Managing ANCA Vasculitis: Guideline ‘Transcends' Specialties

Medscape

13-05-2025

MANCHESTER, England — A soon-to-be-released guidance from the British Society for Rheumatology on the management of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) emphasizes not only the need for more aggressive management but also the importance of cross-specialty services that can be accessed quickly throughout the United Kingdom.
The revised recommendations are timely as they coincide with a National Health Service (NHS) England initiative that is looking at how to improve rheumatology services across the board generally through its Getting It Right First Time initiative. One of the first steps in this initiative for improving AAV services in particular has been to set up a national cohort of patients that can be tracked through the healthcare system to see what improvements are needed in order to optimize overall care and service outcomes.
'The management of vasculitis transcends specialty,' Neil Basu, MBChB, PhD, professor of musculoskeletal medicine and vasculitis at the University of Glasgow, Glasgow, Scotland, said in introducing the updated AAV guidelines, which he was a part of, at the British Society for Rheumatology (BSR) 2025 Annual Meeting. 'I think it's entirely appropriate, and great, that we have a nephrologist leading the way with our BSR guidelines.'
Lorraine Harper, MBChB, PhD
That nephrologist is Lorraine Harper, MBChB, PhD, a consultant and professor at the University of Birmingham, Birmingham, England, and chair of the multidisciplinary team of experts who have been involved in updating the guidance.
Harper noted at the BSR session that it was high time that the recommendations for managing AAV in the United Kingdom were reprised: 'The 2014 guidelines really did significantly impact the way we managed patients with vasculitis, but there's a lot gone on since 2014, and it now doesn't reflect best practice.'
Moreover, the previous guidance did not 'span the age range,' Harper said, a consideration that has now been included in the AAV guidance update, as well as many other BSR clinical guidelines that have been updated recently.
In comments to Medscape Medical News , Chetan Mukhtyar, MD, PhD, a consultant rheumatologist for Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, England, who was not involved with creating the guidelines, said 'there are some emerging data that have now demonstrated what we have always known in vasculitis, that it is not something that should be taken lightly; it has significant immediate mortality, and it has long-term implications on resources. We need to get it right, quickly and first time, and the recommendations will help us get there, but the resource implications will need to be recognized by the wider NHS.'
Building on Existing Evidence
Members of the British AAV guideline working group consulted recent recommendations from other organizations, including that from the American College of Rheumatology (ACR) published in 2021, the European Alliance of Associations for Rheumatology (EULAR) published last year, and the Kidney Disease: Improving Patient Outcomes (KDIGO) organization, also published in 2024.
'Although we used the BSR methodology, we did adapt a little bit, so we didn't do the literature search from 2014; where the area we're looking at was covered by EULAR, we used their literature search. So that we weren't just reinventing the wheel,' Harper said.
To produce the guidance, 30 experts across the five specialties of rheumatology, nephrology, otolaryngology, respiratory medicine, and pediatrics formed five small working groups to look at specific topic areas. These were the treatment of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA); the treatment of subglottic stenosis and ear, nose, and throat (ENT) disease associated with GPA; the treatment of eosinophilic granulomatosis with polyangiitis (EGPA); service specification; and patient education and support.
Key Update Examples
The revised recommendations, which are expected to be published in early June, include a change to how immunosuppression should be used in the initial treatment of GPA and MPA, with a more aggressive approach than previously.
'Back in 2014, we recommended [intravenous] pulsed cyclophosphamide or rituximab for organ- or life-threatening disease. We've amended that now to suggest that all patients with active ANCA vasculitis should be considered for intravenous pulsed cyclophosphamide or rituximab,' Harper said.
In addition, treatment with rituximab should be preferred for patients with relapsing disease. This aligns with the 2024 EULAR guidance but differs from the 2021 ACR guidance, she said.
The revised British guidance states that methotrexate and mycophenolate mofetil 'may be considered' as alternatives for induction therapy for patients with active disease but without any evidence of life- or organ-threatening disease, but that cyclophosphamide and rituximab are preferred.
'Plasma exchange remains a contentious issue, and should we use it?' Harper asked. In the PEXIVAS trial, there was no difference seen in the combined outcome endpoint of death and end stage kidney disease. However, post hoc data suggest there could be earlier and fuller recovery of renal function with plasma exchange.
Based on available data, the British recommendation 'takes a pragmatic view' to think about using plasma exchange only in adult patients with active GPA or MPA and severe renal involvement if they have a serum creatinine level > 300 mmol/L (3.4 mg/dL).
The use of adjunctive plasma exchange needs to be carefully balanced against the risk for potential adverse events, Harper cautioned. And while its use in pediatrics should be limited to a case-by-case basis, plasma exchange does appear to have beneficial role in managing pulmonary hemorrhage, so long as there is no severe kidney involvement.
