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    Interventional procedure overview of radiofrequency denervation for osteoarthritic knee pain

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    Evidence summary

    Population and studies description

    This interventional procedures overview is based on approximately 2,896 patients from 1 systematic review and network meta-analysis, 2 systematic reviews and meta-analyses, 1 RCT, 1 long-term cohort study that was a single-arm extension of an RCT, 1 cohort study, 1 narrative review and 2 case reports. There was some overlap in studies included in the systematic reviews. Of these patients, approximately 2,047 had the procedure. This is a rapid review of the literature, and a flow chart of the complete selection process is shown in figure 1. This overview presents 9 studies as the key evidence in table 2 and table 3, and lists 48 other relevant studies in table 5.

    Of the 9 key evidence studies, 3 were systematic reviews and meta-analyses. Wu (2022) is a comprehensive network meta-analysis of RCTs that compares the efficacy of all modalities of RF denervation with each other, non-RF comparators, and placebo. Chou (2021) is a meta-analysis of RCTs and observational studies of the treatment effect of RF denervation (before versus after treatment). Liu (2022) is a meta-analysis of RF denervation versus several comparators pooled into a single group.

    One further comparative study was an RCT of conventional RF versus sham versus control (best supportive care only; Kumaran, 2019). This study was also included in the Liu (2022) meta-analysis.

    Long-term data is reported in a long-term cohort study which was a long-term extension of an RCT (Lyman, 2022). This study reported 2-year outcomes of cooled RF denervation. An observational study (Chen, 2021) provides real-world outcomes of RF denervation and reports prognostic factors. A narrative review and 2 case reports are included to report unique safety events (McCormick, 2021; Mateev, 2021; Jorge 2019).

    In the Liu (2022) systematic review, there were 7 studies from China, 2 from the US, and 1 each from the UK, Italy, Korea, Iran, Turkey, and Egypt. The locations of studies were not well reported in the other systematic reviews; of the other studies, Chen (2021) and Lyman (2022) were conducted in the US; Kumaran (2019) was conducted in the UK. Follow-up periods were typically 6 to 12 months.

    Table 2 presents study details.

    Figure 1 Flow chart of study selection

    Table 2 Study details

    No.

    Author, date

    Location

    Patients (m:f) Studies

    Age

    Study design

    Inclusion criteria

    Intervention

    Follow up

    1

    Wu, 2022

    Various

    21 studies

    n=1,818 (657 non-RF comparator)

    NR

    Systematic review and network meta-analysis of RCTs

    RCTs with at least 1 treatment arm using a RF denervation treatment and a comparator arm using placebo or other active treatment;

    Studies including patients with knee osteoarthritis;

    Studies containing pain or functional outcome scores;

    Studies fully reporting the numbers of patients and involved knees and the time of follow up;

    Studies completely reporting the RF denervation methodology, target, and number of electrodes;

    Studies diagnosing OA clinically and radiographically.

    Conventional RF: 10 studies

    Pulsed RF: 11 studies

    Cooled RF: 2 studies

    (some studies used multiple types)

    Network meta-analysis consisted of all treatments vs. all comparators

    Various; only 3 and 6 month results included in network meta-analysis.

    2

    Chou, 2021

    Various

    20 studies

    n=605

    148 male; 343 female

    Means ranged from 53.3 to 77.2

    Systematic review and meta-analysis of RCTs and observational studies

    Articles investigating the efficacy of pulsed, conventional, or cooled RF denervation techniques;

    Patients with knee osteoarthritis;

    VAS or NRS used to evaluate pain;

    Articles written in English or Chinese.

    Conventional RF: 11 studies

    Pulsed RF: 8 studies

    Cooled RF: 2 studies

    Meta-analysis was conducted on before vs. after treatment

    Up to 12 months

    3

    Liu, 2022

    Various

    15 studies

    n=1,009 (506 non-RF comparator)

    309 male; 594 female

    Means ranged from 47.8 to 70.9

    Systematic review and meta-analysis of RCTs

    Patients were diagnosed with knee osteoarthritis;

    Patients in the experimental group received RF therapy;

    The trial had a control group;

    Included the following outcome measurements: VAS or NRS, WOMAC, Oxford Knee Score, Global Perceived Effect scale, and adverse effects at different time points after treatment;

    Studies were RCTs.

    Conventional RF: 9 studies

    Pulsed RF: 4 studies

    Cooled RF: 2 studies

    Meta-analysis was conducted on RF denervation vs. comparator

    Up to 24 weeks

    4

    Kumaran, 2019

    UK

    n=45 (15 conventional RF; 15 sham; 15 control)

    18 male;27 female

    Mean RF 63; mean sham 63; mean control 60

    RCT

    Symptomatic for a minimum of 6 months;

    A prior clinical and/or radiological diagnosis of osteoarthritis knee meeting the American College of Rheumatology criteria.

