Self-reported treatment-associated symptoms among patients with urea cycle disorders participating in glycerol phenylbutyrate clinical trials

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• 作者：Sandesh C.S. Nagamani^a ; ^{Nagamani@bcm.edu" class="auth_mail" title="E-mail the corresponding author} ; George A. Diaz^b ; William Rhead^c ; Susan A. Berry^d ; Cynthia Le Mons^e ; Uta Lichter-Konecki^f ; James Bartley^g ; Annette Feigenbaum^h ; Andreas Schulzeⁱ ; Nicola Longo^j ; William Berquist^k ; Renata Gallagher^l ; Dennis Bartholomew^m ; Cary O. Hardingⁿ ; Mark S. Korson^o ; Shawn E. McCandless^p ; Wendy Smith^q ; Jerry Vockley^r ; David Kronn^s ; Robert Zori^t ; Stephen Cederbaum^u ; J. Lawrence Merritt II^v ; Derek Wong^u ; Dion F. Coakley^w ; Bruce F. Scharschmidt^w ; Klara Dickinson^x ; Miguel Marinoⁿ ; Brendan H. Lee^a ; Masoud Mokhtarani^w
• 关键词：GPB ; glycerol phenylbutyrate ; NaPBA ; sodium phenylbutyrate ; HRQoL ; health-related quality of life ; UCD ; urea cycle disorder
• 刊名：Molecular Genetics and Metabolism
• 出版年：2015
• 出版时间：September-October 2015
• 年：2015
• 卷：116
• 期：1-2
• 页码：29-34
• 全文大小：525 K

文摘

Health care outcomes have been increasingly assessed through health-related quality of life (HRQoL) measures. While the introduction of nitrogen-scavenging medications has improved survival in patients with urea cycle disorders (UCDs), they are often associated with side effects that may affect patient compliance and outcomes.

Methods

Symptoms commonly associated with nitrogen-scavenging medications were evaluated in 100 adult and pediatric participants using a non-validated UCD-specific questionnaire. Patients or their caregivers responded to a pre-defined list of symptoms known to be associated with the use of these medications. Responses were collected at baseline (while patients were receiving sodium phenylbutyrate [NaPBA]) and during treatment with glycerol phenylbutyrate (GPB).

Results

After 3 months of GPB dosing, there were significant reductions in the proportion of patients with treatment-associated symptoms (69% vs. 46%; p < 0.0001), the number of symptoms per patient (2.5 vs. 1.1; p < 0.0001), and frequency of the more commonly reported individual symptoms such as body odor, abdominal pain, nausea, burning sensation in mouth, vomiting, and heartburn (p < 0.05). The reduction in symptoms was observed in both pediatric and adult patients. The presence or absence of symptoms or change in severity did not correlate with plasma ammonia levels or NaPBA dose.

Conclusions

The reduction in symptoms following 3 months of open-label GPB dosing was similar in pediatric and adult patients and may be related to chemical structure and intrinsic characteristics of the product rather than its effect on ammonia control.