Combined treatment for acromegaly with long-acting somatostatin analogs and pegvisomant: long-term safety for up to 4.5 years (median 2.2 years) of follow-up in 86 patients.
BACKGROUND
We previously reported on the efficacy, safety, and quality of life (QoL) of long-acting somatostatin analogs (SSA) and (twice) weekly pegvisomant (PEG-V) in acromegaly and improvement after the addition of PEG-V to long-acting SSA.


OBJECTIVE
To assess the long-term safety in a larger group of acromegalic patients over a larger period of time: 29.2 (1.2-57.4) months (mean (range)).


METHODS
Pegvisomant was added to SSA monotherapy in 86 subjects (37 females), to normalize serum IGF1 concentrations (n=63) or to increase the QoL. The median dosage was 60.0 (20-200) mg weekly.


RESULTS
After a mean treatment period of 29.2 months, 23 patients showed dose-independent PEG-V related transient liver enzyme elevations (TLEE). TLEE occurred only once during the continuation of combination therapy, but discontinuation and re-challenge induced a second episode of TLEE. Ten of these patients with TLEE also suffered from diabetes mellitus (DM). In our present series, DM had a 2.28 odds ratio (CI 1.16-9.22; p=0.03) higher risk for developing TLEE. During the combined therapy, a clinical significant decrease in tumor size by more than 20% was observed in 14 patients. Two of these patients were previously treated by pituitary surgery, 1 with additional radiotherapy and all other patients received primary medical treatment.


CONCLUSIONS
Long-term combined treatment with SSA and twice weekly PEG-V up to more than 4 years seems to be safe. Patients with both acromegaly and DM have a 2.28 higher risk of developing TLEE. Clinical significant tumor shrinkage was observed in 14 patients during combined treatment.
Neggers
S J C M M
SJ
Department of Medicine, Erasmus University, Erasmus MC, Rotterdam, The Netherlands. s.neggers@erasmusmc.nl
de Herder
W W
WW
Janssen
J A M J L
JA
Feelders
R A
RA
van der Lely
A J
AJ
D000172:Acromegaly / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D048909:Diabetes Complications / Q000503:physiopathology; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D019382:Human Growth Hormone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000627:therapeutic use; D010456:Peptides, Cyclic / Q000627:therapeutic use; D011986:Receptors, Somatotropin / Q000037:antagonists & inhibitors*; D013004:Somatostatin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D055815:Young Adult
D010456:Peptides, Cyclic; D011986:Receptors, Somatotropin; C060347:lanreotide; D019382:Human Growth Hormone; D013004:Somatostatin; C406545:pegvisomant; D015282:Octreotide