Q&A: Dr. Jim Oates on Hard-to-Treat Lupus in Black Patients

July 9, 2019

The prevalence of systemic lupus erythematosus (SLE) is higher among black patients. They can present with a worsened disease state and mortality rates can be higher. This suggests a need for better therapeutic options, says Jim C. Oates, M.D., of Medical University of South Carolina. In this Q&A, Dr. Oates addresses treatment challenges black patients face.

The prevalence of systemic lupus erythematosus (SLE) is higher among black patients. They can present with a worsened disease state and as a result, mortality rates can be higher. This suggests a need for better therapeutic options, says Jim C. Oates, M.D., director of the division of rheumatology, Medical University of South Carolina, Charleston.

Dr. Oates recently spoke with Rheumatology Network about treating black patients with lupus.

In this Q&A, we ask Dr. Oates:

Why do black patients have a higher prevalence of lupus?

“This is a complicated question. Certainly, disease is more prevalent and results in greater damage in individuals of African descent. There are data to support several hypotheses, including increased inherited predisposition, environmental stressors, and socioeconomic disadvantages.”

What contributes to higher mortality?

“Mortality among black women with lupus is close to four times higher for lupus-related death and 1.2 times higher for death of all causes. Blacks die at a younger age as well for several possible reasons. First, many have observed increased disease severity and prolonged activity among blacks. This may be due to an inherited predisposition to lupus and more severe lupus manifestations as blacks are diagnosed with lupus an average of six years sooner than whites and are more likely to have lupus kidney disease. One of the medications that we use to treat the lupus―prednisone―can lead to long-term damage to multiple organs and predisposition to death by infection and cardiovascular disease.

“This is why steroid sparing medications are so important. Lack of access to these medications can lead to an over-reliance on them and, thus, increased mortality. There is also an inherited predisposition to end-stage renal failure among black patients that is due to a gene that is actually unrelated to lupus but makes outcomes and lupus kidney disease worse. Finally, blacks are less likely to receive preventative health services, which may contribute to a delay in diagnosis and treatment.”

What makes belimumab a wonder drug for lupus?

“Many use that term for belimumab because it is the first drug to be approved for the treatment of lupus over 50 years. Among individuals who have failed standard treatments, belimumab significantly reduces the signs and symptoms of lupus. Four randomized controlled trials demonstrated significant improvements, but the magnitude of the improvement was not that large. Patients will sometimes tell you that belimumab has a significant effect on their fatigue. The medication is most effective in individuals who have more clinically and serologically active disease.”

Most studies do not look at lupus in black populations. How can you get more black patients to enroll in trials?

“This is the first trial of its kind in lupus to evaluate the efficacy of the drug in black lupus patients. It highlights the need for more effective therapies in this important segment of the lupus population. With regards to how to enroll more black patients in clinical trials, the first and most important step is to develop trusting relationships with patients who are referred for clinical trials. There are historical and contemporary events that have led to distrust in clinical research among blacks. Patients need to see and believe that their providers have their best interests at heart. Centers with a track record of evaluating and taking measures to reduce health disparities probably have an advantage informing that relationship.”

You recently presented belimumab findings at the International Congress on Systemic Lupus Erythematosus (LUPUS 2019) held in San Francisco in April. The patients in the trial did not reach the primary endpoint, but some improvements were observed in subgroups of patients with high disease activity. What does that tell us?
 

“The magnitude of the effect in this trial was slightly lower than in the previous four randomized clinical trials. In addition, the number of patients enrolled in this trial was lower than previous trials, making it harder to achieve clinical significance. In a pre-specified subgroup analysis of the primary endpoint, black patients with more clinically and serologically active disease at enrollment were significantly more likely to respond. Clinically meaningful responses, particularly among the more common manifestations of lupus, are not well captured by our current response metrics.”

What’s next?

“Certainly, as a clinician, I feel comfortable giving this medication to black patients who have clinically and serologically active disease and have failed conventional therapy. This has been my practice and the practice of my colleagues for some time. For lupus clinical trials in general, my hope is that there will be an ongoing dialogue between the FDA and the research community about clinically meaningful response endpoints.”

REFERENCES:

1. David D’Cruz, Kathleen Maksimowicz-McKinnon, Jim Oates, et al. "200 Efficacy and safety of belimumab in patients of black race with systemic lupus erythematosus: results from the EMBRACE study," Lupus Science and Medicine. 2019;6 DOI: 10.1136/lupus-2019-lsm.200. This study was also presented at the International Congress on Systemic Lupus Erythematosus (LUPUS 2019) held in San Francisco in April.

2. Navarra SV, Guzmán RM, Gallacher AE, et al. BLISS-52 Study Group Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet 2011;377:721–731.

3. Furie R, Petri M, Zamani O, et al. BLISS-76 Study Group A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis Rheum 2011;63:3918–3930.

4. Zhang F, Bae SC, Bass D, et al. A pivotal phase III, randomised, placebo-controlled study of belimumab in patients with systemic lupus erythematosus located in China, Japan and South Korea. Ann Rheum Dis 2018;77:355–363.

5. Stohl W, Schwarting A, Okada M, et al. Efficacy and safety of subcutaneous belimumab in systemic lupus erythematosus: a fifty-two-week randomized, double-blind, placebo-controlled study. Arthritis Rheumatol. 2017;69:1016–1027.