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Morales E, Rúa-Figueroa I, Callejas Rubio JL, Ávila Bernabéu A, Blanco Alonso R, Cid Xutgla MC, Fernández Juárez G, Mena-Vázquez N, Ríos Blanco JJ, Manrique Escola J, Narváez García FJ, Sopeña B, Quintana Porras LF, Romero-Yuste S, Solans Laqué R. Recommendations for the diagnosis and treatment of anti-neutrophil cytoplasmic autoantibody associated vasculitis. Nefrologia 2025; 45:15-58. [PMID: 39855968 DOI: 10.1016/j.nefroe.2025.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Accepted: 07/30/2024] [Indexed: 01/27/2025] Open
Abstract
Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis is characterised by small vessel necrotising inflammatory vasculitis. Prior to immunosupressant therapy availability it usually led to a fatal outcome. Current treatment has changed ANCA-associated vasculitis into a condition with a significant response rate, although with a not negligible relapse occurrence and cumulative organ lesions, mostly due to drug-related toxicities. The use of glucocorticoids, cyclophosphamide and other immunosupressants (such as azathioprine, mychophenolate and methotrexate) was optimised in a series of clinical trials that established the treatment of reference. In recent years, a better knowledge of B lymphocyte function and the role of complement inhibition has transformed the course of this disease while minimising treatment-related adverse effects. This multidisciplinary document of recommendations is based on the consensus of three scientific societies (Internal Medicine, Nephrology and Rheumatology) and on the best available evidence on diagnosis, treatment and follow-up of patients with ANCA-associated vasculitis, including some special situations. The aim of this document is to provide updated information and well-grounded clinical recommendations to practising physicians as to how to improve the diagnosis and treatment outcome of our patients.
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Affiliation(s)
- Enrique Morales
- Servicio de Nefrología, Hospital Universitario 12 de Octubre, Instituto de investigación i + 12 de Hospital 12 de Octubre, Departamento de Medicina de la Universidad Complutense de Madrid, Madrid, Spain.
| | - Iñigo Rúa-Figueroa
- Servicio de Reumatología, Hospital de Gran Canaria Doctor Negrín, Las Palmas, Spain
| | - José Luis Callejas Rubio
- Unidad de Enfermedades Sistémicas, Servicio de Medicina Interna, Hospital Universitario Clínico San Cecilio, Granada, Spain
| | - Ana Ávila Bernabéu
- Servicio de Nefrología, Hospital Universitario Doctor Peset, Valencia, Spain
| | - Ricardo Blanco Alonso
- Servicio de Reumatología, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain
| | - María C Cid Xutgla
- Servicio de Enfermedades Autoinmunes, Hospital Clínic, Universidad de Barcelona, IDIBAPS, Barcelona, Spain
| | | | - Natalia Mena-Vázquez
- UGC de Reumatología, Instituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma Bionand, Hospital Regional Universitario de Málaga, Málaga, Spain
| | - Juan José Ríos Blanco
- Unidad de Enfermedades Autoinmunes, Servicio de Medicina Interna, Hospital Universitario La Paz, Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ), Madrid, Spain
| | | | | | - Bernardo Sopeña
- Unidad de Enfermedades Autoinmunes Sistémicas, Servicio de Medicina Interna, Hospital Clínico Universitario de Santiago, Facultad de Medicina, Santiago de Compostela, Spain
| | - Luis F Quintana Porras
- CSUR Enfermedad Glomerular Compleja, Servicio de Nefrología y Trasplante Renal, Hospital Clinic, Universidad de Barcelona, Barcelona, Spain
| | - Susana Romero-Yuste
- Servicio de Reumatología, Complexo Hospitalario Universitario de Pontevedra, Pontevedra, Spain
| | - Roser Solans Laqué
- Unidad de Enfermedades Sistémicas Autoinmunes, Departamento de Medicina Interna, Hospital Universitario Vall d'Hebron, Barcelona, Spain
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Ni A, Xu Y, Chen J, Han F. Advances in the Assessment and Treatment of Anti-Neutrophil Cytoplasmic Antibody-Associated Glomerulonephritis. J Inflamm Res 2024; 17:11881-11900. [PMID: 39802155 PMCID: PMC11725264 DOI: 10.2147/jir.s494848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Accepted: 12/15/2024] [Indexed: 01/16/2025] Open
Abstract
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune diseases primarily cause inflammation of small blood vessels. Renal involvement occurs frequently and often leads to end-stage renal disease (ESRD), which significantly impacts patient health and survival. Early diagnosis and appropriate treatment are essential to improving patient outcomes. This review provides an overview of the latest advances in the assessment and treatment of ANCA-associated glomerulonephritis (AAGN). The assessment section covers diagnostic tools, disease activity assessment, and risk stratification, with the introduction of the latest ANCA kidney risk score (AKRiS), which aids in identifying high-risk patients and facilitates personalized treatment strategies. The treatment section discusses induction and maintenance therapy, including immunosuppressive agents and emerging therapies. Recent advances have moved treatment away from reliance on cytotoxic agents, focusing on targeted biological therapies to induce and maintain disease remission, while prioritizing the reduction of corticosteroid toxicity. Overall, these advancements have greatly improved patient outcomes and provided new avenues for personalized management of AAGN.
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Affiliation(s)
- Anqi Ni
- Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China
- Institute of Nephrology, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China
| | - Ying Xu
- Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China
- Institute of Nephrology, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China
| | - Jianghua Chen
- Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China
- Institute of Nephrology, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China
| | - Fei Han
- Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China
- Institute of Nephrology, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China
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Chen SF, Li ZY, Zhao MH, Chen M. Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis in China: Epidemiology, Management, Prognosis, and Outlook. KIDNEY DISEASES (BASEL, SWITZERLAND) 2024; 10:407-420. [PMID: 39430288 PMCID: PMC11488837 DOI: 10.1159/000540514] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Accepted: 07/20/2024] [Indexed: 10/22/2024]
Abstract
Background Increasing evidence indicates that clinicopathologic phenotypes and ANCA serotypes may differ ethnically and geographically. This review highlights the progress in the prevalence, pathogenesis, management, and outcomes of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in China. Summary AAV is not rare in China. Cumulative evidence has demonstrated a significant preponderance of microscopic polyangiitis (MPA) and myeloperoxidase (MPO)-ANCA AAV in China. Even in patients with granulomatosis with polyangiitis (GPA), there is a predominance of MPO-ANCA over proteinase 3 (PR3)-ANCA, presenting a unique subset. The pathogenesis of AAV is multifactorial, with the role of complement activation being highlighted during recent years. Treatment strategies for AAV in China have also been refined recently. A rapid tapering of glucocorticoids to minimize exposure has been recommended by the Chinese guidelines. Along with a better understanding of the disease, B cell-targeted therapy and complement-targeted therapy are developing. A considerable number of patients in China received rituximab treatment and achieved remission. However, infection risk and associated mortality still remain concerns. Therefore, less rituximab exposure should be considered and evaluated in Chinese AAV patients. Prognostic factors have been reviewed. Of note, along with improved outcomes, there is an increase of cardiovascular and malignant-related death, warranting specific care. Recently, a modified renal risk score model has been validated for early risk prediction in Chinese AAV patients. Moreover, emerging biomarkers for AAV, including complement components, have been identified in Chinese patients. Key Messages There is a preponderance of MPA and MPO-ANCA in China. Treatment strategies for Chinese AAV patients generally align with those in western countries, and to some extent, less aggressive. Prognostic factors and emerging biomarkers for AAV in China have been identified. Further challenges include optimizing interventions, minimizing treatment-related comorbidities, improving disease monitoring, and enhancing life qualities of AAV patients.
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Affiliation(s)
- Su-Fang Chen
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China
- Institute of Nephrology, Peking University, Beijing, China
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
- Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China
| | - Zhi-Ying Li
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China
- Institute of Nephrology, Peking University, Beijing, China
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
- Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China
| | - Ming-Hui Zhao
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China
- Institute of Nephrology, Peking University, Beijing, China
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
- Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China
| | - Min Chen
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China
- Institute of Nephrology, Peking University, Beijing, China
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
- Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China
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Younger DS. Headaches and Vasculitis. Neurol Clin 2024; 42:389-432. [PMID: 38575258 DOI: 10.1016/j.ncl.2023.12.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/06/2024]
Abstract
Vasculitis refers to heterogeneous clinicopathologic disorders that share the histopathology of inflammation of blood vessels. Unrecognized and therefore untreated, vasculitis of the nervous system leads to pervasive injury and disability making this a disorder of paramount importance to all clinicians. Headache may be an important clue to vasculitic involvement of central nervous system (CNS) vessels. CNS vasculitis may be primary, in which only intracranial vessels are involved in the inflammatory process, or secondary to another known disorder with overlapping systemic involvement. Primary neurologic vasculitides can be diagnosed with assurance after intensive evaluation that incudes tissue confirmation whenever possible.
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Affiliation(s)
- David S Younger
- Department of Medicine, Section of Neuroscience, City University of New York School of Medicine, New York, NY, USA; Department of Neurology, White Plains Hospital, White Plains, NY, USA.
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Sada KE, Nagasaka K, Kaname S, Nango E, Kishibe K, Dobashi H, Hiromura K, Kawakami T, Bando M, Wada T, Amano K, Murakawa Y, Harigai M. Clinical practice guidelines of the Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis for the management of microscopic polyangiitis and granulomatosis with polyangiitis: The 2023 update - secondary publication. Mod Rheumatol 2024; 34:559-567. [PMID: 37599461 DOI: 10.1093/mr/road081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Accepted: 07/05/2023] [Indexed: 08/22/2023]
Abstract
OBJECTIVE To revise the 2017 clinical practice guidelines (CPG) for the management of microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) to reflect advancements in the field. METHODS Similar to the 2017 CPG, the Grading of Recommendations, Assessment, Development, and Evaluation system was adopted for this revision. The intended users of this CPG include patients diagnosed with MPA or GPA in Japan and their families and healthcare professionals, including specialists and non-specialists. Based on a scoping review, four clinical questions (CQs) of the 2017 guidelines were modified, and six new CQs were added. RESULTS We suggest a combination of glucocorticoid and cyclophosphamide or rituximab for remission induction therapy. In cases where cyclophosphamide or rituximab is used, we suggest the use of avacopan over high-dose glucocorticoid. Furthermore, we suggest against the use of plasma exchange in addition to the standard treatment in severe cases of MPA/GPA. Finally, we suggest the use of glucocorticoid and rituximab over glucocorticoid and azathioprine for remission maintenance therapy. CONCLUSIONS The recommendations have been updated based on patient preference, certainty of evidence, benefit and risk balance, and cost.
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Affiliation(s)
| | - Kenji Nagasaka
- Department of Rheumatology, Ome Municipal General Hospital, Ome, Japan
- Department of Rheumatology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan
| | - Shinya Kaname
- Department of Nephrology and Rheumatology, Kyorin University School of Medicine, Tokyo, Japan
| | - Eishu Nango
- Department of Family Medicine, Seibo International Catholic Hospital, Tokyo, Japan
| | - Kan Kishibe
- Department of Otolaryngology-Head & Neck Surgery, Asahikawa Medical University, Asahikawa, Japan
| | - Hiroaki Dobashi
- Division of Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Keiju Hiromura
- Department of Nephrology and Rheumatology, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Tamihiro Kawakami
- Division of Dermatology, Tohoku Medical and Pharmaceutical University, Sendai, Japan
| | - Masashi Bando
- Division of Pulmonary Medicine, Department of Medicine, Jichi Medical University, Tochigi, Japan
| | | | - Koichi Amano
- Department of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan
| | - Yohko Murakawa
- Department of Internal Medicine III, Shimane University Faculty of Medicine, Izumo, Japan
| | - Masayoshi Harigai
- Division of Rheumatology, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan
- Department of Clinical Epidemiology, Kochi Medical School, Nankoku, Japan
- Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
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Li S, Yao S, Tie X, Shi X, Feng R, Su X, Wang L. Enteric-coated Mycophenolate Sodium therApy versus cyclophosphamide for induction of Remission in Microscopic PolyAngiitis (EMSAR-MPA trial): study protocol for a randomised controlled trial. BMJ Open 2024; 14:e074662. [PMID: 38471694 PMCID: PMC10936518 DOI: 10.1136/bmjopen-2023-074662] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Accepted: 02/22/2024] [Indexed: 03/14/2024] Open
Abstract
INTRODUCTION Several studies have demonstrated that mycophenolate mofetil (MMF) may be an excellent alternative to cyclophosphamide (CYC) or rituximab for the induction of remission in non-life-threatening anti-neutrophil cytoplasmic antibodies associated vasculitis because of its strong immunosuppressive potency and low toxicity profile. Enteric-coated mycophenolate sodium (EC-MPS) was introduced to reduce gastrointestinal adverse reactions of MMF. This study will evaluate the efficacy and safety of EC-MPS combined with glucocorticoid in patients with active and non-life-threatening microscopic polyangiitis (MPA). METHODS AND ANALYSIS This study is a multicentre, open-label, randomised controlled, non-inferiority trial. A total of 110 patients with active and non-life-threatening MPA from 11 hospitals in Shanxi Province of China will be recruited and randomised in a 1:1 ratio to receive either EC-MPS or CYC. All patients will receive the same glucocorticoid plan. We will compare oral EC-MPS (720-1440 mg/day) with intravenous pulsed CYC (7.5-15 mg/kg) administered for 3-6 months. All patients will be switched from their assigned treatment (EC-MPS or CYC) to oral azathioprine (2 mg/kg/day) after remission has been achieved, between 3 and 6 months. Azathioprine will be continued until the study ends at 18 months. The primary end point of efficacy is the remission rate at 6 months. Follow-up will continue for 18 months in order to detect an influence of induction regimen on subsequent relapse rates. ETHICS AND DISSEMINATION This study has received approval from the Ethics Committee of the Second Hospital of Shanxi Medical University (2022YX-026). All participants are required to provide written informed consent and no study-related procedures will be performed until consent is obtained. The results of this trial will be published in peer-reviewed journals and presented at conferences. TRIAL REGISTRATION NUMBER ChiCTR2200063823.
