Real world use of avacopan for ANCA-associated vasculitis. First experiences in Ireland.

Real world use of avacopan for... | HRB Open Research dataLayer = dataLayer || []; // Standard GTM initialization - Google Consent Mode handles consent automatically (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start': new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0], j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src= 'https://www.googletagmanager.com/gtm.js?id='+i+dl+ '>m_auth=hzk0Vc3qFsQYhCrIoHz68A>m_preview=env-1>m_cookies_win=x';f.parentNode.insertBefore(j,f); })(window,document,'script','dataLayer','GTM-MWFK8L5J'); ;window.NREUM||(NREUM={});NREUM.init={distributed_tracing:{enabled:true},privacy:{cookies_enabled:true},ajax:{deny_list:["bam.nr-data.net"]}}; ;NREUM.loader_config={accountID:"438030",trustKey:"438030",agentID:"772317073",licenseKey:"97f8f67f26",applicationID:"772317073"} ;NREUM.info={beacon:"bam.nr-data.net",errorBeacon:"bam.nr-data.net",licenseKey:"97f8f67f26",applicationID:"772317073",sa:1} ;/*! For license information please see nr-loader-spa-1.236.0.min.js.LICENSE.txt */ (()=>{"use strict";var e,t,r={5763:(e,t,r)=>{r.d(t,{P_:()=>l,Mt:()=>g,C5:()=>s,DL:()=>v,OP:()=>T,lF:()=>D,Yu:()=>y,Dg:()=>h,CX:()=>c,GE:()=>b,sU:()=>_});var n=r(8632),i=r(9567);const o={beacon:n.ce.beacon,errorBeacon:n.ce.errorBeacon,licenseKey:void 0,applicationID:void 0,sa:void 0,queueTime:void 0,applicationTime:void 0,ttGuid:void 0,user:void 0,account:void 0,product:void 0,extra:void 0,jsAttributes:{},userAttributes:void 0,atts:void 0,transactionName:void 0,tNamePlain:void 0},a={};function s(e){if(!e)throw new Error("All info objects require an agent identifier!");if(!a[e])throw new Error("Info for ".concat(e," was never set"));return a[e]}function c(e,t){if(!e)throw new Error("All info objects require an agent identifier!");a[e]=(0,i.D)(t,o),(0,n.Qy)(e,a[e],"info")}var u=r(7056);const d=()=>{const e={blockSelector:"[data-nr-block]",maskInputOptions:{password:!0}};return{allow_bfcache:!0,privacy:{cookies_enabled:!0},ajax:{deny_list:void 0,enabled:!0,harvestTimeSeconds:10},distributed_tracing:{enabled:void 0,exclude_newrelic_header:void 0,cors_use_newrelic_header:void 0,cors_use_tracecontext_headers:void 0,allowed_origins:void 0},session:{domain:void 0,expiresMs:u.oD,inactiveMs:u.Hb},ssl:void 0,obfuscate:void 0,jserrors:{enabled:!0,harvestTimeSeconds:10},metrics:{enabled:!0},page_action:{enabled:!0,harvestTimeSeconds:30},page_view_event:{enabled:!0},page_view_timing:{enabled:!0,harvestTimeSeconds:30,long_task:!1},session_trace:{enabled:!0,harvestTimeSeconds:10},harvest:{tooManyRequestsDelay:60},session_replay:{enabled:!1,harvestTimeSeconds:60,sampleRate:.1,errorSampleRate:.1,maskTextSelector:"*",maskAllInputs:!0,get blockClass(){return"nr-block"},get ignoreClass(){return"nr-ignore"},get maskTextClass(){return"nr-mask"},get blockSelector(){return e.blockSelector},set blockSelector(t){e.blockSelector+=",".concat(t)},get maskInputOptions(){return e.maskInputOptions},set maskInputOptions(t){e.maskInputOptions={...t,password:!0}}},spa:{enabled:!0,harvestTimeSeconds:10}}},f={};function l(e){if(!e)throw new Error("All configuration objects require an agent identifier!");if(!f[e])throw new Error("Configuration for ".concat(e," was never set"));return f[e]}function h(e,t){if(!e)throw new Error("All configuration objects require an agent identifier!");f[e]=(0,i.D)(t,d()),(0,n.Qy)(e,f[e],"config")}function g(e,t){if(!e)throw new Error("All configuration objects require an agent identifier!");var r=l(e);if(r){for(var n=t.split("."),i=0;i {r.d(t,{D:()=>i});var n=r(50);function i(e,t){try{if(!e||"object"!=typeof e)return(0,n.Z)("Setting a Configurable requires an object as input");if(!t||"object"!=typeof t)return(0,n.Z)("Setting a Configurable requires a model to set its initial properties");const r=Object.create(Object.getPrototypeOf(t),Object.getOwnPropertyDescriptors(t)),o=0===Object.keys(r).length?e:r;for(let a in o)if(void 0!==e[a])try{"object"==typeof e[a]&&"object"==typeof t[a]?r[a]=i(e[a],t[a]):r[a]=e[a]}catch(e){(0,n.Z)("An error occurred while setting a property of a Configurable",e)}return r}catch(e){(0,n.Z)("An error occured while setting a Configurable",e)}}},6818:(e,t,r)=>{r.d(t,{Re:()=>i,gF:()=>o,q4:()=>n});const n="1.236.0",i="PROD",o="CDN"},385:(e,t,r)=>{r.d(t,{FN:()=>a,IF:()=>u,Nk:()=>f,Tt:()=>s,_A:()=>o,il:()=>n,pL:()=>c,v6:()=>i,w1:()=>d});const n="undefined"!=typeof window&&!!window.document,i="undefined"!=typeof WorkerGlobalScope&&("undefined"!=typeof self&&self instanceof WorkerGlobalScope&&self.navigator instanceof WorkerNavigator||"undefined"!=typeof globalThis&&globalThis instanceof WorkerGlobalScope&&globalThis.navigator instanceof WorkerNavigator),o=n?window:"undefined"!=typeof WorkerGlobalScope&&("undefined"!=typeof self&&self instanceof WorkerGlobalScope&&self||"undefined"!=typeof globalThis&&globalThis instanceof WorkerGlobalScope&&globalThis),a=""+o?.location,s=/iPad|iPhone|iPod/.test(navigator.userAgent),c=s&&"undefined"==typeof SharedWorker,u=(()=>{const e=navigator.userAgent.match(/Firefox[/\s](\d+\.\d+)/);return Array.isArray(e)&&e.length>=2?+e[1]:0})(),d=Boolean(n&&window.document.documentMode),f=!!navigator.sendBeacon},1117:(e,t,r)=>{r.d(t,{w:()=>o});var n=r(50);const i={agentIdentifier:"",ee:void 0};class o{constructor(e){try{if("object"!=typeof e)return(0,n.Z)("shared context requires an object as input");this.sharedContext={},Object.assign(this.sharedContext,i),Object.entries(e).forEach((e=>{let[t,r]=e;Object.keys(i).includes(t)&&(this.sharedContext[t]=r)}))}catch(e){(0,n.Z)("An error occured while setting SharedContext",e)}}}},8e3:(e,t,r)=>{r.d(t,{L:()=>d,R:()=>c});var n=r(2177),i=r(1284),o=r(4322),a=r(3325);const s={};function c(e,t){const r={staged:!1,priority:a.p[t]||0};u(e),s[e].get(t)||s[e].set(t,r)}function u(e){e&&(s[e]||(s[e]=new Map))}function d(){let e=arguments.length>0&&void 0!==arguments[0]?arguments[0]:"",t=arguments.length>1&&void 0!==arguments[1]?arguments[1]:"feature";if(u(e),!e||!s[e].get(t))return a(t);s[e].get(t).staged=!0;const r=[...s[e]];function a(t){const r=e?n.ee.get(e):n.ee,a=o.X.handlers;if(r.backlog&&a){var s=r.backlog[t],c=a[t];if(c){for(var u=0;s&&u {let[t,r]=e;return r.staged}))&&(r.sort(((e,t)=>e[1].priority-t[1].priority)),r.forEach((e=>{let[t]=e;a(t)})))}function f(e,t){var r=e[1];(0,i.D)(t[r],(function(t,r){var n=e[0];if(r[0]===n){var i=r[1],o=e[3],a=e[2];i.apply(o,a)}}))}},2177:(e,t,r)=>{r.d(t,{c:()=>f,ee:()=>u});var n=r(8632),i=r(2210),o=r(1284),a=r(5763),s="nr@context";let c=(0,n.fP)();var u;function d(){}function f(e){return(0,i.X)(e,s,l)}function l(){return new d}function h(){u.aborted=!0,u.backlog={}}c.ee?u=c.ee:(u=function e(t,r){var n={},c={},f={},g=!1;try{g=16===r.length&&(0,a.OP)(r).isolatedBacklog}catch(e){}var p={on:b,addEventListener:b,removeEventListener:y,emit:v,get:x,listeners:w,context:m,buffer:A,abort:h,aborted:!1,isBuffering:E,debugId:r,backlog:g?{}:t&&"object"==typeof t.backlog?t.backlog:{}};return p;function m(e){return e&&e instanceof d?e:e?(0,i.X)(e,s,l):l()}function v(e,r,n,i,o){if(!1!==o&&(o=!0),!u.aborted||i){t&&o&&t.emit(e,r,n);for(var a=m(n),s=w(e),d=s.length,f=0;fn,p:()=>i});var n=r(2177).ee.get("handle");function i(e,t,r,i,o){o?(o.buffer([e],i),o.emit(e,t,r)):(n.buffer([e],i),n.emit(e,t,r))}},4322:(e,t,r)=>{r.d(t,{X:()=>o});var n=r(5546);o.on=a;var i=o.handlers={};function o(e,t,r,o){a(o||n.E,i,e,t,r)}function a(e,t,r,i,o){o||(o="feature"),e||(e=n.E);var a=t[o]=t[o]||{};(a[r]=a[r]||[]).push([e,i])}},3239:(e,t,r)=>{r.d(t,{bP:()=>s,iz:()=>c,m$:()=>a});var n=r(385);let i=!1,o=!1;try{const e={get passive(){return i=!0,!1},get signal(){return o=!0,!1}};n._A.addEventListener("test",null,e),n._A.removeEventListener("test",null,e)}catch(e){}function a(e,t){return i||o?{capture:!!e,passive:i,signal:t}:!!e}function s(e,t){let r=arguments.length>2&&void 0!==arguments[2]&&arguments[2],n=arguments.length>3?arguments[3]:void 0;window.addEventListener(e,t,a(r,n))}function c(e,t){let r=arguments.length>2&&void 0!==arguments[2]&&arguments[2],n=arguments.length>3?arguments[3]:void 0;document.addEventListener(e,t,a(r,n))}},4402:(e,t,r)=>{r.d(t,{Ht:()=>u,M:()=>c,Rl:()=>a,ky:()=>s});var n=r(385);const i="xxxxxxxx-xxxx-4xxx-yxxx-xxxxxxxxxxxx";function o(e,t){return e?15&e[t]:16*Math.random()|0}function a(){const e=n._A?.crypto||n._A?.msCrypto;let t,r=0;return e&&e.getRandomValues&&(t=e.getRandomValues(new Uint8Array(31))),i.split("").map((e=>"x"===e?o(t,++r).toString(16):"y"===e?(3&o()|8).toString(16):e)).join("")}function s(e){const t=n._A?.crypto||n._A?.msCrypto;let r,i=0;t&&t.getRandomValues&&(r=t.getRandomValues(new Uint8Array(31)));const a=[];for(var s=0;s {r.d(t,{Bq:()=>n,Hb:()=>o,oD:()=>i});const n="NRBA",i=144e5,o=18e5},7894:(e,t,r)=>{function n(){return Math.round(performance.now())}r.d(t,{z:()=>n})},7243:(e,t,r)=>{r.d(t,{e:()=>o});var n=r(385),i={};function o(e){if(e in i)return i[e];if(0===(e||"").indexOf("data:"))return{protocol:"data"};let t;var r=n._A?.location,o={};if(n.il)t=document.createElement("a"),t.href=e;else try{t=new URL(e,r.href)}catch(e){return o}o.port=t.port;var a=t.href.split("://");!o.port&&a[1]&&(o.port=a[1].split("/")[0].split("@").pop().split(":")[1]),o.port&&"0"!==o.port||(o.port="https"===a[0]?"443":"80"),o.hostname=t.hostname||r.hostname,o.pathname=t.pathname,o.protocol=a[0],"/"!==o.pathname.charAt(0)&&(o.pathname="/"+o.pathname);var s=!t.protocol||":"===t.protocol||t.protocol===r.protocol,c=t.hostname===r.hostname&&t.port===r.port;return o.sameOrigin=s&&(!t.hostname||c),"/"===o.pathname&&(i[e]=o),o}},50:(e,t,r)=>{function n(e,t){"function"==typeof console.warn&&(console.warn("New Relic: ".concat(e)),t&&console.warn(t))}r.d(t,{Z:()=>n})},2587:(e,t,r)=>{r.d(t,{N:()=>c,T:()=>u});var n=r(2177),i=r(5546),o=r(8e3),a=r(3325);const s={stn:[a.D.sessionTrace],err:[a.D.jserrors,a.D.metrics],ins:[a.D.pageAction],spa:[a.D.spa],sr:[a.D.sessionReplay,a.D.sessionTrace]};function c(e,t){const r=n.ee.get(t);e&&"object"==typeof e&&(Object.entries(e).forEach((e=>{let[t,n]=e;void 0===u[t]&&(s[t]?s[t].forEach((e=>{n?(0,i.p)("feat-"+t,[],void 0,e,r):(0,i.p)("block-"+t,[],void 0,e,r),(0,i.p)("rumresp-"+t,[Boolean(n)],void 0,e,r)})):n&&(0,i.p)("feat-"+t,[],void 0,void 0,r),u[t]=Boolean(n))})),Object.keys(s).forEach((e=>{void 0===u[e]&&(s[e]?.forEach((t=>(0,i.p)("rumresp-"+e,[!1],void 0,t,r))),u[e]=!1)})),(0,o.L)(t,a.D.pageViewEvent))}const u={}},2210:(e,t,r)=>{r.d(t,{X:()=>i});var n=Object.prototype.hasOwnProperty;function i(e,t,r){if(n.call(e,t))return e[t];var i=r();if(Object.defineProperty&&Object.keys)try{return Object.defineProperty(e,t,{value:i,writable:!0,enumerable:!1}),i}catch(e){}return e[t]=i,i}},1284:(e,t,r)=>{r.d(t,{D:()=>n});const n=(e,t)=>Object.entries(e||{}).map((e=>{let[r,n]=e;return t(r,n)}))},4351:(e,t,r)=>{r.d(t,{P:()=>o});var n=r(2177);const i=()=>{const e=new WeakSet;return(t,r)=>{if("object"==typeof r&&null!==r){if(e.has(r))return;e.add(r)}return r}};function o(e){try{return JSON.stringify(e,i())}catch(e){try{n.ee.emit("internal-error",[e])}catch(e){}}}},3960:(e,t,r)=>{r.d(t,{K:()=>a,b:()=>o});var n=r(3239);function i(){return"undefined"==typeof document||"complete"===document.readyState}function o(e,t){if(i())return e();(0,n.bP)("load",e,t)}function a(e){if(i())return e();(0,n.iz)("DOMContentLoaded",e)}},8632:(e,t,r)=>{r.d(t,{EZ:()=>u,Qy:()=>c,ce:()=>o,fP:()=>a,gG:()=>d,mF:()=>s});var n=r(7894),i=r(385);const o={beacon:"bam.nr-data.net",errorBeacon:"bam.nr-data.net"};function a(){return i._A.NREUM||(i._A.NREUM={}),void 0===i._A.newrelic&&(i._A.newrelic=i._A.NREUM),i._A.NREUM}function s(){let e=a();return e.o||(e.o={ST:i._A.setTimeout,SI:i._A.setImmediate,CT:i._A.clearTimeout,XHR:i._A.XMLHttpRequest,REQ:i._A.Request,EV:i._A.Event,PR:i._A.Promise,MO:i._A.MutationObserver,FETCH:i._A.fetch}),e}function c(e,t,r){let i=a();const o=i.initializedAgents||{},s=o[e]||{};return Object.keys(s).length||(s.initializedAt={ms:(0,n.z)(),date:new Date}),i.initializedAgents={...o,[e]:{...s,[r]:t}},i}function u(e,t){a()[e]=t}function d(){return function(){let e=a();const t=e.info||{};e.info={beacon:o.beacon,errorBeacon:o.errorBeacon,...t}}(),function(){let e=a();const t=e.init||{};e.init={...t}}(),s(),function(){let e=a();const t=e.loader_config||{};e.loader_config={...t}}(),a()}},7956:(e,t,r)=>{r.d(t,{N:()=>i});var n=r(3239);function i(e){let t=arguments.length>1&&void 0!==arguments[1]&&arguments[1],r=arguments.length>2?arguments[2]:void 0,i=arguments.length>3?arguments[3]:void 0;return void(0,n.iz)("visibilitychange",(function(){if(t)return void("hidden"==document.visibilityState&&e());e(document.visibilityState)}),r,i)}},1214:(e,t,r)=>{r.d(t,{em:()=>v,u5:()=>N,QU:()=>S,_L:()=>I,Gm:()=>L,Lg:()=>M,gy:()=>U,BV:()=>Q,Kf:()=>ee});var n=r(2177);const i="nr@original";var o=Object.prototype.hasOwnProperty,a=!1;function s(e,t){return e||(e=n.ee),r.inPlace=function(e,t,n,i,o){n||(n="");var a,s,c,u="-"===n.charAt(0);for(c=0;c 2?n-2:0),o=2;o {r(A[T],e,w),r(E[T],e,w)})),r(l._A,"fetch",y),t.on(y+"end",(function(e,r){var n=this;if(r){var i=r.headers.get("content-length");null!