mycophenolic-acid and Anti-Neutrophil-Cytoplasmic-Antibody-Associated-Vasculitis

ANCA-associated vasculitis is an autoimmune disease that usually involves the small vessel walls. It is difficult to find the presence of ANCA-associated vasculitis in the great arteries, especially the thoracic and abdominal aorta.. This is an 86-year-old Chinese man with ANCA-associated vasculitis and abdominal aortic aneurysm who presented with epigastric pain. Considering his age and physical condition, the patient was treated with methylprednisolone and mycophenolate mofetil instead of surgery.. The patient's epigastric pain symptoms were relieved after 2 months of conservative treatment. Imaging at follow-up 2 years later showed signs of aneurysm enlargement because of irregular medication.. Patients with ANCA-associated vasculitis combined with aortic aneurysm often require surgical management. But for patients with stable disease and poor physical conditions, conservative treatment is also an effective treatment method, which can bring benefits to the patient's survival.

Topics: Aged, 80 and over; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Aortic Aneurysm; Aortic Aneurysm, Abdominal; Humans; Male; Mycophenolic Acid; Pain

Uncertainties exist about the use of mycophenolate mofetil (MMF) in anti-neutrophil cytoplasmatic antibody (ANCA)-associated vasculitis (AAV), particularly for remission maintenance.. Systematic review and meta-analysis of phase II and III trials assessing the use of MMF in AAV, granulomatosis with polyangiitis and microscopic polyangiitis (MPA). A comprehensive search of several databases (Medline, EMBASE, Cochrane, Web of Science, Scopus) from inception to 5 May 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.. From 565 articles captured, 10 met the predefined criteria, 5 phase II and 5 III trials; 4 assessed remission-induction, 3 remission maintenance and 3 both. The pooled OR for remission-induction at 6 months was 1.06 (95% confidence interval 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% and 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%.. In AAV, MMF use was significantly associated with higher sustained remission rates in trials enrolling only patients with kidney involvement. These findings might influence clinical practice.

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Humans; Immunosuppressive Agents; Microscopic Polyangiitis; Mycophenolic Acid; Peroxidase; Remission Induction

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor prognosis. Patients with IPF represent a heterogeneous population with several described clinical phenotypes. More recently, the development of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in IPF patients, with an incidence higher than that in the general population, has drawn attention.. A 64-year-old woman previously diagnosed with IPF presented to the emergency department with hemoptysis and hypoxemic respiratory failure.. High-resolution chest computed tomography revealed bilateral ground-glass opacities associated with areas of consolidation superimposed on the patient's fibrotic background pattern. Diffuse alveolar hemorrhage was confirmed by the presence of hemorrhagic bronchoalveolar lavage fluid. Hematological and biochemical investigations revealed an inflammatory syndrome, moderate anemia, and rapidly progressive glomerulonephritis. Serological analysis revealed perinuclear antineutrophil cytoplasmic antibody positivity and high levels of antimyeloperoxidase antibodies antibodies. The patient underwent kidney biopsy, which revealed necrotizing glomerulonephritis. Clinical and laboratory findings were diagnostic of microscopic polyangiitis with lung and renal involvement.. Cyclophosphamide in combination with methylprednisolone was administered as remission induction therapy. The maintenance therapy consisted of mycophenolate mofetil and prednisone.. The patient achieved clinical, radiological, and serological remission within six weeks of treatment.. The association between IPF and ANCA-associated vasculitis may represent a distinct clinical phenotype. Autoimmune testing for ANCAs should be considered part of the diagnostic work-up and follow-up of patients with IPF because of the clinical and therapeutic implications of developing vasculitis in an already vulnerable patient.

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Cyclophosphamide; Female; Hemorrhage; Humans; Idiopathic Pulmonary Fibrosis; Methylprednisolone; Middle Aged; Mycophenolic Acid; Prednisone

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).. 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.. 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 (I. 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.. ZIEL: Ziel der vorliegenden Studie war es, die Wirksamkeit und Sicherheit von Mycophenolatmofetil (MMF) vs. Cyclophosphamid (CYC) bei Patienten mit aktiver, mit antineutrophilen zytoplasmatischen Antikörpern (ANCA) assoziierter Vaskulitis (AAV) zu untersuchen.. Es wurde eine Metaanalyse von 4 randomisierten klinischen Studien (300 Patienten) durchgeführt, um die relative Wirksamkeit und Sicherheit von MMF im Vergleich zu CYC bei Patienten mit aktiver AAV zu untersuchen.. Bei der Remission nach 6 Monaten gab es keinen signifikanten Unterschied zwischen MMF und CYC (Odds Ratio, OR: 1,311; 95%-Konfidenzintervall, 95%-KI: 0,570–3,017; p = 0,524). Darüber hinaus unterschied sich die Rezidivrate nicht zwischen der MMF- und der CYC-Gruppe (OR: 1,331; 95%-KI: 0,497–3,568; p = 0,570). Auch gab es keinen signifikanten Unterschied bei der Rate an schweren unerwünschten Ereignissen (SAE; OR: 1,232; 95%-KI: 0,754–2,014; p = 0,404) und Infektionen (OR: 0,958; 95%-KI: 0,561–1,634; p = 0,873) zwischen der MMF- und der CYC-Gruppe. Eine gewisse Heterogenität in der Metaanalyse der Remissions- und Rezidivraten war festzustellen (I. Der Behandlungsansatz mit MMF erwies sich als Alternative zu CYC mit gleicher Wirksamkeit, und in Bezug auf die Sicherheit war MMF vergleichbar mit CYC bei Patienten mit aktiver AAV, was darauf hindeutet, dass MMF als Alternative zu CYC für die Induktion einer Remission bei AAV eingesetzt werden kann.

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Cyclophosphamide; Humans; Immunosuppressive Agents; Lupus Nephritis; Mycophenolic Acid; Randomized Controlled Trials as Topic; Remission Induction; Treatment Outcome

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.

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Azathioprine; Cyclophosphamide; Glucocorticoids; Humans; Immunosuppressive Agents; Methotrexate; Mycophenolic Acid; Remission Induction; Rituximab

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.. 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.. 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).. 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.

