Article. Long-Term Maintenance Therapy Using Rituximab-Induced Continuous B-Cell Depletion in Patients with ANCA Vasculitis
|
|
- Candice Nicholson
- 6 years ago
- Views:
Transcription
1 Article Long-Term Maintenance Therapy Using Rituximab-Induced Continuous B-Cell Depletion in Patients with ANCA Vasculitis William F. Pendergraft III,* Frank B. Cortazar, Julia Wenger, Andrew P. Murphy, Eugene P. Rhee, Karen A. Laliberte, and John L. Niles Abstract Background and objectives Remission in the majority of ANCA vasculitis patients is not sustained after a single course of rituximab, and risk of relapse warrants development of a successful strategy to ensure durable remission. Design, setting, participants, & measurements A retrospective analysis of ANCA vasculitis patients who underwent maintenance therapy using rituximab-induced continuous B-cell depletion for up to 7 years was performed. Maintenance therapy with rituximab was initiated after achieving remission or converting from other prior maintenance therapy. Continuous B-cell depletion was achieved in all patients by scheduled rituximab administration every 4 months. Disease activity, serologic parameters, adverse events, and survival were examined. Results In the study, 172 patients (mean age=60 years, 55% women, 57% myeloperoxidase ANCA) treated from April of 2006 to March of 2013 underwent continuous B-cell depletion with rituximab. Median remission maintenance follow-up time was 2.1 years. Complete remission (Birmingham Vasculitis Activity Score [BVAS]=0) was achieved in all patients. Major relapse (BVAS$3) occurred in 5% of patients and was associated with weaning of other immunosuppression drugs. Remission was reinduced in all patients. Survival mirrored survival of a general age-, sex-, and ethnicity-matched United States population. Conclusion This analysis provides evidence for long-term disease control using continuous B-cell depletion. This treatment strategy in ANCA vasculitis patients also seems to result in survival rates comparable with rates in a matched reference population. These findings suggest that prospective remission maintenance treatment trials using continuous B-cell depletion are warranted. Clin J Am Soc Nephrol 9: , doi: /CJN Introduction ANCA vasculitis is a systemic autoimmune disease characterized by small vessel inflammation caused by pathogenic autoantibodies directed against proteinase 3 (PR3) or myeloperoxidase (MPO) (1 3). Immunosuppressive therapy can result in remission; however, most patients relapse, which results in additional injury (4). Furthermore, chronic immunosuppression leads to additional toxicity. Rituximab, a humanized murine monoclonal antibody directed against CD20 located on the surface of B lymphocytes (B cells), is effective in depleting B cells. The Rituximab in ANCA-Associated Vasculitis (RAVE) and Rituximab versus Cyclophosphamide in ANCA- Associated Renal Vasculitis (RITUXVAS) trials have shown efficacy of rituximab with steroids for induction of remission in ANCA vasculitis, similar to cyclophosphamide and steroids (5,6), and rituximab is now approved by the Food and Drug Administration and European Medicines Agency for this purpose. The use of anti B cell therapy for early induction of remission in ANCA vasculitis is not surprising given that ANCA are pathogenic in vitro and in vivo (2,3). It is clear that remission in many patients is not sustained with a single induction course of rituximab (7 11). Relapses of ANCA vasculitis often occur after B-cell repopulation (9,10), suggesting that scheduled serial dosing of rituximab could result in sustained remission. In April of 2006, our group began to give rituximab every 4 months to our most resistant cases. We subsequently reported that continuous B-cell depletion using rituximab was highly successful for early maintenance of remission in 39 patients with ANCA vasculitis (12). This maintenance strategy was the first to use a regimen of scheduled rituximab administration to prevent B-cell repopulation. With this regimen, we no longer waited for B-cell repopulation, ANCA titer, or signs and symptoms of relapse before giving the next dose. Here, we review our 7-year experience in 172 patients treated with rituximab-induced continuous B-cell depletion for *Joint Nephrology Fellowship Program, Brigham and Women s Hospital and Massachusetts General Hospital, Boston, Massachusetts; and Division of Nephrology, Department of Medicine, Vasculitis and Glomerulonephritis Clinic, Division of Nephrology, and Categorical Internal Medicine Residency Program, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts Correspondence: Dr. John L. Niles, Division of Nephrology, Department of Medicine, Massachusetts General Hospital, 151 Merrimac Street, Floor 3, Boston, MA jlniles@partners.org 736 Copyright 2014 by the American Society of Nephrology Vol 9 April, 2014
2 Clin J Am Soc Nephrol 9: , April, 2014 Continuous B-Cell Depletion in ANCA, Pendergraft et al. 737 maintenance of remission. Specific attention is directed to disease control, medication burden, adverse events, and survival. Materials and Methods Study Population We performed a single center retrospective analysis of patients with ANCA vasculitis who underwent rituximabinduced continuous B-cell depletion for maintenance of remission. We included 172 consecutive patients treated between April of 2006 and March of 2013 at the Vasculitis and Glomerulonephritis Clinic in the Nephrology Division at the Massachusetts General Hospital. Patients were considered to have ANCA vasculitis if they had a positive test for PR3- or MPO-ANCA, which was detected by ELISA in the Massachusetts General Hospital ANCA Clinical Laboratory (12), together with a history of clinical and laboratory features consistent with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), or related variant forms of vasculitis (13). New patients and patients with disease relapse (Birmingham Vasculitis Activity Score [BVAS] Wegener s Granulomatosis [WG]$3) were included in this retrospective analysis when they were transitioned to continuous maintenance rituximab after undergoing induction therapy and entering full remission (defined as BVAS- WG=0 while on prednisone,10 mg/d). Patients who were already in complete or partial remission (BVAS-WG#2) were included in the study when continuous rituximab was added to their maintenance therapy. We excluded patients who did not receive a subsequent scheduled rituximab maintenance dose. We also excluded patients whose disease was associated with levamisoleadulterated cocaine exposure and/or who showed active illicit drug abuse. The Partners HealthCare System Human Research Committee approved this study, and this study was in adherence with the Declaration of Helsinki. Treatment Protocol Rituximab. All patients were initiated on a strategy to maintain complete and continuous peripheral blood B cell depletion using rituximab. Patients who transitioned from induction therapy that included rituximab (Supplemental Figure 1) were continued on one dose every 4 months. Patients who transitioned from other maintenance therapy were started with two doses of rituximab separated by approximately 2 weeks followed by one dose every 4 months. Historically, B-cell return was seen by 6 months in several of our patients; therefore, we modified our dosing strategy early on to every 4 months. Most patients received 1000 mg rituximab at each infusion. Before each rituximab dose, patients received treatment with intravenous hydrocortisone (100 mg) one time, oral diphenhydramine, and oral acetaminophen. Rituximab administration frequency was shortened to every3monthsamongpatientswhoshowedb-cellreturnat 4 months just before rituximab administration. Other Immunosuppression Medications. Other immunosuppressants were generally weaned at 2- to 4-month intervals as tolerated. For