Lupus Research Highlights From American College of Rheumatology’s 2024 Scientific Meeting
The American College of Rheumatology (ACR) 2024 Convergence has just concluded, showcasing significant advancements and groundbreaking discoveries in lupus research. The annual meeting, held from November 14-19 in Washington D.C., featured thousands of new studies that showcased progress and sparked excitement across the lupus community.
The Lupus Foundation of America (LFA) proudly continues to support, contribute, and propel advancements in lupus research. This year, LFA presentations focused on new insights regarding solutions to reduce disparities in health outcomes from our Lupus Addressing Health Inequities in Minorities (Lupus AIM) program and learnings from our Research Accelerated by You (RAY®) patient registry, both of which received the ARP Presidential Award. Other LFA research included persistent social determinants of health (SDOH), Strategies to Embrace Living with Lupus Fearlessly (SELF) online self-management program, as well as understandings in clinical trial participation decision-making amongst people living with lupus.
Our Inside Lupus Research team covered the meeting, and we’ve brought you some of the top highlights below.
Lupus Nephritis
Conveying the essence and objectives of the conference and the lupus community to enhance patient outcomes through scientific advancements, this year the American College of Rheumatology introduced a summary guideline for the screening, treatment and management of lupus nephritis (LN). The guideline offers evidence-based, expert recommendations for adults and children with lupus and kidney involvement. The guideline focuses on preserving kidney function and minimizing life-threatening outcomes of LN while minimizing medication-related toxicities.
The LFA supported the development of this guideline by providing valuable perspectives from people living with lupus who are enrolled in the Foundation’s Research Accelerated by You (RAY®) registry. Read more about the summary guideline and what it means for people with lupus.
Researchers and LFA award receipts Drs. Michelle Petri and LFA's Medical-Scientific Advisory Council (MSAC) Board member Diane Kamen, along with Dr. Daniel Wallace looked at genetic variations influencing glomerular filtration rate (eGFR) variability which can serve as a proxy for identifying LN in people with systemic lupus erythematosus (SLE). The study identified a genome-wide significant locus for eGFR variability specific to people of African ancestry. Future work will include analyses encompassing all global ancestries and investigate the biological link between identified loci and LN.
Lupus Treatment News
Encouraging advancements on several existing and investigational drugs were shared during the meeting.
- Obinutuzmab – In research co-authored by LFA 2021 Evelyn V. Hess Award recipient and MSAC member Dr. Richard Furie, obinutuzmab combined with standard therapy showed favorable effects and was found to be beneficial regardless of baseline levels of proteinuria.
- Deucravacitinib – In the phase 2 PAISLEY trial, deucravacitinib demonstrated superiority to the placebo with increased SRI(4), BLICA, CLASI-50, and JC-50 response rates in people with SLE. Findings will be further validated in an ongoing phase 3 trial.
- Belimumab – Following clinical trial analysis, researchers including Chair of the LFA MSAC, Dr. Karen Costenbader and LFA's Chief Advisor for Clinical Development, Dr. Joan Merrill, found that belimumab (BENLYSTA) reduces disease flares compared to the placebo in adults with early active SLE. Future studies are needed to confirm results.
- Anifrolumab – A phase 3 trial found long-term treatment of anifrolumab (Saphnelo™) is more effective against organ damage than standard treatment alone in people with moderate to severe SLE. Anifrolumab helps control disease activity, reduce flares, and reduce oral glucocorticoid use, but study findings suggest the drug may also delay the onset of irreversible organ damage and damage accrual.
- Dapirolizumab pegol (DZP) – In a phase 3 study, DZP treatment in people with moderate to severe SLE resulted in significant improvement in disease activity and allowed for gradual reduction of corticosteroids.
CAR cell therapy continues to emerge as a groundbreaking treatment for lupus and other autoimmune diseases, strategically engineering proteins to alter the functioning of immune cells within the body. Exciting CAR Treatment News includes:
- CC-97540 – Preliminary data from the ongoing phase 1 study shows promising safety and efficacy of CC-97540 at low doses with robust CAR T cell expansion and complete B cell depletion. This investigational CD19-targeted CAR T cell therapy uses the same CD19 CAR as the FDA-approved lisocabtagene maraleucel (liso-cel, used to treat large B cell lymphoma), but is created using a process which aims to shorten manufacturing time, improve potency, and optimize the phenotypic attributes of the CAR T cell product.
