CanVasc recommendations for the management of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides – Executive summary

The Canadian Vasculitis research network (CanVasc) is composed of physicians from different medical specialties, including rheumatology and nephrology and researchers with expertise in vasculitis. One of its aims was to develop recommendations for the diagnosis and management of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides in Canada. This executive summary features the 19 recommendations and 17 statements addressing general AAV diagnosis and management, developed by CanVasc group based on a synthesis of existing international guidelines, other published supporting evidence and expert consensus considering the Canadian healthcare context.

ANCA-associated vasculitides (AAV, including granulomatosis with polyangiitis [GPA], microscopic polyangiitis [MPA] and eosinophilic granulomatosis with polyangiitis [EGPA]) are potentially life-threatening vasculitides characterized by inflammation of small-sized blood vessels with resultant ischemic events, hemorrhagic events or both [1]. Their rarity and the heterogeneous nature of AAV mean that the management of individual patients can be extremely challenging and may vary markedly across different geographical regions and medical disciplines. Existing guidelines were initially developed prior to 2010, most have not yet been updated, and did not take into account the specificities of health care system delivery, access to services and drug treatments in Canada [2–11].

The Canadian Vasculitis research network (CanVasc) was created in November 2010 and its core committee includes physicians of different specialties, though primarily rheumatologists and nephrologists. One of the first major objectives of CanVasc was the development of recommendations for the management of patients with AAV within Canada, based on a synthesis of existing international guidelines, supporting evidence and expert consensus of a national Canadian AAV clinical and research network.

Contexte

Les vascularites associées aux ANCA (les VAA, incluant la granulomatose avec polyangéite [GPA], la polyangéïte microscopique [MPA], et la granulomatose éosinophilique avec polyangéite [EGPA]) sont des vascularites caractérisées par une inflammation de la paroi des vaisseaux sanguins de petit calibre, aboutissant à des complications ischémiques ou hémorragiques, et qui mettent souvent en jeu le pronostic vital. Leur rareté, de même que leur présentations cliniques variées, rendent la prise en charge des patients extrêmement ardue, surtout si elle diffère selon les régions géographiques et les disciplines médicales. Les recommandations internationales de prise en charge des VAA existantes ont été développées avant 2010; la plupart n’ont pas encore été mises à jour et aucune ne tenait compte des spécificités de prestation des soins, d’accès aux services et aux divers traitements pharmacologiques dans le réseau de santé canadien.

Le groupe de recherche canadien sur les vascularites (CanVasc) a été créé en novembre 2010. Il est constitué de médecins de diverses spécialités, quoique surtout des rhumatologues et néphrologues. L’un des objectifs principaux de CanVasc était l’élaboration de recommandations de prise en charge des patients atteints de VAA au Canada, en se basant sur les recommandations internationales déjà existantes, les autres preuves scientifiques et publications dans le domaine des VAA, et un processus avec plusieurs étapes afin d’aboutir à un consensus.

Prior to initiating the development of these recommendations, a national Needs Assessment Questionnaire was disseminated to identify the specific areas of need, possible knowledge gaps and outline key questions [12]. The international existing clinical practice guidelines and consensus statements on the management of AAV published in English or French between 2006 and May 2014 were then reviewed, in addition to Cochrane library and PubMed Medline searches for all therapeutic studies published after the 2009 European League against Rheumatism/European Vasculitis Society (EULAR/EUVAS) recommendations and May 2014. The first draft of these recommendations was developed by the core group of the CanVasc recommendation working group and included 37 recommendations, with the rationale behind each of them, the corresponding recommendations and guidance from other societies, when existing and the level of evidence categorized and graded according to the criteria previously endorsed by EULAR/EUVAS [2, 13]. This first draft was reviewed by all members of the CanVasc recommendation working group (using a modified Delphi method) with a phone conference held thereafter to reach consensus on all debated recommendations, especially those not agreed upon by >80 % of the reviewers. A revised version of recommendations was then developed and distributed again for review to the same working group and a broader spectrum of other reviewers, including members of several professional medical societies and specialists and the administrative bureau of the Canadian support group for vasculitis patients (Vasculitis Foundation Canada). The comments were gathered and discussed during a second teleconference with the members of the CanVasc recommendation working group to reach consensus on the final version of the document, which was endorsed by the Canadian Rheumatology Association (CRA) Guidelines Committee on March 21st, 2015.

