Effect of four monthly doses of a human monoclonal anti-FGF23 antibody (KRN23) on quality of life in X-linked hypophosphatemia.
X-linked hypophosphatemia (XLH) is characterized by lower extremity deformities that lead to bone and/or joint pain that result from decreased renal tubular reabsorption leading to hypophosphatemia caused by elevated levels of fibroblast growth factor 23 (FGF23).


OBJECTIVE
Validate the use of SF-36v2 Health Survey (SF-36v2) and the Western Ontario and McMaster Osteoarthritis Index (WOMAC) to measure previously unstudied health-related quality of life (HRQoL) in XLH patients and determine the change in HRQoL before and after treatment with KRN23, a human monoclonal anti-FGF23 antibody.


METHODS
Twenty-eight adult outpatients with XLH received up to four doses of KRN23 administered subcutaneously every 28 days. General HRQoL was measured with the SF-36v2 and condition-related HRQoL with the WOMAC at baseline and study endpoint as a secondary outcome of a Phase 1/2, open-label, multicenter, dose-escalation trial.


RESULTS
Testing for scale discriminant validity and convergent-divergent validity supported the use of these scales in the assessment of HRQoL in XLH. Both instruments indicated impairment of physical function at baseline with all mean scores showing a trend to improved health at study endpoint compared to baseline. When corrected for multiple comparisons, the score for Role Limitations due to physical health on the SF-36v2 which measures the patient's perception of their own chronic functional impairments due to poor physical health remained significantly improved (P< 0.05), increasing to the mean score of US adults. For the WOMAC, Physical Functioning and Stiffness scores were significantly improved (P< 0.05).


CONCLUSIONS
KRN23 administration was associated with significantly improved patient perception of their Physical Functioning and Stiffness due to their disease. This study demonstrates that the SF-36v2 and WOMAC are valid tools for assessing HRQoL in XLH.
Department of Medicine, Houston Methodist Hospital, Houston, TX, USA.
Mary D
MD
Ruppe
Kyowa Hakko Kirin Pharma Inc., Princeton, NJ, USA.
Xiaoping
X
Zhang
Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Erik A
EA
Imel
Duke Clinical Bone Laboratories, Duke University Medical Center, Durham, North Carolina, USA.
Thomas J
TJ
Weber
Kyowa Hakko Kirin Pharma Inc., Princeton, NJ, USA.
Mark A
MA
Klausner
Kyowa Hakko Kirin Pharma Inc., Princeton, NJ, USA.
Takahiro
T
Ito
Kyowa Hakko Kirin Pharma Inc., Princeton, NJ, USA.
Maria
M
Vergeire
Kyowa Hakko Kirin Pharma Inc., Princeton, NJ, USA.
Jeffrey S
JS
Humphrey
Shriners Hospital for Children, Montreal, Quebec, Canada.
Francis H
FH
Glorieux
Department of Pediatrics, University of California San Francisco, CA, USA.
Anthony A
AA
Portale
Yale Center for X-Linked Hypophosphatemia, Yale University School of Medicine, New Haven, CT, USA.
Karl
K
Insogna
Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Munro
M
Peacock
Yale Center for X-Linked Hypophosphatemia, Yale University School of Medicine, New Haven, CT, USA.
Thomas O
TO
Carpenter
Fibroblast growth factor 23 (FGF23); HRQoL, health-related quality of life; Health-related quality of life; KRN23; MIC, Minimally Important Change; PRO, patient reported outcomes; Rickets; WOMAC, Western Ontario and McMaster Osteoarthritis Index; X-linked hypophosphatemia