Showing papers by "Susan M. Webb published in 2018"

Long-term treatment with pegvisomant: observations from 2090 acromegaly patients in ACROSTUDY.

Abstract: Objectives ACROSTUDY is an international, non-interventional study of acromegaly patients treated with pegvisomant (PEGV), a growth hormone receptor antagonist and has been conducted since 2004 in 15 countries to study the long-term safety and efficacy of PEGV. This report comprises the second interim analysis of 2090 patients as of May 12, 2016. Methods Descriptive analyses of safety, pituitary imaging and outcomes on PEGV treatment up to 12 years were performed. Results Prior to starting PEGV, 96% of patients had reported surgery, radiation, medical therapy or any combinations of those. At start of PEGV, 89% of patients had IGFI levels above the upper limit of normal (ULN). The percentage of patients with normal IGFI levels increased from 53% at year 1 to 73% at year 10, and the average daily dose of PEGV increased from 12.8 mg (year 1) to 18.9 mg (year 10). A total of 4832 adverse events (AEs) were reported in 1137 patients (54.4%), of which 570 were considered treatment related in 337 patients (16.1%). Serious AEs were reported in 22% of patients, of which 2.3% were considered treatment related. Locally reported MRIs showed most patients (72.2%) had no change in tumor size relative to the prior scan; 16.8% had a decrease, 6.8% an increase and 4.3% both. In patients with normal liver tests at PEGV start, an ALT or AST elevation of >3× ULN at any time point during their follow-up was reported in 3%. Conclusions This second interim analysis confirms that long-term use of PEGV is an effective and safe treatment in patients with acromegaly.

Preoperative medical treatment in Cushing’s syndrome: frequency of use and its impact on postoperative assessment: data from ERCUSYN

Abstract: Background: Surgery is the definitive treatment of Cushing's syndrome (CS) but medications may also be used as a first-line therapy Whether preoperative medical treatment (PMT) affects postoperative outcome remains controversial Objective: (1) Evaluate how frequently PMT is given to CS patients across Europe;(2) examine differences in preoperative characteristics of patients who receive PMT and those who undergo primary surgery and (3) determine if PMT influences postoperative outcome in pituitary-dependent CS (PIT-CS) Patients and methods: 1143 CS patients entered into the ERCUSYN database from 57 centers in 26 countries Sixty-nine percent had PIT-CS, 25% adrenal-dependent CS (ADR-CS), 5% CS from an ectopic source (ECT-CS) and 1% were classified as having CS from other causes (OTH-CS) Results: Twenty per cent of patients took PMT ECT-CS and PIT-CS were more likely to receive PMT compared to ADR-CS (P < 0001) Most commonly used drugs were ketoconazole (62%), metyrapone (16%) and a combination of both (12%) Median (interquartile range) duration of PMT was 109 (98) days PIT-CS patients treated with PMT had more severe clinical features at diagnosis and poorer quality of life compared to those undergoing primary surgery (SX) (P < 005) Within 7 days of surgery, PIT-CS patients treated with PMT were more likely to have normal cortisol (P < 001) and a lower remission rate (P < 001) Within 6 months of surgery, no differences in morbidity or remission rates were observed between SX and PMT groups Conclusions: PMT may confound the interpretation of immediate postoperative outcome Follow-up is recommended to definitely evaluate surgical results

Worse Health-Related Quality of Life at long-term follow-up in patients with Cushing's disease than patients with cortisol producing adenoma. Data from the ERCUSYN

