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Abstract Number: 1747

Long-Term Outcomes of Patients with Nonsevere Eosinophilic Granulomatosis with Polyangiitis Given Azathioprine and Glucocorticoids for Remission Induction

Xavier Puéchal1, Christian Pagnoux2, Gabriel Baron3, François Lifermann4, Loïk Geffray5, Thomas Quémeneur6, Jean-Luc Saraux7, Marie Wislez8, Vincent Cottin9, Marc Ruivard10, Nicolas Limal11, Achille Aouba12, Bernard Bonnotte13, Antoine Neel14, Christian Agard15, Pascal Cohen16, Benjamin Terrier17, Claire Le Jeunne17, Luc Mouthon1, Philippe Ravaud3 and Loïc Guillevin for the French Vasculitis Study Group17, 1Department of Internal Medicine, INSERM Unité 1016, Centre de Référence pour les Maladies Auto-immunes Rares, National Referral Center for Rare Systemic Autoimmune Diseases, Paris Cochin, France, Paris, France, 2Division of Rheumatology, Division of Rheumatology, Mount Sinai Hospital, Toronto, ON, Canada, 3Paris Hôtel Dieu, Paris, France, 4Dax, Dax, France, 5Lisieux, Lisieux, France, 6Department of Internal Medicine, CH of Valenciennes, France, Valenciennes, France, 7Eaubonne, Eaubonne, France, 8Paris Tenon, Paris, Gambia, 9Lyon Louis Pradel, Lyon, France, 10Clermont-Ferrand, Clermont Ferrand, France, 11Créteil Henri Mondor, Créteil, France, 12Caen, Caen, France, 13Dijon, Dijon, France, 14Medecine Interne, Nantes Hôtel Dieu, Nantes, France, 15Nantes Hôtel Dieu, Nantes, France, 16Department of Internal Medicine, INSERM Unité 1016, Centre de Référence pour les Maladies Auto-immunes Rares, Hôpital Cochin, Université Paris Descartes, Sorbonne Paris Cité, Paris, France, 17National Referral Center for Rare Systemic Autoimmune Diseases, Paris Cochin, France, Paris, France

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: ANCA, azathioprine, outcomes, randomized trials and vasculitis

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Session Information

Date: Monday, October 22, 2018

Title: Vasculitis – ANCA-Associated Poster I

Session Type: ACR Poster Session B

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

Background/Purpose: At month 24 (M24), CHUSPAN2-trial patients with nonsevere eosinophilic granulomatosis with polyangiitis (EGPA), who received 1 yr of azathioprine (AZA) and glucocorticoids (GC) as remission-induction therapy, did not have lower remission failure, vasculitis relapse-risk or asthma/rhinosinus-exacerbation (ARE) rates, or steroid-sparing (1). These EGPA patients’ long-term outcomes were analyzed to determine whether vasculitis-relapse or isolated ARE rates differed thereafter.

Methods: After M24, treating physicians chose treatments. Long-term outcomes were analyzed according to randomization group (AZA vs placebo). Flares and reasons for GC escalation or immunosuppressant use were reviewed to distinguish vasculitis relapses from isolated AREs according to EGPA Task Force recommendations. Trial entry parameters were evaluated as potential prognostic factors for vasculitis relapse or isolated ARE during follow-up.

Results: The 50 EGPA patients (25 men, mean age 53.4 yr, mean eosinophilia 5,900/µL) were followed for a median [IQR] of 6.3 [5.4‒7.6] yr. Two (4%) patients (1 after remission-induction failed) died 11 months postinclusion. At M24, 21/48 (43.8%) patients had vasculitis relapse and 14/50 (28%) had isolated AREs. Among the 48 follow-up patients analyzed, 1 died 4.8 yr postinclusion (probable infection); 19.6% (9/46) had subsequent vasculitis relapses of whom 3 had their 1st relapse after M24; 25/45 (55.6%) patients had later isolated AREs, the 1st for 17 only after M24. From M24 to last update, conventional immunosuppressants were prescribed for 22/48 (45.8%) patients to control flares (17 AZA, 5 MTX, 4 cyclophosphamide, 1 leflunomide) and, after immunosuppressants failed, rituximab for 7; 4 received mepolizumab and 3 omalizumab, mostly for AREs. At 5 yr, respective vasculitis relapse and isolated ARE rates were 48.3% (95% CI: 34.0–62.6) and 56.2% (95% CI: 41.7–70.8), with no long-term between-arm differences (P=0.16 and P=0.06). For the AZA and placebo arms, respective 5-yr overall survival (OS) rates were 100% and 91.3% (95% CI: 79.7–100; P=0.15). At last update, 78.7% of patients still required GC (median dose: 5 [3.0–8.0] mg/d) to control AREs and/or as vasculitis maintenance therapy. Damage resulted from asthma (n=42), followed by peripheral nerve involvement (n=28) and chronic sinusitis/nasal obstruction (n=27); Vasculitis Damage Indexes (mean±SD) were comparable for AZA (2.8±1.5) and placebo (2.2±0.9) groups (P=0.42). Among the 18 (36%) patients MPO-ANCA+ at entry, 13 had ANCA ELISA results at M24: 6 became ANCA– (none relapsed later) and 7 were ANCA+, after having been transiently ANCA– for 3, (2/7 subsequently relapsed). Analyses retained no entry clinical or biological parameter, including blood eosinophil count and ANCA status, as significantly associated with vasculitis relapse or ARE during follow-up.

Conclusion: These results confirmed that 1 yr of AZA and GC obtained good OS but had no long-term benefit for EGPA patients. Extrapulmonary vasculitis relapses, occurring mostly during the first 2 yr, and isolated AREs, predominating thereafter, remain worrisome and require further studies to prevent them.

1 Puéchal X. et al. Arthritis Rheumatol 2017;69:2175–86.


Disclosure: X. Puéchal, None; C. Pagnoux, None; G. Baron, None; F. Lifermann, None; L. Geffray, None; T. Quémeneur, None; J. L. Saraux, None; M. Wislez, None; V. Cottin, None; M. Ruivard, None; N. Limal, None; A. Aouba, None; B. Bonnotte, None; A. Neel, None; C. Agard, None; P. Cohen, None; B. Terrier, None; C. Le Jeunne, 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, Baron G, Lifermann F, Geffray L, Quémeneur T, Saraux JL, Wislez M, Cottin V, Ruivard M, Limal N, Aouba A, Bonnotte B, Neel A, Agard C, Cohen P, Terrier B, Le Jeunne C, Mouthon L, Ravaud P, Guillevin for the French Vasculitis Study Group L. Long-Term Outcomes of Patients with Nonsevere Eosinophilic Granulomatosis with Polyangiitis Given Azathioprine and Glucocorticoids for Remission Induction [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/long-term-outcomes-of-patients-with-nonsevere-eosinophilic-granulomatosis-with-polyangiitis-given-azathioprine-and-glucocorticoids-for-remission-induction/. Accessed .
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