Rituximab plus cyclophosphamide for resistant lupus-nephritis

Swedish researchers report that rituximab plus cyclophosphamide is an effective option for lupus nephritis patients who fail conventional immunosuppressive therapy.Lead author Dr Iva Gunnarsson, (Karolinska University Hospital, Stockholm) and colleagues write, "Treatment with the monoclonal antibody rituximab (anti-CD20) is commonly used in patients with B cell lymphomas and has in recent years also been tested in several rheumatologic diseases?.Reports of the beneficial effects of rituximab in patients with proliferative lupus nephritis have also been published during the last few years".To explore further the researchers enrolled seven women with treatment-resistant lupus nephritis. Previous treatment failure was defined as persistence of histopathologic findings of active proliferative lupus nephritis in a recent renal biopsy despite cyclophosphamide therapy. All subjects received a rituximab plus cyclophosphamide protocol and were reviewed on a scheduled basis with renal biopsies performed before and after six months of treatment.The investigators report, "Improvement was achieved in all patients at six months of follow-up, both with regard to clinical variables and with regard to renal histopathology on repeat biopsies."Disease Activity scores (SLEDAI) reduced from a mean of 15 (range 6-32) to three (range 0-10, p=0.0022) at six-month follow-up. Also anti-double-stranded DNA antibody levels fell from 174 IU/mL to 56 IU/mL and anti-C1q antibody levels fell from a mean of 35 units/mL at baseline to 22 units/mL at six months.Gunnarsson's group also notes improvement in the histologic class of nephritis in most patients and reduction in renal activity index from six to three after six months of combination therapy."Although a number of reports have described the clinical effects of rituximab in patients with lupus nephritis, almost no data regarding repeat renal biopsies have been published to date." The authors add, "We previously demonstrated that patients with lupus nephritis may still have histopathologically active disease after immunosuppressive treatment, despite apparent clinical improvement. Therefore, to identify patients with ongoing renal inflammation, the performance of repeat renal biopsies may be fundamental."The investigators conclude, "For lupus nephritis patients who fail to respond to conventional immunosuppressive therapy including cyclophosphamide, combined treatment with rituximab and cyclophosphamide can be very effective and constitutes a promising new treatment possibility."Reference...