    Conventional RF

    3 months

    5

    Lyman, 2022

    US

    n=32

    Male:female breakdown NR

    NR

    Prospective cohort study

    (Single arm, multicentre, long-term extension of an RCT [Chen, 2020 in the appendix])

    Baseline NRS score of 6 or more (usual daily pain) for the index knee was required for enrolment in the RCT

    Baseline of score of 2 or 3 on WOMAC question A1 (pain while walking on flat surface) and a baseline mean score of 1.5 to 3.5 on all five questions of the WOMAC subscale A (pain)

    Only people initially randomised to cooled RF denervation were eligible for the extension.

    Cooled RF

    Up to 24 months

    6

    Chen, 2021

    US

    n=265

    96 male;169 female

    Mean 64.3

    Retrospective, multicentre, cohort study

    Patients with a primary complaint of knee pain treated with a radiofrequency procedure(s).

    Conventional RF: n=103

    Pulsed RF: n=7

    Cooled RF: n=151

    3 months or more

    Safety studies – the following studies were included to show unique safety events

    7

    McCormick, 2021

    5 studies

    n=8

    Male:female breakdown NR

    NR

    Narrative review

    NR

    Conventional RF: 2 study

    Cooled RF: 3 studies

    NR

    8

    Matveev, 2021

    US

    n=1

    Male

    49

    Case report

    NR

    Conventional RF

    NR

    9

    Jorge, 2019

    US

    n=1

    Male

    76

    Case report

    NR

    Conventional RF

    NR

    Table 3 Study outcomes

    Author, date

    Efficacy outcomes

    Safety outcomes

    Wu, 2022

    Network meta-analysis

    VAS pain

    3 months

    • Network comprised of 16 studies and 1,401 patients

    • All treatments except for exercise had statistically significantly decreased VAS compared to placebo at 3 months.

    • Top 5 treatment rankings were (MD of treatment vs. placebo [95% CI] shown):

      1. Cooled monopolar genicular nerve RF, -4.0 (-4.6 to -3.4)

      2. Pulsed bipolar articular cavity RF, -3.8 (-4.8 to -2.8)

      3. Conventional monopolar genicular nerve RF, -3.5 (-3.8 to -3.2)

      4. Pulsed monopolar articular cavity RF combined with intra-articular platelet-rich plasma injection, -3.5 (-4.3 to -2.6)

      5. Intra-articular erythropoietin injection, -3.1 (-4.5 to -1.7)

    6 months

    • Network comprised of 10 studies and 1,021 patients

    • All treatments except for NSAIDs had statistically significantly improved VAS compared to exercise at 6 months (placebo was not included in the network).

    • Top 5 treatment rankings were (MD of placebo vs. treatment [95% CI] shown):

      1. Conventional bipolar genicular nerve RF, 5.5 (4.3 to 6.7)

      2. Cooled monopolar genicular nerve RF, 4.7 (3.8 to 5.6)

      3. Conventional monopolar genicular nerve RF, 3.5 (3.1 to 3.9)

      4. Pulsed monopolar articular cavity RF combined with intra-articular protein-rich plasma, 3.3 (2.6 to 3.9)

      5. Pulsed monopolar genicular nerve RF, 2.5 (2.2 to 2.8)

    WOMAC

    3 months

    • Network comprised of 14 studies and 1,091 patients

    • All treatments except for exercise, NSAIDs, and pulsed monopolar saphenous nerve RF, had statistically significantly decreased WOMAC compared to placebo at 3 months.

    • Top 5 treatment rankings were (MD of treatment vs. placebo [95% CI] shown):

      1. Cooled monopolar genicular nerve RF, -32 (-41 to -22)

      2. Pulsed bipolar articular cavity RF, -26 (-37 to -14)

      3. Conventional bipolar genicular nerve RF, -25 (-34 to -16)

      4. Pulsed monopolar articular cavity RF, -22 (-34 to -10)

      5. Conventional monopolar genicular nerve RF, -20 (-29 to -12)

    6 months

    • Network comprised of 9 studies and 821 patients

    • All treatments had statistically significantly decreased WOMAC compared to exercise at 6 months (placebo was not included in the network).

    • Top 5 treatment rankings were (MD of exercise vs. treatment [95% CI] shown):

      1. Cooled monopolar genicular nerve RF, 33 (29 to 37)

      2. Pulsed monopolar articular cavity RF combined with intra-articular platelet-rich plasma injection, 30 (27 to 33)

      3. Conventional bipolar genicular nerve RF, 24 (20 to 28)

      4. Conventional monopolar genicular nerve RF, 20 (18 to 22)

      5. Pulsed monopolar articular cavity RF, not reported

    Adverse events were reported in 6 studies, comprising 836 patients.

