0986: Impact of Weight and Race on Renal Response to Cyclophosphamide in the Abatacept and Cyclophosphamide Combination Efficacy and Safety Study (ACCESS)

Julia Ford, William McCune, Neil Kamdar and Michael O'Leary, University of Michigan, Ann Arbor, MI

Background/Purpose: ACCESS assessed the efficacy of abatacept (ABA) as induction therapy in lupus nephritis (LN), randomizing 134 patients to ABA vs. placebo on a background of glucocorticoids and fixed-dose IV CYC per Euro Lupus Nephritis Trial (ELNT) [1]. While no renal response to ABA was found, the data provide an opportunity to examine predictors of renal response to fixed-dose IV CYC in a racially diverse cohort. Whether fixed-dose IV CYC is equally efficacious for larger vs. smaller patients in LN, particularly Black patients who are at risk for worse outcomes, is unknown. We performed a post-hoc analysis examining the impact of weight and race on renal response in ACCESS.

Methods: The study population was defined as participants in ACCESS excluding those who did not have a 24-hour urine protein measurement at week 24. The primary exposure was baseline weight (≥50^th vs. < 50^th percentile); secondary exposure was race (Black vs. non-Black). The outcome was proportion of subjects achieving urine protein < 0.8 g/day at week 24. We used multivariable logistic regression to examine the association between the interaction of weight/race with the outcome, adjusting for ABA exposure and baseline estimated glomerular filtration rate.

Results: Characteristics of the 104 patients included in our analysis are shown in Table 1. Black subjects in ≥50^th percentile weight were less likely to achieve the outcome (OR 0.28, 90% CI 0.09-0.89) compared to Black subjects in < 50^th percentile body weight; however, we did not observe a similar within-race effect of weight in non-Black subjects (Figure 1). In Black subjects in ≥50^th percentile weight, 23.1% met the outcome, vs. 53.9% of all other subjects (p=0.01; OR 0.25 [90% CI 0.10, 0.59]).

Conclusion: In ACCESS (wherein all subjects received fixed-dose IV CYC in addition to ABA vs. placebo), Black subjects of higher weight were less likely to achieve a renal response than lighter Black patients. These findings identify Black patients of higher body weight as a high-risk group for which more aggressive dosing of IV CYC for LN (as opposed to the one-size-fits-all approach of ELNT) might be considered.

References:
1. Treatment of lupus nephritis with abatacept: the Abatacept and Cyclophosphamide Combination Efficacy and Safety Study. Arthritis Rheumatol, 2014. 66(11): p. 3096-104.
Except where indicated otherwise, values are the number (%). IQR= interquartile range; GFR = glomerular filtration rate; MAP = mean arterial pressure; LN = lupus nephritis.
**Significant at the p < 0.10 level.
a Denotes comparison of proportion of Black subjects who did/did not meet the outcome.

Adjusted odds ratios are reported with 90% confidence intervals.
Disclosures: J. Ford, None; W. McCune, None; N. Kamdar, None; M. O'Leary, None.