Predictors of treatment response in a Lupus Nephritis population: Lessons from the Aspreva Lupus Management Study (ALMS) Trial

Abstract

Objectives: To identify predictors of overall lupus and lupus nephritis (LN) responses in patients with LN.

Methods: Data from the Aspreva Lupus Management Study (ALMS) trial cohort was used to identify baseline predictors of response at 6 months. Endpoints were Major Clinical Response (MCR), Improvement, Complete Renal Response (CRR) and Partial Renal Response (PRR). Univariate and multivariate logistic regressions with LASSO and cross-validation in randomly split samples were utilised. Predictors were ranked by the percentage of times selected by LASSO and prediction performance was assessed by the Area Under the Receiver Operating Characteristics Curve (AUROC).

Results: We studied 370 patients in the ALMS induction trial. Improvement at 6 months was associated with older age (OR=1.03 [95% CI: 1.01,1.05] per year), normal haemoglobin (1.85 [1.16, 2.95] vs low haemoglobin), active lupus (BILAG A or B) in haematological and mucocutaneous domains (0.61 [0.39, 0.97] and 0.50 [0.31, 0.81]), baseline damage (SDI >1 vs. =0) (0.38 [ 0.16,0.91]) and 24-hour urine protein (0.63 [0.50, 0.80]). LN duration 2-4 years (0.43 [0.19, 0.97] vs < 1 year) and 24-hour urine protein (0.63 [0.45, 0.89]) were negative predictors of CRR. LN duration 2-4 years (0.45 [0.24, 0.83] vs <1 year) negatively predicted PRR. The AUROCs of models for improvement, CRR and PRR were 0.56, 0.55 and 0.51 respectively.

Conclusions: Baseline variables predicted 6-month outcomes in SLE patients. Whilst the modest performance of models emphasises the need for new biomarkers to advance this field, the factors identified can help identify those patients who may require novel treatment strategies.