New Jersey Society of Interventional Pain Physicians
An Affiliate of the American Society of Interventional Pain Physicians
Our Society supports the use of thermal radiofrequency ablation, also known as thermal ablation or denervation for patients diagnosed with moderate to severe osteoarthritis of the knee. Patients afflicted with knee OA who may be refractory to conservative care including hyaluronic acid and corticosteroid injection, do not have durable non-surgical alternatives available to deliver pain relief and functional improvement beyond a few weeks to months1,2.
Based upon the review of the body of peer-reviewed published evidence, approval by the United States Food and Drug Administration (FDA), real world experience and long-term patient outcomes, NJSIPP recommends qualified physicians consider use of this minimally invasive intervention and inform patients in their treatment plans based upon the clinical need and presentation. Because of proven safety and durable effectiveness, radiofrequency ablation of the genicular nerves of the knee using thermal RFA systems are within the clinical community’s standard of care for their indicated use. Based upon the body of Level I-IV peer-reviewed published evidence, FDA approval, and demonstration of cost-effectiveness, NJSIPP further recommends policymakers and payers enable timely access to thermal radiofrequency ablation of the genicular nerves for osteoarthritis of the knee when prescribed by a qualified physician who has used his or her best medical judgement for care most suitable to the individual diagnosed with moderate to severe knee osteoarthritis when this therapy is the best suited for the patient given their clinical presentation, when refractory to standard treatment, or when comorbidities preclude alternate treatment.
Knee Osteoarthritis: Burden of Disease
Although knee osteoarthritis, or degenerative joint disease of the knee, is closely correlated with age, it is typically the result of wear and tear and progressive loss of articular cartilage. It frequently manifests as a progressive disease leading to disability.3 Osteoarthritis of the knee is the most common type of arthritis affecting more than 30 million adults in the United States.4
Among the 18 million symptomatic OA knee pain sufferers, 6 million are between age 45- 65 and 2 million are under 45 years of age.5 A significant treatment gap exists for many of these people due to the low efficacy and short duration of current conservative therapies, lack of patient access to safe and effective minimally invasive treatments and need for avoidance of surgery. 6
Clinical presentation, patient history along with radiographic confirmation of osteoarthritis, via x-ray, MRI, or CT, of grade 2 (mild), 3(moderate) or 4 (severe) in the past 12 months, pain of at least 6 out of 10 on a NRS is supported by the inclusion criteria of studies used to obtain FDA clearance for use of genicular radiofrequency ablation for knee OA pain.
The intensity of knee OA symptoms vary from individual to individual.
The clinical symptoms of Knee OA include a chief complaint of knee pain:
Articular cartilage is composed of type II collagen, proteoglycans, chondrocytes, and water. In healthy joints, equilibrium between these components is maintained in that any degradation of cartilage is matched by synthesis. With osteoarthritis, the matrix metalloproteases, or degradative enzymes, are overexpressed resulting in loss of collagens and proteoglycans. 7 I
n the early stages of OA, chondrocytes secrete tissue inhibitors in an attempt to increase the synthesis of proteoglycans to overcome the degradation, but this reparative attempt is not enough and eventually a loss of equilibrium results in loss of articular cartilage and elasticity, cracking and fissuring and erosion of the articular surface.
Primary knee osteoarthritis is the result of degenerative articular cartilage without any known reason. This may be due to age or wear and tear. Secondary knee osteoarthritis results from a known reason and can be due to trauma, surgery, limb malformation or malposition, chondrocalcinosis, infectious or psoriatic arthritis or other disease process.
Physical examination findings include visual inspection of the knee and may reveal periarticular erythema and swelling, quadriceps atrophy or varus/valgus deformity. Range of motion is an important finding with typical OA presenting as gross limitation of flexion and slight limitation of extension.
Low Efficacy & Durability of Non-Operative Alternatives
Medications aimed to treat inflammatory conditions may help, but they do not slow the progression and to date there are no disease modifying agents for the treatment of knee osteoarthritis.8 Non-surgical treatment for the pain and dysfunction of OA of the knee has remain largely unchanged over the past 20 years.