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Cyclophosphamide; Humans; Immunosuppressive Agents; Leukopenia; Mycophenolic Acid; Randomized Controlled Trials as Topic; Recurrence; Remission Induction; Treatment Outcome

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Cyclophosphamide; Drug Therapy, Combination; Female; Forecasting; Glucocorticoids; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Patient Safety; Precision Medicine; Randomized Controlled Trials as Topic; Remission Induction; Risk Assessment; Severity of Illness Index; Treatment Outcome

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of disorders characterized by inflammation and destruction of small- and medium-sized blood vessels and the presence of circulating ANCA. Clinical disease phenotypes include granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, and renal-limited vasculitis. Serologic classification of AAV into proteinase 3-ANCA disease and myeloperoxidase-ANCA disease correlates with a number of disease characteristics. AAV has a predilection for the kidney, with >75% of patients having renal involvement characterized by rapidly progressive glomerulonephritis. The cause and pathogenesis of AAV are multifactorial and influenced by genetics, environmental factors, and responses of the innate and adaptive immune system. Randomized controlled trials in the past 2 decades have refined the therapy of AAV and transformed AAV from a fatal disease to a chronic illness with relapsing course and associated morbidity. This article in AJKD's Core Curriculum in Nephrology series provides a detailed review of the epidemiology, pathogenesis, diagnosis, and advances in the management of AAV.

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Churg-Strauss Syndrome; Cyclophosphamide; Disease Progression; Glomerulonephritis; Glucocorticoids; Granulomatosis with Polyangiitis; Humans; Immunosuppressive Agents; Kidney Transplantation; Microscopic Polyangiitis; Mycophenolic Acid; Myeloblastin; Peroxidase; Remission Induction; Renal Dialysis; Rituximab

The long-term survival of patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) has improved dramatically as a direct result of evolving therapy. This review summarizes evidence-based treatment strategies with currently approved immunosuppressive medications to serve as a guide for practitioners in the management of patients with AAV.. Targeted therapy aimed at minimizing treatment-related adverse effects while optimizing effectiveness is a propagated approach. Such tailored therapy considers disease severity and is especially warranted in those at high risk for relapsing vasculitis. As treatment options for AAV become available, the need to tailor therapy has become increasingly relevant to optimize patient outcomes.

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Cyclophosphamide; Humans; Immunosuppressive Agents; Mycophenolic Acid; Plasma Exchange; Remission Induction; Rituximab

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) refers to a complex group of systemic vasculitides that are characterized by primary small-to-medium sized blood vessel inflammation with the presence of autoantibodies known as ANCA. AAV diseases include Granulomatosis with Polyangiitis (GPA), Eosinophilic Granulomatosis with Polyangiitis (EGPA), and Microscopic Polyangiitis (MPA). AAVs are challenging conditions associated with high cumulative disease and treatment related morbidity and mortality. Given its rarity and the resulting paucity of pediatric-specific clinical trial evidence, pediatric rheumatologists have had to often extrapolate from adult literature for management and therapeutic decisions. The aim of this review is to provide a comprehensive overview of the important findings and overall conclusions of critical landmark clinical trials in the induction and maintenance treatments in adult AAV for the pediatric rheumatologist. This review also highlights the outcomes of recent pediatric AAV observational studies and discusses the future research priorities in pediatric AAV management.

Topics: Adult; Anti-Inflammatory Agents; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Azathioprine; Child; Churg-Strauss Syndrome; Cyclophosphamide; Drug Substitution; Drug Therapy, Combination; Forecasting; Glucocorticoids; Granulomatosis with Polyangiitis; Humans; Leflunomide; Methotrexate; Mycophenolic Acid; Plasma Exchange; Prednisone; Randomized Controlled Trials as Topic; Recurrence; Retrospective Studies; Rituximab; Severity of Illness Index

Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) has the propensity to acquire a devastating disease course. Despite the advances in therapeutics, a significant proportion of patients progress to end-stage renal disease (ESRD). Renal transplantation is being increasingly employed in this population, with gradual improvement in outcomes over the years, however, recurrence of disease requires constant surveillance and is associated with graft failure. Areas covered: A structured literature search in PubMed and Medline and abstracts of international conferences was performed to identify cases and cohorts of AAV patients who had undergone renal transplantation for ESRD. The primary objective was to describe the long-term allograft and patient survival and to reflect on current trends in transplantation in AAV and provide recommendations for the phases of pre- and post-transplantation. Expert commentary: Renal transplantation is the treatment of choice for AAV patients with ESRD. The risk of relapse is low with modern immunosuppressive regimes employing mycophenolate mofetil and tacrolimus. It is recommended that the vasculitis be in clinical remission for 12 months prior to transplantation. Although ANCA positivity is not a contraindication for renal transplantation, these patients should be monitored closely for vasculitis relapse post-transplant.

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Graft Rejection; Humans; Immunosuppression Therapy; Kidney Failure, Chronic; Kidney Transplantation; Mycophenolic Acid; Survival Analysis; Tacrolimus; Treatment Outcome

Vasculitis is more often a disease of women beyond their reproductive years, leaving the challenges of pregnancy management difficult to study. Pregnancy complications, including pregnancy loss and preterm birth, are higher among women with all forms of vasculitis. It seems that controlling the disease before pregnancy may improve the chances of pregnancy success. Many medications used for vasculitis are considered low risk in pregnancy, including prednisone, colchicine, azathioprine, and tumor necrosis factor inhibitors. Cyclophosphamide, methotrexate, and mycophenolate mofetil should be avoided in pregnancy. Controlling disease with low-risk medications may allow women with vasculitis to have the pregnancies they desire.

