-
The Journal of Rheumatology Sep 2023To clarify seasonal and other environmental effects on the onset of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).
Seasonal Influence on Development of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Retrospective Cohort Study Conducted at Multiple Institutions in Japan (J-CANVAS).
OBJECTIVE
To clarify seasonal and other environmental effects on the onset of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).
METHODS
We enrolled patients with new-onset eosinophilic granulomatosis with polyangiitis (EGPA), microscopic polyangiitis (MPA), and granulomatosis with polyangiitis (GPA) registered in the database of a Japanese multicenter cohort study. We investigated the relationship between environmental factors and clinical characteristics. Seasons were divided into 4 (spring, summer, autumn, and winter), and the seasonal differences in AAV onset were analyzed using Pearson chi-square test, with an expected probability of 25% for each season.
RESULTS
A total of 454 patients were enrolled, with a mean age of 70.9 years and a female proportion of 55.5%. Overall, 74, 291, and 89 patients were classified as having EGPA, MPA, and GPA, respectively. Positivity for myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA was observed in 355 and 46 patients, respectively. Overall, the seasonality of AAV onset significantly deviated from the expected 25% for each season ( = 0.001), and its onset was less frequently observed in autumn. In ANCA serotypes, seasonality was significant in patients with MPO-ANCA ( < 0.001), but not in those with PR3-ANCA ( = 0.97). Additionally, rural residency of patients with AAV was associated with PR3-ANCA positivity and biopsy-proven pulmonary vasculitis.
CONCLUSION
The onset of AAV was influenced by seasonal variations and was less frequently observed in autumn. In contrast, the occurrence of PR3-ANCA was triggered, not by season, but by rural residency.
Topics: Humans; Female; Aged; Granulomatosis with Polyangiitis; Antibodies, Antineutrophil Cytoplasmic; Seasons; Churg-Strauss Syndrome; Retrospective Studies; Cohort Studies; Japan; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Myeloblastin; Microscopic Polyangiitis; Peroxidase
PubMed: 37263656
DOI: 10.3899/jrheum.2023-0040 -
Long-term safety and efficacy of mogamulizumab (anti-CCR4) for treating virus-associated myelopathy.Brain : a Journal of Neurology Aug 2023Some carriers of human T-cell leukaemia virus type 1 (HTLV-1), a retrovirus that primarily infects CD4+ T cells and causes lifelong infection, develop HTLV-1-associated...
Some carriers of human T-cell leukaemia virus type 1 (HTLV-1), a retrovirus that primarily infects CD4+ T cells and causes lifelong infection, develop HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Current treatments for HAM/TSP are insufficient with problematic long-term side effects. This study evaluated the long-term safety and efficacy of the anti-CCR4 antibody mogamulizumab in patients with HAM/TSP over a 4-year period. We conducted an open-label, extended long-term study (UMIN trial number: UMIN000019942) of a phase 1-2a trial with mogamulizumab for HAM/TSP (UMIN000012655). The study participants were patients with corticosteroid-resistant HAM/TSP who could walk 10 m with or without assistive tools. Mogamulizumab was administered at 0.01, 0.03, 0.1 or 0.3 mg/kg at intervals of ≥8 weeks (0.01 and 0.03 mg/kg) or ≥12 weeks (0.1 and 0.3 mg/kg). HTLV-1 proviral load, CSF inflammatory markers and clinical symptoms were summarized by descriptive statistics. Missing observations were imputed using the last-observation-carried-forward method. As a post hoc analysis, we evaluated the therapeutic effect of mogamulizumab on gait function by comparing it with contemporary control data from a HAM/TSP patient registry. Of the 21 participants in the phase 1-2a, 18 (86%) enrolled in the long-term study and 15 (71%) continued repeated doses of mogamulizumab for 4 years. The median dose was 0.1 mg/kg after 4 years. Seventeen of 21 participants (81%) experienced grade 1-2 skin-related adverse events. Observed grade 3 drug-related adverse effects included three cases of lymphopenia and one case each of microscopic polyangiitis, elevated levels of aspartate aminotransferase, and neutropenia. Four of 21 participants (19%) developed neutralizing antibodies. After 4 years, the peripheral blood proviral load and the number of infected cells in CSF decreased by 60.7% and 66.3%, respectively. Neopterin and CXCL10 CSF concentrations decreased by 37.0% and 31.0%, respectively. Among the 18 participants, spasticity and Osame Motor Disability Score (OMDS) improved in 17 (94%) and four (22%), respectively. However, 10 m walking time worsened by 7.3% on average. Comparison with the contemporary control group demonstrated that mogamulizumab inhibited OMDS progression (P = 0.02). The results of the study suggest that mogamulizumab has long-term safety and inhibitory effects on lower limb motor disability progression in corticosteroid-treated patients with HAM/TSP. This will provide a basis for the application of mogamulizumab in HAM/TSP treatment.