    51 adverse events were reported as probably related to treatment, including:

    • RF: 43 adverse events in 513 patients (8.4%)

    • Comparators: 8 adverse events in 323 patients (2.5%)

    20 (3.9%) major adverse events were possibly related to RF denervation:

    • Pain, n=5

    • Postprocedural pain, n=7

    • Falls, n=5

    • Stiffness, n=1

    • Swelling, n=2

    Chou, 2021

    Meta-analysis

    Pain (VAS or NRS)

    1 month

    • Overall effect (all 3 modalities; 17 studies): statistically significant decrease in pain after treatment compared to baseline, SMD 3.25 (95% CI 2.56 to 3.93; I2=93%; p<0.00001)

    • There was no statistically significant difference in pain relief observed between the treatments (p=0.25)

    3 months

    • Overall effect (all 3 modalities; 14 studies): statistically significant decrease in pain after treatment compared to baseline, SMD 3.39 (95% CI 2.47 to 4.31; I2=96%; p<0.00001)

    • There was no statistically significant difference in pain relief observed between the treatments (p=0.95)

    6 months

    • Overall effect (all 3 modalities; 12 studies): statistically significant decrease in pain after treatment compared to baseline, SMD 4.84 (95% CI 3.62 to 6.03; I2=95%; p<0.00001)

    • There was no statistically significant difference in pain relief observed between the treatments (p=0.14)

    12 months

    • Overall effect (conventional and cooled RF; 4 studies): statistically significant decrease in pain after treatment compared to baseline, SMD 2.71 (95% CI 1.23 to 4.18; I2=94%; p=0.00003)

    • There was no statistically significant difference in pain relief observed between the treatments (p=0.58)

    Adverse events were reported in 14 studies.

    No serious or adverse events or complications related to RF were reported.

    Liu, 2022

    Meta-analysis

    Pain (VAS or NRS)

    1 to 2 weeks

    • Overall effect (conventional and pulsed RF; 10 studies): statistically significant decrease in pain after RF denervation compared to control, WMD -1.72 (95% CI -2.17 to -1.30; I2=78%; p<0.00001)

    4 weeks

    • Overall effect (all 3 modalities; 9 studies): statistically significant decrease in pain after RF denervation compared to control, WMD 1.49 (95% CI -1.76 to -1.21; I2=66%; p<0.00001)

    12 weeks

    • Overall effect (all 3 modalities; 11 studies): statistically significant decrease in pain after RF denervation compared to control, WMD 1.83 (95% CI -2.39 to -1.26; I2=88%; p<0.00001)

    24 weeks

    • Overall effect (all 3 modalities; 6 studies): statistically significant decrease in pain after RF denervation compared to control, WMD 1.96 (95% CI -2.89 to -1.04; I2=97%; p<0.0001)

    WOMAC

    4 weeks

    • Overall effect (all 3 modalities; 4 studies): statistically significant decrease in WOMAC score after RF denervation compared to control, WMD -10.64 (95% CI -13.11 to -8.17; I2=1%; p<0.00001)

    12 weeks

    • Overall effect (all 3 modalities; 4 studies): statistically significant decrease in WOMAC score after RF denervation compared to control, WMD -6.12 (95% CI -7.67 to -4.57; I2=0%; p<0.00001)

    24 weeks

    • Overall effect (all 3 modalities; 4 studies): statistically significant decrease in WOMAC score after RF denervation compared to control, WMD -10.89 (95% CI -12.28 to -9.51; I2=57%; p<0.00001)

    Global Perceived Effect

    4 weeks

    • Overall effect (conventional and cooled RF; 3 studies): no statistically significant difference in Global Perceived Effect scores between RF denervation and comparator, WMD 0.63 (95% CI –0.15 to 1.42; I2=93%; p=0.12)

    12 weeks

    • Overall effect (conventional and cooled RF; 3 studies): statistically significant difference in Global Perceived Effect scores in favour of control, WMD 1.12 (95% CI 0.61 to 1.63; I2=78%; p<0.0001)

    • Note that this analysis appears to have been conducted incorrectly – the 3 studies cited all report that Global Perceived Effect improvement was statistically significantly greater in the RF denervation arm.

    Adverse events

    • Overall risk (all 3 modalities; 13 studies): No statistically significant difference in the occurrence of adverse events between the RF denervation and control groups, RD 0.03 (95% CI -0.01 to 0.06; I2=7%; p=0.14)

    Kumaran, 2019

    RCT

    Pain (VAS)

    • There was a statistically significant main effect for time (within group change) (F [2.1, 88]=16, p<0.001) and a significant interaction between group and time (F[4.2]=5.2, p=0.001).

    • This infers that the type of intervention made a statistically significant difference to pain, and that there was a statistically significant overall difference between pre, post, 1 month, and 3 months.

    Post-treatment

    • RF group: MD of 1.2 (95% CI 0.81 to 1.5) vs. baseline.

    • Sham group: MD of 0.25 (95% CI -0.10 to 0.61) vs. baseline.

    • Control group: MD of 0.11 (95% CI -0.25 to 0.47) vs. baseline.

    • Note all MDs are of the transformed square root data; the non-transformed data show a clinically significant improvement in the RF group.

    3 months

    • RF group: MD of 0.76 (95% CI 0.18 to 1.3) vs. baseline.

    • Sham group: MD of 0.43 (95% CI -0.15 to 1.0) vs. baseline.

    • Control group: MD of 0.30 (95% CI -0.28 to 0.88) vs. baseline.

