How Athletes Respond to Extended Release Corticosteroids

In December 2019, a panel of retired profession sports athletes took the stage to give their personal experience with extended release corticosteroids, specifically Flexion Therapeutics, Inc. injectable Zilretta^® at Orthopaedic Summit 2019: Evolving Techniques (OSET) in Las Vegas, Nevada.

OTW attended the seminar.

Extended release corticosteroids are a new innovation in knee pain management, having received FDA approval just a couple years ago. More than 100,000 patients have been treated so far. It was very interesting to hear the candid experiences of these high profile, retired athletes—each of whom suffers from chronic knee pain due to osteoarthritis (OA).

Orthopaedic Summit 2019

Orthopaedic Summit is a three-and-a-half day conference put on by the Orthopaedic Summit Board of Directors. The event gathers international experts in spine and trauma surgery, total joint, foot & ankle, arthroscopic and sports medicine. Conference presenters included orthopedic surgeons, physician assistants, nurse practitioners, athletic trainers and both physical and occupational therapists. Professionals explored innovative techniques in orthopedic care alongside world-renowned experts in the field.

The 2019 Orthopaedic Summit offered cadaveric and live surgical demonstrations, including a cementless total knee arthroplasty by R. Michael Meneghini, M.D., a complex rotator cuff repair by Bradley Edwards, M.D., a total shoulder replacement performed by Gregory P. Nicholson, M.D., and a fresh osteochondral allograft reconstruction surgery done by William Bugbee, M.D.

The Orthopaedic Summit also included symposia, rapid-fire debates, panel and group discussions on current researched-based techniques for arthroplasty, arthroscopy, sports medicine, trauma and spine and opportunities for networking. Several of these discussions explored approaches to osteoarthritis.

Using Time-Released Corticosteroids to Treat Pain in Osteoarthritic Knees

Depending on the severity of OA, treatments can range from physical therapy or weight loss recommendations to intra-articular injections or surgery. For many, OA is debilitating. Pain can limit mobility and the range of life experiences that are accessible. More invasive treatments are indicated depending on the severity of the disease and symptoms.

Zilretta (triamcinolone acetonide release injectable suspension) is the first time-released corticosteroid. It has been on the market for just over two years and has now been successfully administered to over 100,000 patients.

While typical steroids dissipate quickly after injection and thus require significant doses, Zilretta dissipates slowly over 60 to 90 days, allowing a smaller dose to have longer pain-relief effects.

Zilretta is manufactured by Burlington, Massachusetts-based Flexion Therapeutics, “a biopharmaceutical company focused on the development and commercialization of novel, local therapies for the treatment of patients with musculoskeletal conditions, beginning with osteoarthritis (OA), a type of degenerative arthritis.”

Zilretta consists of a suspension of microspheres With “small crystals of TA are embedded in a poly lactic-co-glycolic acid (PLGA) co-polymer matrix.” Flexion reports that, “In vitro, release of TA from the microsphere nano-channels, limit both egress of TA from the microsphere’s interior and internal hydration of the polymer,” prolonging drug release.

John Richmond, M.D. on How to Use Time Release Corticosteroids

John C. Richmond, M.D., the former chairman of orthopedic surgery at New England Baptist Hospital, Boston Sports and Shoulder Center, spoke about the unique benefits of Zilretta. Dr. Richmond is a spokesperson and consultant for Zilretta, a medical provider who administers Zilretta, and a patient who has received injection himself. He said that Zilretta “truly does what we want a corticosteroid to do.”

Richmond explained that the treatment is injected into the synovial space and “stays there with measurable quantities within the joint.” He explained, “The extended release corticosteroid Zilretta is designed specifically to stay within the joint space so when it’s injected intra-articularly. You want to keep it within the synovial space so there’s a huge concentration of corticosteroid intra-articularly.”

As a side benefit, Richmond noted, “at the same time it actually has a secondary benefit… it keeps it out of the plasma which is one of the potential issues with corticosteroid injections.” Richmond pointed out that this is particularly significant for type 2 diabetes patients suffering from OA, as standard corticosteroid injections can increase blood glucose levels past amounts recommended by the American Diabetes Association.

Richmond explained that pain relief reports by patients have been significant. In a clinical research trial including only patients with moderate to severe pain, 15% had no to mild pain 7 days after the injection and 70% still reported no to mild pain 12 weeks after injection.

According to Richmond, research has not indicated any significant adverse reactions. Contraindications are common to other corticosteroids and include injection into infected sites, repeated use with risk of endocrine disruption, and injection into sites other than intra-articular space. Zilretta literature indicates that its common side effects “include sinus infections (sinusitis), cough bruising, and joint swelling.”

Zilretta is not yet intended for repeat use. FDA approval requires additional research for more than a single injection. A phase 3 study completed and has been submitted to FDA.

Professional Athletes Report Benefits

Flexion’s Zilretta discussion panel did not consist of just any patients; patient speakers at the summit talk were high profile, retired professional athletes for whom the daily toll of having played professional sports includes chronic knee pain.

