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ImportanceResults of randomized clinical trials have demonstrated rituximab’s noninferiority to cyclophosphamide as induction therapy for antineutrophil cytoplasm antibody (ANCA)–associated vasculitides (AAV), with neither treatment having a specific advantage for granulomatosis with polyangiitis (GPA). However, post hoc analysis results have suggested that rituximab might be more effective than cyclophosphamide in inducing remission in patients with proteinase 3–positive AAV.ObjectiveTo compare the effectiveness of rituximab and cyclophosphamide in inducing GPA remission in a large population of unselected patients.Design, Setting, and ParticipantsThis comparative effectiveness study used multicenter target trial emulation observational data from 32 French hospitals in the French Vasculitis Study Group Registry. Groups were determined according to treatments received, without any intervention from the investigators. Inverse probability of treatment weighting was used to correct for baseline imbalance between groups. Participants included patients with newly diagnosed or relapsing GPA who satisfied American College of Rheumatology classification criteria and/or Chapel Hill Consensus Conference nomenclature. Data were analyzed from October 1, 2021, to May 31, 2022.ExposuresAt least 1 infusion of rituximab or cyclophosphamide for induction therapy between April 1, 2008, and April 1, 2018.Main Outcomes and MeasuresThe primary outcome was remission rate at month 6 (±2 months), with remission defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 and prednisone dose of 10 mg/d or less. The BVAS is a validated tool for small-vessel vasculitis and used to assess the level of disease activity, with a numerical weight attached to each involved organ system. The BVAS has a range of 0 to 63 points; a score of 0 indicates no disease activity. Subgroup analyses included the primary outcome for patients with a new diagnosis, for most recently treated patients, and for patients with myeloperoxidase-ANCA positivity.ResultsAmong 194 patients with GPA included in the analysis (mean [SD] age, 54 [15] years; 110 men [56.7%]), 165 (85.1%) had a new diagnosis, and 147 of 182 with data available (80.8%) had proteinase 3–ANCA positivity. Sixty-one patients received rituximab and 133 received cyclophosphamide for induction therapy. In the weighted analysis, the primary outcome was reached for 73.1% of patients receiving rituximab vs 40.1% receiving cyclophosphamide (relative risk [RR], 1.82 [95% CI, 1.22-2.73]; risk difference, 33.0% [95% CI, 12.2%-53.8%]; E value for RR, 3.05). Similar results were observed in the subgroup of patients with newly diagnosed GPA and those with a more recent treatment. In the subset of 27 patients with myeloperoxidase-ANCA–positive GPA, 8 of 10 rituximab recipients and 8 of 17 cyclophosphamide recipients met the primary end point (unweighted RR, 1.73 [95% CI, 0.96-3.11]).Conclusions and RelevanceIn this comparativeness effectiveness study using clinical data, rituximab induction therapy for GPA was more frequently associated with remission than cyclophosphamide. These results inform clinical decision-making concerning the choice of remission induction therapy for this subset of patients with AAV.

ObjectiveTo investigate whether antineutrophil cytoplasm antibody (ANCA)-negative and myeloperoxidase (MPO)-ANCA–positive granulomatosis with polyangiitis (GPA) differ from proteinase-3 (PR3)-ANCA–positive GPA.MethodsDiagnostic characteristics and outcomes of newly diagnosed French Vasculitis Study Group Registry patients with ANCA-negative, MPO-ANCA–positive or PR3-ANCA–positive GPA satisfying American College of Rheumatology criteria and/or Chapel Hill Conference Consensus Nomenclature were compared.ResultsAmong 727 GPA, 62 (8.5%) were ANCA-negative, 119 (16.4%) MPO-ANCA–positive and 546 (75.1%) PR3-ANCA–positive. ANCA-negative patients had significantly (pConclusionsBased on this large cohort, ANCA-negative versus ANCA-positive patients more frequently had limited disease but similar RFS and OS. MPO-ANCA–positive patients had similar RFS but lower OS due to their older age. PR3-ANCA–positive GPA patients’ RFS was lower than those of the two other subsets combined but that difference did not persist when comparing only PR3 versus MPO-ANCA–positive patients.