patients transitioned from other maintenance therapy, rituximab was added to the other therapy. Some of these patients had low levels of grumbling disease activity (BVAS-WG#2) and persistent ANCA positivity at the time of rituximab initiation. For such patients, other immunosuppression was weaned slowly after BVAS- WG=0 was achieved and ANCA titers showed improvement. Weaning of prednisone was limited at times by adrenal insufficiency among patients who had been on prednisone continuously for several years. In patients on rituximab who relapsed, rituximab was continued along with some increase of other maintenance immunosuppression medications followed by a slower taper. Ancillary Treatment Considerations. Additional considerations included measurement of urine human chorionic gonadotropin before every rituximab infusion for women of childbearing age, trimethoprim-sulfamethoxazole or one of it equivalents for prevention of Pneumocystis jirovecii pneumonia, a proton pump inhibitor to prevent corticosteroidinduced gastric ulcers, and calcium and vitamin D to prevent corticosteroid-induced osteoporosis. A bisphosphonate was added for patients at highest risk for osteoporosis. Care was taken to give every patient an annual influenza vaccine as well as pneumococcal, tetanus, diphtheria, and acellular pertussis vaccines and test for Hepatitis B virus (HBV) before initiation of therapy. Lamivudine or entecavir was prescribed to any HBV core antibody-positive patient to prevent HBV reactivation, unless HBV surface antibodies were present in high titer. P. jirovecii pneumonia and gastric ulcer prophylaxis were typically discontinued on corticosteroid withdrawal. Clinical Assessment, Definitions, Measurements, and Data Collection Clinical assessments and laboratory measurements were maintained prospectively at each visit in a Filemaker Pro 9.0 database. Patients were evaluated at each rituximab infusion and typically, halfway between infusions. These flow sheets were reviewed retrospectively. ANCA vasculitis disease activity was measured using the BVAS-WG (14). The BVAS-WG was adopted by our group at the time of the Wegener s Granulomatosis-Entretien trial, because it seemed more focused and specific to ANCA vasculitis than all vasculitis. The BVAS-WG was also used in the RAVE trial (5). BVAS-WG=2 means that a patient has two minor features of disease that are not organ-threatening. BVAS-WG=3 means one major feature of disease or three minor features. Patients were monitored by measurement of serum creatinine, ANCA, and peripheral B-cell counts every 4 months. Complete blood counts were checked every 2 months, and Ig levels were checked every 4 12 months. Complete disease remission was defined as BVAS-WG=0. A minor relapse was recorded if the patient developed BVAS- WG=2 after achieving BVAS-WG=0. A major relapse was recorded if the patient developed BVAS-WG$3. Adverse Events All serious adverse events (AEs) were recorded at time of event and included any event requiring hospitalization and/or death. Causes of death were determined by chart review, discussion with outside clinicians, and/or discussion with first-degree relatives. Statistical Analyses Patient characteristics stratified by PR3- or MPO-ANCA are presented as mean6sd for age, median (interquartile
3 738 Clinical Journal of the American Society of Nephrology range) for creatinine, and number (percent) for all categorical variables and compared using t tests for continuous variables and chi-squared tests where appropriate. ANCA titers were log-transformed because of non-normality for parametric testing. Unadjusted overall time to relapse as well as mortality were described using Kaplan Meier curves. A log-rank test was used to compare cumulative survival of the cohort with the survival of an age-, sex-, and ethnicity-matched general United States population based on data retrieved from National Vital Statistics Reports (15). Univariate Cox proportional hazards models were used to compare mortality by sex, serotype, and age. Graphs were created using GraphPad Prism 5.0d. Heat maps were created using GENE-E Dev. Statistical analyses were conducted in SAS, version 9.2. Two-tailed P values,0.05 were considered significant. Results Baseline Characteristics Table 1 illustrates the study population, which was comprised of 172 patients who underwent rituximab-induced continuous B cell depletion for maintenance of remission. We did not assign specific diagnosesofgpaor MPA given uncertainties involved in categorizing subsets of ANCA vasculitides (12). Furthermore, it is now becoming clear that ANCA autoantigen specificity may reflect phenotype more accurately than GPA or MPA (16). All patients were ANCA-positive at diagnosis: 98 (57%) patients had MPO-ANCA, and 74 (43%) patients had PR3-ANCA. There were no patients with both MPO- ANCA and PR3-ANCA. There were significantly more women in the MPO-ANCA group (62% versus 46%, P=0.04). There were more constitutional signs and symptoms (60% versus 38%, P=0.01) and ear, nose, and throat findings (76% versus 44%, P,0.001) measured by the modified BVAS-WG scoring system in the PR3-ANCA group. Induction of Remission and Weaning of Ancillary Immunosuppression Patients transitioned from induction therapy were in remission at time of entry, and residual prednisone doses were weaned. All patients who transitioned from maintenance therapy had BVAS-WG scores of two or less. In each case, BVAS-WG became zero, and ancillary immunosuppression was weaned as shown in Figure 1. Continuous B-Cell Depletion and ANCA Titers B-cell depletion was highly effective, because over 96% of tests showed no detectable B cells, defined as B-cell concentration,1 cell/mm 3 (data not shown). Less than 1% of samples had.10 B cells/mm 3 at any point during the entire study period. Rituximab dosing frequency was increased in these few instances. MPO- and PR3- ANCA titers were measured every 3 4 months in most patients (Figure 2). Despite continuous B-cell depletion, over 50% of MPO-ANCA patients and 25% of PR3- ANCA patients had positive titers throughout the study period. Disease Relapse Median remission maintenance follow-up time was 2.1 years. All patients achieved complete remission (defined as BVAS-WG=0). Durable maintenance of remission was achieved in the majority of patients (Figure 3). Relapse (BVAS-WG$2) occurred in 20% (n=35) of patients. Major relapse (BVAS-WG$3) occurred in nine patients (5%, median BVAS-WG=4, range=4 5) and was associated with weaning of other immunosuppression. Remission was reinduced and maintained in all nine patients with the addition of prednisone and another immunosuppressive agent. Patients with minor relapse (BVAS- WG=2) responded to short courses of corticosteroid recycling and did not experience additional relapses. There were no statistically significant differences between patients who received induction therapy and Table 1. Baseline characteristics of ANCA vasculitis patients undergoing continuous B-cell depletion Characteristics Total MPO-ANCA PR3-ANCA P Value Number of patients Age, mean6sd a Women, n (%) 95 (55) 61 (62) 34 (46) 0.04 b Organ involvement Constitutional signs/symptoms, n (%) 81 (47) 37 (38) 44 (60) b Cutaneous involvement, n (%) 17 (10) 9 (9) 8 (11) 0.80 Mucous membranes and eyes, n (%) 15 (9) 6 (6) 9 (12) 0.18 Ear, nose, and/or throat, n (%) 99 (58) 43 (44) 56 (76),0.001 b Lung involvement, n (%) 75 (44) 41 (42) 34 (46) 0.64 Kidney involvement, n (%) 106 (62) 61 (62) 45 (61) 0.88 Neurologic involvement, n (%) 8 (5) 4 (4) 4 (5) 0.73 Entry creatinine (mg/dl), median (IQR) 1.3 ( ) 1.5 ( ) 1.2 ( ) 0.10 Birmingham Vasculitis Activity Score (BVAS) Wegener s Granulomatosis (WG) items represent those items at the time of initial patient evaluations. MPO, myeloperoxidase; PR3, proteinase 3; IQR, interquartile range. a Age at diagnosis. b Significant at P,0.05.
