Medical Treatments for Acromegaly: A Systematic Review and Network Meta-Analysis

Leonart, Letícia Paula; Ferreira, Vinicíus Lins; Tonin, Fernanda S.; Fernández-Llimós, Fernando; Pontarolo, Roberto

doi:10.1016/j.jval.2017.12.014

Cited by 15 publications

(14 citation statements)

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“…The efficacy of drugs was retrieved from a systematic review [8] and a clinical trial [30]. In both publications, treatment efficacy was defined as the achievement of IGF-1 normal levels for sex and age.…”

Section: Methodsmentioning

confidence: 99%

“…The drugs used in acromegaly treatment include the first-generation somatostatin analogues (SSAs) octreotide LAR and lanreotide autogel, the second-generation SSA pasireotide, and the GH receptor antagonist pegvisomant. Dopamine agonists such as cabergoline are also used in clinical practice, but their efficacy has never been assessed in clinical trials [8]. The first-generation SSAs are usually employed as a first-line strategy, and pasireotide or pegvisomant are only used if disease control is not achieved, usually because they are more expensive [9, 7].…”

Section: Introductionmentioning

confidence: 99%

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Pharmacological Acromegaly Treatment: Cost-Utility and Value of Information Analysis

et al. 2020

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Objectives: To conduct a cost-utility analysis comparing drug strategies involving octreotide, lanreotide, pasireotide, and pegvisomant for the treatment of patients with acromegaly who have failed surgery, from a Brazilian public payer perspective. Methods: A probabilistic cohort Markov model was developed. One-year cycles were employed. The patients started at 45 years of age and were followed lifelong. Costs, efficacy, and quality of life parameters were retrieved from the literature. A discount rate (5%) was applied to both costs and efficacy. The results were reported as costs per quality-adjusted life year (QALY), and incremental cost-effectiveness ratios (ICERs) were calculated when applicable. Scenario analyses considered alternative dosages, discount rate, tax exemption, and continued use of treatment despite lack of response. Value of information (VOI) analysis was conducted to explore uncertainty and to estimate the costs to be spent in future research. Results: Only lanreotide showed an ICER reasonable for having its use considered in clinical practice (R$ 112,138/US$ 28,389 per QALY compared to no treatment). Scenario analyses corroborated the base-case result. VOI analysis showed that much uncertainty surrounds the parameters, and future clinical research should cost less than R$ 43,230,000/US$ 10,944,304 per year. VOI also showed that almost all uncertainty that precludes an optimal strategy choice involves quality of life. Conclusions: With current information, the only strategy that can be considered cost-effective in Brazil is lanreotide treatment. No second-line treatment is recommended. Significant uncertainty of parameters impairs optimal decision-making, and this conclusion can be generalized to other countries. Future research should focus on acquiring utility data.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pharmacological Acromegaly Treatment: Cost-Utility and Value of Information Analysis

et al. 2020

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“…PEG is very well tolerated and efficacious, making it a preferred medication for acro-megaly therapy. However, high cost and route of administration can produce practical limitations [78]. The cost of treatment for patients taking PEG is high [79]; exceeding that of SRLs by 3-4 times [79,80].…”

Section: Acromegalymentioning

confidence: 99%

Updates in the Medical Treatment of Pituitary Adenomas

2019

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Pituitary adenomas represent approximately 15% of brain tumors; incidence is significantly on the increase due to widespread use of magnetic resonance imaging. Surgery remains the first-line treatment for most tumors overall. The role of dopaminergic agonists (DAs) and somatostatin receptor ligands (SRLs) in the treatment of pituitary adenomas is quite well established for prolactinomas and growth hormone (GH) excess. However, over the last decade new multi-receptor binding SRLs are increasingly used for treatment of acromegaly and Cushing’s disease. SRLs/DA chimeric compounds seem to have enhanced potency and efficacy when compared to that of individual SRLs or DA receptor agonists according to preclinical data. However, following negative results, more research is needed to determine if this interesting mechanism will translate into positive clinical effects for acromegaly patients. Furthermore, new agents that block adrenal steroidogenesis have been developed in phase III clinical trials for Cushing’s disease and several new compounds working at the pituitary level and/or blocking the glucocorticoid receptor are also in development. Combination therapy of drugs with similar or different mechanisms (possibly synergistic) are also on the increase. A growing awareness regarding all mechanisms involved in both control of pituitary secretion and cellular proliferation might allow for sole medical treatment of pituitary adenomas, especially macroadenomas, rather than surgery and/or radiation therapy, in the future. Moreover, the underlying decision on how to treat patients with pituitary adenomas should be individualized on a case-by-case basis with not only a goal of tumor shrinkage and biochemical control, but also of improving patients’ quality of life.