==i&&(n.rxSize=i),t.emit(y+"done",[null,r],n)}else t.emit(y+"done",[e],n)})),t}const O={},j=["pushState","replaceState"];function S(e){const t=function(e){return(e||n.ee).get("history")}(e);return!l.il||O[t.debugId]++||(O[t.debugId]=1,s(t).inPlace(window.history,j,"-")),t}var P=r(3239);const C={},R=["appendChild","insertBefore","replaceChild"];function I(e){const t=function(e){return(e||n.ee).get("jsonp")}(e);if(!l.il||C[t.debugId])return t;C[t.debugId]=!0;var r=s(t),i=/[?&](?:callback|cb)=([^&#]+)/,o=/(.*)\.([^.]+)/,a=/^(\w+)(\.|$)(.*)$/;function c(e,t){var r=e.match(a),n=r[1],i=r[3];return i?c(i,t[n]):t[n]}return r.inPlace(Node.prototype,R,"dom-"),t.on("dom-start",(function(e){!function(e){if(!e||"string"!=typeof e.nodeName||"script"!==e.nodeName.toLowerCase())return;if("function"!=typeof e.addEventListener)return;var n=(a=e.src,s=a.match(i),s?s[1]:null);var a,s;if(!n)return;var u=function(e){var t=e.match(o);if(t&&t.length>=3)return{key:t[2],parent:c(t[1],window)};return{key:e,parent:window}}(n);if("function"!=typeof u.parent[u.key])return;var d={};function f(){t.emit("jsonp-end",[],d),e.removeEventListener("load",f,(0,P.m$)(!1)),e.removeEventListener("error",l,(0,P.m$)(!1))}function l(){t.emit("jsonp-error",[],d),t.emit("jsonp-end",[],d),e.removeEventListener("load",f,(0,P.m$)(!1)),e.removeEventListener("error",l,(0,P.m$)(!1))}r.inPlace(u.parent,[u.key],"cb-",d),e.addEventListener("load",f,(0,P.m$)(!1)),e.addEventListener("error",l,(0,P.m$)(!1)),t.emit("new-jsonp",[e.src],d)}(e[0])})),t}var k=r(5763);const H={};function L(e){const t=function(e){return(e||n.ee).get("mutation")}(e);if(!l.il||H[t.debugId])return t;H[t.debugId]=!0;var r=s(t),i=k.Yu.MO;return i&&(window.MutationObserver=function(e){return this instanceof i?new i(r(e,"fn-")):i.apply(this,arguments)},MutationObserver.prototype=i.prototype),t}const z={};function M(e){const t=function(e){return(e||n.ee).get("promise")}(e);if(z[t.debugId])return t;z[t.debugId]=!0;var r=n.c,o=s(t),a=k.Yu.PR;return a&&function(){function e(r){var n=t.context(),i=o(r,"executor-",n,null,!1);const s=Reflect.construct(a,[i],e);return t.context(s).getCtx=function(){return n},s}l._A.Promise=e,Object.defineProperty(e,"name",{value:"Promise"}),e.toString=function(){return a.toString()},Object.setPrototypeOf(e,a),["all","race"].forEach((function(r){const n=a[r];e[r]=function(e){let i=!1;[...e||[]].forEach((e=>{this.resolve(e).then(a("all"===r),a(!1))}));const o=n.apply(this,arguments);return o;function a(e){return function(){t.emit("propagate",[null,!i],o,!1,!1),i=i||!e}}}})),["resolve","reject"].forEach((function(r){const n=a[r];e[r]=function(e){const r=n.apply(this,arguments);return e!==r&&t.emit("propagate",[e,!0],r,!1,!1),r}})),e.prototype=a.prototype;const n=a.prototype.then;a.prototype.then=function(){var e=this,i=r(e);i.promise=e;for(var a=arguments.length,s=new Array(a),c=0;c e())),t};function m(e,t){i.inPlace(t,["onreadystatechange"],"fn-",E)}function b(){var e=this,t=r.context(e);e.readyState>3&&!t.resolved&&(t.resolved=!0,r.emit("xhr-resolved",[],e)),i.inPlace(e,f,"fn-",E)}if(function(e,t){for(var r in e)t[r]=e[r]}(o,p),p.prototype=o.prototype,i.inPlace(p.prototype,J,"-xhr-",E),r.on("send-xhr-start",(function(e,t){m(e,t),function(e){h.push(e),a&&(y?y.then(A):u?u(A):(w=-w,x.data=w))}(t)})),r.on("open-xhr-start",m),a){var y=c&&c.resolve();if(!u&&!c){var w=1,x=document.createTextNode(w);new a(A).observe(x,{characterData:!0})}}else t.on("fn-end",(function(e){e[0]&&e[0].type===d||A()}));function A(){for(var e=0;e {r.d(t,{t:()=>n});const n=r(3325).D.ajax},6660:(e,t,r)=>{r.d(t,{A:()=>i,t:()=>n});const n=r(3325).D.jserrors,i="nr@seenError"},3081:(e,t,r)=>{r.d(t,{gF:()=>o,mY:()=>i,t9:()=>n,vz:()=>s,xS:()=>a});const n=r(3325).D.metrics,i="sm",o="cm",a="storeSupportabilityMetrics",s="storeEventMetrics"},4649:(e,t,r)=>{r.d(t,{t:()=>n});const n=r(3325).D.pageAction},7633:(e,t,r)=>{r.d(t,{Dz:()=>i,OJ:()=>a,qw:()=>o,t9:()=>n});const n=r(3325).D.pageViewEvent,i="firstbyte",o="domcontent",a="windowload"},9251:(e,t,r)=>{r.d(t,{t:()=>n});const n=r(3325).D.pageViewTiming},3614:(e,t,r)=>{r.d(t,{BST_RESOURCE:()=>i,END:()=>s,FEATURE_NAME:()=>n,FN_END:()=>u,FN_START:()=>c,PUSH_STATE:()=>d,RESOURCE:()=>o,START:()=>a});const n=r(3325).D.sessionTrace,i="bstResource",o="resource",a="-start",s="-end",c="fn"+a,u="fn"+s,d="pushState"},7836:(e,t,r)=>{r.d(t,{BODY:()=>A,CB_END:()=>E,CB_START:()=>u,END:()=>x,FEATURE_NAME:()=>i,FETCH:()=>_,FETCH_BODY:()=>v,FETCH_DONE:()=>m,FETCH_START:()=>p,FN_END:()=>c,FN_START:()=>s,INTERACTION:()=>l,INTERACTION_API:()=>d,INTERACTION_EVENTS:()=>o,JSONP_END:()=>b,JSONP_NODE:()=>g,JS_TIME:()=>T,MAX_TIMER_BUDGET:()=>a,REMAINING:()=>f,SPA_NODE:()=>h,START:()=>w,originalSetTimeout:()=>y});var n=r(5763);const i=r(3325).D.spa,o=["click","submit","keypress","keydown","keyup","change"],a=999,s="fn-start",c="fn-end",u="cb-start",d="api-ixn-",f="remaining",l="interaction",h="spaNode",g="jsonpNode",p="fetch-start",m="fetch-done",v="fetch-body-",b="jsonp-end",y=n.Yu.ST,w="-start",x="-end",A="-body",E="cb"+x,T="jsTime",_="fetch"},5938:(e,t,r)=>{r.d(t,{W:()=>o});var n=r(5763),i=r(2177);class o{constructor(e,t,r){this.agentIdentifier=e,this.aggregator=t,this.ee=i.ee.get(e,(0,n.OP)(this.agentIdentifier).isolatedBacklog),this.featureName=r,this.blocked=!1}}},9144:(e,t,r)=>{r.d(t,{j:()=>m});var n=r(3325),i=r(5763),o=r(5546),a=r(2177),s=r(7894),c=r(8e3),u=r(3960),d=r(385),f=r(50),l=r(3081),h=r(8632);function g(){const e=(0,h.gG)();["setErrorHandler","finished","addToTrace","inlineHit","addRelease","addPageAction","setCurrentRouteName","setPageViewName","setCustomAttribute","interaction","noticeError","setUserId"].forEach((t=>{e[t]=function(){for(var r=arguments.length,n=new Array(r),i=0;i 1?r-1:0),i=1;i {e.exposed&&e.api[t]&&o.push(e.api[t](...n))})),o.length>1?o:o[0]}(t,...n)}}))}var p=r(2587);function m(e){let t=arguments.length>1&&void 0!==arguments[1]?arguments[1]:{},m=arguments.length>2?arguments[2]:void 0,v=arguments.length>3?arguments[3]:void 0,{init:b,info:y,loader_config:w,runtime:x={loaderType:m},exposed:A=!0}=t;const E=(0,h.gG)();y||(b=E.init,y=E.info,w=E.loader_config),(0,i.Dg)(e,b||{}),(0,i.GE)(e,w||{}),(0,i.sU)(e,x),y.jsAttributes??={},d.v6&&(y.jsAttributes.isWorker=!0),(0,i.CX)(e,y),g();const T=function(e,t){t||(0,c.R)(e,"api");const h={};var g=a.ee.get(e),p=g.get("tracer"),m="api-",v=m+"ixn-";function b(t,r,n,o){const a=(0,i.C5)(e);return null===r?delete a.jsAttributes[t]:(0,i.CX)(e,{...a,jsAttributes:{...a.jsAttributes,[t]:r}}),x(m,n,!0,o||null===r?"session":void 0)(t,r)}function y(){}["setErrorHandler","finished","addToTrace","inlineHit","addRelease"].forEach((e=>h[e]=x(m,e,!0,"api"))),h.addPageAction=x(m,"addPageAction",!0,n.D.pageAction),h.setCurrentRouteName=x(m,"routeName",!0,n.D.spa),h.setPageViewName=function(t,r){if("string"==typeof t)return"/"!==t.charAt(0)&&(t="/"+t),(0,i.OP)(e).customTransaction=(r||"http://custom.transaction")+t,x(m,"setPageViewName",!0)()},h.setCustomAttribute=function(e,t){let r=arguments.length>2&&void 0!==arguments[2]&&arguments[2];if("string"==typeof e){if(["string","number"].includes(typeof t)||null===t)return b(e,t,"setCustomAttribute",r);(0,f.Z)("Failed to execute setCustomAttribute.\nNon-null value must be a string or number type, but a type of was provided."))}else(0,f.Z)("Failed to execute setCustomAttribute.\nName must be a string type, but a type of was provided."))},h.setUserId=function(e){if("string"==typeof e||null===e)return b("enduser.id",e,"setUserId",!0);(0,f.Z)("Failed to execute setUserId.\nNon-null value must be a string type, but a type of was provided."))},h.interaction=function(){return(new y).get()};var w=y.prototype={createTracer:function(e,t){var r={},i=this,a="function"==typeof t;return(0,o.p)(v+"tracer",[(0,s.z)(),e,r],i,n.D.spa,g),function(){if(p.emit((a?"":"no-")+"fn-start",[(0,s.z)(),i,a],r),a)try{return t.apply(this,arguments)}catch(e){throw p.emit("fn-err",[arguments,this,"string"==typeof e?new Error(e):e],r),e}finally{p.emit("fn-end",[(0,s.z)()],r)}}}};function x(e,t,r,i){return function(){return(0,o.p)(l.xS,["API/"+t+"/called"],void 0,n.D.metrics,g),i&&(0,o.p)(e+t,[(0,s.z)(),...arguments],r?null:this,i,g),r?void 0:this}}function A(){r.e(439).then(r.bind(r,7438)).then((t=>{let{setAPI:r}=t;r(e),(0,c.L)(e,"api")})).catch((()=>(0,f.Z)("Downloading runtime APIs failed...")))}return["actionText","setName","setAttribute","save","ignore","onEnd","getContext","end","get"].forEach((e=>{w[e]=x(v,e,void 0,n.D.spa)})),h.noticeError=function(e,t){"string"==typeof e&&(e=new Error(e)),(0,o.p)(l.xS,["API/noticeError/called"],void 0,n.D.metrics,g),(0,o.p)("err",[e,(0,s.z)(),!1,t],void 0,n.D.jserrors,g)},d.il?(0,u.b)((()=>A()),!0):A(),h}(e,v);return(0,h.Qy)(e,T,"api"),(0,h.Qy)(e,A,"exposed"),(0,h.EZ)("activatedFeatures",p.T),T}},3325:(e,t,r)=>{r.d(t,{D:()=>n,p:()=>i});const n={ajax:"ajax",jserrors:"jserrors",metrics:"metrics",pageAction:"page_action",pageViewEvent:"page_view_event",pageViewTiming:"page_view_timing",sessionReplay:"session_replay",sessionTrace:"session_trace",spa:"spa"},i={[n.pageViewEvent]:1,[n.pageViewTiming]:2,[n.metrics]:3,[n.jserrors]:4,[n.ajax]:5,[n.sessionTrace]:6,[n.pageAction]:7,[n.spa]:8,[n.sessionReplay]:9}}},n={};function i(e){var t=n[e];if(void 0!==t)return t.exports;var o=n[e]={exports:{}};return r[e](o,o.exports,i),o.exports}i.m=r,i.d=(e,t)=>{for(var r in t)i.o(t,r)&&!i.o(e,r)&&Object.defineProperty(e,r,{enumerable:!0,get:t[r]})},i.f={},i.e=e=>Promise.all(Object.keys(i.f).reduce(((t,r)=>(i.f[r](e,t),t)),[])),i.u=e=>(({78:"page_action-aggregate",147:"metrics-aggregate",242:"session-manager",317:"jserrors-aggregate",348:"page_view_timing-aggregate",412:"lazy-feature-loader",439:"async-api",538:"recorder",590:"session_replay-aggregate",675:"compressor",733:"session_trace-aggregate",786:"page_view_event-aggregate",873:"spa-aggregate",898:"ajax-aggregate"}[e]||e)+"."+{78:"ac76d497",147:"3dc53903",148:"1a20d5fe",242:"2a64278a",317:"49e41428",348:"bd6de33a",412:"2f55ce66",439:"30bd804e",538:"1b18459f",590:"cf0efb30",675:"ae9f91a8",733:"83105561",786:"06482edd",860:"03a8b7a5",873:"e6b09d52",898:"998ef92b"}[e]+"-1.236.0.min.js"),i.o=(e,t)=>Object.prototype.hasOwnProperty.call(e,t),e={},t="NRBA:",i.l=(r,n,o,a)=>{if(e[r])e[r].push(n);else{var s,c;if(void 0!==o)for(var u=document.getElementsByTagName("script"),d=0;d {s.onerror=s.onload=null,clearTimeout(h);var i=e[r];if(delete e[r],s.parentNode&&s.parentNode.removeChild(s),i&&i.forEach((e=>e(n))),t)return t(n)},h=setTimeout(l.bind(null,void 0,{type:"timeout",target:s}),12e4);s.onerror=l.bind(null,s.onerror),s.onload=l.bind(null,s.onload),c&&document.head.appendChild(s)}},i.r=e=>{"undefined"!=typeof Symbol&&Symbol.toStringTag&&Object.defineProperty(e,Symbol.toStringTag,{value:"Module"}),Object.defineProperty(e,"__esModule",{value:!0})},i.j=364,i.p="https://js-agent.newrelic.com/",(()=>{var e={364:0,953:0};i.f.j=(t,r)=>{var n=i.o(e,t)?e[t]:void 0;if(0!==n)if(n)r.push(n[2]);else{var o=new Promise(((r,i)=>n=e[t]=[r,i]));r.push(n[2]=o);var a=i.p+i.u(t),s=new Error;i.l(a,(r=>{if(i.o(e,t)&&(0!==(n=e[t])&&(e[t]=void 0),n)){var o=r&&("load"===r.type?"missing":r.type),a=r&&r.target&&r.target.src;s.message="Loading chunk "+t+" failed.\n("+o+": "+a+")",s.name="ChunkLoadError",s.type=o,s.request=a,n[1](s)}}),"chunk-"+t,t)}};var t=(t,r)=>{var n,o,[a,s,c]=r,u=0;if(a.some((t=>0!==e[t]))){for(n in s)i.o(s,n)&&(i.m[n]=s[n]);if(c)c(i)}for(t&&t(r);u {i.r(o);var e=i(3325),t=i(5763);const r=Object.values(e.D);function n(e){const n={};return r.forEach((r=>{n[r]=function(e,r){return!1!==(0,t.Mt)(r,"".concat(e,".enabled"))}(r,e)})),n}var a=i(9144);var s=i(5546),c=i(385),u=i(8e3),d=i(5938),f=i(3960),l=i(50);class h extends d.W{constructor(e,t,r){let n=!(arguments.length>3&&void 0!==arguments[3])||arguments[3];super(e,t,r),this.auto=n,this.abortHandler,this.featAggregate,this.onAggregateImported,n&&(0,u.R)(e,r)}importAggregator(){let e=arguments.length>0&&void 0!==arguments[0]?arguments[0]:{};if(this.featAggregate||!this.auto)return;const r=c.il&&!0===(0,t.Mt)(this.agentIdentifier,"privacy.cookies_enabled");let n;this.onAggregateImported=new Promise((e=>{n=e}));const o=async()=>{let t;try{if(r){const{setupAgentSession:e}=await Promise.all([i.e(860),i.e(242)]).then(i.bind(i,3228));t=e(this.agentIdentifier)}}catch(e){(0,l.Z)("A problem occurred when starting up session manager. This page will not start or extend any session.",e)}try{if(!this.shouldImportAgg(this.featureName,t))return void(0,u.L)(this.agentIdentifier,this.featureName);const{lazyFeatureLoader:r}=await i.e(412).then(i.bind(i,8582)),{Aggregate:o}=await r(this.featureName,"aggregate");this.featAggregate=new o(this.agentIdentifier,this.aggregator,e),n(!0)}catch(e){(0,l.Z)("Downloading and initializing ".concat(this.featureName," failed..."),e),this.abortHandler?.(),n(!1)}};c.il?(0,f.b)((()=>o()),!0):o()}shouldImportAgg(r,n){return r!