scholarly journals Which patients with acromegaly are treated with pegvisomant? An overview of methodology and baseline data in ACROSTUDY

2009 ◽  
Vol 161 (suppl_1) ◽  
pp. S11-S17 ◽  
Author(s):  
Thierry Brue ◽  
Frederic Castinetti ◽  
Frida Lundgren ◽  
Maria Koltowska-Häggström ◽  
Patrick Petrossians ◽  
...  
Keyword(s):  
Dopamine Agonists ◽  
Radiation Treatment ◽  
Gradual Increase ◽  
Somatostatin Analogues ◽  
Web Based ◽  
Gh Receptor ◽  
Gh Receptor Antagonist ◽  
Baseline Characteristics ◽  
Severity Of The Disease

Context Pegvisomant (Somavert, Pfizer Inc.) is the first and only available GH receptor antagonist. ACROSTUDY is an international surveillance study that offers inclusion in a web-based registry to all patients with acromegaly treated with pegvisomant; it aims at monitoring long-term safety and efficacy of this compound. Patients and methods This report summarizes the main baseline characteristics of this particular population of patients. In February 2009, over 300 centres in 10 countries had contributed 792 patients. A gradual increase in cumulative patient recruitment was observed since the launching of ACROSTUDY in 2004: from 116 patients in 2005, it steeply increased to 792 at the latest data freeze in February 2009. At the time of enrolment, 91.8% of patients were already treated with pegvisomant but baseline was considered at the time of pegvisomant start. IGF1 concentrations were measured at local laboratories. Results Of all patients, 80% were reported to have had surgery and 33% to have received radiation therapy. Of the 792 patients, 14% had received no prior medical treatment before pegvisomant start, 65.9% had received somatostatin analogues and 18.6% dopamine agonists. Interestingly, 66.7% had received only pegvisomant at study start, while it was taken in association with dopamine agonists in 5.7%, with somatostatin analogues in 23.4% and with both types of agents in 3.8%. Mean IGF1 at baseline was 522 ng/ml. Conclusion Analysis of the baseline features of these patients treated with pegvisomant and reported in the ACROSTUDY database underscores the severity of the disease in this subset of the population of patients with acromegaly previously unresponsive to several medical, surgical or radiation treatment approaches.

scholarly journals Increasing frequency of combination medical therapy in the treatment of acromegaly with the GH receptor antagonist pegvisomant

2018 ◽  
Vol 178 (4) ◽  
pp. 321-329 ◽  
Author(s):  
Christian J Strasburger ◽  
Anders Mattsson ◽  
Patrick Wilton ◽  
Ferah Aydin ◽  
Judith Hey-Hadavi ◽  
...  
Keyword(s):  
Clinical Care ◽  
Somatostatin Analogues ◽  
Treatment Modalities ◽  
Gh Receptor ◽  
Igf I ◽  
Gh Receptor Antagonist ◽  
Long Acting ◽  
Combination Regimens ◽  
To Receive

Pegvisomant monotherapy is effective and safe in treatment of acromegaly. However, some clinicians combine pegvisomant with somatostatin analogues (SSA) or dopamine agonist (DA). In this analysis of ACROSTUDY, a long-term non-interventional study, the use of combination regimens was evaluated. Based on their baseline treatment, 2043 patients were retrospectively categorized as: long-acting SSA combined with pegvisomant, ‘Combo SSA’ 768 patients (38%); DA combined with pegvisomant, ‘Combo DA’ 123 (6%); pegvisomant monotherapy, ‘Peg mono’ 1128 (55%). Treatment patterns changed over the 10-year period, with recent patients more likely to receive any combination (20% in 2003 vs 54% in 2012). Combo SSA use varied widely among countries from 22% to 78%. Exposure periods of the three treatment modalities were defined from pegvisomant start until the last visit in ACROSTUDY; patients could switch treatment categories. At year 4, IGF-I was normal in 62% of Combo SSA, 63% of Combo DA and 65% of Peg mono groups. Pegvisomant was initiated as daily injections in 94% of patients in the Peg mono group, 66% of Combo SSA and 91% of Combo DA patients. During 6169 years of treatment exposure, 3424 adverse events (AEs) were reported in 946 (51%) patients, of which 617 (18%) were serious and 401 (12%) were considered treatment related. The reported incidence of serious AEs and treatment-related non-serious AEs were similar among the three treatment modalities. This analysis describes real-world clinical care and shows favorable efficacy and safety for Peg mono and combinations. Novel findings include an increased use of combination therapy over time and variability in treatment modalities between countries.

scholarly journals Pegvisomant in combination with long-acting somatostatin analogues in acromegaly: the role of the GH receptor deletion of exon 3

