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キーワード:
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要旨:
Background: Effective treatment of acromegaly with pegvisomant (PEGV), a
growth hormone receptor antagonist, requires an appropriate dose
titration. PEGV doses vary widely among individual patients, and various
covariates may affect its dosing and pharmacokinetics.
Objective: To identify predictors of the PEGV dose required to normalize
insulin-like growth factor I (IGF-I) levels during PEGV monotherapy and
in combination with long-acting somatostatin analogues (LA-SSAs).
Design: Two retrospective cohorts (Rotterdam + Lisge Acromegaly Survey
(LAS), total n = 188) were meta-analyzed as a form of external
replication to study the predictors of PEGV dosing in addition to
LA-SSA, the LAS (n = 83) was used to study the predictors of PEGV
monotherapy dosing. Multivariable regression models were used to
identify predictors of the PEGV dose required to normalize IGF-I levels.
Results: For PEGV dosing in combination with LA-SSA, IGF-I levels,
weight, height and age, were associated with the PEGV normalization
dosage (P = 0.001, P = 0.001, P = 0.028 and P = 0.047 respectively).
Taken together, these characteristics predicted the PEGV normalization
dose correctly in 63.3% of all patients within a range of +/- 60 mg/week
(21.3% within a range of +/- 20 mg/week). For monotherapy, only weight
was associated with the PEGV normalization dose (P = 0.001) and
predicted this dosage correctly in 77.1% of all patients within a range
of +/- 60 mg/week (31.3% within a range of +/- 20 mg/week).
Conclusion: In this study, we show that IGF-I levels, weight, height and
age can contribute to define the optimal PEGV dose to normalize IGF-I
levels in addition to LA-SSA. For PEGV monotherapy, only the patient's
weight was associated with the IGF-I normalization PEGV dosage.