==e.D.sessionReplay||!1!==(0,t.Mt)(this.agentIdentifier,"session_trace.enabled")&&(!!n?.isNew||!!n?.state.sessionReplay)}}var g=i(7633),p=i(7894);class m extends h{static featureName=g.t9;constructor(r,n){let i=!(arguments.length>2&&void 0!==arguments[2])||arguments[2];if(super(r,n,g.t9,i),("undefined"==typeof PerformanceNavigationTiming||c.Tt)&&"undefined"!=typeof PerformanceTiming){const n=(0,t.OP)(r);n[g.Dz]=Math.max(Date.now()-n.offset,0),(0,f.K)((()=>n[g.qw]=Math.max((0,p.z)()-n[g.Dz],0))),(0,f.b)((()=>{const t=(0,p.z)();n[g.OJ]=Math.max(t-n[g.Dz],0),(0,s.p)("timing",["load",t],void 0,e.D.pageViewTiming,this.ee)}))}this.importAggregator()}}var v=i(1117),b=i(1284);class y extends v.w{constructor(e){super(e),this.aggregatedData={}}store(e,t,r,n,i){var o=this.getBucket(e,t,r,i);return o.metrics=function(e,t){t||(t={count:0});return t.count+=1,(0,b.D)(e,(function(e,r){t[e]=w(r,t[e])})),t}(n,o.metrics),o}merge(e,t,r,n,i){var o=this.getBucket(e,t,n,i);if(o.metrics){var a=o.metrics;a.count+=r.count,(0,b.D)(r,(function(e,t){if("count"!==e){var n=a[e],i=r[e];i&&!i.c?a[e]=w(i.t,n):a[e]=function(e,t){if(!t)return e;t.c||(t=x(t.t));return t.min=Math.min(e.min,t.min),t.max=Math.max(e.max,t.max),t.t+=e.t,t.sos+=e.sos,t.c+=e.c,t}(i,a[e])}}))}else o.metrics=r}storeMetric(e,t,r,n){var i=this.getBucket(e,t,r);return i.stats=w(n,i.stats),i}getBucket(e,t,r,n){this.aggregatedData[e]||(this.aggregatedData[e]={});var i=this.aggregatedData[e][t];return i||(i=this.aggregatedData[e][t]={params:r||{}},n&&(i.custom=n)),i}get(e,t){return t?this.aggregatedData[e]&&this.aggregatedData[e][t]:this.aggregatedData[e]}take(e){for(var t={},r="",n=!1,i=0;i t.max&&(t.max=e),e 2&&void 0!==arguments[2])||arguments[2];super(e,r,j.t,n),c.il&&((0,t.OP)(e).initHidden=Boolean("hidden"===document.visibilityState),(0,N.N)((()=>(0,s.p)("docHidden",[(0,p.z)()],void 0,j.t,this.ee)),!0),(0,O.bP)("pagehide",(()=>(0,s.p)("winPagehide",[(0,p.z)()],void 0,j.t,this.ee))),this.importAggregator())}}var P=i(3081);class C extends h{static featureName=P.t9;constructor(e,t){let r=!(arguments.length>2&&void 0!==arguments[2])||arguments[2];super(e,t,P.t9,r),this.importAggregator()}}var R,I=i(2210),k=i(1214),H=i(2177),L={};try{R=localStorage.getItem("__nr_flags").split(","),console&&"function"==typeof console.log&&(L.console=!0,-1!==R.indexOf("dev")&&(L.dev=!0),-1!==R.indexOf("nr_dev")&&(L.nrDev=!0))}catch(e){}function z(e){try{L.console&&z(e)}catch(e){}}L.nrDev&&H.ee.on("internal-error",(function(e){z(e.stack)})),L.dev&&H.ee.on("fn-err",(function(e,t,r){z(r.stack)})),L.dev&&(z("NR AGENT IN DEVELOPMENT MODE"),z("flags: "+(0,b.D)(L,(function(e,t){return e})).join(", ")));var M=i(6660);class B extends h{static featureName=M.t;constructor(r,n){let i=!(arguments.length>2&&void 0!==arguments[2])||arguments[2];super(r,n,M.t,i),this.skipNext=0;try{this.removeOnAbort=new AbortController}catch(e){}const o=this;o.ee.on("fn-start",(function(e,t,r){o.abortHandler&&(o.skipNext+=1)})),o.ee.on("fn-err",(function(t,r,n){o.abortHandler&&!n[M.A]&&((0,I.X)(n,M.A,(function(){return!0})),this.thrown=!0,(0,s.p)("err",[n,(0,p.z)()],void 0,e.D.jserrors,o.ee))})),o.ee.on("fn-end",(function(){o.abortHandler&&!this.thrown&&o.skipNext>0&&(o.skipNext-=1)})),o.ee.on("internal-error",(function(t){(0,s.p)("ierr",[t,(0,p.z)(),!0],void 0,e.D.jserrors,o.ee)})),this.origOnerror=c._A.onerror,c._A.onerror=this.onerrorHandler.bind(this),c._A.addEventListener("unhandledrejection",(t=>{const r=function(e){let t="Unhandled Promise Rejection: ";if(e instanceof Error)try{return e.message=t+e.message,e}catch(t){return e}if(void 0===e)return new Error(t);try{return new Error(t+(0,D.P)(e))}catch(e){return new Error(t)}}(t.reason);(0,s.p)("err",[r,(0,p.z)(),!1,{unhandledPromiseRejection:1}],void 0,e.D.jserrors,this.ee)}),(0,O.m$)(!1,this.removeOnAbort?.signal)),(0,k.gy)(this.ee),(0,k.BV)(this.ee),(0,k.em)(this.ee),(0,t.OP)(r).xhrWrappable&&(0,k.Kf)(this.ee),this.abortHandler=this.#e,this.importAggregator()}#e(){this.removeOnAbort?.abort(),this.abortHandler=void 0}onerrorHandler(t,r,n,i,o){"function"==typeof this.origOnerror&&this.origOnerror(...arguments);try{this.skipNext?this.skipNext-=1:(0,s.p)("err",[o||new F(t,r,n),(0,p.z)()],void 0,e.D.jserrors,this.ee)}catch(t){try{(0,s.p)("ierr",[t,(0,p.z)(),!0],void 0,e.D.jserrors,this.ee)}catch(e){}}return!1}}function F(e,t,r){this.message=e||"Uncaught error with no additional information",this.sourceURL=t,this.line=r}let U=1;const q="nr@id";function G(e){const t=typeof e;return!e||"object"!==t&&"function"!==t?-1:e===c._A?0:(0,I.X)(e,q,(function(){return U++}))}function V(e){if("string"==typeof e&&e.length)return e.length;if("object"==typeof e){if("undefined"!=typeof ArrayBuffer&&e instanceof ArrayBuffer&&e.byteLength)return e.byteLength;if("undefined"!=typeof Blob&&e instanceof Blob&&e.size)return e.size;if(!("undefined"!=typeof FormData&&e instanceof FormData))try{return(0,D.P)(e).length}catch(e){return}}}var X=i(7243);class W{constructor(e){this.agentIdentifier=e,this.generateTracePayload=this.generateTracePayload.bind(this),this.shouldGenerateTrace=this.shouldGenerateTrace.bind(this)}generateTracePayload(e){if(!this.shouldGenerateTrace(e))return null;var r=(0,t.DL)(this.agentIdentifier);if(!r)return null;var n=(r.accountID||"").toString()||null,i=(r.agentID||"").toString()||null,o=(r.trustKey||"").toString()||null;if(!n||!i)return null;var a=(0,_.M)(),s=(0,_.Ht)(),c=Date.now(),u={spanId:a,traceId:s,timestamp:c};return(e.sameOrigin||this.isAllowedOrigin(e)&&this.useTraceContextHeadersForCors())&&(u.traceContextParentHeader=this.generateTraceContextParentHeader(a,s),u.traceContextStateHeader=this.generateTraceContextStateHeader(a,c,n,i,o)),(e.sameOrigin&&!this.excludeNewrelicHeader()||!e.sameOrigin&&this.isAllowedOrigin(e)&&this.useNewrelicHeaderForCors())&&(u.newrelicHeader=this.generateTraceHeader(a,s,c,n,i,o)),u}generateTraceContextParentHeader(e,t){return"00-"+t+"-"+e+"-01"}generateTraceContextStateHeader(e,t,r,n,i){return i+"@nr=0-1-"+r+"-"+n+"-"+e+"----"+t}generateTraceHeader(e,t,r,n,i,o){if(!("function"==typeof c._A?.btoa))return null;var a={v:[0,1],d:{ty:"Browser",ac:n,ap:i,id:e,tr:t,ti:r}};return o&&n!==o&&(a.d.tk=o),btoa((0,D.P)(a))}shouldGenerateTrace(e){return this.isDtEnabled()&&this.isAllowedOrigin(e)}isAllowedOrigin(e){var r=!1,n={};if((0,t.Mt)(this.agentIdentifier,"distributed_tracing")&&(n=(0,t.P_)(this.agentIdentifier).distributed_tracing),e.sameOrigin)r=!0;else if(n.allowed_origins instanceof Array)for(var i=0;i 2&&void 0!==arguments[2])||arguments[2];super(r,n,Z.t,i),(0,t.OP)(r).xhrWrappable&&(this.dt=new W(r),this.handler=(e,t,r,n)=>(0,s.p)(e,t,r,n,this.ee),(0,k.u5)(this.ee),(0,k.Kf)(this.ee),function(r,n,i,o){function a(e){var t=this;t.totalCbs=0,t.called=0,t.cbTime=0,t.end=E,t.ended=!1,t.xhrGuids={},t.lastSize=null,t.loadCaptureCalled=!1,t.params=this.params||{},t.metrics=this.metrics||{},e.addEventListener("load",(function(r){_(t,e)}),(0,O.m$)(!1)),c.IF||e.addEventListener("progress",(function(e){t.lastSize=e.loaded}),(0,O.m$)(!1))}function s(e){this.params={method:e[0]},T(this,e[1]),this.metrics={}}function u(e,n){var i=(0,t.DL)(r);i.xpid&&this.sameOrigin&&n.setRequestHeader("X-NewRelic-ID",i.xpid);var a=o.generateTracePayload(this.parsedOrigin);if(a){var s=!1;a.newrelicHeader&&(n.setRequestHeader("newrelic",a.newrelicHeader),s=!0),a.traceContextParentHeader&&(n.setRequestHeader("traceparent",a.traceContextParentHeader),a.traceContextStateHeader&&n.setRequestHeader("tracestate",a.traceContextStateHeader),s=!0),s&&(this.dt=a)}}function d(e,t){var r=this.metrics,i=e[0],o=this;if(r&&i){var a=V(i);a&&(r.txSize=a)}this.startTime=(0,p.z)(),this.listener=function(e){try{"abort"!==e.type||o.loadCaptureCalled||(o.params.aborted=!0),("load"!==e.type||o.called===o.totalCbs&&(o.onloadCalled||"function"!=typeof t.onload)&&"function"==typeof o.end)&&o.end(t)}catch(e){try{n.emit("internal-error",[e])}catch(e){}}};for(var s=0;s 1?e[1]=i:e.push(i)}else e[0]&&e[0].headers&&s(e[0].headers,n)&&(this.dt=n);function s(e,t){var r=!1;return t.newrelicHeader&&(e.set("newrelic",t.newrelicHeader),r=!0),t.traceContextParentHeader&&(e.set("traceparent",t.traceContextParentHeader),t.traceContextStateHeader&&e.set("tracestate",t.traceContextStateHeader),r=!0),r}}function x(e,t){this.params={},this.metrics={},this.startTime=(0,p.z)(),this.dt=t,e.length>=1&&(this.target=e[0]),e.length>=2&&(this.opts=e[1]);var r,n=this.opts||{},i=this.target;"string"==typeof i?r=i:"object"==typeof i&&i instanceof Y?r=i.url:c._A?.URL&&"object"==typeof i&&i instanceof URL&&(r=i.href),T(this,r);var o=(""+(i&&i instanceof Y&&i.method||n.method||"GET")).toUpperCase();this.params.method=o,this.txSize=V(n.body)||0}function A(t,r){var n;this.endTime=(0,p.z)(),this.params||(this.params={}),this.params.status=r?r.status:0,"string"==typeof this.rxSize&&this.rxSize.length>0&&(n=+this.rxSize);var o={txSize:this.txSize,rxSize:n,duration:(0,p.z)()-this.startTime};i("xhr",[this.params,o,this.startTime,this.endTime,"fetch"],this,e.D.ajax)}function E(t){var r=this.params,n=this.metrics;if(!this.ended){this.ended=!0;for(var o=0;o 2&&void 0!==arguments[2])||arguments[2];super(e,t,we.t,r),this.importAggregator()}}new class{constructor(e){let t=arguments.length>1&&void 0!==arguments[1]?arguments[1]:(0,_.ky)(16);c._A?(this.agentIdentifier=t,this.sharedAggregator=new y({agentIdentifier:this.agentIdentifier}),this.features={},this.desiredFeatures=new Set(e.features||[]),this.desiredFeatures.add(m),Object.assign(this,(0,a.j)(this.agentIdentifier,e,e.loaderType||"agent")),this.start()):(0,l.Z)("Failed to initial the agent. Could not determine the runtime environment.")}get config(){return{info:(0,t.C5)(this.agentIdentifier),init:(0,t.P_)(this.agentIdentifier),loader_config:(0,t.DL)(this.agentIdentifier),runtime:(0,t.OP)(this.agentIdentifier)}}start(){const t="features";try{const r=n(this.agentIdentifier),i=[...this.desiredFeatures];i.sort(((t,r)=>e.p[t.featureName]-e.p[r.featureName])),i.forEach((t=>{if(r[t.featureName]||t.featureName===e.D.pageViewEvent){const n=function(t){switch(t){case e.D.ajax:return[e.D.jserrors];case e.D.sessionTrace:return[e.D.ajax,e.D.pageViewEvent];case e.D.sessionReplay:return[e.D.sessionTrace];case e.D.pageViewTiming:return[e.D.pageViewEvent];default:return[]}}(t.featureName);n.every((e=>r[e]))||(0,l.Z)("".concat(t.featureName," is enabled but one or more dependent features has been disabled (").concat((0,D.P)(n),"). This may cause unintended consequences or missing data...")),this.features[t.featureName]=new t(this.agentIdentifier,this.sharedAggregator)}})),(0,T.Qy)(this.agentIdentifier,this.features,t)}catch(e){(0,l.Z)("Failed to initialize all enabled instrument classes (agent aborted) -",e);for(const e in this.features)this.features[e].abortHandler?.();const r=(0,T.fP)();return delete r.initializedAgents[this.agentIdentifier]?.api,delete r.initializedAgents[this.agentIdentifier]?.[t],delete this.sharedAggregator,r.ee?.abort(),delete r.ee?.get(this.agentIdentifier),!1}}}({features:[J,m,S,class extends h{static featureName=oe;constructor(t,r){if(super(t,r,oe,!(arguments.length>2&&void 0!==arguments[2])||arguments[2]),!c.il)return;const n=this.ee;let i;(0,k.QU)(n),this.eventsEE=(0,k.em)(n),this.eventsEE.on(se,(function(e,t){this.bstStart=(0,p.z)()})),this.eventsEE.on(ae,(function(t,r){(0,s.p)("bst",[t[0],r,this.bstStart,(0,p.z)()],void 0,e.D.sessionTrace,n)})),n.on(ce+ne,(function(e){this.time=(0,p.z)(),this.startPath=location.pathname+location.hash})),n.on(ce+ie,(function(t){(0,s.p)("bstHist",[location.pathname+location.hash,this.startPath,this.time],void 0,e.D.sessionTrace,n)}));try{i=new PerformanceObserver((t=>{const r=t.getEntries();(0,s.p)(te,[r],void 0,e.D.sessionTrace,n)})),i.observe({type:re,buffered:!0})}catch(e){}this.importAggregator({resourceObserver:i})}},C,xe,B,class extends h{static featureName=de;constructor(e,r){if(super(e,r,de,!(arguments.length>2&&void 0!==arguments[2])||arguments[2]),!c.il)return;if(!(0,t.OP)(e).xhrWrappable)return;try{this.removeOnAbort=new AbortController}catch(e){}let n,i=0;const o=this.ee.get("tracer"),a=(0,k._L)(this.ee),s=(0,k.Lg)(this.ee),u=(0,k.BV)(this.ee),d=(0,k.Kf)(this.ee),f=this.ee.get("events"),l=(0,k.u5)(this.ee),h=(0,k.QU)(this.ee),g=(0,k.Gm)(this.ee);function m(e,t){h.emit("newURL",[""+window.location,t])}function v(){i++,n=window.location.hash,this[ve]=(0,p.z)()}function b(){i--,window.location.hash!==n&&m(0,!0);var e=(0,p.z)();this[pe]=~~this[pe]+e-this[ve],this[ye]=e}function y(e,t){e.on(t,(function(){this[t]=(0,p.z)()}))}this.ee.on(ve,v),s.on(be,v),a.on(be,v),this.ee.on(ye,b),s.on(ge,b),a.on(ge,b),this.ee.buffer([ve,ye,"xhr-resolved"],this.featureName),f.buffer([ve],this.featureName),u.buffer(["setTimeout"+le,"clearTimeout"+fe,ve],this.featureName),d.buffer([ve,"new-xhr","send-xhr"+fe],this.featureName),l.buffer([me+fe,me+"-done",me+he+fe,me+he+le],this.featureName),h.buffer(["newURL"],this.featureName),g.buffer([ve],this.featureName),s.buffer(["propagate",be,ge,"executor-err","resolve"+fe],this.featureName),o.buffer([ve,"no-"+ve],this.featureName),a.buffer(["new-jsonp","cb-start","jsonp-error","jsonp-end"],this.featureName),y(l,me+fe),y(l,me+"-done"),y(a,"new-jsonp"),y(a,"jsonp-end"),y(a,"cb-start"),h.on("pushState-end",m),h.on("replaceState-end",m),window.addEventListener("hashchange",m,(0,O.m$)(!0,this.removeOnAbort?.signal)),window.addEventListener("load",m,(0,O.m$)(!0,this.removeOnAbort?.signal)),window.addEventListener("popstate",(function(){m(0,i>1)}),(0,O.m$)(!0,this.removeOnAbort?.signal)),this.abortHandler=this.