Moderator Solomon Wilcots, retired NFL player and current broadcaster explained, “Many of us have been blessed enough to have careers where we could change the trajectory of our lives. What allowed us to do that is first being able to have good health. Anytime that trajectory is interrupted, we have to call on wonderful, bright, people like the surgeons in this room. And we need you—in order to continue our careers and to stay in the game.”

All panel members had all received Zilretta treatment for chronic, osteoarthritic knee pain. These patients included Mike Eruzione, 1980 U.S. Olympic Hockey Team Captain and Gold Medalist, Rod Woodson, retired NFL player and Hall of Fame Member, and Chris Dickerson, retired MLB player.

Efficacy and Durability of Treatment

Scott Kelley, M.D. Chief Medical Officer at Flexion, spoke to OTW about Zilretta’s efficacy. When asked to explain the benefits of Zilretta he said, “Like we heard tonight, so many patients noticed the fast onset of incredible magnitude of pain relief—and durability is what they really noticed.” Some panel participants reported pain relief from severe osteoarthritic knee pain for 2 to 4 or more months after receiving the treatment. Most of the professional athletes who spoke were surprised at how long the pain relief benefits lasted.

Improved Quality of Life

Dr. Kelley, an anesthesiologist by trade, also noted how patients in general and the athletes speaking at the seminar emphasized their dramatically improved quality of life. “Pain has this big umbrella effect on life, right? And if we take away the pain, then suddenly the other elements of your life can just really emerge,” he said. “Every one of them just had a good example of how their life was restored when the osteoarthritic knee pain was treated and went away.”

“It can change the way somebody functions dramatically,” said Kelley.

Each athlete explained how Zilretta improved the quality of his life.

Rod Woodson

Rod Woodson played 17 seasons of NFL football, had 71 career interceptions (the third most on record) and was inducted into the NFL Hall of Fame in 2009. He suffered ongoing chronic pain and retired in 2003. “I had five knee surgeries,” he stated. “It was one of the main reasons I retired.”

Woodson reflected, “As a human being you think I’m never going to get hurt—and if I do get hurt I’ll just fight through it. But when you live with it for over 15 years, you’re like, this is going to be a little thorn in my side that I can’t get rid of. This is one of those things that bothered me throughout my years…I finally found a solution.”

“When I got the shot and the treatment…I didn’t think it was going to work,” he said. In the coming weeks, he was surprised that he was able to walk for hours on a Grand Canyon trip with his wife, to play golf (“Normally around hole 14 my knee would just be in pain.”) and, more recently, to go for a run for the first time in 10 years.

“The one thing I love about Zilretta; it let me get back to my normal life,” said Woodson.

Chris Dickerson

Chris Dickerson played 15 seasons of professional baseball and retired in 2017 after years of chronic OA pain. “For a while there…it had a very significant effect,” he said. “It impacted me…every day I had to go and find solutions.” Dickerson a received Zilretta from his doctor. He said, “It really bothered me until I found a solution. Honestly it’s been a game changer for me.”

Dickerson said, for him, the pain decreased within several hours after the injection. Dickerson talked about how small things like helping at his child’s soccer game bring him happiness. “It’s been a tremendous help for me.”

Mike Eruzione

Mike Eruzione made the winning goal against the Soviet Union in the 1980 Olympic games, noted as one of the most played highlights in American sports. It was voted the greatest highlight of all time by ESPN and was portrayed in the Disney film, “Miracle.”

After retiring from his hockey career, Eruzione remained active in competitive golf, playing baseball and generally being active. He said that OA pain increased and eventually affected daily activities such as climbing stairs or using a treadmill or bike. “It was a big change for me. I wasn’t sure what I was going to do.”

“I wanted to be able to do the things I enjoy doing,” said Eruzione. He is now able to play with his grandchildren, snowblow after a storm, and play golf. Like the other athletes, he explained the importance of getting his everyday quality of life back.

Looking Forward

Dr. Richmond conducted the study of 180 patients and found evidence supportive of two doses for safe and effective treatment of osteoarthritic knee pain. Dr. Kelley said that he, himself, is currently conducting research utilizing MRI imaging to look at synovitis or inflammation of the knee in 100 athletes and how synovitis changes over time after treatment. Dr. Richmond and Dr. Kelley are interested in the way Zilretta targets drug delivery to the anatomy of the knee that drives pain.

Dr. Kelley also told OTW that Flexion looks forward to potential use of Zilretta for shoulder pain in the future. “There are just a lot of shoulder conditions in the United States. We’re a very active population. We do a lot of things with our arms and people are bothered by their shoulders. So, whether it’s osteoarthritis or this condition called frozen shoulder, we’re pretty hopeful that our treatment, based on the pharmacology, will have an impact there.”

“We have other things in our pipeline that will focus on bringing new, innovative treatments to both osteoarthritis and other areas of musculoskeletal,” Dr. Kelley said.