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.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/impact-of-weight-and-race-on-renal-response-to-cyclophosphamide-in-the-abatacept-and-cyclophosphamide-combination-efficacy-and-safety-study-access/