4 Clin J Am Soc Nephrol 9: , April, 2014 Continuous B-Cell Depletion in ANCA, Pendergraft et al. 739 Figure 1. Ancillary immunosuppression use in ANCA vasculitis patients undergoing continuous B-cell depletion. Heat maps depict use of prednisone, cyclophosphamide (CYC), azathioprine (AZA), mycophenolate mofetil (MMF), and methotrexate (MTX) throughout the study period. Each square represents maximum daily medication dose in milligrams for prednisone, CYC, AZA, and MMF and weekly medication dose in milligrams for MTX during each 90-day period. Squares from left to right represent each 90-day time period. Squares from top to bottom represent each individual patient. Gray squares within study period represent missing data, and each individual patient row becomes gray at the end of study period. were then transitioned to rituximab maintenance therapy and patients who were transitioned from other immunosuppressive maintenance therapy to rituximab maintenance therapy (Table 2). AEs Infusion Reactions. All rituximab infusions were well tolerated and completed without acute anaphylactic reactions (Tables 3 and 4). Occasional minor infusion reactions
5 740 Clinical Journal of the American Society of Nephrology Figure 2. ANCA titers in ANCA vasculitis patients undergoing continuous B cell depletion. (A) Myeloperoxidase (MPO)-ANCA and (B) proteinase 3 (PR3)-ANCA titers were measured in each patient throughout the study duration. The dashed line represents the lower limit of a positive test, which is 2.8 and 20 units for MPO- and PR3-ANCA, respectively. Error bars represent median and interquartile range. Titers were significantly lower at all time points compared with the 0- to 90-day time period for all time periods with greater than five samples (*P,0.05). Figure 3. Minor and major relapse-free survival of ANCA vasculitis patients undergoing continuous B-cell depletion. Kaplan Meier curves comparing major (circles) and minor (triangles) relapse-free remission and survival. occurred, and all were managed by immediately halting the infusion. Typical minor reactions included jaw tingling, throat irritation, and/or pruritus. In each case, the reaction dissipated, and the infusion was resumed at a slower rate. No major infusion reactions occurred. Delayed Infusion Reactions. Delayed infusion-related symptoms were reported by several patients over subsequent days and included fever, hoarseness, and arthralgias. These symptoms were typically minor and inconsistently recorded and quantified. One patient was admitted to the hospital for
6 Clin J Am Soc Nephrol 9: , April, 2014 Continuous B-Cell Depletion in ANCA, Pendergraft et al. 741 Table 2. Minor and major relapses among ANCA vasculitis patients undergoing continuous B cell depletion Characteristics Total Induction Transition P Value a Number of patients Age, mean6sd b Women, n (%) 95(55) 42(55) 53(55) 0.99 PR3-ANCA, n (%) 74 (43) 36 (47) 38 (40) 0.31 Any relapse, n patients (%) 15 (20) c 7 (19) 8 (21) 0.86 Minor relapse, n patients (%) 14 (19) 6 (17) 8 (21) 0.63 Minor relapse, n events Major relapse, n patients (%) 3 (4) 2 (6) 1 (3) 0.52 Major relapse, n events MPO-ANCA, n (%) 98 (57) 40 (53) 58 (60) 0.31 Any relapse, n patients (%) 20 (20) c 7 (18) 13 (22) 0.55 Minor relapse, n patients (%) 16 (16) 7 (18) 9 (16) 0.79 Minor relapse, n events Major relapses, n patients (%) 6 (6) 1 (3) 5 (9) 0.21 Major relapse, n events There were 41 relapses in 35 patients (1 patient had four relapses and 3 patients had two relapses). Induction, patients who underwent induction therapy by our group before remission maintenance therapy; Transition, patients who were on alternative remission maintenance immunosuppression and transitioned by our group to rituximab. a Significant at P,0.05. b Age at diagnosis. c P=0.98. Table 3. Adverse events of ANCA vasculitis patients undergoing continuous B cell depletion Adverse Events Infections requiring hospitalization 25 Pulmonary 9 Disease-related hospitalizations 7 Flare 2 Tracheal/subglottic stenosis 5 Hypogammaglobulinemia 17 (IgG,400 mg/dl) on RTX Late-onset neutropenia a 17 Requiring hospitalization 4 Requiring GCSF (filgrastim) 13 Other events requiring hospitalization 52 Renal 6 Cardiac 12 Gastrointestinal 12 Orthopedic 7 Malignancy (bladder cancer) 1 Neuro 5 Miscellaneous 8 Malignancies 2 Melanoma 0 Nonmelanoma skin cancer ND Bladder cancer 1 Lung cancer 1 Major infusion reactions b 1 Delayed 1 RTX, rituximab; GCSF, granulocyte colony-stimulating factor; ND, not determined. a Median absolute neutrophil count (ANC) nadir=350 cells/mcl. b None acute. n 1 night for flu-like symptoms together with relative hypotension after an infusion. Infections Requiring Hospitalization. Twenty patients had at least 1 serious infection, with a total of 25 serious infections occurring overall, and 9 were pulmonary infections. Minor outpatient infections could not be quantitated. Late-Onset Neutropenia. Seventeen patients developed late-onset neutropenia (LON; defined as absolute neutrophil count,1000 cells/mm 3 ). Four episodes resolved without intervention by the time of repeat blood work. However, 13 episodes were treated with granulocyte colony-stimulating factor (filgrastim). Four patients had associated fever and were hospitalized for intravenous antibiotics. In all patients, neutropenia subsequently resolved, and rituximab was not discontinued because of this effect in any patient. Hypogammaglobulinemia. Seventeen episodes of hypogammaglobulinemia to an IgG level of,400 mg/dl developed in 17 patients (10% of cohort), and rituximab was discontinued in 9 patients. None of these patients had a disease relapse, and six patients were hospitalized for infection; however, three infections were associated with fever in the setting of LON. Malignancy. Other than nonmelanoma skin cancers, there were two malignancies, which included one bladder cancer and one lung cancer. Miscellaneous. Three of five HBV core antibody-positive patients received lamivudine or entecavir along with rituximab treatment, and HBV reactivation did not occur. There were no cases of progressive multifocal leukoencephalopathy. Pregnancy While receiving rituximab, women were counseled extensively to avoid pregnancy or plan to conceive after stopping
7 742 Clinical Journal of the American Society of Nephrology rituximab. Of note, 22 women under 40 years of age were treated with rituximab, and urine levels of human chorionic gonadotropin were measured and negative before each Table 4. Patients with ANCA vasculitis undergoing continuous B-cell depletion who died Deaths Age (yr) Gender Cause 1 72 Woman COPD exacerbation 2 71 Man End stage pulmonary fibrosis 3 70 Man Normal pressure hydrocephalus 4 73 Man Urolith-induced uroseptic shock 5 53 Man HCV end stage liver disease 6 87 Man Heart failure 7 83 Woman Myocardial infarction 8 83 Woman Lung cancer 9 90 Woman Aortic stenosis Man Found dead at home COPD, chronic obstructive pulmonary disease; HCV, hepatitis Cvirus. dose. When patients became pregnant, rituximab was discontinued, and maintenance immunosuppression was minimized to prednisone and/or azathioprine. High-risk obstetrical care at our center was initiated, and visit frequency in our clinic was increased to every 2 months. Five women in this age group achieved six pregnancies, resulting in five healthy offspring. One pregnancy resulted in fetal demise at 15 weeks. Only one patient (39 years) in the cohort who desired pregnancy was unable to conceive. Survival Survival is illustrated in Figure 4, and it mirrors survival of an age-, sex-, and ethnicity-matched United States population (P=0.94). There were 10 deaths, which are listed in Table 4. There was also no significant survival difference among ANCA patients based on sex or ANCA serotype. The only significant mortality risk factor in this group was age older than 80 years (hazard ratio, 9.02; 95% confidence interval, 2.41 to 33.79; P=0.001). Discussion This study describes the long-term results of 172 ANCA vasculitis patients who underwent rituximab-induced continuous B-cell depletion for maintenance of remission. Remission was maintained in the majority of patients, with a low rate of major relapse. This remission maintenance Figure 4. Survival of ANCA vasculitis patients undergoing continuous B-cell depletion compared with survival of the general population. Kaplan Meier survival curves comparing cumulative survival of the cohort (diamonds) with the survival of an age-, sex-, and ethnicity-matched general United States population (dashes) based on data retrieved from National Vital Statistics Reports. There was no statistically significant difference in survival over time (P=0.94).
