THU0301 A Phase II Trial of Retinoids on Lupus Nephritis in A Single Center

BackgroundAlthough immunosuppressants such as corticosteroids or cyclophosphamide can suppress the progression of LN, a major manifestation of systemic lupus erythematosus (SLE), some cases are resistant to those agents, and severe adverse reactions (ARs) may occur. Therefore, development of new effective drugs with fewer ARs is important. Recently, all-trans retinoic acid (ATRA), one of natural retinoids, has been reported to differentiate regulatory T cells and suppress Th17 cells in the models of autoimmune diseases. We have reported that ATRA improved proteinuria, survival rate as well as renal pathology in lupus-prone mice (ref). On the other hand, AM80, a synthetic retinoid, has been reported to suppress the expression of inflammatory cytokines in collagen-induced arthritis and EAE.ObjectivesEffectiveness and safety of these retinoids for the treatment of LN were examined.MethodsTwenty-three patients with LN who fulfilled the ACR's revised criteria for classification of SLE were enrolled. Those unable to prevent pregnancy for more than 2 years, and who had been newly given any immunosuppressants within 8 weeks before this study were excluded. ATRA (10 mg/day) was administered to 9 patients (group A) and AM80 (4 mg/day) to 14 (group B) for 6M. Six in group B dropped out due to ARs, and effectiveness was analyzed using data of 8 patients. Through the study, the dose of steroid was not increased but allowed to be reduced if the clinical course was improved. Urinary protein (UP), serum albumin (Alb) and creatinine (Cr) levels, titer of the serum anti-double-strand DNA antibody (ADNA), serum complement levels (C3, C4) and activity (CH50) were determined every month.ResultsIn group A, Average of UP decreased at 6M after the treatment (3.2 to 0.4 g/g Cr, p