Amy Belba

This doctoral thesis aimed to improve the treatment of individuals with chronic knee pain by targeting the genicular nerves, using a rigorous mixed-methods, patient-centred approach. In the context of the growing burden of osteoarthritis (OA) and persistent postsurgical pain (PPSP), genicular nerve interventions, first described in 2011, have the potential to reduce disease burden. The evidence base for radiofrequency (RF) treatment of the genicular nerves is currently advancing from effectiveness trials toward cost-effectiveness and implementation studies in OA, while research in PPSP is still limited. For this thesis, 5 studies were designed between 2017 and 2026 to address effectiveness, cost-effectiveness, and treatment relevance in OA and PPPS. This thesis was structured using the Joanna Briggs Institute ( JBI) FAME framework—Feasibility, Appropriateness, Meaningfulness, and Effectiveness— providing a structured approach for generation of clinically and socially relevant evidence. In chapters 1, 2, and 3, evidence from the observational cohort and prospective pilot randomized trial supports the fact that RF of the genicular nerves is effective in patients suffering from therapy-resistant knee OA and PPSP in relation to pain and patient-reported outcomes. The effect size of the primary outcomes, however, points toward the need for adequate patient selection and a possibly important placebo effect that should not be dismissed in future trials. When compared to OA, the evidence on RF of the genicular nerves on PPSP is scarcer. This PhD also lays the groundwork for a cost-effectiveness analysis, where preliminary data indicate that cooled RF, compared to conventional RF, could be more cost-effective in PPSP; with conventional RF being more cost-effective in OA. Effectiveness and cost-effectiveness results from the COCOGEN trial will be translated to stronger evidence by the COGENIUS trial. Future studies need to focus on the evaluation and clinical comparison of protocols involving more nerves as a means of improving effectiveness. In chapters 4 and 7, alongside the two previously mentioned trials, evidence is gathered on the potential adverse events after RF of the genicular nerves and the general perceived periprocedural burden. Data from studies from this doctoral thesis are congruent with the literature and identify RF to be a well-tolerated, minimally invasive treatment with an acceptable burden. The prevalence of adverse events is relatively low at 15%, and when present, they are typically temporary and self-resolving. Specific severe adverse events, such as the development of a complex regional pain syndrome, as in the case report included in this thesis, might, despite being rare, require immediate and adequate treatment. Acknowledgement that queries on long-term safety, especially in the case of a repeated procedure or when more nerves are targeted, form a large obstacle in the large-scale implementation of this technique should prompt research programs in the form of long-term real-world cohorts. Chapter 5 explores the genicular nerve block in the setting of acute knee pain, as a valuable derivate from the chronic pain equivalent. The genicular nerve block, due to its motor-sparing qualities, could find a place in enhanced recovery protocols for knee surgery. The GENIFEM pilot trial laid the groundwork for a larger powered trial using the genicular nerve block along a posterior knee capsule block for pain during placement of a knee prosthesis. This trial is the first to evaluate the analgesic capabilities of the block for the anterior aspect of the knee. Larger scale powered trials are needed, to assess the value of the genicular nerve block for acute knee pain. In Chapter 6, the first qualitative study is presented on patient perceptions on the RF treatment in knee OA patients included in the COGENIUS trial. Patient identify experiencing an important disease burden and they experience the RF of the genicular nerves as an appropriate and meaningful treatment option. This study identifies that knee patients in Belgium undergo a long and highly variable treatment trajectory that does not systematically include a bio-psychosocial approach. Education and information of patient and health care providers on the treatment possibilities is an essential starting point. An important strength of this study is the exploration of patient preferences on future research trials and identifies that patients are open to multiple nerve treatment protocols when appropriate sedation is used and the periprocedural burden is acceptable. As such, data from this qualitative trial will further aid the interpretation of the results of the COGENIUS trial, creates a bases for shared decision making and for patient driven research. In conclusion, this doctoral thesis shows that radiofrequency ablation of the genicular nerves is an effective and possibly cost-effective intervention for chronic knee pain, with a relatively low incidence of adverse events and potential applicability in both chronic and acute pain settings, including postoperative pain after knee arthroplasty. At the same time, the combined findings on effectiveness, cost-effectiveness, safety, and patient experience suggest that the added value of RF lies in its potential role within a broader knee pain care pathway, rather than in the intervention as a stand-alone treatment. As the evidence base strengthens—particularly through large trials such as COGENIUS—the next step lies in a health technology assessment–driven evaluation of how RF can be responsibly implemented in routine care. Rather than being offered as a stand-alone solution, RF should be embedded within a carefully designed, integrated care pathway for knee pain that supports personalized decision-making, interdisciplinary collaboration, and a focus on functioning and participation alongside pain relief. Such an approach aligns technological innovation with an integral vision on health and maximizes the likelihood that RF contributes to sustainable, high-value care for people with knee osteoarthritis.