8 Clin J Am Soc Nephrol 9: , April, 2014 Continuous B-Cell Depletion in ANCA, Pendergraft et al. 743 strategy also seems to result in survival rates comparable with a matched reference population, which may reflect a benefit of the treatment strategy described. Interestingly, most women in this study who wanted to achieve pregnancy were successful, even after perigestational rituximab exposure, perhaps related to improved quality of life. Only one patient has requested to be transitioned from rituximab to another primary maintenance immunosuppressant. There have been 10 deaths to date in this cohort. The only significant predictor of death within this cohort was increased risk of death in patients who achieve remission at an age greater than 80 years, which is not surprising. Other AEs occurred, with pulmonary infections comprising the majority of serious AEs, which is expected based on prior reports of longitudinal examinations of ANCA vasculitis patients (17). Another main AE associated with rituximab use (also described with other rheumatic diseases) (18) was LON with concomitant risk of infection. Fortunately, LON resolves with granulocyte colony-stimulating factor use and typically does not recur, thereby allowing for rituximab continuation. Hypogammaglobulinemia was a late and modest complication without apparent major sequelae, which led to discontinuation of rituximab in several patients. These results differ from a previous report showing a marked decline in Ig levels, especially with rituximab administration after cyclophosphamide use (19). Explanations for this discrepancy may relate to small cohort size, cyclophosphamide dosing, and cumulative exposure to other immunosuppressants in the other cohort. Unfortunately, there does not seem to be any predictor for patients who develop LON or hypogammaglobulinemia. Despite what seem to be impressive results, this study has several limitations. Success of this regimen may be less related to rituximab use and more related to the clinical care provided. Our patients are closely monitored through frequent clinic visits, telephone conversations, and correspondence. Furthermore, many patients were exposed to other immunosuppressants because of grumbling disease activity (BVAS-WG=1 2), and these other drugs likely contributed to improved disease control. Interestingly, despite exposure to other immunosuppressants, overall toxicity was low, and survival was excellent. Success of this treatment regimen may also be, in part, related to the induction regimens used. A more complete induction regimen that includes cyclophosphamide, which was used in many of our patients, may be helpful to allow for maintenance therapy using rituximab alone. The results could be different compared with an induction regimen consisting of rituximab without a cytotoxic agent or high-dose steroids (5 8). A fixed rituximab dosing schedule seems safe and effective; however, patients with ANCA vasculitis likely cannot remain on rituximab indefinitely. Redosing of rituximab based on B-cell return, rather than on a fixed schedule, may also be effective (9). A trial comparing continuous-scheduled rituximab with dosing based on B-cell return is now underway to address these questions (MAINtenance of remission using RITuximab in Systemic ANca associated vasculitis Trial, MAINRITSAN 2; NCT ). There must also be additional investigation into determining predictive markers for individuals who need fixed versus intermittent dosing. It seems that higher relative percentages of peripheral regulatory B cells at the time of B-cell repopulation after rituximab may be associated with more prolonged remission (20,21). This finding could imply an increased risk of relapse at the time of rituximab cessation. Regardless, these findings need to be validated in other centers, and predictors of sustained remission are needed. Great strides have been made with regards to induction of remission in ANCA vasculitis with the introduction of rituximab-induced B-cell depletion (5,6); however, it is clear that long-term remission cannot be maintained without additional immunosuppression (10). We and others have shown successful maintenance of remission using continuous rituximab for 2 years (10,12); however, this study is the first long-term study showing success beyond the 2-year mark. Ideally, goals for durable maintenance of remission in ANCA vasculitis should include therapeutic agents that provide excellent protection from autoimmune insults with little to no toxicity, improved quality of life, and survival that matches survival of the general population. This study is the largest of its kind to date, which brings us closer to these goals. Our findings provide highly granular support for rituximab as an effective agent for durable maintenance of remission. Acknowledgments The authors thank the patients as well as the clinic nurses dedicated to their care in the Vasculitis and Glomerulonephritis Clinic, including Donna Hagstrom, Kate Cosgrove, Eleanor Coughlin, Laura Chambers White, Chelsea Barrett, Stefanie Navarro, and Luke Cogswell. Part of this work was presented at the 16th International Vasculitis and ANCA Workshop in Paris, France (April 14 17, 2013). Disclosures J.L.N. has served as a rituximab-specific advisory board member for Genentech, is currently participating in the Genentechsponsored Rituximab in ANCA-Associated Vasculitis Registry (RAVER) study, and is receiving clinical research funding from Alexion Pharmaceuticals. References 1. Jennette JC, Falk RJ, Gasim AH: Pathogenesis of antineutrophil cytoplasmic autoantibody vasculitis. Curr Opin Nephrol Hypertens 20: , Gómez-Puerta JA, Quintana LF, Stone JH, Ramos-Casals M, Bosch X: B-cell depleting agents for ANCA vasculitides: A new therapeutic approach. Autoimmun Rev 11: , Jennette JC, Falk RJ, Hu P, Xiao H: Pathogenesis of antineutrophil cytoplasmic autoantibody-associated small-vessel vasculitis. Annu Rev Pathol 8: , Smith RM, Jones RB, Jayne DR: Progress in treatment of ANCAassociated vasculitis. Arthritis Res Ther 14: 210, Stone JH, Merkel PA, Spiera R, Seo P, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Turkiewicz A, Tchao NK, Webber L, Ding L, Sejismundo LP, Mieras K, Weitzenkamp D, Ikle D, Seyfert-Margolis V, Mueller M, Brunetta P, Allen NB, Fervenza FC, Geetha D, Keogh KA, Kissin EY, Monach PA, Peikert T, Stegeman C, Ytterberg SR, Specks U; RAVE-ITN Research Group: Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med 363: , Jones RB, Tervaert JW, Hauser T, Luqmani R, Morgan MD, Peh CA, Savage CO, Segelmark M, Tesar V, van Paassen P, Walsh D, Walsh M, Westman K, Jayne DR; European Vasculitis Study Group: Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med 363: , Mansfield N, Hamour S, Habib AM, Tarzi R, Levy J, Griffith M, Cairns T, Cook HT, Pusey CD, Salama AD: Prolonged disease-free
9 744 Clinical Journal of the American Society of Nephrology remission following rituximab and low-dose cyclophosphamide therapy for renal ANCA-associated vasculitis. Nephrol Dial Transplant 26: , Roubaud-Baudron C, Pagnoux C, Méaux-Ruault N, Grasland A, Zoulim A, LE Guen J, Prud homme A, Bienvenu B, de Menthon M, Camps S, LE Guern V, Aouba A, Cohen P, Mouthon L, Guillevin L; French Vasculitis Study Group: Rituximab maintenance therapy for granulomatosis with polyangiitis and microscopic polyangiitis. J Rheumatol 39: , Cartin-Ceba R, Golbin JM, Keogh KA, Peikert T, Sánchez- Menéndez M, Ytterberg SR, Fervenza FC, Specks U: Rituximab for remission induction and maintenance in refractory granulomatosis with polyangiitis (Wegener s): Ten-year experience at a single center. Arthritis Rheum 64: , Smith RM, Jones RB, Guerry MJ, Laurino S, Catapano F, Chaudhry A, Smith KG, Jayne DR: Rituximab for remission maintenance in relapsing antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 64: , Roll P, Ostermeier E, Haubitz M, Lovric S, Unger L, Holle J, Kötter I, Henes JC, Bergner R, Rubbert-Roth A, Specker C, Schulze- Koops H, Müller-Ladner U, Fleck M, Burmester GR, Hiepe F, Heitmann S, Aringer M, Fischer-Betz R, Dörner T, Tony HP: Efficacy and safety of rituximab treatment in patients with antineutrophil cytoplasmic antibody-associated vasculitides: Results from a German registry (GRAID). J Rheumatol 39: , Rhee EP, Laliberte KA, Niles JL: Rituximab as maintenance therapy for anti-neutrophil cytoplasmic antibody-associated vasculitis. Clin J Am Soc Nephrol 5: , Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, Flores- Suarez LF, Gross WL, Guillevin L, Hagen EC, Hoffman GS, Jayne DR, Kallenberg CG, Lamprecht P, Langford CA, Luqmani RA, Mahr AD, Matteson EL, Merkel PA, Ozen S, Pusey CD, Rasmussen N, Rees AJ, Scott DG, Specks U, Stone JH, Takahashi K, Watts RA: 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum 65: 1 11, Stone JH, Hoffman GS, Merkel PA, Min YI, Uhlfelder ML, Hellmann DB, Specks U, Allen NB, Davis JC, Spiera RF, Calabrese LH, Wigley FM, Maiden N, Valente RM, Niles JL, Fye KH, McCune JW, St Clair EW, Luqmani RA; International Network for the Study of the Systemic Vasculitides (INSSYS): A disease-specific activity index for Wegener s granulomatosis: Modification of the Birmingham Vasculitis Activity Score. Arthritis Rheum 44: , Finkelstein DM, Muzikansky A, Schoenfeld DA: Comparing survival of a sample to that of a standard population. J Natl Cancer Inst 95: , Lyons PA, Rayner TF, Trivedi S, Holle JU, Watts RA, Jayne DR, Baslund B, Brenchley P, Bruchfeld A, Chaudhry AN, Cohen Tervaert JW, Deloukas P, Feighery C, Gross WL, Guillevin L, Gunnarsson I, Harper L, Hrušková Z, Little MA, Martorana D, Neumann T, Ohlsson S, Padmanabhan S, Pusey CD, Salama AD, Sanders JS, Savage CO, Segelmark M, Stegeman CA, Tesar V, Vaglio A, Wieczorek S, Wilde B, Zwerina J, Rees AJ, Clayton DG, Smith KG: Genetically distinct subsets within ANCA-associated vasculitis. N Engl J Med 367: , Wall N, Harper L: Complications of long-term therapy for ANCAassociated systemic vasculitis. Nat Rev Nephrol 8: , Tesfa D, Ajeganova S, Hägglund H, Sander B, Fadeel B, Hafström I, Palmblad J: Late-onset neutropenia following rituximab therapy in rheumatic diseases: Association with B lymphocyte depletion and infections. Arthritis Rheum 63: , Venhoff N, Effelsberg NM, Salzer U, Warnatz K, Peter HH, Lebrecht D, Schlesier M, Voll RE, Thiel J: Impact of rituximab on immunoglobulin concentrations and B cell numbers after cyclophosphamide treatment in patients with ANCA-associated vasculitides. PLoS One 7: e37626, Bunch DO, McGregor JG, Khandoobhai NB, Aybar LT, Burkart ME, Hu Y, Hogan SL, Poulton CJ, Berg EA, Falk RJ, Nachman PH: Decreased CD5+ B cells in active ANCA vasculitis and relapse after rituximab. Clin J Am Soc Nephrol 8: , Wilde B, Thewissen M, Damoiseaux J, Knippenberg S, Hilhorst M, van Paassen P, Witzke O, Cohen Tervaert JW: Regulatory B cells in ANCA-associated vasculitis. Ann Rheum Dis 72: , 2013 Received: July 10, 2013 Accepted: November 27, 2013 Present address: William F. Pendergraft III, UNC Kidney Center, Division of Nephrology and Hypertension, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Published online ahead of print. Publication date available at www. cjasn.org. This article contains supplemental material online at asnjournals.org/lookup/suppl/doi: /cjn /-/ DCSupplemental. See related editorial, Should Rituximab Be Used to Prevent Relapse in Patients with ANCA-Associated Vasculitis?, on pages
Rituximab treatment for ANCA-associated vasculitis in childhood
Rituximab treatment for ANCA-associated vasculitis in childhood DISCLOSURE I have no relevant financial relationships to disclose Katharine Moore MD Nov 14, 2012 University of Colorado School of Medicine
More informationSupplementary Appendix
Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Jones RB, Cohen Tervaert JW, Hauser T, et al. Rituximab versus
More informationTITLE: Rituximab for Granulomatosis with Polyangiitis or Microscopic Polyangiitis: A Review of the Clinical and Cost-effectiveness
TITLE: Rituximab for Granulomatosis with Polyangiitis or Microscopic Polyangiitis: A Review of the Clinical and Cost-effectiveness DATE: 28 January 2015 CONTEXT AND POLICY ISSUES Granulomatosis with polyangiitis
More informationRecent advances in management of Pulmonary Vasculitis. Dr Nita MB
Recent advances in management of Pulmonary Vasculitis Dr Nita MB 23-01-2015 Overview of the seminar Recent classification of Vasculitis What is new in present classification? Trials on remission induction
More informationCombination Therapy With Rituximab and Cyclophosphamide for Remission Induction in ANCA Vasculitis
1 2 3 4 5 6 7 8 9 1 11 12 13 14 15 16 17 18 19 21 22 23 24 25 26 27 28 29 3 31 32 33 34 35 36 37 38 39 41 42 43 44 45 46 47 48 49 5 51 Combination Therapy With Rituximab and Cyclophosphamide for Remission
More informationGranulomatosis With Polyangiitis (Wegener s) Impact of Maintenance Therapy Duration
Granulomatosis With Polyangiitis (Wegener s) Impact of Maintenance Therapy Duration Jason Springer, MD,* Benjamin Nutter, MS, Carol A. Langford, MD, MHS, FACP, Gary S. Hoffman, MD, MS, MACR, and Alexandra
More informationClinical Commissioning Policy: Rituximab For ANCA Vasculitis. December Reference : NHSCB/ A3C/1a
Clinical Commissioning Policy: Rituximab For ANCA Vasculitis December 2012 Reference : NHSCB/ A3C/1a NHS Commissioning Board Clinical Commissioning Policy: Rituximab For The Treatment Of Anti-Neutrophil
More informationImmunoglobulin levels and infection risk with rituximab induction for anti-neutrophil cytoplasmic antibody-associated vasculitis
Clinical Kidney Journal, 2017, vol. 10, no. 4, 470 474 doi: 10.1093/ckj/sfx014 Advance Access Publication Date: 12 April 2017 Original Article ORIGINAL ARTICLE Immunoglobulin levels and infection risk
More informationTREATMENT OF ANCA-ASSOCIATED VASCULITIS
TREATMENT OF ANCA-ASSOCIATED VASCULITIS Loïc Guillevin Hôpital Cochin, Université Paris Descartes Cours DU, 11 mars 2016 1 Disclosure of interest regarding this presentation Roche has provided, in part,
More informationEfficacy and Safety of Rituximab in the Treatment of Rheumatoid Arthritis and ANCA-associated Vasculitis
New Evidence reports on presentations given at ACR/ARHP 2010 Efficacy and Safety of Rituximab in the Treatment of Rheumatoid Arthritis and ANCA-associated Vasculitis Report on ACR/ARHP 2010 presentations
More informationWhere a licence is displayed above, please note the terms and conditions of the licence govern your use of this document.
Rituximab for treatment of severe renal disease in ANCA associated vasculitis Geetha, Duvuru; Hruskova, Zdenka; Segelmark, Marten; Hogan, Jonathan; Morgan, Matthew; Cavero, Teresa; Eriksson, Per; Seo,
More informationNew Evidence reports on presentations given at EULAR Rituximab for the Treatment of Rheumatoid Arthritis and Vasculitis
New Evidence reports on presentations given at EULAR 2011 Rituximab for the Treatment of Rheumatoid Arthritis and Vasculitis Report on EULAR 2011 presentations Anti-TNF failure and response to rituximab
More informationANCA+ VASCULITIDES CYCAZAREM,
ANCA+ VASCULITIDES CYCAZAREM, q Comparison of 3 to 6 mo. oral CYC + CS then azathioprine or oral CYC for 12 mo.+ 10 mg/d CS. After 12 mo all the patients were treated with azathioprine q 150 patients followed
More informationGlucocorticoids and Relapse and Infection Rates in Anti-Neutrophil Cytoplasmic Antibody Disease
Article Glucocorticoids and Relapse and Infection Rates in Anti-Neutrophil Cytoplasmic Antibody Disease JulieAnne G. McGregor, Susan L. Hogan, Yichun Hu, Caroline E. Jennette, Ronald J. Falk, and Patrick
More informationTreatment of Severe Renal Disease in ANCA Positive and Negative Small Vessel Vasculitis with Rituximab
American Journal of Nephrology Original Report: Patient-Oriented, Translational Research Am J Nephrol 2015;41:296301 Received: March 12, 2015 Accepted: May 6, 2015 Published online: June 2, 2015 Treatment
More informationIntravenous Cyclophosphamide and Plasmapheresis in Dialysis-Dependent ANCA-Associated Vasculitis
Article Intravenous Cyclophosphamide and Plasmapheresis in Dialysis-Dependent ANCA-Associated Vasculitis Ruth J. Pepper,* Dimitrios Chanouzas, Ruth Tarzi, Mark A. Little,* Alina Casian, Michael Walsh,
More informationAN OVERVIEW OF ANCA-ASSOCIATED VASCULITIS
GRANULOMATOSIS WITH POLYANGIITIS (GPA), MICROSCOPIC POLYANGIITIS (MPA), and EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS (EGPA) AN OVERVIEW OF ANCA-ASSOCIATED VASCULITIS What is ANCA-associated Vasculitis?
