Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2022 May;9(1):e000584.
doi: 10.1136/lupus-2021-000584.

Predictors of treatment response in a lupus nephritis population: lessons from the Aspreva Lupus Management Study (ALMS) trial

Stephen McDonald  1 , Sean Yiu  2 , Li Su  2 , Caroline Gordon  3 , Matt Truman  4 , Laura Lisk  4 , Neil Solomons  4 , Ian N Bruce  5   6 ; MASTERPLANS Consortium
Collaborators, Affiliations
Clinical Trial

Predictors of treatment response in a lupus nephritis population: lessons from the Aspreva Lupus Management Study (ALMS) trial

Stephen McDonald et al. Lupus Sci Med. 2022 May.

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 least absolute shrinkage and selection operator (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 (AUROC) curve.

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 to 1.05) per year), normal haemoglobin (1.85 (1.16 to 2.95) vs low haemoglobin), active lupus (British Isles Lupus Assessment Group A or B) in haematological and mucocutaneous domains (0.61 (0.39 to 0.97) and 0.50 (0.31 to 0.81)), baseline damage (SDI>1 vs =0) (0.38 (0.16 to 0.91)) and 24-hour urine protein (0.63 (0.50 to 0.80)). LN duration 2-4 years (0.43 (0.19 to 0.97) vs <1 year) and 24-hour urine protein (0.63 (0.45 to 0.89)) were negative predictors of CRR. LN duration 2-4 years (0.45 (0.24 to 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 patients with SLE. While 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.

Keywords: cyclophosphamide; lupus nephritis; treatment.

PubMed Disclaimer

Conflict of interest statement

Competing interests: CG has received personal fees for honoraria from consultancy work and/or advisory boards from the Center for Disease Control, AstraZeneca, BMS, GSK, MGP, Sanofi, UCB, Aspreva Pharmaceuticals, Genentech and Roche Pharmaceuticals; personal fees for speakers bureau from UCB and GSK; previous educational grants from Aspreva Pharmaceuticals to the University of Birmingham, and from UCB to Sandwell and West Birmingham Hospitals NHS Trust that have supported her research work independent of any specific drug. LL and NS are employees of Aurinia Pharmaceuticals Inc. and holds stock in the company. LL and NS were both previously an employee of Aspreva Pharmaceuticals and Vifor Pharmaceuticals at the time of the conduct of the ALMS trial and held stock options in the companies. MT has a paid consultancy for Aurinia Pharmaceuticals Inc and previously held a paid consultancy for Aspreva Pharmaceuticals and Vifor Pharmaceuticals. INB has received grant/research support from Genzyme/Sanofi, GSK, Roche and UCB; received consulting fees from Eli Lilly, GSK, Merck Serono, UCB and ILTOO; and was a speaker for AstraZeneca, GSK and UCB.

Figures

Figure 1
Figure 1
Univariate analysis of improvement, partial renal response (PRR) and complete renal response (CRR) at 6 months. Red circles/bars represent odds ratios and 95% CI of statistically significant predictors (p≤0.05) for PRR and CRR, and blue circles/bars represent ORs and 95% CI of non-significant predictors for PRR and CRR. aCL, anticardiolipin; BILAG, British Isles Lupus Assessment Group; eGFR, estimated glomerular filtration rate; LN, lupus nephritis; SDI, SLICC/ACR damage index; SLICC, Systemic Lupus International Collaborating Clinics.
See this image and copyright information in PMC

References

    1. Teh CL, Phui VE, Ling GR, et al. Causes and predictors of mortality in biopsy-proven lupus nephritis: the Sarawak experience. Clin Kidney J 2018;11:56–61. 10.1093/ckj/sfx063 - DOI - PMC - PubMed
    1. Appel GB, Contreras G, Dooley MA, et al. Mycophenolate Mofetil versus Cyclophosphamide for Induction Treatment of Lupus Nephritis. JASN 2009;20:1103–12. 10.1681/ASN.2008101028 - DOI - PMC - PubMed
    1. Dall'Era M, Levesque V, Solomons N, et al. Identification of clinical and serological factors during induction treatment of lupus nephritis that are associated with renal outcome. Lupus Sci Med 2015;2:e000089. 10.1136/lupus-2015-000089 - DOI - PMC - PubMed
    1. Nagafuchi Y, Shoda H, Fujio K. Immune profiling and precision medicine in systemic lupus erythematosus. Cells 2019;8:140. 10.3390/cells8020140 - DOI - PMC - PubMed
    1. Fung WA, Su J, Touma Z. Predictors of good long-term renal outcomes in lupus nephritis: results from a single lupus cohort. Biomed Res Int 2017;2017:1–8. 10.1155/2017/5312960 - DOI - PMC - PubMed

Publication types

MeSH terms