THE OFFICIAL NEWS SOURCE OF ACR CONVERGENCE 2022 • NOVEMBER 10-14



Evidence shows role inflammatory response plays in OA

New research shows that inflammatory pathways may play a role in osteoarthritis development and progression.

“For decades, everybody thought of OA as a degenerative disease in which the cartilage breaks down,” said William H. Robinson, MD, PhD, Professor of Medicine in the Division of Immunology and Rheumatology at Stanford University. “There is emerging evidence that an inflammatory response plays a role. We think it’s a key driver in OA.”

Dr. Robinson will explore the current state of research into Novel Inflammatory Pathways in OA on Sunday from 11:00 am – 12:00 pmin Room W183a. New findings on inflammatory pathways offer the first hope of effective treatment for what is by far the most common rheumatic disease.

In rheumatoid arthritis and other autoimmune diseases, it is clear that autoimmune inflammation is the root cause of disease, Dr. Robinson said. In OA, the inflammation is low-grade, an order of magnitude lower than in RA.

The lack of clear causation between inflammation and OA has led many clinicians and researchers to conclude that there must be some other driving factor. Injury and altered biomechanics are leading candidates, especially knowing that both meniscal and ACL tears increase the risk of developing OA approximately five-fold. And because the prevalence of OA increases with age, it is tempting to assume accumulated wear and tear somehow leads to the development of OA.

“OA will affect the vast majority of us,” Dr. Robinson said. “By the time you are 70, 80, 90 years old, 50, 60, 70 percent of us will develop symptomatic OA. If you are fortunate enough to live to 100, you will almost certainly have OA, and it will interfere with your life by causing pain or some degree of immobility. Currently, we don’t have anything that slows disease progression to offer patients.

“We have joint replacement and pain control, but we don’t see people with OA for routine management because we don’t have disease-slowing therapeutic modalities to offer them. This is an underserved disease, but it is a massive one. It represents tremendous need and tremendous opportunity.”

The problem, he said, is that OA research has taken a back seat to research in RA and other rheumatoid diseases with more readily defined autoimmune pathology. In terms of need to the general population, OA arguably surpasses the other diseases rheumatologists study and treat.

Researchers and clinicians have already tried almost every drug, biologic, and therapeutic regimen that affects pathways that are active in RA and other autoimmune diseases in OA. Nearly every attempt has failed.

“We believe OA is the result of inflammatory pathways that are fundamentally different from those involved in RA and other autoimmune diseases,” Dr. Robinson said. “There is a subset of degenerative diseases, OA, Alzheimer’s, macular degeneration and others, that involve the primitive innate immune system. It is these innate inflammatory pathways that are activated and drive the disease we know as osteoarthritis.”

Focused research in RA and other classical autoimmune diseases has resulted in a variety of well-defined pathways and clear targets such as TNF and IL-6. Inhibitors that block these pathways bring enormous clinical and quality of life benefits to RA patients. OA needs similarly focused research to further define and refine OA disease pathways, identify targets, and develop effective therapeutics.

Rheumatologists should champion research and care guidelines for OA, though rheumatologists may not be the clinicians who ultimately deliver the bulk of OA care. Like hypocholesteremia and low-grade coronary artery disease, primary care will most likely provide the bulk of OA patient care.

“There will be 30 million Americans with OA in the coming decades, and we rheumatologists don’t have the bandwidth to care for them,” Dr. Robinson said. “But we should be the champions defining the mechanisms of the disease and developing the therapies and treatment paradigms that the field of medicine as a whole is going to need to implement to prevent and to treat OA.”