Abstract: Objective: Hypercortisolism in Cushing's syndrome (CS) is associated with impaired health-related quality of life (HRQoL), which may persist despite remission. We used the data entered into the European Registry on Cushing's syndrome (ERCUSYN) to evaluate if patients with CS of pituitary origin (PIT-CS) have worse HRQoL, both before and after treatment than patients with adrenal causes (ADR-CS). Methods: Data from 595 patients (492 women; 83%) who completed the CushingQoL and/or EQ-5D questionnaires at baseline and/or following treatment were analysed. Results: At baseline, HRQoL did not differ between PIT-CS (n = 293) and ADR-CS (n = 120) on both EuroQoL and CushingQoL. Total CushingQoL score in PIT-CS and ADR-CS was 41 ± 18 and 44 ± 20, respectively (P = .7). At long-time follow-up (>1 year after treatment) total CushingQoL score was however lower in PIT-CS than ADR-CS (56 ± 20 vs 62 ± 23; P = .045). In a regression analysis, after adjustment for baseline age, gender, remission status, duration of active CS, glucocorticoid dependency and follow-up time, no association was observed between aetiology and HRQoL. Remission was associated with better total CushingQoL score (P < .001), and older age at diagnosis with worse total score (P = .01). Depression at diagnosis was associated with worse total CushingQoL score at the last follow-up (P < .001). Conclusion: PIT-CS patients had poorer HRQoL than ADR-CS at long-term follow-up, despite similar baseline scoring. After adjusting for remission status, no interaetiology differences in HRQoL scoring were found. Age and presence of depression at diagnosis of CS may be potential predictors of worse HRQoL regardless of CS aetiology.

Patient-centered assessment on disease burden, quality of life, and treatment satisfaction associated with acromegaly

Abstract: The study aimed to assess the economic burden, health-related quality of life (HRQoL), and acromegaly treatment satisfaction in the USA. A web-based, cross-sectional survey was distributed to members of Acromegaly Community. Data related to comorbidities, treatment patterns, and treatment satisfaction were collected. The costs over the past 3 months included out-of-pocket cost, sick leave, leave of absence, direct loss of job due to acromegaly, unemployment, assistance to perform household chores, and family member loss of income. The HRQoL was assessed by Acromegaly Quality of Life (AcroQoL) and EQ-5D-3L questionnaires. Among 106 patients who completed the survey (mean age: 46 years, female: 76.4%), 44.3% presented with ≥5 comorbidities, and 90.6% reporting acromegaly-related symptoms. Compared with the low-symptom group 0–3 (n=41), the 4+ symptoms group (n=65) was more likely to have depression (OR=2.3, 95% CI 1.1 to 5.2) and cardiovascular disease (OR=5.8, 95% CI 2.0 to 16.7), and experienced higher costs (loss of job: $8874 vs $1717, P=0.02; unemployment disability: $17,102 vs $429, P=0.003; household chores: $2160 vs $932, P=0.0003; family members’ income loss: $692 vs $122, P=0.03). The high-symptom group had lower HRQoL scores, compared with the low-symptom group (EQ-5D-3L: 0.53 vs 0.75, P

Quality of Life in Cushing's disease: A long term issue?

Abstract: The purpose of this review is to describe how quality of life (QoL) is impaired in patients with hypercortisolism due to Cushing's syndrome of any aetiology, including pituitary-dependent Cushing's disease. It is worse in active disease, but improvement after successful therapy is often incomplete, due to persistent physical and psychological co-morbidities, even years after endocrine "cure". Physical symptoms like extreme fatigability, central obesity with limb atrophy, hypertension, fractures, and different skin abnormalities severely impair the affected patients' everyday life. Psychological and cognitive problems like bad memory, difficulties to concentrate and emotional distress, often associated with anxiety and depression, make it difficult for many patients to overcome the aftermath of treated Cushing's syndrome. Recent studies have shown diffuse structural abnormalities in the central nervous system during active hypercortisolism, thought to be related to the wide distribution of glucocorticoid receptors throughout the brain. Even though they improve after treatment, normalization is often not complete. Shortening the exposure to active Cushing's syndrome by reducing the often long delay to diagnosis and promptly receiving effective treatment is highly desirable, together with preparing the patient for the difficult periods, especially after surgery. In this way they are prepared for the impairments they perceive in every day life, and live with the hope of later improvement, which can be therapeutic in many instances.

