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European ANCA-associated vasculitis guidance gets first makeover since 2009

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Recommendations serve as framework for building individualized care

The prior 2009 EULAR recommendations were very much in need of updating given the plethora of studies in the past 7 years addressing ANCA-associated vasculitis (AAV). The emergence of rituximab as an effective therapy in AAV had to be considered and included in these newer guidelines. Its potential role in both remission induction, as well as remission maintenance of AAV, is addressed.

The recommendations are somewhat complicated, particularly as eosinophilic granulomatosis with polyangiitis (EGPA, previously referred to as Churg-Strauss syndrome) has been included, but most of the well-done prospective clinical trials addressing remission induction and remission maintenance in AAV were limited to patients with granulomatosis with polyangiitis or microscopic polyangiitis and did not include patients with EGPA. The role of plasma exchange is also discussed, but the results of the PEXIVAS trial, which will address that more definitively, are not yet forthcoming. Those results are anticipated in the not too distant future and will much better define that component of management in those most severely ill patients with AAV.

Dr. Robert Spiera

These recommendations serve as a framework for helping clinicians understand what is widely accepted as standard of care for these diseases but in no way can define individual treatment decisions as the authors acknowledge. Such decisions must become very personalized in relation to details of the patient’s individual comorbidities and other features of their medical and even socioeconomic status. For example, when choosing between rituximab and cyclophosphamide for remission induction in a young woman (or man, for that matter), future fertility concerns (which cyclophosphamide could potentially compromise) are very relevant. Moreover, the costs of rituximab are substantial, and the lack of superiority of rituximab over cyclophosphamide in many situations, particularly in patients with new severe disease, could be an important factor to consider when choosing which immunosuppressive will be used.

Many of the unanswered questions await results of ongoing or upcoming trials, including some addressing the relative efficacy of various remission maintenance regimens (rituximab vs. azathioprine) or the role of plasmapheresis. Many questions in AAV are not easily addressable in clinical trials, such as whether there are some groups of patients in whom remission maintenance therapy should never be withdrawn. However, such questions may be addressed through observational studies of the well-defined patient cohorts and registries that have been developed in the United States and Europe.

Robert F. Spiera, MD, is director of the Scleroderma, Vasculitis, & Myositis Center at the Hospital for Special Surgery, N.Y. He is also professor of clinical medicine at Cornell University, N.Y. He has received research funding and consulting fees from Roche/Genentech, which markets rituximab.




LONDON – Updated management recommendations for patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis from the European League Against Rheumatism and the European Renal Association-European Dialysis and Transplant Association aim to provide clinicians with reliable guidance on the best approach to treatment.

The update, presented at the European Congress of Rheumatology and recently published online in Annals of the Rheumatic Diseases (Ann Rheum Dis. 2016 Jun 23. doi:10.1136/annrheumdis-2016-209133), reassessed items in the 2009 recommendations for the management of primary systemic vasculitis and focused only on the management of ANCA-associated vasculitis (AAV), according to recommendations task force member Dr. Max Yates.

Dr. Max Yates

Dr. Max Yates

“In the past 5 years, 1,691 papers have been published on primary systemic vasculitis in internal medicine, rheumatology, and nephrology journals. Together with the licensing of rituximab for AAV, it was an opportune time to update the recommendations with an AAV focus,” Dr. Yates explained. The revised guidance is based on a systematic literature review from January 2007 to February 2015, focusing in particular on specific items that needed updating, such as the importance of ANCA testing and biopsy in diagnosis and follow-up, disease staging at diagnosis, the choices for remission-induction and remission-maintenance therapies, and the drug choices for relapsing and refractory disease. The task force considered for the first time the choice of immunosuppressive drugs and biologic agents (principally rituximab) and immunologic monitoring. They identified patient education as another priority.

“These updated recommendations provide a framework of practice and should apply to the majority of patients with AAV,” added Dr. Yates, who is a clinical fellow at Norwich Medical School at the University of East Anglia and works in the department of rheumatology at the Norfolk and Norwich (England) University Hospital.

The 22-member task force included rheumatologists, internists, nephrologists, a clinical immunologist, an otorhinolaryngologist, a chest physician, an ophthalmologist, a vasculitis nurse, and a patient with vasculitis from 11 countries in Europe and the United States. The task force was convened by rheumatologist Dr. Chetan Mukhtyar of the Norfolk and Norwich University Hospital on behalf of EULAR and by vasculitis and renal specialist Dr. David Jayne of Addenbrooke’s Hospital in Cambridge (England) on behalf of the European Renal Association-European Dialysis and Transplant Association.

The recommendations now contain one single, simple overarching principle, Dr. Mukhtyar said at the congress. That is, the need for shared decision making between the patient and the clinician. This principle is also included as the first point in many of the other recently updated EULAR recommendations on the management of rheumatic diseases.

Both previous and updated versions of the vasculitis recommendations contain 15 recommendations, with some changed and others combined. One key recommendation is about who should treat patients with AAV; it states that patients “should be managed in close collaboration with, or at, centers of expertise,” Dr. Mukhtyar said.“Patients with ANCA-associated vasculitis have often very complex presentations that involve several different specialties, and it is always worthwhile that these patients are looked after by people who commonly see them, because these are rare conditions,” he observed.

Deciding when to perform a biopsy is also covered, with the recommendation being that it can be used to establish a new diagnosis and to further evaluate cases of suspected relapsing vasculitis. “When do you do a biopsy?” Dr. Mukhtyar asked. “Well, every time you can, every time it is clinically feasible,” he suggested.

As for treatment, there are different recommendations depending on whether the aim is to induce or maintain remission and whether there has been a major relapse. In patients with organ- or life-threatening disease, for example, the advice is to use glucocorticoids and either cyclophosphamide or rituximab to induce remission, Dr. Mukhtyar said. The specific dosing or administration of glucocorticoids is not specified as this will depend on the clinical situation, but the advice is to taper down when possible, somewhere between month 3 and 5.

For remission induction in less severe (non–organ threatening) disease, the recommendation is to use glucocorticoids plus either methotrexate or mycophenolate mofetil. Situations when methotrexate or mycophenolate mofetil should and should not be used are specified, notably when cyclophosphamide or rituximab are not available or are contraindicated.

For maintenance of remission, the task force advised using low-dose glucocorticoids plus azathioprine, rituximab, methotrexate, or mycophenolate mofetil.

Guidance on when to use plasma exchange is given for patients with severe disease and options following failure of remission-induction therapy, and when to switch therapy is also covered.

There are also several follow-up recommendations, such as the periodic assessment of cardiovascular risk, and patient-focused recommendations on awareness of the nature, benefits, and risks of therapy.


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