    • Note all MDs are of the transformed square root data; the non-transformed data show a clinically significant improvement in the RF group.

    WOMAC

    • There was a statistically significant main effect for time (within group change) (F [2.2, 91]=18, p<0.001) and a significant interaction between group and time (F[4.3]=2.7, p=0.031).

    • This infers that the type of intervention made a statistically significant difference to WOMAC score, and that there was a statistically significant overall difference between pre, post, 1 month, and 3 months.

    Post-treatment

    • RF group: MD of 1.9 (95% CI 1.1 to 2.8) vs. baseline.

    • Sham group: MD of 0.98 (95% CI 0.16 to 1.8) vs. baseline.

    • Control group: MD of 0.09 (95% CI -0.73 to 0.92) vs. baseline.

    • Note all MDs are of the transformed square root data; the non-transformed data show a clinically significant improvement in the RF group.

    3 months

    • RF group: MD of 1.7 (95% CI 0.41 to 2.9) vs. baseline.

    • Sham group: MD of 1.4 (95% CI 0.15 to 2.7) vs. baseline.

    • Control group: MD of 1.1 (95% CI -0.20 to 2.3) vs. baseline.

    • Note all MDs are of the transformed square root data; the non-transformed data show a clinically significant improvement in the RF group.

    Walking ability

    • There was a statistically significant main effect for time (F [2, 85]=15, p<0.001); however, there was no significant interaction between group and time.

    • This infers that the type of intervention did not make a statistically significant difference to walking ability.

    Knee ROM

    • There was a statistically significant main effect for time (within group change) (F [3, 126)=9.1, p<0.001) and a significant interaction between group and time (F(6)=2.6, p=0.023).

    • This infers that the type of intervention made a statistically significant difference to knee ROM, and that there was a statistically significant overall difference between pre, post, 1 month, and 3 months.

    Post-treatment

    • RF group: MD of 0.48 (95% CI 0.16 to 7.9) vs. baseline.

    • Sham group: MD of 0.06 (95% CI -0.26 to 0.37) vs. baseline.

    • Control group: MD of 0.02 (95% CI -0.30 to 0.34) vs. baseline.

    • Note all MDs are of the transformed square root data.

    3 months

    • RF group: MD of 0.29 (95% CI -0.06 to 0.64) vs. baseline.

    • Sham group: MD of 0.22 (95% CI -0.14 to 0.57) vs. baseline.

    • Control group: MD of 0.26 (95% CI -0.09 to 0.61) vs. baseline.

    • Note all MDs are of the transformed square root data.

    No adverse events were reported.

    Lyman, 2022

    Cohort study (single arm, long-term extension of an RCT)

    NRS

    18 and 24 months

    • The NRS pain score for people treated with cooled RF denervation statistically significantly decreased from 6.8 (SD 0.8; n=32) at baseline to 2.4 (SD 2.5; n=32) at 18 months and 3.4 (SD 3.2; n=27) at 24 months after treatment (p<0.0001).

    • The NRS score at 1 month after treatment was 2.8 (SD 2.6; n=32) and at 12 months was 1.9 (SD 1.9; n=32).

    • Kaplan-Meier analysis suggested that patients had approximately a 50% chance of maintaining 50% or greater pain relief through 700 days after treatment.

    WOMAC

    18 and 24 months

    • The WOMAC total score for people treated with cooled RF denervation statistically significantly decreased from 64.4 (SD 14.7; n=32) at baseline to 29.3 (SD 25.3; n=32) at 18 months (p<0.0001) and 41.3 (SD 29.9; n=27) at 24 months after treatment (p=0.0007).

    • The WOMAC total score at 1 month after treatment was 34.1 (SD 23.8; n=32) and at 12 months was 27.4 (SD 23.2; n=32).

    Global Perceived Effect

    18 and 24 months

    • At 18 months, 75% (24/32) of patients reported a perceived improvement in pain. At 24 months, 63% (17/27) of patients reported a perceived improvement in pain.

    • At 1 month, 78.1% (25/32) of patients reported a perceived improvement in pain. At 12 months, 78.1% (25/32) of patients reported a perceived improvement in pain.

    Radiographic changes

    24 months

    • At 24 months, 68.2% (15/22) of patients had no change in Kellgren-Lawrence grade, 22.7% (5/22) showed worsening of 1 grade, and 9.1% of subjects (2/22) showed worsening by 2 grades.

    EQ-5D

    18 and 24 months

    • The total EQ-5D-5L score statistically significantly increased from baseline by 0.15 points at 18 months (p<0.0001) and 0.07 points at 24 months (p=0.0146).

    There were no adverse events related to cooled RF denervation reported at 18- and 24-months following treatment.

    Chen, 2021

    Cohort study

    Patients were categorised as having either a positive or negative outcome:

    • Positive: at least 30% pain relief lasting at least 3 months after RF denervation

    • Negative: less than 30% pain relief or not relief not lasting for 3 months after RF denervation

    Factors associated with positive outcome

    In total, 162/265 patients had a positive outcome (61.1%).