#e,this.importAggregator()}#e(){this.removeOnAbort?.abort(),this.abortHandler=void 0}}],loaderType:"spa"})})(),window.NRBA=o})(); const cookieDomain = window.location.hostname; const tld = buildTLD(); function buildTLD() { const domainParts = cookieDomain.split('.'); while (domainParts.length > 2) { domainParts.shift(); } return domainParts.join('.'); } function deleteCookie(cookieName) { if (!cookieName) { return; } const cookiePath = (cookieName.startsWith('retraction_warning_') || cookieName.startsWith('version_warning_')) ? '/articles/' + cookieName : '/'; // Yes, these three slightly different ways to try and remove cookies are necessary document.cookie = cookieName + '=; path=' + cookiePath + '; domain=' + cookieDomain + '; expires=Thu, 01 Jan 1970 00:00:01 GMT;'; document.cookie = cookieName + '=; path=' + cookiePath + '; domain=.' + tld + '; expires=Thu, 01 Jan 1970 00:00:01 GMT;'; document.cookie = cookieName + '=; path=' + cookiePath + '; expires=Thu, 01 Jan 1970 00:00:01 GMT;'; } function deleteGroupCookies(group) { if (!group) { return; } const domainData = OneTrust.GetDomainData(), cookies = domainData.Groups.filter(cookieGroup => cookieGroup.OptanonGroupId === group)[0].Cookies; cookies.forEach(cookie => deleteCookie(cookie.Name)); } function OptanonWrapper() { const cookieConsentGroups = []; for (group of OneTrust.GetDomainData().Groups) { cookieConsentGroups.push(group.OptanonGroupId); } OneTrust.OnConsentChanged(function(e) { const cookieConsentActiveGroups = OnetrustActiveGroups.split(',').filter(activeGroup => activeGroup); cookieConsentGroups.forEach(group => { if (!cookieConsentActiveGroups.includes(group)) { deleteGroupCookies(group); }; }); }); } window.jQuery || document.write(' ') CKEDITOR_BASEPATH='https://hrbopenresearch.org/js/vendor/ckeditor/' window.reactTheme = 'HRB'; window.MathJax = { CommonHTML: { linebreaks: { automatic: true } }, 'HTML-CSS': { linebreaks: { automatic: true } }, SVG: { linebreaks: { automatic: true } }, AuthorInit: function() { MathJax.Hub.Register.MessageHook('End Process', function () { let timeout = false; // holder for timeout id const delay = 250; // delay after event is "complete" to run callback const reflowMath = function() { const dispFormulas = document.querySelectorAll('.disp-formula.panel'); if (!dispFormulas) { return; } for (const dispFormula of dispFormulas) { const child = dispFormula.querySelector('.MathJax_Preview').nextSibling.firstChild; const isMultiline = MathJax.Hub.getAllJax(dispFormula)[0].root.isMultiline; if (dispFormula.offsetWidth < child.offsetWidth || isMultiline) { MathJax.Hub.Queue(['Rerender', MathJax.Hub, dispFormula]); } } }; window.addEventListener('resize', function() { clearTimeout(timeout); // clear the timeout timeout = setTimeout(reflowMath, delay); // start timing for event "completion" }); }); }, }; if (window.location.hash == '#_=_'){ window.location = window.location.href.split('#')[0] } !function(f,b,e,v,n,t,s){if(f.fbq)return;n=f.fbq=function() {n.callMethod? n.callMethod.apply(n,arguments):n.queue.push(arguments)} ;if(!f._fbq)f._fbq=n; n.push=n;n.loaded=!0;n.version='2.0';n.queue=[];t=b.createElement(e);t.async=!0; t.src=v;s=b.getElementsByTagName(e)[0];s.parentNode.insertBefore(t,s)}(window, document,'script','https://connect.facebook.net/en_US/fbevents.js'); fbq('init', '1641728616063202'); fbq('track', "PixelInitialized", {}); Skip to content HRB Open Research file_upload Submit your research search clear search menu close clear Search Browse Gateways & Collections How to Publish Submit your Research My Submissions Article Guidelines Article Guidelines (New Versions) Data Guidelines Prepublication Checks Production Process Article Processing Charges Finding Article Reviewers About How it Works For Reviewers National Steering Group Policies Glossary FAQs Contact Blog My Account Submissions Content and Tracking Alerts My Details Sign In file_upload Submit your research { "@context": "https://schema.org", "@type": "ScholarlyArticle", "mainEntityOfPage": { "@type": "WebPage", "@id": "https://hrbopenresearch.org/articles/8-108" }, "headline": "Real world use of avacopan for ANCA-associated vasculitis. First experiences in Ireland.", "datePublished": "2025-09-26T16:15:41", "dateModified": "2025-09-26T16:15:41", "author": [ { "@type": "Person", "name": "Andrew Cummiskey" }, { "@type": "Person", "name": "Eithne Nic An Riogh" }, { "@type": "Person", "name": "Cliona Cowhig" }, { "@type": "Person", "name": "Sinead Stoneman" }, { "@type": "Person", "name": "Sarah Moran" }, { "@type": "Person", "name": "Ciara Magee" }, { "@type": "Person", "name": "Susan McAnallen" }, { "@type": "Person", "name": "Catherine Wall" }, { "@type": "Person", "name": "Michael R Clarkson" }, { "@type": "Person", "name": "Mark A Little" } ], "publisher": { "@type": "Organization", "name": "HRB Open Research", "logo": { "@type": "ImageObject", "url": "https://hrbopenresearch.org/img/AMP/HRB_image.png", "height": 566, "width": 60 } }, "image": { "@type": "ImageObject", "url": "https://hrbopenresearch.org/img/AMP/HRB_image.png", "height": 1200, "width": 127 }, "description": " Background Avacopan, a selective complement 5a receptor (C5aR) antagonist, is used for the treatment of severe active granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) in combination with rituximab or cyclophosphamide. By reducing glucocorticoid exposure and associated toxicity, avacopan can improve patient outcomes. This report presents the first clinical experience with avacopan in the treatment of ANCA-associated vasculitis (AAV) in the Republic of Ireland. Methods Ten patients received avacopan between December 2017 and April 2024 through the Irish early access program and the ADVOCATE trial (n=2). Data were extracted from the RITA Ireland Vasculitis (RIV) database and retrospective chart review. Collected variables included the commencement date, indication for avacopan initiation, ANCA subtype, organ involvement, number of relapses, concurrent and prior immunosuppressive medications, and adverse events. Results Avacopan was primarily initiated for patients requiring a steroid-sparing regimen due to contraindications such as severe osteoporosis, prior eating disorders, anxiety, or steroid-induced psychosis, as well as patient preference to avoid corticosteroids. On average, patients received 2.285 grams of prednisolone equivalent prior to avacopan initiation (range: 0–8.125 grams). Most patients achieved disease control without requiring further steroid therapy. Avacopan is generally well-tolerated. The reported adverse events in this cohort were headache, limited maculopapular rash, neutropenia, and liver dysfunction. Two patients experienced disease relapse upon discontinuation of avacopan, both of whom had the longest follow-up durations. Conclusion This study is the first real-world evaluation of avacopan use in Ireland. Although the sample size was small, avacopan demonstrated a favourable safety profile and efficacy in reducing corticosteroid dependence. As of July 1, 2024, avacopan was funded by the Irish Health Service Executive, improving accessibility. Further long-term follow-up is warranted to assess the relapse risk and establish the optimal treatment duration. " } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://hrbopenresearch.org/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://hrbopenresearch.org/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://hrbopenresearch.org/articles/8-108", "name": "Real world use of avacopan for ANCA-associated vasculitis. First experiences..." } } ] } Home Browse Real world use of avacopan for ANCA-associated vasculitis. First experiences... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Cummiskey A, Nic An Riogh E, Cowhig C et al. Real world use of avacopan for ANCA-associated vasculitis. First experiences in Ireland. [version 1; peer review: 1 approved with reservations, 1 not approved] . HRB Open Res 2025, 8 :108 ( https://doi.org/10.12688/hrbopenres.14159.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Research Article Real world use of avacopan for ANCA-associated vasculitis. First experiences in Ireland. [version 1; peer review: 1 approved with reservations, 1 not approved] Andrew Cummiskey https://orcid.org/0000-0003-0772-4274 1 , Eithne Nic An Riogh 2,3 , Cliona Cowhig 4 , [...] Sinead Stoneman 4 , Sarah Moran 4,5 , Ciara Magee 6 , Susan McAnallen 7 , Catherine Wall 3 , Michael R Clarkson 4,5 , Mark A Little https://orcid.org/0000-0001-6003-397X 2,3 Andrew Cummiskey https://orcid.org/0000-0003-0772-4274 1 , Eithne Nic An Riogh 2,3 , [...] Cliona Cowhig 4 , Sinead Stoneman 4 , Sarah Moran 4,5 , Ciara Magee 6 , Susan McAnallen 7 , Catherine Wall 3 , Michael R Clarkson 4,5 , Mark A Little https://orcid.org/0000-0001-6003-397X 2,3 PUBLISHED 26 Sep 2025 Author details Author details 1 Mater Misericordiae University Hospital, Dublin, Leinster, Ireland 2 Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Leinster, Ireland 3 Tallaght University Hospital, Dublin, Leinster, Ireland 4 Cork University Hospital, Cork, County Cork, Ireland 5 Beaumont Hospital, Dublin, Leinster, Ireland 6 St James's Hospital, Dublin, Leinster, Ireland 7 Trinity College Dublin, Trinity Health Kidney Centre, Dublin, Ireland Andrew Cummiskey Roles: Data Curation, Formal Analysis, Writing – Original Draft Preparation, Writing – Review & Editing Eithne Nic An Riogh Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Cliona Cowhig Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Sinead Stoneman Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Sarah Moran Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Ciara Magee Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Susan McAnallen Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Catherine Wall Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Michael R Clarkson Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Mark A Little Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS Abstract Background Avacopan, a selective complement 5a receptor (C5aR) antagonist, is used for the treatment of severe active granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) in combination with rituximab or cyclophosphamide. By reducing glucocorticoid exposure and associated toxicity, avacopan can improve patient outcomes. This report presents the first clinical experience with avacopan in the treatment of ANCA-associated vasculitis (AAV) in the Republic of Ireland. Methods Ten patients received avacopan between December 2017 and April 2024 through the Irish early access program and the ADVOCATE trial (n=2). Data were extracted from the RITA Ireland Vasculitis (RIV) database and retrospective chart review. Collected variables included the commencement date, indication for avacopan initiation, ANCA subtype, organ involvement, number of relapses, concurrent and prior immunosuppressive medications, and adverse events. Results Avacopan was primarily initiated for patients requiring a steroid-sparing regimen due to contraindications such as severe osteoporosis, prior eating disorders, anxiety, or steroid-induced psychosis, as well as patient preference to avoid corticosteroids. On average, patients received 2.285 grams of prednisolone equivalent prior to avacopan initiation (range: 0–8.125 grams). Most patients achieved disease control without requiring further steroid therapy. Avacopan is generally well-tolerated. The reported adverse events in this cohort were headache, limited maculopapular rash, neutropenia, and liver dysfunction. Two patients experienced disease relapse upon discontinuation of avacopan, both of whom had the longest follow-up durations. Conclusion This study is the first real-world evaluation of avacopan use in Ireland. Although the sample size was small, avacopan demonstrated a favourable safety profile and efficacy in reducing corticosteroid dependence. As of July 1, 2024, avacopan was funded by the Irish Health Service Executive, improving accessibility. Further long-term follow-up is warranted to assess the relapse risk and establish the optimal treatment duration. READ ALL READ LESS Keywords avacopan, complement, vasculitis, anti-neutrophil cytoplasm antibody, cytokines, renal Corresponding Author(s) Andrew Cummiskey ( [email protected] ) Eithne Nic An Riogh ( [email protected] ) Mark A Little ( [email protected] ) Close