“Decades of incredible work conducted by lupus researchers have resulted in major advancements in lupus treatments over the last year,” says Stevan W. Gibson, the president and CEO of the Lupus Foundation of America. “Some of the longest and largest clinical trials for lupus drug treatments have been conducted. In the last six months alone, we have seen two treatments receive U.S. Food and Drug Administration [FDA] approval for lupus nephritis [kidney damage related to lupus].” COVID-19 called a halt to many clinical trials that were underway or gearing up to recruit participants in 2020, says Albert Roy, the executive director of the Lupus Research Alliance affiliate Lupus Therapeutics, the administrative agent of the Lupus Clinical Investigators Network (a group of 57 academic research medical centers working on the development of lupus therapies). “Despite that, this was an exciting year with some wonderful outcomes. We have the first new, approved lupus therapies since 2011, as well as another potential lupus treatment called anifrolumab under consideration by the FDA, too.” Here are eight lupus advances that expand our understanding of this autoimmune condition.
1. New Drug Approvals for People With Lupus Nephritis
In December 2020, the FDA approved use of the lupus drug Benlysta (belimumab) to also treat lupus nephritis, the potentially life-threatening kidney inflammation that affects up to 60 percent of adults with lupus, according to the Lupus Foundation of America. A month later, in January 2021, the FDA approved a second new lupus nephritis treatment, called Lupkynis (voclosporin). “These approvals are a real high point and begin a new chapter for treating lupus nephritis,” says Roy. Doctors had previously made off-label use of other therapies like high-dose steroids, organ-rejection drugs, and even medicines for malaria to treat lupus nephritis; but these two newly approved drugs are the first ever authorized by the FDA specifically for the treatment of this common lupus complication, according to the Lupus Foundation of America. Both medications work by reducing inflammation in the kidneys. Belimumab, given as an infusion or as an injection, is a laboratory-built monoclonal antibody — a protein that, in this case, attaches to immune-system cells called B cells that trigger inflammation. (Belimumab was already an approved drug for treating lupus.) Voclosporin, a pill, works by binding to a protein called calcineurin and preventing it from activating immune-system T cells also involved in kidney inflammation.
2. Heart Disease and Stroke Risks Are Much Higher for Black Women and Men With Lupus
People with lupus face a higher risk for heart disease and stroke. But a University of Wisconsin School of Medicine and Public Health study, presented November 6, 2020, at the American College Rheumatology’s 2020 annual meeting, found that for Black women and men with lupus, the risks are even greater. The study of 336 people with lupus found that for Black participants, risk of stroke was three times higher, and risk of ischemic heart disease (chest pain when the heart muscle doesn’t receive enough blood because of narrow or clogged arteries) was 24 times higher than for the non-Black participants. In a press release from the American College of Rheumatology, the lead study author, Shivani Garg, MD, an assistant professor of medicine at the University of Wisconsin School of Medicine and Public Health in Madison, noted that this information can help people with lupus and their doctors take steps to protect cardiovascular health sooner. “Timely interventions could help reduce cardiovascular disparities in lupus and reduce CVD-related morbidity and mortality in young lupus patients, who are at relatively higher risk of premature CVD,” Dr. Garg noted in the press release.
3. Drug Combinations May Lower Risk of Heart Complications Over Steroids Alone
Researchers from Australia’s Monash University found a potential reason why people with lupus often need high steroid doses to control their condition. In a study published in Lancet Rheumatology in March 2021, the researchers showed that an immune-system protein called type 1 interferon can block the activity of steroids, creating a problem called “steroid resistance.” Researchers have known that some people with lupus can have high levels of type 1 interferon, says Teodora Staeva, PhD, the chief scientific officer for the Lupus Research Alliance. The LRA funded the research, but Dr. Staeva was not involved in the study. The good news, she adds: “There are medications in development, including one under consideration by the FDA called anifrolumab, that target type 1 interferon. In one clinical trial of anifrolumab, participants were able to use lower steroid doses.” And that’s good news, because high doses of corticosteroids taken for long periods of time can damage organs. A study from the University of Leeds published December 3, 2020, in the journal PLoS Medicine, for instance, found that steroid use was associated with a two- to fourfold higher risk for heart attacks, heart failure, and offbeat heart rhythms called atrial fibrillation over five years. Researchers looked at 87,795 people with a variety of inflammatory conditions involving the immune system — including 3,951 with lupus. “All patients requiring long-term steroid treatment should be prescribed the lowest effective steroid dose and have a personalized cardiovascular disease risk prevention plan that takes into account current and prior steroid use,” the study authors wrote, noting that one in four people in the study had other heart risks for which evidence-based interventions exist, such as smoking, high blood pressure, or obesity.
4. Doctors Want Women With Lupus to Know They Can Safely Breastfeed
Many women with lupus and their rheumatologists worry that a new mother’s autoimmune condition or medication could interfere with breastfeeding — even though lupus drugs like hydroxychloroquine are considered safe while nursing. Two recent studies illustrate that new mothers with lupus can safely and successfully nurse their new babies, but reluctance remains. In a study of 265 pregnant women with rheumatic conditions including lupus, published in April 2021 in the journal Lupus, researchers from Duke University in Durham, North Carolina, found that while 80 percent of the women with lupus planned to breastfeed, the number who were nursing their babies seven and a half weeks after birth was 57 percent. Among all study participants, fears about medications were the biggest reason women didn’t try to breastfeed at all — even though most were taking medications considered safe. “Current guidelines from the American College of Rheumatology (ACR), the British Society of Rheumatology (BSR), and the European League Against Rheumatism (EULAR) all agree that most medications used to manage rheumatic diseases are compatible with breastfeeding, including antimalarials, sulfasalazine, azathioprine, ciclosporin, tacrolimus, colchicine, intravenous immunoglobulin, glucocorticoids, and all biologicals,” the researchers noted. An Italian study of 43 women with lupus, published in May 2021 in Lupus, found that 88 percent of women who took hydroxychloroquine before, during, and after their pregnancy were still breastfeeding six months after their baby was born, compared with 54 percent who weren’t taking the drug. By reducing flares, the medication may simply make it easier to continue nursing, the researchers note.