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Affiliation(s)
- Sijia Li
- Division of Nephrology, Shanxi Medical University Second Hospital, Shanxi Kidney Disease Institute, Taiyuan, Shanxi, People's Republic of China
| | - Shulei Yao
- Division of Nephrology, Shanxi Medical University Second Hospital, Shanxi Kidney Disease Institute, Taiyuan, Shanxi, People's Republic of China
| | - Xuan Tie
- Division of Nephrology, Shanxi Medical University Second Hospital, Shanxi Kidney Disease Institute, Taiyuan, Shanxi, People's Republic of China
| | - Xiaojing Shi
- Division of Nephrology, Shanxi Medical University Second Hospital, Shanxi Kidney Disease Institute, Taiyuan, Shanxi, People's Republic of China
| | - Rongrong Feng
- Division of Nephrology, Shanxi Medical University Second Hospital, Shanxi Kidney Disease Institute, Taiyuan, Shanxi, People's Republic of China
| | - Xiaole Su
- Division of Nephrology, Shanxi Medical University Second Hospital, Shanxi Kidney Disease Institute, Taiyuan, Shanxi, People's Republic of China
| | - Lihua Wang
- Division of Nephrology, Shanxi Medical University Second Hospital, Shanxi Kidney Disease Institute, Taiyuan, Shanxi, People's Republic of China
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Floege J, Jayne DR, Sanders JSF, Tesar V, Rovin BH. KDIGO 2024 Clinical Practice Guideline for the Management of Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis. Kidney Int 2024; 105:S71-S116. [PMID: 38388102 DOI: 10.1016/j.kint.2023.10.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Accepted: 10/20/2023] [Indexed: 02/24/2024]
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Hellmich B, Sanchez-Alamo B, Schirmer JH, Berti A, Blockmans D, Cid MC, Holle JU, Hollinger N, Karadag O, Kronbichler A, Little MA, Luqmani RA, Mahr A, Merkel PA, Mohammad AJ, Monti S, Mukhtyar CB, Musial J, Price-Kuehne F, Segelmark M, Teng YKO, Terrier B, Tomasson G, Vaglio A, Vassilopoulos D, Verhoeven P, Jayne D. EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update. Ann Rheum Dis 2024; 83:30-47. [PMID: 36927642 DOI: 10.1136/ard-2022-223764] [Citation(s) in RCA: 227] [Impact Index Per Article: 227.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Accepted: 02/21/2023] [Indexed: 03/18/2023]
Abstract
BACKGROUND Since the publication of the EULAR recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in 2016, several randomised clinical trials have been published that have the potential to change clinical care and support the need for an update. METHODS Using EULAR standardised operating procedures, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 16 countries. We modified existing recommendations and created new recommendations. RESULTS Four overarching principles and 17 recommendations were formulated. We recommend biopsies and ANCA testing to assist in establishing a diagnosis of AAV. For remission induction in life-threatening or organ-threatening AAV, we recommend a combination of high-dose glucocorticoids (GCs) in combination with either rituximab or cyclophosphamide. We recommend tapering of the GC dose to a target of 5 mg prednisolone equivalent/day within 4-5 months. Avacopan may be considered as part of a strategy to reduce exposure to GC in granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Plasma exchange may be considered in patients with rapidly progressive glomerulonephritis. For remission maintenance of GPA/MPA, we recommend rituximab. In patients with relapsing or refractory eosinophilic GPA, we recommend the use of mepolizumab. Azathioprine and methotrexate are alternatives to biologics for remission maintenance in AAV. CONCLUSIONS In the light of recent advancements, these recommendations provide updated guidance on AAV management. As substantial data gaps still exist, informed decision-making between physicians and patients remains of key relevance.
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Affiliation(s)
- Bernhard Hellmich
- Klinik für Innere Medizin, Rheumatologie und Immunologie, Medius Kliniken, Akademisches Lehrkrankenhaus der Universität Tübingen, Kirchheim unter Teck, Germany
| | | | - Jan H Schirmer
- Rheumatology & Clinical Immunology and Cluster of Excellence Precision Medicine in Chronic Inflammation, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Alvise Berti
- CIBIO, Universita degli Studi di Trento, Trento, Italy
- Rheumatology, Santa Chiara Hospital, Trento, Italy
| | - Daniel Blockmans
- Department of Internal Medicine, University Hospital of Leuven, Leuven, Belgium
| | - Maria C Cid
- Department of Autoimmune Diseases, Hospital Clinic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain
| | - Julia U Holle
- Rheumazentrum Schleswig-Holstein Mitte, Neumuenster, Germany
| | - Nicole Hollinger
- Klinik für Innere Medizin, Rheumatologie und Immunologie, Medius Kliniken, Akademisches Lehrkrankenhaus der Universität Tübingen, Kirchheim unter Teck, Germany
| | - Omer Karadag
- Division of Rheumatology, Department of Internal Medicine, Vasculitis Research Center, Hacettepe University School of Medicine, Anakra, Turkey
| | - Andreas Kronbichler
- Department of Internal Medicine IV, Medical University, Innsbruck, Austria
- Department of Medicine, University of Cambridge, Cambridge, UK
| | - Mark A Little
- Trinity Health Kidney Centre, Trinity College Dublin, Dublin, Ireland
| | - Raashid A Luqmani
- Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Science (NDORMs), University of Oxford, Oxford, UK
| | - Alfred Mahr
- Klinik für Rheumatologie, Kantonspital St Gallen, St Gallen, Switzerland
| | - Peter A Merkel
- Division of Rheumatology, Department of Medicine, Division of Epidemiology, Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Aladdin J Mohammad
- Department of Medicine, University of Cambridge, Cambridge, UK
- Department of Clinical Sciences, Lund University & Department of Rheumatology, Skåne Hospital, Lund, Sweden
| | - Sara Monti
- Department of Internal Medicine and Therapeutics, Università di Pavia, Pavia, Italy
- Division of Rheumatology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Chetan B Mukhtyar
- Vasculitis Service, Rheumatology Department, Norfolk and Norwich University Hospital NHS Trust, Norwich, UK
| | - Jacek Musial
- 2nd Department of Internal Medicine, Jagiellonian University Medical College, Kraków, Poland
| | | | - Mårten Segelmark
- Division of Nephrology, Department of Clinical Sciences, Lund University, Skane University Hospital, Lund, Sweden
| | - Y K Onno Teng
- Centre of Expertise for Lupus-, Vasculitis-, and Complement-Mediated Systemic Autoimmune Diseases (LuVaCs), Department of Internal Medicine, Section Nephrology, Leiden University Medical Centre, Leiden, The Netherlands
| | - Benjamin Terrier
- National Referral Center for Rare Systemic Autoimmune Diseases, Université Paris Descartes, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (APHP), Paris, France
| | - Gunnar Tomasson
- Department of Epidemiology and Biostatistics, Faculty of Medicine, University of Iceland, Reykjavik, Iceland
- Department of Rheumatology and Centre for Rheumatology Research, University Hospital Reykjavik, Reykjavik, Iceland
| | - Augusto Vaglio
- Nephrology Unit, Meyer Children's Hospital, and Department of Biomedical, Experimental and Clinical Science, University of Florence, Florence, Italy
| | - Dimitrios Vassilopoulos
- 2nd Department of Medicine and Laboratory, Clinical Immunology-Rheumatology Unit, National and Kapodistrian University of Athens, School of Medicine, Hippokration General Hospital, Athens, Greece
| | - Peter Verhoeven
- Dutch Patient Vasculitis Organization, Haarlem, The Netherlands
| | - David Jayne
- Department of Medicine, University of Cambridge, Cambridge, UK
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Younger DS. Systemic vasculitis and headache. Curr Opin Neurol 2023; 36:631-646. [PMID: 37865837 PMCID: PMC10624412 DOI: 10.1097/wco.0000000000001223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2023]
Abstract
PURPOSE OF REVIEW Vasculitis refers to heterogeneous clinicopathologic disorders that share the histopathology of inflammation of blood vessels. Unrecognized and therefore untreated, vasculitis of the nervous system or so called neurovasculitides, lead to pervasive injury and disability making these disorder of paramount importance to clinicians. RECENT FINDINGS Headache is an important clue to vasculitic involvement of central nervous system (CNS) vessels. CNS vasculitis may be primary, in which only intracranial vessels are involved in the inflammatory process, or secondary to another known disorder with overlapping systemic involvement. A suspicion of vasculitis based on the history, clinical examination, or laboratory studies warrants prompt evaluation and treatment to forestall progression and avert cerebral ischemia or infarction. There has been remarkable progress in the pathogenesis, diagnosis, and treatment of primary adult and pediatric CNS vasculitides predicated on achievements in primary systemic forms. SUMMARY Vasculitis can be diagnosed with certainty after intensive evaluation that includes tissue confirmation whenever possible. Clinicians must choose from among the available immune modulating, suppressive, and targeted immunotherapies to induce and maintain remission status and prevent relapse, tempered by the recognition of anticipated medication side effects.
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Affiliation(s)
- David S Younger
- Department of Medicine, Section of Neuroscience, City University of New York School of Medicine, New York, NY; Department of Neurology, White Plains Hospital, White Plains, New York, USA
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10
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Casal Moura M, Gauckler P, Anders HJ, Bruchfeld A, Fernandez-Juarez GM, Floege J, Frangou E, Goumenos D, Segelmark M, Turkmen K, van Kooten C, Tesar V, Geetha D, Fervenza FC, Jayne DRW, Stevens KI, Kronbichler A. Management of antineutrophil cytoplasmic antibody-associated vasculitis with glomerulonephritis as proposed by the ACR 2021, EULAR 2022 and KDIGO 2021 guidelines/recommendations. Nephrol Dial Transplant 2023; 38:2637-2651. [PMID: 37164940 PMCID: PMC10615627 DOI: 10.1093/ndt/gfad090] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2023] [Indexed: 05/12/2023] Open
Abstract
Updated guidelines on the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) were released in 2021 by the American College of Rheumatology jointly with the Vasculitis Foundation and, subsequently, in 2022 by the European Alliance of Associations for Rheumatology. In addition, in 2021, the Kidney Disease: Improving Global Outcomes had released updated recommendations on the treatment of AAV with glomerulonephritis (AAV-GN). Kidney involvement is particularly relevant in microscopic polyangiitis and granulomatosis with polyangiitis, but is less frequent in eosinophilic granulomatosis with polyangiitis. The management of AAV-GN has been a focus for drug development and change over the past 10 years. Avoidance of progression to end-stage kidney disease (ESKD) or kidney failure is one of the main unmet needs in the management of AAV, with ESKD having a major impact on morbidity, health costs and mortality risk. Relevant changes in AAV-GN management are related to remission-induction treatment of patients with severe kidney disease, the use of glucocorticoids and avacopan, and remission-maintenance treatment. All the documents provide guidance in accordance with the evidence-based standard of care available at the time of their release. With our work we aim to (i) show the progress made and identify the differences between guidelines and recommendations, (ii) discuss the supporting rationale for those, and (iii) identify gaps in knowledge that could benefit from additional research and should be revised in subsequent updates.
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Affiliation(s)
- Marta Casal Moura
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
- Faculdade de Medicina da Universidade do Porto, Departamento de Biomedicina, Porto, Portugal
| | - Philipp Gauckler
- Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Innsbruck, Austria
| | - Hans-Joachim Anders
- Department of Internal Medicine IV, Hospital of the Ludwig Maximilians University, Munich, Germany
| | - Annette Bruchfeld
- Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
- Department of Renal Medicine, Karolinska University Hospital and CLINTEC Karolinska Institutet, Stockholm, Sweden
| | | | - Jürgen Floege
- Division of Nephrology, RWTH Aachen University Hospital, Aachen, Germany
| | - Eleni Frangou
- Department of Nephrology, Limassol General Hospital, SHSO, Cyprus; Medical School, University of Nicosia, Nicosia, Cyprus
| | - Dimitrios Goumenos
- Department of Nephrology and Renal Transplantation, Patras University Hospital, Patras, Greece
| | - Marten Segelmark
- Division of Nephrology, Department of Clinical Sciences Lund, Lund University and Skane University Hospital, Lund, Sweden
| | - Kultigin Turkmen
- Division of Nephrology, Department of Internal Medicine, Necmettin Erbakan University, Konya, Turkey
| | - Cees van Kooten
- Division of Nephrology and Transplant Medicine, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Vladimir Tesar
- Department of Nephrology, First Faculty of Medicine and General University Hospital, Charles University, Prague, Czechia
| | - Duvuru Geetha
- Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America
| | - Fernando C Fervenza
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
| | - David R W Jayne
- Department of Medicine, University of Cambridge, Cambridge, United Kingdom
| | - Kate I Stevens
- Division of Nephrology and Transplantation, Queen Elizabeth University Hospital, Glasgow, United Kingdom
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11
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Watanabe R, Oshima M, Nishioka N, Sada KE, Nagasaka K, Akiyama M, Ando T, Higuchi T, Inoue Y, Kida T, Mutoh T, Nakabayashi A, Onishi A, Sakai R, Waki D, Yamada Y, Yajima N, Tamura N, Kaname S, Harigai M. Systematic review and meta-analysis for 2023 clinical practice guidelines of the Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis for the management of ANCA-associated vasculitis. Mod Rheumatol 2023; 33:982-989. [PMID: 36112482 DOI: 10.1093/mr/roac114] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 08/24/2022] [Indexed: 08/27/2023]
Abstract
OBJECTIVES The objective of this study is to provide evidence for the revision of clinical practice guidelines for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis by the Japan Research Committee for Intractable Vasculitis. METHODS PubMed, CENTRAL, and the Japan Medical Abstracts Society databases were searched for articles published between 2015 and 2020 to update the systematic review for existing clinical questions, while PubMed, CENTRAL, EMBASE, and the Japan Medical Abstracts Society were searched for articles published between 2000 and 2020 to conduct a systematic review for newly developed clinical questions. The certainty of evidence was assessed with the GRADE approach. RESULTS For remission induction, when used in conjunction with cyclophosphamide or rituximab, reduced-dose glucocorticoid lowered the risk of serious adverse events compared to standard-dose glucocorticoid. Avacopan improved sustained remission at 12 months compared to high-dose glucocorticoid. Addition of plasma exchange to remission induction therapy did not reduce the risk of death, end-stage kidney disease, or relapse. For remission maintenance, rituximab reduced the risk of relapse compared to azathioprine. Long-term rituximab or azathioprine reduced the risk of relapse compared to short-term rituximab or azathioprine, respectively. CONCLUSIONS This systematic review provided evidence required to develop the 2023 clinical practice guideline for the management of ANCA-associated vasculitis.
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Affiliation(s)
- Ryu Watanabe
- Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Megumi Oshima
- Department of Nephrology and Laboratory Medicine, Kanazawa University, Kanazawa, Japan
| | - Norihiro Nishioka
- Department of Preventive Services, Kyoto University School of Public Health, Kyoto, Japan
| | - Ken-Ei Sada
- Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Okayama University, Okayama, Japan
- Department of Clinical Epidemiology, Kochi Medical School, Kochi University, Nankoku, Japan
| | - Kenji Nagasaka
- Department of Rheumatology, Ome Municipal General Hospital, Ome, Japan
- Department of Rheumatology and Medicine, Tokyo Medical and Dental University (TMDU), Tokyo, Japan
| | - Mitsuhiro Akiyama
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Taiki Ando
- Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan
| | - Tomoaki Higuchi
- Division of Multidisciplinary Management of Rheumatic Diseases, Tokyo Women's Medical University School of Medicine, Tokyo, Japan
| | - Yoshino Inoue
- First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Takashi Kida
- Department of Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Tomoyuki Mutoh
- Department of Rheumatology, Osaki Citizen Hospital, Osaki, Japan
- Department of Rheumatology, Tohoku University Hospital, Sendai, Japan
| | - Akihiko Nakabayashi
- Department of Rheumatology and Allergology, National Hospital Organization Osaka Minami Medical Center, Osaka, Japan
| | - Akira Onishi
- Department of Advanced Medicine for Rheumatic diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Ryota Sakai
- Department of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan
| | - Daisuke Waki
- Department of Endocrinology and Rheumatology, Kurashiki Central Hospital, Kurashiki, Japan
| | - Yosuke Yamada
- Department of Nephrology, Shinshu University School of Medicine, Nagano, Japan
| | - Nobuyuki Yajima
- Division of Rheumatology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan
| | - Naoto Tamura
- Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan
| | - Shinya Kaname
- Department of Nephrology and Rheumatology, Kyorin University School of Medicine, Mitaka, Japan
| | - Masayoshi Harigai
- Division of Rheumatology, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan
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12
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Schirmer JH, Sanchez-Alamo B, Hellmich B, Jayne D, Monti S, Luqmani RA, Tomasson G. 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. RMD Open 2023; 9:e003082. [PMID: 37479496 PMCID: PMC10364171 DOI: 10.1136/rmdopen-2023-003082] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Accepted: 05/16/2023] [Indexed: 07/23/2023] Open
Abstract
OBJECTIVE To summarise and update evidence to inform the 2022 update of the EULAR recommendations for the management of antineutrophil cytoplasm antibody-associated vasculitis (AAV). METHODS A systematic literature review (SLR) was performed to identify current evidence regarding treatment of AAV. PubMed, EMBASE and the Cochrane library were searched from 1 February 2015 to 25 February 2022. The evidence presented here is focused on the treatment of granulomatosis with polyangiitis and microscopic polyangiitis. RESULTS 3517 articles were screened and 175 assessed by full-text review. Ninety articles were included in the final evidence synthesis. Cyclophosphamide and rituximab (RTX) show similar efficacy for remission induction (level of evidence (LoE) 1a) but RTX is more effective in relapsing disease (LoE 1b). Glucocorticoid (GC) protocols with faster tapering result in similar remission rates but lower rates of serious infections (LoE 1b). Avacopan can be used to rapidly taper and replace GC (LoE 1b). Data on plasma exchange are inconsistent depending on the analysed trial populations but meta-analyses based on randomised controlled trials demonstrate a reduction of the risk of end-stage kidney disease at 1 year but not during long-term follow-up (LoE 1a). Use of RTX for maintenance of remission is associated with lower relapse rates compared with azathioprine (AZA, LoE 1b). Prolonged maintenance treatment results in lower relapse rates for both, AZA (LoE 1b) and RTX (LoE 1b). CONCLUSION This SLR provides current evidence to inform the 2022 update of the EULAR recommendations for the management of AAV.