The final document (the full version of the recommendations is available online at http://www.jrheum.org) includes 19 recommendations and 17 statements addressing general management strategies for AAV, including their diagnosis, treatments with glucocorticoids, traditional immunosuppressants and biologic agents, and follow up for rheumatologists, nephrologists, respirologists, general internists, general practitioners and all other health care professionals more occasionally involved in the management of patients with AAV in community and academic practice settings. Each therapeutic recommendation and statement is accompanied by supporting text, which reports on the expected health benefits, potential side effects and risks, and Canadian system factors that may influence their applicability. Therapeutic recommendations are presented with a level of evidence and strength (Table 1 of the executive summary). Statements are for non-therapeutic recommendations and working group consensus, for which there is no strong supporting evidence from controlled studies are not graded. For each recommendation and statement, we also present in the extended version (available online with the full version of the recommendations at http://www.jrheum.org) corresponding recommendations and guidance previously published on the same topic from other societies, when available.

This document will serve as useful knowledge to support decision-making for any physician involved in the care of patients with AAV, including adults and children. Best clinical judgment must however always prevail when confronted with each specific patient scenario. New information from ongoing research may already have become available by the time the present document is published. Regular updates will thus be mandatory.

In addition to the authors, the following persons participated in the development of these recommendations (reviewers): Drs. Corisande Baldwin, Maria Bagovich, Claire Barber, Joanne Bargman, David Barth, Sankalp Bhavsar, Ken Blocka, Gilles Boire, Boussier, Robert Ferrari, Michele Hladunewich, Susan Huang, Jacob Karsh, Kim Legaut, Emil Nashi, Maxime Rhéaume, Nathalie Roy, Evelyn Sutton, Yves Troyanov, Pearce G. Wilcox; and the Vasculitis Foundation Canada (Jon Stewart, Katherine Smith and Barbara Tuntoglu, from the administrative board). Sandra Messier provided administrative coordination and support and Dr. Shahin Jamal and the CRA therapeutic committee provided guidance throughout the development of these recommendations.

Disclosures

The development of these recommendations was entirely self-funded. None of the authors received any fees, grants or emoluments for the development of these recommendations. No funding support from pharmaceutical companies was received; no representatives of pharmaceutical companies were involved at any step in the development of these recommendations. Potential conflicts for each working group member including industry funding, consultancies, commercial interests and direct involvement in any guidelines included in the systematic review are listed in the Appendices (available online at http://www.jrheum.org).

Affiliations

1. Department of Rheumatology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada

   • Lucy McGeoch
   • , Simon Carette
   •  & Christian Pagnoux

2. Current address: Centre for Rheumatic Diseases, Glasgow Royal Infirmary, Glasgow, UK

   • Lucy McGeoch

3. Division of Pediatric Rheumatology, Alberta Children’s Hospital, University of Calgary, Calgary, Alberta, Canada

   • Marinka Twilt
   •  & Susan Benseler

4. Division of Rheumatology, McMaster University, Hamilton and Langs Community Centre, Cambridge, Canada

   • Leilani Famorca

5. Division of Rheumatology, QEII Health Sciences Centre and Dalhousie University, Halifax, Nova Scotia, Canada

   • Volodko Bakowsky

6. Division of Rheumatology, St. Joseph’s Health Care, London, Ontario, Canada

   • Lillian Barra

7. Division of Pediatric Rheumatology, BC Children’s Hospital and University of British Columbia, Vancouver, British Columbia, Canada

   • David A. Cabral

8. Division of Respirology, McMaster University, St. Joseph’s Healthcare, Hamilton, Ontario, Canada

   • Gerald P. Cox

9. Division of Nephrology, Dalhousie University, Halifax, Nova Scotia

   • Navjot Dhindsa

10. Section of Rheumatology, University of Manitoba, Arthritis Centre, Winnipeg, Manitoba, Canada

    • Christine Dipchand

11. University of Calgary, Calgary, Alberta, Canada

    • Aurore Fifi-Mah

12. Division of Internal Medicine, Hôpital Du Sacré-Coeur, Montréal, Québec, Canada

    • Michele Goulet

13. Division of Rheumatology, McMaster University, Hamilton, Ontario, Canada

    • Nader Khalidi

14. Division of Rheumatology, Memorial University of Newfoundland, Nexus Clinical Research, St. Johns, Newfoundland, Canada

