Injectables Provide Noninvasive Option for Knee Osteoarthritis, Especially for Young Patients

The incidence of osteoarthritis (OA) of the knee is increasing steadily, and it is estimated that more than half of people with OA of the knee will undergo total knee arthroplasty (TKA) during their lifetime. During the AAOS 2024 Annual Meeting, a panel of experts discussed the efficacy and status of current injectable options for the management of OA of the knee during the Instructional Course Lecture “Injectables in the Management of OA of the Knee.”

“There are limited nonoperative alternatives [to TKA], and currently available guidelines are not particularly valuable for guiding how we care for patients,” said presenter John C. Richmond, MD, FAAOS, professor of orthopaedic surgery at Tufts University School of Medicine. Because some dissatisfaction still exists with TKA, it is important to offer patients other options. Among those options is injection therapy.

Viscosupplementation
Younger patients with symptomatic chondromalacia have several nonoperative options, including weight loss, NSAIDs, and physical therapy, but those options have variable levels of success with patients, according to Jack M. Bert, MD, FAAOS, adjunct professor emeritus at University of Minnesota School of Medicine. However, there is significant public interest in viscosupplementation—also known as hyaluronic acid (HA) injections. Additionally, HA has been shown to have the highest effect size of all knee OA treatments.

Given that the average age of patients with physician-diagnosed OA of the knee has decreased in recent decades, the estimated average treatment duration for these patients has increased, Dr. Bert noted. Although viscosupplementation does have some limitations, it is not as costly, invasive, or as “end stage” as TKA.

The 2021 AAOS Clinical Practice Guideline (CPG) on Management of Osteoarthritis of the Knee (Non-Arthroplasty) gave a moderate recommendation against “routine use” of HA but added that for high-molecular-weight (HMW) HA, “viscosupplementation can represent a viable option for some patients that failed other treatments.” That recommendation is likely due to evidence supporting HMW HA as superior to low-molecular-weight HA in clinical outcomes regarding pain relief in OA of the knee. Increased residence time is also an important component of effective HA treatment. Several clinical questions still must be addressed regarding the use of HA, including frequency of injections, whether the injections have any effect in delaying TKA, whether HMW HA slows the progression of cartilage degeneration, and what patient perceptions of HA are.

Corticosteroids
Next, Andrew I. Spitzer, MD, FAAOS, professor of orthopaedic surgery at Cedars-Sinai Medical Center, discussed triamcinolone acetonide extended release (TA-ER [Zilretta]), which he called a “true game changer” in the management of OA of the knee. “Among the various modalities, injection therapy is appealing to patients and physicians alike, especially surgeons, because it is as my friend and mentor David Waddell, MD, FAAOS, suggests, ‘a local treatment for a local disease,’” Dr. Spitzer said.

Intra-articular injection of corticosteroids is among the older, tried-and-true injection options. The mechanism of action is not fully understood, but it is believed to act by decreasing inflammatory pathways; however, the steroid itself has been suggested to potentially cause chondrotoxicity as well, Dr. Spitzer noted.

Although the use of intra-articular corticosteroids is not disputed, the duration of action is generally short, likely due to the rapid efflux of steroid from the joint. There is a need to balance the early onset of action with a sustained duration of efficacy.

TA-ER is triamcinolone embedded in microspheres of poly(lacto-co-glycolic acid), which is the same material as vicryl suture. TA-ER behaves differently than other steroid preparations and has been shown to have measurable levels in the joint at 12 weeks; the slow release into the joint results in lower plasma concentration, which reduces any systemic pharmacodynamic effect. A phase 3 study of TA-ER showed a greater than 50 percent reduction in average daily pain scores from weeks 1 to 12, extending through week 16, compared with saline placebo. “Pain and stiffness were significantly reduced, and function was improved, along with quality of life, and all of that was achieved with less need for rescue medications,” Dr. Spitzer said.

The CPG on Management of Osteoarthritis of the Knee said, “Our analyses demonstrated that extended release intra-articular steroids can be used over immediate release to improve patient outcomes,” and the recommendation was given with moderate strength.

Biologics
The final presentation was on the modern use of biologics for cartilage restoration or treatment of OA symptoms, given by Jason L. Dragoo, MD, FAAOS, director of UCHealth Steadman Hawkins Clinic Denver and chair of the AAOS Committee on Devices, Biologics, and Technology. “It is always a challenge to talk about biologics, and it is increasingly challenging every year,” Dr. Dragoo said, adding that by boiling down current data on biologics, it may slightly oversimplify certain aspects of their use. Currently, orthobiologics used for symptom control include leukocyte-poor and leukocyte-rich platelet-rich plasma (PRP), micro-fragmented adipose tissue (mFAT), and bone marrow aspirate concentrate (BMAC).

There is mounting evidence that PRP may be more effective for improving clinical outcomes compared with HA for OA of the knee, according to Dr. Dragoo. “One truth of PRP is that it works, but another truth is that it doesn’t work in some patients,” Dr. Dragoo said, adding that although there are good data showing pain relief and anti-inflammatory effects, there is no evidence of a restorative effect.

Dr. Dragoo also discussed mFAT, a nonsurgical treatment that uses a patient’s own adipose tissue to try to repair and heal. There is evidence that mFAT has an anti-inflammatory effect and that administration can lead to pain reduction in knee OA. Additionally, recent data suggest that mFAT may be even more effective for pain reduction than HA, PRP, or both combined.

Numerous ongoing clinical trials are attempting to identify specific doses required for these biologics and methods for consistent improvement. The 2021 guideline downgraded the recommendation for PRP from strong to limited, due to “the heterogeneity of results and the difference in early and late-stage OA results.” Dr. Richmond acknowledged that biologics have been a bit like the Wild West, and the FDA and Federal Trade Commission are now paying closer attention and are “in the game.”

Leah Lawrence is a freelance medical writer for AAOS Now.

References

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