SAFETY RESULTS FROM A RANDOMIZED CONTROLLED TRIAL (RCT) OF LJP 394 IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) PATIENTS WITH A HISTORY OF RENAL DISEASE

Daniel J Wallace, Mario H Cardiel, James A Tumlin, Richard Furie, Claudia Hura, Vibeke Strand, Shaw-Ling Wang, Irina Yushmanova, Kenneth R Heilbrunn

Purpose:
To assess the safety and efficacy of LJP 394 in the treatment of SLE patients with a history of renal disease.

Methods:
A multi-center, phase 3 RCT was conducted to compare weekly intravenous administration of 100 mg LJP 394 with placebo in SLE patients with a history of renal disease for a treatment period of up to 22 months. Safety analyses included assessment of adverse events and changes in laboratory parameters and vital signs reported in all 317 randomized patients (158 LJP 394, 159 placebo). Because of the morbidity and mortality associated with SLE, patients in the study were permitted to receive concomitant medications, including immunosuppressive agents.

Results:
Baseline characteristics were similar between treatment groups. Mean duration of treatment exposure was 315 days (range 1 to 641) in LJP 394 and 336 days (range 1 to 646) in placebo groups, respectively. There were no differences in the overall incidence of serious adverse events (SAE's) or adverse events (AE's) between treatment groups. SAE's were reported in 62 patients: LJP 394: 30/158 (19.0%); placebo: 32/159 (20.1%). Three SAE's were considered possibly related to study drug administration, 2 LJP 394 (angioedema and nephritis); 1 placebo (fever). Four deaths were reported during protocol treatment or within 30 days of discontinuing study drug, 3 LJP 394 (2 sepsis, 1 pneumonia) and 1 placebo (sepsis). One patient receiving LJP 394 died due to cardiac arrest 59 days after discontinuing study drug. All deaths were assessed as not related to study drug administration.

AE's were reported in 139 (88.0%) patients receiving LJP 394 and 142 (89.3%) placebo treatment, respectively. Types and severity of reported AE's were not different between treatment groups. 8 patients in each group discontinued study drug administration due to adverse events, abnormal labs or deterioration in clinical status. Changes from baseline in laboratory parameters and vital signs in LJP 394 and placebo treated patients were comparable.

In both treatment groups, 83% patients were receiving prednisone <20 mg/day at baseline; in the LJP 394 and placebo groups, 48% and 42%, respectively, were taking other immunosuppressive agents at baseline (azathioprine, leflunomide, methotrexate, or mycophenolate).

Conclusions:
Weekly intravenous administration of LJP 394 100 mg was well tolerated for as long as 22 months in SLE patients with a history of renal disease.

Presented at the
67th Annual Meeting of the American College of Rheumatology
Orlando, FL
October 23-28, 2003