Background/Purpose: Multi-target therapy for lupus nephritis (LN) had first reported by Bao et al. 2008 regarding the treatment of mixed diffuse proliferative and membranous LN using a combination of corticosteroids, mycophenolate mofetil and tacrolimus (Tac). Following this, several studies had suggested the efficacy of combination therapies utilizing two or more immunosuppressive agents with different mechanisms of action. The objective of this retrospective study is to assess the effectiveness of multi-target therapy with cyclophosphamide (CY) and Tac for class III and IV LN as a remission induction therapy in our single center experience and to discuss the potentiality of this multi-target therapy with renal pathological findings.

Methods: We evaluated 43 patients with active LN who performed renal biopsies at Saitama Medical Center between January 2007 and August 2012. The complete renal remission was defined as spot urine protein: creatinine ratio <0.5g/gCr or under plus and minus values in urinalysis and normal GFR or improvement of GFR according to the EULAR/ERA-EDTA recommendation. Renal pathological findings were assessed according to the 2003 ISN/RPS classification for LN. Crescents, fibrinoid necrosis, interstitial cell infiltration and chronicity were evaluated as well.

Results: The number of patients in each class was as follows; II: 9, III: 4, IV: 28, V: 2. In 32 cases with class III/IV, crescents: 15 (46.9%), fibrinoid necrosis: 8 (25.0%), interstitial cell infiltration: 15 (46.9%) and chronicity: 18 (56.3%). Four cases (12.5%) had membranous nephropathy (Class IV + V). CY was initiated in 24 cases with class III/IV. Eleven out of 24 (45.8%) cases received multi-target therapy with Tac (CY + Tac group) as a remission induction therapy. In the other 13 (54.2%) cases various immunosuppressants (Tac, azathioprine, cyclosporine, mizoribine pulse) were prescribed as a maintenance therapy after CY (CY-IS group). The complete remission rate at 12 months was 45.5% in CY + Tac group and 69.2% in CY-IS group (p=0.41). However patients’ background of each group was quite different. Although chronicity was observed more commonly in CY + Tac group (p=0.047), the remission rate in patients with chronicity was 44.4% in CY + Tac group and 20.0% in CY-IS group (p=0.58).

Conclusion: Multi-target therapy such as CY + Tac may be effective for refractory LN with chronicity in renal pathological findings.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-potentiality-of-multi-target-therapy-with-cyclophosphamide-and-tacrolimus-for-lupus-nephritis/