Treatment Individualization Using Pharmacokinetic Studies and Joint Ultrasound Imaging in Pediatric Patients With Hemophilia

Abstract

Hemophilia is characterized by bleeding diathesis, primarily affecting the joints. Prophylactic use of missing factor aims at limiting the number of bleeds and, in the long term, the risk of permanent joint damage. However, standard prophylactic regimens are usually applied empirically, not adjusting for variations in bleeding phenotype or drug metabolism. Aim of the present study was to evaluate the need for individualizing prophylaxis, with guidance of pharmacokinetic (PK) studies and joint ultrasound in a setting of everyday clinical practice. To evaluate adequacy of applied regimens, joint status was assessed using the Hemophilia Joint Health Score as well as ultrasound imaging, while PK studies were performed using the Web-Accessible Population Pharmacokinetic Service-Hemophilia. Imaging results were consistent with early joint damage in a large proportion of pediatric patients, whereas PK measures were indicative of inadequate prophylaxis in many cases-despite the limited number of bleeds reported by patients. The study revealed the need for prophylaxis adjustment in the majority of patients. Real world data confirm that traditional prophylaxis is often unable to achieve therapeutic goals, while an individualized approach, guided by the use of novel modalities, may be of great benefit to young hemophilia patients.

Screening for subclinical synovial proliferation in haemophilia: A systematic review and meta‐analysis comparing physical examination and ultrasound

“…The reasons for excluding studies based on full text are summarized in Supplement S2. Eventually, 15 studies 11,12,15,24,29,[38][39][40][41][42][43][44][45][46][47] were included in the systematic review. The 15 included studies reported on occurrence of swelling and synovial proliferation in 2890 joints of 627 patients.…”

“…Eleven out of 15 included studies were considered 'screening of index joints' studies 24,29,[38][39][40][41][43][44][45][46][47] and were thus included in a bivariate random-effects model to determine summary estimates for sensitivity and specificity. Subclinical synovial proliferation was found in 4.6-41.7% of the joints in these studies.…”