EU Looks to Okay Ketoconazole for Use in Cushing’s Syndrome

Posted on September 27, 2014 by MaryO

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended granting a marketing authorization for ketoconazole (Ketoconazole HRA; Laboratoire HRA Pharma) for the treatment of Cushing’s syndrome, a rare hormonal disorder sometimes called hypercortisolism.

Cushing’s syndrome is characterized by an excess of the hormone cortisol in the blood, which may be caused by a tumor. Treatment options currently available in the European Union include surgery to remove the tumor responsible for the high cortisol levels and radiotherapy, as well as several medicines that reduce the production of cortisol.

But pharmacological options remain very limited, and there is an unmet medical need for additional treatments, especially when surgery fails or for patients who cannot undergo surgery or take other medications. For this reason, the EMA’s CHMP evaluated the medicine under expedited review.

The opinion adopted by the CHMP at its September 2014 meeting is an intermediary step on Ketoconazole HRA’s path to patient access.

The CHMP opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorization. Once a marketing authorization has been granted, decisions about price and reimbursement will then take place at the level of each member state considering the potential role/use of this medicine in the context of the national health system of that country.

The recommendation is that Ketoconazole HRA is to be prescribed only by physicians specialized in treating Cushing’s syndrome, as the dosing needs to be individualized for each patient.

This is because oral ketoconazole was previously suspended in the European Union for the indication it was first approved for, fungal infections, due to risk for liver injury. The US Food and Drug Administration (FDA) also decreed, at the same time, that doctors should no longer prescribe ketoconazole tablets as a first-line therapy for any fungal infection, for the same reason.

Information will be sent to healthcare professionals to allow them to advise patients and prescribe the medicine safely and effectively.

A Medicine Used Off-Label for More than 30 Years

Doctors have used ketoconazole to treat Cushing’s syndrome for more than 30 years, although it has never been authorized for this indication in the European Union. The drug is also frequently used off-label in the United States and elsewhere for this purpose.

The CHMP’s recommendation builds on information from published literature and documented off-label use in clinical practice.

At the time of the suspension of ketoconazole for fungal infections, healthcare professionals and patients were concerned that ketoconazole would no longer be available for patients with Cushing’s syndrome.

The CHMP therefore reviewed Ketoconazole HRA through accelerated assessment to facilitate patients’ access to a fully authorized medicine as soon as possible with evidence-based information for patients and doctors.

When assessing Ketoconazole HRA for the treatment of Cushing’s syndrome, the CHMP considered that “in this rare and potentially life-threatening condition, the medicine’s benefits are greater than its risks, which can be manageable in clinical practice by specific measures mitigating the risk of liver toxicity, including close monitoring of the patients’ liver function.”

In 2012, it was estimated that the disease affected approximately 46,000 people in the European Union. Cushing’s syndrome is a long-lasting condition that can be life-threatening because of its complications, including diabetes, high blood pressure, and depression.

From http://www.medscape.com/viewarticle/832399?src=rss

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Long-term remission and recurrence rate in a cohort of Cushing’s disease: the need for long-term follow-up

Posted on June 9, 2014 by MaryO

Pituitary. 2014 Apr 19. [Epub ahead of print]


Aranda G1, Enseñat J, Mora M, Puig-Domingo M, Martínez de Osaba MJ, Casals G, Verger E, Ribalta MT, Hanzu FA, Halperin I.

Author information

 Abstract

OBJECTIVE:

Transsphenoidal surgery is the procedure of choice in Cushing disease (CD), with immediate post-operative remission rates ranging between 59 and 94 % and recurrence rates between 3 and 46 %, both depending upon the definition criteria and the duration of the follow-up. Our aim was to assess the rate of remission, recurrence and persistence of the disease after the first treatment and to identify predictors of remission in the CD population of our center.

METHODS:

Retrospective cohort study of the patients diagnosed of CD and with follow-up in our center between 1974 and 2011. We analyzed 41 patients (35 women and 6 men) with a mean age at diagnosis of 34 ± 13 years. The mean follow-up was 14 ± 10 years (range 1-37 years) and the median of follow-up period was 6.68 years.

RESULTS:

Thirty-five (85.4 %) patients underwent transsphenoidal surgery as first treatment option. Histopathological evidence of a pituitary adenoma was registered in 17 (48.5 %) patients. Thirty-two (78 %) patients achieved disease remission after the first treatment, 21 (65.6 %) of them presented disease recurrence. Persistent disease was observed in 9 (22 %) patients. Twelve (29.3 %) subjects developed post-surgical adrenal insufficiency, 7 of which (70 %) achieved stable remission. Two parameters were found to be significant predictors of remission after the first treatment: age at disease diagnosis and the development of adrenal insufficiency (cortisol ❤ μg/dl) in the immediate post-operative state.

CONCLUSIONS:

We report a high recurrence rate, at least partially attributable to the long follow-up time. Early post-surgery adrenal insufficiency predicts remission. Hypopituitarism was also very prevalent, and strongly associated with radiotherapy. These results lead us to the conclusion that CD needs a life-long strict follow-up.

PMID:

 

24748528

 

[PubMed – as supplied by publisher]

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Cushing’s syndrome – A structured short- and long-term management plan for patients in remission

Posted on August 30, 2013 by MaryO

European Journal of Endocrinology, 08/30/2013  Review Article

harvey-bookRagnarsson O et al. – One–hundred years have passed since Harvey Williams Cushing presented the first patient with the syndrome that bears his name.

The focus of the long–term specialized care should be to identify cognitive impairments and psychiatric disorders, evaluate cardiovascular risk, follow pituitary function and to detect possible recurrence of Cushing’s syndrome.

Source

O Ragnarsson, Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden.

Abstract

One-hundred years have passed since Harvey Williams Cushing presented the first patient with the syndrome that bears his name. In patients with Cushing’s syndrome body composition, lipid-, carbohydrate- and protein-metabolism is dramatically affected and psychopathology and cognitive dysfunction is frequently observed.

Untreated patients with Cushing’s syndrome have a grave prognosis with an estimated five-year survival of only 50%. Remission can be achieved by surgery, radiotherapy and sometimes with medical therapy.

Recent data indicate that the adverse metabolic consequences of Cushing’s syndrome are present for years after successful treatment. In addition, recent studies have demonstrated that health related quality of life and cognitive function is impaired in patients with Cushing’s syndrome in long-term remission.

The focus of specialized care should therefore not only be on the diagnostic work-up and the early post-operative management, but also the long-term follow-up.

In this paper we review the long-term consequences in patients with Cushing’s syndrome in remission with focus on the neuropsychological effects and discuss the importance of these findings for long-term management. We also discuss three different phases in the postoperative management of surgically treated patients with Cushing’s syndrome, each phase distinguished by specific challenges; the immediate post-operative phase, the glucocorticoid dose tapering phase and the long-term management. The focus of the long-term specialized care should be to identify cognitive impairments and psychiatric disorders, evaluate cardiovascular risk, follow pituitary function and to detect possible recurrence of Cushing’s syndrome.

PMID:
23985132
[PubMed – as supplied by publisher]

From http://www.ncbi.nlm.nih.gov/pubmed/23985132

Filed under: Cushing's, pituitary, Rare Diseases | Tagged: , , , , , , , , , | Leave a comment »

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