Corresponding authors: Andrew Cummiskey, Eithne Nic An Riogh, Mark A Little Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2025 Cummiskey A et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Cummiskey A, Nic An Riogh E, Cowhig C et al. Real world use of avacopan for ANCA-associated vasculitis. First experiences in Ireland. [version 1; peer review: 1 approved with reservations, 1 not approved] . HRB Open Res 2025, 8 :108 ( https://doi.org/10.12688/hrbopenres.14159.1 ) First published: 26 Sep 2025, 8 :108 ( https://doi.org/10.12688/hrbopenres.14159.1 ) Latest published: 26 Sep 2025, 8 :108 ( https://doi.org/10.12688/hrbopenres.14159.1 ) Introduction ANCA-associated vasculitis (AAV) is a necrotising small-vessel vasculitis that leads to systemic inflammation and organ dysfunction and predominantly affects the lungs and kidneys. The 2012 Revised International Chapel Hill Consensus Conference categorises AAV into three primary subtypes: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA) 1 . Epidemiological studies indicate an incidence of 24.7 per million in Northern Europe and 33 per million in the United States 2 , 3 . Conventional treatment involves induction and maintenance of immunosuppressive therapy, typically rituximab or cyclophosphamide, in combination with prolonged glucocorticoid administration. However, long-term corticosteroid use is associated with substantial morbidity, including an increased risk of infection, which remains the leading cause of mortality in AAV 4 . Avacopan is a first-in-class selective C5aR antagonist that offers a steroid-sparing alternative for the management of GPA and MPA. Initially approved in Japan in September 2021, avacopan subsequently received regulatory approval in the United States and Europe 5 , 6 . The ADVOCATE trial, a multinational, phase III, randomised, double-blind, active-controlled study, evaluated avacopan in AAV 7 . The trial demonstrated that avacopan was non-inferior to prednisone in achieving remission at 26 weeks and superior in sustaining remission at 52 weeks, with additional benefits to renal function among patients with active glomerulonephritis. However, further research is needed to determine its long-term role, particularly in patients with advanced kidney disease (estimated glomerular filtration rate [eGFR] <15 mL/min/1.73m²). This study details the first clinical experience with avacopan in Ireland prior to its reimbursement under a high-tech scheme in July 2024. Currently, avacopan prescriptions are restricted to Nephrologists, Rheumatologists, and Immunologists. Methods This report describes all patients in the Republic of Ireland who received avacopan between January 2017 and June 2024. Patients receiving avacopan with AAV were identified through the RITA-Ireland Vasculitis (RIV) Registry and Biobank, and through collaboration with treating physicians. The RIV registry collates clinical data and bio-samples from patients with vasculitis and from disease and healthy controls at a national level with the aim of improving long-term outcomes in patients with rare kidney disease 8 . Central ethical approval was granted by Tallaght University Hospital/St James’s Hospital Joint Research Ethics Committee (reference 2019-08 List 29 (07) on August 30, 2019, and locally by study site. All the participants provided written informed consent. Central storage of anonymised registry data is hosted on the secure password-protected web application REDCap 9 . Data were collected between January 2024 and March 2025 using the patient’s unique RIV identifier. Eligible patients had a definite diagnosis of GPA or MPA and were administered avacopan. Multiple data points were collected, including demographics, antibody status, organ involvement, number of flares, previous treatment, reason for commencing avacopan, cumulative steroid dose before and during avacopan treatment, and any adverse events. The data collection points are listed in Table 1 . Table 1. Clinical characteristics and treatment outcomes of patients receiving avacopan (n=10). Characteristic Value Demographics Total patients (n) 10 Sex Male: 5 (50%), female: 5 (50%) Age (years) Mean: 53.7 (range: 18–69) Disease characteristics ANCA subtype MPO-positive: 5 (50%), PR3-positive: 5 (50%) Renal involvement 9 (90%) Pulmonary involvement 7 (70%) (granulomatous, haemorrhagic, other) Other organ involvement Musculoskeletal: 3 (30%), ear, nose, throat (ENT): 2 (20%), CNS: 2 (20%), cutaneous: 1 (10%), abdominal: 2 (20%) Baseline disease activity BVAS at treatment initiation (n=8) Mean: 17.75 (range 0–34). Treatment details Duration of avacopan 12 months (range 4–20 months) Concurrent rituximab therapy 8 (80%) Prednisolone prior to avacopan Mean: 2.285 g (range: 0.0 – 8.125g) Outcomes Remission rate 90% (9 of 10 patients) Patients with relapse post avacopan discontinuation 2 patients (20%) Total number of relapses post avacopan 3 (2 minor, 1 major) Adverse events Neutropenia, persistent liver dysfunction, maculopapular rash, COVID-19 pneumonia Results Ten patients (n=10) commenced avacopan therapy through an early access program between December 2017 and June 2024. Five patients were male and five were female, with an average age of 53.7 years (range: 18–69 years). Five patients were MPO-positive and five were PR3-positive. Five patients had newly diagnosed AAV, whereas five had established disease. 90% of the included patients had renal involvement with a mean pre-treatment estimated glomerular filtration rate (eGFR) of 44 mL/min/1.73 m 2 (range 13-108 mL/min/1.73 m 2 ). EGFR improved in four patients and decreased in three patients following the commencement of avacopan treatment. In those patients whose eGFRs improved, pre-treatment eGFRs were on average 22 mL/min/1.73m 2 (range 16-27 mL/min/1.73 m 2 ), improving to 32.75 mL/min/1.73 m 2 following treatment with avacopan. In patients whose eGFRs worsened, pre-treatment eGFRs were on average 73 mL/min/1.73 m 2 (range 13-108 mL/min/1.73 m 2 ), disimproving to 57 mL/min/1.73 m 2 following treatment with avacopan. 70% of patients had pulmonary involvement. Other organ system involvement included musculoskeletal (30%); ear, nose, and throat (20%); central nervous system (20%); cutaneous (10%); and abdominal (20%). The mean follow-up duration following the commencement of avacopan was 41.4 months (range 13 – 87 months). The average BVAS (data collected in 8/10 patients) at the commencement of avacopan treatment was 17.75 (range 0–34). The average duration of avacopan treatment was 12 months (range 4–20 months). The majority of patients (n=8) received rituximab as concurrent therapy with avacopan. On average, patients received 2.285 grams of prednisolone equivalent prior to the commencement of avacopan. Although it is challenging to estimate the prednisolone dose range from the available clinical data, we estimated this as a range of 0–8.125 grams per patient. Two patients relapsed after the discontinuation of avacopan. One patient had low disease activity one month after avacopan discontinuation, which was classified as a minor relapse. This patient had a subsequent relapse five years post-avacopan (major relapse). The second patient experienced a minor relapse 8 months post-avacopan. All relapses after avacopan were treated with oral prednisolone and rituximab. Relapses occurred among the patients with the longest follow-up duration. Other immunosuppressive agents administered alongside avacopan for AAV treatment in this cohort were rituximab (n=8), cyclophosphamide (n=2), azathioprine (n=1), and mycophenolate mofetil (n=1). One patient underwent a plasma exchange. Adverse events were observed in three patients in this cohort. Reported adverse events that may be related to avacopan include neutropenia, persistent liver dysfunction, pinpoint maculopapular rash on the legs and lower abdomen, and COVID-19 pneumonia. Overall, avacopan was well-tolerated. Discussion To our knowledge, this is the first study on the use of avacopan for the management of AAV in the Irish population. Baseline patient characteristics and treatment outcomes were comparable to those of European cohorts. The Spanish Avacopan early access program (Draibe J et al .) analysed 29 patients with AAV 10 . When comparing with the Irish data there was a similar sex distribution (41.4% male (Spain) vs 50% male (Irish)) and a similar age profile (56 years (Spain) vs 53.7 years (Irish)). Renal involvement was observed in 79.31% of patients in the Spanish early access program compared to 90% of patients in the Irish cohort. Mean eGFRs pre-commencement were lower in the Spanish cohort, 23.2 ± 11.2 mL/min/1.73m 2 compared to 36.0 ± 29.54 mL/min/1.73m 2 among patients with renal involvement in the Irish cohort. Comparing with a US cohort of 92 patients with AAV, the mean eGFR among patients with renal involvement (n=71) was 33 ± 26.7mL/min/1.73m 2 11 . There was a predominance of MPO (72.4%, Spain; 72%, USA) in the Spanish and US cohorts. In a multicentre observational study on avacopan for AAV (Zimmerman J et al .), the baseline eGFR was 37 mL/min/.73m 2 which more closely aligns with Irish data 12 . Furthermore, of the 39 patients in Zimmerman’s study, 56% were PR3 positive with the remaining 44% being either MPO-or MPO and anti-GBM positive which closely aligns with the Irish data. Although the overall pre-avacopan eGFR was comparatively high in the Irish cohort, the patients were in the chronic kidney disease (CKD) 3b category, which is consistent with international data. Furthermore, the high standard deviation and small sample size (n=10) in the Irish cohort makes it difficult to draw any meaningful conclusions from these data. In the ADVOCATE trial, significant improvements in the eGFR were observed in the avacopan arm. Among those with an eGFR < 30 mL/min/1.73m 2 , the mean improvement at week 52 in the avacopan arm was 13.7 mL/min/1.73m 2 compared to 8.2 mL/min/1.73 m 2 in the prednisone arm. Among the four patients in the Irish early access program whose eGFR improved following treatment with avacopan, the average pretreatment eGFR was 22 mL/min/1.73m 2 , improving to 32.75 mL/min/1.73m 2 . In this subset of patients, the patient with the longest follow-up had creatinine measured nine times after the commencement of avacopan. Additionally, this patient had the highest baseline creatinine level in this subset. Creatinine trends pre- and post-avacopan are shown in Figure 1 . Consistent improvements in eGFR can be observed across other early access programs. In the Spanish early access cohort, eGFR improved from 23.2 mL/min/1.73m 2 to 38.38 mL/min/1.73m 2 . Similarly, in a USA cohort, the mean eGFR improved from 37 to 51 mL/min1.73m 2 over a 12-month period. Figure 1. Creatinine trends pre and post avacopan. The mean BVAS score in the Irish population was 17.75, which was similar to the mean BVAS score of 16 in the ADVOCATE trial. A similar BVAS was observed in other European studies. The average treatment duration with avacopan in the Irish population was 12 months (range: 4–20 months). Although the treatment duration range is variable, the real-world duration of treatment with avacopan is between 37 – 48 weeks 13 . The ADVOCATE trial cites liver dysfunction as the most common side effect secondary to avacopan use (5.4% in the avacopan group and 3.7% in the prednisone group) with complete normalisation of liver enzymes after discontinuation of avacopan. One patient in this cohort had deranged liver function tests. Recovery of liver function tests to baseline was slow in this patient; however, it transpired that they had developed sludge and gallstones in the gallbladder with their liver dysfunction fully resolved following successful endoscopic retrograde cholangiopancreatography (ERCP). Avacopan had been discontinued in this patient prior to this, although predominantly due to persistent neutropenia and concerns regarding infection risk. Avacopan was not recommenced and the patient remained in clinical remission. Conclusion This study provided the first real-world data on avacopan use in the Republic of Ireland. Avacopan offers an effective alternative to traditional therapies such as corticosteroids. Its targeted mechanism of action, which inhibits the complement system, is a promising option for patients who experience adverse effects from long-term corticosteroid use. Avacopan has demonstrated efficacy as a steroid-sparing agent with a favourable safety profile, reducing reliance on corticosteroids and mitigating their associated toxicities. While remission rates are promising, further follow-up is necessary to evaluate long-term relapse risks. With avacopan now funded by the Health Service Executive in Ireland, future audits and research should focus on long-term outcomes and cost-effectiveness. These findings support the integration of avacopan into AAV treatment guidelines in Ireland, with the potential to improve AAV clinical outcomes. Data availability statement Underlying data While the underlying patient data is pseudonymised, due to the rarity of ANCA-associated vasculitis, coupled with the identifiable nature of the data included in our analyses, it is not possible in practice to fully anonymise the dataset. Individuals could potentially be re-identified quite easily. Therefore, raw data must remain confidential and cannot be freely shared on an open platform. We would invite any potential research collaborations or data requests through the corresponding author, Professor Mark Little ( [email protected] ), on reasonable request, as agreed by participants in their written informed consent (detailed on page 3: https://www.tcd.ie/medicine/thkc/assets/pdf/RKD-Vasculitis-Patient-PIL-ICF-Version-5-07AUG19.pdf ). Requests will be considered on a case-by-case basis. This approach is endorsed in a publication in The Lancet, from another large Irish longitudinal cohort study, TILDA. Brayne C, O'Mahoney P, Feeney J, et al. : The challenges of open access data. Lancet. 