Genicular Artery Embolization: Beyond the Placebo Effect, and Planning for the Long Road Ahead

Abstract

Genicular artery embolization (GAE) has emerged in the field of interventional radiology as a treatment for knee pain related to osteoarthritis. This novel treatment is based on the hypothesis by Okuno et al and supported by multiple small single-arm studies ( 1 Okuno Y. Korchi A.M. Shinjo T. et al. Transcatheter arterial embolization as a treatment for medial knee pain in patients with mild to moderate osteoarthritis. Cardiovasc Intervent Radiol. 2015; 38: 336-343 Crossref PubMed Scopus (50) Google Scholar , 2 Okuno Y. Korchi A.M. Shinjo T. et al. Midterm clinical cutcomes and MR imaging changes after transcatheter arterial Embolization as a treatment for mild to moderate radiographic knee osteoarthritis resistant to conservative treatment. J Vasc Interv Radiol. 2017; 28: 995-1002 Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar , 3 Lee S.H. Hwang J.H. Kim D.H. et al. Clinical outcomes of transcatheter arterial embolisation for chronic knee pain: mild-to-moderate versus severe knee osteoarthritis. Cardiovasc Intervent Radiol. 2019; 42: 1530-1536 Crossref PubMed Scopus (40) Google Scholar , 4 Landers S. Hely R. Page R. et al. Genicular artery embolization to improve pain and function in early-stage knee osteoarthritis-24-month pilot study results. J Vasc Interv Radiol. 2020; 31: 1453-1458 Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar , 5 Bagla S. Piechowiak R. Hartman T. et al. Genicular artery embolization for the treatment of knee pain secondary to osteoarthritis. J Vasc Interv Radiol. 2020; 31: 1096-1102 Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar , 6 Little M.W. 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: 931-940 Crossref PubMed Scopus (26) Google Scholar ) that pain is in part due to hypervascularity and inflammation, but several considerations need to be addressed. These include GAE's indications, mode of action, mechanism of clinical success achieved by short-term embolization using imipenem/cilastatin crystals vs other embolics, and the possibility of symptom improvement due to the placebo effect. In particular, concern about the placebo effect is plausible given that embolization using imipenem/cilastatin crystals, which are smaller and more rapidly soluble than typical embolic materials ( 7 Yamada K. Jahangiri Y. Li J. et al. Embolic characteristics of imipenem-cilastatin particles in vitro and in vivo: implications for transarterial embolization in joint arthropathies. J Vasc Interv Radiol. 2021; 32: 1031-1039.e2 Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar ), have yielded outcomes similar to those of permanent embolic materials ( 2 Okuno Y. Korchi A.M. Shinjo T. et al. Midterm clinical cutcomes and MR imaging changes after transcatheter arterial Embolization as a treatment for mild to moderate radiographic knee osteoarthritis resistant to conservative treatment. J Vasc Interv Radiol. 2017; 28: 995-1002 Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar ). Osteoarthritic pain response is also highly susceptible to the placebo effect ( 8 Doherty M. Dieppe P. The “placebo” response in osteoarthritis and its implications for clinical practice. Osteoarthritis Cartilage. 2009; 17: 1255-1262 Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar ). Therefore, a sham-controlled study is extremely valuable to assess the efficacy of GAE. However, it is difficult to justify a sham-controlled study in the field of interventional radiology because subjects in the control arm would be at risk of adverse events that may not be trivial, such as infection or bleeding after arterial access.