David Felson, MD, MPH, often steps out of his physician’s role to help patients with osteoarthritis (OA). “I have one now who needed me to write to her landlord to get her to a ground floor apartment because she’s unable to navigate the stairs,” said Dr. Felson, a professor of medicine and epidemiology at Boston University.
Dr. David Felson
Rheumatologists don’t have a lot of options to treat patients with OA, Dr. Felson said. The most effective treatments are NSAIDs. While reasonably effective, they have a lot of side effects and are not always safe to use, he said.
Exercise also works, but people don’t adhere to it after a while. “Another useful strategy is getting cortisone injections into the affected joint, but that doesn’t last for very long, and I think we’re all reluctant to do it over and over again,” Dr. Felson said.
Some might say, “Well, why can’t they just get a knee replacement?” Many patients don’t want the surgery, and others are too frail to qualify. They’re also not 100% successful. Patients after the surgery sometimes say that they’re still in pain.
There’s an urgent need for more effective therapies, said Dr. Felson, who’s been working on a unique approach to target patients at high risk for OA by studying two specific populations who sustain knee injury.
Previous clinical trials have failed
Clinical trials to test OA treatments have run into some roadblocks. The market for this is enormous, with the potential to benefit millions of patients, Dr. Felson continued.
However, very few large pharmaceutical companies or even biotech companies are pursuing treatment development in osteoarthritis because there have been a lot of expensive failures. “It’s made them gun shy,” Dr. Felson noted.
One issue is OA has a long disease course, taking decades to progress and see changes, said Jason Kim, PhD, vice president for osteoarthritis research at the Arthritis Foundation in Atlanta.
Ron Hester
Dr. Jason Kim
The typical clinical trial window runs just 2-5 years, which is insufficient to see adequate results in a disease like OA. Longer trials are prohibitively costly, especially for corporations with near-term pressures, Dr. Kim said.
Many of these trials also apply disease-modifying drugs to participants with OA who are “too far gone” and beyond repair. By the time older people present with OA to the doctor, their disease is far advanced, and it may not be reversible or even stoppable, Dr. Felson said.
Finding patients with ACL reconstruction with ‘bad outcomes’
Dr. Kim and Dr. Felson have joined other researchers to test a new approach, using people with anterior cruciate ligament (ACL) reconstruction as a starting block to sleuth out OA tendencies years before it even begins.
When someone gets an ACL or meniscal tear, the knee in many cases begins the process of developing OA. However, that process can take 10-20 years, or sometimes even longer.
“We can’t do trials that last that long,” Dr. Felson said. But there are a few people who do quickly develop OA when they sustain those injuries. “If we can grab those people and get them involved in a study where we test treatments, we could probably figure out what kinds of treatments would be effective,” Dr. Felson explained.
The challenge is finding enough patients with ACL reconstruction with bad outcomes to effectively study OA prevention and treatment. While that sounds unfortunate, “it’s what we needed,” Dr. Felson said.
A longitudinal study known as the MOON trial that tracked 2,340 ACL reconstruction cases offered some initial clues, providing a foundation for future research. Dr. Felson and Dr. Kim joined lead researcher Kurt Spindler, MD, to create the “MOON” cohort for people who underwent surgery after an ACL tear, following them for a decade.
Through the MOON trial, Spindler et al. were able to assess how many people developed OA over 2, 6, and 10 years of follow-up, and how many experienced pain.
“It allowed us to guesstimate whether we were going to have enough numbers of people getting bad outcomes to see if we could get enough numbers to treat,” Dr. Felson said.