    In multivariate analysis, the following factors were associated with positive outcome:

    • Being obese, OR 3.68 (95% CI 1.66 to 8.19, p=0.001)

    • Not using opioids, OR 0.35 (95% CI 0.16 to 0.77, p=0.009)

    • Not being depressed, OR 0.29 (95% CI 0.10 to 0.82, p=0.02)

    • Use of cooled RF, OR 3.88 (95% CI 1.63 to 9.23, p=0.002)

    • Performing multiple lesions at each neural target, OR 15.88 (95% CI 4.24 to 59.50, p<0.001)

    Not reported.

    Safety studies – the following studies were included to show unique safety events

    McCormick, 2021

    Narrative review

    Not reported.

    Adverse events:

    • Septic arthritis, n=1

    • Pes anserine tendon injury, n=1

    • Skin burn, n=1

    • Periarticular hematoma and/or hemarthrosis, n=5

    Matveev, 2021

    Case report

    Not reported.

    Adverse event:

    • Foot drop, n=1

    Jorge, 2019

    Case report

    Not reported.

    Adverse event:

    • Vascular injury, n=1

    Procedure technique

    All 3 modalities of RF denervation were included in the overview. In addition, the Wu (2022) network meta-analysis included comparisons between polarity of RF treatment (bipolar vs. monopolar) and target of RF (genicular nerve vs. saphenous nerve vs. articular cartilage). The Chen (2021) cohort study also identified treatment characteristics associated with a positive outcome.

    Efficacy

    Pain relief

    Six studies reported on pain relief.

    In the Wu (2022) network meta-analysis, pain relief (as measured by VAS) was assessed at 3 and 6 months. At 3 months, the network was comprised of 16 RCTs (16 interventions) of 1,401 patients, for a total of 120 paired estimates (17 direct and indirect evidence; 103 indirect evidence only). All treatments except for exercise had statistically significantly decreased VAS compared to placebo at 3 months. According to the surface under the cumulative ranking curve (SUCRA), the treatment rankings were as follows (best to worst; MD of treatment vs. placebo [95% CI] shown):

    1. Cooled monopolar genicular nerve RF, -4.0 (-4.6 to -3.4)

    2. Pulsed bipolar articular cavity RF, -3.8 (-4.8 to -2.8)

    3. Conventional monopolar genicular nerve RF, -3.5 (-3.8 to -3.2)

    4. Pulsed monopolar articular cavity RF combined with intra-articular platelet-rich plasma injection, -3.5 (-4.3 to -2.6)

    5. Intra-articular erythropoietin injection, -3.1 (-4.5 to -1.7)

    6. Intra-articular platelet-rich plasma injection, -2.8 (-3.7 to -1.9)

    7. Pulsed monopolar genicular nerve RF, -2.8 (-3.2 to -2.5)

    8. Pulsed monopolar articular cavity RF, -2.8 (-3.8 to -1.8)

    9. Intra-articular anaesthesia, -2.0 (-2.5 to -1.5)

    10. Intra-articular dextrose injection, -2.0 (-3.4 to -0.6)

    11. Intra-articular sodium hyaluronate injection, -1.8 (-2.3 to -1.3)

    12. Pulsed monopolar saphenous nerve RF, -1.6 (-2.1 to -1.1)

    13. Intra-articular corticosteroid injection, -1.6 (-2.5 to -0.7)

    14. NSAIDs, -1.4 (-1.7 to -1.0)

    15. Exercise, -0.2 (-0.7 to 0.3)

    16. Placebo, reference

    At 6 months, the network was comprised of 10 RCTs (10 interventions) of 1,021 patients, for a total of 45 paired estimates (10 direct and indirect evidence; 35 indirect evidence only). All treatments except for NSAIDs had statistically significantly improved VAS compared to exercise at 6 months (placebo was not included in the network). According to the SUCRA, the treatment rankings were as follows (best to worst; MD of exercise vs. treatment [95% CI] shown):

    1. Conventional bipolar genicular nerve RF, 5.5 (4.3 to 6.7)

    2. Cooled monopolar genicular nerve RF, 4.7 (3.8 to 5.6)

    3. Conventional monopolar genicular nerve RF, 3.5 (3.1 to 3.9)

    4. Pulsed monopolar articular cavity RF combined with intra-articular protein-rich plasma, 3.3 (2.6 to 3.9)

    5. Pulsed monopolar genicular nerve RF, 2.5 (2.2 to 2.8)

    6. Intra-articular corticosteroid injection, 1.9 (1.1 to 2.7)

    7. Intra-articular sodium hyaluronate injection, 1.9 (1.0 to 2.7)

    8. Intra-articular platelet-rich plasma injection, 1.5 (0.4 to 2.6)

    9. NSAIDs, 0.06 (-0.7 to 0.9)

    10. Exercise, reference

    In the Chou (2021) meta-analysis, there was a statistically significant decrease in pain from before treatment to 1, 3, 6, and 12 months after treatment. There was no statistically significant difference in pain relief between the RF modalities at any time point.

