Talk: Efficacy and Safety of Rituximab in Subjects with Active Proliferative Lupus Nephritis (LN): Results From the Randomized, Double-Blind Phase III LUNAR Study (2009 ACR/ARHP Annual Scientific Meeting)

Monday, October 19, 2009: 11:45 AM

Ballroom AB (Pennsylvania Convention Center)

R. Furie¹, R. J. Looney², B. Rovin³, Kevin M. Latinis⁴, G. Appel⁵, J. Sanchez-Guerrero⁶, F.C. Fervenza⁷, R. Maciuca⁸, P. Brunetta⁹, D. Zhang⁸ and J. Garg⁸, ¹North Shore-LIJ Health System, Lake Success, NY, ²University of Rochester, Rochester, NY, ³Ohio State, Columbus, OH, ⁴KS Univ Med Ctr, Kansas City, KS, ⁵Columbia, New York, NY, ⁶Inst Nacional, Mexico City DF, Mexico, ⁷Mayo Clinic, Rochester, MN, ⁸Genentech, South San Francisco, CA, ⁹Genentech, Inc., South San Francisco, CA

Presentation Number: 1149

Purpose: Small, uncontrolled LN studies have suggested that RTX may be efficacious. The efficacy and safety of RTX compared to placebo (PLA) added on to background therapy of mycophenolate mofetil (MMF) and corticosteroids in pts with proliferative LN was studied.

Methods: Pts with class III/IV LN and urine protein to creatinine ratio (UPCR) >1 were randomized 1:1 to receive RTX (1000mg) or PLA on days 1, 15, 168, and 182. Primary endpoint (EPS) was % pts with complete (CRR) or partial renal responses (PRR) at Wk 52 and was analyzed by a stratified Wilcoxon rank sum test.

Results: 72 pts were randomized to each arm and were similar at baseline (BL). Overall mean age at entry was ~30 yrs, ~90% were female, 28% were Black, 36% Hispanic, 31% White, and 67% had class IV LN. BL mean UPCR was 4.0 ą2.8 and serum creatinine was 1.0 ą0.5 mg/dL Mean daily MMF dose was 2.4ą0.63g in PLA and 2.7ą0.41g in RTX. There were no statistically significant differences in the primary or clinical secondary EPS. Blacks and Hispanics randomized to RTX had greater responses compared to PLA than Whites, but statistical significance was not achieved. RTX had a greater effect on levels of anti-dsDNA and complement at Wk 52. Peripheral CD19+ B cells were depleted in all RTX pts and maintained in most pts until Wk 52. Serious adverse events (SAEs) and infectious SAEs were similar between groups. Neutropenia (1 vs 4), leukopenia (3 vs 9), and hypotension (3 vs 9) occurred more frequently in RTX. Two deaths (sepsis and pneumonitis) occurred in the RTX group.

Conclusion: To date, LUNAR is the largest randomized, placebo-controlled trial to evaluate RTX as an intervention in LN. Although there were numerically more responders in the RTX group (57% vs 46%), the study did not show a statistically significant difference in primary or clinical secondary EPS. RTX had a significantly greater effect on levels of anti-dsDNA and complement, although the clinical significance of this is unclear. AEs and SAEs were similar in frequency between groups, with no new or unexpected safety signals.

Table: Efficacy EPS and Safety

PLA
(N=72)
N (%)

RTX
(N=72)
N (%)

p-value*

Primary

CRR
PRR

22 (30.6)
11 (15.3)

19 (26.4)
22 (30.6)

0.55

Key Secondary

Pts with BL UPCR>3 to UPCR<1

53.7

47.4

0.51

% change from BL in anti-dsDNA

50

69

<0.01

Mean Change from BL in C3 (mg/dL)

25.9

37.5

<0.03

Exploratory

Pts with BILAG Renal Domain Score C at Wk52

28 (38.9)

39 (54.2)

0.07

Overall response (CRR+PRR)

33 (45.8)

41 (56.9)

0.18

Black

9/20 (45)

14/20 (70)

0.20

Hispanic

11/23 (48)

16/29 (55)

0.78

White

13/26 (50)

10/19 (53)

1.00

Pts with new immunosuppressant prior to Wk52

8 (11.1)

1 (1.4)

0.03

Safety

(N=71)

(N=73)

SAE

25 (35.2)

22 (30.1)

Infusion-related SAE

2 (2.8)

1 (1.4)

Infection AE

61 (85.9)

61 (83.6)

Infection SAE

12 (16.9)

12 (16.4)

HACA+

4 (5.6)

8 (11.1)

Deaths

0 (0)

2 (2.7)

*P-values are 2-sided and not adjusted for multiplicity

1149 - Efficacy and Safety of Rituximab in Subjects with Active Proliferative Lupus Nephritis (LN): Results From the Randomized, Double-Blind Phase III LUNAR Study