Cost-effectiveness analysis of second-line medical therapies in acromegaly: a real-life study

Abstract

Introduction: Acromegaly is an uncommon disease with important comorbidity and economic cost. Although the pharmacological cost of second-line treatment for refractory acromegaly has been theoretically analyzed, real-life studies are needed.

Objectives: To assess the use of pasireotide and pegvisomant in a third-level center under routine clinical practice.

Methods: Acromegaly patients that had been treated with pasireotide and/or pegvisomant were included in (A) a cross-sectional study (two years after starting these drugs) to analyze the cost of acromegaly, hormone replacement, and type 2 diabetes mellitus (T2DM) treatments, and the cost of surgery and radiotherapy; and (B) a retrospective cohorts study (May 2006-October 2024) to analyze efficacy, safety (adverse events, fasting glucose, glycated hemoglobin, and T2DM diagnosis), and dose evolution. Descriptive statistics were 10% trimmed means and standard deviation. Two-tailed hypothesis testing with Yuen's t and Fisher's test had a P < 0.05 significance.

Results: 25 participants were included in the transversal study and 31 participants in the longitudinal study. A typical patient with a poorly granulated GH-producing adenoma underwent in-center surgery once and received radiotherapy. In the transversal study, total pharmacological cost was 34,139.29 (13,472.09) €/person/year, with 33,874.88 (13,468.36) €/person/year for second-line acromegaly drugs. Pasireotide displayed 9,423.26 €/person/year worth of savings (P = .12), reaching 30,415.98 €/person/year at high dose (P < 0.001). In the longitudinal study, pasireotide dose was reduced (P = .06) regardless of treatment modality. Pasireotide affected carbohydrate metabolism (P = .001), but the effect was generally mild.

Conclusions: Pasireotide was found to be a more cost-effective option in patients with first-line treatment failure.

Keywords: acromegaly; cost analysis; pasireotide; pegvisomant; radiotherapy.

Figure 1

Flow diagram of the participants. Our whole cohort of refractory acromegaly cases is represented in the upper rectangle. From it, participants for the longitudinal study are extracted after completing the inclusion and exclusion criteria from Table 1 , with an excluded case depicted in a pink rectangle that horizontally diverges from the top-to-bottom direction of the figure. Then, participants for the transversal study are extracted after completing the inclusion and exclusion criteria from Table 1 , with n = 6 excluded cases depicted in a pink rectangle that horizontally diverges from the top-to-botton direction of the figure. In all cases, pasireotide treatment is represented in red and pegvisomant treatment in green. Coadjuvant treatments such as cabergoline and first generation synthetic somatostatin analogues (1^st gen. SSAs) are represented in subsequent rectangles in different tones of grey, with participants taking both kind of coadjuvant drugs represented within a tangent circle.

Figure 2

Box and whisker plot (with 10% trimmed mean represented as a reddish dot) with overlapping violin plot and point cloud diagram geometries. P-values of the robust test for comparisons of trimmed means (Yuen’s t test) are shown at the top. Annual cost per person (expressed in €/person/year, with each thousand units replaced by factor k) of second-line acromegaly drugs on the Y-axis in all cases. Type of second-line acromegaly drugs (pasireotide or pegvisomant) on the X-axis in the overall sample (A), in patients on low-dose (B), and on high-dose (C) treatment. Presence of radiotherapy on the X-axis in the overall sample (D), in patients treated with pasireotide (E), and with pegvisomant (F).

Figure 3

Box and whisker plot (with 10% trimmed mean represented as a reddish dot) with overlapping violin plot and point cloud diagram geometries. Total annual drug cost per person (expressed in euros/person/year, with each thousand units replaced by factor k) on the X-axis according to second-line acromegaly drugs on the Y-axis (A), with p-values of the robust test for comparisons of trimmed means (Yuen’s t test) shown at the top, and broken down by type of cost (treatment of diabetes, hormone replacement therapy, treatment of acromegaly) in the sample on the Y-axis (B).

Figure 4

Box and whisker plot (with 10% trimmed mean represented as a reddish dot) with overlapping violin plot and point cloud diagram geometries. Posology (in milligrams) for second-line treatment of acromegaly (pasireotide in mg/month, pegvisomant in mg/week) on the Y-axis, treatment time (baseline, final) on the X-axis. Results of Yuen’s t-test shown at top. The intraindividual before-after evolution is indicated as solid lines in grey according to the identifier of the participant. All analyses were performed per protocol, including only currently active chronic treatments after excluding participants who discontinued the drug due to side effects or cure. Dose course in the case of pasireotide (A) or pegvisomant (D). Dose course in surgery with radiotherapy group treated with pasireotide (B) or pegvisomant (E). Dose course in surgery without radiotherapy group treated with pasireotide (C) or pegvisomant (F).

Figure 5

Box and whisker plot (with 10% trimmed mean represented as a reddish dot) with overlapping violin plot and point cloud diagram geometries. Type of second-line treatment for acromegaly: pasireotide (left half of the figure); or pegvisomant (right half of the figure), and time of treatment (baseline, final) on the X-axis. Results of Yuen’s t-test shown at top. Fasting plasma glucose (Glu) on the Y-axis in the first row (A–D) and glycated hemoglobin (HbA1c) on the Y-axis in the second row (E–H). Intent-to-treat analysis for pasireotide (A, E) and pegvisomant (C, G). Per protocol analysis for pasireotide (B, F) and pegvisomant (D, H). Chronicity of the treatment marked in color (blue continued, red discontinued). In all cases, the yellow and red dotted horizontal lines mark the pre-T2DM diagnosis limit and the T2DM diagnosis limit, respectively. Fasting plasma glucose is expressed in both mg/dl (left) and mmol/l (right), while glycated hemoglobin is expressed in percentages (%).