Conservative treatment options begin with weight loss, physical therapy, opioid or non- opioid medications and typically progress to corticosteroid or hyaluronic acid injections with the definitive treatment for OA of the knee being total knee arthroplasty (TKA). However, a significant treatment gap exists for millions of symptomatic OA knee pain sufferers due to low efficacy conservative therapies. The mean duration of their pain from onset is 10 years with 7 years of disability.9 Even when TKA is an appropriate option, factors including age, BMI or comorbidities are often considered and may preclude or necessitate deferment of surgery until more optimal medical conditions exist.
Intra-articular steroid (IAS) injection has long been a standard of care for the treatment of OA knee pain. However, IAS injections offer only short-term relief, often pose side effects, and lack strong evidence of efficacy. The reported duration of pain relief of intraarticular corticosteroid injections is one to two weeks with some trials demonstrating pain relief of up to three to four weeks. 10
Viscosupplementation with hyaluronic acid, or its derivatives, is injected into the affected knee as a multi- or single dose application to provide lubrication and shock absorption. While some studies suggest reduced pain through 26 weeks, 11 the FDA has questioned its mechanism of action and current clinical practice guidelines do not support use of HA for the treatment of OA knee pain.12,13
Neither opioids, IAS nor HA are recommended by the American Academy of Orthopedic Surgeons (AAOS) for the treatment of knee osteoarthritis in their Clinical Practice Guidelines.14
Radiofrequency ablation (RFA) was first described in the literature for treating chronic back pain in 1975.15 Radiofrequency is a minimally invasive, non-surgical outpatient procedure used to target the genicular nerves of the knee causing chronic pain. The procedure involves minimal sedation and typically is completed in less than 45 minutes using a RF generator to transmit a small current of RF thermal energy through an insulated electrode placed within the tissue.
Radiofrequency ablation delivers targeted thermal damage in excess of 43˚ C to neuronal tissue in order to modulate transmission of pain signals using a simple electrode structure that generates RF energy.16 While genicular nerve course variability is high, the consensus and data supports clinical effect from targeting the following three primary nerve targets: the superomedial and inferomedial branches of the saphenous nerve and the superolateral branch of the femoral nerve.17,18 Radiofrequency of the genicular nerves can address the treatment gap between conservative therapy and TKA by offering a clinically superior and more durable option when patients are refractory to current standard care. Studies show that radiofrequency of the genicular nerves can reduce pain and improve function for at least 6-12 months.
With a projected 401% growth in demand for TKA’s over the next twenty years,19 thermal radiofrequency for OA of the knee can combat this escalating trajectory by deferring surgery for younger patients, of which 40% are performed on patients under age 65,20 and reduce the lifetime risk and cost associated with TKA revisions.
Prior to genicular thermal radiofrequency ablation, OHSIPP recommends conservative care for at least 3-6 months, the choice of what options for which should be individualized to the specific needs of the patients and be at the discretion of the treating physician.
Physician Qualification & Patient Selection
Thermal radiofrequency ablation should be performed only by qualified physicians,trained in the management of patients suffering from chronic pain of osteoarthritisand experienced in the application of radiofrequency ablation and nerve denervationin patients for which the procedure is appropriately indicated.
Thermal radiofrequency ablation is intended for creating radiofrequency lesions of thegenicular nerves for the management of moderate to severe knee pain of more than 6months in patients with radiologically-confirmed osteoarthritis (grade 2-4) and apositive response (≥50% reduction in pain) to a diagnostic genicular nerve block. Select candidates may have undergone prior conservative therapy, includingmedication. Prior treatments received may include physical therapy, weight loss,exercise, NSAIDs, opioids, and intraarticular steroid or hyaluronic acid injections.
Patients with imaging studies correlative with presentation of the patient’s signs and symptoms, refractory to conservative care, or those for whom conservative therapies are not indicated and who otherwise meet the indications for thermal radiofrequency of the genicular nerves should be considered as well as those medically incapable or unwilling to undergo surgical intervention.
Treatment options, risks associated with conservative care, injections, opioid use, andsurgical options must be well understood by the patient when developing care plansfor the individual. Physicians must ensure informed consent of the patient.
