Session Information
Date: Tuesday, November 10, 2015
Title: Systemic Lupus Erythematosus - Clinical Aspects and Treatment Poster Session III
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Tabalumab is a monoclonal antibody
that neutralizes membrane and soluble B-cell activating factor. Two 52-week,
randomized, double-blinded, placebo-controlled Phase 3 trials, designated BCDS
and BCDT, were done to evaluate the safety and efficacy of tabalumab in non-renal
disease manifestations in patients with systemic lupus erythematosus (SLE).
Methods: Patients with moderate-severe active
SLE but without severe active lupus nephritis (defined as a urine
protein/creatinine ratio of >200 mg/mmol or an estimated creatinine
clearance of <30 mL/min) were randomized 1:1:1 to receive tabalumab (120 mg subcutaneously
every 4 weeks or 120 mg subcutaneously every 2 weeks) or placebo for 52 weeks. Serum creatinine, glomerular
filtration rate, urine
protein/creatinine ratio, and renal adverse events were determined monthly. Data were analyzed for the
intent-to-treat population and for intent-to-treat patients with a baseline urine
protein/creatinine ratio >20 mg/mmol using an ANCOVA model.
Results: The trials enrolled 2262 patients. At
baseline, demographics, SLE disease activity, use of SLE drugs, serum creatinine, glomerular
filtration rate, and urine
protein/creatinine ratio were similar among the treatment arms. In the two populations,
there were no differences between treatment arms in baseline-to-endpoint change
in serum creatinine,
glomerular filtration rate, and urine protein/creatinine ratio (Tables 1-2). Renal adverse
events were not different among treatment arms.
Conclusion: Compared to placebo, tabalumab did
not significantly affect serum creatinine, glomerular filtration rate, and urine protein/creatinine ratio over
52 weeks in the intent-to-treat population or intent-to-treat patients with a baseline
urine protein/creatinine ratio >20 mg/mmol. There were no significant renal safety
signals.
TABLE 1: Change in Renal Laboratory Parameters, Baseline to
Week 52: Intention-to-Treat Set
|
|
BCDS |
|
BCDT |
|
BCDS+BCDT |
||||||
|
|
TAB Q2W (N=301) |
TAB Q4W (N=293) |
PBO (N=287) |
|
TAB Q2W (N=296) |
TAB Q4W (N=290) |
PBO (N=288) |
|
TAB Q2W (N=597) |
TAB Q4W (N=583) |
PBO (N=575) |
|
ΔSCr (umol/L) |
0.90±10.2 |
0.03±8.5 |
-0.19±10.5 |
|
0.18±11.1 |
0.19±11.0 |
0.81±12.2 |
|
0.54±10.7 |
0.11±9.8 |
0.31±11.4 |
|
p-value vs PBO |
.153 |
.758 |
|
|
.731 |
.924 |
|
|
.549 |
.897 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
ΔGFR (MDRD) (mL/min/bsa) |
-1.28±17.3 |
1.30±14.3 |
0.36±17.3 |
|
1.63±17.8 |
-0.06±15.3 |
0.41±15.9 |
|
0.17±17.6 |
0.63±14.8 |
0.38±16.6 |
|
p-value vs PBO |
.239 |
.574 |
|
|
.595 |
.396 |
|
|
.622 |
.805 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
ΔuPCR (mg/mmol) |
4.46±67.8 |
-0.20±61.9 |
3.78±56.5 |
|
-3.68±32.5 |
-0.40±38.7 |
-0.02±27.7 |
|
0.44±53.4 |
-0.30±51.6 |
1.87±44.4 |
|
p-value vs PBO |
.998 |
.412 |
|
|
.468 |
.834 |
|
|
.718 |
.517 |
|
TAB Q2W=tabalumab 120 mg every 2 weeks;
TAB Q4W=tabalumab 120 mg every 4 weeks; PBO=placebo
SCr=serum creatinine; GFR=glomerular
filtration rate (GFR); uPCR=urine
protein/creatinine ratio; bsa=body surface area
mean± SD
Table 2: Change in Renal Laboratory Parameters, Baseline
to Week 52: Intention-to-Treat Set with Baseline uPCR >20 mg/mmol
|
|
BCDS |
|
BCDT |
|
BCDS+BCDT |
||||||
|
|
TAB Q2W (N=70) |
TAB Q4W (N=66) |
PBO (N=58) |
|
TAB Q2W (N=47) |
TAB Q4W (N=50) |
PBO (N=33) |
|
TAB Q2W (N=117) |
TAB Q4W (N=116) |
PBO (N=91) |
|
ΔSCr (umol/L) |
3.31±11.4 |
2.23±9.0 |
2.00±14.5 |
|
-0.74±15.0 |
0.36±15.4 |
4.00±14.3 |
|
1.68±13.0 |
1.42±12.1 |
2.73±14.4 |
|
p-value vs PBO |
.685 |
.900 |
|
|
.136 |
.360 |
|
|
.471 |
.655 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
ΔGFR (MDRD) (mL/min/bsa) |
-3.67±17.3 |
-0.52±13.5 |
-2.07±21.5 |
|
3.29±20.6 |
1.35±18.9 |
-2.26±19.7 |
|
-0.87±18.9 |
0.29±16.0 |
-2.14±20.7 |
|
p-value vs PBO |
.983 |
.597 |
|
|
.321 |
.602 |
|
|
.604 |
.559 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
ΔuPCR (mg/mmol) |
-2.34±91.0 |
-6.58±127.9 |
3.50±117.2 |
|
-28.12±75.5 |
-12.35±87.9 |
-26.93±68.4 |
|
-12.52±85.8 |
-9.08±111.8 |
-7.53±102.9 |
|
p-value vs PBO |
.316 |
.282 |
|
|
.879 |
.776 |
|
|
.383 |
.434 |
|
TAB Q2W=tabalumab 120 mg every 2 weeks;
TAB Q4W=tabalumab 120 mg every 4 weeks; PBO=placebo
SCr=serum creatinine; GFR=glomerular
filtration rate (GFR); uPCR=urine
protein/creatinine ratio; bsa=body surface area
mean± SD
To cite this abstract in AMA style:
Dooley MA, Rovin BH, Radhakrishnan J, Ginzler EM, Forrester T, Anderson P. The Impact of Tabalumab on the Kidney in Systemic Lupus Erythematosus: Results from Two Phase 3 Randomized Clinical Trials [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/the-impact-of-tabalumab-on-the-kidney-in-systemic-lupus-erythematosus-results-from-two-phase-3-randomized-clinical-trials/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-impact-of-tabalumab-on-the-kidney-in-systemic-lupus-erythematosus-results-from-two-phase-3-randomized-clinical-trials/