More informationTell me more about vasculitis. Lisa Willcocks Consultant in Nephrology and Vasculitis, Addenbrooke s Hospital
Tell me more about vasculitis Lisa Willcocks Consultant in Nephrology and Vasculitis, Addenbrooke s Hospital Talk overview Case study ANCA-associated vasculitis What is ANCA vasculitis? What causes ANCA
More informationThe European and French networks. Christian Pagnoux, MD, MSc, MPH Mount Sinai Hospital, Toronto, Canada Cochin Hospital, Paris, France
The European and French networks Christian Pagnoux, MD, MSc, MPH Mount Sinai Hospital, Toronto, Canada Cochin Hospital, Paris, France French Vasculitis Study Group December 1980: L. Guillevin no research,
More informationanti-neutrophil cytoplasmic antibody, myeloperoxidase, microscopic polyangiitis, cyclophosphamide, corticosteroid
Online publication June 24, 2009 ANCA JMAAV 1 2 ANCA JMAAV MPO-ANCA 18 17 50 J Jpn Coll Angiol, 2009, 49: 53 61 anti-neutrophil cytoplasmic antibody, myeloperoxidase, microscopic polyangiitis, cyclophosphamide,
More informationANCA associated vasculitis in China
ANCA associated vasculitis in China Min Chen Renal Division, Peking University First Hospital, Beijing 100034, P. R. China 1 General introduction of AAV in China Disease spectrum and ANCA type Clinical
More informationRate of infections in severe necrotising vasculitis patients treated with cyclophosphamide induction therapy: a meta-analysis
Rate of infections in severe necrotising vasculitis patients treated with cyclophosphamide induction therapy: a meta-analysis M. Jung 1, L. Barra 2 1 Division of Rheumatology, Department of Medicine, University
More informationPredictors of Treatment Outcomes in ANCA-Associated Vasculitis with Severe Kidney Failure
Article Predictors of Treatment Outcomes in ANCA-Associated Vasculitis with Severe Kidney Failure Taewoo Lee,* Adil Gasim, Vimal K. Derebail,* Yunro Chung, JulieAnne G. McGregor,* Sophia Lionaki, Caroline
More informationVascularites associées aux ANCA Traitement par le RITUXIMAB
Vascularites associées aux ANCA Traitement par le RITUXIMAB Philippe Vanhille Néphrologie Médecine Interne Hôpital de Valenciennes Aix- en- Provence 2013 Cyclophosphamide therapy of severe systemic necrotizing
More informationEfficacy of Remission-Induction Regimens for ANCA-Associated Vasculitis
original article Efficacy of Remission-Induction Regimens for ANCA-Associated Vasculitis Ulrich Specks, M.D., Peter A. Merkel, M.D., M.P.H., Philip Seo, M.D., Robert Spiera, M.D., Carol A. Langford, M.D.,
More informationCase Rep Nephrol Urol 2013;3: DOI: / Published online: January 27, 2013
Published online: January 27, 2013 1664 5510/13/0031 0016$38.00/0 This is an Open Access article licensed under the terms of the Creative Commons Attribution- NonCommercial-NoDerivs 3.0 License (www.karger.com/oa-license),
More informationTREATMENT OF ANCA-ASSOCIATED VASCULITIS AN UPDATE. Loïc Guillevin. Hôpital Cochin, Université Paris Descartes. DU MALADIES SYSTEMIQUES, 7 March 2014
TREATMENT OF ANCA-ASSOCIATED VASCULITIS AN UPDATE Loïc Guillevin Hôpital Cochin, Université Paris Descartes DU MALADIES SYSTEMIQUES, 7 March 2014 1 Disclosure of interest regarding this presentation Former
More informationLong-term outcome of patients with ANCAassociated vasculitis treated with plasma exchange: a retrospective, single-centre study
Frausová et al. Arthritis Research & Therapy (2016) 18:168 DOI 10.1186/s13075-016-1055-5 RESEARCH ARTICLE Open Access Long-term outcome of patients with ANCAassociated vasculitis treated with plasma exchange:
More informationVascularites rénales associées aux ANCA
Vascularites rénales associées aux ANCA Société Médicale des Hôpitaux de Paris 16 Mars 2012 Philippe Vanhille Néphrologie et Médecine Interne Hôpital de Valenciennes Classification of systemic vasculitis:
More informationNIH Public Access Author Manuscript Ann Rheum Dis. Author manuscript; available in PMC 2011 July 19.
NIH Public Access Author Manuscript Published in final edited form as: Ann Rheum Dis. 2009 January ; 68(1): 103 106. doi:10.1136/ard.2008.097758. Comparison of disease activity measures for anti-neutrophil
More informationEstimating Renal Survival Using the ANCA-Associated GN Classification
Estimating Renal Survival Using the ANCA-Associated GN Classification Marc Hilhorst, Benjamin Wilde, Peter van Breda Vriesman, Pieter van Paassen, and Jan Willem Cohen Tervaert, for the Limburg Renal Registry
More informationEnd-stage renal disease in ANCA-associated vasculitis
Nephrol Dial Transplant (2017) 32: 248 253 doi: 10.1093/ndt/gfw046 Advance Access publication 6 April 2016 End-stage renal disease in ANCA-associated vasculitis Sergey Moiseev 1, Pavel Novikov 1, David
More informationPlasma exchanges in ANCA-associated vasculitis
Plasma exchanges in ANCA-associated vasculitis Xavier Puéchal, MD, PhD Centre de Référence des Maladies auto-immunes systémiques rares d Ile de France Hôpital Cochin Université Paris Descartes http://www.vascularites.org
More informationRituximab (MabThera) maintenance therapy for granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA)
NIHR Innovation Observatory Evidence Briefing: August 2017 Rituximab (MabThera) maintenance therapy for granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) NIHRIO (HSRIC) ID: 12979
More informationRenal transplantation in anti-neutrophil cytoplasmic antibody-associated vasculitis
Nephrol Dial Transplant (2015) 30: i159 i163 doi: 10.1093/ndt/gfu328 Advance Access publication 16 October 2014 Full Review Renal transplantation in anti-neutrophil cytoplasmic antibody-associated vasculitis
More informationAnnual Rheumatology & Therapeutics Review for Organizations & Societies
Annual Rheumatology & Therapeutics Review for Organizations & Societies Update on Granulomatosis with Polyangiitis (Wegener s) Learning Objectives Identify the clinical features of granulomatosis with
More informationANCA Glomerulonephritis and Vasculitis
CJASN epress. Published on August 25, 2017 as doi: 10.2215/CJN.02500317 ANCA Glomerulonephritis and Vasculitis J. Charles Jennette and Patrick H. Nachman Abstract ANCA vasculitis has an associated autoimmune
More informationManaging Acute Medical Problems, Birmingham Vasculitis. David Jayne. University of Cambridge
Managing Acute Medical Problems, Birmingham 2016 Vasculitis David Jayne University of Cambridge Disclosures Astra Zeneca, Aurinia, BIOGEN, Boehringer, Chemocentryx, Genzyme/Sanofi, GSK, Lilly, Medimmune,
More informationANCA-associated vasculitis. Vladimir Tesar Department of Nephrology, General University Hospital, Prague, Czech Republic
ANCA-associated vasculitis Vladimir Tesar Department of Nephrology, General University Hospital, Prague, Czech Republic Disclosure of Interests Abbvie, Amgen, Baxter, Bayer, Boehringer-Ingelheim, Calliditas,
More informationOlder patients with ANCA-associated vasculitis and dialysis dependent renal failure: a retrospective study
Manno et al. BMC Nephrology (2015) 16:88 DOI 10.1186/s12882-015-0082-9 RESEARCH ARTICLE Open Access Older patients with ANCA-associated vasculitis and dialysis dependent renal failure: a retrospective
More informationRenal transplantation
NEPHROLOGY 2008; 13, S37 S43 doi:10.1111/j.1440-1797.2008.00996.x Renal transplantation Date written: November 2006 Final submission: July 2007 Author: Nigel Toussaint GUIDELINES No recommendations possible
More informationRituximab versus Cyclophosphamide for ANCA-Associated Vasculitis
The new england journal of medicine original article Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis John H. Stone, M.D., M.P.H., Peter A. Merkel, M.D., M.P.H., Robert Spiera, M.D., Philip
More informationRATIONALE. K Without therapy, ANCA vasculitis with GN is associated. K There is high-quality evidence for treatment with
http://www.kidney-international.org chapter 13 & 2012 KDIGO Chapter 13: Pauci-immune focal and segmental necrotizing glomerulonephritis Kidney International Supplements (2012) 2, 233 239; doi:10.1038/kisup.2012.26
More informationCitation for published version (APA): Stassen, P. M. (2008). ANCA-associated vasculitis. Triggers and treatment s.n.
University of Groningen ANCA-associated vasculitis. Triggers and treatment Stassen, Patricia Maria IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite
More informationRenal transplantation in ANCA-associated vasculitis
Renal transplantation in ANCA-associated vasculitis Mårten Segelmark Linköping University Post Print N.B.: When citing this work, cite the original article. Original Publication: Mårten Segelmark, Renal
More informationRheumatology Advance Access published March 7, Induction treatment of ANCA-associated vasculitis with a single dose of rituximab
Original article Rheumatology Advance Access published March 7, 2014 RHEUMATOLOGY 262 doi:10.1093/rheumatology/ket489 Induction treatment of ANCA-associated vasculitis with a single dose of rituximab Tabitha
More informationNIH Public Access Author Manuscript N Engl J Med. Author manuscript; available in PMC 2011 July 15.
