Cost-utility analysis of second line acromegaly treatment in France.

Objective: This updated French cost-utility analysis aimed to assess the efficacy of the second-line pharmacological treatment - pegvisomant, pasireotide or pegvisomant combined with first generation somatostatin analogues (FGSA) - considering first-line treatment (surgery, FGSA, cabergoline and combination), radiotherapy and the impact of treatment on tumor volume.

Methods: The original three-state Markov model was revised to include an additional health state, representing patients controlled without pharmacological treatment following successful radiotherapy. The model also accounted for the history of first-line treatments as additional costs upon patients' entry. A cohort of 1,000 simulated patients was followed over a lifetime horizon from a collective perspective. Treatment efficacy is defined on normalization of insulin growth factor-1 and was determined through a network meta-analysis. Cost and utility data were sourced from French databases and literature.

Results: All the evaluated treatments were included in an efficiency frontier. The incremental cost-utility ratio (ICUR) of pegvisomant compared to pasireotide was 27,805 euro per quality-adjusted life year (QALY) gained. The ICUR of pegvisomant combined with FGSA compared to pegvisomant was 253,854 euro/QALY. Sensitivity analyses showed the robustness of the results. The addition of radiotherapy has shown improved quality of life and lower costs for all second-line treatments.

Conclusion: This model explores the cost-effectiveness of second-line pharmacological treatments of acromegaly accounting for the overall management recommended in France. Radiotherapy appears as a key therapeutic option allowing long-term remission of patients even after pharmacological treatment failure. This study is an additional tool for treatment choice including both a clinical and economic perspective.

Significance statement: The aim of this study is to assess the cost-utility of second-line treatments of acromegaly accounting for the overall management recommended in France, considering surgery, first-line treatments, radiotherapy and the impact of treatments on tumor volume, in addition to IGF-1 normalization. All evaluated treatments were included in an efficiency frontier. This addition has shown that radiotherapy and the impact on tumor volume are decisive in the management of second-line treatments for acromegaly. Indeed, radiotherapy enables patients to achieve complete remission, i.e. without the need for drug treatment. This is an important factor for patients, given that acromegaly treatments are chronic and usually lifelong. This study is an additional tool for treatment choice including both a clinical and economic perspective.