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Azathioprine; Behcet Syndrome; Contraindications; Cyclophosphamide; Deprescriptions; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Methotrexate; Mycophenolic Acid; Pregnancy; Pregnancy Complications; Takayasu Arteritis; Tumor Necrosis Factor-alpha; Vasculitis

The authors review the nomenclature of vasculitides and the classification of antineutrophil cytoplasm antibody associated vasculitides and present the method of measuring disease activity (Five-factor Score, Birmingham Vasculitis Activity Score) and its role in defining therapeutical needs. They discuss the treatment algorithm of antineutrophil cytoplasm antibody associated vasculitides, present the sometimes equipotential medications used during the induction therapy followed by a maintenance regimen, and outline their usage and possible side-effects that may require medical attention. They point out the importance of plasmapheresis as an adjunctive treatment in some cases, as well as indications and possible outcome of kidney transplantation in therapy-resistant cases. Finally, they review several ongoing clinical studies, as their outcome will probably influence therapeutical opportunities of antineutrophil cytoplasm antibody associated vasculitides in the next few years.

Topics: Algorithms; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Azathioprine; Clinical Trials as Topic; Granulomatosis with Polyangiitis; Humans; Immunosuppressive Agents; Kidney Transplantation; Methotrexate; Microscopic Polyangiitis; Mycophenolic Acid; Plasmapheresis; Prognosis; Rituximab; Severity of Illness Index; Terminology as Topic

To determine the comparative efficacy of non-biologic treatments for remission maintenance in ANCA-associated vasculitis.. We identified all randomized trials comparing leflunomide, azathioprine, methotrexate or mycophenolate mofetil in adult patients with granulomatosis with polyangiitis or microscopic polyangiitis. Relapse-free survival was compared through hazard ratios (HR) using a Bayesian fixed-effects network meta-analysis. Multiple sensitivity analyses were performed to explore biases identified in one trial using original trial data.. Three trials were available (leflunomide-methotrexate, methotrexate- azathioprine, azathioprine-mycophenolate). Mycophenolate was inferior to all treatments, although the 95% credible interval (CrI) of the HR relative to methotrexate crossed 1. Leflunomide was superior to azathioprine (HR 0.43 [95% CrI: 0.14-1.3]) and methotrexate (HR 0.47 [95% CrI: 0.18-1.2]), although the 95% CrI also crossed 1. There was a 90% probability that leflunomide was the best treatment. After down weighting the effect of leflunomide vs. methotrexate for early trial termination and slow MTX dose escalation, there remained a 55% probability leflunomide was best.. Based on indirect evidence, leflunomide is effective in maintaining remission in granulomatosis with polyangiitis or microscopic polyangiitis relative to other non-biologic treatments. Further randomized trials of leflunomide are needed for confirmation.

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Azathioprine; Female; Humans; Immunosuppressive Agents; Isoxazoles; Leflunomide; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Randomized Controlled Trials as Topic; Remission Induction; Treatment Outcome

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a small-vessel vasculitis that primarily comprises 2 clinical syndromes: granulomatosis with polyangiitis and microscopic polyangiitis. Cyclophosphamide and glucocorticoids have traditionally been used for induction of remission. However, more recent studies have shown that rituximab is as effective as cyclophosphamide for induction therapy in patients with newly diagnosed severe AAV and superior for patients with relapsing AAV. There is also accumulating evidence indicating a potential role of rituximab for maintenance therapy in AAV. In this article, we will review the evidence supporting the various treatment choices for patients with AAV.

Topics: Adrenal Cortex Hormones; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Monoclonal, Murine-Derived; Cyclophosphamide; Humans; Immunosuppressive Agents; Mycophenolic Acid; Plasma Exchange; Rituximab

Clinical outcomes in ANCA-associated vasculitis (AAV) and lupus nephritis have improved greatly with treatment regimens containing high-dose glucocorticoids and cyclophosphamide. However, with the use of these medications come significant adverse events, most notably infections, cytopenias, malignancies, and reproductive abnormalities. Multiple recent randomized controlled trials in AAV and lupus nephritis have compared cyclophosphamide-based regimens with agents such as rituximab, mycophenolate mofetil, and azathioprine, with the hope of providing better clinical outcomes with improved safety profiles. Although some of these newer regimens are now considered first-line treatments of these diseases, their adverse event profiles have been disappointingly similar to those of cyclophosphamide-based protocols. Physicians and patients should consider the adverse event profiles generated by these trials in the context of their extensive use in other patient populations, as well as available measures to prevent such events, when choosing the ideal regimen for an individual patient.

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Monoclonal, Murine-Derived; Cyclophosphamide; Humans; Immunologic Factors; Immunosuppressive Agents; Lupus Nephritis; Mycophenolic Acid; Randomized Controlled Trials as Topic; Rituximab

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Monoclonal, Murine-Derived; Azathioprine; Cooperative Behavior; Cyclophosphamide; Drug Therapy, Combination; Follow-Up Studies; Glucocorticoids; Humans; Immunosuppressive Agents; Interdisciplinary Communication; Methotrexate; Mycophenolic Acid; Randomized Controlled Trials as Topic; Remission Induction; Rituximab; Secondary Prevention; Standard of Care; Treatment Outcome

Crescentic glomerulonephritis (GN) is a life-threatening clinical syndrome characterized by crescents which are morphological manifestations of severe glomerular injury. Immunologically, crescentic GN are classified as anti-glomerular basement membrane nephritis, immune complex-mediated GN and pauci-immune GN. Conventional treatment for crescentic GN mainly consists of corticosteroids, immunosuppressants and plasma exchange. Plasmapheresis is beneficial for patients with Goodpasture's syndrome and those with severe pauci-immune GN. Recently, new therapeutic agents have emerged, such as monoclonal antibodies to T cells, B cells and cytokines (e.g. anti-CD20 antibodies and TNF-α inhibitors) and signal transduction inhibitors, which may provide satisfactory alternatives. However, most of these treatments have only been established in experimental crescentic GN, described in single cases or reported in open-label trials; thus, the safety and efficacy of these agents remain to be investigated via controlled clinical trials.

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Monoclonal, Murine-Derived; Antigen-Antibody Complex; Autoantibodies; Glomerulonephritis; Humans; Mycophenolic Acid; Rituximab; Tumor Necrosis Factor-alpha

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.