Topics: Humans; Disabled Persons; Motor Disorders; Paraparesis, Tropical Spastic; Human T-lymphotropic virus 1
PubMed: 37093965
DOI: 10.1093/brain/awad139 -
Rheumatology (Oxford, England) Apr 2024To evaluate the effectiveness and safety of two different intravenous methylprednisolone (IVMP) pulse doses in patients with severe microscopic polyangiitis (MPA) and...
OBJECTIVES
To evaluate the effectiveness and safety of two different intravenous methylprednisolone (IVMP) pulse doses in patients with severe microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA).
METHODS
We emulated a target trial using observational data from the nationwide registry in Japan. Patients with severe glomerulonephritis or diffuse alveolar haemorrhage were selected and pseudo-randomised into three groups using propensity score-based overlap weighting as follows: non-IVMP, IVMP 0.5 g/day, and IVMP 1.0 g/day. The primary outcome was all-cause death, and the secondary outcomes were composite all-cause death and kidney failure, severe relapse, and serious infection from 2 to 48 weeks after treatment initiation. To estimate the treatment effects, the Cox proportional hazard model and Fine-Gray subdistribution hazard model were used.
RESULTS
In this emulated target trial, of 201 eligible patients (MPA, 175; GPA, 26), 6 (2.8%) died, 4 (2.0%) had kidney failure, 11 (5.3%) had severe relapse, and 40 (19.8%) had severe infections. Hazard ratios (HR) for IVMP 0.5 g/day and IVMP 1.0 g/day pulse groups compared with non-IVMP pulse were as follows: all-cause death = 0.46 (95% confidence interval [95%CI]: 0.07-2.81) and 0.07 (95%CI: 0.01-0.41); all-cause death/kidney failure = 1.18 (95%CI: 0.26-5.31) and 0.59 (95%CI: 0.08-4.52); subdistribution HRs for severe relapse = 1.26 (95%CI: 0.12-13.70) and 3.36 (95%CI: 0.49-23.29); and serious infection = 1.88 (95%CI: 0.76-4.65) and 0.94 (95%CI: 0.28-3.13).
CONCLUSIONS
IVMP 1.0 g/day pulse may improve 48-week mortality in patients with severe MPA/GPA.
PubMed: 38608193
DOI: 10.1093/rheumatology/keae219 -
International Journal of Rheumatic... Dec 2023This study aimed to investigate the clinical outcomes of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) under rituximab induction and...
OBJECTIVES
This study aimed to investigate the clinical outcomes of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) under rituximab induction and reinduction therapy in Taiwan.
METHODS
We performed a retrospective study in patients with GPA or MPA receiving rituximab therapy from August 2008 to July 2020 in seven medical centers in Taiwan. The clinical characteristics and outcomes of these patients were analyzed.
