Overall renal outcomes for children with systemic lupus erythematosus (SLE) have improved in recent years, but racial gaps persist, according to Joyce Chang, MD, Assistant Professor of Pediatrics in the Division of Immunology at Boston Children’s Hospital and Harvard Medical School.
Dr. Chang reported results from the first of six studies presented during Plenary II. The session was originally presented Sunday, Nov. 7, and can be viewed by registered meeting participants through March 11, 2022.
In the first study, researchers used the Pediatric Health Information System inpatient database to build a cohort of 7,434 SLE patients between ages 5 and 21 at index admission in the study period, 2006 to 2019. Adverse renal outcome burden was assessed in three time periods: 2006-2010, 2011-2015, and 2016-2019.
Over the entire study period, there was a significant decrease in SLE hospitalizations associated with end-stage renal disease, dialysis, or renal transplant (OR=0.5). But compared to white children, Black children carried a higher burden of adverse renal outcomes over the entire study period (OR=2.5), Dr. Chang reported.
The racial gap has increased over time in areas where ≥50% of children hospitalized with SLE were Black, from an OR=1.8 in the 2006-2010 study period to OR=7.6 in the 2016-2019 study period.
“A focus on care quality alone is not likely to prove sufficient to close the gap in racial disparities,” Dr. Chang said. “We need to understand individual and area-level social determinants of health to understand the differential risks so we can design care processes around these issues.”
Vitamin D, fish oil show modest prevention benefit
Vitamin D and omega-3 (n-3) fatty acids showed modest benefits in the prevention of autoimmune disease in the VITAL trial, reported Karen H. Costenbader, MD, MPH, Director of the Lupus Program at Brigham and Women’s Hospital and Professor of Medicine at Harvard Medical School.
The VITAL trial randomized 25,871 men (age ≥50 years) and women (≥55 years) to vitamin D or placebo and n-3 fatty acids or placebo for a mean of 5.3 years. Cancer and cardiovascular disease outcomes from the trial have already been published.
Compared to placebo, vitamin D reduced the risk of autoimmune disease (HR=0.78, p=0.45), while n-3 fatty acids showed a nonsignificant numerical reduction (HR=0.85, p=0.20), Dr. Costenbader said. Similarly, vitamin D and a combination of vitamin D and n-3 fatty acids reduced the risk of incident autoimmune disease over five years (HR=0.68, p=0.02 and HR=0.69, p=0.03, respectively) compared to placebo, while n-3 fatty acids alone did not (HR=0.74, p=0.07).
“The clinical importance of these results is high, given that these are well-tolerated, nontoxic supplements and that there are no known effective therapies to reduce the incidence of autoimmune diseases,” Dr. Costenbader said.
Tofacitinib shows numerical increase in MACE vs. TNF inhibitors
ORAL Surveillance, a randomized, open-label, noninferiority safety trial, showed a numerical but not statistically significant increased risk of major adverse cardiovascular events (MACE) for tofacitinib versus TNF inhibitors in adults with active, moderate-severe RA.
The trial followed 4,110 patients with at least one known risk factor for MACE from March 2014 to July 2020. Study participants were 60 years of age on average and 70% were female.
The incidence of MACE was higher with tofacitinib versus TNF inhibition (HR=1.24 for tofacitinib 5 mg BID; HR=1.43 for tofacitinib 10 mg BID), but all confidence intervals crossed 1. The key independent risk factors were current smoking (HR=2.18, p<0.001), aspirin use (HR=2.11, p=0.0004), age ≥65 years (HR=1.81, p=0.0011), and male sex (HR=1.81, p=0.0015). Baseline cardiovascular risk was similar across all groups.
“Across treatment groups, MACE — and [myocardial infarction] in particular — were largely associated with baseline cardiovascular risk,” said Christina Charles-Schoeman, MD, MS, Professor of Medicine and Chief of Rheumatology at the University of California, Los Angeles, David Geffen School of Medicine. “These data emphasize the importance of assessing baseline cardiovascular risk when treating patients with RA.”
Reducing, stopping HCQ increases SLE flare risk
Clinicians and SLE patients have long debated the need to reduce or discontinue hydroxychloroquine (HCQ) therapy during remission or periods of low disease activity to limit the potential for long-term toxicity.
An analysis of patients in the SLICC Inception Cohort show that decreasing or discontinuing HCQ brings significant risk of flare, reported Sasha Bernatsky, MD, PhD, James McGill Professor and Senior Scientist in the Centre for Health Outcomes Research at McGill University Faculty of Medicine and Health Sciences in Montreal, Canada.
Compared to HCQ maintenance dosing, reducing HCQ carries a hazard ratio of 1.2 and discontinuing HCQ boosts flare risk to 1.56, she said. For patients in remission, stopping HCQ boosts the risk of flare to 2.77 and reducing HCQ boosts the risk of flare to 2.14.
The study cohort included 1,460 patients with new-onset SLE with annual follow-up from 1999 through 2019. For the purposes of the study, flare was defined as hospitalization due to SLE, increased disease activity, or therapy augmentation.
“Patient preferences must be considered, but given the significant flare rates across all groups, keep working to optimize SLE treatments,” Dr. Bernatsky said.
Early biologic, DMARD combo can improve outcomes in polyarticular JIA
Initial therapy can affect long-term outcomes in children with polyarticular juvenile idiopathic arthritis (pJIA), but there has been little evidence to support the best time to begin biologics.
STOP-JIA compared conventional step up (SU) therapy to an early combination (EC) of DMARD plus biologic as the initial therapy, and biologic first (BF) as monotherapy.
The non-randomized, observational cohort study followed 257 SU, 100 EC, and 43 BF pJIA patients from the CARRA Registry. While all three groups showed improvement, 59.4% of the EC patients had clinically inactive disease at 24 months compared to 48% in the BF group and 40.1% in the SU group, reported Yukiko Kimura, MD, Professor and Chief of Pediatric Rheumatology at Hackensack Meridian Health. The EC versus SU difference, 19.3%, was statistically significant (p=0.0093), she added.
“Starting biologics early in pJIA may lead to better long-term outcomes, though pJIA continues to be a challenging disease to treat,” Dr. Kimura said.
MIS-C patients show interferon gamma dysregulation
Multisystem inflammatory syndrome in children (MIS-C) emerged early in the COVID-19 pandemic as a complication of pediatric SARS-CoV-2 infection, usually after a mild or asymptomatic exposure. The etiology and biology are poorly understood and MIS-C can be fatal if untreated.
An analysis of about 1,500 plasma proteins revealed significant differences between children who had asymptomatic or minimal SARS-CoV-2 infection, severe acute respiratory distress syndrome, MIS-C, and healthy controls, reported Edward Behrens, MD, the Joseph Lee Hollander Chair in Pediatric Rheumatology and Chief of Rheumatology at the Children’s Hospital of Philadelphia. Proteomic signatures alone could distinguish between the four phenotypes, he said.
Children with MIS-C showed protein signatures of blood vessel injury, macrophage activation syndrome, and an outsized interferon gamma (IFNγ) signature, Dr. Behrens reported. Patients with IFNγ overactivity have very different clusters of associated proteins based on activity level, he added, and IFNγ-high patients had lower utilization of cardiac support during hospitalization.
“The IFNγ signature may be useful as a biomarker to predict cardiac outcomes in these children,” Dr. Behrens said.
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