2015 ◽  
Vol 173 (5) ◽  
pp. 553-561 ◽  
Author(s):  
S E Franck ◽  
A J van der Lely ◽  
P J D Delhanty ◽  
J O L Jørgensen ◽  
S J C M M Neggers
Keyword(s):  
Somatostatin Receptor ◽  
Serum Levels ◽  
Somatostatin Analogues ◽  
High Dose ◽  
Gh Receptor ◽  
Hardy Weinberg Equilibrium ◽  
Baseline Characteristics ◽  
Long Acting ◽  
Somatostatin Receptor Ligand

BackgroundDoses of the GH receptor (GHR) antagonist pegvisomant (PEGV) that normalize insulin-like growth factor 1 (IGF1) levels vary widely among acromegaly patients. Predictors for PEGV response are baseline IGF1 levels, sex, body weight and previous radiotherapy. A GHR polymorphism lacking exon 3 (d3-GHR) is frequent in the general population. The influence of d3-GHR on PEGV responsiveness in acromegaly is unclear.ObjectiveTo assess the influence of d3-GHR on IGF1 levels and PEGV responsiveness in acromegaly patients using combined PEGV and long-acting somatostatin receptor ligand (LA-SRIF) treatment.DesignData were collected at the Rotterdam Pituitary Centre between 2004 and 2013. Patients with elevated IGF1 levels (>1.2 upper limit of normal; n=112) and over 6 months of high-dose LA-SRIF treatment were co-treated with PEGV. GHR genotype was assessed using genomic DNA in 104 patients.ResultsD3-GHR was observed in 51 (49.0%) of the patients (7.7% homozygous, 41.3% heterozygous) and was in Hardy–Weinberg equilibrium (P=0.859). Baseline characteristics were similar in d3-GHR and full-length (fl)-GHR genotypes. During PEGV/LA-SRIF treatment IGF1 levels were not different between d3-carriers and non-carriers. Similarly, no difference in PEGV dose required to normalize IGF1 (P=0.337) or PEGV serum levels (P=0.433) was observed between the two groups. However, adenoma size decreased significantly (>20% of largest diameter) in 25.6% of the fl-GHR genotype but only in 7.5% of d3-carriers (P=0.034, OR: 4.6 (CI: 1.1–18.9)).ConclusionsGHR genotype does not predict the IGF1 normalizing dose of PEGV in acromegaly patients using combination PEGV/LA-SRIF treatment. However, fewer d3-carriers showed significant reductions in adenoma size.

Diagnosis and Management of Acromegaly in 2012

2010 ◽  
Vol 8 (1) ◽  
pp. 48
Author(s):  
Laurence Katznelson ◽  
Keyword(s):  
Medical Therapy ◽  
De Novo ◽  
Therapeutic Option ◽  
Premature Mortality ◽  
Somatostatin Analogues ◽  
Gh Secretion ◽  
Gh Receptor Antagonist ◽  
Failed Surgery ◽  
Multimodality Approach

Acromegaly is an insidious disease that, in most cases, is a result of a pituitary adenoma that hypersecretes growth hormone (GH). The goals of therapy are to control excess GH secretion and tumour growth, and to limit, if not reverse, the long-term medical consequences and risk of premature mortality associated with acromegaly. Surgery is the preferred primary therapeutic option because it can lead to rapid reductions in GH levels and prevent mass effects from local tumor growth. Medical therapy, including somatostatin analogues, dopamine agonists, and the GH receptor antagonist pegvisomant, is used most often in an adjuvant, secondary role for patients in whom surgery has been unsuccessful. Radiation therapy is most commonly recommended in the setting of failed surgery and lack of adequate control with medical therapy. A role of primary medical therapy for de novo patients has been proposed, particularly with somatostatin analogues. Using a multimodality approach, successful management of the disease and associated consequences should be achieved in the majority of subjects.

P341Which patients with atrial fibrillation undergo an ablation procedure today in Europe? A report from the ESC-EHRA-EURObservational Research Programme

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
R Tilz ◽  
N Dagres ◽  
E Arbelo ◽  
C H Blomstroem Lundqvist ◽  
E Pokushalov ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Research Programme ◽  
Web Based ◽  
Af Ablation ◽  
Atrial Size ◽  
Great Heterogeneity ◽  
Baseline Characteristics ◽  
Web Based System ◽  
Control Management

