OBJECTIVE:For patients with acromegaly who are suboptimally controlled on long-actingoctreotide (LAR), treatment options are to switch to pegvisomant monotherapy (PM) or add pegvisomant to LAR (P-LAR). Our objective was to evaluate if the safety and efficacy of these regimens differ. DESIGN: This was an open-label, multicentre, randomized, 40-week outpatient study. The control arm consisted of patients controlled on LAR (n = 28). PATIENTS: A total of 27 patients with suboptimally controlled acromegaly [as indicated by a serum IGF-I level > or = 1.3 x upper limit of normal (ULN) of the age-related reference range] were randomized to PM (10 mg once daily initially, then adjusted in 5-mg increments every 8 weeks based on IGF-I levels) and 29 to P-LAR (LAR dosing remained fixed). MEASUREMENTS: The primary end-point was adverse events (AEs). The secondary end-point was biochemical IGF-I-based efficacy. The RIA for IGF-I was discontinued by the manufacturer during the study and a chemiluminescent assay was subsequently used. Previously obtained IGF-I levels were re-analysed. RESULTS:PM and P-LAR were well tolerated and there were no differences in the number of AEs. Patients receiving P-LAR tended to be more likely to have clinically significant increases in hepatic transaminase levels, especially those receiving high-dose LAR. Normalization of IGF-I was similar with both regimens (56% and 62% of patients for PM and P-LAR respectively). The change in IGF-I assay resulted in lower rates of IGF-I normalization than expected. Reductions in fasting glucose levels were greater with PM than with P-LAR (-0.8 mmol/l; 95% confidence interval -1.16, -0.53 mmol/l). CONCLUSIONS: In patients suboptimally controlled on LAR, PM and P-LAR were equally well tolerated and effective in normalizing IGF-I, and overall clinical improvement was observed with both regimens. Thus, pegvisomant monotherapy and adjunctive therapy are equally viable options for the treatment of LAR-resistant acromegaly.
RCT Entities:
OBJECTIVE: For patients with acromegaly who are suboptimally controlled on long-acting octreotide (LAR), treatment options are to switch to pegvisomant monotherapy (PM) or add pegvisomant to LAR (P-LAR). Our objective was to evaluate if the safety and efficacy of these regimens differ. DESIGN: This was an open-label, multicentre, randomized, 40-week outpatient study. The control arm consisted of patients controlled on LAR (n = 28). PATIENTS: A total of 27 patients with suboptimally controlled acromegaly [as indicated by a serum IGF-I level > or = 1.3 x upper limit of normal (ULN) of the age-related reference range] were randomized to PM (10 mg once daily initially, then adjusted in 5-mg increments every 8 weeks based on IGF-I levels) and 29 to P-LAR (LAR dosing remained fixed). MEASUREMENTS: The primary end-point was adverse events (AEs). The secondary end-point was biochemical IGF-I-based efficacy. The RIA for IGF-I was discontinued by the manufacturer during the study and a chemiluminescent assay was subsequently used. Previously obtained IGF-I levels were re-analysed. RESULTS: PM and P-LAR were well tolerated and there were no differences in the number of AEs. Patients receiving P-LAR tended to be more likely to have clinically significant increases in hepatic transaminase levels, especially those receiving high-dose LAR. Normalization of IGF-I was similar with both regimens (56% and 62% of patients for PM and P-LAR respectively). The change in IGF-I assay resulted in lower rates of IGF-I normalization than expected. Reductions in fasting glucose levels were greater with PM than with P-LAR (-0.8 mmol/l; 95% confidence interval -1.16, -0.53 mmol/l). CONCLUSIONS: In patients suboptimally controlled on LAR, PM and P-LAR were equally well tolerated and effective in normalizing IGF-I, and overall clinical improvement was observed with both regimens. Thus, pegvisomant monotherapy and adjunctive therapy are equally viable options for the treatment of LAR-resistant acromegaly.
Authors: M Ragonese; S Grottoli; P Maffei; A Alibrandi; M R Ambrosio; G Arnaldi; A Bianchi; S Puglisi; M C Zatelli; L De Marinis; E Ghigo; A Giustina; F Maffezzoni; C Martini; L Trementino; S Cannavo Journal: J Endocrinol Invest Date: 2017-10-28 Impact factor: 4.256
Authors: Andrea Giustina; Philippe Chanson; David Kleinberg; Marcello D Bronstein; David R Clemmons; Anne Klibanski; Aart J van der Lely; Christian J Strasburger; Steven W Lamberts; Ken K Y Ho; Felipe F Casanueva; Shlomo Melmed Journal: Nat Rev Endocrinol Date: 2014-02-25 Impact factor: 43.330
Authors: Katja Kiseljak-Vassiliades; Shibana Shafi; Janice M Kerr; Tzu L Phang; B K Kleinschmidt-DeMasters; Margaret E Wierman Journal: Endocrine Date: 2012-03-21 Impact factor: 3.633
Authors: Rudolf Fahlbusch; David Kleinberg; Beverly Biller; Vivien Bonert; Michael Buchfelder; Paolo Cappabianca; John Carmichael; William Chandler; Annamaria Colao; Ajax George; Anne Klibanski; Edmond Knopp; Juergen Kreutzer; Neehar Kundurti; Martin Lesser; Adam Mamelak; Rosario Pivonello; Kalmon Post; Brooke Swearingen; Mary Lee Vance; Ariel Barkan Journal: Pituitary Date: 2017-12 Impact factor: 4.107