Long-term outcomes and prognostic factors for survival of patients with ANCA-associated vasculitis
Authors: Sánchez Álamo Beatriz , Moi Laura , Bajema Ingeborg , Faurschou Mikkel , Flossmann Oliver , Hauser Thomas , Hruskova Zdenka , Jayne David , Luqmani Raashid , Mahr Alfred , Åkesson Anna , Westman Kerstin ,   the EUVAS, Andreas Kronbichler , Irmgard Neumann , Daniel Blockmans , Alain Le Moine , Zdenka Hruskova , Vladimir Tesar , Mikkel Faurschou , Wladimir Szpirt , Agneta Ekstrand , Anna Salmela , Alfred Mahr , Solange Gonzalez Chiappe , Marion Haubitz , Raoul Bergner , Michaela Streubert , Matthias Schaier , Wilhelm Schmitt , Ulf Schönenmarck , Kirsten De Groot , Smaragdi Marinaki , John Boletis , Mark Little , Gina Gregorini , Augusto Vaglio , Federico Alberici , Sinico Renato , Giacomo Garibotto , Annalisa Carta , Marisa Santostefano , Maria Brugnano Rachele , Jolanta Dadoniene , Ingeborg Bajema , Annelies Berden , Onno Teng , Maria Cid , Georgina Espigol , Jose Ballarin , Isabel García , Luis Quintana , Pérez Fernández Elia , María Fernández Juárez Gema , Beatriz Sánchez Álamo , Thomas Hauser , Thomas Neumann , Carlo Chizzolini , Jean-François Balavoine , Laura Moi , Annette Bruchfeld , Mårten Segelmark , Kerstin Westman , Anna Åkesson , Iva Gunnarsson , David Jayne , Lorraine Harper , Oliver Flossmann , Raashid Luqmani , Steve Mcadoo , Peter Lanyon , Alan Salama , Karen Dahlsveen , Joe Rosa , Joe Barrett 
Published: January 2023

ABSTRACT

Background
Despite newer treatments with immunosuppressive agents, there still exists a considerable morbidity and mortality risk among patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Since 1994 the European Vasculitis Society (EUVAS) has aimed for an improved outcome for patients with AAV, conducting several prospective randomized controlled trials (RCTs). The aim for the present study was to further evaluate the long-term survival of patients with AAV included in seven RCTs conducted by the EUVAS as well as to identify potential prognostic factors.

Methods
Long-term follow-up data were collected from questionnaires sent to the principal investigators of the original RCTs (1995–2012): MEPEX, NORAM, CYCAZAREM, CYCLOPS, IMPROVE, RITUXVAS and MYCYC, comprising 848 patients, all newly diagnosed with AAV. Relative survival estimates are presented for the study cohorts. Demographic, clinical and laboratory characteristics at trial entry were studied as potential prognostic factors in multivariable models.

Results
A total of 478 (56%) patients had granulomatosis with polyangiitis (GPA) and 370 (44%) had microscopic polyangiitis (MPA) with a mean age at diagnosis of 58 ± 14 years. The median follow-up time was 8 years (interquartile range 2.9–13.6). During the observation period there were 305 deaths and the main causes were infections (26%), cardiovascular disease (14%) and malignancies (13%). When compared with a matched cohort (regarding country, age group and sex) from the background population there were 14.2% more deaths among our cohort of AAV patients at 5 years, 19.9% at 10 years, 28.8% at 15 years and 36.3% at 20 years. The excess mortality occurred in all age groups. The estimated median survival time (from diagnosis) was 17.8 years (95% confidence interval 15.7–20). Among variables measured at baseline, advanced age, male sex, low estimated glomerular filtration rate and low platelet count were identified as predictors of death in a multivariate Cox model.

Conclusions
Patients with AAV still have an increased risk of mortality compared with the general population despite newer therapeutic regimens. Treatment complications and organ damage are the main causes of limited survival and infections remain the leading cause of mortality among patients with AAV.