ACR CONVERGENCE 2021—The Plenary Sessions highlighted select abstracts of interest to the general ACR audience. This year at Plenary Session 2, six researchers shared highlights from their work.
Racial Disparities in Renal Outcomes in Children with SLE
Dr. Joyce Chang
Joyce Chang, MD, MSCE, assistant professor of pediatrics, Harvard Medical School, Boston, kicked off the session talking about a study characterizing trends in renal outcomes over time among hospitalized children with systemic lupus erythematosus (SLE). The researchers tested whether racial disparities in renal outcomes have changed over time.1
So where do we go from here? Dr. Chang noted that a “focus on improving care quality alone won’t be sufficient to close the gap in racial disparities, and we need to know root causes in order to identify processes that preferentially improve outcomes among highest risk groups.”
For next steps, she recommended “systematic collection of local data on individual and area-level social determinants of health to understand why differential risks occur.”
Effects of Vitamin D & Fish Oil
Dr. Karen Costenbader
Karen H. Costenbader, MD, MPH, professor of medicine, Harvard Medical School, and director of the Lupus Program, Brigham and Women’s Hospital, Boston, presented results from the Vitamin D and Omega-3 trial (VITAL), which studied the use of vitamin D and fish oil for the prevention of autoimmune diseases.2
Despite the significant burden of illness of autoimmune diseases, no current preventive measures are at the rheumatologist’s disposal.
Vitamin D and omega-3 fatty acids, commonly known as fish oils due to their abundance in fish, have long been of interest to the scientific community. However, no prospective randomized trials have tested the effects of vitamin D or fish oil supplementation on the incidence of autoimmune disease over time.
VITAL was a randomized controlled trial of more than 25,000 patients who received 2,000 international units of vitamin D daily and 1 g of fish oil daily vs. placebo for the prevention of autoimmune disease in adults. The primary outcome was all incident autoimmune diseases determined via participant self-reporting and extensive medical record review for diagnoses and criteria.
All the intervention groups seemed to have a reduced risk of developing autoimmune disease over time, with vitamin D alone and the combination of vitamin D and fish oil reaching statistical significance. Of note, a high-risk population was not studied, and results pertained only to older adults—women older than 55, and men older than 50. Both agents were safe, without an increase in adverse events.
Dr. Costenbader concluded that the “reduced incidence of rheumatoid arthritis (RA) and polymyalgia rheumatica seen in the trial is important for rheumatology, especially given that these are well-tolerated, non-toxic supplements and no other known effective therapies to reduce the incidence of autoimmune diseases exist.”
When asked if she would recommend these supplements to the children of patients with autoimmune disease, she took care to note, “These data do not address whether people under 50 would benefit, and the participants in this trial were not a high-risk population. … If adult children are over 50, then I think the data supports that recommendation.”
Tofacitinib & Risk Factors for CV Events
Dr. Charles-Schoeman
Christina Charles-Schoeman, MD, MS, professor of medicine, chief of the Division of Rheumatology, University of California, Los Angeles, discussed the ORAL Surveillance study.3 This much-anticipated, phase 3b/4 safety end point study assessed the relative risk of major adverse cardiovascular events and malignancies with 5 or 10 mg of tofacitinib given by mouth twice daily vs. tumor necrosis factor (TNF) inhibitors in patients with active, moderate to severe RA despite methotrexate treatment.
Data showed that in patients with RA who were older than 50 years with one or more cardiovascular (CV) risk factor, the incidence of major adverse cardiovascular events was higher with tofacitinib vs. a TNF inhibitor. Across treatment groups, the baseline covariates of current smoking, aspirin use, age older than 65 years, and being male were the most significant independent overall risk factors for major adverse cardiovascular events in a multivariate analysis.
“Overall, these data emphasize the importance of assessing baseline CV risk when treating patients with RA,” Dr. Charles-Schoeman concluded. “When I see a patient, I tell them the results of the study very briefly, so they understand there may be some risks associated with certain therapies and that we need to weigh those risks and benefits together. It’s our job to know the data so we can provide it to them and counsel them appropriately.”
How SLE Activity Affects Flare Risk after HCQ Maintenance & Discontinuation
Dr. Sasha Bernatsky
Sasha Bernatsky, MD, PhD, James McGill Professor, Department of Medicine, Division of Rheumatology, McGill University Health Centre, Montreal, Quebec, shared data on how baseline SLE disease activity may affect the risk of flare when hydroxychloroquine (HCQ) is stopped or the dose is lowered.4 Although HCQ is the cornerstone of SLE treatment, physicians and patients often consider lowering the dose or stopping the drug during remission and low disease activity to limit long-term toxicity. The study was limited by observational methods, but maintaining the HCQ dose had a lower flare risk in most subgroups evaluated.
Dr. Bernatsky concluded, “Safer subgroups for tapering HCQ may exist, and patient preferences should be considered. But given significant flare rates across all groups, we need to keep working on optimizing SLE treatments.”