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Azathioprine; Cyclophosphamide; Humans; Immunosuppressive Agents; Mycophenolic Acid; Randomized Controlled Trials as Topic

Treatment strategies for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are evolving. Cyclophosphamide (CYC) plus corticosteroids (CSs) is the mainstay of therapy for generalized, multisystemic AAV. Historically, the combination of CYC plus CS was used for a minimum of 12 months, but concern about late toxicities associated with CYC has led to novel treatment approaches. Currently, short-course (3 to 6 months) induction treatment with CYC plus CS, followed by maintenance therapy with less toxic agents (eg, methotrexate, azathioprine, mycophenolate mofetil) is recommended. Further, methotrexate combined with CS may be adequate for limited, non-life-threatening AAV. Recent studies suggest that rituximab may be useful for induction therapy or for CYC-refractory AAV. This article reviews the key agents used to treat AAV, with a focus on pharmacology, toxicities, and monitoring.

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Azathioprine; Cyclophosphamide; Humans; Immunosuppressive Agents; Methotrexate; Mycophenolic Acid; Time Factors

Substantial progress has been made over the last two decades in our understanding of the immunopathogenesis of antineutrophil cytoplasmic antibodies (ANCA) associated vasculitides. Compelling evidence from in vitro studies and experimental models in conjunction with clinical trials has confirmed that ANCA directly contribute to the evolution and progression of the disease process. Continuous development in our understanding of the mechanisms that drive the disease may ultimately allow us to tailor the multitude of novel therapies, which are rapidly becoming available, to the requirements of individual patients. In this review we endeavour to provide a brief overview of the recent advances in ANCA-associated vasculitides and outline basic principles for diagnosis and treatment of these complex multisystem diseases.

Topics: Animals; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Azathioprine; Cyclophosphamide; Disease Models, Animal; Disease Progression; Humans; Immunoglobulin G; Immunosuppressive Agents; Methotrexate; Mycophenolic Acid

The spectrum of small vessel vasculitides includes Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome, Henoch-Schönlein purpura, cutaneous leukocytoclastic vasculitis and essential cryoglobulinemic vasculitis. The first three are characterized by the presence of circulating anti-neutrophil cytoplasmic antibodies (ANCA). The symptoms of vasculitis range from stable or slowly progressive to rapidly progressive glomerulonephritis or alveolar haemorrhage. The diagnosis of small vessel vasculitis should preferably rely on both clinical findings and histopathological examination of the organ involved. Cyclophosphamide combined with glucocorticoids is still standard therapy for remission induction in generalized ANCA-associated vasculitis. In severe cases the use of plasmapheresis treatment has been advocated. Medications suitable for remission maintenance include azathioprine, methotrexate, leflunomide and mycophenolate mofetil. Early experience with biologic drugs, particularly with rituximab, for refractory disease has been quite promising.

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Azathioprine; Cyclophosphamide; Disease Progression; Glucocorticoids; Humans; Immunologic Factors; Immunosuppressive Agents; Isoxazoles; Leflunomide; Methotrexate; Mycophenolic Acid; Plasmapheresis; Rituximab; Vasculitis

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.. 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.. 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).. MMF was non-inferior to cyclophosphamide for remission induction in AAV, but resulted in higher relapse rate.. NCT00414128.

Topics: Adolescent; Adult; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Azathioprine; Child; Cyclophosphamide; Female; Humans; Immunosuppressive Agents; Induction Chemotherapy; Male; Mycophenolic Acid; Recurrence; Treatment Outcome

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.. 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.. 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.

Topics: Adult; Aged; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Cyclophosphamide; Female; Glomerular Filtration Rate; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Recurrence; Remission Induction

Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) treatment strategy is based on immunosuppressive agents. Little information is available concerning mycophenolic acid (MPA) and the area under the curve (AUC) in patients treated for AAV. We evaluated the variations in pharmacokinetics for MPA in patients with AAV and the relationship between MPA-AUC and markers of the disease. MPA blood concentrations were measured through the enzyme-multiplied immunotechnique (C(0), C(30), C(1), C(2), C(3), C(4), C(6) and C(9)) to determine the AUC. Eighteen patients were included in the study. The median (range) MPA AUC(0-12) was 50·55 (30·9-105·4) mg/h/l. The highest coefficient of determination between MPA AUC and single concentrations was observed with C(3) (P < 0·0001) and C(2) (P < 0·0001) and with C(4) (P < 0·0005) or C(0) (P < 0·001). Using linear regression, the best estimation of MPA AUC was provided by a model including C(30), C(2) and C(4): AUC = 8·5 + 0·77 C(30) + 4·0 C(2) + 1·7 C(4) (P < 0·0001). Moreover, there was a significant relationship between MPA AUC(0-12) and lymphocyte count (P < 0·01), especially CD19 (P < 0·005), CD8 (P < 0·05) and CD56 (P < 0·05). Our results confirm the interindividual variability of MPA AUC in patients treated with MMF in AAV and support a personalized therapy according to blood levels of MPA.

Topics: Adult; Aged; Aged, 80 and over; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Area Under Curve; Enzyme Inhibitors; Female; Humans; Linear Models; Lymphocyte Count; Male; Middle Aged; Mycophenolic Acid; Prospective Studies

Late-onset neutropenia (LON) is an underrecognized complication of rituximab treatment. We undertook this study to describe its incidence, risk factors, clinical features, management, and recurrence.. We conducted a single-center retrospective cohort study of 738 adult patients with autoimmune disease who were treated with rituximab to induce continuous B cell depletion. The primary outcome measure was LON, defined as an unexplained absolute neutrophil count of <1,000 cells/µl during B cell depletion. Secondary outcome measures included incidental diagnosis, fever, sepsis, filgrastim use, and recurrent LON. We assessed predictors of LON using Cox proportional hazards regression models. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated.. We identified 107 episodes of LON in 71 patients. The cumulative incidence at 1 year of B cell depletion therapy was 6.6% (95% CI 5.0-8.7). The incidence rate during the first year was higher compared to thereafter (7.2 cases per 100 person-years [95% CI 5.4-9.6] versus 1.5 cases per 100 person-years [95% CI 1.0-2.3]). Systemic lupus erythematosus and combination therapy with cyclophosphamide were each independently associated with an increased risk of LON (adjusted HR 2.96 [95% CI 1.10-8.01] and 1.98 [95% CI 1.06-3.71], respectively). LON was not observed in minimal change disease or focal segmental glomerulosclerosis. The majority of episodes (59.4%) were asymptomatic. Fever and sepsis complicated 31.3% and 8.5% of episodes, respectively. Most patients (69%) were treated with filgrastim. Rituximab rechallenge occurred in 87% of patients, of whom 21% developed recurrent LON.. LON is common and often incidental. Most cases are reversible and respond well to filgrastim. However, LON can be associated with serious infections and thus warrants vigilant monitoring.