RESULTS
In total, 53 patients (18 with GPA and 35 with MPA) were included. Kidney involvement (82.9% vs. 22.2%, p < .001) and initial creatinine (3.25 ± 2.37 vs. 1.07 ± 0.82, p < .001) were significantly higher in MPA. Within 24 weeks after the first course of rituximab, there were seven deaths (five due to infection and two due to active disease) in patients with MPA (7/35, 20%) compared to 0 in patients with GPA. Of 33 patients receiving rituximab for kidney involvement, 23 survived and were free from renal replacement therapy at 24 weeks. Their chronic kidney disease (CKD) stages improved in 2 but progressed in 7, while 24 had stable CKD stages. Death or end-stage renal disease (ESRD) was associated with infection and higher initial creatinine. Reinduction therapy for relapse was required in 18 (39.1%) of 46 survivors, which was associated with anti-proteinase 3 (PR3) positive (odds ratio 3.667, p = .049) and younger age with a cutoff of 49.4 (AUC = 0.679, p = .030, sensitivity = 66.67%, specificity = 75%).
CONCLUSION
Significant mortality occurred after rituximab induction, especially in patients with MPA. In survivors, age younger than 50 and anti-PR3 positive were associated with the risk of relapse requiring reinduction.
Topics: Humans; Rituximab; Microscopic Polyangiitis; Retrospective Studies; Granulomatosis with Polyangiitis; Taiwan; Creatinine; Myeloblastin; Kidney Failure, Chronic; Recurrence
PubMed: 37784228
DOI: 10.1111/1756-185X.14929 -
International Journal of Rheumatic... Aug 2023Pulmonary involvement is an important cause of mortality and morbidity in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). In this study, we...
OBJECTIVE
Pulmonary involvement is an important cause of mortality and morbidity in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). In this study, we aimed to evaluate the type and frequency of pulmonary involvement and investigate the potential relationship between thorax computed tomography (CT) signs and other systemic clinical findings in AAV.
METHODS
A total of 63 patients over the age of 18 and diagnosed with AAV were included in this study. Thoracic CT imaging findings and clinical features of the patients at the time of diagnosis were retrospectively evaluated. The frequency and distribution of detected pathological findings on imaging according to disease types, in addition to the relationship of these findings with other systemic findings and disease severity, were analyzed.
RESULTS
Of 63 patients, 50 (79.4%) had pulmonary symptoms at the time of presentation. Most frequently observed pulmonary finding of thorax CT was nodular opacity. Consolidation, cavitary nodules, bronchiectasis, emphysema and fibrotic sequelae change were more common in the patients with diagnosis of granulomatosis with polyangiitis. Honeycomb, atelectasis, interstitial pneumonia, pulmonary venous congestion and pleural effusion were more common in the patients with diagnosis of microscopic polyangiitis. Ground-glass appearance, central airway disease, peribronchovascular nodules, pericardial effusion and lymphatic adenomegaly (>10 mm) were more common in the patients with diagnosis of eosinophilic granulomatosis with polyangiitis. Interstitial lung disease, pulmonary hemorrhage and severe lung involvement were found significantly increased in patients with myeloperoxidase antibody (MPO)-ANCA positivity (P < 0.05).
CONCLUSION
Lung involvement was detected in almost all of the patients with AAV. Both interstitial lung disease and severe lung involvement were more frequently found in patients with MPO-ANCA positivity compared to other patients. Pulmonary examination by an imaging technique in all patients with AAV may be useful to determine the vasculitis subtype and to determine the extent of the disease.
PRACTITIONER POINTS
Pulmonary involvement is quite common in AAV. Every patient with suspected AAV should be examined with imaging for lung involvement, even in the absence of respiratory symptoms. Severe pulmonary involvement is associated with the presence of severe disease and MPO-ANCA positivity.
