A search for the best treatments for knee osteoarthritis pain

Arthritis hobbles tens of millions of people each year, and the most common variety is osteoarthritis of the knee joint. A national study is underway to find the most effective non-narcotic, non-surgical ways to reduce pain and improve mobility.
April 5, 2023
four older adults hiking on a Colorado trial. The most frequent victim of osteoarthritis is the knee joint, which bears an outsized burden for everyday activities like standing, bending, walking and running.
The most frequent victim of osteoarthritis is the knee joint, which bears an outsized burden for activities like standing, bending, walking, running and hiking. Photo: Getty Images.

For millions of people in the United States, creaking, cracking and grinding are unwelcome notes in the soundtrack of advancing age.

The nagging noises are the result of arthritis, which painfully inflames and deteriorates the joints, tissues and bones around them. The more than 100 forms of the disease affect nearly 60 million Americans. The most common form is osteoarthritis, which results primarily from joint wear-and-tear and inflammation.

Dr. Larry Moreland, professor of Medicine in the Division of Rheumatology at the University of Colorado School of Medicine
Dr. Larry Moreland

“Osteoarthritis is part of the reward we get as we get older, although some people may have other things that trigger it before they get older,” said Dr. Larry Moreland, professor of Medicine in the Division of Rheumatology at the University of Colorado School of Medicine. Moreland treats patients with osteoarthritis and other forms of arthritis in the UCHealth Rheumatology Clinic – Anschutz Medical Campus.

The most frequent victim of osteoarthritis is the knee joint, which bears an outsized burden for everyday activities like standing, bending, walking and running. Those demands generate chronic and debilitating pain for millions of people. Some turn to opioid medications for short-term but risky relief. Joint replacement surgery helps many, but it’s not indicated for all patients, and many endure persistent pain after the procedure.

Moreland leads a study at the University of Colorado – Anschutz Medical Campus that addresses these dilemmas. It examines the effectiveness of various forms of non-narcotic and non-surgical treatments in treating knee osteoarthritis pain. The goal: develop evidence to guide clinicians in selecting the pain-relieving treatment best suited to their patients.

An opportunity to combat knee pain

The national multi-center trial, dubbed SKOAP, sponsored by Johns Hopkins University, in collaboration with the National Institute of Arthritis and Musculoskeletal and Skin Diseases, is the largest study of osteoarthritis knee pain yet undertaken. It is part of the National Institutes of Health-funded HEAL initiative, which funds projects across the country that target the opioid addiction crisis.

The SKOAP study design calls for two phases, both of which aim to measure changes in pain intensity after treatment. The first phase features “conservative” treatments composed of three components. Patients are randomly assigned to one of the three treatment groups.

The groups include:

  • “Best practice” treatments, including medications (nonsteroidal anti‑inflammatory drugs and acetaminophen), physical therapy and “integrative” treatments, such as yoga and acupuncture.
  • Best practice treatments are supplemented with duloxetine, an anti-depressant medication that can also help relieve knee osteoarthritis pain.
  • Best practice treatments, duloxetine, and an eight-week training program to help patients cope with pain.

Finding the most effective non-surgical ways to improve mobility

The first phase of the SKOAP study acts as a “funnel” for patients whose knee osteoarthritis pain resists a straightforward treatment plan, said co-investigator Dr. James Genuario, an orthopedic sports medicine specialist and director of Research and Innovation at the UCHealth Steadman Hawkins Clinic Denver.

Dr. James Genuario, rthopedic sports medicine specialist and director of Research and Innovation at the UCHealth Steadman Hawkins Clinic Denver.
Dr. James Genuario

“As orthopedic surgeons in sports medicine, we see a lot of patients with knee pain,” Genuario said. “In earlier stages, there is a lot we can do operatively,” such as minimally invasive arthroscopy for meniscus tears. Those with “end-stage arthritis” can opt for knee replacement. The SKOAP trial focuses on patients in a “gray zone” who are “not surgical candidates from an arthroscopy standpoint and not yet arthritic enough to be referred for knee replacement,” he explained.

