Clinical Scorecard: Letter to the Editor: Genicular Artery Embolization for Knee Osteoarthritis—Assess the Evidence Before Drawing Conclusions

At a Glance

Key Highlights

• The cited 12-month sham-controlled trial found no significant between-group difference in pain improvement; the letter argues that this does not establish equivalence or ineffectiveness.
• The trial enrolled 29 patients per group. The letter estimates that approximately 450 participants per group would have been needed to detect the observed 3.0-point difference, without specifying the power assumptions.
• Three of 29 participants assigned to GAE had no angiographic blush and did not undergo embolization, reducing treatment separation in the intention-to-treat analysis.
• The letter identifies patient selection, completion of multi-vessel embolization, procedure learning curve, MRI timing, and reader reliability as limitations to consider when interpreting the trial.
• The authors report that more than 12 prospective randomized trials involving over 1,700 patients are underway.

Guideline-Based Recommendations

Diagnosis

• For trials of a procedure directed at synovial inflammation, the letter argues for enrolling patients with clinically meaningful synovitis and suggests MRI confirmation may align eligibility more closely with the treatment target than Kellgren-Lawrence grade alone.

Management

• The letter argues against drawing premature conclusions about GAE efficacy from the cited small, early-phase trial.
• The letter argues that an adequate GAE trial should include complete multi-vessel embolization and account for the procedural learning curve.

Monitoring & Follow-up

• The letter notes that contrast-enhanced MRI in the cited trial was performed only at 1 and 4 months, whereas other investigations reported synovitis reductions at 12–24 months; it raises concern that the trial’s imaging follow-up may have been too short.
• The letter identifies the absence of inter- and intra-reader reliability data as a limitation when interpreting semiquantitative MRI scores.

Risks

• The letter warns that interpreting a non-significant result from an underpowered study as proof of no efficacy conflates absence of evidence with evidence of absence.
• The letter raises concern that premature interpretations could be used by payers to deny reimbursement before GAE’s value has been determined.

Patient & Prescribing Data

GAE is intended to address synovial hypervascularity and neoangiogenesis. The letter reports that embolization was not performed in three assigned participants without angiographic blush. Citing Landers et al., it reports clinically relevant improvement in 77% of patients receiving a multi-vessel approach, compared with 38% of controls.

Clinical Best Practices

• In its appraisal of the cited trial, the letter recommends interpreting non-significant findings in light of sample size, the observed sham response, confidence intervals, and the study’s ability to detect clinically meaningful differences.
• The letter distinguishes intention-to-treat analysis from whether the assigned procedure was technically completed.
• The letter argues that trial eligibility criteria should align with the biological target being treated, including assessment of synovitis for a synovitis-directed procedure.
• The letter identifies procedure maturity, multi-vessel treatment, imaging follow-up duration, and reader reliability as considerations when appraising GAE studies.

Related Resources & Content

• Van Zadelhoff et al. 12-month randomized sham-controlled GAE trial (reference 1 in the letter)
• Nevalainen commentary (reference 2 in the letter)
• Ro et al. rabbit KOA study (reference 4 in the letter)
• Landers et al. GAE trial (reference 6 in the letter)
• ClinicalTrials.gov: GENESIS II (NCT05423587)
• ClinicalTrials.gov: GRAVITY (NCT04682652)
• ClinicalTrials.gov: RESORB (NCT06872567)