    • 1 month (17 studies): SMD 3.25 (95% CI 2.56 to 3.93; I2=93%; p<0.00001)

    • 3 months (14 studies): SMD 3.39 (95% CI 2.47 to 4.31; I2=96%; p<0.00001)

    • 6 months (12 studies): SMD 4.84 (95% CI 3.62 to 6.03; I2=95%; p<0.00001)

    • 12 months (4 studies): SMD 2.71 (95% CI 1.23 to 4.18; I2=94%; p=0.00003)

    In the Liu (2022) meta-analysis, there was a statistically significant decrease in pain compared to control (either sham, intra-articular injection, or oral NSAIDs) at 1 to 2, 4, 12, and 24 weeks after treatment.

    • 1 to 2 weeks (10 studies): WMD -1.72 (95% CI -2.17 to -1.30; I2=78%; p<0.00001)

    • 4 weeks (9 studies): WMD 1.49 (95% CI -1.76 to -1.21; I2=66%; p<0.00001)

    • 12 weeks (6 studies): WMD 1.83 (95% CI -2.39 to -1.26; I2=88%; p<0.00001)

    • 24 weeks (studies): WMD 1.96 (95% CI -2.89 to -1.04; I2=97%; p<0.0001)

    In the Kumaran (2019) RCT of conventional RF vs. sham vs. control, there was a statistically significant main effect for time (within group change) (F [2.1, 88]=16, p<0.001) and a significant interaction between group and time (F[4.2]=5.2, p=0.001). This infers that the type of intervention made a statistically significant difference to VAS pain, and that there was a statistically significant overall difference between pre, post, 1-month, and 3 months. The decrease in VAS score in the RF group was greater than published MCID estimates.

    In the long-term cohort study, patients treated with cooled RF denervation had statistically significantly lower scores on the pain NRS at 18 and 24 months than at baseline (all p<0.0001). In Kaplan-Meier analysis, there was approximately a 50% chance that patients maintained a 50% or greater pain relief through 700 days after treatment (Lyman, 2022). Per the Global Perceived Effect questionnaire, 63% reported a perceived improvement in pain at 24 months (Lyman, 2022).

    In the Chen (2021) cohort study, 162/265 (61.1%) patients had a positive outcome, defined as at least 30% pain relief lasting at least 3 months after RF denervation. In multivariate analysis, the following factors were associated with positive outcome:

    • Being obese, OR 3.68 (95% CI 1.66 to 8.19, p=0.001)

    • Not using opioids, OR 0.35 (95% CI 0.16 to 0.77, p=0.009)

    • Not being depressed, OR 0.29 (95% CI 0.10 to 0.82, p=0.02)

    • Use of cooled RF, OR 3.88 (95% CI 1.63 to 9.23, p=0.002)

    • Performing multiple lesions at each neural target, OR 15.88 (95% CI 4.24 to 59.50, p<0.001)

    Composite knee function and pain measures

    WOMAC

    Four studies reported WOMAC outcomes.

    In the Wu (2022) network meta-analysis, WOMAC score was assessed at 3 and 6 months. At 3 months, the network was comprised of 14 RCTs (14 interventions) of 1,091 patients, for a total of 91 paired estimates (14 direct and indirect evidence; 77 indirect evidence only). All treatments except for exercise, NSAIDs, and pulsed monopolar saphenous nerve RF, had statistically significantly decreased WOMAC compared to placebo at 3 months. According to the SUCRA, the treatment rankings were as follows (best to worst; MD of treatment vs. placebo [95% CI] shown):

    1. Cooled monopolar genicular nerve RF, -32 (-41 to -22)

    2. Pulsed bipolar articular cavity RF, -26 (-37 to -14)

    3. Conventional bipolar genicular nerve RF, -25 (-34 to -16)

    4. Pulsed monopolar articular cavity RF, -22 (-34 to -10)

    5. Conventional monopolar genicular nerve RF, -20 (-29 to -12)

    6. Pulsed monopolar articular cavity RF combined with intra-articular platelet-rich plasma injection, -18 (-27 to -9)

    7. Intra-articular anaesthesia, -18 (-27 to -8.2)

    8. Pulsed monopolar genicular nerve RF, -16 (-24 to -6.9)

    9. Pulsed monopolar saphenous nerve RF, -12 (-30 to 5.1)

    10. Intra-articular corticosteroid injection, -14 (-24 to -5.5)

    11. Intra-articular sodium hyaluronate injection, -13 (-22 to -4.4)

    12. NSAIDs, -7.5 (-16 to 1.2)

    13. Exercise, -0.5 (-8.3, 9.4)

    14. Placebo, reference

    At 6 months, the network was comprised of 9 RCTs (9 interventions) of 821 patients, for a total of 36 paired estimates (10 direct and indirect evidence; 26 indirect evidence only). All treatments had statistically significantly decreased WOMAC compared to exercise at 6 months (placebo was not included in the network). According to the SUCRA, the treatment rankings were as follows (best to worst; MD of exercise vs. treatment [95% CI] shown):