2022; 399 (10324): 517. PubMed Abstract | Publisher Full Text Faculty Opinions recommended References 1. Jennette JC: Overview of the 2012 revised International Chapel Hill Consensus Conference nomenclature of vasculitides. Clin Exp Nephrol. 2013; 17 (5): 603–606. PubMed Abstract | Publisher Full Text | Free Full Text 2. Nilsen AT, Karlsen C, Bakland G, et al. : Increasing incidence and prevalence of ANCA-associated vasculitis in northern Norway. Rheumatology (Oxford). 2020; 59 (9): 2316–2324. PubMed Abstract | Publisher Full Text 3. Berti A, Cornec D, Crowson CS, et al. : The epidemiology of antineutrophil cytoplasmic autoantibody-associated vasculitis in Olmsted County, Minnesota (USA): a twenty-year US population-based study. Arthritis Rheumatol. 2017; 69 (12): 2338–2350. PubMed Abstract | Publisher Full Text | Free Full Text 4. Charlier C, Henegar C, Launay O, et al. : Risk factors for major infections in Wegener granulomatosis: analysis of 113 patients. Ann Rheum Dis. 2009; 68 (5): 658–663. PubMed Abstract | Publisher Full Text 5. Lee A: Avacopan: first approval. Drugs. 2022; 82 (1): 79–85. PubMed Abstract | Publisher Full Text 6. Thorley J: FDA approves avacopan for ANCA-associated vasculitis. Lancet Rheumatol. 2022; 4 (1): E21. Publisher Full Text 7. Jayne DRW, Merkel PA, Schall TJ, et al. : Avacopan for the treatment of ANCA-associated vasculitis. N Engl J Med. 2021; 384 (7): 599–609. Erratum in: N Engl J Med. 2024 Jan 25; 390(4): 388. doi: 10.1056/NEJMx230010 . PubMed Abstract | Publisher Full Text 8. Scott J, Nic an Ríogh E, Al Nokhatha S, et al. : Extended data for 'ANCA-associated vasculitis in Ireland: a multi-centre national cohort study'.2022. Publisher Full Text 9. Harris PA, Taylor R, Thielke R, et al. : Research Electronic Data Capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009; 42 (2): 377–81. PubMed Abstract | Publisher Full Text | Free Full Text 10. Draibe J, Espigol-Frigolé G, Cid MC, et al. : The real-world use and effectiveness of avacopan in routine practice for the treatment of ANCA vasculitis. First experiences in Spain. Rheumatology (Oxford). 2025: 64 (4): 2019–2026. PubMed Abstract | Publisher Full Text 11. Gabilan C, Pfirmann P, Ribes D: Avacopan as first-line treatment in antineutrophil cytoplasmic antibody-associated vasculitis: a steroid-sparing option. Kidney Int Rep. 2022; 7 (5): 1115–1118. PubMed Abstract | Publisher Full Text | Free Full Text 12. Zimmermann J, Sonnemann J, Jabs WJ, et al. : Avacopan in anti-neutrophil cytoplasmic autoantibodies–associated vasculitis in a real-world setting. Kidney Int Rep. 2024; 9 (9): 2803–2808. PubMed Abstract | Publisher Full Text | Free Full Text 13. Zonozi R, Aqeel F, Le D, et al. : Real-world experience with avacopan in antineutrophil cytoplasmic autoantibody-associated vasculitis. Kidney Int Rep. 2024; 9 (6): 1783–1791. PubMed Abstract | Publisher Full Text | Free Full Text Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 26 Sep 2025 ADD YOUR COMMENT Comment Author details Author details 1 Mater Misericordiae University Hospital, Dublin, Leinster, Ireland 2 Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Leinster, Ireland 3 Tallaght University Hospital, Dublin, Leinster, Ireland 4 Cork University Hospital, Cork, County Cork, Ireland 5 Beaumont Hospital, Dublin, Leinster, Ireland 6 St James's Hospital, Dublin, Leinster, Ireland 7 Trinity College Dublin, Trinity Health Kidney Centre, Dublin, Ireland Andrew Cummiskey Roles: Data Curation, Formal Analysis, Writing – Original Draft Preparation, Writing – Review & Editing Eithne Nic An Riogh Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Cliona Cowhig Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Sinead Stoneman Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Sarah Moran Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Ciara Magee Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Susan McAnallen Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Catherine Wall Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Michael R Clarkson Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Mark A Little Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (1) version 1 Published: 26 Sep 2025, 8:108 https://doi.org/10.12688/hrbopenres.14159.1 Copyright © 2025 Cummiskey A et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics VIEWS $counts.viewCount downloads Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Cummiskey A, Nic An Riogh E, Cowhig C et al. Real world use of avacopan for ANCA-associated vasculitis. First experiences in Ireland. [version 1; peer review: 1 approved with reservations, 1 not approved] . HRB Open Res 2025, 8 :108 ( https://doi.org/10.12688/hrbopenres.14159.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 26 Sep 2025 Views 0 Cite How to cite this report: Hiwa R. Reviewer Report For: Real world use of avacopan for ANCA-associated vasculitis. First experiences in Ireland. [version 1; peer review: 1 approved with reservations, 1 not approved] . HRB Open Res 2025, 8 :108 ( https://doi.org/10.21956/hrbopenres.15571.r50447 ) The direct URL for this report is: https://hrbopenresearch.org/articles/8-108/v1#referee-response-50447 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 22 Oct 2025 Ryosuke Hiwa , Kyoto University School of Public Health Department of Health Informatics, Kyoto, Kyoto Prefecture, Japan Not Approved VIEWS 0 https://doi.org/10.21956/hrbopenres.15571.r50447 The authors reported 10 patients with ANCA-associated vasculitis (AAV) who were treated with avacopan. They found that avacopan was effective for disease control and well-tolerated. This study may be important as it represents the first real-world evaluation of avacopan use ... Continue reading READ ALL The authors reported 10 patients with ANCA-associated vasculitis (AAV) who were treated with avacopan. They found that avacopan was effective for disease control and well-tolerated. This study may be important as it represents the first real-world evaluation of avacopan use in Ireland. However, there are several concerns that should be addressed before publication. Major Concerns 1. Insufficient clinical data The authors presented the clinical characteristics of the 10 patients treated with avacopan; however, the data provided are insufficient. Key clinical variables reported in the ADVOCATE trial, such as disease duration, diagnosis according to classification criteria, and daily prednisone-equivalent dose, should be included. Moreover, the course of renal function (shown in Figure 1) should be described in the Results section rather than the Discussion. Additionally, the estimated glomerular filtration rate (eGFR) trend should be presented instead of serum creatinine levels, as it provides a more accurate assessment of renal function. 2. Small sample size without control As the authors noted, the sample size is too small to draw firm conclusions, and the absence of a control group further limits interpretability. Therefore, this report should be considered a case series. If so, a detailed description of each case should be provided. Furthermore, it is stated that half of the patients were established cases, but it is unclear whether they experienced a relapse. The ADVOCATE trial included newly diagnosed and relapsed cases. If avacopan was administered to patients without relapse, these should be reported separately. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? No If applicable, is the statistical analysis and its interpretation appropriate? Not applicable Are all the source data underlying the results available to ensure full reproducibility? No source data required Are the conclusions drawn adequately supported by the results? No Competing Interests: No competing interests were disclosed. Reviewer Expertise: Rheumatology I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Hiwa R. Reviewer Report For: Real world use of avacopan for ANCA-associated vasculitis. First experiences in Ireland. [version 1; peer review: 1 approved with reservations, 1 not approved] . HRB Open Res 2025, 8 :108 ( https://doi.org/10.21956/hrbopenres.15571.r50447 ) The direct URL for this report is: https://hrbopenresearch.org/articles/8-108/v1#referee-response-50447 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Massicotte-Azarniouch D. Reviewer Report For: Real world use of avacopan for ANCA-associated vasculitis. First experiences in Ireland. [version 1; peer review: 1 approved with reservations, 1 not approved] . HRB Open Res 2025, 8 :108 ( https://doi.org/10.21956/hrbopenres.15571.r50440 ) The direct URL for this report is: https://hrbopenresearch.org/articles/8-108/v1#referee-response-50440 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 21 Oct 2025 David Massicotte-Azarniouch , University of Ottawa, Ottawa, Ontario, Canada Approved with Reservations VIEWS 0 https://doi.org/10.21956/hrbopenres.15571.r50440 This article provides data on real-world use of avacopan for treating AAV in Ireland. It is a small cohort, but can. be nonetheless informative. I feel there is missing information that would be required to make the article more relevant ... Continue reading READ ALL This article provides data on real-world use of avacopan for treating AAV in Ireland. It is a small cohort, but can. be nonetheless informative. I feel there is missing information that would be required to make the article more relevant for readers. Methods - Paragraph 1: This is for all patients who received Avacopan, however it would be good to detail how they accessed avacopan (clinical trial, paid out of pocket, private insurance, compassionate supply from drug company), since it is stated in the Abstract that it only became publicly funded after the study period. 10 patients over such a study period must be a very small proportion of patients treated with AAV in Ireland. Would need information of how representative these 10 patients are of the usual patients. Are all patients with AAV in Ireland entered into the RIV registry? Would add in Methods that avacopan became publicly funded in July 2024. Methods - Paragraph 2: How was AAV diagnosed? Was it through kidney biopsy for the 9 with renal involvement? Or clinically/urine microscopy? Would specify Results - Table 1 Would add baseline eGFR, how many presented dialysis dependent. Results - Paragraph 2 Baseline eGFR: I wonder if there is a mistake. The results state eGFR range among the 9 patients with renal involvement was 13-108ml/min, but Figure 1 shows 2 patients who presented dialysis dependent. Please verify. Would add Figure 1 to the results, this is an important finding. Would also clarify if this represents data for the 9 patients with renal involvement (it is what I presume as there seem to be only 9 lines, but should be clarified). Would specify amount of patients presenting dialysis dependent, number who recovered and number who progressed to ESKD. Pre-treatment GC: how much of that is IV methylprednisolone vs oral prednisone. Would specify How was prednisone handled after starting avacopan? Was it continued at low dose, stopped entirely, and if so how quickly was it removed? Along the same line, it would be good to specify how much prednisone participants were exposed to after introduction of avacopan (if data available) When was avacopan started after initial diagnosis/start of treatment for active disease? Results - Paragraph 3 What does persistent liver dysfunction mean? Does it mean that LFT abnormalities persisted after discontinuation of avacopan? Did any of the adverse events lead to discontinuation of avacopan? Results - missing information Would specify the follow-up of patients. Figure 1 suggests 2 patients had extremely short follow-up Would specify reasons for avacopan initiation. In the abstract, reasons are mentioned, but not in the main manuscript Did anyone require re-initiation of prednisone for disease control after avacopan was started? Discussion There is a lot of discussion spent on comparing to other cohorts of real-world data on avacopan use, stating that characteristics of this cohort were similar in many aspects to other cohorts. However, I feel there should be more discussion on how avacopan was used, in what contexts, how did it influence GC use. This would be more informative for a reader, to get a better understanding of how avacopan is used in real-world clinical practice, and how a clinician could approach avacopan use in clinical practice. