A randomized, controlled, multicentre trial comparing pegvisomant alone with combination therapy of pegvisomant and long-acting octreotide in patients with acromegaly.

2.50
Hdl Handle:
http://hdl.handle.net/10541/81975
Title:
A randomized, controlled, multicentre trial comparing pegvisomant alone with combination therapy of pegvisomant and long-acting octreotide in patients with acromegaly.
Authors:
Trainer, Peter J; Ezzat, Shereen; D'Souza, Gwyn A; Layton, Gary; Strasburger, Christian J
Abstract:
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.
Affiliation:
Department of Endocrinology, Christie Hospital, Wilmslow Road, Manchester, UK. Peter.Trainer@manchester.ac.uk
Citation:
A randomized, controlled, multicentre trial comparing pegvisomant alone with combination therapy of pegvisomant and long-acting octreotide in patients with acromegaly. 2009, 71 (4):549-57 Clin. Endocrinol.
Journal:
Clinical Endocrinology
Issue Date:
Oct-2009
URI:
http://hdl.handle.net/10541/81975
DOI:
10.1111/j.1365-2265.2009.03620.x
PubMed ID:
19438906
Type:
Article
Language:
en
ISSN:
1365-2265
Appears in Collections:
All Christie Publications ; Endocrinology

Full metadata record

DC FieldValue Language
dc.contributor.authorTrainer, Peter J-
dc.contributor.authorEzzat, Shereen-
dc.contributor.authorD'Souza, Gwyn A-
dc.contributor.authorLayton, Gary-
dc.contributor.authorStrasburger, Christian J-
dc.date.accessioned2009-09-22T09:23:06Z-
dc.date.available2009-09-22T09:23:06Z-
dc.date.issued2009-10-
dc.identifier.citationA randomized, controlled, multicentre trial comparing pegvisomant alone with combination therapy of pegvisomant and long-acting octreotide in patients with acromegaly. 2009, 71 (4):549-57 Clin. Endocrinol.en
dc.identifier.issn1365-2265-
dc.identifier.pmid19438906-
dc.identifier.doi10.1111/j.1365-2265.2009.03620.x-
dc.identifier.urihttp://hdl.handle.net/10541/81975-
dc.description.abstractOBJECTIVE: 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.en
dc.language.isoenen
dc.subjectPegvisomanten
dc.subjectCombination Therapyen
dc.subjectAcromegalyen
dc.subjectTreatment Optionsen
dc.titleA randomized, controlled, multicentre trial comparing pegvisomant alone with combination therapy of pegvisomant and long-acting octreotide in patients with acromegaly.en
dc.typeArticleen
dc.contributor.departmentDepartment of Endocrinology, Christie Hospital, Wilmslow Road, Manchester, UK. Peter.Trainer@manchester.ac.uken
dc.identifier.journalClinical Endocrinologyen

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