Original Title: Embolización de arterias geniculares para el tratamiento de la artrosis de rodilla

Authors' objectives: The main objective of this health technology assessment report is to evaluate the safety, effectiveness, and cost-effectiveness, as well as the ethical, legal, organizational, social, and environmental aspects of the use of GAE for the treatment of mild or moderate KO refractory to conservative treatment and/or severe KO in individuals not eligible for surgery, with the purpose of informing the decision to include this indication of the technology in the common service portfolio of the Spanish National Health System (SNS).

Authors' results and conclusions: RESULTS: SYSTEMATIC REVIEW OF EFFECTIVENESS AND SAFETY: No high-quality systematic reviews (SRs) that could be included according to the pre-established selection criteria were found. Two randomized controlled trials (RCTs) were finally included, with a total of 80 participants suffering from mild or moderate knee osteoarthritis (KO) refractory to conservative treatment, of which 55 (68.75%) were women. In both studies, genicular artery embolization (GAE) was performed by interventional radiologists using absorbable particles or imipenem/cilastatin sodium, and a simulated GAE procedure was used as a comparator. The overall risk of bias in both RCTs was considered low. The results obtained one month after GAE on pain levels, measured with a visual analogue scale (VAS), show very high heterogeneity. These include findings that GAE may have little to no effect, as well as it might slightly reduce pain levels (MD = 50.1 millimeters; 95% CI: 29.0, 72.3; N = 21 patients). The health-related quality of life (HRQoL) results six months after the intervention revealed significant discrepancies depending on the HRQoL scale used. Following these results, GAE compared to conservative or pharmacological treatment may have little or no effect on HRQoL levels when evaluated with the Quality of Life subscale of the KOOS. However, there may be a slight improvement when assessed with the VAS of the EQ-5D (mean difference [MD] = -10.00; 95% CI: -19.45, -0.55, N = 59 patients). No significant differences were found between GAE and usual treatment in pain levels at six and 12 months; in HRQoL at one month and 12 months; in functional capacity at one month, six months, and 12 months; or in the need for analgesics evaluated at 12 months. No serious adverse effects related to GAE were recorded in either of the two studies, and no differences were observed in minor adverse events between GAE and conservative treatment. The overall quality of the evidence was considered low. COST ANALYSIS: No economic evaluation that met the established criteria was identified by the SR. The cost analysis showed that the inclusion of GAE in the usual treatment would represent an incremental cost of €3,432.37 per patient per year. Assuming a target population of 40 patients per year, the estimated cost of applying GAE would be €137,294.86 per year for a general hospital. In addition, it was estimated that GAE would need to produce an improvement in health of 0.137 QALYs per patient, within the time horizon (a year), for the technology to be considered cost-effective, considering a cost-effectiveness threshold of €25,000 per QALY. Sensitivity analyses revealed a wide range in which the incremental cost can vary, especially due to the influence of the variable related to the number of GAE sessions performed during the time horizon. ETHICAL, LEGAL, ORGANIZATIONAL, SOCIAL, AND ENVIRONMENTAL ASPECTS: No study in which ethical, legal, organizational, social, and environmental aspects related to the evaluated technology were considered was identified. CONCLUSIONS: From the SR on safety, effectiveness, and cost-effectiveness, the economic evaluation, and the analysis of ethical, legal, organizational, social, and environmental aspects conducted for this Health Technology Assessment (HTA) report, the following conclusions can be drawn regarding the incorporation of GAE for the treatment of mild or moderate KO refractory to conservative treatment and/or severe KO in individuals not eligible for surgery: • No scientific evidence regarding the effectiveness and safety of the use of GAE for the treatment of severe OA in individuals not eligible for surgery has been identified. • The best available evidence for the safety and effectiveness of the use of GAE for the treatment of mild or moderate KO refractory to conservative treatment comes from two RCTs with a total of 80 patients with mild to moderate KO according to the Kellgren-Lawrence grading system. These trials evaluate the use of GAE, performed with absorbable particles (one study) or imipenem/cilastatin sodium (one study), compared to conservative or pharmacological treatment plus a simulated GAE procedure. This evidence, considered scarce and of low overall quality, leads to the following conclusions: - No evidence related to the effectiveness and safety of the use of GAE for the treatment of KO in the medium and long term (≥ 1 year) was identified. - The evidence on the effect of GAE for the treatment of mild or moderate KO compared to conservative treatment in pain levels shows very high heterogeneity, which has prevented its synthesis. Preliminary findings reveal significant discrepancies one month after GAE, including both GAE may have little to no effect (1 study, 59 patients) and it may result in a slight decrease in pain levels (1 study, 21 patients) (evidence quality: low ⊕⊕⊖⊖). At six months and 12 months follow-up, GAE probably results in little to no effect (evidence quality: moderate ⊕⊕⊕⊖). - GAE likely have little to no effect on functional capacity at one month (2 studies, 80 patients), six months (1 study, 59 patients), or 12 months (1 study, 59 patients) compared to conservative or pharmacological treatment (evidence quality: moderate ⊕⊕⊕⊖). - GAE likely have little to no effect on HRQoL at one month and 12 months compared to conservative or pharmacological treatment (1 study, 59 patients, evidence quality: moderate ⊕⊕⊕⊖). Preliminary results at six months revealed significant discrepancies depending on the HRQoL scale used, including both GAE may have little or no effect or it may result in a slight improvement of HRQoL levels compared to conservative or pharmacological treatment (1 study, 59 patients, evidence quality: low ⊕⊕⊖⊖). - The use of GAE may have little to no effect on the likelihood of requiring analgesics (1 study, 59 patients, evidence quality: moderate ⊕⊕⊕⊖). - The use of GAE probably does not present significant or serious adverse events such as osteonecrosis or ischemic complications (2 studies, 80 patients, evidence quality: moderate ⊕⊕⊕⊖). - The use of GAE probably results in little to no difference in the rate of minor adverse events between the GAE group and the conservative treatment group (2 studies, 80 patients, evidence quality: moderate ⊕⊕⊕⊖). - With the current evidence, it is not possible to determine if the efficacy of GAE varies according to the level of pain, the severity of KO, or the type of embolizing agent applied. • No published economic evaluations were identified that assessed GAE and met the inclusion criteria established in the SR. • The inclusion of GAE in usual clinical practice would represent an incremental cost of €3,432.37 per patient, from the perspective of the SNS and for a time horizon of a year. • No studies were identified that analyzed ethical, legal, organizational, social, and environmental aspects related to the assessed technology.