Contraindications and Relative Contraindications
Results of a prospective RCT of thermal radiofrequency ablation of the genicular nerves using water-cooled probes (CRFA) compared to hyaluronic acid injection (HA) demonstrates greater improvement in NRS pain scores and WOMAC functional ability in the CRFA group vs the HA group at 6-months and at 12-month follow-up. The mean NRS at 6 months was 2.7±2.3 for the CRFA group and 4.5±2.7 for the HA group (p<0.0001). The mean WOMAC score improvement at 6 months from baseline was 48 % in the CRFA group and 23% in the HA group (p<0.0001). At 6-months 72% of the CRFA subjects reported improvement in Global Perceived Effect compared to 40% in the HA group (p<0.0001). 24 At 12-months, 65.2% of the CRFA cohort reported > 50% pain relief from baseline. Mean NRS was 2.8±2.4 at 12 months (baseline 6.9±0.8), representing a 4.1% decrease in NRS pain score (p<0.0001). Subjects in the CRFA cohort had a 46.2% improvement in total WOMAC score at the 12-month timepoint.25
Similarly, another prospective RCT compared thermal ablation of the genicular nerves using water-cooled probes (CRFA) to intraarticular steroid injection (IAS). At both 6 and 12 months, the CRFA group demonstrated greater pain relief and improved function as measured by NRS and Oxford Knee Score (OKS). At 6 months, the mean NRS was 2.5 ± 2.3 for the CRFA group and 5.9 ± 2.2 for the IAS group (p < 0.0001), representing a 4.9 -point drop in NRS for the CRFA group. The mean OKS was 35.7 ± 8.8 in the CRFA group at 6 months compared to 22.4 ± 8.5 in the IAS group (p < 0.0001). At 6 months, 91.4% of subjects in the CRFA group reported improvement in Global Perceived Effect compared to 23.9% in the IAS group (p < 0.0001). 26 At 12 months, 65% of the original CRFA group had pain reduction ≥50%, as measured by the NRS, and the mean overall drop was 4.3 points (p<0.0001). Seventy-five per cent reported “improved” effects. The OKS increase from baseline in the original CRFA cohort was 17.3±12 points (N=52, p<0.0001, Student’s paired t-test), with an absolute mean of 34.3±11.1 points. 27
A comparison study of thermal radiofrequency (RFA) of the genicular nerves to conventional analgesics demonstrated statistically significant improvement in VAS for RFA patients over analgesics at 3 (2.83±0.5 vs 4.93±0.2) and 6 months (3.13±0.3 vs 5.73±0.26). The total WOMAC index showed significant difference between the two groups by the 6th month only; however, WOMAC domains (pain, and stiffness) showed significant differences in the 3rd, and 6th months, with lower values in the RFA group.28
A trial of thermal radiofrequency (RFA) compared to hyaluronic acid (HA) demonstrated statistically significant improvement in VAS and Lysholm Knee Score (LKS) scores at 3, 6, 9, and 12 months. 29 When compared to sham, thermal genicular radiofrequency (RFA) under fluoroscopic guidance showed VAS scores in the RFA group to be less at 4 (p < 0.001) and 12 (p < 0.001) weeks compared with the control group. Oxford Knee Scores showed similar findings (p < 0.001).30
In their Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hip, Hand and Knee, The American College of Rheumatology states that “radiofrequency ablation is conditionally recommended for patients with OA of the hand, hip and knee. 31
The American Society of Pain and Neuroscience recommends that “genicular nerve radiofrequency neurotomy may be used for the treatment of osteoarthritis related and post-surgical knee joint pain with a GRADE of II-1B.32
A cost-effectiveness analysis based on trial data evaluated the costs and health outcomes of patients undergoing cooled thermal radiofrequency ablation (CRFA) of the genicular nerves for OA knee pain compared to intraarticular steroid injections (IAS). The economic model calculated health benefits in the form of QALYs by mapping trial-based changes in function as measured using the Oxford Knee Score (OKS). The OKS captures patients’ assessment of knee symptoms and function. Costs were derived from the Centers for Medicare and Medicaid Services fee schedules and included standard physician (in-office or in-hospital) and hospital payments for IAS, CRFA and genicular nerve block procedures. At a time-horizon of 6 months post-treatment, CRFA was associated with a 0.091 gain in QALYs and an incremental cost effectiveness ration (ICER)of US$1711 compared with IAS. CRFA therefore cost US$18,773 per QALY gained.
