Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Aspreva Lupus Management Study (ALMS): Extra-Renal Activity Results from the Maintenance Phase.
Isenberg4, David A., Appel1, Gerald B., Dooley6, Mary Anne, Ginzler3, Ellen M., Jayne2, David, Wofsy5, David, Solomons7, Neil
Renal Unit, Addenbrooke's Hospital
SUNY-Downstate Medical Center, Brooklyn, NY
University College London, London, United Kingdom
University of California, San Francisco, San Francisco, CA
University of North Carolina at Chapel Hill, Chapel Hill, NC
Vifor Pharma (formerly Aspreva Pharmaceuticals), Canada
Vifor Pharma, UK
The 36-month maintenance phase of the ALMS study (NCT00377637) compared the efficacy and safety of mycophenolate mofetil (MMF) with azathioprine (AZA) in patients with lupus nephritis (LN) classes III, IV and V achieving a clinical response in the induction phase with corticosteroids (CS) and either MMF or cyclophosphamide (IVC).
Patients were re-randomized 1:1 to a double-blind comparison of either placebo plus either oral MMF (2 g/day) or oral AZA (2 mg/kg/day). Patients were permitted to receive corticosteroids (maximum dose: 10 mg/day prednisone or equivalent). The primary efficacy outcome measure was time to treatment failure (death, end-stage renal disease, sustained doubling of serum creatinine, and/or renal flare [proteinuric or nephritic]). Patients who withdrew before reaching the primary endpoint were censored at the time of withdrawal. Although this was primarily an LN population, substantial extra-renal assessments were performed. Extra-renal secondary parameters included time to major extra-renal flare (British Isles Lupus Assessment Group [BILAG] score category A in one extra-renal system or three systems with concurrent category B scores) and the characterization of extra-renal activity. Immunology secondary parameters (levels of complement proteins C3 and C4, and titers of antibodies to double-stranded DNA [anti-dsDNA]) and adverse events (AEs) were also assessed.
Of 227 patients randomized (intent-to-treat population), 127 completed the full 3 years (MMF, 73/116 [62.9%]; AZA, 54/111 [48.6%]): MMF was superior to AZA in the primary endpoint (p=0.003). Extra-renal disease characteristics and immunology parameters were similar across groups at baseline. There were very few occurrences of major extra-renal flare in either group during the study (8 [6.9%] for MMF, 7 [6.3%] for AZA), and time to major extra-renal flare did not differ between groups (p=0.936). However, there were differences in the characteristics of extra-renal activity. The most common manifestation of major extra-renal flare in the MMF group was mucocutaneous and in the AZA group was hematological. In the MMF group, 75 subjects (65.2%) experienced lupus-related AEs compared with 79 (71.2%) in the AZA group, with musculoskeletal events being the most common in both groups (MMF, 39/115 [33.9%]; AZA, 37/111 [33.3%]). At the end of the study, in patients who had completed 3 years, mean C3 and C4 levels were lower in the AZA group and mean anti-dsDNA titers were lower in the MMF group; differences were not statistically significant.
In this population of LN patients who had responded to induction therapy, there were low levels of extra-renal activity in the maintenance phase in both MMF and AZA groups.
To cite this abstract, please use the following information:
Isenberg, David A., Appel, Gerald B., Dooley, Mary Anne, Ginzler, Ellen M., Jayne, David, Wofsy, David, et al; Aspreva Lupus Management Study (ALMS): Extra-Renal Activity Results from the Maintenance Phase. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1453