ObjectivesPrevious studies have compared mycophenolate mofetil and azathioprine as maintenance therapy for lupus nephritis (LN). Leflunomide is an immunosuppressant widely used in the treatment of rheumatoid arthritis. The aim of this investigator-initiated study was to compare the efficacy and safety of leflunomide versus azathioprine as maintenance therapy for LN.Methods270 adult patients with biopsy-confirmed active LN from 7 Chinese Rheumatology Centres were enrolled. All patients received induction therapy with 6–9 months of intravenous cyclophosphamide plus glucocorticoids. Patients who achieved complete response (CR) or partial response (PR) were randomised to receive prednisone in combination with leflunomide or azathioprine as maintenance therapy for 36 months. The primary efficacy endpoint was the time to kidney flare. Secondary outcomes included clinical parameters, extrarenal flare and adverse effects.ResultsA total of 215 patients were randomly allocated to the leflunomide group (n=108) and azathioprine group (n=107). Kidney flares were observed in 17 (15.7%) leflunomide-treated patients and 19 (17.8%) azathioprine-treated patients. Time to kidney flare did not statistically differ (leflunomide: 16 months vs azathioprine: 14 months, p=0.676). 24-hour proteinuria, serum creatinine, serum albumin, serum C3 and serum C4 improved similarly. Extrarenal flare occurred in two patients from the azathioprine group and one patient from the leflunomide group. The incidence of adverse events was similar in the 2 groups: leflunomide 56.5% and azathioprine 58.9%.ConclusionsThe efficacy and safety profile of leflunomide are non-inferior to azathioprine for maintenance therapy of LN. Leflunomide may provide a new candidate for maintenance therapy in patients with LN.Trial registration numberNCT01172002.

Microscopic polyangiitis (MPA) is a systemic small-vessel vasculitis associated with anti-neutrophil cytoplasmic antibody (ANCA) and predominantly causes kidney and pulmonary injuries. Subarachnoid hemorrhage, a life-threatening manifestation of the central nervous system (CNS), rarely occurs in patients with ANCA-associated vasculitis (AAV). We report the case of a young man with spontaneous SAH recurrence and active nephritis. The patient was treated with a glucocorticoid pulse and intravenous cyclophosphamide (CTX) in combination with decreasing cerebral perfusion pressure and analgesic therapy. All the patients’ symptoms except the proteinuria resolved. We reviewed the clinical characteristics of 34 previously reported cases of SAH with AAV, comprising six cases of MPA, eight cases of granulomatosis with polyangiitis (GPA), and 19 cases of eosinophilic granulomatosis with polyangiitis (EGPA), and one case of unclassified AAV. All the cases showed features of active vasculitis. Concomitant nephritis and peripheral neuropathy were found in the MPA and EGPA cases with SAH, respectively. Renal and pulmonary manifestations were predominant in the patients with GPA and SAH. Ten patients had aneurysmal abnormalities, and six patients had cardiac abnormalities. Thirty-one patients were treated with glucocorticoids, and 18 patients received concurrent immunosuppressants. Patients with SAH had a mortality rate of 38.2%. The presence of cerebrovascular events or cardiac involvement in patients with AAV and SAH is associated with increased mortality of 64.3%. Our study indicates that SAH should be cautioned as a disease occurring in patients with AAV. Early diagnosis with aggressive immunosuppressive therapy can help improve the prognosis of patients with SAH.