A randomised, open-label, parallel group phase 2 study of antisense oligonucleotide therapy in acromegaly

Abstract: Objective: ATL1103 is a second-generation antisense oligomer targeting the human GH receptor. This phase 2 randomised, open-label, parallel-group study assessed the potential of ATL1103 as a treatment for acromegaly. Design: 26 patients with active acromegaly (IGF-I >130% upper limit of normal) were randomised to subcutaneous ATL1103 200 mg either once- or twice-weekly for 13 weeks, and monitored for a further 8-week washout period. Methods: The primary efficacy measures were change in IGF-I at week 14, compared to baseline and between cohorts. For secondary endpoints (IGFBP3, ALS, GH, GHBP), comparison was between baseline and week 14. Safety was assessed by reported adverse events. Results and Conclusions: Baseline median IGF-I was 447 and 649 ng/mL in the once- and twice-weekly groups, respectivey. Compared to baseline, at week 14 twice-weekly ATL1103 resulted in a median fall in IGF-I of 27.8% (p=0.0002). Between cohort comparison at week 14 demonstrated the median fall in IGF-I to be 25.8% (p=0.0012) greater with twice-weekly dosing. In the twice-weekly cohort, IGF-I was still declining at week 14, and at week 21 remained lower than at baseline by a median of 18.7% (p=0.0005). Compared to baseline, by week 14 IGFBP3 and ALS had declined by a median of 8.9% (p=0.027) and 16.7% (p=0.017) with twice-weekly ATL1103; GH had increased by a median of 46% at week 14 (p=0.001). IGFBP3, ALS and GH did not change with weekly ATL1103. GHBP fell by a median of 23.6% and 48.8% in the once- and twice-weekly cohorts (p=0.027 and p=0.005), respectively. ATL1103 was well tolerated, although 84.6% of patients experienced mild to moderate injection-site reactions (ISR). This study provides proof-of-concept that ATL1103 is able to significantly lower IGF-I in patients with acromegaly.

Cushing's disease: major difficulties in diagnosis and management during pregnancy

Abstract: Pregnancy in women with a diagnosis of Cushing' syndrome (CS) is an extremely rare event and its diagnosis and treatment are a real medical challenge. During pregnancy, the hypothalamus-pituitary-adrenal axis undergoes major changes leading to a significant increase in plasma cortisol levels throughout gestation. The difficulties in diagnosis are related to the resemblance of symptoms of CS and those of pregnancy, and to the complex interpretation of the screening tests. Moreover, the diagnostic work up in the postnatal period may be difficult in the first weeks postpartum. Importantly, the etiology of CS in pregnancy differs from non-pregnant status. In pregnancy, the adrenal origin is the most frequent in up to 60% of the cases, in contrast to ACTH-secreting corticotroph adenomas of the pituitary gland, which account for 70% of the cases outside pregnancy. Nevertheless, maternal and fetal outcomes are severely affected in the context of CS whichever the etiology is, with high rates of maternal and fetal morbimortality, and with a rate of overall fetal loss of about 25% of the pregnancies. There is no consensus as to the most effective treatment in these circumstances in terms of improving maternal and fetal outcomes, as there are no studies comparing the different modalities of treatment for CS in pregnancy. However, evidence suggests that patients receiving treatment during pregnancy achieve better fetal outcomes than those who do not receive treatment. We aim to summarize in this review the major diagnostic and management difficulties during pregnancy.

Mapping AcroQoL scores to EQ-5D to obtain utility values for patients with acromegaly.

Abstract: Aims: To estimate a preference-based single index for the disease-specific instrument (AcroQoL) by mapping it onto the EQ-5D to assist in future economic evaluations.Materials and methods: A sample...

Clinical outcomes of childhood craniopharyngioma: can we do better?

