AB0530 Efficacy and Safety of Multi-Target Therapy Using a Combination of Cyclophosphamide and Tacrolimus in Patients with Refractory Lupus Nephritis: A Prospective, Single-Arm, Open-Label Study of 13 Patients. (9th June 2015) - Sakai, R.
Abstract : Background: Pulsed cyclophosphamide (pCYC) for lupus nephritis (LN) has limited effects in some cases; mycophenolate mofetil is an off-label pharmaceutical agent in Japan. Objectives: To assess the effectiveness of multi-target therapy with pCYC and tacrolimus (Tac) for treating LN, including refractory cases. Methods: We have done a prospective, single-arm, open-label study at our center (UMIN4893). Thirteen patients with active LN were enrolled. Prednisolone was started at 1 mg/ kg/day, aiming to reduce the dose to 10 mg/day after 6 months. Intravenous cyclophosphamide was administered as per the Euro-Lupus protocol (500 mg biweekly for 3 months). The trough concentration of Tac was adjusted to 5–10 ng/ml as per National Health Insurance. Complete remission (CR) was defined as a spot urine protein/creatinine (UPCR) ratio of <0.5 g/gCr and normal eGFR or eGFR improvement as per EULAR/ERA-EDTA recommendations and KDIGO guidelines. Results: The mean age was 41.5 years (male:female =2:11); UPCR, 3.4 g/gCr; serum creatinine, 1.00 mg/dl; C3, 44.8 mg/dl (90.0–140.0 mg/dl); and C4, 5.7 mg/dl (18.0–30.0 mg/dl). One, eight and three patients belonged to Classes III, IV, and IV + V, respectively, and one had no data. Eleven out of the 13 patients completed the treatment protocol; 2 patients withdrew. The CR at 6 months was 69.2% (n=9/13). Side effects, including infections, did not increase as compared to conventional therapy with pCYC, except a transient increase in serum creatinine with Tac. Conclusions: Multi-target therapy such as pCYC and Tac can be a therapeutic option for refractory LN. Disclosure of Interest: R. Sakai: None declared, A. Shibata: None declared, K. Chino: None declared, T. Kondo: None declared, A. Okuyama: None declared, H. Takei: None declared, K. Amano Grant/research support from: Astellas, Chugai, Pfizer, Tanabe-Mitsubishi, Consultant for: Zenyaku Kogyo, Paid instructor for: Chugai, Pfizer, Santen, Tanabe-Mitsubishi, Speakers bureau: AbbVie, Actellion, Astellas, Bristol-Myers-Squibb, Chugai, Diichi-Sankyo, Eisai, Pfizer, Tanabe-Mitsubishi