Regular MRI Scans May Help Assess Joint Damage Risk in Hemophilia A
Preventive treatment with factor VIII (FVIII) — the missing blood clotting protein in hemophilia A — was not fully effective at preventing MRI-detected joint changes in boys with severe disease, according to a Canadian study.
Regular evaluation of joints by MRI or ultrasounds, however, may help in identifying those at risk of severe joint damage and in tailoring the frequency of preventive replacement therapy to preserve joint health, its authors noted.
The study, “Magnetic resonance imaging in boys with severe hemophilia A: Serial and end-of-study findings from the Canadian Hemophilia Primary Prophylaxis Study,” was published in the journal Research and Practice in Thrombosis and Haemostasis.
A hallmark of hemophilia A, particularly in severe cases, is recurrent joint bleeding, which can result in arthropathy (joint disease), pain, and a diminished quality of life.
FVIII replacement therapy is a standard preventive (prophylactic) therapy for moderate to severe disease, and usually initiated in patients before age 3. Treatment, which consists of administering the missing FVIII, is usually first given once weekly, but dosing frequency can increase if patients continue to experience persistent joint bleeding.
However, changes in preventive treatment require joint health to be regularly evaluated to determine treatment effectiveness.
MRI scans are currently the most sensitive imaging tests for this, since they can detect changes in both soft and hard tissues. But few studies have reported how disease progresses with regular MRI scans, and whether early MRI findings may help predict joint disease progression.
A team led by researchers at the University of Saskatchewan followed young boys with severe hemophilia A (ages at study entry, 1 to 2.5 years old) enrolled in the Canadian Hemophilia Prophylaxis Study (CHPS).
In total, 46 boys were followed for a median of 9.6 years, during which six joints (ankles, knees, and elbows) were evaluated via MRI scans. While all completed the study, 27 (59%) had MRI and X-ray scans conducted at set intervals up to the study’s end. X-rays and MRIs were independently evaluated by two experienced radiologists.
All participants received FVIII preventative treatment: initially, weekly infusions of 50 international units per kilogram (IU/kg) (step 1), escalating to twice weekly infusions of 30 IU/kg (step 2), and then to three times a week or alternate-day infusions of 25 IU/kg (step 3).
Two of the 46 boys (4%) remained at step 1 of the preventive treatment plan at the study’s end, while 17 others (37%) entered the treatment’s step 2, and 27 (59%) reached step 3.
Overall, by study end, 11 of the 27 (41%) boys with interval MRI scans had dosing adjustments to their treatment regimen.
More than half of these patients (25 boys; 54%) had detectable soft-tissue alterations in at least one joint, as evaluated by MRI scans. Seventeen of them had changes in more than one joint. These alterations were seen in the ankles of 18 boys (39%), in the elbows of 14 (30%), and in the knees of four (9%) others.
Signs of inflammation of the synovium — a thin layer of tissue that lines and lubricates the joints — were evident in 25 (54%) boys and joint bleeding in six (13%).
Eighteen of the 46 boys (39%) had osteochondral alterations — those involving the cartilage and possibly the underlying bone as well — detected by MRI in at least one joint.
Osteochondral changes were seen in the ankles of 10 boys (22%), in the elbows of 10 (22%), as well as in the knees of two boys (4%). Eight of the 18 boys (44%) had osteochondral alterations in more than one joint, for a total of 26 affected joints.
X-rays taken at study end detected 24 joints with osteochondral changes in 17 of the 46 boys (37%). The majority (83.3%) corresponded to the changes previously seen on MRI scans, while four did not. Six of the 26 joints with MRI-confirmed osteochondral changes (23.1%) showed no damage on X-rays.
Overall, X-ray assessment of joint health, evaluated by the Pettersson score, showed an excellent correlation with the MRI scores regarding osteochondral changes, the researchers wrote.
Researchers also found that X-ray and MRI scores moderately matched the number of reported joint bleeds seen in the elbows. The correlation was weaker in joint bleeds affecting the ankles, and completely non-existent for those occurring in the knees.
The 27 boys with regular MRI scans had scans spanning a median of 5.8 years. Twenty also had regular X-rays.
Signs of synovium inflammation and joint bleeding seen during regular MRIs were associated with an increased risk of osteochondral damage in the joints.
In fact, a score above zero in the International Prophylaxis Study Group (IPSG) MRI score, which indicates that changes have begun, during interval MRIs was associated with a 90% greater risk of MRI osteochondral changes by the study’s end. (IPSG MRI score ranges from zero to 17; a score of zero indicates no joint changes.)
Overall, “dose- and frequency-adjusted prophylaxis did not completely prevent the progression of MRI-detected joint changes in boys with hemophilia, with 39% of subjects developing objectively determined joint changes, most notably in ankles and elbows,” the researchers wrote.
Changes seen in regular MRIs were associated with an increased risk of joint damage, indicating that “serial MRIs (or other imaging techniques such as ultrasound) in populations of boys with hemophilia could be beneficial in guiding choice of individualized prophylaxis regimens aimed at minimizing subclinical and clinically overt joint bleeding and thus preserving long-term joint health,” the scientists concluded.