Abstract Aims Great heterogeneity in rhythm control management of patients with atrial fibrillation (AF) has been described. The aim of this study was to investigate how selective the patient cohort referred for AF ablation is, as compared to the general AF population in Europe, and to describe the governing mechanisms for such selection. Methods Descriptive comparative statistical analyses of the baseline characteristics were performed between the cohorts of Atrial Fibrillation Ablation Long-Term (ESC-EORP EHRA AFA-LT) Registry, designed to provide a picture of contemporary real-world AF ablation, and the AF population from the AF-General (ESC-EORP EHRA AF-Gen) PilotRegistry. Data collection was performed using a web-based system. Results In the AFA and in the AFG pilot registries 3593 and 3049 patients were enrolled, respectively. Patients who underwent AF ablation were younger,more commonly male, and had significantly less co-morbidities. Lone AF was predominant in AFA patients who were at lower risk of stroke (CHA2DS2-VASc >5: 2.9% vs. 24.5%, all P<0.001) and bleeding (HAS-BLED ≥2: 8.5% vs. 40.5%, P<0.001) but with EHRA scores >1 and more prevalentAF-related symptoms such as palpitations, fatigue and weakness (all p<0.001)as compared to the general AF patients. AFA patients were significantly more often male, had higher LV ejection fraction (59.5% vs. 52.4%) and smaller left atrial size on echocardiogram (P<0.001 each). Conclusions The comparison of the patient chorts in the AFA and AFG registries showed that AF ablation in European clinical practice is mostly performed in relatively young, symptomatic and otherwise relatively healthy patients. Acknowledgement/Funding Abbott Vascular Int.; Amgen Cardiovascular, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb and Pfizer Alliance

scholarly journals Acromegaly: A New Therapy

2002 ◽  
Vol 9 (3) ◽  
pp. 232-235 ◽  
Author(s):  
Keith E. Friend
Keyword(s):  
Dopamine Agonists ◽  
Serum Insulin ◽  
Therapeutic Option ◽  
Somatostatin Analogs ◽  
Treatment Modalities ◽  
Pharmacological Agents ◽  
Gh Receptor ◽  
Igf I ◽  
Gh Receptor Antagonist ◽  
Multimodality Approach

Background The treatment of acromegaly can be challenging. Despite a multimodality approach (surgery, radiation, dopamine agonists, somatostatin analogs), many patients do not achieve normalization of serum insulin-like growth factor I (IGF-I) concentrations. Methods The author discusses the characteristics and indications of pegvisomant therapy for patients with acromegaly and compares the use of this newly developed GH receptor antagonist with other pharmacological agents such as somatostatin and dopamine agonists. Results Therapy with pegvisomant allows serum IGF-I concentrations to be normalized in up to 97% of patients with acromegaly, including those who have failed other treatment modalities. With this agent, circulating GH levels increase as a result of the drop in IGF-I levels. The rise is rapid (within 2 weeks) and does not appear to be progressive over time. Conclusions Published studies have shown pegvisomant to have efficacy in the treatment of acromegaly. As it appears to be well tolerated and safe, this novel compound may be an important therapeutic option for patients with acromegaly. Additional study of this novel agent and its mode of action is warranted.

scholarly journals Pegvisomant: an advance in clinical efficacy in acromegaly

2003 ◽  
pp. S27-S32 ◽  
Author(s):  
PM Stewart
Keyword(s):  
Premature Mortality ◽  
Pituitary Tumour ◽  
Somatostatin Analogues ◽  
Sleep Apnoea ◽  
Subcutaneous Injections ◽  
Chronic Disorder ◽  
Igf I ◽  
Gh Receptor Antagonist ◽  
Symptomatic Control

Acromegaly is a chronic disorder invariably caused by a growth hormone (GH)-secreting pituitary tumour and is characterised by disabling symptoms (sweating, arthralgia, headache, paraesthesiae, fatigue), significant comorbidities (diabetes mellitus, hypertension, sleep apnoea), and premature mortality. Symptomatic control can be achieved by lowering insulin-like growth factor-I (IGF-I) concentrations to within the age-adjusted normal range, and survival can be improved to match that of the general population. However, even with optimal surgery and current medical therapies (dopamine agonists, somatostatin analogues), 30% to 50% of patients do not achieve target concentrations of IGF-I and GH. Pegvisomant is a new GH-receptor antagonist that blocks GH activity by inhibiting functional dimerisation of GH-receptors. Given as subcutaneous injections at dosages of 10 mg, 15 mg, or 20 mg/day for 3 Months, pegvisomant normalised serum IGF-I concentrations in, respectively, 54%, 81%, and 89% of acromegalic patients. Moreover, long-term pegvisomant therapy normalised IGF-I concentrations in 97% of patients treated for 12 Months or longer, with no evidence of tachyphylaxis. Pegvisomant is the most effective medical therapy, reported to date, in terms of normalisation of circulating IGF-I concentrations. In addition, pegvisomant appears to be safe and well tolerated. Although additional long-term studies are required to further assess safety, the introduction of this innovative treatment should allow for optimal disease control in patients with acromegaly.

