Risk of Serious Infection in Granulomatosis with Polyangiitis or Microscopic Polyangiitis: Long-Term Outcomes of 126 Wegent Trial Patients

Xavier Puéchal¹, Christian Pagnoux², Elodie Perrodeau³, Mohamed Hamidou⁴, Jean-Jacques Boffa⁵, Xavier Kyndt⁶, François Lifermann⁷, Thomas Papo⁸, Dominique Merrien⁹, Amar Smail¹⁰, Philippe Delaval¹¹, Catherine Hanrotel-Saliou¹², Bernard Imbert¹³, Chahéra Khouatra¹⁴, Marc Lambert¹⁵, Charles Leské¹⁶, Kim H. Ly¹⁷, Edouard Pertuiset¹⁸, Pascal Roblot¹⁹, Marc Ruivard²⁰, Jean-François Subra²¹, Jean-Francois Viallard²², Benjamin Terrier²³, Pascal Cohen²³, Luc Mouthon²⁴, Philippe Ravaud³ and Loïc Guillevin for the French Vasculitis Study Group²⁵, ¹National Referral Center for Rare Systemic Autoimmune Diseases, Hôpital Cochin, AP–HP, Université Paris Descartes, Paris, France, ²Mount Sinai Hospital, Toronto, ON, Canada, ³Paris Hotel Dieu, Paris, France, ⁴Medecine Interne, CHU Hôtel Dieu, Nantes, France, ⁵Paris Tenon, Paris, France, ⁶Valenciennes, Valenciennes, France, ⁷Dax, Dax, France, ⁸Paris Bichat, Paris, France, ⁹Compiègne, Compiègne, France, ¹⁰Amiens, Amiens, France, ¹¹Rennes, Rennes, France, ¹²Brest, Brest, France, ¹³Grenoble, Grenoble, France, ¹⁴Lyon, Lyon, France, ¹⁵Lille, Lille, France, ¹⁶Cholet, Cholet, France, ¹⁷Limoges, Limoges, France, ¹⁸Pontoise, Pontoise, France, ¹⁹Poitiers, Poitiers, France, ²⁰CHU Estaing, Department of Internal Medicine, Clermont-Ferrand, France, Clermont Ferrand, France, ²¹Angers, Angers, France, ²²Bordeaux, Bordeaux, France, ²³Service de Médecine Interne, Hôpital Cochin, Centre de référence national pour les maladies systémiques autoimmunes rares d’Ile de France, DHU Authors, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France, Paris, France, ²⁴Service de Médecine Interne, Hôpital Cochin, Centre de référence national pour les maladies systémiques autoimmunes rares d’Ile de France, DHU Authors, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France ;Université Paris Descartes Sorbonne Paris, Paris, France, ²⁵Service de Médecine Interne, Centre de Référence Maladies Auto-Immunes et Auto-Inflammatoires Systémiques Rares, Hôpital Cochin, Paris, France

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: ANCA, infection and vasculitis

Session Information

Date: Monday, November 6, 2017

Title: Vasculitis Poster II: ANCA-Associated Vasculitis

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Adverse events, rather than active vasculitis, are the greatest threat to patients with ANCA-associated vasculitides (AAVs) during the first year of therapy but long-term data on the risk of serious infections are scarce. Results of the randomized–controlled WEGENT trial demonstrated that, after cyclophosphamide-induction therapy, methotrexate or azathioprine is a comparable option to maintain granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) remission but, at long-term follow-up, relapses and serious adverse events (SAEs) remain matters of concern.^1,2

Methods: The long-term outcomes of 126 WEGENT trial patients were ascertained, including survival, immunosuppressant use and serious infections. Follow-up began at trial inclusion and continued until the last follow-up visit, death or 10 years postinclusion, whichever occurred first. Demographic, clinical and laboratory parameters at trial entry were evaluated as potential prognostic factors for serious infection in univariable and multivariable models. Analyses were adjusted to the length of follow-up.

Results: Among the 126 trial participants, long-term follow-up information was available for 124 (98.4%); 27 (21.4%) died before 10 years of follow-up and 14 (11.1%) were lost-to-follow-up. Median follow-up was 11.9 (95% confidence interval [95% CI] 11.3–12.5) years. At 10 years, 68 patients had had at least 1 serious adverse event (SAE), including 31 serious infections (requiring hospitalization) for 25 (20%), corresponding to a 2.5 per 100 patient-years incidence rate. At inclusion, mean (± standard deviation) age of the patients who would develop serious infections was 62.0 ± 13.1 vs. 57.6 ± 12.7 for those who did not (P=0.051). Median (Q1–Q3) time to infection was 2.3 (0.2–4.2) years postinclusion. The most frequent serious infections were 15 lung infections and 5 sepses. Infection led to 4 (3%) deaths (at mean age 74.5 ± 6.5 years), occurring a mean of 4.7 ± 3.4 years postinclusion. The 10-year overall survival rate was 77.5% [95% CI 70.4–85.4%] and the 10-year survival rate without SAE was 42.7% [95% CI 34.8–52.4%]. Univariable analysis variables significantly associated with serious infection at the 20% threshold were age, AAV entity, ANCA-negativity, pulmonary involvement, fewer pre-inclusion cyclophosphamide infusions and lower cumulative cyclophosphamide dose. Multivariable analyses retained AAV (incidence rate ratio GPA vs. MPA 3.60 [95% CI 1.05–12.3]; P=0.043) and previous cumulative cyclophosphamide dose (0.78 [95% CI 0.67–0.91]; P=0.002) as being significantly prognostic of serious infection.

Conclusion: The results of this long-term analysis confirm that serious infections are responsible for high morbidity and potential mortality during long-term AAV-patient follow-up. Serious infections represent nearly half of SAEs and led to the deaths of 3% of the patients. Further studies should examine newer strategies to prevent infections in AAV patients.

References: 1/ Pagnoux C et al. N Engl J Med 2008:359:2790-803. 2/ Puéchal X et al. Arthritis Rheumatol 2016;68:690-701.

Disclosure: X. Puéchal, None; C. Pagnoux, None; E. Perrodeau, None; M. Hamidou, None; J. J. Boffa, None; X. Kyndt, None; F. Lifermann, None; T. Papo, None; D. Merrien, None; A. Smail, None; P. Delaval, None; C. Hanrotel-Saliou, None; B. Imbert, None; C. Khouatra, None; M. Lambert, None; C. Leské, None; K. H. Ly, None; E. Pertuiset, None; P. Roblot, None; M. Ruivard, None; J. F. Subra, None; J. F. Viallard, None; B. Terrier, None; P. Cohen, None; L. Mouthon, None; P. Ravaud, None; L. Guillevin for the French Vasculitis Study Group, None.

To cite this abstract in AMA style:

Puéchal X, Pagnoux C, Perrodeau E, Hamidou M, Boffa JJ, Kyndt X, Lifermann F, Papo T, Merrien D, Smail A, Delaval P, Hanrotel-Saliou C, Imbert B, Khouatra C, Lambert M, Leské C, Ly KH, Pertuiset E, Roblot P, Ruivard M, Subra JF, Viallard JF, Terrier B, Cohen P, Mouthon L, Ravaud P, Guillevin for the French Vasculitis Study Group L. Risk of Serious Infection in Granulomatosis with Polyangiitis or Microscopic Polyangiitis: Long-Term Outcomes of 126 Wegent Trial Patients [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/risk-of-serious-infection-in-granulomatosis-with-polyangiitis-or-microscopic-polyangiitis-long-term-outcomes-of-126-wegent-trial-patients/. Accessed .

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