““We know that if you are active, you do better in all facets of life,“ Genuario said. “The question is, how do we get those patients back out there and mobile?”

Genuario said his research team will work with patients enrolled in the SKOAP study on helping them to improve their pain-coping skills, choose effective therapies and manage their medications. Those who require further pain treatment may move on to phase 2 of the trial, he said.

Interventional pain management for knee osteoarthritis pain

Patients in phase 2 are randomized to receive one of three treatments from study co-investigator Dr. Rachael Rzasa Lynn, an interventional pain specialist and CU associate professor of Anesthesiology who practices in the UCHealth Pain Management Clinic – Anschutz Medical Campus.

Dr. Rachael Rzasa-Lynn, interventional pain specialist and CU associate professor of Anesthesiology who practices in the UCHealth Pain Management Clinic – Anschutz Medical Campus.
Dr. Rachael Rzasa-Lynn

Rzasa Lynn explained that the three treatments involve injections, nerve blocks and nerve ablations in the knee joint:

  • Injections deliver hyaluronic acid, which helps to cushion and lubricate the joint, combined with a corticosteroid and an anesthetic.
  • Nerve blocks deliver a long-acting anesthetic that numbs the nerves around the knee.
  • Nerve ablation gently damages nerves around the knee with heat energy, thus preventing them from delivering pain signals.

Patients who have already exhausted the treatments offered in the first phase can enroll directly in the second phase, Rzasa Lynn said.

Searching for evidence-based solutions for knee osteoarthritis pain

Rzasa Lynn emphasized that the purpose of SKOAP is to gather and sort through evidence gleaned from a variety of treatments. She noted that “there is still plenty of debate about what we should be doing for patients with chronic knee osteoarthritis pain.”

For example, she noted that hyaluronic acid injections have long been widely used by primary care providers, rheumatologists and orthopedists for the problem. “But there are questions about the utility of it compared to newer treatments.”

The SKOAP enrollment target – 2,700 patients nationally – is also important, Rzasa Lynn added. “It is a pragmatic approach to a clinical trial that allows enrollment of a very large number of patients that would be difficult to study in a traditional trial design.”

The data will either support or refute current approaches she and her colleagues use to treat the pain of knee arthritis, she added – and that’s a good thing for establishing a standard of care based on clinical evidence.

“The more data we have, the better we can practice clinically and justify what we’re doing so patients can get their treatments approved and covered,” she said. The data could also help to raise awareness of effective treatment options among patients struggling with pain but “not yet ready to escalate to surgery,” she added.

Promise, not a panacea for knee pain

Moreland emphasized that the SKOAP study was not designed to prevent patients from having knee replacement if it is indicated. Rather, the idea is to gather data with an eye toward developing a “sequenced strategy” to help patients have “less pain and an improved quality of life” that allows them to safely do the activities that are most important to them.

“That will vary from patient to patient,” Moreland said. “We also want to come up with good options that prevent them from getting on narcotics.”

Genuario concluded  that SKOAP promises to help clinicians address “unanswered questions” surrounding the best treatments for patients who sometimes get “bounced around” looking for unproven or even unneeded solutions to their knee pain.

“As surgeons, we look for surgical treatments, but that is not always the best choice,” he said. “The SKOAP trial patient group is one that we often don’t have great answers for. The trial could give us a lot better information about what type of patients respond to different treatments and what stages of knee osteoarthritis they respond to,” he said.

For more information about the SKOAP trial, contact Andrew Clauw: [email protected] or 734-476-1146.

About the author

Tyler Smith has been a health care writer, with a focus on hospitals, since 1996. He served as a writer and editor for the Marketing and Communications team at University of Colorado Hospital and UCHealth from 2007 to 2017. More recently, he has reported for and contributed stories to the University of Colorado School of Medicine, the Colorado School of Public Health and the Colorado Bioscience Association.