Background Increased body mass index (BMI) has been associated with poor functional capacity and systemic inflammation in lupus,¹ alterations in rituximab (RTX) pharmacokinetics,² and failure to achieve trial endpoints among patients treated with RTX for ANCA-associated vasculitis.³ Although RTX is not approved for the treatment of lupus nephritis (LN), current EULAR/ERA-EDTA guidelines include RTX for use in refractory cases.⁴ The effect of BMI on outcomes of patients treated with RTX for LN is unknown.

Objectives To assess the association between pre-treatment BMI and renal response using data from the LUNAR trial.

Methods LUNAR randomized 144 patients with ISN/RPS class III or IV LN to RTX (2 doses of 1000 mg at baseline and month 6) or placebo in combination with mycophenolate and a steroid taper.⁵ BMI was measured at the screening visit. Complete renal response (CRR) was defined as achievement of UPCR <0.5, normal serum creatinine not increased from baseline by >15%, and inactive urinary sediment at week 52. Alternative definitions of response and achievement of CRR at week 78 were also considered. Logistic regression was used to model interactions and to calculate odds ratios (OR) and 95% CI. Peripheral CD19⁺ B cell measurements were examined.

Results We identified qualitative interactions between BMI and treatment for CRR and alternative response measures. In unadjusted analysis, each 5 kg/m² increase in pre-treatment BMI was associated with OR =0.47 (95% CI 0.24–0.92) in the RTX group and OR =1.44 (95% CI 0.93–2.23) in the placebo group for achievement of CRR (P value for interaction =0.006). The results of analysis adjusted for baseline UPCR and serum creatinine are presented in the Table. A sensitivity analysis identified consistent associations between BMI and response in the RTX group only. Among patients in the RTX group, increased BMI was associated with increased time to peripheral CD19⁺ count <5 cells/μL (Figure).

All endpoints were measured at week 52 except where specified.

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Conclusions In this exploratory analysis of the LUNAR trial, BMI was inversely associated with renal response among patients treated with RTX. We did not observe this same relationship between BMI and response among patients in the placebo group, and in fact found evidence of a positive correlation between BMI and one measure of response in this group. Among patients treated with RTX, BMI was associated with time to B cell depletion, generating the hypothesis that the observed differences in response are mediated by differences in the timing and/or degree of B cell depletion. These findings warrant additional analyses to better understand the relationships between patient characteristics, pharmacokinetics, B cell depletion, and treatment response in the LN population.

References

1. Oeser Arthritis Rheumatol 2005.

2. Müller Blood 2012.

3. Bertsias Ann Rheum Dis 2012.

4. Rovin Arthritis Rheumatol 2012.

References

LUNAR trial NCT00282347.

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