Six researchers presented the findings of recent high-impact studies on drug therapies and mechanisms of rheumatic disease in the Monday, November 14, Late-Breaking Abstracts session at ACR Convergence 2022.
The session is available for on-demand viewing for registered ACR Convergence participants through October 31, 2023, on the virtual meeting website.
Glucocorticoids in inflammatory diseases
A recent trial stirred debate around the benefits of glucocorticoids (GCs) in older patients with inflammatory diseases. Giovanni Adami, MD, a Rheumatologist at the University of Verona, Italy, led a longitudinal cohort study of women with inflammatory rheumatic musculoskeletal diseases (iRMDs).
“We know that the bone-safe dose is very difficult to find in iRMD and might be lower than 5 mg per day,” Dr. Adami said.
His study found that GC daily doses as low as 2.5 mg were associated with bone mineral density loss in iRMD patients. However, this effect can be prevented with anti-osteoporotic drugs. Pending more research, this could support anti-osteoporotic treatments for patients taking low-dose GCs, which juxtaposes current GC-induced osteoporosis guidelines, Dr. Adami said.
Bimekizumab in psoriatic arthritis
Christopher Ritchlin, MD, MPH, Professor of Medicine, University of Rochester, led BE OPTIMAL, a study to test the efficacy and safety of the monoclonal IgG1 antibody bimekizumab in the treatment of patients with active psoriatic arthritis (PsA).
The phase 3 trial demonstrated long-term efficacy and tolerability of interleukin-17A (IL-17A) and interleukin-17F (IL-17F) inhibition with bimekizumab treatment in biologic disease-modifying anti-rheumatic drug (bDMARD)-naïve patients with PsA, he said. Bimekizumab-treated patients with PsA demonstrated efficacy across skin and joint outcomes.
CD8 T cells in psoriatic arthritis
PsA often manifests across several domains, including the skin, joints, and spine, which complicates treatment. While recent evidence suggests CD8 T cells play a major role in the pathogenesis of PsA, the function these cells serve in driving disease across individual domains has remained unclear.
Maria de la Luz Garcia-Hernandez, MSc, PhD, Research Assistant Professor, University of Rochester, and her collaborators injected sera and peripheral blood mononuclear cells (PBMCs) from patients with specific phenotypes into immunodeficient mice to evaluate cellular and serum factors that could lead to domain inflammation in PsA.
“Humanized PsA mice are innovative and experimental tools to study skin and synovial PsA pathogenesis, and to test novel targeted and personalized therapies,” Dr. Garcia-Hernandez explained.
The data showed serum factors and CD8 T cells do promote domain-specific phenotypes. While more work is required, this research model could lead to more discoveries related to patient-specific therapies and underlying disease mechanisms, she said.
Checkpoint inhibitory receptors in rheumatic disease
Paul Emery, MD, FRCP, MA, FMedSci, Professor, University of Leeds, and Director, Leeds Musculoskeletal Biomedical Research Centre at Leeds Teaching Hospitals Trust, United Kingdom, reported on a clinical trial that hypothesized peresolimab binding to the checkpoint inhibitory receptor PD-1 could stimulate physiological immune inhibitory pathways to restore immune homeostasis.
Data from the trial represent “the first clinical evidence that agonism of checkpoint inhibitory receptors could be an effective approach to treat rheumatic disease,” Dr. Emery said.
While additional research is required to evaluate the efficacy of peresolimab in care, the initial discoveries from this study could lead to new approaches to treating patients with autoimmune or autoinflammatory diseases.
Denosumab in erosive hand osteoarthritis
Erosive hand osteoarthritis (OA) is a disabling disease that disproportionately affects women, and there are few therapeutic options for patients managing the disease. Ruth Wittoek, MD, PhD, Professor of Rheumatology, Ghent University, and her research team explored the structure-modifying effects of denosumab in patients with erosive hand OA. Her research concluded that the agent has clear structure-modifying effects on the disease compared to placebo.
“This is the first proof of concept study that structure modification is an achievable goal for patients with erosive hand OA,” Dr. Wittoek said.
Tofacitinib versus TNF inhibitors in MACE
ORAL Surveillance, a post-authorization safety study of tofacitinib versus TNF inhibitors (TNFi), found a higher risk of major adverse cardiovascular events (MACE) with tofacitinib than TNFi.
University of Manchester Professor of Rheumatology Maya Buch, MD, led the posthoc analysis of the risk of all adjudicated cardiovascular events as part of extended MACE endpoints. Her research concluded that the risk of composite ischemic cardiovascular events and heart failure did not appear different with tofacitinib versus TNFi. However, across extended MACE endpoints, the risk was higher with tofacitinib than TNFi in patients with a history of atherosclerotic cardiovascular disease.
“These data highlight a few points about the at-risk populations, and particularly a bit of more nuanced thinking is probably needed in terms of the individual cardiovascular events our patients are at risk with,” Dr. Buch concluded.