Reducing Glucocorticoid Dependency
With avacopan (Tavneos) now available, the recommendations are to use it in active GPA or MPA as a potential glucocorticoid-sparing agent; this could be given with or without a short course of steroids, Harper explained, with tapering taking place over a 4-week period.
For patients with organ- or life-threatening disease, the recommendation is to use oral steroids at a starting dose of 50-75 mg, or 1.0 mg/kg/d; dosing is dependent on weight, Harper said, with the maximum daily recommended dose at 75 mg. Oral prednisolone should be tapered in accordance with the schedule used in the PEXIVAS trial, with the aim to get the dose down to 5 mg prednisolone equivalent per day by 4-5 months.
And if the disease is considered neither organ- nor life-threatening, lower steroid-tapering regimens can be considered, starting at a dose of 0.5 mg/kg/d, and tapering according to the schedule used in the LoVAS clinical trial.
For maintenance therapy, Harper reported that the updated recommendation was to use rituximab in preference to other agents, using a fixed dosing regimen of 500-1000 mg every 4-6 months. Such treatment should be continued for at least 2-4 years. This was 'a big change' from the 2014 guidance, but again follows ACR, EULAR, and KDIGO guidance.
'Limited GPA' a Misnomer
'We want to get away from using the term 'limited,' when it comes to talking about GPA-related ENT disease because it underestimates the disease burden,' Harper said. Instead, 'ENT-localized' or 'sino-nasal GPA' would be preferred.
ENT involvement is where multidisciplinary assessment is particularly vital, Harper said. If there is a plan for reconstructive surgery, the patient needs to be in remission for at least 12 months 'otherwise high failure and complication rates are observed,' she said.
Recommendation Updates for EGPA
The presence of asthma, particularly if it is adult-onset, remains important for making an EGPA diagnosis. Asthma combined with chronic rhinosinusitis with or without nasal polyps, eosinophilia (typically ≥ 1.5 × 109/L), and end-organ involvement would be considered indicative of having EGPA.
Harper acknowledged that because of EGPA's heterogeneous clinical phenotype, a specialized multidisciplinary approach is necessary to exclude other eosinophilic syndromes.
For initial treatment, it is recommended that all patients with active disease are assessed for their suitability for induction treatment with glucocorticoids combined with other immunomodulatory agents. Harper noted that the recommended first-line option is intravenous pulsed cyclophosphamide, but if it is contraindicated or unacceptable to the patient, rituximab would be the next choice.
As for newer treatments, the anti–interleukin-5–directed therapies mepolizumab and benralizumab were recommended for induction and maintenance of remission, but only in people with nonorgan– or nonlife–threatening disease, Harper said. This is because the recommendation is based on the findings of the MIRRA and MANDARA trials, which excluded patients with more serious disease. Thus, the current recommendation is only to use these drugs in the same population of patients as had been studied in the trials, Harper said.
Service Recommendations
One of the unique aspects of the guideline update is its detailing of how vasculitis services in the United Kingdom should ideally be set up, and not just based on expert opinion.
Rosemary J. Hollick
This is the first time that specific, patient-led service recommendations have been included in BSR guidelines, or indeed any vasculitis guidelines, said Rosemary J. Hollick, MBChB, PhD, a senior clinical lecturer and rheumatologist at the University of Aberdeen, Aberdeen, Scotland, and the clinical lead for the Scottish Systemic Vasculitis Managed Clinical Network.
The recommendations are based on findings from the Versus Arthritis–funded Vasculitis Outcomes In relation to Care Experience Study (VOICES), which looked at the key components of the best possible service and linked them to patient outcomes.
Prompt Specialist Review
A key recommendation is that people with newly suspected AAV should have a specialist vasculitis review within 7 days. This is backed up by data from VOICES, which showed prompt review to be associated with a 30% reduction in serious infections, a 22% drop in emergency hospital admissions, and a 41% reduction in deaths, Hollick noted.
'Vasculitis has been long overlooked,' Basu told Medscape Medical News in an interview. 'I think we finally have some excellent tools to improve outcomes dramatically, but the challenge is accessing these tools.'
It is important for clinicians, particularly if they are not specialists, to be able to get the support they need to diagnose patients 'really promptly,' Basu added.
Thus, the other key service recommendation in the guideline focuses on how to give that support to clinicians, such as in caring for patients in dedicated, 'cohorted' vasculitis clinics that include nurse-led components of care and regular specialist multidisciplinary team meetings. Data from the VOICES study have suggested that both nurse-led and cohorted clinics result in significant reductions in both serious infections (35% and 25%, respectively) and emergency hospital admissions (25% and 19%, respectively).
A further recommendation is that people with AAV should feel empowered in shared decision-making and collaborate with their healthcare team to make joint decisions about their care. There are many tools already out there to help explain what shared decision-making should look like to patients, Hollick said.
VOICES was funded by Versus Arthritis . Basu and Harper reported no relevant financial relationships. Hollick had received funding unrelated to her presentation from CSL Vifor. Mukhtyar was not involved in the guideline development.