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“…The report of the 2007 meeting concluded that the use of SRLs is most appropriate as first-line therapy when there is a low probability of a surgical cure (4). Leonart et al recently reported the results of a systematic review of 2059 articles of which they included ten randomized controlled trials in a qualitative analysis and seven in a quantitative analysis to conduct the first network meta-analysis simultaneously, comparing all available drugs used in acromegaly treatment so as to provide more robust evidence in this field (5). The network meta-analysis for the efficacy outcome (number of patients achieving IGF-1 control) showed that, not surprisingly, PEGV and lanreotide Autogel ® were statistically superior to placebo (5).…”

Section: Introductionmentioning

confidence: 99%

“…Leonart et al recently reported the results of a systematic review of 2059 articles of which they included ten randomized controlled trials in a qualitative analysis and seven in a quantitative analysis to conduct the first network meta-analysis simultaneously, comparing all available drugs used in acromegaly treatment so as to provide more robust evidence in this field (5). The network meta-analysis for the efficacy outcome (number of patients achieving IGF-1 control) showed that, not surprisingly, PEGV and lanreotide Autogel ® were statistically superior to placebo (5). The probability rank indicated that PEGV and pasireotide have the highest probabilities (33 and 34%, respectively) of being the best therapeutic option (5).…”

Section: Introductionmentioning

confidence: 99%

Pegvisomant and not somatostatin receptor ligands (SRLs) is first-line medical therapy for acromegaly

Lely

Kuhn

Muhammad

et al. 2020

European Journal of Endocrinology

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Current guidelines recommend the use of long-acting somatostatin receptor ligands (SRLs) first when surgery fails to correct GH/IGF-I hypersecretion in patients with acromegaly. In this issue of the journal, a pro- and contra debate will outline which arguments are in favour and which are against positioning pegvisomant (PEGV), a GH receptor antagonist, as the first-line treatment modality of acromegaly. The task of the pros was to promote a paradigm shift towards repositioning PEGV as first-line treatment as PEGV is safe and more effective than the first- and second-generation of SRLs. SRLs, when prescribed together with PEGV can still reduce tumour size when necessary, while they decrease the necessary dose of PEGV by around 50% in the average patient. They conclude that PEGV must move up towards the first-line treatment. For the cons, SRLs remain the first-line medical treatment. Indeed, even if, in recent studies, the remission rate is lower than initially claimed, SRLs are still effective not only for normalizing GH/IGF-I levels in half of the patients but also for inducing tumour shrinkage, improving comorbidities and headaches and reversing excess mortality. They are more convenient for use with their monthly administration and have a remarkable safety profile as demonstrated by the very prolonged experience acquired by more than 30 years of use. Finally, the cost-effectiveness of first-generation SRLs is better than that of PEGV. For all these reasons, cons consider that SRLs remain the best first medical treatment in patients requiring medical therapy.

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Medical Treatments for Acromegaly: A Systematic Review and Network Meta-Analysis

Abstract: Pegvisomant is still a good option for acromegaly treatment, but pasireotide seems to be a promising alternative. Nevertheless, other important key factors such as drug costs and effectiveness (real-world results) should be taken into account when selecting acromegaly treatment.

Cited by 15 publications

References 59 publications

Pharmacological Acromegaly Treatment: Cost-Utility and Value of Information Analysis

Pharmacological Acromegaly Treatment: Cost-Utility and Value of Information Analysis

Updates in the Medical Treatment of Pituitary Adenomas

Pegvisomant and not somatostatin receptor ligands (SRLs) is first-line medical therapy for acromegaly

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