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SAT0242 Measures of peripheral blood b-cell depletion predict renal response in patients with lupus nephritis treated with rituximab
  1. LM Gomez Mendez1,
  2. MD Cascino2,
  3. J Garg2,
  4. P Brunetta2,
  5. M Dall'Era1,
  6. L Dragone2
  1. 1UCSF
  2. 2Genentech, San Francisco, United States

Abstract

Background LUNAR, a randomized controlled trial, investigated the addition of rituximab (RTX) to standard of care for the treatment of lupus nephritis (LN). While this study did not meet its primary endpoint, there was an increase in partial renal response associated with RTX. Subsequent observational studies have suggested that there is variability in the degree of peripheral blood B-cell depletion in patients with SLE following treatment with RTX and that greater B-cell depletion may result in increased therapeutic efficacy.

Objectives To assess the relationship between parameters of B-cell depletion and measures of renal response in patients treated with RTX.

Methods We analyzed data from the LUNAR trial (registry number NCT00282347) who were treated with RTX and for whom complete CD19 measurements and renal endpoints were available (n=70). We developed several parameters to assess the degree, duration and rate of depletion of CD19 counts from randomization through day 364. Complete renal response (CRR) was defined as urine protein to creatinine ratio (UPCR) <0.5, normal serum creatinine or, if normal at baseline, not increased by ≥15%, and inactive urinary sediment. Spearman's correlation was used to identify associations between baseline characteristics and measures of B-cell depletion. The association between measures of B-cell depletion and CRR (at weeks 52 and 78) was examined using logistic regression adjusted for baseline UPCR. Separately, analyses were stratified by baseline anti-double stranded DNA antibody titer status (anti-dsDNA).

Results Baseline UPCR correlated with the degree of B-cell depletion following RTX treatment by several measures (time spent at CD19 =0 cells/ml [r = -0.32]; CD19 nadir [r =0.33]; percent change from baseline to nadir [r =0.3]). Measures of B-cell depletion were associated with CRR and percent change in UPCR at week 78 (Table 1). Achievement of a nadir of CD19 =0 cells/ml had an odds ratio (OR) =5.18 (95% CI: 1.03–26.1); patients who spent greater than the median percent of time at CD19 =0 cells/ml had OR =3.3 (95% CI: 1.14–9.62) for CRR at week 78. In subgroup analyses, associations between these measures of peripheral blood B-cell depletion and renal response were strongest among patients with high baseline anti-dsDNA titer. No measures of B-cell depletion were associated with CRR at week 52.

Conclusions Baseline UPCR was inversely correlated with the degree of peripheral B-cell depletion. B-cell depletion measures were associated with increased odds of achieving CRR and decreased UPCR at week 78 and these associations were strongest among patients with high baseline anti-dsDNA titer. These data support the exploration of high-sensitivity B-cell measurements in future studies of B-cell depleting treatments in LN and suggest that longer duration of follow up may better demonstrate efficacy with B-cell depleting agents.

References

  1. Rovin Arthritis Rheum 2012.

  2. Vital Arthritis Rheum 2011.

References

Disclosure of Interest L. Gomez Mendez Grant/research support from: Genentech/Roche, M. Cascino Employee of: Genentech/Roche, J. Garg Employee of: Genentech/Roche, P. Brunetta Employee of: Genentech/Roche, M. Dall'Era: None declared, L. Dragone Employee of: Genentech/Roche

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