NIH Public Access Author Manuscript Published in final edited form as: N Engl J Med. 2010 July 15; 363(3): 221 232. doi:10.1056/nejmoa0909905. Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis
More informationCombined Infliximab and Rituximab in Necrotising Scleritis
This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License (www.karger.com/oa-license), applicable to the online version of the article
More informationAnti-neutrophil cytoplasmic antibody (ANCA)-associated
Rituximab as Maintenance Therapy for Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis Eugene P. Rhee, Karen A. Laliberte, and John L. Niles Renal Unit, Massachusetts General Hospital, Boston,
More informationNew Developments in ANCA-associated Vasculitis
New Developments in ANCA-associated Vasculitis Second International Renal Conference Bruges, March 2018 Ulrich Specks, M.D. Connor Group Foundation Professor of Medicine Mayo Clinic College of Medicine
More informationNEWS RELEASE Genentech Contacts: Media: Joe St. Martin (650) Investor: Karl Mahler Thomas Kudsk Larsen (973)
NEWS RELEASE Genentech Contacts: Media: Joe St. Martin (650) 467-6800 Investor: Karl Mahler 011 41 61 687 8503 Thomas Kudsk Larsen (973) 235-3655 Biogen Idec Contacts: Media: Christina Chan (781) 464-3260
More informationAnnals of the Rheumatic Diseases 2011; 70(3):
Long-term patient survival in ANCA-associated vasculitis Oliver Floßmann Annelies Berden Kirsten de Groot Chris Hagen Lorraine Harper Caroline Heijl Peter Höglund David Jayne Raashid Luqmani Alfred Mahr
More informationRelation between duration of the prodromal phase and renal damage in ANCA-associated vasculitis
Houben et al. BMC Nephrology (2017) 18:378 DOI 10.1186/s12882-017-0797-x RESEARCH ARTICLE Open Access Relation between duration of the prodromal phase and renal damage in ANCA-associated vasculitis Eline
More informationEULAR/ERA-EDTA recommendations for the management of ANCAassociated
EULAR/ERA-EDTA recommendations for the management of ANCAassociated vasculitis Dr. Meharunnisha Syed III year DNB Resident (General Medicine) Narayana Health-MSH Fifteen recommendations were developed,
More informationOptimizing the Therapeutic Strategies in ANCA-Associated Vasculitis Single Centre Experience with International Randomized Trials
Prague Medical Report / Vol. 107 (2006) No. 2, p. 199 212 199) Optimizing the Therapeutic Strategies in ANCA-Associated Vasculitis Single Centre Experience with International Randomized Trials Vaňková
More informationThe systemic vasculitides were traditionally classified. Treatment of ANCA-associated Systemic Vasculitis. H. Michael Belmont, M.D.
60 Treatment of ANCA-associated Systemic Vasculitis H. Michael Belmont, M.D. Abstract The antineutrophil cytoplasmic antibodies (ANCA)-associated small vessel vasculitides include Wegener s granulomatosis,
More informationIN A STUDY OF PATIENTS WITH GPA & MPA RITUXIMAB REGIMEN DEMONSTRATED CLINICALLY SIGNIFICANT REDUCTION OF MAJOR RELAPSE RATE VS AZA 1
FDA Approved for follow-up treatment 1 * IN A STUDY OF PATIENTS WITH GPA & MPA RITUXIMAB REGIMEN DEMONSTRATED CLINICALLY SIGNIFICANT REDUCTION OF MAJOR RELAPSE RATE VS AZA 1 Rituximab regimen=roche-manufactured,
More informationCanVasc Literature Review YEAR
CanVasc Literature Review YEAR 2013 14 Rituximab for the treatment of eosinophilic granulomatosis with polyangiitis This multicenter retrospective chart review study investigated the efficacy of Rituximab
More informationImproved prognosis in Norwegian patients with glomerulonephritis associated with anti-neutrophil cytoplasmic antibodies
Nephrol Dial Transplant (2015) 30: i67 i75 doi: 10.1093/ndt/gfv008 Advance Access publication 17 February 2015 Original Article Improved prognosis in Norwegian patients with glomerulonephritis associated
More informationDisease Activity, Glucocorticoid Exposure, and Rituximab Determine Body Composition Changes during Induction Treatment of ANCA-Associated Vasculitis
Original Article DOI 10.1002/acr.23099 Disease Activity, Glucocorticoid Exposure, and Rituximab Determine Body Composition Changes during Induction Treatment of ANCA-Associated Vasculitis Zachary S. Wallace,
More informationRevised 2017 international consensus on testing of ANCAs in granulomatosis with polyangiitis and microscopic polyangiitis.
Revised 2017 international consensus on testing of ANCAs in granulomatosis with polyangiitis and microscopic polyangiitis. Bossuyt X, Cohen Tervaert JW, Arimura Y, Blockmans D, Flores-Suárez LF, Guillevin
More informationfor the European Vasculitis Study Group submitted
Predictors of long-term ( 5 year) renal survival in 55 patients with ANCA-associated vasculitis Annelies Berden Oliver Floßmann Kerstin Westman Peter Höglund Chris Hagen Saskia le Cessie Michael Walsh
More informationReview Article. Current concepts in Anti-Neutrophil Cytoplasmic Antibody (ANCA) associated Vasculitis. Milind Aurangabadkar
Review Article Vidarbha Journal of Internal Medicine Volume 23 July 207 Current concepts in Anti-Neutrophil Cytoplasmic Antibody (ANCA) associated Vasculitis Milind Aurangabadkar ABSTRACT Anti-neutrophil
More informationRenal outcome of kidney-transplantation in Korean recipients with ANCA-associated vasculitis
Renal outcome of kidney-transplantation in Korean recipients with ANCA-associated vasculitis E.S. Park, S.S. Ahn, S.M. Jung, J.J. Song, Y.-B. Park, S.-W. Lee Division of Rheumatology, Department of Internal
More informationTRIALS. Walsh et al. Trials 2013, 14:73
Walsh et al. Trials 2013, 14:73 TRIALS STUDY PROTOCOL Open Access Plasma exchange and glucocorticoid dosing in the treatment of anti-neutrophil cytoplasm antibody associated vasculitis (PEXIVAS): protocol
More informationA COST EFFECTIVENESS ANALYSIS OF WEEKLY COMPLETE BLOOD COUNT MONITORING FOR LEUKOPENIA IN PATIENTS WITH GRANULOMATOSIS WITH POLYANGIITIS (GPA) ON
A COST EFFECTIVENESS ANALYSIS OF WEEKLY COMPLETE BLOOD COUNT MONITORING FOR LEUKOPENIA IN PATIENTS WITH GRANULOMATOSIS WITH POLYANGIITIS (GPA) ON CYCLOPHOSPHAMIDE By ATUL ASHOK KHASNIS, MD Submitted in
More informationSMALL TO MEDIUM VASCULITIS: RENAL ASPECT RATANA CHAWANASUNTORAPOJ UPDATE IN INTERNAL MEDICINE 2018
SMALL TO MEDIUM VASCULITIS: RENAL ASPECT RATANA CHAWANASUNTORAPOJ UPDATE IN INTERNAL MEDICINE 2018 OUTLINE Renal involvement in vasculitis Curr Rheumatol Rep 2013 Renal involvement in ANCA vasculitis GN***:
More informationACR 2013 Updates on vasculitis. Dr. Christian Pagnoux Mount Sinai Hospital
ACR 2013 Updates on vasculitis Dr. Christian Pagnoux Mount Sinai Hospital cpagnoux@mtsinai.on.ca Disclosures Consulting and speaker fees Hoffmann-La Roche BMS Advisory boards Hoffmann-La Roche GSK Educational
More informationThe role of biologics in treatment of ANCA-associated vasculitis
Mod Rheumatol (2012) 22:319 326 DOI 10.1007/s10165-011-0548-y REVIEW ARTICLE The role of biologics in treatment of ANCA-associated vasculitis Chethana Dharmapalaiah Richard A. Watts Received: 29 July 2011
More informationConsequences of disease and treatment in ANCA-associated vasculitis Tuin, Janneke
University of Groningen Consequences of disease and treatment in ANCA-associated vasculitis Tuin, Janneke IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish
More informationAntineutrophil cytoplasm antibody associated vasculitis: recent developments
mini review http://www.kidney-international.org & 2013 International Society of Nephrology Antineutrophil cytoplasm antibody associated vasculitis: recent developments Shunsuke Furuta 1 and David R.W.
