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 Acromegaly: recent progress in diagnostics and treatment

2011 ◽  
Vol 57 (1) ◽  
pp. 46-59 ◽  
Author(s):  
N N Molitvoslovova
Keyword(s):  
Recent Progress ◽  
New Technologies ◽  
Somatostatin Analogs ◽  
Normal Range ◽  
Gh Receptor ◽  
Modern Methods ◽  
Igf I ◽  
Gh Receptor Antagonist ◽  
Serious Disease ◽  
Long Acting

Acromegaly is a serious disease with different complications leads to reduced life expectancy and increase mortality. Only early diagnosis and modern methods of management of disease lead to remission. According to consensus on criteria for cure of acromegaly (2010) the measurement of GH and age-matched total IGF-I concentrations are the most important biochemical variables for the diagnosis of acromegaly and for monitoring progression or treatment response. The optimal disease control is now defined as IGF-I level in the age – adjusted normal range, random GH levels less than 1,0 µg/liter and nadir GH level during OGTT less than 0,4 µg/liter. MRI with use a contract substance is the best method of adenoma visualization. The trassphenoidal surgery with new technologies (endoscope, intraoperative blood sampling, neuronavigation, intraoperative MRI), radiosurgery, modern medical treatment (multiligand long-acting somatostatin analogs, GH receptor antagonist) are effective modalities for treatment of acromegaly, which elaborated last decades.

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 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.

scholarly journals Efficacy and safety of switching to pasireotide in acromegaly patients controlled with pegvisomant and somatostatin analogues: PAPE extension study

2018 ◽  
Vol 179 (5) ◽  
pp. 269-277 ◽  
Author(s):  
Ammar Muhammad ◽  
Eva C Coopmans ◽  
Patric J D Delhanty ◽  
Alof H G Dallenga ◽  
Iain K Haitsma ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Secretion ◽  
Somatostatin Analogues ◽  
Tolerance Test ◽  
Extension Study ◽  
Oral Glucose ◽  
Efficacy And Safety ◽  
Igf I ◽  
Core Study ◽  
Long Acting

ObjectiveTo assess the efficacy and safety after 48 weeks of treatment with pasireotide long-acting-release (PAS-LAR) alone or in combination with pegvisomant in patients with acromegaly. In addition, we assessed the relation between insulin secretion and pasireotide-induced hyperglycemia.DesignThe PAPE extension study is a prospective follow-up study until 48 weeks after the core study of 24 weeks.MethodsFifty-nine out of 61 patients entered the extension study. Efficacy was defined as the percentage of patients achieving IGF-I normalization (≤1.2× the upper limit of normal (ULN)) at 48 weeks through protocol-based adjustment of pegvisomant and PAS-LAR doses. At baseline, insulin secretion was assessed by an oral glucose tolerance test (OGTT).ResultsAt the end of the study, median IGF-I was 0.98× ULN, and 77% of patients achieved normal IGF-I levels with a mean pegvisomant dose of 64 mg/week, and an overall cumulative pegvisomant dose reduction of 52%. Frequency of diabetes mellitus increased from 68% at 24 weeks to 77% at 48 weeks, and nine patients discontinued PAS-LAR treatment, mainly because of severe hyperglycemia. Pasireotide-induced hyperglycemia was inversely correlated with baseline insulin secretion (r = −0.37,P < 0.005).ConclusionsPAS-LAR normalizes IGF-I levels in most acromegaly patients, with a 50% pegvisomant-sparing effect. However, PAS-LAR treatment coincided with a high incidence of diabetes mellitus. The risk for developing diabetes during PAS-LAR treatment seems inversely related to insulin secretion at baseline.

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.

Direct transition to long-acting risperidone - analysis of long-term efficacy

2005 ◽  
Vol 19 (5_suppl) ◽  
pp. 15-21 ◽  
Author(s):  
W. Kissling ◽  
S. Heres ◽  
K. Lloyd ◽  
E. Sacchetti ◽  
P. Bouhours ◽  
...  
Keyword(s):  
Symptom Control ◽  
Extension Phase ◽  
Direct Transition ◽  
Treatment Change ◽  
The Mean ◽  
Long Acting ◽  
To Receive ◽  
Treatment Endpoint ◽  
Severity Criteria

This report presents data from the extension phase of a 6-month trial that evaluated the efficacy of risperidone long-acting injectable (RLAI) in stable psychotic patients requiring a treatment change. Patients continued to receive RLAI every 2 weeks for a maximum of 12 months from study entry. Symptoms were assessed using the PANSS after 1, 3, 6, 9 and 12 months of treatment (or treatment endpoint). Remission of severity criteria were defined as ≤3 points in all PANSS items suggested by the Remission in Schizophrenia Working Group. 715 patients (63% male) entered the extension phase and 508 completed the 12-month study. The mean PANSS total score at Day 0 was 74.9±22.7. This was significantly reduced after 1 month (67.7 ±22.3, p≤0.001), with continued improvements over the 12 months of the study until treatment endpoint (59.7±21.9). Significant improvements from Day 0 to endpoint were also seen in the scores for all PANSS subscales and symptom factors. The proportion of patients who met the PANSS severity criteria for remission increased from 29% at Day 0 to 60% at endpoint, and the proportion of patients who met these criteria for ≤ 6 months increased from 24% at Month 6 to 45% at endpoint. Treatment with RLAI for up to 12 months provided significant and sustained improvements in symptom control in patients with schizophrenia. These improvements may help patients to achieve and remain in remission.

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.

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