Long-term efficacy and safety of combined treatment of somatostatin analogs and pegvisomant in acromegaly.
BACKGROUND
We previously reported the efficacy of a combined treatment of active acromegaly with both long-acting somatostatin analogs (SSA) and pegvisomant (PEG-V).


OBJECTIVE
Our objective was to assess long-term efficacy and safety in a larger group of acromegalic patients after a period of 138 (35-149) wk [median (range)].


METHODS
PEG-V was added to high-dose SSA treatment in 32 subjects (13 females) who had not shown a normalization in serum IGF-I concentrations during SSA monotherapy. PEG-V dosage was increased until IGF-I concentration normalized. The maximal dose was 80 mg twice weekly.


RESULTS
After dose finding, IGF-I remained within the normal range in all subjects with PEG-V administered once (n = 24) or twice (n = 8) weekly, on a total weekly dose of 60 (40-160) mg. Baseline IGF-I levels were positively correlated with the required dosage of PEG-V (r = 0.48; P = 0.006). PEG-V-dependent liver enzyme disturbances were observed in 11 (6 diabetic) subjects, of which symptomatic gallstones explained two cases. These liver enzyme disturbances were transient in all subjects without discontinuation or dose adaptation of PEG-V. In our series, diabetic patients had a 5.1 times (odds ratio) (confidence interval, 1.02-25.54; P < 0.05) higher risk for developing liver enzyme disturbances. These liver enzyme disturbances seemed to occur earlier. Pituitary adenoma size decreased in four patients. No increase in tumor size was observed in any of the patients.


CONCLUSIONS
Long-term combined treatment with long-acting SSA and (twice) weekly PEG-V for active acromegaly seems to be effective and safe. Patients with acromegaly and diabetes seem to have a higher risk of developing transient liver enzyme disturbances.
Neggers
Sebastian J C M M
SJ
Department of Internal Medicine, Erasmus University MC Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands. s.neggers@erasmusmc.nl
van Aken
Maarten O
MO
Janssen
Joop A M J L
JA
Feelders
Richard A
RA
de Herder
Wouter W
WW
van der Lely
Aart-Jan
AJ
D000172:Acromegaly / Q000188:drug therapy* / Q000523:psychology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D048909:Diabetes Complications / Q000150:complications / Q000188:drug therapy; D003920:Diabetes Mellitus / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006727:Hormone Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D019382:Human Growth Hormone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D013004:Somatostatin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*
D006727:Hormone Antagonists; D019382:Human Growth Hormone; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; C406545:pegvisomant