More informationNine patients with anti-neutrophil cytoplasmic antibody-positive vasculitis successfully treated with rituximab
Journal of Internal Medicine 2005; 257: 540 548 Nine patients with anti-neutrophil cytoplasmic antibody-positive vasculitis successfully treated with rituximab P. ERIKSSON From the Department of Rheumatology,
More informationThe Journal of Rheumatology Volume 42, no. 12
The Journal Volume 42, no. 12 Clinical and Economic Burden of Antineutrophil Cytoplasmic Antibody associated Vasculitis in the United States Karina Raimundo, Amanda M. Farr, Gilwan Kim and George Duna
More informationManagement of Acute Vasculitis. CMT teaching 3 rd June 2015 Caroline Wroe
Management of Acute Vasculitis CMT teaching 3 rd June 2015 Caroline Wroe Vasculitis pub quiz Match the date with the event Dr Peter McBride, Scottish Otolaryngologist describes a disease of rapid destruction
More informationRisk Factors for Renal Survival in Chinese Patients with Myeloperoxidase-ANCA Associated GN
Article Risk Factors for Renal Survival in Chinese Patients with Myeloperoxidase-ANCA Associated GN Yinghua Chen, Hao Bao, Zhengzhao Liu, Xia Liu, Erzhi Gao, Caihong Zeng, Haitao Zhang, Zhihong Liu, and
More informationAntineutrophil cytoplasmic antibody (ANCA) associated. Article
Annals of Internal Medicine Article Predictors of Relapse and Treatment Resistance in Antineutrophil Cytoplasmic Antibody Associated Small-Vessel Vasculitis Susan L. Hogan, PhD, MPH; Ronald J. Falk, MD;
More informationAperTO - Archivio Istituzionale Open Access dell'università di Torino
AperTO - Archivio Istituzionale Open Access dell'università di Torino Long-term effects of rituximab added to cyclophosphamide in refractory patients with vasculitis. This is the author's manuscript Original
More informationCHECK LIST FORM-MONTH 27 (Please note Month 27 is from enrolment not randomisation)
CHECK LIST FORM-MONTH 27 (Please note Month 27 is from enrolment not randomisation) Participant Initials: Date of Birth: Were the following forms completed for this visit? Follow Up Form Done t Done BVASWG
More informationYear In Review: VasculitisPers. Disclosures. Learning Objectives. none 4/16/2018. Describe new medications for the treatment of vasculitis
Year In Review: VasculitisPers Cailin Sibley, M.D., M.H.S. Director, Vasculitis Clinic April 27 th, 2018 NTEREST DISCLOSURE Disclosures none Learning Objectives Describe new medications for the treatment
More informationLong-term follow-up of patients with severe ANCAassociated vasculitis comparing plasma exchange to intravenous methylprednisolone treatment is unclear
http://www.kidney-international.org & 2013 International Society of Nephrology Long-term of patients with severe ANCAassociated vasculitis comparing plasma exchange to intravenous methylprednisolone treatment
More informationEudraCT number: Page 8 of 42
EudraCT number: 2012-001102-14 Page 8 of 42 5 Trial Synopsis Title Sponsor name North American Sponsor Disease Under Investigation An international, open label, randomised, controlled trial comparing rituximab
More informationPersistent hematuria in patients with. vasculitis during clinical remission: chronic glomerular lesion or low-grade active renal vasculitis?
Lv et al. BMC Nephrology (2017) 18:354 DOI 10.1186/s12882-017-0763-7 RESEARCH ARTICLE Open Access Persistent hematuria in patients with antineutrophil cytoplasmic antibodyassociated vasculitis during clinical
More informationAdditional file 2: Details of cohort studies and randomised trials
Reference Randomised trials Ye et al. 2001 Abstract 274 R=1 WD=0 Design, numbers, treatments, duration Randomised open comparison of: (45 patients) 1.5 g for 3, 1 g for 3, then 0.5 to 0.75 g IV cyclophosphamide
More informationWegener s Granulomatosis JUN-KI PARK
Wegener s Granulomatosis JUN-KI PARK Definition History Epidemiology Clinical symptoms Pathophysiology Treatment Wegener granulomatosis (WG) is a complex, immunemediated disorder, which along with microscopic
More informationNon-commercial use only
Case RepoRt Reumatismo, 2013; 65 (2): 90-94 Granulomatosis polyangiitis associated with meningeal involvement: response to rituximab therapy after failure of cyclophosphamide Corresponding author: Maurizio
More informationRheumatoid factor is correlated with disease activity and inflammatory markers in antineutrophil cytoplasmic antibodyassociated
Watanabe et al. BMC Immunology (2017) 18:53 DOI 10.1186/s12865-017-0234-8 RESEARCH ARTICLE Open Access Rheumatoid factor is correlated with disease activity and inflammatory markers in antineutrophil cytoplasmic
More informationGRANULOMATOSIS WITH POLYANGIITIS
What is granulomatosis with polyangiitis (GPA)? Granulomatosis with polyangiitis (GPA) is a form of vasculitis a family of rare disorders characterized by inflammation of the blood vessels, which can restrict
More informationABSTRACT. n engl j med 363;3 nejm.org july 15,
The new england journal of medicine established in 1812 july 15, 21 vol. 363 no. 3 Rituximab versus Cyclophosphamide in ANCA-Associated Renal Vasculitis Rachel B. Jones, M.R.C.P., M.D., Jan Willem Cohen
More informationAvacopan in addition to standard of care for ANCA-associated vasculitis
EVIDENCE BRIEFING DECEMBER 2018 Avacopan in addition to standard of care for ANCA-associated vasculitis NIHRIO ID 24160 NICE ID 10023 Developer/Company ChemoCentryx and Vifor Pharma UK Ltd UKPS ID N/A
More informationWillcocks et al.,
ONLINE SUPPLEMENTAL MATERIAL Willcocks et al., http://www.jem.org/cgi/content/full/jem.20072413/dc1 Supplemental materials and methods SLE and AASV cohorts The UK SLE cohort (n = 171) was obtained from
More informationVasculitis. Edward Dwyer, M.D. Division of Rheumatology. Vasculitis
Edward Dwyer, M.D. Division of Rheumatology VASCULITIS is a primary inflammatory disease process of the vasculature Determinants of the Clinical Manifestations of : Target organ involved Size of vessel
More informationWegener s Granulomatosis
Wegener s Granulomatosis Authors: Professor Loïc Guillevin 1,2, Doctor Alfred Mahr Creation Date: May 2002 Update: January 2004 1 CHU Hôpital Cochin, 27 Rue du Faubourg Saint-Jacques, 75014 Paris, France
More informationTubular Lesions Predict Renal Outcome in Antineutrophil Cytoplasmic Antibody Associated Glomerulonephritis after Rituximab Therapy
Tubular Lesions Predict Renal Outcome in Antineutrophil Cytoplasmic Antibody Associated Glomerulonephritis after Rituximab Therapy Annelies E. Berden,* Rachel B. Jones, Dianhdra D. Erasmus,* Michael Walsh,
More informationAssociation of Serum Calprotectin (S100A8/A9) Level With Disease Relapse in Proteinase 3 Antineutrophil Cytoplasmic Antibody Associated Vasculitis
ARTHRITIS & RHEUMATOLOGY Vol. 69, No. 1, January 2017, pp 185 193 DOI 10.1002/art.39814 VC 2016, American College of Rheumatology Association of Serum Calprotectin (S100A8/A9) Level With Disease Relapse
More informationEUVAS update June 5 th Marinka Twilt
EUVAS update June 5 th 2012 Marinka Twilt Chapel Hill 2012 Classification Large Vessel Vasculitis (LVV) Medium Vessel Vasculitis (MVV) Small Vessel Vasculitis (SVV) Variable Vessel Vasculitis (VVV) Single
More informationEudraCT number: Page 9 of 46
EudraCT number: 2012-001102-14 Page 9 of 46 5 Trial Synopsis Title Sponsor name North American Sponsor Japan Sponsor Ireland Sponsor Disease Under Investigation An international, open label, randomised,
More informationSmall Vessel Vasculitis
Small Vessel Vasculitis Paul A Brogan Professor of Vasculitis and Consultant Paediatric Rheumatologist Department of Rheumatology Institute of Child Health and Great Ormond St Hospital, London UK P.brogan@ucl.ac.uk
More informationEveryday Vasculitis (or what questions do we get asked most!) Lucy Smyth Renal Consultant
Everyday Vasculitis (or what questions do we get asked most!) Lucy Smyth Renal Consultant What is it? Why have I got it? How can we treat it? Why do I feel like I do? What do the blood tests mean? Will
More informationVASCULITIS. Case Presentation. Case Presentation
VASCULITIS Case Presentation The patient is a 24 year old woman who presented to the emergency room with left-sided weakness. She was confused and complained of a severe headache. She was noted to have
More information