Topics: Humans; Adult; Middle Aged; Antibodies, Antineutrophil Cytoplasmic; Granulomatosis with Polyangiitis; Churg-Strauss Syndrome; Retrospective Studies; Turkey; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Lung Diseases, Interstitial
PubMed: 37287386
DOI: 10.1111/1756-185X.14764 -
Modern Rheumatology Dec 2023The objective of this study was to compare the American College of Rheumatology/European Alliance of Associations for Rheumatology 2022 criteria with the previous...
OBJECTIVE
The objective of this study was to compare the American College of Rheumatology/European Alliance of Associations for Rheumatology 2022 criteria with the previous classification algorithm for anti-neutrophil cytoplasmic antibody-associated vasculitis.
METHODS
We used data from two nationwide, prospective, inception cohort studies. The enrolled patients were classified as having eosinophilic granulomatosis with polyangiitis (EGPA), granulomatosis with polyangiitis (GPA), or microscopic polyangiitis (MPA) according to the new criteria; these criteria were compared with Watts' algorithm.
RESULTS
Among 477 patients, 10.7%, 9.9%, and 75.6% were classified as having EGPA, GPA, and MPA, respectively; 6.1% were unclassifiable. Three patients met both the EGPA and MPA criteria, and eight patients met both the GPA and MPA criteria. Of 78 patients with GPA classified using Watts' algorithm, 27 (34.6%) patients were reclassified as having MPA. Ear, nose, and throat involvement was significantly less frequent in patients reclassified as having MPA than in those reclassified as having GPA. Of 73 patients unclassifiable using Watts' algorithm, 62 were reclassified as having MPA. All patients reclassified as having MPA were myeloperoxidase-anti-neutrophil cytoplasmic antibody positive, and 46 had interstitial lung disease.
CONCLUSION
Although the American College of Rheumatology/European Alliance of Associations for Rheumatology 2022 criteria cause overlapping multiple criteria fulfilments in some patients, those items contribute to classifying unclassifiable patients using Watts' algorithm into MPA.
Topics: Humans; United States; Granulomatosis with Polyangiitis; Churg-Strauss Syndrome; Prospective Studies; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Microscopic Polyangiitis; Antibodies, Antineutrophil Cytoplasmic
PubMed: 36715080
DOI: 10.1093/mr/road017 -
Journal of Internal Medicine May 2024Microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are the two major antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).
BACKGROUND
Microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are the two major antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).
OBJECTIVES
To characterize a homogenous AAV cohort and to assess the impact of clinicopathological profiles and ANCA serotypes on clinical presentation and prognosis. Clinical differences in GPA patients according to ANCA serotype and the diagnostic yield for vasculitis of biopsies in different territories were also investigated.
RESULTS
This retrospective study (2000-2021) included 152 patients with AAV (77 MPA/75 GPA). MPA patients (96.1% myeloperoxidase [MPO]-ANCA and 2.6% proteinase 3 [PR3]-ANCA) presented more often with weight loss, myalgia, renal involvement, interstitial lung disease (ILD), cutaneous purpura, and peripheral nerve involvement. Patients with GPA (44% PR3-ANCA, 33.3% MPO, and 22.7% negative/atypical ANCA) presented more commonly with ear, nose, and throat and eye/orbital manifestations, more relapses, and higher survival than patients with MPA. GPA was the only independent risk factor for relapse. Poor survival predictors were older age at diagnosis and peripheral nerve involvement. ANCA serotypes differentiated clinical features in a lesser degree than clinical phenotypes. A mean of 1.5 biopsies were performed in 93.4% of patients in different territories. Overall, vasculitis was identified in 80.3% (97.3% in MPA and 61.8% in GPA) of patients.
CONCLUSIONS
The identification of GPA presentations associated with MPO-ANCA and awareness of risk factors for relapse and mortality are important to guide proper therapeutic strategies in AAV patients. Biopsies of different affected territories should be pursued in difficult-to-diagnose patients based on their significant diagnostic yield.