Conclusions & Recommendations
The body of Level I-IV published evidence, long-term outcomes demonstrating durable treatment effect, avoidance of more invasive procedures and drug therapies, as well as consideration for the patient populations most likely to be candidates for thermal radiofrequency ablation of the genicular nerves should be considered within the standards of care for osteoarthritis related and post-surgical knee pain.
Policymakers and payers are strongly encouraged to enable timely access to FDA cleared technologies, when deemed medically necessary and indicated for this procedure.
Technology Definitions of Thermal Radiofrequency
Standard Radiofrequency (RFA) is a thermal ablation procedure. Treatment protocols typically apply 90 seconds of heating with a target temperature of 80 -90˚C. While nerve tissue begins to degrade at temperatures greater than 43˚ C, the 80˚ C protocol was derived from in vitro studies and is thought to be related to the highest temperature that early RF generators could attain.33
Water-Cooled Radiofrequency (CRFA) is a thermal ablation procedure offering physicians an alternate probe choice. Circulated water helps to carry heat away from the electrode-tissue interface to reduce charring allowing more energy to be delivered to surrounding tissues creating a larger area for ionic heating to occur. When using water- cooled probes studies have demonstrated the tissue temperature beyond the electrode tissue interface reach 80˚ C and greater and that the lesions created are larger than those of standard RF.34
1 Cheng OT, Souzdalnitski D, Vrooman B, et al. Evidence-based knee injections for the management of arthritis. Pain Med. 2012; 13(6):740-753.
2 Chevalier X, Jerosch J, Goupille P, van Dijk N, Luyten FP, Scott DL, Bailleul F, Pavelka K. Single, intra-articular treatment with 6 ml hylan G-F 20 in patients with symptomatic primary osteoarthritis of the knee: a randomized, multicentre, double-blind, placebo-controlled trial. Ann Rheum Dis. 2010 Jan;69(1):113-9.
3 Hsu H, Siwiec RM. Osteoarthritis, Knee. [Updated 2018 Jun 15]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507884/. Accessed Mar 4, 2022.
4 Cisternas MG, Murphy L, Sacks JJ, Solomon DH, Pasta DJ, Helmick CG. Alternative Methods for Defining Osteoarthritis and the Impact on Estimating Prevalence in a US Population-Based Survey. Arthritis Care Res (Hoboken). 2016; 68(5):574–580. abstract
5 Deshpande B, Katz J, Solomon D, et al. The number of persons with symptomatic knee osteoarthritis in the United States: Impact of race/ethnicity, age, sex and obesity. Arthritis Care Res (Hoboken). 2016 December; 68(12): 1743–1750. doi:10.1002/acr.22897.
6 London N, Miller L, Block J. Clinical and economic consequences of the treatment gap in knee osteoarthritis management. Medical Hypotheses 76 (2011) 887–892
7 Hsu H, Siwiec RM. Osteoarthritis, Knee. [Updated 2018 Jun 15]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507884/. Accessed Mar 4, 2022.
8 Hsu H, Siwiec RM. Osteoarthritis, Knee. [Updated 2018 Jun 15]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507884/. Accessed Mar 4, 2022.
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11 Chevalier X, Jerosch J, Goupille P, van Dijk N, Luyten FP, Scott DL, Bailleul F, Pavelka K. Single, intra-articular treatment with 6 ml hylan G-F 20 in patients with symptomatic primary osteoarthritis of the knee: a randomized, multicentre, double-blind, placebo-controlled trial. Ann Rheum Dis. 2010 Jan;69(1):113-9.
12FDA Intent to Consider the Appropriate Classification of Hyaluronic Acid Intra-Articular Products Intended for the Treatment of Pain in Osteoarthritis of the Knee Based on Scientific Evidence. Docket No. FDA-2018-N-4627.
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