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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\n      \u003Ch2\u003ESummary\u003C\/h2\u003E\n      \u003Cp id=\u0022p-1\u0022\u003EThis article discusses the results of the 18-month follow-up from the Rituximab in ANCA-Associated Vasculitis trial [RAVE; \u003Ca href=\u0022\/external-ref?link_type=ISRCTN\u0026amp;access_num=ISRCTN28528813\u0022 class=\u0022external-ref external-ref-type-isrctn\u0022\u003EISRCTN28528813\u003C\/a\u003E; Stone JH et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2010], which found that one course of treatment with rituximab was noninferior to standard course of therapy (cyclophosphamide followed by azathioprine) for remission-induction of severe antineutrophil cytoplasmic antibody-associated vasculitis.\u003C\/p\u003E\n   \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Evasculitis clinical trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n      \u003Cp id=\u0022p-2\u0022\u003EJohn H. Stone, MD, Massachusetts General Hospital, Boston, Massachusetts, USA, presented the results of the 18-month follow-up from the Rituximab in ANCA-Associated Vasculitis trial [RAVE; \u003Ca href=\u0022\/external-ref?link_type=ISRCTN\u0026amp;access_num=ISRCTN28528813\u0022 class=\u0022external-ref external-ref-type-isrctn\u0022\u003EISRCTN28528813\u003C\/a\u003E; Stone JH et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2010], which found that one course of treatment with rituximab was noninferior to standard course of therapy (cyclophosphamide followed by azathioprine) for remission-induction of severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Patients who were at highest risk for flare had relapsing disease at baseline, proteinase 3(PR3)-ANCA positivity, or granulomatosis with polyangiitis (GPA).\u003C\/p\u003E\n      \u003Cp id=\u0022p-3\u0022\u003EThe RAVE trial was a randomized, double-blind, placebo-controlled, noninferiority study. Patients from the original 6-month study were switched from cyclophosphamide to azathioprine or from rituximab to placebo between 3 and 6 months if remission was achieved [Birmingham Vasculitis Activity Score\/Wegener\u0027s Granulomatosis (BVAS\/WG)=0 and complete remission if BVAS\/WG=0 off prednisone] and followed for 18 months. Remission rates were compared for the following subsets using log-rank tests: new diagnosis versus relapsing disease at baseline; myeloperoxidase (MPO)- versus PR3-ANCA; and microscopic polyangiitis (MPA) versus GPA.\u003C\/p\u003E\n      \u003Cp id=\u0022p-4\u0022\u003EAfter 18 months, more than 60% of patients from the original groups remained in the study. There was no significant difference in the cumulative number of severe or limited disease flares between the rituximab and cyclophosphamide-azathioprine treatment groups. By the end of the study, 39% of patients in the rituximab group versus 33% in the cyclophosphamide-azathioprine group met the definition of complete remission (p=NS). In the rituximab group, 77% of the originally treated patients achieved complete remission versus 71% for cyclophosphamide-azathioprine at any time during the study (p=0.69).\u003C\/p\u003E\n      \u003Cp id=\u0022p-5\u0022\u003EWhen analyzed by disease subsets, patients who were MPO-ANCA-positive (79%) had significantly (p=0.01) higher remission rates compared with PR3-ANCA-positive patients (72%). Patients with MPA (79%) had significantly higher (p=0.01) remission rates compared with those with GPA (73%). Patients at study entry who were considered to be in relapse (67%) had significantly lower (p=0.01) remission rates compared with those who entered with a new diagnosis (81%). In all disease types, time to disease flare was longer for those patients with higher remission rates. Disease flares in the two treatment arms did not differ in number or severity.\u003C\/p\u003E\n      \u003Cp id=\u0022p-6\u0022\u003EThe investigators noted that an increasing rise in ANCA titer or B-cell count was not an accurate predictor of disease flare. B-cell depletion occurred with cyclophosphamide-azathioprine, as well as rituximab, but was more prolonged with cyclophosphamide-azathioprine. Among rituximab-treated patients who achieved complete remission, flares occurred only after reconstitution of detectable B-cells. Dr. Stone noted that although flares occur in the absence of both B-cells and ANCA, as long as B-cells remain depleted and ANCA remains negative, the risk of a severe flare is low.\u003C\/p\u003E\n      \u003Cp id=\u0022p-7\u0022\u003EThere were no clinically significant differences in overall or serious adverse events, deaths, infections, or malignancies. In particular, no additional malignancies occurred beyond those reported in the original study.\u003C\/p\u003E\n      \u003Cp id=\u0022p-8\u0022\u003EThese results demonstrate that a single course of rituximab is as effective up to 18 months as standard therapy (cyclophosphamide-azathioprine) for remission induction and maintenance in severe ANCA-associated vasculitis. Relapses are more common in those with PR3-ANCA, GPA, and relapsing disease at baseline. Additional mechanistic studies are needed to define the immunological events that surround relapses more precisely.\u003C\/p\u003E\n   \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2011 MD Conference Express\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/11\/13\/15.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzmw81\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}