    1. Cooled monopolar genicular nerve RF, 33 (29 to 37)

    2. Pulsed monopolar articular cavity RF combined with intra-articular platelet-rich plasma injection, 30 (27 to 33)

    3. Conventional bipolar genicular nerve RF, 24 (20 to 28)

    4. Conventional monopolar genicular nerve RF, 20 (18 to 22)

    5. Pulsed monopolar articular cavity RF, not reported

    6. Intra-articular corticosteroid injection, 13 (10 to 17)

    7. Intra-articular sodium hyaluronate injection, 9.1 (6.1 to 12)

    8. NSAIDs, 9.7 (7.2 to 12)

    9. Exercise, reference

    In the Liu (2022) meta-analysis, there was a statistically significant decrease in WOMAC compared to control (either sham, intra-articular injection, or oral NSAIDs) at 4, 12, and 24 weeks after treatment.

    • 4 weeks (4 studies): WMD -10.64 (95% CI -13.11 to -8.17; I2=1%; p<0.00001)

    • 12 weeks (4 studies): WMD -6.12 (95% CI -7.67 to -4.57; I2=0%; p<0.00001)

    • 24 weeks (4 studies): WMD -10.89 (95% CI -12.28 to -9.51; I2=57%; p<0.00001)

    In the Kumaran (2019) RCT of conventional RF vs. sham vs. control, there was a statistically significant main effect for time (within group change) (F [2.2, 91]=18, p<0.001) and a significant interaction between group and time (F[4.3]=2.7, p=0.031). This infers that the type of intervention made a statistically significant difference to WOMAC score, and that there was a statistically significant overall difference between pre, post, 1 month, and 3 months. The decrease in WOMAC score in the RF group was greater than published MCID estimates.

    In the Lyman (2022) long-term cohort study, the WOMAC total score for people treated with cooled RF denervation statistically significantly decreased from 64.4 (SD 14.7; n=32) at baseline to 29.3 (SD 25.3; n=32) at 18 months (p<0.0001) and 41.3 (SD 29.9; n=27) at 24 months after treatment (p=0.0007).

    Other functional outcomes

    Walking ability

    One study reported walking ability outcomes.

    In the Kumaran (2019) RCT of conventional RF vs. sham vs. control, there was a statistically significant main effect for time (F [2, 85]=15, p<0.001); however, there was no significant interaction between group and time for walking ability as measured by the TUG test. This infers that the type of intervention did not make a statistically significant difference to walking ability.

    Knee ROM

    One study reported walking ability outcomes.

    In the Kumaran (2019) RCT of conventional RF vs. sham vs. control, There was a statistically significant main effect for time (within group change) (F [3, 126)=9.1, p<0.001) and a significant interaction between group and time (F(6)=2.6, p=0.023). This infers that the type of intervention made a statistically significant difference to knee ROM, and that there was a statistically significant overall difference between pre, post, 1 month, and 3 months.

    Radiographic outcomes

    One study reported radiographic outcomes.

    In the Lyman (2022) long-term cohort study, at 24 months, 68.2% (15/22) of patients had no change in Kellgren-Lawrence grade, 22.7% (5/22) showed worsening of 1 grade, and 9.1% of patients (2/22) showed worsening by 2 grades.

    Generic Quality of Life measures

    EQ-5D

    One study reported EQ-5D outcomes.

    In the Lyman (2022) long-term cohort study, the total EQ-5D-5L score statistically significantly increased from baseline by 0.15 points at 18 months (p<0.0001) and 0.07 points at 24 months (p=0.0146).

    Safety

    Rates of complications and major complications

    In the Wu (2022) network meta-analysis, adverse events were reported in 6 studies. There were 43 (8.4%) adverse events in 513 patients treated with RF that were probably related to treatment; 20 (3.9%) major adverse events were possibly related to RF.

    In the Liu (2022) meta-analysis, there was no statistically significant difference in the risk of adverse events between patients treated with RF denervation and patients treated with control, RD 0.03 (95% CI -0.01 to 0.06; I2=7%; p=0.14; all 3 modalities, 13 studies).

    Specific complications

    Pain

    In the Wu (2022) network meta-analysis, 5 people had pain and 7 people had postprocedural pain. These were major adverse events that were deemed possibly related to RF denervation.

    Falls

    In the Wu (2022) network meta-analysis, 5 people experienced falls. These were major adverse events that were deemed possibly related to RF denervation.

    Stiffness

    In the Wu (2022) network meta-analysis, 1 person had stiffness. This was a major adverse event that was deemed possibly related to RF denervation.

    Swelling

    In the Wu (2022) network meta-analysis, 2 people had swelling. These were major adverse events that were deemed possibly related to RF denervation.

    Septic arthritis

    In the McCormick (2021) narrative review, there was a report of 1 person who had septic arthritis after treatment with RF.

    Pes anserine tendon injury

    In the McCormick (2021) narrative review, there was a report of 1 person who had a pes anserine tendon injury after treatment with RF.

    Skin burn

    In the McCormick (2021) narrative review, there was a report of 1 person who had a skin burn after treatment with RF.