Authors' methods: EFFECTIVENESS AND SAFETY: A systematic review (SR) of the literature published from 2013 until October/November 2023 was conducted in the following databases: MEDLINE, Embase, CENTRAL, CINAHL, and Epistemonikos as a metasearcher. The developed comprehensive search strategy included controlled vocabulary and free-text terms. The search was complemented by manually examining the bibliography of the included articles and checking in Google Scholar for studies that reference the selected studies. Original studies evaluating the effectiveness and safety of genicular artery embolization (GAE) in individuals with chronic pain secondary to mild or moderate refractory knee osteoarthritis (OA) and/or severe OA not suitable for surgery compared to usual or conservative treatment, published in English or Spanish, were selected. High-quality systematic reviews and randomized clinical trials (RCTs) were included. In their absence, non-randomized clinical trials and observational studies with a control group were considered. The primary outcome measure was pain. Other outcome measures such as functional capacity, adverse effects and complications, health-related quality of life (HRQoL), and other care-related outcomes or experiences reported by patients were also considered. To assess the risk of bias in SRs and RCTs, the AMSTAR-2 and RoB-2 tools were considered, respectively. Quantitative synthesis of the results was conducted through meta-analysis using the STATA statistical program in its version 17. The assessment of the quality of the evidence and the grading of the strength of the recommendation were carried out following the methodology of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) international working group. ECONOMIC ANALYSIS / COST-EFFECTIVENESS: A SR of economic evaluations of GAE in the treatment of mild or moderate refractory KO was conducted. Economic evaluations (parallel to primary studies or models) reporting any of the following outcomes were sought: incremental cost-effectiveness ratio (ICER), costs expressed in monetary units, and benefits expressed in quality-adjusted life years (QALYs), life years gained (LYG), monetary units, or any of the outcome measures included in the effectiveness section. The appraisal of methodological quality was planned using Drummond et al.'s criteria list and/or OSTEBA's Critical Reading Sheet (CRS) 3.0, along with data extraction and a narrative synthesis with tabulation of results. Furthermore, a partial economic evaluation was performed comparing the costs of two interventions aimed at treating patients with chronic pain secondary to KO who are eligible for GAE: the usual clinical practice in Spain, which includes the application of hyaluronic acid (once a year) plus the prescription of physical exercise, as a first option, versus the addition of GAE to this usual treatment. The analysis was conducted from the perspective of the SNS with a one-year time horizon. Regarding costs, expressed in 2023 euros, only the direct healthcare costs related to GAE were considered, as those related to the usual treatment were considered common costs to both strategies. The incremental cost per patient, the total annual cost for a general hospital, and the health improvement, in terms of QALYs, that GAE would need to produce per patient to be considered cost-effective were estimated. Deterministic one-way and probabilistic sensitivity analyses were conducted to assess uncertainty around the parameters. ETHICAL, LEGAL, ORGANIZATIONAL, SOCIAL, AND ENVIRONMENTAL ASPECTS: The assessment of these aspects was considered from the same population, intervention, and comparison described earlier for the assessment of effectiveness and cost-effectiveness. A manual search of the literature and semi-structured consultations with experts were performed.

Project Status: Completed

Year Published: 2023

URL for published report: https://sescs.es/embolizacion-arterias-geniculares-artrosis-rodilla/

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Spain

Organisation Name: Canary Health Service

Contact Address: Dirección del Servicio. Servicio Canario de la Salud, Camino Candelaria 44, 1ª planta, 38109 El Rosario, Santa Cruz de Tenerife

Contact Name: sescs@sescs.es

Contact Email: sescs@sescs.es