One-year follow-up of patients with acromegaly treated with fixed or titrated doses of lanreotide Autogel®

OBJECTIVE Somatostatin analogue treatment is first-line medical therapy for acromegaly. This study compared the efficacy and tolerability of titrated doses of the long-acting somatostatin analogue preparation lanreotide Autogel((R)) with fixed doses and with lanreotide prolonged release (PR) 30 mg microparticles. PATIENTS Patients entering the initial study had received a diagnosis of active acromegaly within the previous 5 years. DESIGN This open, comparative, multicentre study was a 1-year extension of a previous trial during which patients with acromegaly had switched from lanreotide PR 30 mg microparticles injected intramuscularly every 7, 10 or 14 days, for at least 3 months, to one of three fixed doses of lanreotide Autogel((R)) (120, 90, or 60 mg every 28 days, respectively). In this extension study, patients continued to receive 60, 90, or 120 mg of lanreotide Autogel((R)) by deep subcutaneous injection every 28 days for 1 year. Doses could be titrated at entry or after four or eight injections, according to the GH/IGF-I response (dose increased if GH > 2.5 mug/l, or decreased if GH < 1 mug/l with normal IGF-I). MEASUREMENTS Mean +/- SEM GH and IGF-I concentrations were analysed and gallbladder echography performed at weeks 0, 16, 32, and 48. Acromegaly symptoms were recorded monthly and tolerance and side-effects were monitored throughout the study. RESULTS In total, 130 patients entered this extension phase. After 1 year of treatment with titrated doses of lanreotide Autogel((R)), mean GH (2.4 +/- 0.2 mug/l) and IGF-I (287 +/- 12 mug/l) concentrations were significantly lower than with lanreotide microparticles (GH, 2.8 +/- 0.2 mug/l, P < 0.001; IGF-I, 332 +/- 15 mug/l, P < 0.01) or with fixed-dose lanreotide Autogel((R)) (GH, 3.0 +/- 0.2 mug/l, P < 0.001; IGF-I, 310 +/- 14 mug/l, P = 0.02). GH hypersecretion was reduced to less than or equal to 2.5 mug/l in 68% of patients with titrated-dose lanreotide Autogel((R)) compared with 49% with microparticles (P < 0.001) and 56% with fixed-dose lanreotide Autogel((R)) (P less than or equal to 0.005). In the 65 patients who did not require any dose titration, there was no substantial change in serum lanreotide concentration, GH or IGF-I levels over the 12-month study duration. Acromegaly was effectively controlled (GH less than or equal to 2.5 mug/l and normalized IGF-I) in significantly more patients (43%) compared with microparticles (32%; P < 0.05). There was a trend for improved control of acromegalic symptoms with dose titration, whereas the incidence of gastrointestinal symptoms and local tolerance was similar with lanreotide Autogel((R)) and lanreotide microparticles. Gallbladder echographies showed new lithiasis in 8% of lanreotide Autogel((R)) patients. CONCLUSION Dose titration of lanreotide Autogel((R)) improved GH and IGF-I control in patients with acromegaly beyond that achieved using fixed doses of lanreotide Autogel((R)) or lanreotide microparticles. Titrated long-term lanreotide Autogel((R)) treatment is well tolerated.