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Affiliation(s)
- Jan Henrik Schirmer
- Clinic for Internal Medicine I, Rheumatology and Clinical Immunology, University Medical Center Schleswig-Holstein Campus Kiel, Kiel, Germany
| | - Beatriz Sanchez-Alamo
- Nephrology, Hospital Universitario del Sureste, Arganda del Rey, Madrid, Spain
- Nephrology, Skåne University Hospital, Lund, Sweden
| | - Bernhard Hellmich
- Department of Internal Medicine, Rheumatology and Immunology, Medius Kliniken Kirchheim/Teck, University Tübingen, Kirchheim-Teck, Germany
| | - David Jayne
- Department of Medicine, University of Cambridge, Cambridge, UK
| | - Sara Monti
- Department of Internal Medicine and Therapeutics, University of Pavia; Division of Rheumatology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Raashid Ahmed Luqmani
- Oxford NIHR Biomedical Research Centre, Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - Gunnar Tomasson
- Faculty of Medicine, University of Iceland, Landspitali University Hospital, Reykjavik, Iceland
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13
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Morris A, Geetha D. Advances in remission induction therapy for ANCA-associated vasculitis. Best Pract Res Clin Rheumatol 2023; 37:101828. [PMID: 37244804 DOI: 10.1016/j.berh.2023.101828] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 04/09/2023] [Accepted: 04/23/2023] [Indexed: 05/29/2023]
Abstract
Since its first description 40 years ago, huge strides have been made in the management of ANCA-associated vasculitis with improved patient outcomes. The use of cyclophosphamide and/or B-cell depleting therapy alongside glucocorticoids remains the cornerstone of therapy in organ or life-threatening disease, but recent trials have re-evaluated existing treatment strategies, alongside the development of new treatment targets. This has led to refinement of the role of plasma exchange, the use of reduced dosing of oral glucocorticoids with improved patient outcomes, as well as other treatment adjuvants/options of steroid minimization including C5a receptor antagonism and IL-5 inhibition. In this review we examine developments in remission induction therapy for ANCA-associated vasculitis.
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Affiliation(s)
- Adam Morris
- Renal Medicine, Royal Preston Hospital, Preston, UK
| | - Duvuru Geetha
- Division of Nephrology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
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14
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Berti A, Alsawas M, Jawaid T, Prokop LJ, Lee JM, Jeong GH, Quintana LF, Moiseev S, Vaglio A, Tesar V, Geetha D, Shin JI, Kronbichler A. Induction and maintenance of remission with mycophenolate mofetil in ANCA-associated vasculitis: A systematic review and meta-analysis. Nephrol Dial Transplant 2021; 37:2190-2200. [PMID: 34910216 DOI: 10.1093/ndt/gfab357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Uncertainties exist about the use of mycophenolate mofetil (MMF) in anti-neutrophil cytoplasmatic antibody (ANCA)-associated vasculitis (AAV), particularly for remission maintenance. METHODS Systematic review and meta-analysis of phase II and III trials assessing the use of MMF in AAV (granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA)). A comprehensive search of several databases (Medline, EMBASE, Cochrane, Web of Science, Scopus) from inception to May 5th, 2020 has been conducted. Trial data were extracted to estimate odds ratios (ORs) and estimates (ES) for MMF efficacy (remission-induction and maintenance). Severe adverse effects (SAEs) were collected. RESULTS From 565 articles captured, 10 met the predefined criteria, five phase II and five III trials, 4 assessed remission-induction, 3 remission-maintenance, 3 both. The pooled OR for remission-induction at 6 months was 1.06 (95% CI: [0.74, 1.52]), with no significant difference by subgroup meta-analysis of trials stratified by different study-level features (i.e. kidney disease, MPA, myeloperoxidase-ANCA-positivity, newly diagnosed disease) (p > 0.05).The overall ES for remission-maintenance at the end of follow-up ranged between 51%-91% (I2 = 74.8%). Subgroup meta-analysis identified kidney involvement as a possible source of heterogeneity, yielding a significantly higher rate of sustained remission in trials enrolling only patients with kidney involvement (92% [76%-100%]) versus those enrolling patients with and without kidney involvement (56% [45%-66%]). Results were similar in multiple sensitivity analyses.During follow-up, the frequency of SAEs in MMF-based treatment arms was 31.8%. CONCLUSIONS In AAV, MMF use significantly associated with higher sustained remission rates in trials enrolling only patients with kidney involvement. These findings might influence clinical practice.
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Affiliation(s)
- Alvise Berti
- Santa Chiara Regional Hospital and Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Rheumatology, Trento, Italy
| | - Mouaz Alsawas
- Evidence-Based Practice Center, Mayo Clinic, Rochester, MN, USA.,Department of Pathology, University of Iowa, IA City, IA, USA
| | - Tabinda Jawaid
- Evidence-Based Practice Center, Mayo Clinic, Rochester, MN, USA
| | | | - Jiwon M Lee
- Korea Disease Control and Prevention Agency, Division of Rare Disease Management, Republic of Korea
| | - Gwang Hun Jeong
- College of Medicine, Gyeongsang National University, Jinju, Republic of Korea
| | - Luis F Quintana
- Reference Center in Complex Glomerular Disease of the National Health System (CSUR), Nephrology and Renal Transplantation Department, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain. Institut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Barcelona, Spain
| | - Sergey Moiseev
- Tareev Clinic of Internal Diseases, Sechenov First Moscow State Medical University, Moscow, Russia
| | - August Vaglio
- Department of Biomedical Experimental and Clinical Sciences 'Mario Serio', University of Firenze, and Nephrology Unit, Meyer Children's Hospital, Firenze, Italy
| | - Vladimir Tesar
- Department of Nephrology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czechia
| | - Duvuru Geetha
- Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Jae Il Shin
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Andreas Kronbichler
- Department of Medicine, University of Cambridge, Cambridge, UK.,Vasculitis and Lupus Clinic, Addenbrooke's Hospital, Cambridge University Hospitals, Cambridge, UK
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15
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Rovin BH, Adler SG, Barratt J, Bridoux F, Burdge KA, Chan TM, Cook HT, Fervenza FC, Gibson KL, Glassock RJ, Jayne DR, Jha V, Liew A, Liu ZH, Mejía-Vilet JM, Nester CM, Radhakrishnan J, Rave EM, Reich HN, Ronco P, Sanders JSF, Sethi S, Suzuki Y, Tang SC, Tesar V, Vivarelli M, Wetzels JF, Floege J. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int 2021; 100:S1-S276. [PMID: 34556256 DOI: 10.1016/j.kint.2021.05.021] [Citation(s) in RCA: 1086] [Impact Index Per Article: 271.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 05/25/2021] [Indexed: 12/13/2022]
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Huang X, Chen L, Lan L, Ren P, Ni A, Ma Y, Wang Y, Zhu Y, Xu Y, Chen J, Han F. Antineutrophil Cytoplasmic Antibody-Associated Vasculitis With Acute Kidney Injury: Short-Term Recovery Predicts Long-Term Outcome. Front Immunol 2021; 12:641655. [PMID: 34305886 PMCID: PMC8299708 DOI: 10.3389/fimmu.2021.641655] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Accepted: 04/19/2021] [Indexed: 11/13/2022] Open
Abstract
Background Kidney involvement is common in antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). It tends to be aggressive, and in some patients, the kidney involvement may reach the criteria of acute kidney injury (AKI). Here, we aim to describe the clinical characteristics of these patients and find risk factors for poor outcomes. Methods Patients diagnosed with AAV in our hospital from February 2003 to February 2017 were included. Those who reached the KDIGO AKI criteria were reclassified according to the KDIGO AKI stage. The clinical features of these patients were analyzed. Also, according to the variation of serum creatinine 3 months after AKI episode, patients were further divided into two groups: patients whose serum creatinine (Scr) level at the third month decreased by 30% or more from the peak Scr level was classified into G1 and others were classified into G2. Long-term renal and survival outcomes of these patients were analyzed with a Cox model. The renal endpoint was reaching end-stage renal disease (ESRD), and the survival endpoint was death. Nomograms were built based on cox models. Results Of 141 AAV patients included, during the median follow-up period of 64.0 (IQR 34.8, 85.4) months, 36 (25.5%) patients reached renal endpoints, and 22 (15.6%) patients died. The median renal survival time was 35.9 (IQR 21.3, 72.6) months and the median survival time was 48.4 (IQR 26.8, 82.8) months. Multivariate analysis showed that poor recovery of Scr level at 90 days (P < 0.001, RR = 9.150, 95%CI 4.163-20.113), BVAS score (P = 0.014, RR = 1.110, 95% CI1.021-1.207), and AKI stage 3 (P = 0.012 RR = 3.116, 95%CI 1.278-7.598) were independent risk factors for renal endpoints; poor recovery of Scr level at 90 days (P = 0.010, RR = 3.264, 95%CI 1.326-8.035), BVAS score (P = 0.010, RR = 1.171, 95%CI 1.038-1.320) and age (P = 0.017, RR = 1.046, 95%CI 1.008-1.086) were independent risk factors for all-cause death. The c-index of nomograms is 0.830 for the renal outcome and 0.763 for the survival outcome. Conclusion KDIGO AKI stage 3 is the risk factor for ESRD in AAV patients with AKI. The BVAS score and level of kidney function recovery at 90 days are the independent risk factors for both ESRD and all-cause death and are of predictive value for the outcome.
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Affiliation(s)
- Xiaohan Huang
- Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Institute of Nephrology, Zhejiang University, Hangzhou, China.,Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province, Hangzhou, China
| | - Liangliang Chen
- Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Institute of Nephrology, Zhejiang University, Hangzhou, China.,Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province, Hangzhou, China
| | - Lan Lan
- Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Institute of Nephrology, Zhejiang University, Hangzhou, China.,Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province, Hangzhou, China
| | - Pingping Ren
- Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Institute of Nephrology, Zhejiang University, Hangzhou, China.,Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province, Hangzhou, China
| | - Anqi Ni
- Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Institute of Nephrology, Zhejiang University, Hangzhou, China.,Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province, Hangzhou, China
| | - Yanhong Ma
- Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Institute of Nephrology, Zhejiang University, Hangzhou, China.,Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province, Hangzhou, China
| | - Yaomin Wang
- Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Institute of Nephrology, Zhejiang University, Hangzhou, China.,Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province, Hangzhou, China
| | - Yilin Zhu
- Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Institute of Nephrology, Zhejiang University, Hangzhou, China.,Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province, Hangzhou, China
| | - Ying Xu
- Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Institute of Nephrology, Zhejiang University, Hangzhou, China.,Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province, Hangzhou, China
| | - Jianghua Chen
- Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Institute of Nephrology, Zhejiang University, Hangzhou, China.,Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province, Hangzhou, China
| | - Fei Han
- Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Institute of Nephrology, Zhejiang University, Hangzhou, China.,Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province, Hangzhou, China
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Comparative efficacy and safety of mycophenolate mofetil versus cyclophosphamide in patients with active antineutrophil cytoplasmic antibody-associated vasculitis: a meta-analysis of randomized trials. Z Rheumatol 2021; 80:425-431. [PMID: 32337635 DOI: 10.1007/s00393-020-00803-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
OBJECTIVE This study aimed to assess the efficacy and safety of mycophenolate mofetil (MMF) versus cyclophosphamide (CYC) in patients with active antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS We performed a meta-analysis of four randomized clinical trials (RCTs; 300 patients) to examine the relative efficacy and safety of MMF compared to CYC in patients with active AAV. RESULTS There was no significant difference in remission at 6 months between MMF and CYC (odds ratio [OR] 1.311, 95% confidence interval [CI] 0.570-3.017, P = 0.524). Additionally, the relapse rate did not differ between the MMF and CYC groups (OR 1.331, 95% CI 0.497-3.568, P = 0.570). There was no significant difference in serious adverse event (SAE; OR 1.232, 95% CI 0.754-2.014, P = 0.404) and infection rates (OR 0.958, 95% CI 0.561-1.634, P = 0.873) between the MMF and CYC groups. Some heterogeneity was found in the meta-analysis of remission and relapse rates (I2 = 57.4%, 63.4%), but no between-study heterogeneity was found during the meta-analysis of SAE and infection rate. Egger's regression test showed no evidence of publication bias (Egger's regression test P-values >0.1). CONCLUSION MMF was an equally effective alternative treatment to CYC and MMF was comparable to CYC in patients with active AAV in terms of safety, suggesting that MMF can be used as an alternative to CYC for remission induction in AAV.
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Kuzuya K, Morita T, Kumanogoh A. Efficacy of mycophenolate mofetil as a remission induction therapy in antineutrophil cytoplasmic antibody: associated vasculitis-a meta-analysis. RMD Open 2021; 6:rmdopen-2020-001195. [PMID: 32371435 PMCID: PMC7299518 DOI: 10.1136/rmdopen-2020-001195] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2020] [Revised: 03/25/2020] [Accepted: 03/29/2020] [Indexed: 01/01/2023] Open
Abstract
Objectives A few studies on antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) treatments have shown the therapeutic efficacy of mycophenolate mofetil (MMF). However, the therapeutic efficacy of MMF compared with that of cyclophosphamide (CYC) in patients with AAV has not been established. We conducted a systematic review and meta-analysis to assess the efficacy of MMF as a remission induction therapy in patients with AAV comparing it with the efficacy of CYC. Methods We searched randomised controlled trials (RCTs) comparing the efficacy of MMF with that of CYC in patients with AAV on three different websites: PubMed, Cochrane Library and Google Scholar. We compared the difference in the relative risk (RR) of each outcome based on a Mantel-Haenszel random-effects model. Results We analysed data from four RCTs with 300 patients for the study. The 6-month remission rate (RR 1.09, 95% CI 0.86 to 1.38, p=0.48), the 6-month ANCA negativity (RR 1.31, 95% CI 0.91 to 1.90, p=0.15) and the long-term relapse rate (RR 1.36, 95% CI 0.80 to 2.31, p=0.26) were all similar between the two treatments. The rates of death, infection and leucopenia were also similar between the two groups (RR 1.05, 95% CI 0.40 to 2.74, p=0.93; RR 1.26, 95% CI 0.79 to 2.01, p=0.33; RR 0.45, 95% CI 0.16 to 1.32, p=0.15, respectively). Conclusions We found no difference between the therapeutic efficacy of MMF and that of CYC in patients with AAV. MMF may be an alternative remission induction therapy in patients with non-life-threatening AAV.
