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

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 ±â€…1375 per month), arm C was most expensive (mean, $22543 ±â€…11158 per month), and arm A had an intermediate cost (mean, $14261 ±â€…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.

The utility of oral glucose tolerance testing for diagnosis and assessment of treatment outcomes in 166 patients with acromegaly.

CONTEXT: GH suppression after oral glucose load [oral glucose tolerance test (OGTT)] and normal age- and gender-matched IGF-I levels reflect biochemical control of acromegaly. The OGTT is the gold standard for determining control of GH secretion at diagnosis and after surgical treatment, but the usefulness of performing an OGTT in patients treated with medical therapy has not been determined. OBJECTIVE: Our objective was to assess relationships between basal GH levels (basal GH), GH responses to OGTT [GH nadir (GHn)], and IGF-I levels. DESIGN: This was a retrospective electronic database review. SETTING: This study was performed at a tertiary outpatient pituitary center. PATIENTS: A total of 166 patients with acromegaly (79 females, 87 males) were included in the study. Four categories of testing were performed: diagnosis, postoperative assessment without medication, testing during somatostatin analog (SA) therapy, and testing during dopamine agonist (DA) therapy. MAIN OUTCOME MEASURES: Basal serum GH and IGF-I levels and GH levels 2 h after 75 g OGTT were measured. RESULTS: A total of 482 simultaneous OGTT and IGF-I measurements were observed from 1985--2008. Discordant results of oral glucose tolerance testing (GHn and IGF-I) were observed 33, 48, and 18% in postoperative assessment without medication, SA, and DA categories, respectively. In the SA category, 42% of tests were discordant with normal IGF-I and nonsuppressed GHn. In contrast, 4% of tests were discordant with normal IGF-I and nonsuppressed GH in those treated with DA. No significant differences in discordance were observed when basal GH was used. CONCLUSIONS: Both basal and GHn levels are highly discordant with IGF-I levels during medical therapy with SAs. The OGTT is not useful in assessing biochemical control in these subjects.