Background/Purpose: Although overall survival of patients with systemic necrotizing vasculitides (SNVs) has improved markedly over the last 20 years, infectious complications remain a major cause of morbidity and mortality. This study aimed to identify factors predicting severe infections in SNV patients and assess the impact of the different therapeutic regimens.

Methods: Data were pooled from 5 randomized–controlled trials conducted by the FVSG—CHUSPAN1, CHUSPAN2, WEGENT, CORTAGE, MAINRITSAN—that enrolled 733 patients between 1993 and 2012. Those trials evaluated therapeutic strategies to treat polyarteritis nodosa (PAN), granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and/or eosinophilic granulomatosis with polyangiitis (EGPA). The primary endpoint of this study was the occurrence of severe infection, defined as a severe adverse event, requiring hospitalization, intravenous antibiotics and/or resulting in death. Univariate and multivariate analyses were computed to identify associations between baseline characteristics and 2- and 5-year severe infection rates.

Results: SNV diagnoses were: 238 (32.5%) MPA, 224 (30.6%) GPA, 186 (25.4%) EGPA and 85 (11.6%) PAN. Baseline characteristics were: mean ± SD age 58 ± 12 years, 55% men, 61% with pulmonary involvement, 55% with nervous system involvement, Five Factor Score = 0 for 59%, glomerular filtration rate <60 ml/min in 35%. Induction therapies were glucocorticoids alone (15%), glucocorticoids & azathioprine (16%) or glucocorticoids & cyclophosphamide (69%). Maintenance regimens were azathioprine for 28% of the patients, methotrexate for 9%, rituximab for 8% or none for 55%. After median follow-up of 5.2 (IQR 3–9.7) years, 148 (20.2%) patients experienced ≥1 severe infection(s). Median inclusion-to-severe-infection interval was 14.9 (4.3–51.7) months. Among all severe infections 48% were bronchopulmonary and 57% were bacterial. Patients with ≥1 severe infection(s) had a higher risk of death (22% vs 8%; P<0.001). At 2 years, patients with ≥1 severe infection(s) were older, had more frequent pulmonary involvement, nervous system involvement and FFS >0, and were more likely to have received cyclophosphamide for induction. Multivariate analyses retained pulmonary [OR 2.11 (1.18–3.77); P=0.01] and nervous system involvements [OR 1.82 (1.01–3.30), P=0.048] as independent predictors of severe infection. At 5-years, baseline characteristics were the same for patients with ≥1 severe infection(s) but they had more likely received rituximab for maintenance therapy. Multivariate analyses retained pulmonary involvement [OR 1.71 (1.10–2.65); P=0.02] and age [OR 1.19 (1.02–1.38) per 10 years, P=0.02] as independent predictors of severe infection.

Conclusion: Severe infections, frequent adverse events in SNV patients, mostly occurred >1 year post-inclusion, and substantially impacted mortality. Age and pulmonary involvement were independent predictors of severe infection. Patients who had taken cyclophosphamide or rituximab had more severe infections than other regimens.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/factors-predicting-severe-infections-in-patients-with-systemic-necrotizing-vasculitides-based-on-data-from-733-patients-enrolled-in-randomized-controlled-trials/