Topics: Adult; Aged; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Asymptomatic Diseases; Autoimmune Diseases; Azathioprine; Cyclophosphamide; Drug Therapy, Combination; Female; Fever; Filgrastim; Glomerulonephritis, Membranous; Glomerulosclerosis, Focal Segmental; Hematologic Agents; Humans; Immunologic Factors; Incidence; Lupus Erythematosus, Systemic; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Nephrosis, Lipoid; Neutropenia; Proportional Hazards Models; Recurrence; Retrospective Studies; Risk Factors; Rituximab; Sepsis

ANCA-associated vasculitis (AAV) is a small vessel vasculitis that commonly presents in the elderly. However, there are few long-term outcome data for these patients. Here, we assessed long-term outcomes in a single-centre cohort of elderly patients with AAV. Additionally, we tested whether a pre-morbid frailty score could aid prognosis.. Using a prospectively-compiled dataset, we investigated patients over the age of 65 who presented with AAV between 2005 and 2017 to a regional vasculitis centre. We used a Cox model to determine the factors associated with mortality. We also compared outcomes in pre-specified subgroups stratified by baseline frailty score, ANCA serotype and induction immunosuppression (with cyclophosphamide, rituximab or mycophenolate mofetil used as the main glucocorticoid-sparing agent).. 83 patients were included in the study and were followed for a median of 1203 days. Median age was 74 years (range 65-92). Two- and five-year survival in the overall cohort were 83% (95% CI 75, 92%) and 75% (95% CI 65, 86%), respectively. The median cumulative dose of oral prednisolone was 2030 mg during the first three months. Only one patient received intravenous glucocorticoids. Age, frailty score and CRP at presentation were independently associated with mortality; all deaths occurred in patients aged over 75 at presentation. Patients treated with a cyclophosphamide-based induction regimen tended to be younger than those treated with rituximab or mycophenolate mofetil. Survival was better in the cyclophosphamide-treated group.. In the contemporary era, the overall prognosis of AAV in elderly patients is good. Baseline frailty associates with disease outcomes including mortality. A low-dose glucocorticoid regimen (avoiding intravenous methylprednisolone) can be used to treat AAV effectively in elderly patients.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Databases, Factual; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Frailty; Geriatric Assessment; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Prednisolone; Retrospective Studies; Risk Assessment; Severity of Illness Index; Survival Analysis; Time

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Cyclophosphamide; Humans; Mycophenolic Acid; Remission Induction

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Cyclophosphamide; Humans; Mycophenolic Acid; Remission Induction

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Cyclophosphamide; Humans; Mycophenolic Acid; Remission Induction

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Cyclophosphamide; Humans; Mycophenolic Acid; Remission Induction

Topics: Abdominal Pain; Adolescent; Anemia; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Arthralgia; Arthritis; Biopsy; Computed Tomography Angiography; Diagnosis, Differential; Drug Therapy, Combination; Exanthema; Female; Humans; Hypertension; IgA Vasculitis; Immunologic Factors; Kidney; Methylprednisolone; Mycophenolic Acid; Myeloblastin; Nephritis; Pulse Therapy, Drug; Rituximab; Urticaria

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Cyclophosphamide; Humans; Mycophenolic Acid; Recurrence; Remission Induction

To characterize the early disease course in childhood-onset antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and the 12-month outcomes in children with AAV.. Eligible subjects were children entered into the Pediatric Vasculitis Initiative study who were diagnosed before their eighteenth birthday as having granulomatosis with polyangiitis (Wegener's), microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis (Churg-Strauss), or ANCA-positive pauci-immune glomerulonephritis. The primary outcome measure was achievement of disease remission (Pediatric Vasculitis Activity Score [PVAS] of 0) at 12 months with a corticosteroid dosage of <0.2 mg/kg/day. Secondary outcome measures included the rates of inactive disease (PVAS of 0, with any corticosteroid dosage) and rates of improvement at postinduction (4-6 months after diagnosis) and at 12 months, presence of damage at 12 months (measured by a modified Pediatric Vasculitis Damage Index [PVDI]; score 0 = no damage, score 1 = one damage item present), and relapse rates at 12 months.. In total, 105 children with AAV were included in the study. The median age at diagnosis was 13.8 years (interquartile range 10.9-15.8 years). Among the study cohort, 42% of patients achieved remission at 12 months, 49% had inactive disease at postinduction (4-6 months), and 61% had inactive disease at 12 months. The majority of patients improved, even if they did not achieve inactive disease. An improvement in the PVAS score of at least 50% from time of diagnosis to postinduction was seen in 92% of patients. Minor relapses occurred in 12 (24%) of 51 patients after inactive disease had been achieved postinduction. The median PVDI damage score at 12 months was 1 (range 0-6), and 63% of patients had ≥1 PVDI damage item scored as present at 12 months.. This is the largest study to date to assess disease outcomes in pediatric AAV. Although the study showed that a significant proportion of patients did not achieve remission, the majority of patients responded to treatment. Unfortunately, more than one-half of this patient cohort experienced damage to various organ systems early in their disease course.

