pegvisomant
Sources réglementaires consultées
Indications approuvées
- Acromégalie chez l’adulte ayant une réponse insuffisante à la chirurgie/radiothérapie et chez qui les analogues de la somatostatine ne normalisent pas l’IGF-I ou ne sont pas tolérés.
Contre-indications
Absolues
- Hypersensibilité.
Mises en garde cliniques
- Mise en garde majeure · Mesurer ALAT, ASAT, bilirubine et phosphatases alcalines avant le traitement puis périodiquement ; arrêter et évaluer en cas d’atteinte hépatique. — CIMA/AEMPS, ficha técnica 02240001
- Mise en garde majeure · Surveiller la tumeur hypophysaire en raison d’une possible expansion et ajuster uniquement selon l’IGF-I, et non la GH, car le pegvisomant interfère avec les dosages de GH. — CIMA/AEMPS, ficha técnica 02240001
Interactions médicamenteuses
- SévèreInsuline ou hypoglycémiants oraux
Mécanisme: Le pegvisomant améliore la sensibilité à l’insuline et peut augmenter le risque d’hypoglycémie.
Recommandation: Surveiller la glycémie et envisager de réduire le traitement hypoglycémiant.
CIMA/AEMPS, ficha técnica 02240001https://cima.aemps.es/cima/dochtml/ft/02240001/FT_02240001.html
Effets indésirables
Communs (≥1%)
Céphalées · Arthralgie · Diarrhée · Réaction au site d’injection · Œdème périphérique
Rares mais graves
Atteinte hépatique · Expansion de la tumeur hypophysaire · Anaphylaxie ou réaction anaphylactoïde · Hypoglycémie
Grossesse et allaitement
Non recommandé pendant la grossesse ni chez les femmes en âge de procréer sans contraception. Ne pas utiliser pendant l’allaitement ; celui-ci peut se poursuivre si le pegvisomant est arrêté.
Bibliographie récente (PubMed)
Acromegaly is typically caused by a growth hormone-secreting pituitary adenoma, driving excess secretion of insulin-like growth factor 1. Acromegaly may result in a variety of cardiovascular, respiratory, endocrine, metabolic, musculoskeletal, and neoplastic comorbidities. Early diagnosis and adequate treatment are essential to mitigate excess mortality associated with acromegaly. PubMed searches were conducted using the keywords growth hormone, acromegaly, pituitary adenoma, diagnosis, treatment, pituitary surgery, medical therapy, and radiation therapy (between 1981 and 2021). The diagnosis of acromegaly is confirmed on biochemical grounds, including elevated serum insulin-like growth factor 1 and lack of growth hormone suppression after glucose administration. Pituitary magnetic resonance imaging is advised in patients with acromegaly to identify an underlying pituitary adenoma. Transsphenoidal pituitary surgery is generally first-line therapy for patients with acromegaly. However, patients with larger and invasive tumors (macroadenomas) are often not in remission postoperatively. Medical therapies, including somatostatin receptor ligands, cabergoline, and pegvisomant, can be recommended to patients with persistent disease after surgery. Select patients may also be candidates for preoperative medical therapy. In addition, primary medical therapy has a role for patients without mass effect on the optic chiasm who are unlikely to be cured by surgery. Clinical, endocrine, imaging, histologic, and molecular markers may help predict the response to medical therapy; however, confirmation in prospective studies is needed. Radiation therapy is usually a third-line option and is increasingly administered by a variety of stereotactic techniques. An improved understanding of the pathogenesis of acromegaly may ultimately lead to the design of novel, efficacious therapies for this serious condition.
The 15th Acromegaly Consensus Conference in September 2023 updated recommendations on therapeutic outcomes for acromegaly. Since the publication of medical management guidelines in 2018, new pharmacological agents and new treatment approaches have been developed. Fifty-two experts in the management of acromegaly reviewed the current literature and assessed changes in drug approvals, clinical practice standards and management. Current outcome goals were considered, with a focus on the effect of current and emerging somatostatin receptor ligands, the growth hormone receptor antagonist pegvisomant and the dopamine agonist cabergoline on biochemical control, clinical control, adenoma mass and surgical outcomes. Participants assessed factors that determine pharmacological choices, as well as the proposed use of each agent. Here, we present consensus recommendations highlighting how an evidence-based acromegaly management algorithm could be optimized in clinical practice. Limited data indicate that pegvisomant is poorly excreted into breastmilk. Because pegvisomant is not orally absorbed, it is unlikely to adversely affect the breastfed infant. Polyethylene glycol is not excreted into breastmilk.[1]
Acromegaly is due in almost all cases to a GH-secreting pituitary tumor. GH and IGF-1 excesses lead to its multi-system clinical manifestations and comorbidities. Acromegaly is under-diagnosed and typically presents with advanced disease. When early or mild, clinical recognition and biochemical confirmation are especially challenging. Individualized treatment may optimize patient outcome. This review covers challenges to diagnosing acromegaly and reviews therapies for acromegaly with a focus on those aspects that can be individualized. The first step in diagnosing acromegaly is recognizing it clinically. To improve this, increase awareness and education of the general population and healthcare professionals about the acromegaly phenotype is needed. Once suspected clinically, IGF-1 measurement is the initial step in making the biochemical diagnosis. GH may be < 1.0 µg/L after oral glucose suppression in early/mild cases. GH and IGF-1 should be considered in concert. Providers should be aware of conditions that can alter GH and IGF-1 levels and each assay's performance. An individualized treatment approach is best employed. Surgery is preferred as initial treatment and medical therapy as initial adjuvant therapy. In individualizing therapy, the advantages and disadvantages of each option and predictors of response to them should be considered.
Somatotroph adenomas are usually controlled with standard therapy, which can include surgery, medical treatment and radiotherapy. Some tumors have a more aggressive behavior and are refractory to standard therapy. In this review, we summarize the phenotype of these tumors and the current options for their management.