Rituximab as maintenance therapy for ANCA-associated vasculitides: pooled analysis and long-term outcome of 277 patients included in the MAINRITSAN trials.

OBJECTIVE: To compare the long-term efficacy and safety of azathioprine (AZA), 18-month fixed-schedule rituximab (RTX), 18-month tailored RTX and 36-month RTX in preventing relapses in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis who achieved a complete remission after induction therapy. Patients treated with 36-month RTX received either a fixed or a tailored regimen for the first 18 months and a fixed regimen for the last 18 months (36-month fixed/fixed RTX and 36-month tailored/fixed RTX, respectively). METHODS: The Maintenance of Remission using Rituximab in Systemic ANCA-associated Vasculitis (MAINRITSAN) trials sequentially compared: 18-month fixed-schedule RTX versus AZA (MAINRITSAN); 18-month fixed-schedule RTX versus 18-month tailored-RTX (MAINRITSAN2); and extended therapy to 36 months with four additional RTX infusions after MAINRITSAN2 versus placebo (MAINRITSAN3). Patients were then followed prospectively through month 84 and their data were pooled to analyse relapses and adverse events. The primary endpoint was relapse-free survival at month 84. RESULTS: 277 patients were enrolled and divided in 5 groups: AZA (n=58), 18-month fixed-schedule RTX (n=97), 18-month tailored-RTX (n=40), 36-month tailored/fixed RTX (n=42), 36-month fixed/fixed RTX (n=41). After adjustment for prognostic factors, 18-month fixed-schedule RTX was superior to AZA in preventing major relapses at month 84 (HR 0.38, 95% CI 0.20 to 0.71). The 18-month tailored-RTX regimen was associated with an increased risk of major relapse compared with fixed-schedule regimen (HR 2.92, 95% CI 1.43 to 5.96). The risk of major relapse was similar between 36-month fixed/fixed and 18-month fixed-RTX (HR 0.69, 95% CI 0.38 to 1.25). CONCLUSIONS: According to these results, it appears that the 84-month remission rate is higher with an 18-month fixed RTX regimen compared with AZA and 18-month tailored RTX. Also, extending RTX to 36 months does not appear to reduce the long-term relapse rate compared with the 18-month fixed RTX regimen. However, as this study was underpowered to make this comparison, further prospective studies are needed to determine the potential long-term benefits of extending treatment in these patients.

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.

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.

Giardia lamblia infection in a patient with myotonic dystrophy.

Myotonic dystrophy is an autosomal dominant muscle disorder characterized by muscle wasting and weakness and a number of other systemic abnormalities. Some patients have hypo-IgG that is asymptomatic in most of them. We report the case of a 42-year-old woman with myotonic dystrophy and hypo-IgG who experienced asthenia and weight loss secondary to Giardia lamblia bowel infection.