Background/Purpose: Lupus nephritis (LN) is associated with high treatment failure rates and the development of new therapies for LN is limited by the lack of validated predictors of clinical response. Recent analyses have identified early predictors of renal outcome in LN.^1,2 The combined placebo control arms of two multi-center, double blinded placebo controlled trials in LN patients (LUNAR and BELONG), where standard of care immunosuppression was given, provide the opportunity to explore the association of clinical variables with renal response.^3,4

Methods: The analysis population included 146 patients given standard of care immunosuppression plus placebo infusions. Response was assessed in the following 3 mutually exclusive categories at one year: complete renal response (CRR), defined as urine protein/creatinine ratio (UPCR) <0.5 on 24-hour urine collection and serum creatinine ²25% above baseline; partial renal response (PRR), defined as ³50% reduction in UPCR, reduction of UPCR to <3 if screening value >3, and serum creatinine ²25% above baseline; and nonresponse (NR), no CRR or PRR. Multivariate logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the associations between independent variables and renal response. These associations were examined in univariate and multivariate models to identify variables independently associated with response.  

Results: All patients had biopsy-proven ISN/RPS 2003 class III or IV LN with 38 (26%) having concomitant class V. Mean UPCR was 4.1 ± 2.9 and mean estimated glomerular filtration rate (eGFR) was 87 ± 38 mL/min/1.73 m² at baseline. 85% were treated with mycophenolate mofetil and 15% with the Euro-Lupus cyclophosphamide regimen. In multivariate analysis (Table 1), baseline UPCR (OR 1.18 for each 1 unit decrease, 95% CI 1.01 to 1.37) and the presence of concomitant class V nephritis (OR 2.8, 95% CI 1.17 to 6.7) were associated with achievement of CRR. ³25% reduction in UPCR at week 8 was associated with CRR in univariate but not multivariate models. ³25% reduction in UPCR at week 8 (OR 0.33, 95% CI 0.15 to 0.76) and the presence of concomitant class V nephritis (OR 0.32, 95% CI 0.13 to 0.79) were associated with a decreased likelihood of NR.

Conclusion: In this pooled population from two phase III randomized trials of LN treated with standard of care immunosuppression, baseline UPCR, concomitant class V LN, and achievement of 25% reduction in UPCR at week 8 were independently associated with renal response. These findings build upon an emerging literature of early predictors of clinical response in LN with the ultimate goals of individualizing treatment decisions based on patient risk and accelerating the development of new therapeutics for LN. References:

1.    Dall’era M Arthritis Rheumatol 2015

2.    Dall’era M Lupus Sci Med 2015

3.    Rovin B Arthritis Rheumatol 2012

4.    Mysler E Arthritis Rheumatol 2013   Table 1: Adjusted odds ratios and 95% confidence intervals for the association between selected variables and renal response at one year

* P < 0.05, ** P < 0.01