Introduction: Renal involvement is a severe manifestation of antineutrophil cytoplasmic antibody-associated vasculitis. Patients often progress to end-stage renal disease. The potential for renal recovery after the first flare has seldom been studied. Our objectives were to describe the evolution of the estimated glomerular filtration rate (eGFR) and identify factors associated with the change in the eGFR between diagnosis and the follow-up at 3 months (ΔeGFRM0–M3). Methods: This was a retrospective study over the period 2003–2018 of incident patients in the Nord-Pas-de-Calais (France). The primary outcome was the ΔeGFRM0–M3. Results: One hundred and seventy-seven patients were included. The eGFR at 3 months was significantly higher than at diagnosis (mean ± standard deviation, 40 ± 24 vs. 28 ± 26 mL/min/1.73 m2, p < 0.001), with a ΔeGFRM0–M3 of 12 ± 19 mL/min/1.73 m2. The eGFR at 12 months was higher than at 3 months (44 ± 13 vs. 40 ± 24 mL/min/1.73 m2, p = 0.003). The factors significantly associated with the ΔeGFRM0–M3 in multivariate analysis were the percentage of cellular crescents and neurological involvement. The mean increase in the eGFR was 2.90 ± 0.06 mL/min/1.73 m2 for every 10-point gain in the percentage of cellular crescents. Conclusions: Early renal recovery after the first flare of pauci-immune glomerulonephritis occurred mainly in the first 3 months of treatment. The percentage of cellular crescents was the main independent predictor of early renal recovery.

Renal disease in ANCA-associated vasculitis (AAV) is characterized by a pauci-immune necrotizing glomerulonephritis. Renal biopsy is essential for diagnosis, treatment strategy and also for the long-term prognosis of AAV. The prospective randomized trials conducted by the EUVAS and GFEV have contributed to define therapeutic guidelines. The current standard of care can be divided into two phases: initial immunosuppression for rapid and effective onset of remission and subsequent maintenance therapy to prevent relapses. Despite these recent therapeutic advances, mortality and morbidity, such as end-stage renal failure, remain high, related to diagnosis delay, drug-related toxicity, refractory disease and propensity of AAV to relapse. Conventional therapies need to be optimized, especially in high-risk patients. Targeting B-cells with rituximab is a new and attractive therapeutic option, but long term benefits and safety are still unknown.

The prevalence of anticardiolipin antibodies (aCL) and of vascular diseases increases with age, and aCL may be associated with various diseases in the elderly. So the significance of aCL in the elderly remains difficult to determine. We sought to determine the significance of persistent antiphospholipid antibodies (aPL) in the elderly.We retrospectively analyzed the files of 327 patients [149 patients with antiphospholipid syndrome (APS); 64 patients ageor= 65 yrs] with 2 positive aPL [lupus anticoagulant (LAC) and/or aCL].The frequency of APS was 40.8% (n = 134) in our 263 young patients (65 yrs) and 23.4% (n = 15) in our 64 elderly patients (or= 65 yrs). The clinical characteristics of patients with persistent aPL were the same in those under and over 65 years. LAC was positive in all but one elderly patient with APS, and occurred in this group more frequently than in the young patients (93.3% vs 44.6%; p0.006). The presence of LAC allowed to discriminate APS patients in our elderly population (93.3% in APS vs 48.9% in non-APS patients; p0.009).Interpretation of a positive determination of APL is difficult in the elderly; persistent LAC may be the most valuable biological marker of APS in the elderly.

Takayasu arteritis is an inflammatory arteritis affecting large vessels, predominantly the aorta and its main branches. Thickening of the vessel wall is an early hallmark of the disease and leads to stenosis, thrombosis, and sometimes aneurysm formation. Reported incidence ranges from 1.2 to 2.6/million/year. Women aged 20 to 40 are most likely to suffer from the disease than men. Manifestations are very polymorphous, with presentations ranging from asymptomatic to neurologic catastrophes. Prognosis depends essentially on complications (retinopathy, hypertension, aneurysm, aortic insufficiency) and initial disease aggressivity. Diagnosis is based on imaging methods. Doppler ultrasound, computed tomography, and magnetic resonance imaging are fast and reliable methods for assessing vessel anatomy and luminal status. Positron emission tomography with fluorodeoxyglucose appears to be a highly sensitive and effective method for detecting disease activity, especially since standard inflammatory markers seem ineffective. Until now, corticosteroids have been the treatment of choice. If remission does not occur, methotrexate is added. Percutaneous transluminal angioplasty and sometimes vascular surgery is necessary in cases of critical ischemia or threatening aneurysm. Duration of treatment, choice of second-line treatment, and protocol for tapering medication currently depend more on experience than on evidence-based medicine. Multicenter studies are needed to guide future practice.