Results from the 104-week JUNIPERA trial show that secukinumab is safe and effective in treating children with active enthesitis-related arthritis and juvenile psoriatic arthritis, the pediatric equivalents of axial spondyloarthritis (axSpA) and adult psoriatic arthritis (PsA). Secukinumab is currently approved for adult non-radiographic axSpA, PsA, and ankylosing spondylitis.
“Secukinumab demonstrated significantly longer time-to-flare and number of flares versus placebo,” reported Hermine Brunner, MD, MSc, MBA, Professor of Medicine at the University of Cincinnati and Chief of Rheumatology and Director of the Lupus Center at Cincinnati Children’s Hospital. “Most of the improvement was seen in the first 12 weeks, and sustained improvements continued through week 104.”
Dr. Brunner presented JUNIPERA results during Plenary III on Monday, Nov. 8. The session can be viewed on demand by registered meeting participants through March 11, 2022.
Secukinumab reduced the risk of flare by 72% (HR=0.68, p=0.001) versus placebo, with similar improvements in secondary endpoints, Dr. Brunner reported. There were no new safety signals.
Extended LN outcomes with voclosporin
Voclosporin, a novel calcineurin inhibitor, was approved for adult lupus nephritis in 2021 based on the 52-week AURORA 1 trial with an odds ratio of 2.65 for complete renal response compared to placebo (p<0.001). An interim report on the 36-month AURORA 2 extended trial showed similar results, according to Amit Saxena, MD, who presented the data during Plenary III.
Mean urine protein:creatinine ratio at month 30 was 0.58 mg in the voclosporin arm versus 1.34 mg in the placebo arm, similar to the original 12-month AURORA 1 findings, he said. Mean estimated glomerular filtration rate (eGFR) also remained stable in both arms through month 30.
“This is the largest successful lupus nephritis clinical program to date,” Dr. Saxena said. “Patients in the voclosporin arm of AURORA 2 maintained meaningful reductions in proteinuria with no change in mean eGFR at 30 months of treatment. We will report the primary outcome, a composite of renal outcomes, at the end of the 36-month study.”
Risk factors for VEXAS syndrome
According to other research presented during the session, genotype is a key risk factor for early mortality in adults with VEXAS syndrome, a newly identified adult-onset inflammatory disease caused by a somatic mutation to the UBA1 gene in bone marrow stem cells responsible for the ubiquitin-activating enzyme. VEXAS has significant overlap with other autoimmune conditions, including polychondritis, Sweet syndrome, polyarteritis nodosa, and giant cell arteritis.
An observational study of 83 VEXAS patients showed median survival of 10 years, but patients with a p.Met41 valine (p.Met41Val) variant had median survival of nine years and 100% mortality at 12 years, reported Marcela A. Ferrada, MD, the Lawrence Schulman Scholar at the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Residual ubiquitin-activating enzyme activity is lower in the p.Met41Val variant than in other major VEXAS variants, p.Met41 leucine and p.Met41 threonine, she added.
Across the entire cohort, key independent risk factors for mortality included transfusion dependence (HR=4.47, p<0.005) and p.Met41Val (HR=2.56, p=0.05).
“These findings should inform risk assessment and clinical management in patients with VEXAS syndrome,” Dr. Ferrada said.
Effect of statins on CVD, type 2 diabetes in RA
Chronic inflammation in RA is known to increase the risk for both cardiovascular disease and type 2 diabetes. And while statins have been studied extensively in the general population, there are limited data regarding statin use in RA patients.
An observational study of 22,331 RA patients in United Kingdom databases compared outcomes in new statin users to statin nonusers between 1989 and 2018. Statin use was associated with a 32% reduction in CVD (HR=0.68), a 54% reduction in all-cause mortality (HR=0.46), and a 33% increase in type 2 diabetes (HR=1.33), reported Gulsen Ozen, MD, Rheumatology Fellow at the University of Nebraska Medical Center.
“This is the first cohort study to explore the balance of CVD, mortality, and type 2 diabetes risk with statins in RA,” Dr. Ozen said. “Statins were associated with important reductions in CVD and all-cause mortality risk that outweighed the modest type 2 diabetes risk in RA patients. It’s important to assess eligibility for statin initiation while on RA treatment with monitoring for type 2 diabetes.”
Glucocorticoids and MACE in RA
A retrospective cohort study of glucocorticoid use and major adverse cardiovascular events (MACE) in Veterans Affairs patients with RA found that glucocorticoids, which are used by up to half of RA patients on a long-term basis, significantly increased the risk of MACE in the six months after treatment, reported Beth Wallace, MD, MSc, Assistant Professor at Michigan Medicine and Staff Physician at the VA Ann Arbor Healthcare System.
VA patients with RA are already at increased risk for MACE due to obesity, hypertension, type 2 diabetes, tobacco use, and other risk factors, noted Dr. Wallace. But the effect of glucocorticoid use on MACE risk was unknown.
Researchers used VA patient data from 2013 to 2018 to assess glucocorticoid use over six-month periods and incident MACE in the following six months. MACE included acute myocardial infarction, stroke or TIA, cardiac arrest, or coronary revascularization.
“Just 30 days of glucocorticoid use in a six-month period, even if discontinuous, can lead to a 15% increase in the odds of MACE in the succeeding six months,” Dr. Wallace said.
First-in-human trial for novel SLE agent
Alpine Immune Sciences has launched a first-in-human trial of a novel BAFF/APRIL antagonist (ALPN-3030) to treat systemic lupus erythematosus (SLE). The new agent was engineered using directed evolution to inhibit BAFF (B-cell activating factor of the TNF family) and APRIL (a proliferation-inducing ligand), both of which play a key role in B-cell development and function.
In preclinical studies, the combined agent showed superior B-cell suppression compared to existing BAFF and APRIL antagonists alone or in combination, said Stacey Dillon, PhD, Senior Director of Translational Sciences at Alpine Immune Sciences. Many patients respond poorly to current agents, including belimumab, atacicept, and telitacicept, or have clinically significant flares, leaving a significant unmet medical need in lupus, she added.
ALPN-3030 showed more potency than existing agents in cell-based assays, mouse models of SLE, and in nonhuman primates.
“A first-in-human study in healthy volunteers has been initiated and we expect results before the end of the year,” Dr. Dillon said. “Additional indications are under consideration.”
ACR CONVERGENCE ON DEMAND
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