Infectious Complications in Systemic Necrotizing Vasculitides: Pooled Analysis of Five Prospective, Randomized, Controlled Trials

Lafarge Antoine¹, Christian Pagnoux², Xavier Puéchal³, Maxime Samson⁴, Mohamed Hamidou⁵, Alexandre Karras⁶, Thomas Quémeneur⁷, Matthieu Groh⁸, Luc Mouthon⁹, Loïc Guillevin for the French Vasculitis Study Group³ and Benjamin Terrier¹⁰, ¹Medecine Interne, Hôpital Cochin, Paris, France, ²Mount Sinai Hospital, Toronto, ON, Canada, ³Service de Médecine Interne, Centre de Référence Maladies Auto-Immunes et Auto-Inflammatoires Systémiques Rares, Hôpital Cochin, Paris, France, ⁴Department of Internal Medicine and Clinical Immunology, Hôpital François Mitterrand, CHU de Dijon, Dijon, France, ⁵Medecine Interne, CHU Hôtel Dieu, Nantes, France, ⁶nephrology, HEGP, Paris, France, ⁷Service de néphrologie, médecine interne et vasculaire, Hôpital de Valenciennes, Valenciennes, France, ⁸National Referral Center for Rare Systemic Autoimmune Diseases, Hôpital Cochin, AP–HP, Université Paris Descartes, Paris, France, ⁹Université Paris Descartes Sorbonne Paris, Paris, France, ¹⁰Internal Medicine, Cochin University Hospital, Paris, France

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: immunosuppressants, Infection, tolerance and vasculitis

Session Information

Date: Tuesday, November 7, 2017

Title: Vasculitis Poster III: Other Vasculitis Syndromes

Session Type: ACR Poster Session C

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

Background/Purpose:

Prognosis of patients with systemic necrotizing vasculitides has been markedly improved during the last 2 decades. However, infectious complications remain a major cause of morbidity and mortality. In majority of therapeutic studies on systemic vasculitides, number of patients is estimated to assess treatment efficacy and not tolerance. The aim of this study is to describe and analyse infectious complications in patients with systemic necrotizing vasculitides.

Methods:

Data from 5 prospective, randomized, controlled trials conducted by the French Vasculitis Study Group (FVSG) (CHUSPAN 1, CHUSPAN 2, WEGENT, CORTAGE, MAINRITSAN), were pooled and analysed. These studies evaluated therapeutic strategy for the treatment of polyarteritis nodosa (PAN), granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). Primary endpoint of this study was the occurrence of a severe infection, defined by the need of a hospitalization, intravenous treatment or leading to death.

Results:

Seven hundred and thirty-three patients were included between 1993 and 2012, including 398 men (54.3%), with a median age of 60 years old (IQR 47-70). Vasculitis diagnoses were MPA in 231 (31.5%) patients, GPA in 226 (30.8%), GEPA in 186 (25.4%) and PAN in 85 (11.6%). Five Factor Score was greater than or equal to 1 in 289 patients (39.4%), and median Birmingham Vasculitis Activity Score at inclusion was 4.5 (0-14).

After a median follow-up of 5.2 years (IQR 3-9.7), 269 (36.7%) patients experienced 431 infections, among which 148 (20.2%) patients having 174 severe infections, including 84 (48.3%) bronchopulmonary infections, among which 2 aspergillosis and 2 nocardiosis, 28 (16.1%) gastrointestinal infections, 12 (6.9%) urinary infections, 11 (6.3%) septicemias, 11 (6.3%) cutaneous infections, 7 (4%) ENT infections, 6 zoster infections (3.4%), 2 Candida oesophagitis (1.1%), 2 endocarditis (1.1%) and 1 malignant anguillulosis (0,6%).

Proportion of patients with severe infection remained stable over time. All patients developing at least one severe infection (n=148) received glucocorticoids, including pulses of methyprednisolone initially in 68 (45.9%) patients. Median glucocorticoid dose at the time of severe infection was 10 mg/day (IQR 5-25.8). Fifty-five percent of patients were also receiving immunosuppressive agents: including cyclophosphamide (16.9%), azathioprine (14.8%), rituximab (10.6%) or methotrexate (8.5%).

Median time from treatment initiation to first severe infection was 14.5 months (IQR 4.1-55.1). Finally, 22 severe infections directly led to death, representing 19.3% of all causes of death.

Statistical analysis of variables associated with severe infections is ongoing in order to identify high-risk patients.

Conclusion:

Severe infections are a frequent adverse in systemic necrotizing vasculitides, mostly occurring after 12 months, and with a substantial impact on morbidity and mortality. These findings highlight the need for better preventive measures in these immunocompromised patients. Statistical analysis will enable us to identify patients at risk of severe infections.

Disclosure: L. Antoine, None; C. Pagnoux, None; X. Puéchal, None; M. Samson, None; M. Hamidou, None; A. Karras, None; T. Quémeneur, None; M. Groh, None; L. Mouthon, None; L. Guillevin for the French Vasculitis Study Group, None; B. Terrier, None.

To cite this abstract in AMA style:

Antoine L, Pagnoux C, Puéchal X, Samson M, Hamidou M, Karras A, Quémeneur T, Groh M, Mouthon L, Guillevin for the French Vasculitis Study Group L, Terrier B. Infectious Complications in Systemic Necrotizing Vasculitides: Pooled Analysis of Five Prospective, Randomized, Controlled Trials [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/infectious-complications-in-systemic-necrotizing-vasculitides-pooled-analysis-of-five-prospective-randomized-controlled-trials/. Accessed .

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