Design and Development of a Web-based Delirium Preventive Application for Long-term Care Facilities: A Methodological Study (Preprint)

2020 ◽  
Author(s):  
Kyoung Ja Moon ◽  
Chang-Sik Son ◽  
Jong-Ha Lee ◽  
Mina Park
Keyword(s):  
Risk Factors ◽  
Long Term Care ◽  
Cloud System ◽  
Evidence Based ◽  
Methodological Study ◽  
Term Care ◽  
Web Based ◽  
Care Facilities ◽  
Delirium Prevention

BACKGROUND Long-term care facilities demonstrate low levels of knowledge and care for patients with delirium and are often not properly equipped with an electronic medical record system, thereby hindering systematic approaches to delirium monitoring. OBJECTIVE This study aims to develop a web-based delirium preventive application (app), with an integrated predictive model, for long-term care (LTC) facilities using artificial intelligence (AI). METHODS This methodological study was conducted to develop an app and link it with the Amazon cloud system. The app was developed based on an evidence-based literature review and the validity of the AI prediction model algorithm. Participants comprised 206 persons admitted to LTC facilities. The app was developed in 5 phases. First, through a review of evidence-based literature, risk factors for predicting delirium and non-pharmaceutical contents for preventive intervention were identified. Second, the app, consisting of several screens, was designed; this involved providing basic information, predicting the onset of delirium according to risk factors, assessing delirium, and intervening for prevention. Third, based on the existing data, predictive analysis was performed, and the algorithm developed through this was calculated at the site linked to the web through the Amazon cloud system and sent back to the app. Fourth, a pilot test using the developed app was conducted with 33 patients. Fifth, the app was finalized. RESULTS We developed the Web_DeliPREVENT_4LCF for patients of LTC facilities. This app provides information on delirium, inputs risk factors, predicts and informs the degree of delirium risk, and enables delirium measurement or delirium prevention interventions to be immediately implemented with a verified tool. CONCLUSIONS This web-based application is evidence-based and offers easy mobilization and care to patients with delirium in LTC facilities. Therefore, the use of this app improves the unrecognized of delirium and predicts the degree of delirium risk, thereby helping initiatives for delirium prevention and providing interventions. This would ultimately improve patient safety and quality of care. CLINICALTRIAL none

scholarly journals Long-term remission of acromegaly after somatostatin analogues withdrawal: a single-centre experience

2021 ◽  
Author(s):  
E. Sala ◽  
G. Carosi ◽  
G. Del Sindaco ◽  
R. Mungari ◽  
A. Cremaschi ◽  
...  
Keyword(s):  
Median Time ◽  
Pituitary Surgery ◽  
Somatostatin Analogues ◽  
Exclusion Criterion ◽  
Single Centre ◽  
Disease Evolution ◽  
Single Centre Experience ◽  
Pituitary Irradiation

Abstract Purpose A long-lasting remission of acromegaly after somatostatin analogues (SAs) withdrawal has been described in some series. Our aim was to update the disease evolution after SAs withdrawal in a cohort of acromegalic patients. Methods We retrospectively evaluated 21 acromegalic patients previously included in a multicentre study (Ronchi et al. 2008), updating data at the last follow-up. We added further 8 patients selected for SAs withdrawal between 2008–2018. Pituitary irradiation represented an exclusion criterion. The withdrawal was suggested after at least 9 months of clinical and hormonal disease control. Clinical and biochemical data prior and after SAs withdrawal were analysed. Results In the whole cohort (29 patients) mean age was 50 ± 14.9 years and 72.4% were females. In 69% pituitary surgery was previously performed. Overall, the median time of treatment before SAs withdrawal was 53 months (IQR = 24–84). At the last follow up in 2019, 23/29 patients (79.3%) had a disease relapse after a median time of 6 months (interquartile range or IQR = 3–12) from the drug suspension, while 6/29 (20.7%) were still on remission after 120 months (IQR = 66–150). IGF-1 levels were significantly lower before withdrawal in patients with persistent remission compared to relapsing ones (IGF-1 SDS: -1.5 ± 0.6 vs -0.11 ± 1, p = 0.01). We did not observe any other difference between patients with and without relapse, including SAs formulation, dosage and treatment duration. Conclusion A successful withdrawal of SAs is possible in a subset of well-controlled acromegalic patients and it challenges the concept that medical therapy is a lifelong requirement.

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