    • Majed M. Khraishi

15. Division of Rheumatology, Centre Hospitalier Universitaire de Sherbrooke, Québec, Canada

    • Patrick Liang

16. Division of Rheumatology, the Ottawa Hospital/University of Ottawa, Ottawa, Ontario, Canada

    • Nataliya Milman

17. Division of Rheumatology, Lupus and Vasculitis Clinic, McGill University, Montréal, Québec, Canada

    • Christian A. Pineau

18. Gabor Zellerman Chair in Nephrology Research of Toronto, Division of Nephrology, University Health Network, Toronto, Ontario, Canada

    • Heather Reich

19. Division of Rheumatology and the Arthritis Program Research Group in Newmarket, Newmarket, Ontario, Canada

    • Nooshin Samadi

20. Division of Rheumatology, Arthritis Research Canada, University of British Columbia, Vancouver, British Columbia, Canada

    • Kam Shojania

21. Division of Rheumatology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

    • Regina Taylor-Gjevre

22. Department of Medicine, Queen’s University, Kingston, Ontario, Canada

    • Tanveer E. Towheed

23. Division of Rheumatology, CHAU Hôtel-Dieu de Lévis, Université Laval, Québec, Canada

    • Judith Trudeau

24. Department of Medicine and Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada

    • Michael Walsh

25. Division of Rheumatology, University of Alberta, Edmonton, Alberta

    • Elaine Yacyshyn

Consortia

Corresponding author

Correspondence to Christian Pagnoux.

Competing interests

Lucy McGeoch, Marinka Twilt, Leilani Famorca, Susan Benseler, David Cabral, Simon Carette, Christine Dipchand, Michelle Goulet, Majed Khraishi, Nataliya Milman, Nooshin Samadi, Regina Taylor-Gjevre, Tanveer A. Towheed, Michael Walsh and Elaine Yacyshyn: These authors declare that they have no competing interests. Volodko Bakowsky: Fees for serving on advisory boards from Hoffman-LaRoche. Lillian Barra: Honoraria from Hoffman-LaRoche, Abbvie, Amgen and UCB (<$5,000). Gerard P. Cox: Fees for serving on advisory board from Hoffman-LaRoche (2013). Navjot Dhindsa: Honoraria from Hoffman-LaRoche and Abbvie. Aurore Fifi-Mah: Fees for serving on advisory boards from Hoffman-LaRoche. Nader Khalidi: Fees for serving on advisory Boards from Hoffman-LaRoche, Bristol-Myers Squibb, UCB; lecture fees from Hoffman-LaRoche. Patrick Liang: Honorarium for lectures from Hoffman-LaRoche, Abbvie, Bristol-Myers Squibb, Janssen, Pfizer; financial support for clinical project from Hoffman-LaRoche. Christian A. Pineau: Fees for serving on advisory boards from Hoffman-LaRoche. Heather Reich: Fees for providing advisory services to Hoffman-LaRoche, AMGEN and Alexion. Kam Shojania: Lecture and consultation fees from Hoffman-LaRoche (<$5,000). Judith Trudeau: Fees for serving on advisory boards for Hoffman-LaRoche and Bristol-Myers Squibb; grant for attending scientific meetings on vasculitis by Hoffman-LaRoche. Christian Pagnoux: Fees for serving on advisory boards from Hoffman-La Roche, Genzyme and GlaxoSmithKline; lecture fees from Roche, Bristol-Myers Squibb and EuroImmune; grant support from Hoffman-La Roche Roche; coordinator of the 2007 French Vasculitis Study Group recommendations (Protocole national de diagnostic et de soins - vascularites nécrosantes systémiques; under the aegis of the Haute Autorité de Santé).

Authors' contributions

CP organized and led the development of this document; LM, MT and LF wrote the first draft and edited the second and final draft of this document; all authors participated in the development of this document in its different stages (as detailed in the Methods), read and approved the final manuscript.

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