Team: EMBRACE, aka “EMBRACE Diversity”

Base Article: Ginzler E, Guedes Barbosa LS, D’Cruz D, et al. Phase III/IV, Randomized, Fifty-Two-Week Study of the Efficacy and Safety of Belimumab in Patients of Black African Ancestry With Systemic Lupus Erythematosus. Arthritis Rheumatol. 2022;74(1):112-123. doi:10.1002/art.41900

Authors: Northwestern Rheumatology Fellowship

1. Laura Arneson, MD, rheumatology fellow, Northwestern University
2. Brian Jaros, MD, rheumatology fellow, Northwestern University
3. Stephanie Kao, MD, rheumatology fellow, Northwestern University
4. Natania Field, MD, PhD, rheumatology fellow, Northwestern University
5. Clarice Lin, MD, rheumatology fellow, Northwestern University

Team Overview

Systemic lupus erythematosus (SLE) disproportionately affects patients of Black / African ancestry in prevalence, morbidity, and mortality (1). However, this population has been under-represented in most clinical trials for SLE, leading to confusion about treatment for some of the patients who need it most (2). In particular, a pooled analysis of phase III data raised concern that belimumab was ineffective specifically in patients of Black / African ancestry (3). The EMBRACE trial entered the arena to address this question and set a new standard for racial equity in clinical trials.

EMBRACE was the first randomized, placebo-controlled trial for SLE that exclusively enrolled patients of self-identified Black race (4). 448 patients were randomized to belimumab vs. placebo. The primary endpoint of SRI-SLEDAI-2K at 52 weeks was numerically (though not statistically significantly) higher in the belimumab group (48.7%) vs. placebo (41.6%), with trends toward lower risk of severe flares and greater steroid tapering with belimumab. Patients with baseline SELENA-SLEDAI-SLEDAI-2K scores ≥ 10, positive anti-dsDNA antibodies, or low complement showed greater responses to belimumab, findings that can guide clinical practice.

Though the EMBRACE did not meet statistical significance, potentially due to under-enrollment, it provided reassurance that belimumab is a viable option for patients of Black / African ancestry. As a result, a cautionary statement was removed from the belimumab label (5). Most importantly, EMBRACE demonstrated how to re-center research to serve populations that have historically been excluded from its benefits.

Want to learn more?

See the Q&A on theMednet.org about the following question: How can ethnic representation in clinical research studies in childhood and adult SLE be improved?

Next Report: PRODERM

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References:

1. Feldman CH, Hiraki LT, Liu J, Fischer MA, Solomon DH, Alarcon GS, et al. Epidemiology and sociodemographics of systemic lupus erythematosus and lupus nephritis among US adults with Medicaid coverage, 2000–2004. Arthritis Rheum 2013;65:753–63.
2. Falasinnu T, Chaichian Y, Bass MB, Simard JF. The representation of gender and race/ethnic groups in randomized clinical trials of individuals with systemic lupus erythematosus. Curr Rheumatol Rep 2018; 20:20.
3. Benlysta prescribing information. Philadelphia (PA): GlaxoSmithKline; 2021. URL: https://www.gsksource.com/pharma/content/dam/ GlaxoSmithKline/US/en/Prescribing_Information/Benlysta/pdf/BENL YSTA-PI-MG-IFU-COMBINED.PDF.
4. Ginzler E, Guedes Barbosa LS, D’Cruz D, Furie R, Maksimowicz-McKinnon K, Oates J, Santiago MB, Saxena A, Sheikh S, Bass DL, Burriss SW, Gilbride JA, Groark JG, Miller M, Pierce A, Roth DA, Ji B. Phase III/IV, Randomized, Fifty-Two-Week Study of the Efficacy and Safety of Belimumab in Patients of Black African Ancestry With Systemic Lupus Erythematosus. Arthritis Rheumatol. 2022 Jan;74(1):112-123. doi: 10.1002/art.41900. Epub 2021 Dec 9. PMID: 34164944; PMCID: PMC9300099.
5. Sheikh, S.Z., Englund, T.R., Burriss, S.W., Bull, J., Harry, A., Groark, J.G., Hall, A.M., Miller, M. and Roth, D.A. (2022), EMBRACE: One Small Story in Lupus—One Giant Challenge in Clinical Trials. ACR Open Rheumatology, 4: 747-752. https://doi.org/10.1002/acr2.11477