Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.

Effect of Rituximab (RTX) On Anti-dsDNA and C3 Levels and Relationship to Response: Results From the LUNAR Trial

Furie¹, R., Rovin², B., Appel³, G., Kamen⁴, D.L., Fervenza⁵, F.C., Spindler⁶, A., Maciuca⁷, R.

NSLIJHS, Lake Success, NM
Ohio State University Medical Center, Columbus, OH
Columbia, New York, NY
MUSC PO Box 250637, Charleston, SC
Mayo Clinic, Rochester, MN
Universidad Nacional Tucumán, Tucuman, Argentina
Genentech, Inc., South San Francisco, CA

Purpose:

Previous studies have suggested that improvements in anti-dsDNA titers and complement C3 levels are associated with remissions in lupus nephritis (LN). Changes in these serologic markers and relationship to renal response were assessed in the LUNAR trial.

Method:

Pts with a diagnosis of active class III/IV LN and urine protein to creatinine ratio > 1 were randomized 1:1 to receive RTX (1000mg) or placebo (PLA) on days 1, 15, 168, and 182. Changes in anti-dsDNA titers and complement C3 levels were assessed at Week 52 and correlated to renal responses.

Results:

144 randomized pts (72 to each arm) comprised the intent-to-treat population. Mean daily MMF dose was 2.4±0.63g in PLA and 2.7±0.41g in RTX. Overall, there was no signficant difference in achieving a renal response between the PLA and RTX groups (p=0.55). Baseline median anti-dsDNA and mean C3 were 168.5 IU/mL and 74.1 mg/dL in the placebo group, respectively, and 122.5 IU/mL and 73.6 mg/dL in the RTX group. At Wk 52, there was a greater decrease in anti-dsDNA (p=.007) and greater increase in C3 (p=.025) in the RTX group compared to PLA. Changes by response status are presented in the table. Spearman's correlation coefficient between improvement in C3 and renal response was 0.55 (p<0.001) in PLA and 0.03 (p=0.8) in RTX. Correlation of change in anti-dsDNA to response was not statistically signfificant in either PLA or RTX.

Conclusion:

RTX statistically significantly lowered anti-dsDNA titers and increased C3 levels compared to PLA. However, these changes did not translate into a significant clinical benefit for achievement of renal responses. There was a similar level of improvement in anti-dsDNA titers and absolute C3 levels in both RTX responders and RTX non-responders, suggesting that changes in these serologic markers at one year do not correlate with renal response in RTX-treated pts.

	PLA				RTX
	All (n=72)	Resp (n=33)	NR (n=39)	Diff est* 95% CI	All (n=72)	Resp (n=41)	NR (n=31)	Diff est* 95% CI
Median % reduction in log (anti-dsDNA)	15.2	17.6	12.3	7.3 (-2.3, 17.6)	22.1	24.8	19.4	3.8 (-3.8, 11.1)
% Pts with anti-dsDNA<30	33.3	39.4	28.2	11.2 (-11.4, 33.8)	41.7	43.9	38.7	5.2 (-18.5, 28.9)
Mean increase C3	25.9	44	10.6	33.5 (20.3, 46.7)	37.5	40.9	33.1	7.8 (-5.8, 21.4)
% Pts with C3>=90	63.9	81.8	48.7	33.1 (12.0, 54.2)	80.6	80.5	80.6	0.16 (-19.2, 18.9)
* Difference estimate between responders and non-responders. Hodges-Lehmann estimates of shift, and corresponding 95% CI are calculated for the anti-dsDNA row.

To cite this abstract, please use the following information:
Furie, R., Rovin, B., Appel, G., Kamen, D.L., Fervenza, F.C., Spindler, A., et al; Effect of Rituximab (RTX) On Anti-dsDNA and C3 Levels and Relationship to Response: Results From the LUNAR Trial [abstract]. Arthritis Rheum 2009;60 Suppl 10 :271
DOI: 10.1002/art.25354

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