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Affiliation(s)
- Kentaro Kuzuya
- Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Takayoshi Morita
- Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Japan .,Laboratory of Immunopathology, World Premier International Immunology Frontier Research Center, Suita, Japan
| | - Atsushi Kumanogoh
- Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Japan.,Laboratory of Immunopathology, World Premier International Immunology Frontier Research Center, Suita, Japan.,Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita, Japan
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Nozaki Y. New Insights Into Novel Therapeutic Targets in ANCA-Associated Vasculitis. Front Immunol 2021; 12:631055. [PMID: 33868250 PMCID: PMC8047311 DOI: 10.3389/fimmu.2021.631055] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 03/18/2021] [Indexed: 11/13/2022] Open
Abstract
Biologics targeting inflammation-related molecules in the immune system have been developed to treat rheumatoid arthritis (RA), and these RA treatments have provided revolutionary advances. Biologics may also be an effective treatment for anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, particularly in patients with resistance to standard treatments. Despite the accumulation of clinical experience and the increasing understanding of the pathogenesis of vasculitis, it is becoming more difficult to cure vasculitis. The treatment of vasculitis with biologics has been examined in clinical trials, and this has also enhanced our understanding of the pathogenesis of vasculitis. A humanized anti-interleukin-5 monoclonal antibody known as mepolizumab was recently demonstrated to provide clinical benefit in the management of eosinophilic granulomatosis with polyangiitis in refractory and relapsing disease, and additional new drugs for vasculitis are being tested in clinical trials, while others are in abeyance. This review presents the new findings regarding biologics in addition to the conventional immunosuppressive therapy for ANCA-associated vasculitis.
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Affiliation(s)
- Yuji Nozaki
- Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, Osaka-sayama, Japan
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Xiong A, Xiong C, Yang G, Shuai Y, Liu D, He L, Guo Z, Zhang L, Liu Y, Yang Y, Cui B, Shuai S. The Role of Mycophenolate Mofetil for the Induction of Remission in ANCA-Associated Vasculitis: A Meta-Analysis. Front Med (Lausanne) 2021; 8:609924. [PMID: 33732714 PMCID: PMC7956966 DOI: 10.3389/fmed.2021.609924] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Accepted: 02/10/2021] [Indexed: 02/05/2023] Open
Abstract
Objectives: The successful introduction of mycophenolate mofetil (MMF) as a treatment for renal allograft reduced the incidence of acute rejection. The inspiring effects obtained by the MMF have led to an evaluation of its therapeutic potency on ANCA-associated vasculitis (AAV). However, there is little evidence of the MMF's efficacy on the AAV. The meta-analysis is carried out to evaluate the efficacy of MMF as a remission induction therapy in AAV. Methods: Up to June 30th, 2020, PubMed, Cochrane Library, and Embase have been searched comprehensively. According to heterogeneity, the pooled remission rates are synthesized by either fixed-effect or random-effect models. Results: The eight included studies comprising 230 patients who were treated with MMF as induction therapy are included in our analysis. The pooled overall remission rate is 74% (95% CI: 0.68–0.80). The remission rate, the infection rate and the rate of leukopenia of four randomized controlled trials aimed at comparing the effects of MMF with cyclophosphamide (CYC) during induction therapy for AAV have no statistical significance (P > 0.05). Conclusion: MMF may be an alternative to CYC for remission induction therapy in AAV with MPO-ANCA, mild to moderate renal involvement and non-life-threatening state. Whether to observe the effect of MMF in AAV or to compare the difference between MMF and CYC in the future studies, risk stratification and subgrouping of AAV patients should be first carried out to correctly identify the AAV subgroup suitable for MMF.
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Affiliation(s)
- Anji Xiong
- Department of Rheumatology and Immunology, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, China
| | - Chen Xiong
- Department of Rheumatology and Immunology, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, China
| | - Guancui Yang
- Department of Rheumatology and Immunology, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, China
| | - Yu Shuai
- Department of Rheumatology and Immunology, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, China
| | - Deng Liu
- Department of Rheumatology and Immunology, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, China
| | - Linqian He
- Department of Rheumatology and Immunology, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, China
| | - Zepeng Guo
- Department of Rheumatology and Immunology, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, China
| | - Liangwen Zhang
- Department of Rheumatology and Immunology, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, China
| | - Yi Liu
- Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, China
| | - Yuan Yang
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Beibei Cui
- Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, China
| | - Shiquan Shuai
- Department of Rheumatology and Immunology, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, China
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Terrier B, Darbon R, Durel CA, Hachulla E, Karras A, Maillard H, Papo T, Puechal X, Pugnet G, Quemeneur T, Samson M, Taille C, Guillevin L. French recommendations for the management of systemic necrotizing vasculitides (polyarteritis nodosa and ANCA-associated vasculitides). Orphanet J Rare Dis 2020; 15:351. [PMID: 33372616 PMCID: PMC7771069 DOI: 10.1186/s13023-020-01621-3] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Systemic necrotizing vasculitis comprises a group of diseases resembling polyarteritis nodosa and anti-neutrophil cytoplasmic antibody-associated vasculitis (ANCA): granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, and microscopic polyangiitis. The definitive diagnosis is made in cooperation with a reference center for autoimmune diseases and rare systemic diseases or a competency center. The management goals are: to obtain remission and, in the long term, healing; to reduce the risk of relapses; to limit and reduce the sequelae linked to the disease; to limit the side effects and the sequelae linked to the treatments; to improve or at least maintain the best possible quality of life; and to maintain socio-professional integration and/or allow a rapid return to school and/or professional activity. Information and therapeutic education of the patients and those around them are an integral part of the care. All health professionals and patients should be informed of the existence of patient associations. The treatment of vasculitis is based on variable combinations of glucocorticoids and immunosuppressants, chosen and adapted according to the disease concerned, the severity and/or extent of the disease, and the underlying factors (age, kidney function, etc.). Follow-up clinical and paraclinical examinations must be carried out regularly to clarify the progression of the disease, detect and manage treatment failures and possible relapses early on, and limit sequelae and complications (early then late) related to the disease or treatment. A distinction is made between the induction therapy, lasting approximately 3–6 months and aimed at putting the disease into remission, and the maintenance treatment, lasting 12–48 months, or even longer. The role of the increase or testing positive again for ANCA as a predictor of a relapse, which has long been controversial, now seems to have greater consensus: Anti-myeloperoxidase ANCAs are less often associated with a relapse of vasculitis than anti-PR3 ANCA.
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Affiliation(s)
| | | | | | | | | | | | - Thomas Papo
- Internal Medicine, CHU Bichat, AP-HP, Paris, France
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Monti S, Quinn KA, Christensen R, Jayne D, Langford C, Lanier GE, Mahr A, Pagnoux C, Viðarsdóttir MB, Merkel PA, Tomasson G. Use and reporting of outcome measures in randomized trials for anti-neutrophil cytoplasmic antibody-associated vasculitis: a systematic literature review. Semin Arthritis Rheum 2020; 50:1314-1325. [DOI: 10.1016/j.semarthrit.2020.09.010] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Revised: 09/02/2020] [Accepted: 09/09/2020] [Indexed: 11/28/2022]
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Mendel A, Ennis D, Go E, Bakowsky V, Baldwin C, Benseler SM, Cabral DA, Carette S, Clements-Baker M, Clifford AH, Cohen Tervaert JW, Cox G, Dehghan N, Dipchand C, Dhindsa N, Famorca L, Fifi-Mah A, Garner S, Girard LP, Lessard C, Liang P, Noone D, Makhzoum JP, Milman N, Pineau CA, Reich HN, Rhéaume M, Robinson DB, Rumsey DG, Towheed TE, Trudeau J, Twilt M, Yacyshyn E, Yeung RSM, Barra LB, Khalidi N, Pagnoux C. CanVasc Consensus Recommendations for the Management of Antineutrophil Cytoplasm Antibody-associated Vasculitis: 2020 Update. J Rheumatol 2020; 48:555-566. [PMID: 32934123 DOI: 10.3899/jrheum.200721] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/05/2020] [Indexed: 12/14/2022]
Abstract
OBJECTIVE In 2015, the Canadian Vasculitis Research Network (CanVasc) created recommendations for the management of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) in Canada. The current update aims to revise existing recommendations and create additional recommendations, as needed, based on a review of new available evidence. METHODS A needs assessment survey of CanVasc members informed questions for an updated systematic literature review (publications spanning May 2014 to September 2019) using Medline, Embase, and Cochrane. New and revised recommendations were developed and categorized according to the level of evidence and strength of each recommendation. The CanVasc working group used a 2-step modified Delphi procedure to reach > 80% consensus on the inclusion, wording, and grading of each new and revised recommendation. RESULTS Eleven new and 16 revised recommendations were created and 12 original (2015) recommendations were retained. New and revised recommendations are discussed in detail within this document. Five original recommendations were removed, of which 4 were incorporated into the explanatory text. The supplementary material for practical use was revised to reflect the updated recommendations. CONCLUSION The 2020 updated recommendations provide rheumatologists, nephrologists, and other specialists caring for patients with AAV in Canada with new management guidance, based on current evidence and consensus from Canadian experts.
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Affiliation(s)
- Arielle Mendel
- A. Mendel, MD, MSc, C.A. Pineau, MD, Division of Rheumatology, Lupus and Vasculitis Clinic, McGill University, Montréal, Québec;
| | - Daniel Ennis
- D. Ennis, MD, C. Baldwin, MD, N. Dehghan, MD, N. Dhindsa, MD, Division of Rheumatology, University of British Columbia, Vancouver, British Columbia
| | - Ellen Go
- E. Go, MD, R.S. Yeung, MD, PhD, Division of Rheumatology, Hospital for Sick Children, University of Toronto, Toronto, Ontario
| | - Volodko Bakowsky
- V. Bakowsky, MD, Division of Rheumatology, QEII Health Sciences Centre, Dalhousie University, Halifax, Nova Scotia
| | - Corisande Baldwin
- D. Ennis, MD, C. Baldwin, MD, N. Dehghan, MD, N. Dhindsa, MD, Division of Rheumatology, University of British Columbia, Vancouver, British Columbia
| | - Susanne M Benseler
- S.M. Benseler, MD, PhD, M. Twilt, MD, PhD, Division of Rheumatology, Department of Pediatrics, Alberta Children's Hospital, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta
| | - David A Cabral
- D.A. Cabral, MBBS, Division of Pediatric Rheumatology, BC Children's Hospital, University of British Columbia, Vancouver, British Columbia
| | - Simon Carette
- S. Carette, MD, MPhil, C. Pagnoux, MD, MSc, MPH, Division of Rheumatology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario
| | - Marie Clements-Baker
- M. Clements-Baker, MD, T.E. Towheed, MD, MS, Division of Rheumatology, Queen's University, Kingston, Ontario
| | - Alison H Clifford
- A.H. Clifford, MD, J.W. Cohen Tervaert, MD, PhD, E. Yacyshyn, MD, Division of Rheumatology, University of Alberta, Edmonton, Alberta
| | - Jan Willem Cohen Tervaert
- A.H. Clifford, MD, J.W. Cohen Tervaert, MD, PhD, E. Yacyshyn, MD, Division of Rheumatology, University of Alberta, Edmonton, Alberta
| | - Gerard Cox
- G. Cox, MB, Firestone Institute for Respiratory Health, McMaster University, Hamilton, Ontario
| | - Natasha Dehghan
- D. Ennis, MD, C. Baldwin, MD, N. Dehghan, MD, N. Dhindsa, MD, Division of Rheumatology, University of British Columbia, Vancouver, British Columbia
| | - Christine Dipchand
- C. Dipchand, MD, MSc, Division of Nephrology, QEII Health Sciences Centre, Dalhousie University, Halifax, Nova Scotia
| | - Navjot Dhindsa
- D. Ennis, MD, C. Baldwin, MD, N. Dehghan, MD, N. Dhindsa, MD, Division of Rheumatology, University of British Columbia, Vancouver, British Columbia
| | - Leilani Famorca
- L. Famorca, MD, S. Garner, MD, MSc, N. Khalidi, MD, Division of Rheumatology, McMaster University, Hamilton, Ontario
| | - Aurore Fifi-Mah
- A. Fifi-Mah, MD, Division of Rheumatology, University of Calgary, Calgary, Alberta
| | - Stephanie Garner
- L. Famorca, MD, S. Garner, MD, MSc, N. Khalidi, MD, Division of Rheumatology, McMaster University, Hamilton, Ontario
| | - Louis-Philippe Girard
- L.P. Girard, MD, MSc, Division of Nephrology, University of Calgary, Calgary, Alberta
| | - Clode Lessard
- C. Lessard, MD, Centre de Recherche Musculo-Squelettique, Trois-Rivières, Québec
| | - Patrick Liang
- P. Liang, MD, Division of Rheumatology, Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, Sherbrooke, Québec
| | - Damien Noone
- D. Noone, MB, BCh, BAO, MSc, Division of Nephrology, Hospital for Sick Children, University of Toronto, Toronto, Ontario
| | - Jean-Paul Makhzoum
- J.P. Makhzoum, MD, M. Rhéaume, MD, Division of Internal Medicine, Hôpital du Sacré-Coeur de Montréal, Université de Montréal, Montréal, Québec
| | - Nataliya Milman
- N. Milman, MD, MSc, Division of Rheumatology, The Ottawa Hospital, University of Ottawa and Ottawa Hospital Research Institute, Ottawa, Ontario
| | - Christian A Pineau
- A. Mendel, MD, MSc, C.A. Pineau, MD, Division of Rheumatology, Lupus and Vasculitis Clinic, McGill University, Montréal, Québec
| | - Heather N Reich
- H.N. Reich, MD, PhD, Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario
| | - Maxime Rhéaume
- J.P. Makhzoum, MD, M. Rhéaume, MD, Division of Internal Medicine, Hôpital du Sacré-Coeur de Montréal, Université de Montréal, Montréal, Québec
| | - David B Robinson
- D.B. Robinson, MD, MSc, Section of Rheumatology, University of Manitoba, Winnipeg, Manitoba
| | - Dax G Rumsey
- D.G. Rumsey, MD, MSc, Division of Pediatric Rheumatology, University of Alberta, Edmonton, Alberta
| | - Tanveer E Towheed
- M. Clements-Baker, MD, T.E. Towheed, MD, MS, Division of Rheumatology, Queen's University, Kingston, Ontario
| | - Judith Trudeau
- J. Trudeau, MD, Division of Rheumatology, CISSS Chaudière-Appalaches, Université Laval, Québec City, Québec
| | - Marinka Twilt
- S.M. Benseler, MD, PhD, M. Twilt, MD, PhD, Division of Rheumatology, Department of Pediatrics, Alberta Children's Hospital, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta
| | - Elaine Yacyshyn
- A.H. Clifford, MD, J.W. Cohen Tervaert, MD, PhD, E. Yacyshyn, MD, Division of Rheumatology, University of Alberta, Edmonton, Alberta
| | - Rae S M Yeung
- E. Go, MD, R.S. Yeung, MD, PhD, Division of Rheumatology, Hospital for Sick Children, University of Toronto, Toronto, Ontario
| | - Lillian B Barra
- L.B. Barra, MD, Division of Rheumatology, Department of Medicine, Western University, London, Ontario, Canada
| | - Nader Khalidi
- L. Famorca, MD, S. Garner, MD, MSc, N. Khalidi, MD, Division of Rheumatology, McMaster University, Hamilton, Ontario
| | - Christian Pagnoux
- S. Carette, MD, MPhil, C. Pagnoux, MD, MSc, MPH, Division of Rheumatology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario
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Jain S, Chattopadhyay A, Naidu S, Sharma A. MYCYC: unravelling the long road ahead in ANCA-associated vasculitis. Ann Rheum Dis 2020; 79:e57. [PMID: 30894345 DOI: 10.1136/annrheumdis-2019-215241] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2019] [Accepted: 02/17/2019] [Indexed: 11/03/2022]
Affiliation(s)
- Siddharth Jain
- Clinical Immunology and Rheumatology Services, Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Arghya Chattopadhyay
- Clinical Immunology and Rheumatology Services, Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Shankar Naidu
- Clinical Immunology and Rheumatology Services, Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Aman Sharma
- Clinical Immunology and Rheumatology Services, Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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Abstract
Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) is a small to medium vessel vasculitis associated with excess morbidity and mortality. This review explores how management of AAV has evolved over the past two decades with pivotal randomized controlled trials shaping the management of induction and maintenance of remission. Contemporary AAV care is characterized by approaches that minimize the cumulative exposure to cyclophosphamide and glucocorticoids, increasingly use rituximab for remission induction and maintenance, and consider therapies with less toxicity (for example, methotrexate, mycophenolate mofetil) for manifestations of AAV that do not threaten organ function or survival. Simultaneously, improvements in outcomes, such as renal and overall survival, have been observed. Additional trials and observational studies evaluating the comparative effectiveness of agents for AAV in various patient subgroups are needed. Prospective studies are necessary to assess the effect of psychosocial interventions on patient reported outcomes in AAV. Despite the expanding array of treatments for AAV, little guidance on how to personalize AAV care is available to physicians.
