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How to improve effectiveness of pegvisomant treatment in acromegalic patients

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Abstract

Purpose

Pegvisomant (PEGV) treatment in acromegaly patients resistant to somatostatin analogues is less effective in the real life than in clinical trials. This is a multicenter, observational, retrospective, longitudinal study. The aim was to detect characteristics which improve long-term PEGV effectiveness.

Methods

87 acromegalic patients treated with PEGV have been enrolled in seven referral Italian centres. PEGV was administered for up to 4 years, at doses up titrated until IGF-1 normalization or to ≥ 30 mg/day. The rate of patients who reached IGF-1 normalization at last visit has been calculated.

Results

IGF-1 was normalized in 75.9% of patients after 1 year and in 89.6% at last visit. Disease control was associated with lower baseline GH, IGF-1 and IGF-1 xULN and was more frequent when baseline IGF-1 was < 2.7 × ULN (p < 0.02). PEGV dose was dependent on baseline IGF-1 > 2.7 × ULN (p < 0.05) and doses > 1.0 mg/BMI/day were administered more frequently when baseline IGF-1 was > 2.0 × ULN (p = 0.03). PEGV resistance was associated with higher BMI (p = 0.006) and was more frequent when BMI was > 30 kg/m2 (p = 0.07). There were no significant differences between patients treated with monotherapy or combined treatment. IGF-1 normalization, PEGV dose and rate of associated treatment were similar between males and females. PEGV effectiveness was independent from previous management. Diabetic patients needed higher doses of PEGV than non-diabetic ones.

Conclusions

PEGV effectiveness improves when up titration is appropriate. Higher PEGV doses at start and a more rapid up-titration are necessary in patients with obesity and/or IGF-1 > 2.7 × ULN.

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Funding

This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

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Authors and Affiliations

  1. Dipartimento di Patologia Umana dell’adulto e dell’età evolutiva “G. Barresi”, AOU Policlinico G. Martino, University of Messina, Via Consolare Valeria, 1, 98125, Messina, Italy

    M. Ragonese, S. Puglisi & S. Cannavo

  2. Divisione di Endocrinologia, Diabetologia E Metabolismo, Dipartimento di Scienze Mediche, AO Città Della Salute E Della Scienza di Torino, Università di Torino, Turin, Italy

    S. Grottoli & E. Ghigo

  3. Dipartimento di Medicina, AO di Padova, Padua, Italy

    P. Maffei & C. Martini

  4. Dipartimento di Economia, Sezione di Scienze Statistiche E Matematiche, Università di Messina, Messina, Italy

    A. Alibrandi

  5. Dipartimento di Scienze Mediche, Sezione di Endocrinologia E Medicina Interna, Università di Ferrara, Ferrara, Italy

    M. R. Ambrosio & M. C. Zatelli

  6. SOD Clinica di Endocrinologia E Malattie Del Metabolismo, AOU Ospedali Riuniti di Ancona, Università di Ancona, Torrette, Ancona, Italy

    G. Arnaldi & L. Trementino

  7. UOS Patologia Ipofisaria, Istituto di Patologia Medica, Policlinico Universitario A. Gemelli, Rome, Italy

    A. Bianchi & L. De Marinis

  8. Struttura Ambulatoriale di Endocrinologia, AO Spedali Civili di Brescia, Università di Brescia, Brescia, Italy

    A. Giustina & F. Maffezzoni

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  1. M. Ragonese
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  2. S. Grottoli
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Corresponding author

Correspondence to S. Cannavo.

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Conflict of interest

SP, AA, MRA, GA, AB, MCZ, LDM, EG, FM, CM and LT nothing to disclosure. SG, PM consultants for Pfizer. AG consultant for IPSEN, Novartis and Pfizer. SC consultant for Pfizer, Novartis and Italfarmaco, MR consultant for Italfarmaco.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Ragonese, M., Grottoli, S., Maffei, P. et al. How to improve effectiveness of pegvisomant treatment in acromegalic patients. J Endocrinol Invest 41, 575–581 (2018). https://doi.org/10.1007/s40618-017-0773-0

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  • DOI: https://doi.org/10.1007/s40618-017-0773-0

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