Novel therapies have transformed the treatment of hemophilia in recent decades, but these new approaches also raise new challenges for clinicians who monitor joint health in persons with hemophilia, a specialist said.
“Patient-reported outcomes should be combined with other, more objective outcome measures for joint health monitoring, and joint ultrasound is a promising tool for objective joint health monitoring, although, due to its relatively recent introduction in clinical practice, we lack objective data and standardization,” said Roberta Gualtierotti, MD, PhD, from the Università Degli Studi of Milan.
She reviewed the challenges and approaches to monitoring joint health in persons with hemophilia during the annual congress of the European Association for Haemophilia and Allied Disorders.
Over the last decades the target of hemophilia treatment has shifted from prolonging survival to improving joint health and quality of life, and care has improved with the introduction of novel therapies such as extended half-life replacement products, nonreplacement therapies, and gene therapy, she noted.
However, “due to different pharmacodynamics and pharmacokinetics profiles, the currently available therapies cannot be compared to each other on several levels,” Dr. Gualtierotti said.
Laboratory monitoring of replacement therapies with standard coagulation assays may be unreliable, and depending on the mechanism of action and type of administration of nonreplacement agents, patients may experience breakthrough bleeding, especially after traumatic injury, she said.
Until the specific noncoagulatory effects of factor VIII on bone and joint health is better understood, close monitoring of patients will be required, she added.
Outcome measures
Subjective measures of joint health include patient-reported bleeding rates and health-related quality of life. These are practical for home management, but patients may not be able to distinguish symptoms of acute joint bleeding from chronic arthritis pain, with the potential for either under- or overtreatment, and subjective reporting is likely to miss subclinical bleeding that can occur even when patients are on prophylaxis.
Health-related quality of life tools, whether generic or specific for hemophilia, are not sensitive to small improvements, and they are not always used in routine clinical practice.
Objective measures include physical examination with scoring according to the World Federation of Hemophilia (Gilbert Scale) score or Hemophilia Joint Health Score, but these measures have limited ability to identify early or subclinical joint abnormalities.
“Therefore, joint physical examination on its own is not a sufficient measure of treatment efficacy, and it should be used in combination with other tools more objective, such as imaging,” Dr. Gualtierotti said.
Get the picture?
Imaging with x-rays, MRI, and, recently in some centers, point-of-care ultrasound can provide clinicians with important real-time information about the joint stability and health.
Point-of-care ultrasound in particular offers promise as a practical tool, with no ionizing radiation and high sensitivity for synovial hyperplasia subclinical joint effusion. It’s relatively inexpensive, can be used to image multiple joints, and allows for ease of follow-up, she said. The technique requires specialized training, however, and there is a lack of prospective data about its utility in hemophilia.
Various ultrasound scoring systems have been proposed, and home-based ultrasound is currently being explored in several clinical trials, Dr. Gualtierotti noted.
Other avenues for remote joint health monitoring under consideration are serum or synovial biomarkers for joint bleeding and arthropathy that could be employed at bedside or at home, smartphone apps for breakthrough bleeding and patient-reported outcomes, and sensors for detecting abnormalities in gait that may signal joint dysfunction, she said.