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Long-term maintenance therapy using rituximab-induced continuous B-cell depletion in patients with ANCA vasculitis.

ABSTRACT: 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.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.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.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.

SUBMITTER: Pendergraft WF

PROVIDER: S-EPMC3974359 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Long-term maintenance therapy using rituximab-induced continuous B-cell depletion in patients with ANCA vasculitis.

Pendergraft William F WF Cortazar Frank B FB Wenger Julia J Murphy Andrew P AP Rhee Eugene P EP Laliberte Karen A KA Niles John L JL

Clinical journal of the American Society of Nephrology : CJASN 20140313 4

<h4>Background and objectives</h4>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.<h4>Design, setting, participants, & measurements</h4>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 ...[more]

PMID: 24626432

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Project description:ObjectivesFollowing a maintenance course of rituximab (RTX) for ANCA-associated vasculitis (AAV), relapses occur on cessation of therapy, and further dosing is considered. This study aimed to develop relapse and infection risk prediction models to help guide decision making regarding extended RTX maintenance therapy.MethodsPatients with a diagnosis of AAV who received 4-8 grams of RTX as maintenance treatment between 2002 and 2018 were included. Both induction and maintenance doses were included; most patients received standard departmental protocol consisting of 2× 1000 mg 2 weeks apart, followed by 1000 mg every 6 months for 2 years. Patients who continued on repeat RTX dosing long-term were excluded. Separate risk prediction models were derived for the outcomes of relapse and infection.ResultsA total of 147 patients were included in this study with a median follow-up of 63 months [interquartile range (IQR): 34-93]. Relapse: At time of last RTX, the model comprised seven predictors, with a corresponding C-index of 0.54. Discrimination between individuals using this model was not possible; however, discrimination could be achieved by grouping patients into low- and high-risk groups. When the model was applied 12 months post last RTX, the ability to discriminate relapse risk between individuals improved (C-index 0.65), and once again, clear discrimination was observed between patients from low- and high-risk groups. Infection: At time of last RTX, five predictors were retained in the model. The C-index was 0.64 allowing discrimination between low and high risk of infection groups. At 12 months post RTX, the C-index for the model was 0.63. Again, clear separation of patients from two risk groups was observed.ConclusionWhile our models had insufficient power to discriminate risk between individual patients they were able to assign patients into risk groups for both relapse and infection. The ability to identify risk groups may help in decisions regarding the potential benefit of ongoing RTX treatment. However, we caution the use of these prediction models until prospective multi-centre validation studies have been performed.

Project description:BackgroundCyclophosphamide and glucocorticoids have been the cornerstone of remission-induction therapy for severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis for 40 years. Uncontrolled studies suggest that rituximab is effective and may be safer than a cyclophosphamide-based regimen.MethodsWe conducted a multicenter, randomized, double-blind, double-dummy, noninferiority trial of rituximab (375 mg per square meter of body-surface area per week for 4 weeks) as compared with cyclophosphamide (2 mg per kilogram of body weight per day) for remission induction. Glucocorticoids were tapered off; the primary end point was remission of disease without the use of prednisone at 6 months.ResultsNine centers enrolled 197 ANCA-positive patients with either Wegener's granulomatosis or microscopic polyangiitis. Baseline disease activity, organ involvement, and the proportion of patients with relapsing disease were similar in the two treatment groups. Sixty-three patients in the rituximab group (64%) reached the primary end point, as compared with 52 patients in the control group (53%), a result that met the criterion for noninferiority (P<0.001). The rituximab-based regimen was more efficacious than the cyclophosphamide-based regimen for inducing remission of relapsing disease; 34 of 51 patients in the rituximab group (67%) as compared with 21 of 50 patients in the control group (42%) reached the primary end point (P=0.01). Rituximab was also as effective as cyclophosphamide in the treatment of patients with major renal disease or alveolar hemorrhage. There were no significant differences between the treatment groups with respect to rates of adverse events.ConclusionsRituximab therapy was not inferior to daily cyclophosphamide treatment for induction of remission in severe ANCA-associated vasculitis and may be superior in relapsing disease. (Funded by the National Institutes of Allergy and Infectious Diseases, Genentech, and Biogen; ClinicalTrials.gov number, NCT00104299.)

