Cost-Effectiveness and Efficacy of a Novel Combination Regimen in Acromegaly: A Prospective, Randomized Trial

J Clin Endocrinol Metab. 2020 Sep 1;105(9):dgaa444. doi: 10.1210/clinem/dgaa444.

Abstract

Context: Combination therapy with somatostatin receptor ligand (SRL) plus pegvisomant for patients with acromegaly is recommended after a maximizing dose on monotherapy. Lower-dose combination regimens are not well studied.

Objective: To compare cost-effectiveness and efficacy of 3 lower-dose combination regimens in controlled and uncontrolled acromegaly.

Design and setting: Prospective, randomized, open-label, parallel arm study at a tertiary referral pituitary center.

Patients: Adults with acromegaly regardless of response to prior SRL and biochemical control status at baseline, stratified by an SRL dose required for insulin-like growth factor (IGF)-I normalization during any 3-month period within 12 months preceding enrollment.

Intervention: Combination therapy for 24 to 32 weeks on arm A, high-dose SRL (lanreotide 120 mg/octreotide long-acting release [LAR] 30 mg) plus weekly pegvisomant (40-160 mg/week); arm B, low-dose SRL (lanreotide 60 mg/octreotide LAR 10 mg) plus weekly pegvisomant; or arm C, low-dose SRL plus daily pegvisomant (15-60 mg/day).

Main outcome measure: Monthly treatment cost in each arm in participants completing ≥ 24 weeks of therapy.

Results: Sixty patients were enrolled and 52 were evaluable. Fifty of 52 (96%) demonstrated IGF-I control regardless of prior SRL responsiveness (arm A, 14/15 [93.3%]; arm B, 22/23 [95.7%]; arm C, 14/14 [100%]). Arm B was least costly (mean, $9837 ± 1375 per month), arm C was most expensive (mean, $22543 ± 11158 per month), and arm A had an intermediate cost (mean, $14261 ± 1645 per month). Approximately 30% of patients required pegvisomant dose uptitration. Rates of adverse events were all < 10%.

Conclusions: Low-dose SRL plus weekly pegvisomant represents a novel dosing option for achieving cost-effective, optimal biochemical control in patients with uncontrolled acromegaly requiring combination therapy.

Trial registration: ClinicalTrials.gov NCT01538966.

Keywords: Acromegaly; combination therapy; pegvisomant; somatostatin receptor ligand.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acromegaly / drug therapy*
  • Acromegaly / economics*
  • Adult
  • Cost-Benefit Analysis
  • Delayed-Action Preparations
  • Dosage Forms
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Costs
  • Drug Therapy, Combination / adverse effects
  • Drug Therapy, Combination / economics
  • Female
  • Human Growth Hormone / administration & dosage
  • Human Growth Hormone / adverse effects
  • Human Growth Hormone / analogs & derivatives*
  • Human Growth Hormone / economics
  • Humans
  • Male
  • Middle Aged
  • Octreotide / administration & dosage*
  • Octreotide / adverse effects
  • Octreotide / economics
  • Peptides, Cyclic / administration & dosage*
  • Peptides, Cyclic / adverse effects
  • Peptides, Cyclic / economics
  • Receptors, Somatostatin / agonists
  • Somatostatin / administration & dosage
  • Somatostatin / adverse effects
  • Somatostatin / analogs & derivatives*
  • Somatostatin / economics
  • Therapies, Investigational / adverse effects
  • Therapies, Investigational / economics
  • Therapies, Investigational / methods
  • Treatment Outcome

Substances

  • Delayed-Action Preparations
  • Dosage Forms
  • Peptides, Cyclic
  • Receptors, Somatostatin
  • lanreotide
  • Human Growth Hormone
  • Somatostatin
  • pegvisomant
  • Octreotide

Associated data

  • ClinicalTrials.gov/NCT01538966