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Affiliation(s)
- Zachary S Wallace
- Clinical Epidemiology Program, Division of Rheumatology, Allergy, and Immunology, Mongan Institute, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
- Rheumatology Unit, Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Eli M Miloslavsky
- Rheumatology Unit, Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
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Abstract
BACKGROUND Renal vasculitis presents as rapidly progressive glomerulonephritis and comprises of a group of conditions characterised by acute kidney injury (AKI), haematuria and proteinuria. Treatment of these conditions involve the use of steroid and non-steroid agents in combination with plasma exchange. Although immunosuppression overall has been very successful in treatment of these conditions, many questions remain unanswered in terms of dose and duration of therapy, the use of plasma exchange and the role of new therapies. This 2019 publication is an update of a review first published in 2008 and updated in 2015. OBJECTIVES To evaluate the benefits and harms of any intervention used for the treatment of renal vasculitis in adults. SEARCH METHODS We searched the Cochrane Kidney and Transplant Register of Studies up to 21 November 2019 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA Randomised controlled trials investigating any intervention for the treatment of renal vasculitis in adults. DATA COLLECTION AND ANALYSIS Two authors independently assessed study quality and extracted data. Statistical analyses were performed using a random effects model and results expressed as risk ratio (RR) with 95% confidence intervals (CI) for dichotomous outcomes or mean difference (MD) for continuous outcomes. MAIN RESULTS Forty studies (3764 patients) were included. Studies conducted earlier tended to have a higher risk of bias due to poor (or poorly reported) study design, broad inclusion criteria, less well developed disease definitions and low patient numbers. Later studies tend to have improved in all areas of quality, aided by the development of large international study groups. Induction therapy: Plasma exchange as adjunctive therapy may reduce the need for dialysis at three (2 studies: RR 0.43, 95% CI 0.23 to 0.78; I2 = 0%) and 12 months (6 studies: RR 0.45, 95% CI 0.29 to 0.72; I2 = 0%) (low certainty evidence). Plasma exchange may make little or no difference to death, serum creatinine (SCr), sustained remission or to serious or the total number of adverse events. Plasma exchange may increase the number of serious infections (5 studies: RR 1.26, 95% CI 1.03 to 1.54; I2 = 0%; low certainty evidence). Remission rates for pulse versus continuous cyclophosphamide (CPA) were equivalent but pulse treatment may increase the risk of relapse (4 studies: RR 1.79, 95% CI 1.11 to 2.87; I2 = 0%) (low certainty evidence) compared with continuous cyclophosphamide. Pulse CPA may make little or no difference to death at final follow-up, or SCr at any time point. More patients required dialysis in the pulse CPA group. Leukopenia was less common with pulse treatment; however, nausea was more common. Rituximab compared to CPA probably makes little or no difference to death, remission, relapse, severe adverse events, serious infections, or severe adverse events. Kidney function and dialysis were not reported. A single study reported no difference in the number of deaths, need for dialysis, or adverse events between mycophenolate mofetil (MMF) and CPA. Remission was reported to improve with MMF however more patients relapsed. A lower dose of steroids was probably as effective as high dose and may be safer, causing fewer infections; kidney function and relapse were not reported. There was little of no difference in death or remission between six and 12 pulses of CPA. There is low certainty evidence that there were less relapses with 12 pulses (2 studies: RR 1.57, 95% CI 0.96 to 2.56; I2 = 0%), but more infections (2 studies: RR 0.79, 95% CI 0.36 to 1.72; I2 = 45%). One study reported severe adverse events were less in patients receiving six compared to 12 pulses of CPA. Kidney function and dialysis were not reported. There is limited evidence from single studies about the effectiveness of intravenous immunoglobulin, avacopan, methotrexate, immunoadsorption, lymphocytapheresis, or etanercept. Maintenance therapy: Azathioprine (AZA) has equivalent efficacy as a maintenance agent to CPA with fewer episodes of leucopenia. MMF resulted in a higher relapse rate when tested against azathioprine in remission maintenance. Rituximab is an effective remission induction and maintenance agent. Oral co-trimoxazole did not reduce relapses in granulomatosis with polyangiitis. There were fewer relapses but more serious adverse events with leflunomide compared to methotrexate. There is limited evidence from single studies about the effectiveness of methotrexate versus CPA or AZA, cyclosporin versus CPA, extended versus standard AZA, and belimumab. AUTHORS' CONCLUSIONS Plasma exchange was effective in patients with severe AKI secondary to vasculitis. Pulse cyclophosphamide may result in an increased risk of relapse when compared to continuous oral use but a reduced total dose. Whilst CPA is standard induction treatment, rituximab and MMF were also effective. AZA, methotrexate and leflunomide were effective as maintenance therapy. Further studies are required to more clearly delineate the appropriate place of newer agents within an evidence-based therapeutic strategy.
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Affiliation(s)
- Giles D Walters
- The Canberra HospitalDepartment of Renal MedicineYamba DriveCanberraACTAustralia2605
| | - Narelle S Willis
- The University of SydneySydney School of Public HealthSydneyNSWAustralia2006
- The Children's Hospital at WestmeadCochrane Kidney and Transplant, Centre for Kidney ResearchLocked Bag 4001WestmeadNSWAustralia2145
| | - Tess E Cooper
- The Children's Hospital at WestmeadCochrane Kidney and Transplant, Centre for Kidney ResearchLocked Bag 4001WestmeadNSWAustralia2145
| | - Jonathan C Craig
- The Children's Hospital at WestmeadCochrane Kidney and Transplant, Centre for Kidney ResearchLocked Bag 4001WestmeadNSWAustralia2145
- Flinders UniversityCollege of Medicine and Public HealthAdelaideSAAustralia5001
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Schirmer JH, Aries PM, de Groot K, Hellmich B, Holle JU, Kneitz C, Kötter I, Lamprecht P, Müller-Ladner U, Reinhold-Keller E, Specker C, Zänker M, Moosig F. [S1 guidelines Diagnostics and treatment of ANCA-associated vasculitis]. Z Rheumatol 2019; 76:77-104. [PMID: 29204681 DOI: 10.1007/s00393-017-0394-1] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Affiliation(s)
- Jan Henrik Schirmer
- Klinik für Innere Medizin I, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Arnold-Heller-Str. 3, 24105, Kiel, Deutschland.
| | - Peer M Aries
- Rheumatologie im Struenseehaus, Hamburg, Deutschland
| | - Kirsten de Groot
- Medizinische Klinik III, Sana Klinikum Offenbach, Offenbach, Deutschland
- KfH Nierenzentrum Offenbach, Offenbach, Deutschland
| | - Bernhard Hellmich
- Klinik für Innere Medizin, Rheumatologie und Immunologie, Vaskulitiszentrum Süd, Medius Klinik Kirchheim, Kirchheim, Deutschland
| | - Julia U Holle
- Rheumazentrum Schleswig-Holstein Mitte, Neumünster, Deutschland
| | - Christian Kneitz
- Klinik für Innere Medizin II, Rheumatologie, klinische Immunologie und Geriatrie, Klinikum Südstadt, Rostock, Deutschland
| | - Ina Kötter
- Abteilung für Rheumatologie, klinische Immunologie und Nephrologie, Asklepios Klinikum Altona, Hamburg, Deutschland
| | - Peter Lamprecht
- Klinik für Rheumatologie und klinische Immunologie, Universität zu Lübeck, Lübeck, Deutschland
| | - Ulf Müller-Ladner
- Abteilung für Rheumatologie und Klinische Immunologie, Campus Kerckhoff, Justus-Liebig Universität Giessen, Bad Nauheim, Deutschland
| | - Eva Reinhold-Keller
- Klinik für Rheumatologie und klinische Immunologie, Klinikum Bad Bramstedt, Bad Bramstedt, Deutschland
| | - Christof Specker
- Klinik für Rheumatologie und klinische Immunologie, Universitätsmedizin Essen, St. Josef Krankenhaus Werden, Essen, Deutschland
| | - Michael Zänker
- Abteilung für Innere Medizin, Immanuel Klinikum Bernau Herzzentrum Brandenburg, Bernau, Deutschland
- Medizinische Hochschule Brandenburg, Neuruppin, Deutschland
| | - Frank Moosig
- Rheumazentrum Schleswig-Holstein Mitte, Neumünster, Deutschland
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Koukoulaki M, Iatrou C. The role of mycophenolate in the treatment of antineutrophil cytoplasmic antibody-associated vasculitis. World J Nephrol 2019; 8:75-82. [PMID: 31523631 PMCID: PMC6715575 DOI: 10.5527/wjn.v8.i4.75] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Revised: 07/09/2019] [Accepted: 07/16/2019] [Indexed: 02/06/2023] Open
Abstract
Mycophenolic acid, the active metabolite for mycophenolate mofetil and mycophenolic sodium, is a strong, noncompetitive, reversible inhibitor of inosine monophosphate dehydrogenase, the key enzyme in de novo synthesis of guanosine nucleotides leading to selective inhibition of lymphocyte proliferation. Mycophenolic acid has been evaluated as induction and remission maintenance agent in the treatment of antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Since the course of disease of AAV usually requires long term immunosuppression, mycophenolate has been explored as a less toxic agent compared to cyclophosphamide and azathioprine. Mycophenolate is a potent immunosuppressive agent in the therapy of AAV, non-inferior to other available drugs with comparable side effect profile. Therefore, it could be a valuable alternative in cases of toxicity with life threatening side effects or intolerance to cyclophosphamide or azathioprine, in cases with high cumulative dose of cyclophosphamide, but also in cases with insufficient response. Several studies have shown a higher relapse rate following discontinuation of mycophenolate or in mycophenolate treated subjects that raises concerns about its usefulness in the treatment of AAV. This review describes the efficacy of mycophenolate in AAV as remission induction agent, as remission maintenance agent, and as therapeutic option in relapsing AAV disease, the relapse rate following discontinuation of mycophenolate, and the adverse events related to mycophenolate treatment.
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Affiliation(s)
- Maria Koukoulaki
- Center for Nephrology “G. Papadakis”, General Hospital of Nikaia – Piraeus “Agios Panteleimon”, Piraeus, Nikaia 18454, Greece
| | - Christos Iatrou
- Center for Nephrology “G. Papadakis”, General Hospital of Nikaia – Piraeus “Agios Panteleimon”, Piraeus, Nikaia 18454, Greece
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Tuin J, Stassen PM, Bogdan DI, Broekroelofs J, van Paassen P, Cohen Tervaert JW, Sanders JS, Stegeman CA. Mycophenolate Mofetil Versus Cyclophosphamide for the Induction of Remission in Nonlife-Threatening Relapses of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Randomized, Controlled Trial. Clin J Am Soc Nephrol 2019; 14:1021-1028. [PMID: 31253599 PMCID: PMC6625631 DOI: 10.2215/cjn.11801018] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2018] [Accepted: 05/17/2019] [Indexed: 11/23/2022]
Abstract
BACKGROUND AND OBJECTIVES Cyclophosphamide has been the mainstay of treatment of ANCA-associated vasculitis. However, cyclophosphamide has unfavorable side effects and alternatives are needed. Evidence suggests that mycophenolate mofetil can induce sustained remission in nonlife-threatening disease. The purpose of this study was to compare the efficacy and safety of mycophenolate mofetil versus cyclophosphamide for the induction treatment of nonlife-threatening relapses of proteinase 3-ANCA- and myeloperoxidase-ANCA-associated vasculitis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We conducted a multicenter randomized, controlled trial. Participants with a first or second relapse of ANCA-associated vasculitis were randomized to induction treatment with cyclophosphamide or mycophenolate mofetil both in combination with glucocorticoids. Maintenance therapy consisted of azathioprine in both arms. Primary outcome was remission at 6 months, and secondary outcomes included disease-free survival at 2 and 4 years. RESULTS Eighty-four participants were enrolled, of whom 41 received mycophenolate mofetil and 43 received cyclophosphamide. Eighty-nine percent of participants were proteinase 3-ANCA positive. At 6 months, 27 (66%) mycophenolate mofetil-treated participants versus 35 (81%) cyclophosphamide-treated participants were in remission (P=0.11). Disease-free survival rates at 2 and 4 years were 61% and 39% for cyclophosphamide, respectively, and 43% and 32% for mycophenolate mofetil, respectively (at 4 years, log rank test, P=0.17). CONCLUSIONS We did not demonstrate mycophenolate mofetil to be similarly effective as cyclophosphamide in inducing remission of relapsed ANCA-associated vasculitis. However, mycophenolate mofetil might be an alternative to cyclophosphamide for the treatment of selected patients with nonlife-threatening relapses.
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Affiliation(s)
- Janneke Tuin
- Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands;
| | | | - Daria I Bogdan
- Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Jan Broekroelofs
- Division of Nephrology, Department of Internal Medicine, Medisch Centrum Leeuwarden, Leeuwarden, The Netherlands; and
| | - Pieter van Paassen
- Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Jan Willem Cohen Tervaert
- Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.,Department of Medicine, University of Alberta, Edmonton, Canada
| | - Jan-Stephan Sanders
- Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Coen A Stegeman
- Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
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Jones RB, Hiemstra TF, Ballarin J, Blockmans DE, Brogan P, Bruchfeld A, Cid MC, Dahlsveen K, de Zoysa J, Espigol-Frigolé G, Lanyon P, Peh CA, Tesar V, Vaglio A, Walsh M, Walsh D, Walters G, Harper L, Jayne D. Mycophenolate mofetil versus cyclophosphamide for remission induction in ANCA-associated vasculitis: a randomised, non-inferiority trial. Ann Rheum Dis 2019; 78:399-405. [PMID: 30612116 DOI: 10.1136/annrheumdis-2018-214245] [Citation(s) in RCA: 144] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Revised: 11/30/2018] [Accepted: 12/05/2018] [Indexed: 02/06/2023]
Abstract
OBJECTIVES Cyclophosphamide induction regimens are effective for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but are associated with infections, malignancies and infertility. Mycophenolate mofetil (MMF) has shown high remission rates in small studies of AAV. METHODS We conducted a randomised controlled trial to investigate whether MMF was non-inferior to cyclophosphamide for remission induction in AAV. 140 newly diagnosed patients were randomly assigned to MMF or pulsed cyclophosphamide. All patients received the same oral glucocorticoid regimen and were switched to azathioprine following remission. The primary endpoint was remission by 6 months requiring compliance with the tapering glucocorticoid regimen. Patients with an eGFR <15 mL/min were excluded from the study. RESULTS At baseline, ANCA subtype, disease activity and organ involvement were similar between groups. Non-inferiority was demonstrated for the primary remission endpoint, which occurred in 47 patients (67%) in the MMF group and 43 patients (61%) in the cyclophosphamide group (risk difference 5.7%, 90% CI -7.5% to 19%). Following remission, more relapses occurred in the MMF group (23 patients, 33%) compared with the cyclophosphamide group (13 patients, 19%) (incidence rate ratio 1.97, 95% CI 0.96 to 4.23, p=0.049). In MPO-ANCA patients, relapses occurred in 12% of the cyclophosphamide group and 15% of the MMF group. In PR3-ANCA patients, relapses occurred in 24% of the cyclophosphamide group and 48% of the MMF group. Serious infections were similar between groups (26% MMF group, 17% cyclophosphamide group) (OR 1.67, 95% CI 0.68 to 4.19, p=0.3). CONCLUSION MMF was non-inferior to cyclophosphamide for remission induction in AAV, but resulted in higher relapse rate. TRIAL REGISTRATION NUMBER NCT00414128.
