No 'Significant Renal Safety Signals' With Tabalumab in SLE
SAN FRANCISCO, CA—Treatment with tabalumab did not significantly affect serum creatinine, glomerular filtration rate, or urine protein/creatinine ratio over 52 weeks vs. placebo, investigators reported at the 2015 ACR/ARHP Annual Meeting.
"There were no significant renal safety signals," noted Mary Anne Dooley, MD, from the University of North Carolina at Chapel Hill, Chapel Hill, NC.,
Tabalumab neutralizes membrane and soluble B-cell activating factor. Dr. Dooley and colleagues conducted two 52-week, randomized, double-blinded, placebo-controlled Phase 3 trials to evaluate the safety and efficacy of tabalumab in non-renal disease manifestations in patients with systemic lupus erythematosus (SLE).
The two trials, which were identical in design, enrolled 2,262 patients with moderate-severe active SLE but without severe active lupus nephritis (urine protein/creatinine ratio >200mg/mmol or an estimated CrCl <30mL/min). They were randomly assigned to receive a tabalumab 240mg loading dose, followed by 120mg subcutaneously every 4 weeks (n=753) or every 2 weeks (n=754) or placebo (n=755) for 52 weeks.
Each month, patients' serum creatinine, glomerular filtration rate, urine protein/creatinine ratio, and renal adverse events were assessed. Data were analyzed for the intent-to-treat population and for those patients with a baseline urine protein/creatinine ratio >20mg/mmol.
For both trials combined, in the intent-to-treat set, changes in serum creatinine were 0.54±10.7mmol/L, 0.11±9.8mmol/L, and 0.31±11.4mmol/L for tabalumab every 2 weeks, tabalumab every 4 weeks, and placebo, respectively. Changes in glomerular filtration were 0.17±17.6mL/min/1.73m2 , 0.63mL±14.8/min/1.73m2 , and 0.38±16.6mL/min/1.73m2 , respectively.
In the intent-to-treat set with baseline urine protein/creatinine ratio >20mg/mmol, the changes in serum creatinine were 1.68±13.0mmol/L, 1.42±12.1mmol/L, and 2.73±14.4mmol/L, respectively. Changes in glomerular filtration were -0.87±18.9mL/min/1.73m2, 0.29±16.0mL/min/1.73m2, and -2.14±20.7mL/min/1.73m2, respectively.
"Over 52 weeks, compared to placebo, tabalumab did not significantly affect serum creatinine, glomerular filtration rate, and urine protein/creatinine ratio, either in the intent-to-treat population or in intent-to-treat patients with a baseline urine protein/creatinine ration>20mg/mmol," they concluded.