Start Time of Biologics in Polyarticular JIA
Dr. Yukiko Kimura
Yukiko Kimura, MD, professor of pediatrics, Department of Pediatrics, Division of Pediatric Rheumatology, Hackensack Meridian School of Medicine, Hackensack, NJ, discussed 24-month outcomes from the STOP-JIA trial.5 We know that polyarticular juvenile idiopathic arthritis (pJIA) patients are at risk of poor outcomes, but little evidence currently exists to support a best time to start biologics. STOP-JIA aimed to identify the optimal timing for administration of these agents.
Note: STOP-JIA compared three Childhood Arthritis and Rheumatology Research Alliance (CARRA) consensus treatment plans: 1) step up (SU)—starting a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) and adding a biologic (b)DMARD, if needed, after three or more months; 2) early combination (EC)—csDMARD and bDMARD started together; and 3) biologic first (BF)—starting bDMARD monotherapy, adding a csDMARD, if needed, after three or more months. Data were collected every three months using the CARRA registry for the first 12 months and every six months thereafter. Patients with 24 months of follow-up were included in this analysis. The primary outcome was the proportion of children achieving clinically inactive disease (CID) off glucocorticoids (GC) at 24 months.
Although it was an observational, non-randomized study, the study found a significant difference in CID in the patients who received the early combination compared with the step-up therapy or biologic-first therapy approaches.
“In summary, it’s encouraging that outcomes in all three treatment groups continued to improve at 24 months after starting treatment,” said Dr. Kimura. “However, this data suggests starting biologics early in pJIA may lead to better long-term outcomes, although pJIA still remains a challenging disease to treat. Fortunately, the Childhood Arthritis and Rheumatology Research Alliance [CARRA] registry follow-up will continue for these patients for 10 or more years. So more important data regarding the durability of this response will become available over time.”
Proteomic Profiling of MIS-C Patients
Dr. Edward M. Behrens
Edward M. Behrens, MD, chair in pediatric rheumatology, chief of the Division of Rheumatology, Perelman School of Medicine at the University of Pennsylvania, Philadephia, discussed proteomic profiling in multisystem inflammatory syndrome of children (MIS-C), a post-infectious complication of pediatric SARS-CoV-2 infection that may be fatal if left untreated.6 His group measured plasma proteins using the Olink platform and found proteomic signature distinguished SARS-CoV-2 phenotypes.
“MIS-C shows clinical and proteomic heterogeneity, with a mixture of thrombotic microangiopathy and macrophage activation syndrome-like signals,” Dr. Behrens summarized. “They showed an outsized interferon-γ [IFNγ] responsiveness, and IFNγ-high MIS-C patients had milder cardiac disease compared to IFNγ-low patients.”
Conclusion
ACR Convergence Plenary sessions highlight some of the most interesting abstracts of the past year. Conference attendees may access slides and watch the session on demand until March 11, 2022.
Samantha C. Shapiro, MD, is an academic rheumatologist and an affiliate faculty member of the Dell Medical School at the University of Texas at Austin. She received her training in internal medicine and rheumatology at Johns Hopkins University, Baltimore. She is also a member of the ACR Insurance Subcommittee.
References
- Chang J, Sears C, Torres V, et al. Racial disparities in renal outcomes over time among hospitalized children with SLE and effects of hospital minority composition [abstract: 0956]. Arthritis Rheumatol. 2021 Oct;73(suppl 10).
- Hahn J, Cook N, Alexander E, et al. Vitamin D and marine n-3 fatty acid supplementation and prevention of autoimmune disease in the VITAL randomized controlled trial [abstract: 0957]. Arthritis Rheumatol. 2021 Oct;73(suppl 10).
- Charles-Schoeman C, Buch M, Dougados M, et al. Risk factors for major adverse cardiovascular events in patients aged ≥ 50 years with RA and ≥ 1 additional cardiovascular risk factor: Results from a phase 3b/4 randomized safety study of tofacitinib vs. TNF inhibitors [abstract: 0958]. Arthritis Rheumatol. 2021 Oct;73(suppl 10).
- Brasil C, Hanly J, Urowitz M, et al. Impact of systemic lupus disease activity state on flare risk after hydroxychloroquine maintenance, reduction or discontinuation in a multinational inception cohort [abstract: 0959]. Arthritis Rheumatol. 2021 Oct;73(suppl 10).
- Kimura Y, Ringold S, Tomlinson G, et al. The Childhood Arthritis and Rheumatology Research Alliance start time optimization of biologic therapy in polyarticular JIA (STOP-JIA) study: 24-month outcomes [abstract: 0960]. Arthritis Rheumatol. 2021 Oct;73(suppl 10).
- Diorio C, Shraim R, Vella L, et al. Proteomic profiling of MIS-C patients reveals heterogeneity relating to interferon gamma dysregulation and vascular endothelial dysfunction [abstract: 0961]. Arthritis Rheumatol. 2021 Oct;73(suppl 10).