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Affiliation(s)
- Rachel B Jones
- Department of Renal Medicine, Addenbrooke's Hospital, Cambridge, UK
| | - Thomas F Hiemstra
- School of Clinical Medicine, University of Cambridge, Cambridge, UK
- Cambridge Clinical Trials Unit, Addenbrooke's Hospital, Cambridge, UK
| | - Jose Ballarin
- Department of Nephrology, Fundació Puigvert, Barcelona, Spain
| | | | - Paul Brogan
- Department of Paediatric Rheumatology, University College London Great Ormond Street Institute of Child Health, London, UK
- Department of Paediatric Rheumatology, Great Ormond Street Hospital NHS Foundation Trust, London, UK
| | - Annette Bruchfeld
- Department of Renal Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Maria C Cid
- Department of Autoimmune Diseases, Hospital Clinic, University of Barcelona, Institut d'investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Karen Dahlsveen
- Department of Renal Medicine, Addenbrooke's Hospital, Cambridge, UK
| | - Janak de Zoysa
- Renal Service, Waitemata District Health Board, Auckland, New Zealand
- Department of Medicine, University of Auckland, Auckland, New Zealand
| | - Georgína Espigol-Frigolé
- Department of Autoimmune Diseases, Hospital Clinic, University of Barcelona, Institut d'investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Peter Lanyon
- Department of Rheumatology, Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - Chen Au Peh
- Department of Renal Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Vladimir Tesar
- Department of Nephrology, Charles University and General University Hospital, Prague, Czech Republic
| | - Augusto Vaglio
- Department of Biomedical, Experimental and Clinical Sciences 'Mario Serio', University of Firenze, Firenze, Italy
- Nephrology and Dialysis Unit, Meyer Children's University Hospital, Firenze, Italy
| | - Michael Walsh
- Departments of Medicine and Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
| | - Dorothy Walsh
- Department of Renal Medicine, Addenbrooke's Hospital, Cambridge, UK
| | - Giles Walters
- Department of Renal Medicine, Canberra Hospital, Canberra, Australian Capital Territory, Australia
| | - Lorraine Harper
- Institute of Clinical Sciences, University of Birmingham, Birmingham, UK
| | - David Jayne
- Department of Renal Medicine, Addenbrooke's Hospital, Cambridge, UK
- School of Clinical Medicine, University of Cambridge, Cambridge, UK
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Nagasaka K, Harigai M, Hagino N, Hara A, Horita T, Hayashi T, Itabashi M, Ito S, Katsumata Y, Kawashima S, Naniwa T, Sada KE, Nango E, Nakayama T, Tsutsumino M, Yamagata K, Homma S, Arimura Y. Systematic review and meta-analysis for 2017 clinical practice guidelines of the Japan research committee of the ministry of health, labour, and welfare for intractable vasculitis for the management of ANCA-associated vasculitis. Mod Rheumatol 2018; 29:119-129. [PMID: 29996690 DOI: 10.1080/14397595.2018.1500111] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES To provide evidence for the revision of clinical practice guideline (CPG) for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) by the Japan Research Committee for Intractable Vasculitis. METHODS PubMed, CENTRAL, and the Japan Medical Abstracts Society were searched for articles published between January 1994 and January 2015 to conduct systematic review (SR), and the quality of evidence was assessed with GRADE approach. RESULTS Nine randomized controlled trials (RCTs) and two non-RCTs were adopted for remission induction therapy, three RCTs and two non-RCTs for plasma exchange, and five RCTs and one non-RCT for remission maintenance therapy. A significant difference was found in efficacy and safety for the following comparisons. In the non-RCT adopted for remission induction therapy, glucocorticoid (GC) + cyclophosphamide (CY) was significantly superior to GC monotherapy regarding remission. GC + intravenous CY for remission induction therapy was superior to GC + oral CY regarding death at one year, serious adverse events, and serious infection. Concomitant use of plasma exchange for remission induction therapy of AAV with severe renal dysfunction reduced risk of end-stage renal disease versus non-users at month 3. CONCLUSION This SR provided necessary evidence for developing CPG for the management of ANCA-associated vasculitis.
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Affiliation(s)
- Kenji Nagasaka
- a Department of Rheumatology , Ome Municipal General Hospital , Tokyo , Japan.,b Department of Pharmacovigilance, Graduate School of Medical and Dental Sciences , Tokyo Medical and Dental University , Tokyo , Japan
| | - Masayoshi Harigai
- c Division of Epidemiology and Pharmacoepidemiology, Department of Rheumatology, School of Medicine , Tokyo Women's Medical University , Tokyo , Japan
| | - Noboru Hagino
- d Division of Hematology and Rheumatology , Teikyo University Chiba Medical Center , Chiba , Japan
| | - Akinori Hara
- e Department of Environmental and Preventive Medicine, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences , Kanazawa University , Ishikawa , Japan
| | - Tetsuya Horita
- f Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine , Hokkaido University , Hokkaido , Japan
| | - Taichi Hayashi
- g Department of Internal Medicine, Faculty of Medicine , University of Tsukuba , Ibaraki , Japan
| | - Mitsuyo Itabashi
- h Department of Nephrology , Tokyo Metropolitan Geriatric Hospital , Tokyo , Japan
| | - Satoshi Ito
- i Department of Rheumatology , Niigata Rheumatic Center , Niigata , Japan
| | - Yasuhiro Katsumata
- j Department of Rheumatology, School of Medicine , Tokyo Women's Medical University , Tokyo , Japan
| | - Soko Kawashima
- k Department of Nephrology and Rheumatology, First Department of Internal Medicine , Kyorin University School of Medicine , Tokyo , Japan
| | - Taio Naniwa
- l Department of Respiratory Medicine, Allergy and Clinical Immunology , Nagoya City University Graduate School of Medical Sciences , Nagoya , Japan
| | - Ken-Ei Sada
- m Department of Nephrology, Rheumatology, Endocrinology and Metabolism , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama , Japan
| | - Eishu Nango
- n Department of General Medicine , Tokyo Kita Medical Center , Tokyo , Japan
| | - Takeo Nakayama
- o Department of Health Informatics, Graduate School of Medicine and Public Health , Kyoto University , Kyoto , Japan
| | - Michi Tsutsumino
- j Department of Rheumatology, School of Medicine , Tokyo Women's Medical University , Tokyo , Japan
| | - Kunihiro Yamagata
- p Department of Nephrology, Faculty of Medicine , University of Tsukuba , Ibaraki , Japan
| | - Sakae Homma
- q Department of Respiratory Medicine , Toho University Omori Medical Center , Tokyo , Japan
| | - Yoshihiro Arimura
- k Department of Nephrology and Rheumatology, First Department of Internal Medicine , Kyorin University School of Medicine , Tokyo , Japan
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Harigai M, Nagasaka K, Amano K, Bando M, Dobashi H, Kawakami T, Kishibe K, Murakawa Y, Usui J, Wada T, Tanaka E, Nango E, Nakayama T, Tsutsumino M, Yamagata K, Homma S, Arimua Y. 2017 Clinical practice guidelines of the Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis for the management of ANCA-associated vasculitis. Mod Rheumatol 2018; 29:20-30. [PMID: 30001655 DOI: 10.1080/14397595.2018.1500437] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE The Japan Research Committee for Intractable Vasculitis has fully revised the clinical practice guidelines (CPG) for the management of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) to improve and standardize the medical treatment of the disease in Japan. METHODS The previous CPG was published in a classical review style in Japanese in 2011 and 2014. We adopted the Grading of Recommendations Assessment, Development and Evaluation system for this revision, and various stakeholders, including patients, participated in it. The expected users of this CPG are AAV patients in Japan and their families and healthcare professionals, including both AAV specialists and non-specialists. We set clinical questions concerning the three important clinical topics of remission induction therapy, plasma exchange, remission maintenance therapy, and developed eight recommendation statements. RESULTS For remission induction therapy for newly developed AAV, we weakly recommend glucocorticoid (GC) plus intravenous cyclophosphamide pulse (IVCY) or oral cyclophosphamide (POCY) rather than GC alone, and IVCY rather than POCY. We also weakly recommend CY rather than rituximab. In the case of AAV with severe renal impairment, we weakly recommend plasma exchange as a conjunction therapy. We weakly recommend azathioprine for remission maintenance therapy. CONCLUSION The revised CPG has demonstrated evidence-based treatment recommendations for AAV.
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Affiliation(s)
- Masayoshi Harigai
- a Division of Epidemiology and Pharmacoepidemiology, Department of Rheumatology, School of Medicine , Tokyo Women's Medical University , Tokyo , Japan
| | - Kenji Nagasaka
- b Department of Rheumatology , Ome Municipal General Hospital , Tokyo , Japan.,c Department of Pharmacovigilance, Graduate School of Medical and Dental Sciences , Tokyo Medical and Dental University , Tokyo , Japan
| | - Koichi Amano
- d Department of Rheumatology and Clinical Immunology, Saitama Medical Center , Saitama Medical School , Saitama , Japan
| | - Masashi Bando
- e Division of Pulmonary Medicine, Department of Medicine , Jichi Medical University , Tochigi , Japan
| | - Hiroaki Dobashi
- f Division of Hematology , Rheumatology and Respiratory Medicine Department of Internal Medicine Faculty of Medicine Kagawa University , Kagawa , Japan
| | - Tamihiro Kawakami
- g Department of Dermatology , St. Marianna University School of Medicine , Kanagawa , Japan
| | - Kan Kishibe
- h Department of Otolaryngology-Head and Neck Surgery , Asahikawa Medical University , Hokkaido , Japan
| | - Yohko Murakawa
- i Department of Rheumatology , Shimane University Faculty of Medicine , Shimane , Japan
| | - Joichi Usui
- j Department of Nephrology, Faculty of Medicine , University of Tsukuba , Ibaraki , Japan
| | - Takashi Wada
- k Department of Nephrology and Laboratory Medicine, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences , Kanazawa University , Ishikawa , Japan
| | - Eiichi Tanaka
- l Department of Rheumatology, School of Medicine , Tokyo Women's Medical University , Tokyo , Japan
| | - Eishu Nango
- m Department of General Medicine , Tokyo Kita Medical Center , Tokyo , Japan
| | - Takeo Nakayama
- n Department of Health Informatics, Graduate School of Medicine and Public Health , Kyoto University , Kyoto , Japan
| | - Michi Tsutsumino
- l Department of Rheumatology, School of Medicine , Tokyo Women's Medical University , Tokyo , Japan
| | - Kunihiro Yamagata
- j Department of Nephrology, Faculty of Medicine , University of Tsukuba , Ibaraki , Japan
| | - Sakae Homma
- o Department of Respiratory Medicine , Toho University Omori Medical Center , Tokyo , Japan
| | - Yoshihiro Arimua
- p Division of Nephrology and Rheumatology, First Department of Internal Medicine , Kyorin University School of Medicine , Tokyo , Japan
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Hellmich B. [Current guidelines on ANCA-associated vasculitides : Common features and differences]. Z Rheumatol 2017; 76:133-142. [PMID: 27848024 DOI: 10.1007/s00393-016-0223-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
The results of a number of prospective randomized controlled clinical trials have led to changes in established strategies for the treatment of antineutrophil cytoplasmic antibody (ANCA) associated vasculitides (AAV) in recent years. Since 2014, a total of 4 scientific societies and study groups have systematically reviewed the new data and have formulated evidence-based recommendations for the management of AAV based on the analysis. These recommendations contain information on diagnosis, treatment (induction and maintenance), supportive care and monitoring of disease activity and resulting damage. This review compares the recently published recommendations of the German Society of Rheumatology (Deutschen Gesellschaft für Rheumatologie, DGRh), the European League Against Rheumatism (EULAR)/European Renal Association (ERA), the British Society of Rheumatology (BSR) and the Canadian Vasculitis Research Network (CanVasc). The comparative analysis reveals a high level of agreement on numerous topics but also shows some minor and even a few major differences in the respective recommended approach to diagnosis and treatment of AAV. Divergent recommendations predominantly exist in areas with little scientific evidence from clinical studies. Furthermore, some differences result from different interpretation of existing data or are influenced by characteristic features of the respective national healthcare system.
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Affiliation(s)
- B Hellmich
- Vaskulitiszentrum Süd, Klinik für Innere Medizin, Rheumatologie und Immunologie, Klinik Kirchheim, Akademisches Lehrkrankenhaus der Universität Tübingen, Eugenstr. 3, 73230, Kirchheim u. Teck, Deutschland.
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Morishita KA, Tiller G, Cabral DA. Therapeutic Management of Pediatric Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis. CURRENT TREATMENT OPTIONS IN RHEUMATOLOGY 2017. [DOI: 10.1007/s40674-017-0077-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Puéchal X, Pagnoux C, Baron G, Quémeneur T, Néel A, Agard C, Lifermann F, Liozon E, Ruivard M, Godmer P, Limal N, Mékinian A, Papo T, Ruppert AM, Bourgarit A, Bienvenu B, Geffray L, Saraux JL, Diot E, Crestani B, Delbrel X, Sailler L, Cohen P, Le Guern V, Terrier B, Groh M, Le Jeunne C, Mouthon L, Ravaud P, Guillevin L. Adding Azathioprine to Remission-Induction Glucocorticoids for Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss), Microscopic Polyangiitis, or Polyarteritis Nodosa Without Poor Prognosis Factors: A Randomized, Controlled Trial. Arthritis Rheumatol 2017; 69:2175-2186. [PMID: 28678392 DOI: 10.1002/art.40205] [Citation(s) in RCA: 103] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2016] [Accepted: 06/29/2017] [Indexed: 11/09/2022]
Abstract
OBJECTIVE In most patients with nonsevere systemic necrotizing vasculitides (SNVs), remission is achieved with glucocorticoids alone, but one-third experience a relapse within 2 years. This study was undertaken to determine whether the addition of azathioprine (AZA) to glucocorticoids could achieve a higher sustained remission rate of newly diagnosed nonsevere eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA), microscopic polyangiitis (MPA), or polyarteritis nodosa (PAN). METHODS All patients included in this double-blind trial received glucocorticoids, gradually tapered over 12 months, and were randomized to receive AZA or placebo for 12 months, with stratification according to SNV (EGPA or MPA/PAN). The primary end point was the combined rate of remission induction failures and minor or major relapses at month 24. RESULTS Ninety-five patients (51 with EGPA, 25 with MPA, and 19 with PAN) met the inclusion criteria, were randomized, and received at least 1 dose of AZA (n = 46) or placebo (n = 49). At month 24, 47.8% of the patients receiving AZA versus 49% of the patients receiving placebo had remission induction failures or relapses (P = 0.86). Secondary end points were comparable between the AZA and placebo arms. These included initial remission rate (95.7% versus 87.8%), total relapse rate (44.2% versus 40.5%), and glucocorticoid use. Two patients in the placebo arm died; 22 patients in the AZA arm (47.8%) and 23 patients in the placebo arm (46.9%) experienced ≥1 severe adverse event. For EGPA patients, the primary end point (48% in the AZA arm versus 46.2% in the placebo arm) and the percent of patients who experienced asthma/rhinosinusitis exacerbations (24% in the AZA arm versus 19.2% in the placebo arm) were comparable between treatment arms. CONCLUSION Addition of AZA to glucocorticoids for the induction of remission of nonsevere SNVs does not improve remission rates, lower relapse risk, spare steroids, or diminish the EGPA asthma/rhinosinusitis exacerbation rate.
