Better understanding of OA fuels hope for new treatment options

The future of osteoarthritis treatment is starting to take shape. The emerging recognition of multiple clinical phenotypes, improved animal models, and deeper insights into the pathogenesis of OA are opening new avenues to disease management.

“We have had 20 years of molecular discovery in OA and are really understanding the disease for the first time,” said Tonia Vincent, MD, PhD, FRCP, Professor of Musculoskeletal Biology and Director of the Centre for Osteoarthritis Pathogenesis, and Consultant Rheumatologist at the University of Oxford in the United Kingdom. “We can begin to imagine what effective disease-modifying treatments are going to look like. And they look very different now to what we thought they would look like 10 or 20 years ago.”

Dr. Vincent is one of the featured speakers in the session Updates in OA: Distinguishing OA Subtypes & Illuminating Future Therapies, which will be held from 4 – 5 p.m. ET Saturday, Nov. 6. The session also will be available on demand for registered meeting participants through March 11, 2022.

Long considered largely untreatable beyond pain management and eventual joint replacement for a subset of patients, OA now appears to be amenable to biological manipulation. Recent genome-wide association studies suggest that OA may be driven primarily by a failure of joint repair rather than by inflammation, as previously thought.

Molecular studies have also identified growth factors resident in the joint cartilage matrix, ready to be released in response to injury. In OA, the repair process fails due to a loss of the ability to release trapped growth factors. But early trials suggest that restoring growth factor signaling can modify and perhaps reverse OA.

That failure of repair mechanisms aligns well with some of the emerging definitions of clinical phenotypes of OA, said Carla Scanzello, MD, PhD, Associate Professor of Medicine at the University of Pennsylvania Perelman School of Medicine and Chief of Rheumatology at the Philadelphia VA Medical Center. She will discuss variability in the clinical presentations among patients with OA, as well as two of the best characterized phenotypes, erosive hand OA and rapidly progressive OA.

“This isn’t just a disease of cartilage degeneration as we assumed for many years. It’s a disease of the whole joint,” Dr. Scanzello said. “Investigating how all the tissues of the joint communicate and interact is showing promise for future therapies. Major changes in our understanding of OA are revealing paths to getting the joint back to homeostasis through communication and interaction between multiple tissues.”

While there are no effective disease-modifying agents currently available for OA, nonpharmacologic, lifestyle-modifying strategies continue to be the standard of care to limit progression.

“Weight loss, exercise, diet have been proven to benefit patients,” Dr. Vincent said. “We already know that people with OA who lose weight and work to keep muscles strong to support that joint are less likely to progress. Those same people are more likely to benefit from new agents as they are introduced into the patient population. So there is plenty that we can do now to prepare ourselves and our patients as these new agents move through trials and hopefully approval.”