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly Competing Interests: No competing interests were disclosed. Reviewer Expertise: Nephrology - Glomerulonephritis I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Massicotte-Azarniouch D. Reviewer Report For: Real world use of avacopan for ANCA-associated vasculitis. First experiences in Ireland. [version 1; peer review: 1 approved with reservations, 1 not approved] . HRB Open Res 2025, 8 :108 ( https://doi.org/10.21956/hrbopenres.15571.r50440 ) The direct URL for this report is: https://hrbopenresearch.org/articles/8-108/v1#referee-response-50440 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 26 Sep 2025 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 Version 1 26 Sep 25 read read David Massicotte-Azarniouch , University of Ottawa, Ottawa, Canada Ryosuke Hiwa , Kyoto University School of Public Health Department of Health Informatics, Kyoto, Japan Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Hiwa R. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 22 Oct 2025 | for Version 1 Ryosuke Hiwa , Kyoto University School of Public Health Department of Health Informatics, Kyoto, Kyoto Prefecture, Japan 0 Views copyright © 2025 Hiwa R. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Not Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The authors reported 10 patients with ANCA-associated vasculitis (AAV) who were treated with avacopan. They found that avacopan was effective for disease control and well-tolerated. This study may be important as it represents the first real-world evaluation of avacopan use in Ireland. However, there are several concerns that should be addressed before publication. Major Concerns 1. Insufficient clinical data The authors presented the clinical characteristics of the 10 patients treated with avacopan; however, the data provided are insufficient. Key clinical variables reported in the ADVOCATE trial, such as disease duration, diagnosis according to classification criteria, and daily prednisone-equivalent dose, should be included. Moreover, the course of renal function (shown in Figure 1) should be described in the Results section rather than the Discussion. Additionally, the estimated glomerular filtration rate (eGFR) trend should be presented instead of serum creatinine levels, as it provides a more accurate assessment of renal function. 2. Small sample size without control As the authors noted, the sample size is too small to draw firm conclusions, and the absence of a control group further limits interpretability. Therefore, this report should be considered a case series. If so, a detailed description of each case should be provided. Furthermore, it is stated that half of the patients were established cases, but it is unclear whether they experienced a relapse. The ADVOCATE trial included newly diagnosed and relapsed cases. If avacopan was administered to patients without relapse, these should be reported separately. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? No If applicable, is the statistical analysis and its interpretation appropriate? Not applicable Are all the source data underlying the results available to ensure full reproducibility? No source data required Are the conclusions drawn adequately supported by the results? No Competing Interests No competing interests were disclosed. Reviewer Expertise Rheumatology I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. reply Respond to this report Responses (0) Hiwa R. Peer Review Report For: Real world use of avacopan for ANCA-associated vasculitis. First experiences in Ireland. [version 1; peer review: 1 approved with reservations, 1 not approved] . HRB Open Res 2025, 8 :108 ( https://doi.org/10.21956/hrbopenres.15571.r50447) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://hrbopenresearch.org/articles/8-108/v1#referee-response-50447 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Massicotte-Azarniouch D. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 21 Oct 2025 | for Version 1 David Massicotte-Azarniouch , University of Ottawa, Ottawa, Ontario, Canada 0 Views copyright © 2025 Massicotte-Azarniouch D. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This article provides data on real-world use of avacopan for treating AAV in Ireland. It is a small cohort, but can. be nonetheless informative. I feel there is missing information that would be required to make the article more relevant for readers. Methods - Paragraph 1: This is for all patients who received Avacopan, however it would be good to detail how they accessed avacopan (clinical trial, paid out of pocket, private insurance, compassionate supply from drug company), since it is stated in the Abstract that it only became publicly funded after the study period. 10 patients over such a study period must be a very small proportion of patients treated with AAV in Ireland. Would need information of how representative these 10 patients are of the usual patients. Are all patients with AAV in Ireland entered into the RIV registry? Would add in Methods that avacopan became publicly funded in July 2024. Methods - Paragraph 2: How was AAV diagnosed? Was it through kidney biopsy for the 9 with renal involvement? Or clinically/urine microscopy? Would specify Results - Table 1 Would add baseline eGFR, how many presented dialysis dependent. Results - Paragraph 2 Baseline eGFR: I wonder if there is a mistake. The results state eGFR range among the 9 patients with renal involvement was 13-108ml/min, but Figure 1 shows 2 patients who presented dialysis dependent. Please verify. Would add Figure 1 to the results, this is an important finding. Would also clarify if this represents data for the 9 patients with renal involvement (it is what I presume as there seem to be only 9 lines, but should be clarified). Would specify amount of patients presenting dialysis dependent, number who recovered and number who progressed to ESKD. Pre-treatment GC: how much of that is IV methylprednisolone vs oral prednisone. Would specify How was prednisone handled after starting avacopan? Was it continued at low dose, stopped entirely, and if so how quickly was it removed? Along the same line, it would be good to specify how much prednisone participants were exposed to after introduction of avacopan (if data available) When was avacopan started after initial diagnosis/start of treatment for active disease? Results - Paragraph 3 What does persistent liver dysfunction mean? Does it mean that LFT abnormalities persisted after discontinuation of avacopan? Did any of the adverse events lead to discontinuation of avacopan? Results - missing information Would specify the follow-up of patients. Figure 1 suggests 2 patients had extremely short follow-up Would specify reasons for avacopan initiation. In the abstract, reasons are mentioned, but not in the main manuscript Did anyone require re-initiation of prednisone for disease control after avacopan was started? Discussion There is a lot of discussion spent on comparing to other cohorts of real-world data on avacopan use, stating that characteristics of this cohort were similar in many aspects to other cohorts. However, I feel there should be more discussion on how avacopan was used, in what contexts, how did it influence GC use. This would be more informative for a reader, to get a better understanding of how avacopan is used in real-world clinical practice, and how a clinician could approach avacopan use in clinical practice. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise Nephrology - Glomerulonephritis I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Massicotte-Azarniouch D. Peer Review Report For: Real world use of avacopan for ANCA-associated vasculitis. First experiences in Ireland. [version 1; peer review: 1 approved with reservations, 1 not approved] . HRB Open Res 2025, 8 :108 ( https://doi.org/10.21956/hrbopenres.15571.r50440) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://hrbopenresearch.org/articles/8-108/v1#referee-response-50440 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions Adjust parameters to alter display View on desktop for interactive features Includes Interactive Elements View on desktop for interactive features Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. Consider the following examples, but note that this is not an exhaustive list: Examples of 'Non-Financial Competing Interests' Within the past 4 years, you have held joint grants, published or collaborated with any of the authors of the selected paper. You have a close personal relationship (e.g. parent, spouse, sibling, or domestic partner) with any of the authors. You are a close professional associate of any of the authors (e.g. scientific mentor, recent student). You work at the same institute as any of the authors. You hope/expect to benefit (e.g. favour or employment) as a result of your submission. You are an Editor for the journal in which the article is published. Examples of 'Financial Competing Interests' You expect to receive, or in the past 4 years have received, any of the following from any commercial organisation that may gain financially from your submission: a salary, fees, funding, reimbursements. You expect to receive, or in the past 4 years have received, shared grant support or other funding with any of the authors. You hold, or are currently applying for, any patents or significant stocks/shares relating to the subject matter of the paper you are commenting on. Stay Updated Sign up for content alerts and receive a weekly or monthly email with all newly published articles Register with HRB Open Research Already registered? Sign in Not now, thanks close PLEASE NOTE If you are an AUTHOR of this article, please check that you signed in with the account associated with this article otherwise we cannot automatically identify your role as an author and your comment will be labelled as a “User Comment”. If you are a REVIEWER of this article, please check that you have signed in with the account associated with this article and then go to your account to submit your report, please do not post your review here. If you do not have access to your original account, please contact us . All commenters must hold a formal affiliation as per our Policies . The information that you give us will be displayed next to your comment. User comments must be in English, comprehensible and relevant to the article under discussion. We reserve the right to remove any comments that we consider to be inappropriate, offensive or otherwise in breach of the User Comment Terms and Conditions . Commenters must not use a comment for personal attacks. When criticisms of the article are based on unpublished data, the data should be made available. I accept the User Comment Terms and Conditions Please confirm that you accept the User Comment Terms and Conditions. Affiliation ✕ refresh Please enter your institution. Note: To add your institution or organisation, start typing the name and then select the correct name from the list. Where applicable, the name will appear in both the original language and in English. Do not paste in the name. If the name does not appear in the drop-down list, we will display the information you have entered. ✕ refresh Country/Region * USA UK Canada China France Germany Afghanistan Aland Islands Albania Algeria American Samoa Andorra Angola Anguilla Antarctica Antigua and Barbuda Argentina Armenia Aruba Australia Austria Azerbaijan Bahamas Bahrain Bangladesh Barbados Belarus Belgium Belize Benin Bermuda Bhutan Bolivia Bosnia and Herzegovina Botswana Bouvet Island Brazil British Indian Ocean Territory British Virgin Islands Brunei Bulgaria Burkina Faso Burundi Cambodia Cameroon Canada Cape Verde Cayman Islands Central African Republic Chad Chile China Christmas Island Cocos (Keeling) Islands Colombia Comoros Congo Cook Islands Costa Rica Cote d'Ivoire Croatia Cuba Cyprus Czech Republic Democratic Republic of the Congo Denmark Djibouti Dominica Dominican Republic Ecuador Egypt El Salvador Equatorial Guinea Eritrea Estonia Ethiopia Falkland Islands Faroe Islands Federated States of Micronesia Fiji Finland France French Guiana French Polynesia French Southern Territories Gabon Georgia Germany Ghana Gibraltar Greece Greenland Grenada Guadeloupe Guam Guatemala Guernsey Guinea Guinea-Bissau Guyana