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Affiliation(s)
- Xavier Puéchal
- National Referral Center for Rare Systemic and Autoimmune Diseases, Department of Internal Medicine, Université Paris Descartes, Hôpital Cochin, AP-HP, Paris, France
| | - Christian Pagnoux
- National Referral Center for Rare Systemic and Autoimmune Diseases, Department of Internal Medicine, Université Paris Descartes, Hôpital Cochin, AP-HP, Paris, France
| | - Gabriel Baron
- Université Paris Descartes, Hôtel-Dieu, AP-HP, Paris, France
| | | | - Antoine Néel
- Centre Hospitalier Universitaire Hôtel-Dieu, Nantes, France
| | | | | | - Eric Liozon
- Centre Hospitalier Universitaire Dupuytren, Limoges, France
| | - Marc Ruivard
- Centre Hospitalier Universitaire Estaing, Clermont-Ferrand, France
| | - Pascal Godmer
- Centre Hospitalier Bretagne Atlantique, Vannes, France
| | - Nicolas Limal
- Hôpital Henri-Mondor, Université Paris-Est Créteil, AP-HP, Créteil, France
| | - Arsène Mékinian
- Hôpital Saint-Antoine, Université Pierre et Marie Curie, AP-HP, Paris, France
| | - Thomas Papo
- Hôpital Bichat-Claude-Bernard, Université Denis-Diderot, AP-HP, Paris, France
| | | | - Anne Bourgarit
- Hôpital Jean-Verdier, Université Léonard-de-Vinci, AP-HP, Bondy, France
| | - Boris Bienvenu
- Centre Hospitalier Universitaire Côte de Nacre, Caen, France
| | | | | | | | - Bruno Crestani
- Hôpital Bichat-Claude-Bernard, Université Denis-Diderot, AP-HP, Paris, France
| | | | | | - Pascal Cohen
- National Referral Center for Rare Systemic and Autoimmune Diseases, Department of Internal Medicine, Université Paris Descartes, Hôpital Cochin, AP-HP, Paris, France
| | - Véronique Le Guern
- National Referral Center for Rare Systemic and Autoimmune Diseases, Department of Internal Medicine, Université Paris Descartes, Hôpital Cochin, AP-HP, Paris, France
| | - Benjamin Terrier
- National Referral Center for Rare Systemic and Autoimmune Diseases, Department of Internal Medicine, Université Paris Descartes, Hôpital Cochin, AP-HP, Paris, France
| | - Matthieu Groh
- National Referral Center for Rare Systemic and Autoimmune Diseases, Department of Internal Medicine, Université Paris Descartes, Hôpital Cochin, AP-HP, Paris, France
| | - Claire Le Jeunne
- National Referral Center for Rare Systemic and Autoimmune Diseases, Department of Internal Medicine, Université Paris Descartes, Hôpital Cochin, AP-HP, Paris, France
| | - Luc Mouthon
- National Referral Center for Rare Systemic and Autoimmune Diseases, Department of Internal Medicine, Université Paris Descartes, Hôpital Cochin, AP-HP, Paris, France
| | - Philippe Ravaud
- Université Paris Descartes, Hôtel-Dieu, AP-HP, Paris, France
| | - Loïc Guillevin
- National Referral Center for Rare Systemic and Autoimmune Diseases, Department of Internal Medicine, Université Paris Descartes, Hôpital Cochin, AP-HP, Paris, France
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Souza AWSD, Calich AL, Mariz HDA, Ochtrop MLG, Bacchiega ABS, Ferreira GA, Rêgo J, Perez MO, Pereira RMR, Bernardo WM, Levy RA. Recommendations of the Brazilian Society of Rheumatology for the induction therapy of ANCA-associated vasculitis. REVISTA BRASILEIRA DE REUMATOLOGIA 2017; 57 Suppl 2:484-496. [PMID: 28754431 DOI: 10.1016/j.rbre.2017.06.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2017] [Accepted: 05/21/2017] [Indexed: 12/31/2022] Open
Abstract
The purpose of these recommendations is to guide the appropriate induction treatment of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) patients with active disease. The recommendations proposed by the Vasculopathies Committee of the Brazilian Society Rheumatology for induction therapy of AAV, including granulomatosis with polyangiitis, microscopic polyangiitis and renal-limited vasculitis, were based on systematic literature review and expert opinion. Literature review was performed using Medline (PubMed), EMBASE and Cochrane database to retrieve articles until October 2016. PRISMA guidelines were used for the systematic review and articles were assessed according to the Oxford levels of evidence. Sixteen recommendations were made regarding different aspects of induction therapy for AAV. The purpose of these recommendations is to serve as a guide for therapeutic decisions by health care professionals in the management of AAV patients presenting active disease.
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Affiliation(s)
- Alexandre Wagner Silva de Souza
- Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM), Disciplina de Reumatologia, São Paulo, SP, Brazil.
| | - Ana Luisa Calich
- Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM), Disciplina de Reumatologia, São Paulo, SP, Brazil
| | | | - Manuella Lima Gomes Ochtrop
- Universidade do Estado do Rio de Janeiro (UERJ), Hospital Universitário Pedro Ernesto, Serviço de Reumatologia, Rio de Janeiro, RJ, Brazil
| | - Ana Beatriz Santos Bacchiega
- Universidade do Estado do Rio de Janeiro (UERJ), Hospital Universitário Pedro Ernesto, Serviço de Reumatologia, Rio de Janeiro, RJ, Brazil
| | - Gilda Aparecida Ferreira
- Universidade Federal de Minas Gerais (UFMG), Faculdade de Medicina, Departamento Aparelho Locomotor, Belo Horizonte, MG, Brazil
| | - Jozelia Rêgo
- Universidade Federal de Goiás (UFG), Faculdade de Medicina, Serviço de Reumatologia, Goiânia, GO, Brazil
| | - Mariana Ortega Perez
- Universidade de São Paulo (USP), Faculdade de Medicina, Disciplina de Reumatologia, São Paulo, SP, Brazil
| | | | | | - Roger Abramino Levy
- Universidade do Estado do Rio de Janeiro (UERJ), Hospital Universitário Pedro Ernesto, Serviço de Reumatologia, Rio de Janeiro, RJ, Brazil
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Souza AWSD, Calich AL, Mariz HDA, Ochtrop MLG, Bacchiega ABS, Ferreira GA, Rêgo J, Perez MO, Pereira RMR, Bernardo WM, Levy RA. Recomendações da Sociedade Brasileira de Reumatologia para a terapia de indução para vasculite associada a ANCA. REVISTA BRASILEIRA DE REUMATOLOGIA 2017. [DOI: 10.1016/j.rbr.2017.05.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
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Rasche FM, Keller F, Rasche WG, Schiekofer S, Boldt A, Sack U, Fahnert J. Why, when and how should immunosuppressive therapy considered in patients with immunoglobulin A nephropathy? Clin Exp Immunol 2016; 186:115-133. [PMID: 27283488 PMCID: PMC5054563 DOI: 10.1111/cei.12823] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2016] [Revised: 05/20/2016] [Accepted: 05/20/2016] [Indexed: 12/13/2022] Open
Abstract
IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Lifelong mesangial deposition of IgA1 complexes subsist inflammation and nephron loss, but the complex pathogenesis in detail remains unclear. In regard to the heterogeneous course, classical immunosuppressive and specific therapeutic regimens adapted to the loss of renal function will here be discussed in addition to the essential common renal supportive therapy. Renal supportive therapy alleviates secondary, surrogate effects or sequelae on renal function and proteinuria of high intraglomerular pressure and subsequent nephrosclerosis by inhibition of the renin angiotensin system (RAASB). In patients with physiological (ΔGFR < 1·5 ml/min/year) or mild (ΔGFR 1·5-5 ml/min/year) decrease of renal function and proteinuric forms (> 1 g/day after RAASB), corticosteroids have shown a reduction of proteinuria and might protect further loss of renal function. In patients with progressive loss of renal function (ΔGFR > 3 ml/min within 3 months) or a rapidly progressive course with or without crescents in renal biopsy, cyclophosphamide with high-dose corticosteroids as induction therapy and azathioprine maintenance has proved effective in one randomized controlled study of a homogeneous cohort in loss of renal function (ΔGFR). Mycophenolic acid provided further maintenance in non-randomized trials. Differentiated, precise, larger, randomized, placebo-controlled studies focused on the loss of renal function in the heterogeneous forms of IgAN are still lacking. Prospectively, fewer toxic agents will be necessary in the treatment of IgAN.
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Affiliation(s)
- F M Rasche
- Department of Internal Medicine, Neurology, Dermatology, Clinic for Endocrinology, Nephrology, Section of Nephrology, University Leipzig, Leipzig, Germany
| | - F Keller
- Department of Internal Medicine I, Division of Nephrology, University Hospital of Ulm, Ulm, Germany.
| | - W G Rasche
- Department of Head Medicine and Oral Health, Department of Ophthalmology, University Leipzig, Leipzig, Germany
| | - S Schiekofer
- Center for Geriatric Medicine at Bezirksklinikum Regensburg, Department of Psychiatry and Psychotherapy, University Regensburg, Regensburg, Germany
| | - A Boldt
- Institute of Clinical Immunology, Medical Faculty, Leipzig, Germany
| | - U Sack
- Institute of Clinical Immunology, Medical Faculty, Leipzig, Germany
| | - J Fahnert
- Department of Diagnostic and Interventional Radiology, University Leipzig, Leipzig, Germany
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Yates M, Watts RA, Bajema IM, Cid MC, Crestani B, Hauser T, Hellmich B, Holle JU, Laudien M, Little MA, Luqmani RA, Mahr A, Merkel PA, Mills J, Mooney J, Segelmark M, Tesar V, Westman K, Vaglio A, Yalçındağ N, Jayne DR, Mukhtyar C. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis 2016; 75:1583-94. [PMID: 27338776 DOI: 10.1136/annrheumdis-2016-209133] [Citation(s) in RCA: 780] [Impact Index Per Article: 86.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2016] [Accepted: 05/27/2016] [Indexed: 12/13/2022]
Abstract
In this article, the 2009 European League Against Rheumatism (EULAR) recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have been updated. The 2009 recommendations were on the management of primary small and medium vessel vasculitis. The 2015 update has been developed by an international task force representing EULAR, the European Renal Association and the European Vasculitis Society (EUVAS). The recommendations are based upon evidence from systematic literature reviews, as well as expert opinion where appropriate. The evidence presented was discussed and summarised by the experts in the course of a consensus-finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) determined. In addition to the voting by the task force members, the relevance of the recommendations was assessed by an online voting survey among members of EUVAS. Fifteen recommendations were developed, covering general aspects, such as attaining remission and the need for shared decision making between clinicians and patients. More specific items relate to starting immunosuppressive therapy in combination with glucocorticoids to induce remission, followed by a period of remission maintenance; for remission induction in life-threatening or organ-threatening AAV, cyclophosphamide and rituximab are considered to have similar efficacy; plasma exchange which is recommended, where licensed, in the setting of rapidly progressive renal failure or severe diffuse pulmonary haemorrhage. These recommendations are intended for use by healthcare professionals, doctors in specialist training, medical students, pharmaceutical industries and drug regulatory organisations.
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Affiliation(s)
- M Yates
- Department of Rheumatology, Norfolk and Norwich University Hospital, Norwich, UK Norwich Medical School, University of East Anglia, Norwich, UK
| | - R A Watts
- Norwich Medical School, University of East Anglia, Norwich, UK Department of Rheumatology, Ipswich Hospital NHS Trust, Ipswich, Suffolk, UK
| | - I M Bajema
- Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
| | - M C Cid
- Vasculitis Research Unit, Department of Autoimmune Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - B Crestani
- Assistance Publique-Hôpitaux de Paris, Department of Pulmonology, Bichat-Claude Bernard University Hospital, Paris, France
| | - T Hauser
- Immunologie-Zentrum Zürich, Zürich, Switzerland
| | - B Hellmich
- Vaskulits-Zentrum Süd, Klinik für Innere Medizin, Rheumatologie und Immunologie, Kreiskliniken Esslingen, Kirchheim-Teck, Germany
| | - J U Holle
- Rheumazentrum Schleswig-Holstein Mitte, Neumünster, Germany
| | - M Laudien
- Department of Otorhinolaryngology, Head and Neck Surgery, University of Kiel, Kiel, Germany
| | - M A Little
- Trinity Health Kidney Centre, Tallaght Hospital, Dublin, Ireland
| | - R A Luqmani
- Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, United Kingdom
| | - A Mahr
- Department of Internal Medicine, Hôpital Saint-Louis, Université Paris 7 René Diderot, Paris, France
| | - P A Merkel
- Division of Rheumatology and the Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - J Mills
- Vasculitis UK, West Bank House, Winster, Matlock, UK
| | - J Mooney
- Department of Rheumatology, Norfolk and Norwich University Hospital, Norwich, UK
| | - M Segelmark
- Department of Medical and Health Sciences, Linköping University, Linköping, Sweden Department of Nephrology, Linköping University, Linköping, Sweden
| | - V Tesar
- Department of Nephrology, 1st School of Medicine, Charles University, Prague, Czech Republic
| | - K Westman
- Department of Nephrology, Lund University, Skåne University Hospital, Lund and Malmö, Sweden
| | - A Vaglio
- Nephrology Unit, University Hospital of Parma, Parma, Italy
| | - N Yalçındağ
- Department of Ophthalmology, School of Medicine, Ankara University, Ankara, Turkey
| | - D R Jayne
- Lupus and Vasculitis Unit, Addenbrooke's Hospital, Cambridge, UK
| | - C Mukhtyar
- Department of Rheumatology, Norfolk and Norwich University Hospital, Norwich, UK
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Han F, Chen LL, Ren PP, Le JY, Choong PJ, Wang HJ, Xu Y, Chen JH. Mycophenolate mofetil plus prednisone for inducing remission of Henoch-Schönlein purpura nephritis: a retrospective study. J Zhejiang Univ Sci B 2016; 16:772-9. [PMID: 26365119 DOI: 10.1631/jzus.b1400335] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
OBJECTIVE The treatment of Henoch-Schönlein purpura (HSP) with moderate proteinuria remains controversial. We retrospectively analyzed the efficacy of immune suppressants, with a particular emphasis on mycophenolate mofetil (MMF). METHODS Ninety-five HSP patients with moderate proteinuria (1.0-3.5 g/24 h) after at least three months of therapy with angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) were divided into three groups: an MMF group (n=33) that received MMF 1.0-1.5 g/d combined with prednisone (0.4-0.5 mg/(kg·d)), a corticosteroid (CS) group (n=31) that received full-dose prednisone (0.8-1.0 mg/(kg·d)), and a control group (n=31). Patients in the MMF and CS groups continued to take ACEI or ARB at the original dose. The patients in the control group continued to take ACEI or ARB but the dose was increased by (1.73±0.58)-fold. The patients were followed up for 6-78 months (median 28 months). RESULTS The baseline proteinuria was higher in the MMF group ((2.1±0.9) g/24 h) than in the control group ((1.6±0.8) g/24 h) (P=0.039). The proteinuria decreased significantly in all groups during follow-up, but only in the MMF group did it decrease significantly after the first month. At the end of follow-up, the proteinuria was (0.4±0.7) g/24 h in the MMF group and (0.4±0.4) g/24 h in the CS group, significantly lower than that in the control group ((0.9±1.1) g/24 h). The remission rates in the MMF group, CS group, and control group were respectively 72.7%, 71.0%, and 48.4% at six months and 72.7%, 64.5%, and 45.2% at the end of follow-up. The overall number of reported adverse events was 17 in the MMF group, 30 in the CS group, and 6 in the control group (P<0.001). CONCLUSIONS MMF with low-dose prednisone may be as effective as full-dose prednisone and tend to have fewer adverse events. Therefore, it is probably superior to conservative treatments of adult HSP patients with moderate proteinuria.