- BMS-986353 - Researchers studied the safety and long-term efficacy of CD19 CAR-T therapy in 30 people with autoimmune diseases, all of whom had uncontrolled, severe disease activity. All 18 people with SLE achieved DORIS remission with efficacy analysis indicating long-standing, drug-free remission.
- Allogenic CD19 CAR-NK Cells - Allogeneic CD19-targeting CAR-NK cell therapy for SLE demonstrated excellent safety and the potential to achieve rapid and long-lasting remission in cases of relapsed and refractory SLE. This promising off-the-shelf and universal cell therapy could offer new hope for patients with SLE.
Other Novel T cell based therapies
- A-319 – A-319 is a highly potent CD3 x CD19 T cell engager (TCE). These bispecific antibody therapies are comprised of antibodies that target antigens on B cells (CD19) and T cells (CD3), bringing the cells together to enhance T cell directed B cell depletion. Researchers examined if A-319, a bispecific antibody based therapy, had the potential to treat and reset autoimmunity in SLE and found evidence of partial B cell recovery after just two weeks of treatment. These promising results suggest that A-319 could rapidly reset autoimmunity.
Health Disparities
Health disparities in lupus are significant and multifaceted, influenced by a variety of factors from socioeconomics, education, access to healthcare, and more. The disparities in lupus disease management and outcomes across racial, ethnic, and socioeconomic lines remain a critical area of exploration and discussion.
While there is not a special “lupus diet,” maintaining a healthy diet can improve lupus symptoms and overall well-being. Researchers and MSAC members, Dr. Christie Bartels and Dr. Rosalind Ramsey-Goldman explored the relationship between neighborhood resources and dietary intake and found that the majority of study participants needed some or big changes to their diets, with significant changes needed in dairy, whole grain, and sodium intake.
SDOH are not routinely screened for in U.S. outpatient rheumatology clinics. The study, Screening for Social Determinants of Health in Patients with SLE: A Point of Care Feasibility Study, highlighted how routine SDOH screening was perceived as valuable by both patients and their care teams. With appropriate resources and trained care teams, SDOH screening can be successfully implemented to inform clinical decision-making and patient care in lupus clinics. Researchers, including LFA MSAC member Dr. S. Sam Lim, noted future studies should evaluate whether regular SDOH screening for patients with SLE can reduce healthcare disparities and improve care management. Another study identified several subgroups of people with higher social disadvantage and a higher SDOH burden who are at risk for SLE. The prevalence of SLE increased with a higher SDOH burden, showcasing the need for targeted interventions to address social determinants and reduce health disparities.
Economic analyses of SLE often overlook indirect costs. In The Forgotten Costs of SLE: Estimating Indirect Costs in a National SLE Cohort, researchers noted the need to accurately weigh the costs and benefits of novel/emerging therapies, and economic analyses should incorporate costs resulting in lost productivity, including those in unpaid labor, particularly because SLE disproportionately affects women.
Early life trauma and neighborhood deprivation are key factors in the early social environment that can detrimentally influence health. The study, The Effects of Early Life Trauma and Socioeconomic Position on Systemic Lupus Erythematosus Risk in Adulthood, suggests that an adverse early life social environment is a potentially important risk factor for developing SLE later in life, highlighting the need for further research and potential interventions targeting early life factors.
In a presentation, LFA MSAC member Dr. Candace Feldman discussed the enduring and significant racial, ethnic, and socioeconomic disparities in SLE care and outcomes. She highlighted promising interventions designed to address these disparities and emphasized the importance of community-engaged research and cross-institutional collaboration to build a more equitable future in lupus care and outcomes.
The LFA is proud to be part of the collective, global fight against lupus, developing tools and resources to help the lupus community treat and manage the disease as well as fight health disparities. Continue to follow Inside Lupus Research for updates on developing research and treatment news.