Evaluating SDoH in Lupus Nephritis: Roger Levy from GSK in a Stimulating Conversation with PharmaShots

Shots:

GSK presented data at the American College of Rheumatology from a multi-center cohort study highlighting the achievement of complete renal response in patients with active lupus nephritis

The study evaluated the attainment of modified complete renal response (mCRR) in patients with systemic lupus erythematosus (SLE) and active lupus nephritis (LN), comparing characteristics between mCRR responders and non-responders

Dr. Roger Levy, Global Medical Expert in Immunology & Specialty Medicine at GSK, spoke with PharmaShots about identifying patient characteristics using the less stringent mCRR criteria.

Saurabh: What were the primary objectives involved in the study of mCRR in Lupus Nephritis patients?

Roger: In clinical trials involving patients with active lupus nephritis (LN) who have never been exposed to biologic treatments, only 30%-40% attain complete renal response (CRR) within 12 months of commencing therapy.

This study assessed kidney response via a modified definition of complete renal response (mCRR) to identify LN patients who achieve a clinically meaningful — albeit not 100% complete— preservation of kidney function.

The hope is that these results will help us identify patient characteristics that are associated with better renal outcomes.

Saurabh: Can you walk us through the study design?

Roger: The authors prospectively followed-up adults with active LN from 2013 to 2020. Active LN was defined if patients had proteinuria defined by The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) criteria.

Measurements of these patients’ renal function were recorded and analyzed to calculate:

mCRR, as measured by urine protein creatinine ratio (uPCR) of less than 0.05 g/mmol and estimated glomerular filtration rate (eGFR) of less than or equal to 10% below that obtained from the first recorded visit.

Modified primary efficacy renal response (mPERR), as measured by uPCR less than 0.07 g/mmol and eGFR less than or equal to 20% below the index value that was obtained from the first recorded visit.

Characteristics between mCRR responders and non-responders were compared using Wilcoxon rank-sum and Chi-square tests, and the likelihood of mCRR attainment in subsequent years in patients who achieved mCRR at Year 2 was assessed using logistic regression analysis.

Saurabh: Would you like to share the results of the study?

Roger: This study found that almost half (45.8%) of patients with LN attained mCRR at least once after proteinuria was first identified in the study’s seven years of observation.

Among patients with at least five years of follow-up data, those who achieved mCRR were older, less likely to be of Asian ethnicity and more likely to come from affluent countries.

In short, evaluating renal response using the less stringent mCRR enabled identification of patient characteristics that dispose them toward potentially better renal outcomes.

Saurabh: Can we talk about SLEDAI-2K criteria and what parameters define LN within these criteria?

Roger: SLEDAI-2K stands for “systemic lupus erythematosus disease activity index 2000.” It was developed in 2002 as a modified version of the older SLEDAI and consists of 24 weighted descriptors of lupus symptoms.

The SLEDAI-2K is the most commonly used disease activity index for modern clinical trials involving lupus. It is a useful tool for assessing the frequency and severity of lupus flares, which are known to contribute to kidney damage.

For this study, we used the proteinuria criteria from the SLEDAI-2K (0.5 g/24 hours) as an indicator of LN.

Saurabh: Can you define the criteria involved in the eligibility or non-eligibility of the patients in this study?

Roger: Patients were deemed eligible for this study if they met the following criteria:

Adults with a diagnosis of SLE.

Had never been exposed to biologic treatments.

Visited the clinic at least twice during the observation period.

Met the proteinuria requirement of the SLEDAI-2K, which is 0.5 g of protein in the 24 hours urine collection.

Saurabh: Why is mCRR defined as a standard in comparison to CRR? What difference does this change in standard created for future research in Lupus Nephritis?

Roger: In this study, we evaluated mCRR, as measured by a uPCR of less than 0.05 g/mmol – which is lower than the 0.05-0.07 g/mmol used for measurement of CRR in other studies, according to 2019 EULAR guidelines – and an eGFR of less than or equal to 10% below that obtained from the first recorded visit – which is the same used for measurement of CRR, according to 2019 EULAR Guidelines. The mCRR doesn’t include the steroids reduction component because it wouldn’t be feasible to look at this component on a historical databank, while on a prospective study with mandatory steroid tapering, it can be evaluated.

Saurabh: What are the other studies that were presented at ACR 2024 related to Lupus Nephritis?

Roger: In addition to the renal response data shared at ACR, GSK highlighted data from a multicenter cohort study evaluating treatment patterns and prevalence of renal biopsy-confirmed LN in patients with systemic lupus erythematosus (SLE) and proteinuria (abstract #0663). Together, these data demonstrate GSK’s commitment to evaluate the importance of timely treatment of lupus to prevent avoidable organ damage and improve long-term outcomes.

Image Source: Canva

About the Author:

Roger A. Levy

Professor Levy is a licensed Adjunct Professor of Rheumatology at The State University of Rio de Janeiro, Brazil, where he started working in 1996. He completed a fellowship programme in Rheumatology in 1989 at HSS/Cornell Medical College and received his PhD in Immunology/Biological Sciences from The Federal University of Rio de Janeiro in 1994.

Professor Levy’s research concerns the clinical and immunological aspects of Systemic Lupus erythematosus (SLE), antiphospholipid syndrome (APS), Sjögren's syndrome and always has a special interest and many publications on the interplay of pregnancy and autoimmune diseases.

He participated in the BLISS-52 study as a principal investigator, as well as in the BASE study, in addition to a large experience in clinical trials for SLE and other rheumatic diseases. He is a member of several scientific journal’s editorial boards, published 3 books and write many book chapters.

Professor Levy joined GSK in early 2018 and is currently a Global Medical Expert in the Special and Medical Care franchise, based in Upper Providence, Philadelphia, USA.