Barbara K Burton1, Kyle Bradford Jones2, Stephen Cederbaum3, Fran Rohr4, Susan Waisbren5, Debra E Irwin6, Gilwan Kim6, Joshua Lilienstein7, Ignacio Alvarez7, Elaina Jurecki8, Harvey Levy4. 1. Ann & Robert Lurie Children's Hospital, 225 E. Chicago Ave., Chicago, IL 60611, United States. 2. University of Utah School of Medicine, Department of Family and Preventive Medicine, 375 Chipeta Way Ste A., Salt Lake City, UT 84108, United States. 3. University of California, Los Angeles, 635 Charles E Young Dr Los Angeles, CA 90095-7332, United States. 4. Boston Children's Hospital and Harvard Medical School, 1 Autumn St., Rm #526, Boston, MA 02115, United States. 5. Boston Children's Hospital and Harvard Medical School, 1 Autumn Street, #525, Boston, MA 02115, United States. 6. Truven Health Analytics, An IBM Watson Health Company, 7700 Old Georgetown Rd, 6th Floor, Bethesda, MD 20814, United States. 7. BioMarin Pharmaceutical Inc., 105 Digital Drive, Novato, CA 94949, United States. 8. BioMarin Pharmaceutical Inc., 105 Digital Drive, Novato, CA 94949, United States. Electronic address: ejurecki@bmrn.com.
Abstract
BACKGROUND: Phenylalanine hydroxylase (PAH) deficiency, otherwise known as phenylketonuria (PKU), is an inborn error of metabolism that requires treatment to be initiated in the newborn period and continued throughout life. Due to the challenges of treatment adherence and the resulting cumulative effects of high and labile blood phenylalanine, PKU exerts a significant burden of disease. Retrospective studies using large databases allow for unique perspectives on comorbidities associated with rare diseases. An evaluation of comorbidities across various organ systems is warranted to understand the disease burden in adult patients. OBJECTIVES: The aim of this insurance claim-based observational study was to assess the prevalence of comorbid conditions across various organ systems (e.g. dermatological, renal, respiratory, gastrointestinal, hematological, and others) among adult PKU patients compared with matched controls from the general population. METHODS: This retrospective, case-controlled study selected patients from United States insurance claims databases from 1998 to 2014 using International Classification of Diseases, Ninth Revision (ICD-9) codes for diagnosis of PKU. The date of first diagnosis during the study period was index date and this was not necessarily the first time the patient was diagnosed with PKU. Cases were matched with a 1:5 ratio with general population (non-PKU controls) on age, sex, race, geographic location, duration of time in the database and insurance type. Prevalence and prevalence ratio (PR) calculations for comorbidities across various organ systems among adults (≥20 years old) with PKU were compared with the general population (non-PKU controls). The conditions were selected based on complications associated with PKU and feedback from clinicians treating PKU patients. RESULTS: A total of 3691 PKU patients and 18,455 matched, non-PKU controls were selected, with an average age of 35 years. The mean healthcare costs incurred by the PKU patients during baseline, were approximately 4 times that of the controls ($4141 vs $1283; p < .0001). The prevalence rates of comorbidities across various organ systems during the follow-up period were significantly higher for those with PKU than in the control group. After adjusting for baseline characteristics, the adjusted prevalence ratios (PR) of 15 conditions studied (asthma, alopecia, urticaria, gallbladder disease, rhinitis, esophageal disorders, anemia, overweight, GERD, eczema, renal insufficiency, osteoporosis, gastritis/esophagitis and kidney calculus) were all above PR = 1.24 and significantly higher for the PKU cohort (p ≤ .001). The highest adjusted PR were for renal insufficiency with hypertension (PR [95% CI]: 2.20 [1.60-3.00]; p < .0001) and overweight (PR [95%CI]: 2.06 [1.85-2.30]; p < .0001). CONCLUSIONS: The prevalence of selected comorbidities across several organ systems is significantly higher among PKU patients than for general population controls. Regular screening for common co-morbidities may be warranted as part of PKU management.
BACKGROUND:Phenylalanine hydroxylase (PAH) deficiency, otherwise known as phenylketonuria (PKU), is an inborn error of metabolism that requires treatment to be initiated in the newborn period and continued throughout life. Due to the challenges of treatment adherence and the resulting cumulative effects of high and labile blood phenylalanine, PKU exerts a significant burden of disease. Retrospective studies using large databases allow for unique perspectives on comorbidities associated with rare diseases. An evaluation of comorbidities across various organ systems is warranted to understand the disease burden in adult patients. OBJECTIVES: The aim of this insurance claim-based observational study was to assess the prevalence of comorbid conditions across various organ systems (e.g. dermatological, renal, respiratory, gastrointestinal, hematological, and others) among adult PKUpatients compared with matched controls from the general population. METHODS: This retrospective, case-controlled study selected patients from United States insurance claims databases from 1998 to 2014 using International Classification of Diseases, Ninth Revision (ICD-9) codes for diagnosis of PKU. The date of first diagnosis during the study period was index date and this was not necessarily the first time the patient was diagnosed with PKU. Cases were matched with a 1:5 ratio with general population (non-PKU controls) on age, sex, race, geographic location, duration of time in the database and insurance type. Prevalence and prevalence ratio (PR) calculations for comorbidities across various organ systems among adults (≥20 years old) with PKU were compared with the general population (non-PKU controls). The conditions were selected based on complications associated with PKU and feedback from clinicians treating PKUpatients. RESULTS: A total of 3691 PKUpatients and 18,455 matched, non-PKU controls were selected, with an average age of 35 years. The mean healthcare costs incurred by the PKUpatients during baseline, were approximately 4 times that of the controls ($4141 vs $1283; p < .0001). The prevalence rates of comorbidities across various organ systems during the follow-up period were significantly higher for those with PKU than in the control group. After adjusting for baseline characteristics, the adjusted prevalence ratios (PR) of 15 conditions studied (asthma, alopecia, urticaria, gallbladder disease, rhinitis, esophageal disorders, anemia, overweight, GERD, eczema, renal insufficiency, osteoporosis, gastritis/esophagitis and kidney calculus) were all above PR = 1.24 and significantly higher for the PKU cohort (p ≤ .001). The highest adjusted PR were for renal insufficiency with hypertension (PR [95% CI]: 2.20 [1.60-3.00]; p < .0001) and overweight (PR [95%CI]: 2.06 [1.85-2.30]; p < .0001). CONCLUSIONS: The prevalence of selected comorbidities across several organ systems is significantly higher among PKUpatients than for general population controls. Regular screening for common co-morbidities may be warranted as part of PKU management.
Authors: K F Trefz; A C Muntau; K M Kohlscheen; J Altevers; C Jacob; S Braun; W Greiner; A Jha; M Jain; I Alvarez; P Lane; C Schröder; F Rutsch Journal: Orphanet J Rare Dis Date: 2019-07-22 Impact factor: 4.123
Authors: Bridget M Stroup; Sangita G Murali; Denise J Schwahn; Emily A Sawin; Emma M Lankey; Hans Peter Bächinger; Denise M Ney Journal: Physiol Rep Date: 2019-10