Project description:ObjectivesTo investigate the clinical features and long-term outcomes of Chinese anti-neutrophil cytoplasmic antibodies (ANCAs)-associated vasculitis (AAV) patients with different ANCA serotypes.MethodsTwo hundred and twenty-four AAV patients from January 2010 to June 2021 were divided into myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA groups. Clinical and long-term outcomes were compared.ResultsIn this study, the average follow-up was 46.4 months (range 0.3-188.4 months). One hundred and seventy-seven (79.0%) patients were MPO-ANCA-positive and 47 were PR3-ANCA-positive; the mean age of MPO-ANCA positive patients at diagnosis was elder than that of PR3-ANCA positive patients (67.0 vs. 60.0 years, p = .004). Among PR3-ANCA-positive patients, ear, nose and throat symptoms were more common (p = .014). Between two ANCA serotypes, there were no differences in complement 3 (C3), Birmingham vasculitis activity score (BVAS), five-factor score (FFS) or other organ involvements. For all AAV patients, the overall survival rates at one, three and five years were 80.0%, 67.0% and 56.4%, respectively. The cumulative relapse-free rates of one, three and five years were 89.5%, 76.4% and 68.4%, respectively. The survival of AAV patients was unaffected by the ANCA serotype (p = .23). The ANCA serotype also had no effect on either disease relapse (p = .20) or remission rates (p = .10). In our study, PR3-ANCA patients showed a better long-term survival, as the 5-year survival rate and the 5-year relapse-free survival rate of PR3-ANCA patients were 60.7% and 76.9%, while that of MPO-ANCA patients were 55.2% and 65.8%, respectively. Rather than ANCA serotype, younger patients with milder kidney involvement and lower disease assessment scores (BVAS and FFS) might be more relevant to better prognosis.ConclusionsThe likelihood of induced remission, patient survival or disease recurrence is all unaffected by ANCA serotypes. A better prognosis is seen in younger patients with milder kidney involvement and lower BVAS/FFS scores.

Project description:BackgroundKidney involvement is common in anti-neutrophil cytoplasm antibody-associated vasculitis (AAV) and the prognosis is determined by the severity of kidney damage. This study focused on long-term kidney outcomes, defining possible risk factors and comparing the performance of three different histological classifications to predict outcomes for patients with AAV.MethodsThe dataset included 848 patients with newly diagnosed AAV who participated in seven randomized controlled trials (RCTs) (1995-2012). Follow-up information was obtained from questionnaires sent to the principal investigators of the original RCTs.ResultsThe cumulative incidence of end-stage kidney disease (ESKD) at 5 and 10 years was 17% and 22%, respectively. Patients who developed ESKD had reduced patient survival compared with those with preserved kidney function (hazard ratio 2.8, P < .001). Comparing patients with AAV and kidney involvement with a matched general population, patients with AAV had poor survival outcomes, even in early stages of chronic kidney disease. The main cause of death was infection followed by cardiovascular disease in patients developing ESKD and malignancy in those who did not. Some 34% of patients with initial need for dialysis recovered kidney function after treatment. Thirty-five out of 175 in need of kidney replacement therapy (KRT) during follow-up received a kidney transplant with good outcome; there was 86% patient survival at 10 years.In the subcohort of 214 patients with available kidney biopsies, three scoring systems were tested: the Berden classification, the Renal Risk Score and the Mayo Clinic Score. The scores highlighted the importance of normal glomeruli and severe glomerulosclerosis on kidney survival (P < .001 and P = .001, respectively). The Renal Risk Score demonstrated a moderate prediction of kidney survival (area under the curve 0.79; standard error 0.03, 95% confidence interval 0.71-0.83).ConclusionsEarly diagnosis of AAV is extremely important. Even milder forms of kidney involvement have an impact on the prognosis. Patients in need of KRT had the lowest survival rates, but kidney transplantation has shown favorable outcomes for eligible AAV patients. The three histologic scoring systems were all identified as independent prognostic factors for kidney outcome.

Dataset Information

Long-term maintenance therapy using rituximab-induced continuous B-cell depletion in patients with ANCA vasculitis.

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Long-term maintenance therapy using rituximab-induced continuous B-cell depletion in patients with ANCA vasculitis.

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