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Treatment of Systemic Necrotizing Vasculitides in Patients Aged Sixty‐Five Years or Older: Results of a Multicenter, Open‐Label, Randomized Controlled Trial of Corticosteroid and Cyclophosphamide–Based Induction Therapy
Author(s) -
Pagnoux Christian,
Quéméneur Thomas,
Ninet Jacques,
Diot Elisabeth,
Kyndt Xavier,
Wazières Benoît,
Reny JeanLuc,
Puéchal Xavier,
Berruyer PierreYves,
Lidove Olivier,
Vanhille Philippe,
Godmer Pascal,
Fain Olivier,
Blockmans Daniel,
Bienvenu Boris,
Rollot Florence,
Aït el GhazPoignant Séverine,
Mahr Alfred,
Cohen Pascal,
Mouthon Luc,
Perrodeau Elodie,
Ravaud Philippe,
Guillevin Loïc
Publication year - 2015
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.39011
Subject(s) - medicine , microscopic polyangiitis , azathioprine , granulomatosis with polyangiitis , cyclophosphamide , randomized controlled trial , surgery , randomization , methotrexate , gastroenterology , adverse effect , polyarteritis nodosa , maintenance therapy , vasculitis , chemotherapy , disease
Objective To investigate a new therapeutic strategy, with rapid corticosteroid dose tapering and limited cyclophosphamide (CYC) exposure, for older patients with systemic necrotizing vasculitides (SNVs; polyarteritis nodosa [PAN], granulomatosis with polyangiitis [Wegnener's] [GPA], microscopic polyangiitis [MPA], or eosinophilic GPA [Churg‐Strauss] [EGPA]). Methods A multicenter, open‐label, randomized controlled trial comprising patients ≥65 years old and newly diagnosed as having SNV was conducted. The experimental treatment consisted of corticosteroids for ∼9 months and a maximum of six 500‐mg fixed‐dose intravenous (IV) CYC pulses, every 2–3 weeks, then maintenance azathioprine or methotrexate. The control treatment included ∼26 months of corticosteroids for all patients, combined with 500 mg/m 2 IV CYC pulses, every 2–3 weeks until remission, then maintenance for all patients with GPA or MPA and for those with EGPA or PAN with a Five‐Factors Score (FFS) of ≥1. Randomization used a 1:1 ratio computer‐generated list and was performed centrally with sealed opaque envelopes. The primary outcome measure was ≥1 serious adverse event (SAE) occurring within 3 years of followup. Secondary outcome measures included remission and relapse rates. Results Among the 108 patients randomized, 4 were excluded (early consent withdrawal or protocol violation). Mean ± SD age at diagnosis was 75.2 ± 6.3 years. Analysis at 3 years included 53 patients (21 GPA, 21 MPA, 8 EGPA, and 3 PAN) in the experimental arm and 51 patients (15 GPA, 23 MPA, 6 EGPA, and 7 PAN) in the conventional arm. In total, 32 (60%) versus 40 (78%) had ≥1 SAE ( P = 0.04), most frequently infections; 6 (11%) versus 7 (14%) failed to achieve remission ( P = 0.71); 9 (17%) versus 12 (24%) died ( P = 0.41); and 20 (44%) of 45 versus 12 (29%) of 41 survivors in remission experienced a relapse ( P = 0.15). Conclusion For older SNV patients, an induction regimen limiting corticosteroid exposure and with fixed low‐dose IV CYC pulses reduces SAEs in comparison to conventional therapy, and does not affect the remission rate. Three‐year relapse rates remain high for both arms.