Rituximab versus oral cyclophosphamide for treatment of relapses of proliferative lupus nephritis: a clinical observational study The clinical course of lupus nephritis is characterised by alterna- tion of quiescences and exacerbations. The potential treatment strategies for renal flares are an important issue considering the potential toxicity and the incomplete efficacy of available drugs. 1–4 Among the new agents for induction of remission, ritux- imab (RTX), an anti-CD20 monoclonal antibody, has emerged as a potential therapeutic alternative. 5–8 In this prospective study, we report the first comparison between RTX and cyclophospha- mide (CY) in the treatment of relapses of proliferative lupus nephritis (PLN). From April 2006 to January 2010, 24 patients with established PLN and a new renal relapse discontinued all immunosuppressive drugs and received one intravenous methyl- prednisolone pulse (MPP) (0.5–1 g each) for 3 days and, based on the patients’ choice or the physician’s clinical judgment: RTX 1 g intravenous at the end of the third infusion of MPP and at day 18 (10 patients, all women) or, as used in our unit, 9 oral CY 1–2 mg/ kg/day for 3 months (14 patients, 13 women, 1 man). To better compare the efficacy of RTX versus CY, both groups received the same dosage of prednisone 0.5 mg/kg/day for 1 month, following which the dosage was tapered. At the beginning of the fourth month, mycophenolate mofetil 1–2 g/day or azathioprine 1–2 mg/kg/day were added to the dosage of both groups. Informed consent from patients and ethical committee approval were obtained. The characteristics of the two groups are reported in table 1. Patients treated with RTX tended to have more severe histological and clinical features. At 3 and 12 months, significant improvement in renal and extra-renal parameters was achieved in both groups without significant differences (table 2). In three patients (one in the RTX group and two in the CY group) with impaired basal renal function, serum creatinine improved at 3 months by at least 30% of the initial value and returned to the basal value at 12 months. At 3 months, proteinuria reduced by 50% or more in 9 of 10 patients in the RTX group and in 10 of 14 in the CY group. At 12 months, complete renal remission (serum creatinine ≤1.2 mg/dl, proteinuria <0.5 g/24 h) occurred in 9 patients of the RTX group and in 10 patients of the CY group, partial renal remission (proteinuria from 0.5 to 2 g/day and serum creatinine ≤1.2 mg/dl) occurred, respectively, in 1 and in 3 patients. One patient in the CY group was a non-responder. During the subsequent 3-year follow-up in the RTX group and 4-year follow-up in the CY group, no renal or extra-renal flares occurred and the results achieved at 12 months were confirmed. At last observation, complete remission occurred in 8 patients in the RTX group (proteinuria <0.2 g/day in 6 patients) and in 13 patients in the CY group (proteinuria <0.2 g/day). The side Table 1 Clinical and histological characteristics of the RTX group (10 patients) and the CY group (14 patients) RTX CY p Value Age at flare (years) 31.4 (36.5-–38.9) 35.2 (28.5–43.5) 0.9 Duration of SLE (years) 14.5 (10.7–15) 10.5 (4.5–14.3) 0.25 Duration of lupus nephritis (years) 8.5 (6–10.7) 3.5 (2–10) 0.13 Class WHO III/IV/III+V/IV+V (No.)* 0/8/0/2 3/8/1/2 0.44 Activity index* 7 (6–7.9) 7 (4.5–8.5) 0.8 Chronicity index* 2 (1–2) 2(1–2.5) 0.6 Previous therapy: CY/AZA/MMF/CsA (No. of patients) 9/6/3/2 6/9/3/2 0.054 for CY Number of previous relapses 2 (2–3) 2 (1–3) 0.2 Clinical status before relapse: complete/partial remission (No. of patients)† 8/2 11/3 0.7 Therapy at time of relapse: ‡Pred alone/Pred+AZA/Pred+MMF/Pred+CsA (No. of patients) 6/2/2/1 8/4/1/1 0.7 Serum creatinine at relapse (mg/dl) 0.8 (0.6–1) 0.8 (0.6–1) 1 Proteinuria at relapse (g/day) 4.8 (3.5–6) 3.4 (3–4) 0.2 Nephrotic syndrome at relapse (No. of patients) 8 (80%) 7 (50%) 0.3 Urinary erythrocytes at relapse (number/high power field) 42 (37–46) 28 (16–39) 0.06 Albumin at relapse (g/dl) 2.7 (2.7–3.2) 3.05 (2.7–3.02) 0.03 Haemoglobin at relapse (g/l) 10.9 (10–12) 11.1 (10.4–12) 0.6 C3 at relapse (mg/dl) 48 (40–59) 65 (57–72) 0.12 C4 at relapse (mg/dl) 7.5 (6–29) 15 (12–16) 0.05 Anti-DNA antibodies at relapse (U/ml) 226 (139–313) 220 (203–304) 0.9 Type of relapse: nephritic/proteinuric (No. of patients)§ 1/9 2/12 0.7 SLE disease activity index at relapse 12 (12–14) 12.5 (8.5–16) 0.9 Cumulative CY dosage, g(mg/kg body weight)¶ 7.07±3.9 (118.4±69.6) Complete CD20 depletion after RTX: duration of depletion (months) 10 (3–8) MMF/AZA as maintenance therapy (No. of patients) 7/3 9/5 0.9 Unless otherwise specified, the numbers reported in the table refer to median and interquartile ranges. p Values between treatment groups have been calculated using the Mann–Whitney test and for dichotomised variables using the χ 2 test. *Renal biopsy was performed at the time of diagnosis of lupus nephritis. †Complete renal remission: serum creatinine ≤1.2 mg/dl, proteinuria <0.5 g/24 h; partial renal remission: proteinuria from 0.5 to 2 g/day and serum creatinine ≤1.2 mg/dl. ‡The dosage of prednisone before renal relapse was between 5 and 7.5 mg/day. §Nephritic relapse defined as sudden (since the last clinical examination of the patient: usually within 3 months) increase in plasma creatinine of at least 30% over the basal value. Proteinuric relapse: increase in proteinuria of at least 2 g/day, if the basal value was less than 3.5 g/day, or doubled if already in the nephrotic range. 1 ¶The cumulative dosage of CY refers to the amount administered during this study. AZA, azathioprine; CsA, cyclosporine; CY, cyclophosphamide; MMF, mycophenolate mofetil; Pred, prednisone; RTX, rituximab; SLE, systemic lupus erythematosus. Ann Rheum Dis October 2012 Vol 71 No 10 1751 Letters group.bmj.com on March 17, 2013 - Published by ard.bmj.com Downloaded from