Topics: Adolescent; Adrenal Cortex Hormones; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Azathioprine; Child; Cohort Studies; Cyclophosphamide; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Kidney Diseases; Lung Diseases; Male; Methotrexate; Mycophenolic Acid; Prospective Studies; Recurrence; Registries; Remission Induction; Retrospective Studies; Rituximab

Primary anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a chronic autoimmune disease associated with multisystem dysfunction. Renal involvement is common and closely associated with outcome. The purpose of this study was to investigate the clinical determinants of mortality of patients with AAV-related renal injury in the first 2 years after diagnosis in a single West Chinese center.. Demographic and laboratory parameters of 123 consecutive patients with AAV-related renal injury diagnosed in Renal Division and Institute of Nephrology, Sichuan Provincial People's Hospital between 2004 and 2012 were collected retrospectively. All patients were followed up for 2 years after diagnosis. Survivors were compared with nonsurvivors to identify the clinical baseline variables associated with mortality. Multivariate Cox regression model was used to determine the independent predictors of mortality.. Of the 123 patients, 46 (37.4%) died by the end of 2 years after diagnosis, with 41 (33.3%) patients dying within the first 12 months. In comparison with the survivors, Birmingham Vasculitis Activity Score (BVAS), the incidence of pulmonary hemorrhage and digestive system (DS) involvement, serum creatinine, and erythrocyte sedimentation rate were significantly higher in nonsurvivors, whereas lymphocyte counts, hemoglobin, and complement 3 (C3) were significantly lower. Renal replacement therapy was more common in nonsurvivors. High BVAS (hazard ratio [HR] = 1.058, 95% confidence interval [CI]: 1.002-1.117; P = 0.042), pulmonary hemorrhage (HR = 1.970, 95% CI: 1.033-3.757; P = 0.04), DS involvement (HR = 2.911, 95% CI: 1.212-6.911; P = 0.017), and serum creatinine >400 μmol/L (HR = 2.910, 95% CI: 1.271-6.664; P = 0.012) were independent predictors of death in patients with AAV-related renal injury.. Patients with AAV-related renal injury have high early mortality. Those with high BVAS (particularly with pulmonary or DS involvement) and serious renal dysfunction should receive aggressive therapy and careful monitoring to reduce the occurrence of adverse events and improve prognosis.

Topics: Adult; Aged; Aged, 80 and over; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Autoantibodies; Autoimmune Diseases; Cyclophosphamide; Humans; Immunosuppressive Agents; Middle Aged; Mycophenolic Acid; Neutrophils; Proportional Hazards Models; Retrospective Studies

A 53-year-old woman attended for a routine outpatient appointment for follow-up of antineutrophil cytoplasmic antibody-positive vasculitis. Her disease had relapsed despite appropriate medical management with mycophenolate mofetil (MMF), as evidenced by rising acute phase response and antimyeloperoxidase titre with ongoing symptoms. On further questioning, she had been taking oral charcoal as part of a detoxification diet, which we postulate was causing significantly impaired MMF absorption. This case report summarises the presentation and highlights the importance of a thorough drug history, and should prompt the reader to keep an open mind with regard to drug interactions and treatment regimen adherence when treatment is, unexpectedly, seemingly failing.

Topics: Absorption, Physicochemical; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Antidotes; Charcoal; Drug Interactions; Female; Humans; Immunosuppressive Agents; Middle Aged; Mycophenolic Acid; Prednisolone; Recurrence

One of the side effects of cyclophosphamide is earlier menopause and primary ovarian insufficiency. This study was undertaken to investigate the onset of menopause and the incidence of primary ovarian insufficiency in women with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), especially after treatment with orally administered cyclophosphamide.. We retrospectively studied the onset of menopause and the influence of cyclophosphamide in women diagnosed as having AAV in our center between 1970 and 2012.. Ninety-four premenopausal women diagnosed as having AAV were included. Sixty-seven patients received cyclophosphamide, and 27 received other, mostly immunosuppressive, medication. Forty-six cyclophosphamide-treated women developed menopause, 22 of whom were considered to have primary ovarian insufficiency. None of the patients who were not treated with cyclophosphamide developed primary ovarian insufficiency. There was a significant association between a cumulative cyclophosphamide dose of >16.6 gm, versus a cumulative dose of <16.6 gm, and menopause (χ(2)  = 8.72, P = 0.003; odds ratio [OR] 2.60 [95% confidence interval 1.38-4.90]). In addition, there was a significant association between a cumulative cyclophosphamide dose of <16.6 gm, versus no cyclophosphamide exposure, and menopause (χ(2)  = 16.37, P < 0.001; OR 7.32 [95% confidence interval 2.79-19.20]). Both women who received cyclophosphamide and those who did not experienced involuntary childlessness.. Earlier menopause and primary ovarian insufficiency frequently develop after oral cyclophosphamide therapy in premenopausal women with AAV. Involuntary childlessness is common after the development of primary ovarian insufficiency, but it also occurs in women not treated with cyclophosphamide. These findings emphasize the importance of the use of drugs that are not toxic to gonadal function in women of childbearing age.

Topics: Adult; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Azathioprine; Case-Control Studies; Cohort Studies; Cyclophosphamide; Dose-Response Relationship, Drug; Female; Humans; Immunosuppressive Agents; Incidence; Maintenance Chemotherapy; Menopause; Methotrexate; Middle Aged; Mycophenolic Acid; Prednisolone; Primary Ovarian Insufficiency; Remission Induction; Retrospective Studies; Risk Factors; Rituximab; Young Adult

