ANCA-associated vasculitis, specifically granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Design, Setting, and Participants: This multicenter cohort study involved 93 patients 75 years and older with ANCA-associated vasculitis from 36 university and nonuniversity hospitals in France. Data were obtained from the French Vasculitis Study Group database between January 1, 2000, and July 1, 2018, and a call for observation sent to French Vasculitis Study Group members on June 6, 2019. Data analysis was performed from November 15 to December 31, 2021. Inclusion criteria included a diagnosis of GPA or MPA according to European Medicines Agency classification criteria and receipt of treatment with rituximab after age 75 years. Patients were excluded if they were missing relevant clinical or biological data. Data on race and ethnicity were not reported because inclusion of this information was not authorized by the ethics committee. Exposure: At least 1 infusion of rituximab as induction or maintenance therapy. Main Outcomes and Measures: Occurrence of remission, relapse, drug discontinuation, death, and serious infections (including types of serious infections). Results: Of 238 patients screened, 93 were included (median [IQR] age, 79.4 [76.7-83.1] years; 51 women [54.8%]); 52 patients (55.9%) had a diagnosis of GPA, and 41 (44.1%) had a diagnosis of MPA. Thirty patients (32.3%) received rituximab as induction therapy in combination with high-dose glucocorticoid regimens, 27 (29.0%) received rituximab as maintenance therapy, and 36 (38.7%) received rituximab as both induction and maintenance therapy. The median (IQR) follow-up was 2.3 (1.1-4.0) years. Among 66 patients who received rituximab as induction therapy, 57 (86.4%) achieved remission, and 2 (3.0%) experienced relapses. The incidence of serious infection was significantly higher when rituximab was used as induction therapy vs maintenance therapy (46.6 [95% CI, 24.8-79.7] per 100 patient-years vs 8.4 [95% CI, 3.8-15.9] per 100 patient-years; P = .004). Most infections (12 of 22 [54.5%]) were gram-negative bacterial infections. The incidence of death was 19.7 (95% CI, 7.2-42.9) per 100 patient-years among those who received rituximab as induction therapy and 5.3 (95% CI, 1.9-11.6) per 100 patient-years among those who received rituximab as maintenance therapy. Conclusions and Relevance: In this cohort study, rituximab therapy was associated with achievement and maintenance of remission in most patients 75 years and older with ANCA-associated vasculitis. The incidence of serious infections and death was high when rituximab was used as induction therapy in combination with high-dose glucocorticoid regimens but not when rituximab was used as maintenance therapy. Efforts might focus on reducing serious infections during the first months of therapy.