Interventional radiology is one of the most exciting and expanding areas for innovations in advancing healthcare. As clinicians and researchers seek less invasive and more personalized approaches to illness and disease, high-quality studies on image-guided procedures, such as ablation and embolization, become ever more critical.
Genicular artery embolization (GAE) appears to be a promising new treatment for knee osteoarthritis, an extremely common, painful, and debilitating condition that’s also one of the leading causes of disability. About 14 million people in the US alone suffer from symptomatic knee osteoarthritis, according to the Arthritis Foundation.1
In a GAE procedure, a small catheter is advanced into one or more of the arteries supplying the knee joint known as the genicular arteries. Embolic microspheres are delivered through the catheter to reduce the blood supply to the vessels, which may decrease inflammation.
GAE was originally used to treat knee hemarthrosis or bleeding into the joint space, however, interventional radiologists have been leveraging the technique since 2012 for treatment of knee osteoarthritis.2 Recent prospective trials3,4 —including GENESIS I, a prospective pilot study investigating the role of embolization microspheres for GAE in patients with mild to moderate osteoarthritis of the knee—have shown promising treatment efficacy for knee osteoarthritis, with a very good safety profile. However, more large-scale randomized trials are needed to provide the clinical data that can help inform guidelines and training to ensure consistent outcomes, as well as educate clinicians across disciplines.
GENESIS I and II
“Data from the original GENESIS I study in 2018 suggest that there is an inflammatory component to knee osteoarthritis, resulting in abnormal neo vessel formation that can be targeted with embolization,” explains Mark Little, FRCR, a consulting interventional radiologist in Reading, UK, and principal investigator for GENESIS II,5 a double-blind sham-controlled randomized trial.
“The goal of GENESIS II is to help us ascertain the efficacy of GAE treatment, which could be a game-changer for the millions of patients who have unmet treatment needs,” he explains. “But we’re also looking at the neuropsychology of knee osteoarthritis—pain management, function, disability, and quality of life—with the objective of gathering a robust set of outcome measurements to aid patient selection and gain a greater understanding about chronic pain.”
As part of its commitment to gathering high-quality clinical data in a systematic way for new procedures and innovations, Varian is sponsoring the single-center GENESIS II study, which started in October 2022. Ultimately, the patient population will comprise 110 subjects who have been suffering with mild to moderate knee pain from osteoarthritis for at least three months. Trial participants will be treated either with GAE or with injection of two milliliters of saline (sham procedure). Those treated with saline in the sham arm will be allowed to cross over and receive GAE at six months.
“Within the clinical outcomes, we’re also looking at imaging outcome through contrast MRIs of each study patient’s knee,” Dr. Little adds. “The study protocol was designed to generate a large amount of data that can provide us with important insights into the procedure and how patients respond.”
GRAVITY
Varian is also supporting another large-scale GAE study known as GRAVITY. The GRAVITY trial is a prospective single-center randomized 100-patient study based in Los Angeles, California, led by Siddharth Padia, MD, a leading interventional radiologist. Enrollment begins in Spring 2023, and the study will follow participants for two years.
Similar to GENESIS II, eligible patients will be randomized to GAE treatment or observation in a 2:1 ratio. For the treatment arm, patients will receive GAE with Varian’s Embozene microspheres, whereas patients in the observational arm will be counseled on conservative management with a physical therapy referral.
GRAVITY goals include comparing GAE to the current standard of care for non-operative candidates, to help determine whether GAE should be part of the treatment algorithm for patients with knee osteoarthritis. In both the UK and the US, the current standard of care has not changed in several decades and relies on physical therapy, anti-inflammatory medications, and corticosteroid injections into the joint.
At regular follow-up visits, subjects in the GRAVITY study will complete the WOMAC, KOOS5, and visual analog scale (VAS) pain score; undergo a directed physical examination; and report any new adverse events (AEs). At six and 24 months of follow-up, all subjects will also undergo dynamic contrast-enhanced knee MRI, and serum and joint aspiration with biochemical analysis. Also at six months, patients in the observation group will have the option to cross over to the GAE treatment arm.
“The comparative arm of the study is essential for multiple reasons,” explains Dr. Padia. “Single-arm studies have shown promising efficacy, but results have been hampered by the placebo effect common with current treatments of knee osteoarthritis. In terms of pain and dysfunction, patients can wax and wane, often getting better on their own.”
Eligible patients for GRAVITY are those who are either too old or frail to undergo a total knee arthroplasty and those who simply don't want to go through knee replacement surgery for multiple reasons. These patients, Dr. Padia says, often have no other option than to live with their pain.
“Our hope is that the data show GAE can provide an added standard-of-care benefit for those who are simply not surgery candidates or who do not want to undergo a total knee replacement,” he says. “It's always possible that they can get a knee replacement after the GAE procedure should they wish; a positive aspect of GAE is that it does not block any downstream options for patients in terms of further therapies.”
In addition to focusing on GAE, the GRAVITY study also will offer ancillary insights from its extensive biomarker and MRI analysis at various time points, complementing the GENESIS II study, he adds.
“Compared to other embolic therapies for disease states such as liver cancer, uterine fibroids, and enlarged prostates, knee osteoarthritis has a prevalence of at least 10 times and so the scope of this therapy is quite large—our center receives up to 20 enquiries a week,” Dr. Padia adds. “Varian has been extraordinarily supportive taking a holistic focus on the disease state to try to make an impact, rather than simply focusing on the device.”
In addition to GRAVITY, Dr. Padia is initiating a trial to study embolization for tennis elbow, also known as lateral epicondylitis.
“I believe there are a lot of possibilities for interventional radiology treatments in the field of musculoskeletal joint embolization and we are excited to get started,” he concludes.
Dr. Little says that he believes Varian’s approach to a patient-driven focus has been instrumental in helping him align his goals for patients in designing GENESIS II to build on the learnings from the GENESIS I study.
“These studies present a significant opportunity to better understand how we can improve the clinical management of knee osteoarthritis in patients with ongoing quality-of-life issues,” says David Hahn, MD, Varian’s Chief Medical Officer, Interventional Solutions. “We are proud to support the GENESIS II and GRAVITY studies as part of our commitment to developing meaningful clinical data within the field of interventional radiology and look forward to seeing the results.”
1Arthritis Foundation. Report: Arthritis by the Numbers. 2020.
2Okuno Y, Korchi AM, Shinjo T, Kato S. Transcatheter arterial embolization as a treatment for medial knee pain in patients with mild to moderate osteoarthritis. Cardiovasc Intervent Radiol. 2014;38(2):336-343. doi:10.1007/s00270-014-0944-8
3Little MW, Gibson M, Briggs J et al. Genicular artEry embolizatioN in patiEnts with oSteoarthrItiS of the Knee (GENESIS) Using Permanent Microspheres: Interim Analysis. Cardiovasc Intervent Radiol. 2021;44(6):931-940. doi: 10.1007/s00270-020-02764-3,
4Padia SA, Genshaft S, Blumstein G et al. Genicular Artery Embolization for the Treatment of Symptomatic Knee Osteoarthritis. JB JS Open Access. 2021 Oct 21;6(4):e21.00085.
5Genicular Artery Embolisation for Knee Osteoarthritis II (GENESISII)