Standard therapy with corticosteroids (CS) and cyclophosphamide (CYC) followed by azathioprine has been shown to improve renal and patient survival in ANCA-associated renal vasculitis (rAAV). Mycophenolate mofetil (MF) has been progressively introduced for the treatment of rAAV in the last years because of its immunosuppressive efficacy combined with a lower toxicity profile. In this study, we retrospectively analyse the results of the introduction of MF for maintenance and induction therapy in rAAV in our institution from 2001 to 2013.. We reported 67 patients treated with MF as a maintenance treatment, divided by baseline serum creatinine (>500 µmol/L: Group 1 and <500 µmol/L: Group 2) and treatment schedule. Twenty-nine of the 67 patients were also treated with MF as induction treatment, mostly in Group 2. During the follow-up (2 years after the diagnosis) creatinine levels for serum glomerular filtration rate, ANCA titres, C-reactive protein and percentage of haematuria decreased in all groups. In Group 2, parameters and also relapse rates were similar at 24 months in patients treated with CYC or MF as an induction treatment (Subgroups 2a and 2b, respectively). Median dose of MF in maintenance treatment was 1000 mg daily and prednisone dose was tapered to 10 mg daily from Month 3. After 24 months, 82% of patients remained on MF therapy, 18% had discontinued the treatment, seven of them due to medical indication and two because of gastrointestinal intolerance. The percentage of patients that started renal replacement therapy was irregular in Group 1 depending on the subgroup (25-100%), and 10% in Group 2. Adverse effects, such as neutropenia, infections and neoplasia, were more prevalent in groups treated with CYC.. In conclusion, in our patients with rAAV, MF demonstrated to be an effective and well-tolerated option for maintenance treatment. As an induction treatment, MF seems to be similar to CYC for patients with moderate renal failure in the diagnosis.

Topics: Aged; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; C-Reactive Protein; Female; Glomerular Filtration Rate; Hospitals, University; Humans; Immunosuppressive Agents; Kidney Diseases; Kidney Function Tests; Male; Middle Aged; Mycophenolic Acid; Recurrence; Retrospective Studies

Mycophenolic acid (MPA) is used in the maintenance therapy of antineutrophil cytoplasm antibody-associated systemic vasculitis (AASV). MPA exerts its immunosuppression by inhibiting inosine 5'-monophosphate dehydrogenase (IMPDH), depleting activated lymphocytes of guanine nucleotides and retarding their proliferation. The purpose of our study was to examine the correlation between clinical outcome and pharmacokinetic-pharmacodynamic (PD) relationships of MPA in patients with AASV.. We studied 358 Caucasian control patients without any MPA therapy to examine basal IMPDH activity. Thirty Caucasian patients with AASV under maintenance therapy with mycophenolate mofetil (MMF) underwent therapeutic drug monitoring.. We observed a high interindividual variability with regard to basal IMPDH activity in patients without any MPA treatment (0.8-35 nmol/mg protein/h). Patients were followed for a mean (±SD) period of 22 ± 8 months. During the observation period, seven patients had a relapse with an elevated Birmingham Vasculitis Activity Score of 9.2 ± 6. The basal IMPDH activity (Abasal) in patients who subsequently relapsed was raised at baseline, before receiving their first dose of MMF, and further increased at the time of relapse, when compared with stable patients. Patients with a relapse during the maintenance therapy had significantly higher levels of IMPDH activity [IMPDH enzyme activity curve (AEC) (0-12)] than stable patients (P = 0.001), indicating inadequate IMPDH suppression. MPA-AUC (0-12) was significantly decreased in relapse patients, in contrast to stable patients (P < 0.05).. Due to the highly variable response to maintenance therapy with MPA, PD drug monitoring is a new tool for detecting inadequate immunosuppression in AASV patients.

Topics: Adult; Aged; Aged, 80 and over; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Biomarkers; Drug Monitoring; Female; Humans; Immunosuppressive Agents; IMP Dehydrogenase; Male; Middle Aged; Mycophenolic Acid; Precision Medicine; Recurrence; Young Adult

We reported a case of vasculitis of anti-neutrophil cytoplasmic antibody after liver transplantation. A 56-year-old male patient underwent orthotopic liver transplantation of the classic style on February 25, 2010 because of alcoholic cirrhosis.. Pathology analysis showed it was nodular cirrhosis. The patient was given conventional treatment programs of FK (tacrolimus) + mycophenolate mofetil + hormone; hormone was suspended at the third month. He began to cough and spit, and there was blood in the sputum in September. Lung CT scanning images showed that there was a visible multiple low-density patchy shadow in both lungs; however, a number of other detecting results were negative.. Considering the patient with contact suspected mold, we improved the inspection and switched to experimental treatment (itraconazole), and the patient improved and was then discharged. Two months later, he complained about appearing hemoptysis. Final diagnostic results showed it was anti-neutrophil cytoplasmic antibody-associated vasculitis after liver transplantation. Then we stopped medication with itraconazole. Treatment with methylprednisolone was continued, and the patient gradually stopped coughing and had no expectoration and hemoptysis.. Reviewing CT respectively showed significant improvement at the 7th and 24th days of hormone therapy; thus, we confirmed it was anti-neutrophil cytoplasmic antibody-associated vasculitis after liver transplantation.

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Diagnosis, Differential; Humans; Liver Cirrhosis, Alcoholic; Liver Transplantation; Lung Diseases; Male; Methylprednisolone; Middle Aged; Mycophenolic Acid; Postoperative Complications; Tomography, X-Ray Computed

To retrospectively investigate clinico-pathological features and outcomes of patients with renal involvement in propylthiouracil (PTU)-associated antineutrophil cytoplasmic autoantibody (ANCA) vasculitis (PTU-AAV).. Clinico-pathological features and outcomes of 12 patients (female 11, average age 32.4 ± 13.8 years) who developed AAV after treatment with PTU were collected and analyzed. ANCA was detected by both immunofluorescence (IF) and enzyme linked immunosorbent assay (ELISA). All patients had renal biopsy.. Twelve patients received PTU for 2-264 months (median 42 months) when PTUAAV was diagnosed. All patients had positive serum P-ANCA, 11 of them were MPO-ANCA, 1 was MPO and PR3-ANCA double positive. All patients presented with hematuria and proteinuria, 5 of them had gross hematuria, urine protein was 1.9 ± 1.6 g/24 h, 7 of 12 (58.3%) patients had renal dysfunction, among them 3 needed initial renal replacement therapy. Renal biopsy showed pauci-immune segmental necrotizing crescentic glomerulonephritis in ten patients, segmental necrotizing glomerulonephritis superimposed on membranous nephropathy in two patients. All patients withdrew PTU and received steroid and immunosuppressive therapy. After a median follow-up of 42 months (range 21-86), 3 patients developed to ESRD, 7 patients entered complete renal remission. Serum ANCA turned negative only in 2 patients, 10 patients had persistent positive serum ANCA. Three patients relapsed with the elevation of serum ANCA level.. Renal damage of PTU-AAV could be pauci-immune necrotizing crescentic glomerulonephritis, and necrotizing glomerulonephritis coexisted with membranous nephropathy. Most patients had persistent positive serum ANCA and had a risk of relapse and progression to ESRD even after PTU withdrawal and immunosuppressive therapy.

