Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.

Effect of Belimumab Treatment on Renal Outcomes: Results From Phase 3 Belimumab Clinical Trials in Patients with Systemic Lupus Erythematosus.

Dooley¹, M.A., Houssiau², F., Aranow³, C., D'Cruz⁴, D.P., Askanase⁵, Anca D., Roth⁶, D., Zhong⁷, Z.J.

University of North Carolina at Chapel Hill, Chapel Hill, NC
Université catholique de Louvain, Brussels, Belgium
Feinstein Institute for Medical Research, Manhasset, NY
St. Thomas' Hospital, London, United Kingdom
NYU School of Medicine, New York, NY
GlaxoSmithKline, King of Prussia, PA
Human Genome Sciences, Inc., Rockville, MD
SUNY-Downstate Medical Center, Brooklyn, NY

Background/Purpose:

To evaluate the effect of belimumab on renal parameters in two phase 3 trials including patients with active systemic lupus erythematosus (SLE) without acute lupus nephritis.

Methods:

Autoantibody-positive (antinuclear antibody >=1:80 or anti-double-stranded DNA [anti-dsDNA]>=30 IU/mL) SLE patients (N = 1684) with Safety of Estrogen in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score >=6 were randomly assigned to belimumab 1 or 10 mg/kg, or placebo, plus standard therapy, for 52 wk (BLISS-52; NCT00424476) or 76 wk (BLISS-76; NCT00410384). The studies were not designed to assess treatment effects on renal outcomes, and patients with severe active lupus nephritis were excluded. Renal parameters collected included renal flares, renal remission, proteinuria, renal items from SELENA-SLEDAI and BILAG, as well as anti-dsDNA and complement (C3/C4) levels. Pooled data are reported through wk 52.

Results:

At baseline, 16.4%, 16.1%, and 15.1% of patients treated with placebo, and belimumab 1 and 10 mg/kg, respectively, had renal involvement by SELENA-SLEDAI; 10.5%, 11.1%, and 10.3% had BILAG A or B renal domain scores; and 5.7%, 5.9%, and 6.0% had proteinuria >=2 g/24 h. Over 52 wk, belimumab-treated patients had numerically lower rates of renal flare, higher rates of renal remission, and shorter time to 1^st renal remission vs those treated with standard therapy alone (Table). In patients with baseline proteinuria >0.5 g/24 h, the median % reduction in proteinuria at wk 52 was numerically greater in the belimumab groups. More belimumab plus standard therapy patients had renal improvement by both SELENA-SLEDAI and BILAG (10 mg/kg only) measures at wk 52 vs standard therapy alone. More patients receiving belimumab plus standard therapy converted from anti-dsDNA–positive at baseline to negative, and had normalized low baseline C3/C4 levels at wk 52 vs standard therapy alone. In patients with low C3/C4 and anti-dsDNA–positivity at baseline, the difference in wk-52 SELENA-SLEDAI renal improvement between belimumab plus standard therapy and standard therapy alone was more pronounced than in the overall population.

	Standard Therapy Plus
Renal Involvement at Baseline and Outcomes at Wk 52: Pooled Data	Placebo (n = 562)	Belimumab 1 mg/kg (n = 559)	Belimumab 10 mg/kg (n = 563)
SELENA-SLEDAI renal involvement at baseline (any of hematuria, proteinuria, pyuria, urinary casts), n (%)	92 (16.4)	90 (16.1)	85 (15.1)
BILAG renal domain A or B score at baseline, n (%)	59 (10.5)	62 (11.1)	58 (10.3)
Renal flare over 52 wk, n (%)^a	16 (2.8)	14 (2.5)	8 (1.4)
Renal remission over 52 wk in patients with baseline proteinuria >=1 g/24 h, (%)^b	n = 44/75 58.7	n = 44/67 65.7	n = 55/78 70.5
Median time to first renal remission, d (min, max)	167 (27, 364)	139 (26, 343)	140 (26, 337)
Median % change in proteinuria from baseline at wk 52^c	n = 116 -27.5	n = 110 -48.3	n = 112 -39.1
Any SELENA-SLEDAI renal improvement at wk 52, %^d,^e	n = 41/92 44.6	n = 46/90 51.1	n = 46/85 54.1
SELENA-SLEDAI proteinuria item improvement, %^f,^g	n = 33/79 41.8	n = 37/78 47.4	n = 31/69 44.9
Any SELENA-SLEDAI renal improvement in low C/ anti-dsDNA+ subgroup at wk 52, %^e,^h	n = 21/62 33.9	n = 25/60 41.7	n = 30/60 50.0
Proteinuria item improvement in lowC/anti-dsDNA+ subgroup at wk 52, %^g,^h	n = 16/53 30.2	n = 21/54 38.9	n = 23/53 43.4
BILAG renal improvement at wk 52, %^e,i	n = 11/22 50.0	n = 10/24 41.7	n = 14/22 63.6
Anti-dsDNA conversion from positive (>=30 IU/mL) at baseline to negative at wk 52, %^j	n = 19/280 6.8	n = 47/314 15.0⁺	n = 50/313 16.0^#
Low baseline C3 conversion to normal/high (>=90 mg/dL) level at wk 52, %^k	n = 30/176 17.0	n = 51/193 26.4*	n = 77/202 38.1^#
Low baseline C4 conversion to normal/high (>=16 mg/dL) level at wk 52, %^k	n = 40/218 18.3	n = 86/246 35.0^#	n = 115/259 44.4^#
*p <0.05;+p <0.01;#p <0.001; otherwise, p = not significant.
^a Renal flare defined as per Alarcón-Segovia D, Tumlin JA, Furie RA, et al. Arthritis Rheum. 48;442–54, 2003;^brenal remission defined as erythrocyte count <10 cells/hpf, absence of cellular casts, and proteinuria <1 g/24 h equivalent without doubling serum creatinine level;^cin patients with baseline proteinuria >0.5 g/24 h;^d in patients with renal involvement at baseline;^ep values not reported because studies were not designed to examine belimumab's treatment effect on individual organ domains and sample sizes are small;^fin patients with renal item involvement at baseline;^gproteinuria decrease of >0.5 g/24 h equivalent or decrease to <=0.5 g/24 h equivalent;^hin patients with positive anti-dsDNA (>=30 IU/mL), low C (C3 <90 mg/dL; C4 <16 mg/dL) and renal organ (or specific item) involvement at baseline;ⁱin patients scored as having active renal disease at baseline by the principal investigator; improvement defined as step down from baseline BILAG A or B score to B, C, or D at wk 52;^jin patients with positive anti-dsDNA at baseline;^kin patients with low C at baseline. C, complement.

Conclusion:

These data from a small subgroup of patients with renal involvement at baseline suggest that belimumab may have beneficial effects on renal outcomes in SLE and support initiation of a randomized trial to evaluate belimumab treatment for lupus nephritis.

To cite this abstract, please use the following information:
Dooley, M.A., Houssiau, F., Aranow, C., D'Cruz, D.P., Askanase, Anca D., Roth, D., et al; Effect of Belimumab Treatment on Renal Outcomes: Results From Phase 3 Belimumab Clinical Trials in Patients with Systemic Lupus Erythematosus. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :2472
DOI:

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