Abstract: Patient-oriented instruments like questionnaires to evaluate a patient’s health-related quality of life (QoL) have become progressively important in recent times, both from a clinical and regulatory points of view [1–3]. For patients, improving their subjective every day-to-day living is of primordial importance, that is, that they can assume their personal, social and family aspirations, as well as their schooling or working responsibilities and enjoy their leisure time with hobbies or sports activities. If a disease determines impairments or problems like chronic pain, extreme fatigability, loss of vision, difficulties in concentrating or the need for frequent medical check-ups or complex therapeutic regimens, this will mean that the affected individuals will have to change their activities, because they cannot do them anymore due to the physical or psychological issues they are experiencing. Some adapt to their limitations more easily than others, take up new hobbies or accept that their personal or professional aims require a change, and usually will experience a better QoL than those who do not adapt to this new situation. In this latter case, depression often occurs, further negatively impacting on QoL. Craniopharyngioma is a histologically benign condition, which, however, is associated with higher morbidity and mortality rates compared to both the general population and with other causes of hypopituitarism. Hypothalamic involvement with ensuing obesity and impaired growth leading to an abnormal body image, as well as loss of vision and impaired pituitary function all tend to affect QoL in a negative way. Growth hormone (GH) deficiency, if present, usually impairs QoL further, whatever the underlying disease [4–7]; in contrast, if QoL is impaired, starting GH substitution therapy leads to improvement after several months, which persists for years [8, 9]. In this new article from the German KRANIOPHARYNGEOM 2007 study [10], which includes nearly 200 patients diagnosed with a childhood-onset craniopharyngioma followed prospectively, 47 were selected; they had been diagnosed of a craniopharyngioma above the age of 5 years and after baseline assessment (within 3 months of diagnosis), had provided QoL evaluation at both 1 and 3 years after diagnosis and surgery. Postoperative endocrine assessment revealed GH deficiency, subsequently treated with GH substitution therapy by the treating physician in 28 patients, while in the other 19 patients, substitution therapy was not prescribed. Both groups (treated or not with GH) were comparable for gender, age at diagnosis, last known functional capacity, additional endocrine deficits, body mass index (BMI) and height standard deviation score (SDS) at baseline and throughout the study period. QoL was assessed both in the patients and their parents using the Paediatric Quality of Life (PEDQOL) questionnaire, that defines seven health-related QoL domains (self-esteem, emotional functionality, body image, cognition, physical function, social functionality in family/among friends); a high score is indicative of worse QoL assessment [11]. Furthermore, functional capacity or daily life abilities and its influence on QoL was evaluated with the German Fertigkeitenskala Münster-Heidelberg (FMH) questionnaire which evaluates the patients capacity for routine actions with 56 items, and has reference ranges with age-dependent percentiles from the normal population [12]. On the whole, parents considered the QoL of their children worse than the patients themselves. This was especially so for emotional stability (significantly worse at 3 months, 1 and 3 years after diagnosis), socialisation among friends (worse at 1 and 3 years), and body image and physical function (different at 1 year). Both patients and parents perceived autonomy, cognition and social issues related to the family similarly. When the patients’ selfassessment was compared between those patients who * Susan M. Webb swebb@santpau.cat

Séquelles cognitives de la maladie de Cushing : étude MEMOCUSH

Abstract: La maladie de Cushing (MC) est une maladie rare. L’hypercortisolisme de la MC active entraine frequemment des troubles psychiatriques, des troubles de la memoire, et une alteration de la qualite de vie (Qol). Quelques etudes recentes ont signale la persistance d’alterations cognitives chez des patients en remission d’une MC. L’objectif de l’etude etait d’evaluer l’etat cognitif de patients en remission prolongee d’une MC a l’aide d’outils conventionnels et d’un outil original developpe par notre groupe, le labyrinthe radiaire virtuel en 3D (LRV3D). Etude pilote transversale cas-temoins, intitulee MemoCush, incluant, de fevrier a juillet 2016, 15 cas et 15 temoins, apparies sur l’âge, le sexe, et le niveau d’education. Nous avons pris le soin d’exclure tout facteur confondant pouvant etre a l’origine de troubles cognitifs (radiotherapie hypophysaire, IMC>30, traitement par antidepresseurs ou anxiolytiques...). Plusieurs tests ont ete realises permettant d’evaluer la memoire (LRV3D, RAVLT, test de fluence verbale, addition spatiale, memoire des symboles, ROCF), la Qol (SF-36, Cushing-QoL) et les troubles psychopathologiques (MADRS, HADS). L’âge moyen etait de 45,9 /- 9,3 ans, 80% de femme, niveau d’education eleve. Les tests cognitifs ont ete realises a 6,2 /- 5,3 ans de la date de remission de la MC. Nous n’observons pas de troubles de la memoire plus marques chez les cas par rapport aux temoins aux differents tests (p entre 0,06 et 0,56). Cependant, nous observons une alteration de la Qol des cas (SF-36 : p=0,006 ; CushingQol : p=0,0003) et une persistance de depression chez les cas au MADRS (p=0,043) avec une correlation entre la duree estimee en hypercortisolisme avant le diagnostic de MC et les resultats aux tests. L’inclusion complementaire de 15 autres cas est prevue prochainement en Espagne pour doubler l’effectif et avoir une puissance statistique pour confirmer ou non nos resultats.