Background/Purpose: To optimize the therapeutic strategy for the elderly with systemic necrotizing vasculitides (SNV; polyarteritis nodosa (PAN), granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) or eosinophilic GPA (EGPA)).

Methods: We conducted a multicenter randomized controlled trial on patients ≥65 years old with newly diagnosed SNV to compare conventional therapy (based on Five-Factor Score-assessed disease severity: for all, ~28 mo of corticosteroids (CS) alone or combined with 500-mg/m²cyclophosphamide (CYC) IV pulses every 2–3 wk until remission for EGPA or PAN with FFS≥1 and GPA or MPA, then switched to maintenance azathioprine (AZA) or methotrexate (MTX)) and an experimental regimen, specifically designed for faster CS dose-tapering and systematic but reduced CYC exposure (for all, ~9 mo of CS and 500-mg fixed-dose IV CYC pulse, given every 2–3 wk, and switched after a maximum of 6 pulses to maintenance AZA or MTX). Trial follow-up closure was scheduled 3 yr after enrollment of the last patient. The primary judgment criterion was time to first severe adverse event (SAE: morbidity and mortality) hypothesizing a 30% reduction of experimental arm SAE rate. Secondary endpoints included first remission, death, relapse rates and quality-adjusted time without symptoms or toxicity (Q-TWiST).

Results: Between July 2005 and February 2008, 108 patients were randomized; 4 were excluded (early consent withdrawn, wrong diagnosis, protocol violations). Mean age at diagnosis of the analyzed patients (52 in each arm; 55 males, 49 females; 8 PAN, 13 EGPA, 37 GPA, 46 MPA; 91 ANCA-positive) was 75.2±6.3 yr, with a maximum of 92 yr for 1 MPA patient. FFS=0 for 7 PAN (4 in the conventional arm, 3 in the experimental arm) and 10 EGPA patients (5 in each arm). Baseline clinical features were evenly distributed between arms (fever, 53%; arthralgias, 38%; lung, 64%; ENT, 40%; kidney, 69%; heart, 20%; skin, 35%; peripheral nervous system, 25%; central nervous system, 3%); mean serum creatinine level at diagnosis was 234±199 µmol/l and C-reactive protein 102±87 mg/l. Mean follow-up was 28±11 mo. Hazard ratio for first SAE (primary endpoint) for experimental vs conventional treatment was 0.61 [95% CI, 0.38–0.97], i.e., 39% lower SAE rate (3-yr event-free survival: 37.6% [95% CI, 26.4–53.7] in experimental vs 19.2% [95% CI, 10.9–34.1] in conventional treatment arms; p=0.04). Ninety-one (88%) patients achieved remission with their assigned treatment (47 in experimental treatment arm vs 44 in conventional; p=0.37); 21 (20%) patients died (8 vs 13, respectively; p=0.22) of uncontrolled vasculitis for 7 of them (2 vs 5) and/or infection for 6 (2 vs 4); 16 vs 11 patients suffered ≥1 relapse(s), with comparable 3-yr relapse-free–survival rates (53.2% [CI 95%, 40.7–69.6] vs 54.2% [95% CI, 41.9–70]). Respective Q-TWiST rates were 30.97 and 28.72 (mean difference, 2.25 [95% CI, –1.72 to 6.76]; p=0.29).

Conclusion: Treating SNV in the elderly with a specific regimen limiting exposure to CS and fixed low-dose IV CYC pulses coud become the standard of care because of its lower SAE risk, and similar 3-yr remission and relapse rates, compared to conventional therapy.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/treatment-of-systemic-necrotizing-vasculitides-in-patients-%e2%89%a565-years-old-results-of-the-multicenter-randomized-cortage-trial/