    Foot drop

    In the Matveev (2021) case report, there was a report of 1 person who had foot drop after treatment with RF.

    Vascular injury

    In the Jorge (2019) case report, there was a report of 1 person who had a vascular injury after treatment with RF.

    Anecdotal and theoretical adverse events

    Expert advice was sought from consultants who have been nominated or ratified by their professional Society or Royal College. They were asked if they knew of any other adverse events for this procedure that they had heard about (anecdotal), which were not reported in the literature. They were also asked if they thought there were other adverse events that might possibly occur, even if they have never happened (theoretical).

    They listed the following anecdotal adverse events:

    • Numbness

    They listed the following theoretical adverse events:

    • Osteomyelitis

    • Injuries to motor nerves

    • Post ablation neuritis

    • Charcot neuropathy

    Three professional expert questionnaires for this procedure were submitted. Find full details of what the professional experts said about the procedure in the specialist advice questionnaires for this procedure.

    Validity and generalisability

    • Nine studies were included in the key evidence summary, including 1 systematic review and network meta-analysis, 2 systematic reviews and meta-analyses, 1 RCT, 1 long-term cohort study that was an extension of an RCT, 1 cohort study, and 3 case series/reports.

    • All 3 modalities of RF denervation were captured in the key evidence studies.

    • Important efficacy data came from the systematic reviews and meta-analyses:

      • The Wu (2022), Chou (2021), and Li (2021) systematic reviews included a large number of RCTs. Chou (2021) additionally included observational studies.

      • Chou (2021) found that RF denervation has a statistically significant beneficial effect on osteoarthritic knee pain compared to baseline, at a magnitude greater than published MCID estimates. Furthermore, there was no statistically significant difference in pain relief between the modalities.

      • Wu (2022) found that whilst all modalities of RF denervation were typically more effective than placebo or exercise, patients responded better to the cooled modality than the conventional and pulsed modalities, and bipolar is more effective than monopolar for pain and function in conventional and pulsed modalities. Several RF modalities saw improvements in pain and WOMAC score greater than published MCID estimates when compared to placebo or exercise.

        • However, the authors caution that the number of studies, including for the cooled modality, is insufficient.

      • Liu (2022) found that RF denervation was statistically significantly better than control in several measures of knee pain and function. Interpretation of whether these statistical differences were clinically important was complicated due to the comparator arm consisting of sham and active comparators.

        • The authors conclude that thought the meta-analysis shows that RF denervation is efficacious, the clinical utility of RF denervation is currently poorly defined and that further studies are required.

    • Further efficacy evidence came from the Kumaran (2019) RCT. This UK-based study demonstrated statistical and clinical significance over sham and control in improving pain and function. However, this study was limited by small sample size and short follow-up.

    • The Lyman (2022) cohort study showed that the treatment effect of RF denervation can last up to 2 years. Some attenuation of treatment effect is expected due to nerve regrowth. This study had high attrition rates.

    • Long-term evidence was generally limited.

    • The Chen (2021) cohort study gave real-world evidence on the effectiveness of RF denervation, with 61.1% of patients having a positive outcome. Significant prognostic factors for a positive outcome included use of cooled RF and performing multiple lesions at each target.

    • In the Wu (2022) network meta-analysis, 5 and 4 out of 21 studies were judged to have 'some concerns' or to be at 'high risk' of bias, respectively. The main reason for having some concern of bias was a lack of description of the randomisation process and the selection of the reported result; the main reason for having a high risk of bias was the selection of the reported result.

    • The studies list various sources of funding, including from companies involved in the manufacture of RF devices. The sources of funding and conflicts of interest were not well described in the systematic reviews.

    • The following ongoing studies were identified:

      • Coolief Cooled Radiofrequency vs. Conventional Radiofrequency to Manage OA Knee Pain. Prospective, multicentre, single-blind RCT of cooled RF versus conventional RF. Enrolment: 153 patients. Estimated study completion: August 2022. NCT04145011

      • Radiofrequency Ablation in the Pain Management of Knee Osteoarthritis. Double-blind RCT of conventional RF versus pulsed RF versus intra-articular steroids. Estimated enrolment: 150 patients. Estimated completion: March 2023. NCT05303766

      • Ultrasound-Guided Pulsed Radiofrequency In The Treatment Of Patients With Osteoarthritis Knee (USPRFGENOAK). Triple-blind RCT of pulsed RF versus sham. Estimated enrolment: 142 patients. Estimated completion: December 2022. NCT02915120.

      • Comparison of Conventional and Cooled Radiofrequency of the Genicular Nerves in Patients With Chronic Knee Pain (COGENIUS). Prospective, multicentre, double-blind RCT of conventional RF versus cooled RF versus sham. Estimated enrolment: 400 patients. Estimated completion September 2026. NCT05407610

      • Innovations in Genicular Outcomes Registry (iGOR). Prospective registry of patients undergoing several pain therapies including RF denervation. Estimated enrolment: 2,000 patients. Estimated completion: March 2025. NCT05495334