Biomarker analysis in GAE

Genicular Artery Embolization for Treatment of Knee Osteoarthritis: Interim Analysis of a Prospective Pilot Trial Including Effect on Serum Osteoarthritis-Associated Biomarkers

Clinical Question

Is genicular artery embolization (GAE) a safe and effective disease modifying treatment for symptomatic knee osteoarthritis (OA)?

Take Away Point

GAE achieved minimal clinical important difference (MCID) in 5 of the 6 patients who completed their 12-month follow-up with significant reduction in mean WOMAC pain score and plasma nerve growth factor (NGF).

Reference

Taslakian B, Swilling D, Attur M, et al. Genicular artery embolization for treatment of knee osteoarthritis: Interim analysis of a prospective pilot trial including effect on serum osteoarthritis-associated biomarkers. Journal of Vascular and Interventional Radiology. Published online August 23, 2023. Link to article

Study Design

Single arm, prospective, observational and ongoing study containing 16 patients, 6 of whom completed treatment course

Funding Source

No reported funding

Setting

Academic, New York University Langone Health, New York, NY

Figure

Summary

Knee osteoarthritis is one of the most common causes of disability. Despite current options prescribed to combat this condition, many patients are either resistant to existing conservative management or poor surgical candidates to more invasive options such as total knee arthroplasty.



Osteoarthritis is a pathological condition hypothesized to be caused by a triad of inflammation, angiogenesis, and neural growth around the cartilage of the joint. The subsequent neural growth adjacent to the neovessels is thought to be the source of the pain. Arresting these new vessel formations secondary to secreted inflammatory cytokines should theoretically subside the pain and is the basis for the treatment strategy of geniculate artery embolization. Furthermore, embolization retarding the cytokine-induced vessel formation should theoretically correlate with decrease in prognostic biomarkers used to measure inflammation and matrix degradation, providing evidence for the disease-modifying role of genicular artery embolization in knee osteoarthritis.



The authors of this paper performed a prospective, single-arm clinical trial. Out of 27 patients, 16 were enrolled with the inclusion criteria being moderate to severe osteoarthritis associated with knee pain resistant to conservative therapy for greater than 3 months. After undergoing genicular artery embolization, patients were followed up at 1 month, 3 months, and 12 months to assess for change in symptoms. Blood samples were collected at baseline and each follow-up visit for biomarker analyses.



Amongst the six patients who completed the 12 month follow up, technical success rate was 100%. Five of them demonstrated clinical success defined as achieving minimal clinically important difference with improvement in pain, stiffness, and function at early follow-up. However, improvement in WOMAC scores at 12-month follow-up did not achieve statistical significance, possibly related to the nature of interim analysis and small cohort. A single sampled biomarker achieved statistically significant decrease: neural growth factor. This decrease in neural growth factor, correlating with pain reduction experienced in patients after genicular artery embolization, highlighted the clinical relevance of NGF and suggested the disease-modifying nature of the procedure. Of note, there was no significant reduction in NGF levels at the 3-month follow-up, demanding further analyses with larger cohort size and timepoint study to determine the relationship of inflammation reduction and reduction in NGF.



Despite the promising results this trial is showing, there are several limitations, the most important of which is the small sample size of six patients who completed the 12-month follow-up. The power of this study will inevitably improve through the ongoing trial of the remaining 10 patients, after which results can be further tabulated and finetuned. The second limitation is the lack of a control group to compare the progress with given the nature of the study. Finally, the third limitation is the possibility that the accumulated fluid in the synovium that was not procured in the study may contain different levels of biomarkers than the ones collected in the plasma and serum.

Commentary

Genicular artery embolization shows immense potential for its widespread use and versatility. Despite the allure of the benefits this procedure can bring to both the members of the healthcare force and the patients, more data is still needed before definitively concluding the efficacy compared to other more established available options. Clinical trials with basic science correlates are also needed to better understand the specific role of embolization in modifying local inflammation, angiogenesis, and neural growth in the context of osteoarthritis. Results from prospective clinical trials, such as the one presented by this article, may eventually alter the algorithmic approach to the treatment of knee osteoarthritis.

Post author

Naeem Patel, DO
Radiology Resident, PGY4
Department of Radiology, Interventional Radiology Division
Hartford Hospital, Hartford, CT
@Naeemp7Patel