Olivia Walker was diagnosed with Lupus when she was just 6 years old. Over the past 25 years, she’s been prescribed “nearly everything on the market.”
For the most part, that consists of over the counter painkillers, corticosteroids, and hydroxychloroquine (yes, the one that some thought could help treat COVID early in the pandemic.) Just recently, she started taking Benlysta (belimumab), a drug approved in 2011 specifically for lupus.
“It has been my favorite of the treatments I’ve taken over the last 25-plus years,” she says. “I find myself having more energy and fewer symptoms.”
But Walker is Black, and for most of the time that Benlysta has been on the market, the data wasn’t exactly clear on whether or not the drug was effective for Black patients. An analysis of the original clinical trial data suggested it might not be. Doctors and patients were left having to decide for themselves whether to take a chance on the only drug designed specifically for lupus, even though studies suggested it might not work in people like them, and they could be risking side effects such as nausea, diarrhea, insomnia and depression for no benefit. Luckily, a new trial, published 10 years after the drug’s initial FDA approval showed that it does work for Black lupus patients.
What Is Lupus and How Is it Treated?
Lupus is an autoimmune disorder in which your body produces too many B lymphocytes, a type of immune cell which then go on to attack healthy tissues in your body. It can be difficult to diagnose because your symptoms will depend on which tissues the cells attack. For example, if they attack your skin, you may get rashes, but if they attack your joints you may get arthritis-like joint pain.
Corticosteroids and non-steroidal anti-inflammatories, both of which broadly dampen many types of inflammation in your body, are often used to treat the disease. The benefit of Benlysta is that it targets these specific B lymphocytes, instead of all types of immune activity, including important immune responses that protect you against infection.
A Tenuous Approval
Scientists conducting clinical trials on Benlysta in the early 2000s recruited about 1,700 patients living in several different countries. Overall, the trial showed that the drug was effective.
Over time patients who took Benlysta experienced fewer side effects and were able to reduce their use of corticosteroids, according to a 2021 Cochrane review of six trials.
But there was one caveat: when researchers isolated just the Black patients in the trial, for a secondary analysis, the efficacy of the drug disappeared.
“This led to controversy in its use in this population,” says Vaneet Sandhu, MD, a rheumatologist at Loma Linda University.
While some providers were reluctant to prescribe it to their Black patients, Sandhu says it was more often her Black patients who were asked about the discrepancy, and some were hesitant to take the medication because of it.
Why Would a Drug Work Differently in Patients of Different Ethnicities?
“There’s only been a couple a handful of publications, but somewhere between 10 and 20% of all FDA approved biologics have some kind of interaction with race or ethnicity,” says Jonathon Jackson,. “So either the drug isn’t expressed as well, its uptake may change, efficacy may change, side effects may differ.” Jackson, PhD, is the Executive Director of the Community Access, Recruitment, and Engagement (CARE) Research Center at Massachusetts General Hospital and Harvard Medical School
Unfortunately, those differences are typically found after a drug is FDA approved and has been used in millions of people. Black women were potentially treated for no possible benefit, but still exposed to side effects and adverse event risks. What happened with Benlysta “is a sadly common story.”
Certain differences in genes and gene expression are more common in particular ethnic groups. These changes may affect how our bodies metabolize or use drugs, explains Sandhu.
For example, women’s bodies process some drugs differently than men’s do, and for all sexes and races, carrying extra weight can also impact how your body responds to certain treatments.
More often than not though, the differences reflect society more than biology, says Jackson. Clinical trials usually aim to enroll patients who have the disease they’re trying to treat, but no other conditions. This was, for a long time, considered good science. The idea is that that makes it easy to see whether or not the drug works, but it means researchers end up with a sample that doesn’t necessarily reflect most people that have the disease.
In many cases, and specifically in lupus, racial and ethnic minority patients are more likely to have comorbid conditions and more severe disease, potentially due to factors like inconsistent access to quality healthcare, so not only are they more likely to be excluded from the trials, but once the trials are complete, the research is less likely to apply to them.
An Updated Trial
Drug companies are supposed to continue studying their drugs for years after they come to market, but this research isn’t scrutinized as closely as pre-market clinical trials.
“It’s pretty much the honor system,” says Jackson.
In the case of Benlysta, the manufacturer decided to recruit 448 patients who self-identified as Black. More than 96% of them were women. In June of 2021, the team published a yearlong study of Benlysta in those patients, demonstrating that the drug was effective in those who had the most severe lupus symptoms.
“Finally we have data on a larger group of patients previously underrepresented. Admittedly, the study was found to be most beneficial in individuals with high disease activity,” says Sandhu.
“But this is to be expected,” she said, since Benlysta is designed to be used primarily in patients with moderate to severe lupus, rather than milder cases.
What You Should Ask Your Doctor
There are questions you should always ask your doctor about any new drug, such as what risks it comes with, what side effects are common, and which are the most dangerous?
But an especially important question, says Jackson, is: “Is this proven to work in people like me?”
Unfortunately, Jackson explains, the answer may often be that we just don’t know for sure.
“What you have to do then is talk with your doctor about some of the assumptions that went into the clinical trial,” he says, adding that many providers may not have this information readily available, and it’s possible you’ll have to have the discussion over two appointments.
Some patients may prefer a doctor who is Black that might relate better to their concerns. If that’s you, you can use BlackDoctor.org to search for culturally sensitive doctors near you. Other sites, such as ZocDoc, can also allow you to check reviews and view demographics such as gender and race of the doctors.
“If you are anyone other than a wealthy white male who lives in an urban center on the east or west coast, has a median income of over $100,000, and has a master’s or doctoral degree… you need to be asking this question of whether you were represented in the clinical trial,” says Jackson. “Because the odds are pretty good that you weren’t.”