Topics: Humans; Granulomatosis with Polyangiitis; Microscopic Polyangiitis; Antibodies, Antineutrophil Cytoplasmic; Retrospective Studies; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Myeloblastin; Recurrence
PubMed: 38462959
DOI: 10.1111/joim.13777 -
Journal of Nephrology Nov 2023Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis is associated with end-organ damage resulting in significant morbidity and mortality. Most recently,...
Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis is associated with end-organ damage resulting in significant morbidity and mortality. Most recently, avacopan, an orally administered selective antagonist of the C5a receptor, was approved by the US Food and Drug Administration as an adjunctive treatment of adult patients with severe, active ANCA-associated vasculitis (granulomatosis with polyangiitis and microscopic polyangiitis) in combination with standard therapy including glucocorticoids. This case study describes a 58-year-old Asian female with severe ANCA-associated vasculitis and acute renal failure who responded to adjunctive therapy with avacopan despite being refractory to rituximab and glucocorticoid therapy.
Topics: Adult; Humans; Female; Middle Aged; Immunosuppressive Agents; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Rituximab; Aniline Compounds; Glucocorticoids; Antibodies, Antineutrophil Cytoplasmic; Granulomatosis with Polyangiitis; Remission Induction
PubMed: 37036661
DOI: 10.1007/s40620-023-01614-y -
Expert Review of Clinical Immunology Jul 2024ANCA-associated vasculitides (AAV), classified into granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis... (Review)
Review
INTRODUCTION
ANCA-associated vasculitides (AAV), classified into granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis represent a group of disorders characterized by necrotizing vasculitis of small vessels, endothelial injury and tissue damage. The outcomes and prognosis of AAV have undergone significant changes with the introduction of glucocorticoids (GCs) and other immunosuppressants (cyclophosphamide, azathioprine, methotrexate, and mycophenolate mofetil). The enhanced understanding of pathogenesis has subsequently led to the incorporation into clinical practice of drugs targeting specific therapeutic targets.
AREAS COVERED
After an extensive literature search of Pubmed, Medline, Embase of the most recent evidence, we provide an overview of available treatments, highlighting how newer drugs have integrated into standard protocols. Our review also explores potential new therapeutic targets, including B cell depletion and inhibition, T cell inhibition, complement inhibition, and IL-5 and IgE inhibition.
EXPERT OPINION
There is hope that the new treatment targets currently under study in AAV may enable a faster and more lasting clinical response, ensuring the reduction of possible side effects from therapies. Moreover, numerous aspects necessitate further exploration in the future, such as tailoring of GCs, integration of GCs-sparing agents, efficacy of combination therapy, optimal maintenance therapy, to reduce organ-damage and improve quality of life.
Topics: Humans; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Immunosuppressive Agents; Glucocorticoids; B-Lymphocytes; T-Lymphocytes; Molecular Targeted Therapy; Interleukin-5; Animals
PubMed: 38445642
DOI: 10.1080/1744666X.2024.2326628 -
Autoimmunity Reviews Jan 2024Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) encompasses a group of rare, multisystem autoimmune disorders characterised by the occurrence of... (Review)
Review
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) encompasses a group of rare, multisystem autoimmune disorders characterised by the occurrence of inflammation and damage to small blood vessels, leading to a wide range of clinical manifestations. They include granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Outcomes for patients with MPA and GPA have been transformed over recent years. However, the establishment of effective maintenance therapy aiming to balance the risks of disease relapse with those related to prolonged immunosuppression has become a clinical priority. This review aims to explore two differing perspectives on this unsolved problem. Pros and Cons of the following approaches will be discussed: "Biomarker-guided personalised approach on top of generic maintenance strategy guidelines" or "ANCA specificity-related personalised maintenance treatment after intensive B-cell depletion"?
Topics: Humans; Granulomatosis with Polyangiitis; Antibodies, Antineutrophil Cytoplasmic; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Microscopic Polyangiitis; Biomarkers
PubMed: 37652397
DOI: 10.1016/j.autrev.2023.103438