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Affiliation(s)
- Fei Han
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University / Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province / the Third Grade Laboratory under the National State, Administration of Traditional Chinese Medicine, Hangzhou 310003, China
| | - Liang-liang Chen
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University / Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province / the Third Grade Laboratory under the National State, Administration of Traditional Chinese Medicine, Hangzhou 310003, China
| | - Ping-ping Ren
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University / Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province / the Third Grade Laboratory under the National State, Administration of Traditional Chinese Medicine, Hangzhou 310003, China
| | - Jing-yun Le
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University / Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province / the Third Grade Laboratory under the National State, Administration of Traditional Chinese Medicine, Hangzhou 310003, China
| | - Pei-jing Choong
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University / Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province / the Third Grade Laboratory under the National State, Administration of Traditional Chinese Medicine, Hangzhou 310003, China
| | - Hong-ju Wang
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University / Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province / the Third Grade Laboratory under the National State, Administration of Traditional Chinese Medicine, Hangzhou 310003, China
| | - Ying Xu
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University / Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province / the Third Grade Laboratory under the National State, Administration of Traditional Chinese Medicine, Hangzhou 310003, China
| | - Jiang-hua Chen
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University / Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province / the Third Grade Laboratory under the National State, Administration of Traditional Chinese Medicine, Hangzhou 310003, China
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Chen Y, Gao E, Yang L, Liu X, Li K, Liu Z, Zeng C, Zhang H, Liu Z, Hu W. Long-term outcome of mycophenolate mofetil treatment for patients with microscopic polyangiitis: an observational study in Chinese patients. Rheumatol Int 2016; 36:967-74. [PMID: 27169414 DOI: 10.1007/s00296-016-3492-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2016] [Accepted: 05/04/2016] [Indexed: 12/14/2022]
Abstract
This study aimed to retrospectively analyze the long-term outcome of mycophenolate mofetil (MMF) therapy for microscopic polyangiitis (MPA) with mild to moderate renal involvement in Chinese patients. Thirty-four MPA patients (24 females, 10 males, aged 44.7 ± 17 years, BVAS score 13.8 ± 3.2, SCr 2.2 ± 1.1 mg/dl) with SCr < 5 mg/dl and who received glucocorticoids plus MMF therapy for inducing and maintaining remission were included in this study. The remission and relapse rates, patient and renal survival rates and adverse events were retrospectively analyzed. We found that 31 (91.2 %) of 34 patients achieved remission and were continuously treated with glucocorticoids plus MMF for maintaining remission. The median duration of MMF treatment was 24 months (IQR 15-53 months) and follow-up time was 86 months (IQR 29-124 months). During the follow-up, 7 (22.6 %) patients relapsed, one patient died, and one patient progressed into end-stage renal disease. The 5-year patient and renal survival rates were 92.8 and 95.2 %, respectively. 11 (32.4 %) patients suffered 16 adverse events, 13 of which were pulmonary infection. In conclusion, glucocorticoids plus MMF regimen as induction and maintenance therapy could achieve high remission rate and good long-term renal survival in MPA patients with mild to moderate renal involvement. Prospective controlled trials with a large sample size are needed to confirm the efficacy of MMF in this population.
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Affiliation(s)
- Yinghua Chen
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing, 210016, Jiangsu, China
| | - Erzhi Gao
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing, 210016, Jiangsu, China
| | - Liu Yang
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing, 210016, Jiangsu, China
| | - Xia Liu
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing, 210016, Jiangsu, China
| | - Kang Li
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing, 210016, Jiangsu, China
| | - Zhengzhao Liu
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing, 210016, Jiangsu, China
| | - Caihong Zeng
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing, 210016, Jiangsu, China
| | - Haitao Zhang
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing, 210016, Jiangsu, China
| | - Zhihong Liu
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing, 210016, Jiangsu, China
| | - Weixin Hu
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing, 210016, Jiangsu, China.
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Sharma P, Yates M, Mukhtyar C. ANCA-associated vasculitis – Should we change the standard of care? INDIAN JOURNAL OF RHEUMATOLOGY 2015. [DOI: 10.1016/j.injr.2015.08.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
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Abstract
BACKGROUND Renal vasculitis presents as rapidly progressive glomerulonephritis which comprises of a group of conditions characterised by acute kidney injury (AKI), haematuria and proteinuria. Treatment of these conditions comprises steroid and non-steroid agents in combination with plasma exchange. Although immunosuppression overall has been very successful in treatment of these conditions, many questions remain unanswered in terms of dose and duration of therapy, the use of plasma exchange and the role of new therapies. This an update of a review first published in 2008. OBJECTIVES To evaluate the benefits and harms of any intervention used for the treatment of renal vasculitis in adults. SEARCH METHODS We searched the Cochrane Kidney and Transplant Specialised Register up to 27 July 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. SELECTION CRITERIA Randomised controlled trials investigating any intervention for the treatment of renal vasculitis in adults. DATA COLLECTION AND ANALYSIS Two authors independently assessed study quality and extracted data. Statistical analyses were performed using a random effects model and results expressed as risk ratio (RR) with 95% confidence intervals (CI) for dichotomous outcomes or mean difference (MD) for continuous outcomes. MAIN RESULTS Thirty one studies (2217 patients) were included. Studies conducted earlier tended to have a higher risk of bias due to poor (or poorly reported) study design, broad inclusion criteria, less well developed disease definitions and low patient numbers. Later studies tend to have improved in all areas of quality, aided by the development of large transnational study groups.Plasma exchange as adjunctive therapy significantly reduces the risk of end-stage kidney disease at three months (2 studies: RR 0.43, 95% CI 0.23 to 0.78) and 12 months (6 studies: RR 0.45, 95% CI 0.29 to 0.72). Four studies (300 patients) compared the use of pulse and continuous administration of cyclophosphamide. Remission rates were equivalent but pulse treatment causes an increased risk of relapse (4 studies: RR 1.79, 95% CI 1.11 to 2.87) compared with continuous cyclophosphamide. Azathioprine has equivalent efficacy as a maintenance agent to cyclophosphamide with fewer episodes of leucopenia. Mycophenolate mofetil may be equivalent to cyclophosphamide as an induction agent but resulted in a higher relapse rate when tested against azathioprine in remission maintenance. Rituximab is an effective remission induction agent. Methotrexate or leflunomide are potential choices in remission maintenance therapy. Oral co-trimoxazole did not reduce relapses significantly in granulomatosis with polyangiitis. AUTHORS' CONCLUSIONS Plasma exchange was effective in patients with severe AKI secondary to vasculitis. Pulse cyclophosphamide results in an increased risk of relapse when compared to continuous oral use but a reduced total dose. Whilst cyclophosphamide is standard induction treatment, rituximab and mycophenolate mofetil were also effective. Azathioprine, methotrexate and leflunomide were effective as maintenance therapy. Further studies are required to more clearly delineate the appropriate place of newer agents within an evidence-based therapeutic strategy.
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Affiliation(s)
- Giles Walters
- Department of Renal Medicine, The Canberra Hospital, Yamba Drive, Garran, ACT, Australia, 2605
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Greenhall GHB, Salama AD. What is new in the management of rapidly progressive glomerulonephritis? Clin Kidney J 2015; 8:143-50. [PMID: 25815169 PMCID: PMC4370308 DOI: 10.1093/ckj/sfv008] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2015] [Accepted: 01/23/2015] [Indexed: 12/20/2022] Open
Abstract
Rapidly progressive glomerulonephritis (RPGN) results from severe crescentic damage to glomeruli and leads to irreversible kidney failure if not diagnosed and managed in a timely fashion. Traditional treatment has relied on glucocorticoids and cyclophosphamide, with additional plasmapheresis for certain conditions. Here we describe updates in the management of RPGN, according to the underlying renal pathology. However, there remains a paucity of trials that have enrolled patients with more advanced renal disease, dialysis dependence or with RPGN, and we are therefore still reliant on extrapolation of data from studies of patients with a less severe form of disease. In addition, reporting bias results in publication of cases or cohorts showing benefit for newer agents in advanced disease or RPGN, but it remains unclear how many unsuccessful outcomes in these circumstances take place. Since clinical trials specifically in RPGN are unlikely, use of biologic registries or combination of sufficient sized cohort series may provide indications of benefit outside of a clinical trial setting and should be encouraged, in order to provide some evidence for the efficacy of therapeutic regimens in RPGN and advanced renal disease.
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Affiliation(s)
| | - Alan D Salama
- UCL Centre for Nephrology , Royal Free Hospital , London , UK
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45
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Affiliation(s)
- Lindsay Lally
- Department of Medicine/Division of Rheumatology, Hospital for Special Surgery, New York, NY 10021; ,
| | - Robert Spiera
- Department of Medicine/Division of Rheumatology, Hospital for Special Surgery, New York, NY 10021; ,
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A retrospective study of microscopic polyangiitis patients presenting with pulmonary fibrosis in China. BMC Pulm Med 2014; 14:8. [PMID: 24468083 PMCID: PMC3914364 DOI: 10.1186/1471-2466-14-8] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2014] [Accepted: 01/27/2014] [Indexed: 11/16/2022] Open
Abstract
Background Pulmonary involvement is a common feature of MPA. Although alveolar hemorrhage is the most common pulmonary manifestation of MPA, a few recent studies have described instances of MPA patients with pulmonary fibrosis. Pulmonary fibrosis was seen to predate, be concomitant with, or occur after the diagnosis of MPA. The goal of this study was to describe the clinical features and prognosis of microscopic polyangiitis (MPA) patients whose initial respiratory presentation was pulmonary fibrosis. Methods We conducted a retrospective analysis of 19 MPA patients who presented with pulmonary fibrosis at Peking Union Medical College Hospital between 1990 and 2012. Results Of 67 total MPA cases, 19 patients presented with pulmonary fibrosis. There were 8 males and 11 females, with a median age of 63.6 years. Common clinical manifestations included fever (89.5%), cough (84.2%), dyspnea (78.9%) and velcro rales (84.2%). Eleven patients experienced weight loss, several had kidney involvement, and most had an increased erythrocyte sedimentation rate and C-reactive protein. All were positive for myeloperoxidase-anti-neutrophil cytoplasmic antibody (ANCA), with 6 patients being positive at the time of their initial diagnosis of pulmonary fibrosis. Every patient had typical features of usual interstitial pneumonia on High-resolution CT. All were treated with corticosteroids and cyclophosphamide, which lead to an improvement in twelve cases. One of the remaining patients progressed slowly, whereas six died. Conclusions Patients with MPA, who also presented with pulmonary fibrosis in our cohort, were more likely to be older, female, and have extrapulmonic involvement. Most patients had a delayed positive ANCA. Corticosteroids plus cyclophosphamide was the remission-induction treatment scheme for all cases. The current prognosis for MPA patients with pulmonary fibrosis appears to be poor, suggesting that they may be candidates for new therapies.
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Lourdudoss C, Vollenhoven RV. Mycophenolate mofetil in the treatment of SLE and systemic vasculitis: experience at a single university center. Lupus 2014; 23:299-304. [DOI: 10.1177/0961203313519158] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Mycophenolate mofetil (MMF) is used off-label for systemic lupus erythematosus (SLE) and systemic vasculitis. The study aim was to investigate clinical use and treatment results with MMF in patients with SLE and systemic vasculitis. This study included patients with SLE or systemic vasculitis with ongoing or previous MMF treatment. Data on treatment outcome were obtained through medical record reviews. A total of 135 of 648 (21%) patients with SLE and 43 of 455 (9%) patients with systemic vasculitis had ongoing or previous MMF treatment. Among SLE patients, the most common organ manifestation at baseline (treatment start) was renal involvement (50%). Most of the systemic vasculitis patients had Wegener’s granulomatosis (GPA) (65%). Median dose of MMF was 2000 mg/day. Glucocorticoid (GC) doses were significantly reduced during MMF treatment from 21.7 mg/day at baseline to 8.3 mg/day at 12 months ( p < 0.05). Forty-six percent of the patients were good responders after 12 months. The most common adverse events (AES) leading to discontinuation were side effects in the gastrointestinal tract (40%) and general side effects (30%). “Survival-on-drug” analysis suggested that 40% of the patients remained on long-term MMF treatment. In conclusion, MMF was used in 21% of the SLE patients and 9% of the systemic vasculitis patients. MMF appeared to be effective with a reasonable survival-on-drug and a GC-sparing effect.
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Affiliation(s)
- C Lourdudoss
- Karolinska University Hospital, Solna, Stockholm, Sweden
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Abstract
The introduction of (oral) cyclophosphamide (CYC) in the treatment of ANCA-associated vasculitides (AAV) has strongly improved prognosis but the side effects of long-term CYC treatment are serious. A number of recent randomized controlled studies have shown that the cumulative dose of CYC can be strongly reduced in the treatment of AAV or even reduced to zero. Maintenance treatment can be performed with azathioprine (AZA), or methotrexate (MTX) in case of intolerance, although the intensity and duration of maintenance treatment is still under discussion. More insight into the mechanisms involved in relapsing disease might allow individualized treatment. Induction of remission can be achieved in cases of mild disease expression with MTX but requires maintenance treatment to prevent relapses. Generalized disease can be treated with pulses of i.v. CYC or, possibly, with MMF. However, recent studies demonstrate the efficacy of RTX in inducing remission without the concomitant use of immunosuppressives. Corticosteroids are part of treatment in all regimens but the intensity and duration of steroid treatment is still being discussed. In life-threatening disease, the adjunctive efficacy of plasma exchange has been demonstrated and its usefulness in less severe disease is under investigation. Taken together, there are, indeed, alternatives for CYC in AAV.
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Affiliation(s)
- Cees G M Kallenberg
- Department of Rheumatology & Clinical Immunology, AA21, University of Groningen, University Medical Center Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands.
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Abstract
Cyclophosphamide has greatly improved prognosis in anti-neutrophil cytoplasmic autoantibody-associated vasculitis (AAV) and proliferative lupus nephritis (LN). However, the side effects of long-term cyclophosphamide treatment are considerable prompting a search for alternatives to cyclophosphamide. For maintenance treatment in AAV, azathioprine is the preferred drug with methotrexate as an alternative in the case of intolerance to azathioprine. Data on mycophenolate mofetil (MMF) for the induction of remission in AAV are being awaited, but rituximab appears as effective as cyclophosphamide in newly diagnosed patients with AAV, and is probably even better for relapsing patients, while the possibility of maintenance treatment with intermittent low-dose infusions of rituximab is being explored. In LN, low-dose intravenous cyclophosphamide is as effective as high-dose cyclophosphamide for the induction of remission, with azathioprine being used for maintenance treatment. MMF can be used in the case of intolerance to cyclophosphamide and might be the first choice in black and Hispanic patients. In the case of intolerance to both cyclophosphamide and MMF, azathioprine with pulses of methylprednisolone can be used. Here, the role of rituximab has not been established. In conclusion, alternatives are available for cyclophosphamide both in AAV and proliferative LN.
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Affiliation(s)
- Cees G M Kallenberg
- Department of Rheumatology & Clinical Immunology, AA21 PO Box 30.001, Groningen 9700 RB, The Netherlands.
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