5. Hearing Loss Is More Common for People With Lupus
When researchers from the Medical University of South Carolina in Charleston reviewed 17 studies involving 1,326 people for a review published February 27, 2021, in the journal Lupus, they found that 27 percent of those with lupus had some degree of hearing loss. In contrast, just 2 percent of those without lupus had hearing problems. The ability to detect low-frequency sounds — like the bass guitar in a band or the rumble of thunder — was often reduced. This finding confirms results from many smaller studies in recent years. Experts aren’t certain how the two health conditions are related, but suspect that autoimmune attacks in lupus may damage tiny blood vessels in the inner ear that supply oxygen and nutrients to microscopic hair cells that help transmit sound signals to the brain. Researchers recommend that people with lupus have frequent hearing checks. If you have lupus, talk with your doctor about how often you need one.
6. COVID-19 Vaccines Are Safe for People With Lupus
Now that eligibility for the COVID-19 vaccine has expanded to everyone age 16 and older in the United States, two studies from Johns Hopkins University in Baltimore, published in late March, report good news about vaccine safety, as well as some cautions about effectiveness of the first dose for people with rheumatic and musculoskeletal diseases (RMDs) including lupus. Since people with rheumatic disease were for the most part excluded from clinical trials of these vaccines, questions have lingered about their safety and effectiveness — especially for those taking immune-suppressing drugs, the researchers note. One study, published March 19, 2021, in the Annals of the Rheumatic Diseases, involved 325 people, 28 percent with lupus, who received their first dose of the Pfizer-BioNTech or Moderna vaccine. Side effects were similar to those of the general public, including arm pain and swelling at the injection spot as well as fatigue afterward. No one had an allergic reaction. In a second study, published March 23, 2021, in the Annals of the Rheumatic Diseases, the researchers looked at immune-system responses to the first vaccine dose (again, for the Pfizer and Moderna vaccines) in 123 people with a rheumatic disease (including 24 with lupus). They found 74 percent showed antibody responses 18 to 26 days afterward regardless of type or disease or type of medication they took. “Nearly half of the patients with [rheumatic disease] have expressed hesitancy or unwillingness to receive a SARS-CoV-2 mRNA vaccine due to a paucity of data,” the researchers for this March 23 study noted in their paper. “This report can provide reassurance to patients and their providers.” But there were important exceptions. People who took biologic or nonbiologic disease-modifying antirheumatic drugs (DMARDs) had, overall, a 15 percent lower antibody response than people who didn’t use these medications. (Nonbiologic DMARDs include azathioprine, hydroxychloroquine, leflunomide, methotrexate, mycophenolate, sulfasalazine, and tacrolimus, and biologic DMARDs include adalimumab, certolizumab, etanercept, infliximab, tocilizumab, ustekinumab, ixekizumab, belimumab, rituximab, tofacitinib, and abatacept, according to the study.) The researchers plan to follow study participants after their second dose and hope to learn more about vaccine effectiveness.
7. Overall, Lupus Is Less Common Than Previously Thought, but Big Disparities Persist
In the first national nationwide estimate of how many people are living with lupus — and who they are — a study published January 20, 2021 in Arthritis & Rheumatology produced a surprise that experts say may push lupus research further: A total of 204,295 people had lupus in 2018 in the United States. This data comes from large, statewide registries, whereas previous lupus incidence estimates had been based on extrapolations from smaller data sets. That’s almost low enough for lupus to qualify as a rare disease under the U.S. Rare Diseases Act, which could make drug development easier by reducing the number of participants required in clinical trials. Researchers are just starting to explore this possibility, Roy notes. “It could be very advantageous,” he says. “You could run smaller more refined studies.” Meanwhile, the study also confirmed something experts and people with lupus have long suspected: There are sharp racial and ethnic disparities when it comes to who has lupus. Rates of this autoimmune condition are nine times higher in women than men and are highest in American Indian, Black, and Hispanic women. For men, rates were highest in Black men followed by Hispanic, Asian, and white men. RELATED: New Data Reveals Disparities in Lupus Rates, Particularly for BIPOC Women
8. Smoking Boosts Risk of Skin Problems in People With Lupus
University of Wisconsin in Madison researchers confirmed a link between tobacco use and lupus skin disease in a study of 632 smokers with this autoimmune condition, according to a study published February 24, 2021, in the journal Lupus. Heavy tobacco users, those who smoked the equivalent of 20 cigarettes a day for more than 10 years, were twice as likely to have chronic skin damage than nonsmokers. Those with a 5- to 10-year history of smoking 20 cigarettes daily had a higher risk for short-term damage such as a malar rash, a reddish-purple, butterfly-shaped rash across the cheeks and nose. And even light smokers had higher odds of skin problems than nonsmokers. It’s another compelling reason to quit smoking, the researchers note.
