Glucocorticoids (GCs) are one of the most commonly prescribed treatments for systemic lupus erythematosus (SLE) and are critical for SLE-associated kidney inflammation or lupus nephritis. However, GC use causes severe adverse effects. Approximately 50% of the complications patients with SLE develop in the first five years after diagnosis are related to GC use. Complications of GC use include infections, diabetes, osteoporosis, and increased mortality. While GCs are pivotal in the management of SLE and lupus nephritis, there is a lack of guidelines to inform appropriate dosing strategies.  As a result, there is high variability of GC use in clinical practice and clinical trials. Healthcare disparities in lupus have been extensively studied; however, the impact of GC prescribing variation on SLE outcomes in minority groups has not been explored. Dr. Duarte-García will assess the safety and efficacy of different GC regimens and the varying GC use among racial and ethnic minority groups to develop a standardized GC regimen and reduce racial disparities.

Dr. Duarte-García will compare GC prescribing in a large, multiethnic cohort of patients with lupus nephritis to determine whether social and economic factors, including race/ethnicity, gender, and whether the patients live in rural areas, contribute to the high variability of GC prescribing. These findings will highlight populations needing interventions to optimize GC therapy and reduce GC-related complications. Dr. Duarte-García will then assess the effectiveness and safety of various GC dosages and treatment durations in patients with SLE from several clinical trials to determine the dose at which GCs effectively lower relapse rates and increase remission. There have been no comprehensive studies on the efficacy and side effects of low-dose versus high-dose GC regimens. Dr. Duarte-García plans to conduct this pivotal research to inform the development of standardized GC therapy that will inform clinical practice and future clinical trial design and ultimately decrease GC-related comorbidity, or the simultaneous presence of two or more medical conditions, and improve survival.

What this study means for people with lupus:

The results of Dr. Duarte-García’s study will establish a gold-standard GC regimen for patients with lupus nephritis and reduce the variability of GC prescribing. By doing this, Dr. Duarte-García aims to maximize the benefits of GC while reducing their undesirable effects, including infections, osteoporosis, and increased mortality.

Patients with systemic lupus erythematosus (SLE) have increased morbidity and mortality compared to the general population. This may be due, at least in part, to the use of glucocorticoids. Glucocorticoids remain one of the main therapies for SLE with major organ involvement, such as lupus nephritis. Yet, there is a lack of evidence regarding the safest dose and duration of glucocorticoid regimens for lupus nephritis treatment.

The overarching objective of this proposal is to fill critical knowledge gaps in the management of lupus nephritis with immediate translation to practice, improving the effectiveness and safety of glucocorticoid regimens. We plan to achieve this through three specific aims:

Aim 1. To characterize the patterns of glucocorticoid prescribing in patients with lupus nephritis. We will use OptumLabs Data Warehouse and identify trajectories of glucocorticoid use in the first three years after lupus nephritis diagnosis. We will test the hypotheses that (i) the use of glucocorticoid therapy in the treatment of lupus nephritis is highly heterogeneous; and (ii) glucocorticoid utilization differs by sex, race/ethnicity, rurality, the specialty of the clinician, baseline glomerular filtration rate, and proteinuria.

Aim 2. To evaluate the effect of different glucocorticoid regimens on relapse rates and infections among patients with lupus nephritis. We will perform an individual patient data meta-analysis of the standard of care arms in clinical trials using a structured glucocorticoid regimen. We will test the hypotheses that (i) the number of relapses and proportion of those achieving remission using glucocorticoid induction therapy is similar between low-dose and standard-dose glucocorticoid regimens; and (ii) the number of infections using glucocorticoid induction therapy is lower in low-dose compared to the standard dose glucocorticoid regimens.

Aim 3. To develop and validate a standardized glucocorticoid steroid regimen for proliferative lupus nephritis. We will use consensus methods to develop a standardized glucocorticoid regimen for lupus nephritis that can inform clinical practice, be used in clinical trials, and serve as a benchmark to be compared against other glucocorticoid protocols.

We have a unique opportunity to identify evidence-based glucocorticoid regimens for lupus nephritis with the lowest effective doses and exposure. Findings from this novel research will provide the necessary fundamental information to inform contemporary practice and the design of clinical trials to define evidence-based glucocorticoid regimens that will reduce infections, glucocorticoid-­associated comorbidities, and mortality.