Haiti Heard Island and Mcdonald Islands Holy See (Vatican City State) Honduras Hong Kong Hungary Iceland India Indonesia Iran Iraq Ireland Israel Italy Jamaica Japan Jersey Jordan Kazakhstan Kenya Kiribati Kosovo (Serbia and Montenegro) Kuwait Kyrgyzstan Lao People's Democratic Republic Latvia Lebanon Lesotho Liberia Libya Liechtenstein Lithuania Luxembourg Macao Madagascar Malawi Malaysia Maldives Mali Malta Marshall Islands Martinique Mauritania Mauritius Mayotte Mexico Minor Outlying Islands of the United States Moldova Monaco Mongolia Montenegro Montserrat Morocco Mozambique Myanmar Namibia Nauru Nepal Netherlands Antilles New Caledonia New Zealand Nicaragua Niger Nigeria Niue Norfolk Island North Korea North Macedonia Northern Mariana Islands Norway Oman Pakistan Palau Palestinian Territory Panama Papua New Guinea Paraguay Peru Philippines Pitcairn Poland Portugal Puerto Rico Qatar Reunion Romania Russian Federation Rwanda Saint Helena Saint Kitts and Nevis Saint Lucia Saint Pierre and Miquelon Saint Vincent and the Grenadines Samoa San Marino Sao Tome and Principe Saudi Arabia Senegal Serbia Seychelles Sierra Leone Singapore Slovakia Slovenia Solomon Islands Somalia South Africa South Georgia and the South Sandwich Is South Korea South Sudan Spain Sri Lanka Sudan Suriname Svalbard and Jan Mayen Swaziland Sweden Switzerland Syria Taiwan Tajikistan Tanzania Thailand The Gambia The Netherlands Timor-Leste Togo Tokelau Tonga Trinidad and Tobago Tunisia Turkey Turkmenistan Turks and Caicos Islands Tuvalu UK USA Uganda Ukraine United Arab Emirates United States Virgin Islands Uruguay Uzbekistan Vanuatu Venezuela Vietnam Wallis and Futuna West Bank and Gaza Strip Western Sahara Yemen Zambia Zimbabwe Please select your country/region. You must enter a comment. Competing Interests Please disclose any competing interests that might be construed to influence your judgment of the article's or peer review report's validity or importance. Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. Consider the following examples, but note that this is not an exhaustive list: Examples of 'Non-Financial Competing Interests' Within the past 4 years, you have held joint grants, published or collaborated with any of the authors of the selected paper. You have a close personal relationship (e.g. parent, spouse, sibling, or domestic partner) with any of the authors. You are a close professional associate of any of the authors (e.g. scientific mentor, recent student). You work at the same institute as any of the authors. You hope/expect to benefit (e.g. favour or employment) as a result of your submission. You are an Editor for the journal in which the article is published. Examples of 'Financial Competing Interests' You expect to receive, or in the past 4 years have received, any of the following from any commercial organisation that may gain financially from your submission: a salary, fees, funding, reimbursements. You expect to receive, or in the past 4 years have received, shared grant support or other funding with any of the authors. You hold, or are currently applying for, any patents or significant stocks/shares relating to the subject matter of the paper you are commenting on. Please state your competing interests The comment has been saved. An error has occurred. Please try again. Cancel Post var lTitle = "Real world use of avacopan for ANCA-associated...".replace("'", ''); var linkedInUrl = "http://www.linkedin.com/shareArticle?url=https://hrbopenresearch.org/articles/8-108/v1" + "&title=" + encodeURIComponent(lTitle) + "&summary=" + encodeURIComponent('Read the article by '); var deliciousUrl = "https://del.icio.us/post?url=https://hrbopenresearch.org/articles/8-108/v1&title=" + encodeURIComponent(lTitle); var redditUrl = "http://reddit.com/submit?url=https://hrbopenresearch.org/articles/8-108/v1" + "&title=" + encodeURIComponent(lTitle); linkedInUrl += encodeURIComponent('Cummiskey A et al.'); var offsetTop = /chrome/i.test( navigator.userAgent ) ? 4 : -10; var addthis_config = { ui_offset_top: offsetTop, services_compact : "facebook,twitter,www.linkedin.com,www.mendeley.com,reddit.com", services_expanded : "facebook,twitter,www.linkedin.com,www.mendeley.com,reddit.com", services_custom : [ { name: "LinkedIn", url: linkedInUrl, icon:"/img/icon/at_linkedin.svg" }, { name: "Mendeley", url: "http://www.mendeley.com/import/?url=https://hrbopenresearch.org/articles/8-108/v1/mendeley", icon:"/img/icon/at_mendeley.svg" }, { name: "Reddit", url: redditUrl, icon:"/img/icon/at_reddit.svg" }, ] }; var addthis_share = { url: "https://hrbopenresearch.org/articles/8-108", templates : { twitter : "Real world use of avacopan for ANCA-associated vasculitis. First.... Cummiskey A et al., published by " + "@HRBOpenRes" + ", https://hrbopenresearch.org/articles/8-108/v1" } }; if (typeof(addthis) != "undefined"){ addthis.addEventListener('addthis.ready', checkCount); addthis.addEventListener('addthis.menu.share', checkCount); } $(".f1r-shares-twitter").attr("href", "https://twitter.com/intent/tweet?text=" + addthis_share.templates.twitter); $(".f1r-shares-facebook").attr("href", "https://www.facebook.com/sharer/sharer.php?u=" + addthis_share.url); $(".f1r-shares-linkedin").attr("href", addthis_config.services_custom[0].url); $(".f1r-shares-reddit").attr("href", addthis_config.services_custom[2].url); $(".f1r-shares-mendelay").attr("href", addthis_config.services_custom[1].url); function checkCount(){ setTimeout(function(){ $(".addthis_button_expanded").each(function(){ var count = $(this).text(); if (count !== "" && count != "0") $(this).removeClass("is-hidden"); else $(this).addClass("is-hidden"); }); }, 1000); } close How to cite this report {{reportCitation}} Cancel Copy Citation Details $(function(){R.ui.buttonDropdowns('.dropdown-for-downloads');}); $(function(){R.ui.toolbarDropdowns('.toolbar-dropdown-for-downloads');}); $.get("/articles/acj/14159/15571") new F1000.Clipboard(); new F1000.ThesaurusTermsDisplay("articles", "article", "15571"); $(document).ready(function() { $( "#frame1" ).on('load', function() { var mydiv = $(this).contents().find("div"); var h = mydiv.height(); console.log(h) }); var tooltipLivingFigure = jQuery(".interactive-living-figure-label .icon-more-info"), titleLivingFigure = tooltipLivingFigure.attr("title"); tooltipLivingFigure.simpletip({ fixed: true, position: ["-115", "30"], baseClass: 'small-tooltip', content:titleLivingFigure + " " }); tooltipLivingFigure.removeAttr("title"); $("body").on("click", ".cite-living-figure", function(e) { e.preventDefault(); var ref = $(this).attr("data-ref"); $(this).closest(".living-figure-list-container").find("#" + ref).fadeIn(200); }); $("body").on("click", ".close-cite-living-figure", function(e) { e.preventDefault(); $(this).closest(".popup-window-wrapper").fadeOut(200); }); $(document).on("mouseup", function(e) { var metricsContainer = $(".article-metrics-popover-wrapper"); if (!metricsContainer.is(e.target) && metricsContainer.has(e.target).length === 0) { $(".article-metrics-close-button").click(); } }); var articleId = $('#articleId').val(); if($("#main-article-count-box").attachArticleMetrics) { $("#main-article-count-box").attachArticleMetrics(articleId, { articleMetricsView: true }); } }); var figshareWidget = $(".new_figshare_widget"); if (figshareWidget.length > 0) { window.figshare.load("f1000", function(Widget) { // Select a tag/tags defined in your page. In this tag we will place the widget. _.map(figshareWidget, function(el){ var widget = new Widget({ articleId: $(el).attr("figshare_articleId") //height:300 // this is the height of the viewer part. [Default: 550] }); widget.initialize(); // initialize the widget widget.mount(el); // mount it in a tag that's on your page // this will save the widget on the global scope for later use from // your JS scripts. This line is optional. //window.widget = widget; }); }); } close Error Close Add Reset F1000.MICROSERVICES.AFFILIATION = ''; $(document).ready(function () { $('.js-affiliations-form').each((index, form) => { new AffiliationForm({ formId: form.id, institutionErrorSelector: '.comment-enter-institution', departmentErrorSelector: '.comment-enter-department', placeSelector: '.js-add-comment-place', stateSelector: '.js-add-comment-state', zipCodeSelector: '.js-add-comment-zipcode', countrySelector: '.js-add-comment-country', countryErrorSelector: '.comment-enter-country', }); }); }); $(document).ready(function () { var reportIds = { "50438": 0, "50439": 0, "50440": 16, "50441": 0, "50442": 0, "50443": 0, "50444": 0, "50445": 0, "50446": 0, "50447": 15, }; $(".referee-response-container,.js-referee-report").each(function(index, el) { var reportId = $(el).attr("data-reportid"), reportCount = reportIds[reportId] || 0; $(el).find(".comments-count-container,.js-referee-report-views").html(reportCount); }); var uuidInput = $("#article_uuid"), oldUUId = uuidInput.val(), newUUId = "0647f000-af78-45d1-899a-cd46ccf58022"; uuidInput.val(newUUId); $("a[href*='article_uuid=']").each(function(index, el) { var newHref = $(el).attr("href").replace(oldUUId, newUUId); $(el).attr("href", newHref); }); }); Are you a HRB-funded researcher? Submission to HRB Open Research is open to all HRB grantholders or people working on a HRB-funded/co-funded grant on or since 1 January 2017. Sign up for information about developments, publishing and publications from HRB Open Research. First Name * You must provide your first name Last Name * You must provide your last name Email * You must provide a valid email address Institution You must provide an institution. Submit Thank you! We'll keep you updated on any major new updates to HRB Open Research HRB Open Research Browse How to Publish About Contact RSS Cookie Notice Privacy Notice Legal Submit Your Research © F1000 Research Limited and its licensors ISSN 2515-4826 | Legal background var F1000platform = new F1000.Platform({ name: "hrb", displayName: "HRB Open Research", hostName: "hrbopenresearch.org", id: "5", editorialEmail: "[email protected]", infoEmail: "[email protected]" }); Sign In Remember me Forgotten your password? Sign In Cancel Email or password not correct. Please try again Please wait... $(function(){ // Note: All the setup needs to run against a name attribute and *not* the id due the clonish // nature of facebox... $("a[id=googleSignInButton]").click(function(event){ event.preventDefault(); $("input[id=oAuthSystem]").val("GOOGLE"); $("form[id=oAuthForm]").submit(); }); $("a[id=facebookSignInButton]").click(function(event){ event.preventDefault(); $("input[id=oAuthSystem]").val("FACEBOOK"); $("form[id=oAuthForm]").submit(); }); $("a[id=orcidSignInButton]").click(function(event){ event.preventDefault(); $("input[id=oAuthSystem]").val("ORCID"); $("form[id=oAuthForm]").submit(); }); }); If you've forgotten your password, please enter your email address below and we'll send you instructions on how to reset your password. The email address should be the one you originally registered with F1000. Email address not valid, please try again You registered with F1000 via Google, so we cannot reset your password. To sign in, please click here . If you still need help with your Google account password, please click here . You registered with F1000 via Facebook, so we cannot reset your password. To sign in, please click here . If you still need help with your Facebook account password, please click here . Code not correct, please try again Reset password Cancel Email us for further assistance. Server error, please try again. If your email address is registered with us, we will email you instructions to reset your password. If you think you should have received this email but it has not arrived, please check your spam filters and/or contact for further assistance. Please wait... Register $(document).ready(function () { signIn.createSignInAsRow($("#sign-in-form-gfb-popup")); $(".target-field").each(function () { var uris = $(this).val().split("/"); if (uris.pop() === "login") { $(this).val(uris.toString().replace(",","/")); } }); }); (function(){function c(){var b=a.contentDocument||a.contentWindow.document;if(b){var d=b.createElement('script');d.innerHTML="window.__CF$cv$params={r:'9ff7906f2d71df88',t:'MTc3OTQwODI3Mw=='};var a=document.createElement('script');a.src='/cdn-cgi/challenge-platform/scripts/jsd/main.js';document.getElementsByTagName('head')[0].appendChild(a);";b.getElementsByTagName('head')[0].appendChild(d)}}if(document.body){var a=document.createElement('iframe');a.height=1;a.width=1;a.style.position='absolute';a.style.top=0;a.style.left=0;a.style.border='none';a.style.visibility='hidden';document.body.appendChild(a);if('loading'!==document.readyState)c();else if(window.addEventListener)document.addEventListener('DOMContentLoaded',c);else{var e=document.onreadystatechange||function(){};document.onreadystatechange=function(b){e(b);'loading'!==document.readyState&&(document.onreadystatechange=e,c())}}}})();