Topics: Adolescent; Adult; Anti-Inflammatory Agents; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antithyroid Agents; Child; Cyclophosphamide; Disease Progression; Hematuria; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Glomerulus; Kidney Tubules; Male; Middle Aged; Mycophenolic Acid; Prednisone; Propylthiouracil; Proteinuria; Recurrence; Remission Induction; Renal Replacement Therapy; Retrospective Studies; Thyroid Diseases; Young Adult

B-lymphocytes play a pivotal role in ANCA-associated vasculitides (AAV). The homeostasis of peripheral human B-lymphocyte subpopulations is tightly regulated, but may be disturbed in autoimmune disease or following immunosuppressive therapies. To elucidate the effect of immunosuppression and the relevance of B-lymphocyte disturbances, the B-lymphocyte compartment was analysed in 61 AAV patients. After immunosuppressive treatment a general B-lymphocytopenia developed in AAV patients. Within the B-lymphocyte subpopulations transitional B cells are the first maturation stage found in the peripheral blood. Transitional B-lymphocytes were significantly lower in AAV patients after immunosuppressive therapy compared to healthy controls. Furthermore, marginal zone B cells--a B-lymphocyte population protecting against encapsulated bacteria--were markedly lowered after immunosuppressive therapy in AAV patients. AAV patients treated with immunosuppressants had lower numbers of naïve and memory B-lymphocytes. Numbers of marginal zone B cells, memory B cells and plasmablasts correlated with concentrations of immunoglobulins. We evaluated plasmablasts for a potential correlation with disease activity. Different from what has been reported for e.g. large vessel vasculitis, absolute numbers of plasmablasts were not increased in patients with AAV and showed no correlation to disease activity. As low transitional B cells after treatment with immunosuppressants indicated an impaired early B-lymphocyte development, seven patients treated with the B cell depleting agent rituximab (RTX) because of relapsing disease activity were analysed for their B cell repopulation kinetics. In the majority of these patients repopulation of the peripheral B cell compartment by newly formed transitional B cells after RTX treatment was constricted and delayed.

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Monoclonal, Murine-Derived; Azathioprine; B-Lymphocyte Subsets; Cyclophosphamide; Female; Homeostasis; Humans; Immunosuppressive Agents; Isoxazoles; Leflunomide; Lymphocyte Count; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Rituximab

The past year has been characterized by significant novelties from the point of view of the clinical immunologist. With the BLISS 52 study showing that belimumab has the ability to decrease the activity of systemic lupus erythematosus (SLE) resistant to conventional therapy an important step towards the control of this difficult disease has been carried forward. In addition, the long-term results of the ALMS study have demonstrated that mycophenolate mofetil is superior to azathioprine in maintaining the remission in patients with severe lupus nephritis. Furthermore, the results of the RAVE and RITUXVASC studies have documented that rituximab is a valid alternative to cyclophosphamide in the control of ANCA associated vasculitis.

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Antirheumatic Agents; Azathioprine; Cardiovascular Diseases; Drug Therapy, Combination; Evidence-Based Medicine; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lupus Nephritis; Mycophenolic Acid; Randomized Controlled Trials as Topic; Remission Induction; Rituximab; Severity of Illness Index; Treatment Outcome

Standard therapy for granulomatosis with polyangiitis and other vasculitides is a combination of cyclophosphamide and glucocorticoids. Although most patients achieve remission, relapses and treatment-related morbidities are common. Clinical trials have yielded a wealth of data about less toxic alternatives to standard therapy, including new agents and methods of delivery. All aim to reduce long-term exposure to cyclophosphamide and glucocorticoids and so maintain safety while effectively preventing relapse. Individualized evaluation of risk and treatment selection will help maximize effectiveness and minimize toxicity.

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Cyclophosphamide; Glucocorticoids; Guanidines; Humans; Immunosuppressive Agents; Methotrexate; Mycophenolic Acid

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Bundle-Branch Block; C-Reactive Protein; Coronary Angiography; Coronary Artery Disease; Electric Countershock; Glomerulonephritis; Heart Arrest; Humans; Immunosuppressive Agents; Magnetic Resonance Angiography; Male; Middle Aged; Mycophenolic Acid; Prednisone; Ventricular Fibrillation

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antirheumatic Agents; Area Under Curve; Azathioprine; Dose-Response Relationship, Drug; Humans; Mycophenolic Acid; Reproducibility of Results; Secondary Prevention; Treatment Outcome

Topics: Adrenal Cortex Hormones; Adult; Aged; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Cyclophosphamide; Humans; Immunosuppressive Agents; Influenza Vaccines; Middle Aged; Mycophenolic Acid

Whether autoimmune or rheumatic disease may be precipitated after vaccination is controversially discussed among experts. Here we describe 4 cases of new onset or relapsing antineutrophil cytoplasmic antibodies associated vasculitis occurring in timely association with influenza vaccination. In the literature different subtypes of vasculitis have been repeatedly reported after influenza vaccination. Several trials in patients with preexisting auto-immune disease failed to indicate an increased risk for disease recurrence after influenza vaccination but these investigations might be underpowered to detect this very rare but relevant side effect. Although our report does not prove a causal association between vaccination and vasculitis, it seems possible that in rare cases vaccination might induce vasculitic disease.

Topics: Adrenal Cortex Hormones; Adult; Aged; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Cyclophosphamide; Female; Humans; Immunosuppressive Agents; Influenza Vaccines; Male; Middle Aged; Mycophenolic Acid; Risk Factors