Optimal use of pegvisomant in acromegaly: are we getting there?

Abstract

Several consensus statements on the medical management of acromegaly are available [1–4]. In fact, acromegaly due to growth hormone (GH)-secreting pituitary adenoma although quite rare is a serious clinical condition due to a concomitance of factors: surprisingly persistent diagnostic delay which leads to high prevalence of macroadenomas at diagnosis and in turn to difficult surgical radicality [5]; severe complications affecting multiple GH/insulin-like growth factor 1 (IGF-1) target organs with impaired quality of life and increased mortality risk [6–11]; biological aggressiveness/invasiveness of the neoplasm [12] and variability of the GH and IGF-1 responses to medical treatment [1–3]. In fact, use as recommended of conventional treatment tools (surgery, somatostatin receptor ligands—SRLs, and even radiotherapy) may lead to ‘‘cure’’ of the disease [13–16] which, however, despite their appropriate and also combined use may not be adequately controlled in a relevant part of acromegaly patients [17, 18]. Therefore, the advent of pegvisomant, which acts at the tissue level blocking the GH receptor and GH action, in the clinical scenario more than a decade ago has been surrounded by many hopes and expectations for a potential global control of acromegaly [19]. However, despite accumulating clinical experience and ad hoc designed surveillance studies specific guidelines for pegvisomant in acromegaly are limited [20], and its use appears still not always to be optimal. Why? In this issue of Endocrine, Grottoli et al. report data from acromegaly patients who have been included in the Italian Acrostudy registry [21] a world-wide non-interventional, post-marketing surveillance study initiated in 2004 not only to monitor mainly the safety but also outcomes of pegvisomant in clinical practice [22]. This single country experience (which adds to the long-term one obtained in Germany) [23] performed on a relevant number of patients ([300) with a long-term follow-up period ([4 years) offers some hints that may help to elaborate on this topic. First of all, although the surveillance study is global in its design data reported come prevalently from centers that have large experience with this treatment modality. In fact, despite patients being enrolled in 25 different sites more than a half were enrolled in 6 centers. This aspect, which is somewhat expected since current indications for pegvisomant use are focused on acromegaly patients ‘‘resistant to other treatments,’’ has double implications: on one side, this means that use of the drug is still likely confined to difficult long standing (mean duration of acromegaly before pegvisomant start was 8 years) acromegaly patients who are seen in very selected institutions, and therefore, most endocrine centers have a very limited experience with the drug; on the other side, this implies that Acrostudy data are really the best available reflecting the practice of endocrinologists with the largest experience with this treatment. Interestingly, slightly less than one quarter of the patients in this Italian experience were only treated medically before starting pegvisomant [21]. In fact, the main safety issue with pegvisomant so far, that greatly limited its use in clinical practice, has been the concern of a potential tumor (re)growth. Bases for this concern ranged from the concept that the pituitary was not the target of treatment to potential Nelson syndrome-like effect on the GH-secreting tumor of the negative feed-back induced by the lowering of IGF-1 A. Giustina (&) Chair of Endocrinology, University of Brescia, A.O. Spedali Civili, Via Biseo 17, 25123 Brescia, Italy e-mail: a.giustina@libero.it