Early Treatment Linked to Less Joint Damage in Severe Hemophilia A

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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In boys and men with severe hemophilia A, joint damage accumulates with age, and can be prevented if replacement therapy is started at a younger age, according to a small, single-center study in China.

In addition, poor adherence to preventive, or prophylactic treatment was significantly associated with greater joint damage.

These findings highlight the importance of both early treatment and compliance with the therapy plan in this patient population, the researchers noted, adding that larger studies are needed to confirm these results.

The study, “Joint status and related risk factors in patients with severe hemophilia A: a single-center cross-sectional study,” was published in the journal Hematology.

Severe hemophilia A, caused by extremely low levels of clotting factor VIII (FVIII), is characterized by recurrent bleeds often affecting the joints, which ultimately result in joint disease, called arthropathy, and pain, as well as a lower quality of life.

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FVIII replacement therapy, which delivers the missing FVIII directly to a patient’s blood, is the gold standard treatment for hemophilia A.

Continuous, prophylactic treatment starting before age 3 and the onset of clinical arthropathy is “the most effective regimen and is strongly recommended for joint protection,” the researchers wrote.

However, “inadequate treatment is common in the real world,” they wrote, noting that many severe hemophilia A patients have a delay in initial treatment or receive replacement therapy only on demand or intermittently.

In addition, non-adherence to a prescribed treatment plan, specifically preventive therapy, is common due to several social and economic reasons.

“Only a small portion of [patients with severe hemophilia A] can afford continuous prophylaxis,” the team wrote.

As such, it is imperative to regularly assess joint health in these patients to “recognize early reversible joint impairment and promptly optimize treatment regimens accordingly,” the researchers wrote.

Now, investigators from Xiangya Hospital, in China, analyzed the joint status of 31 boys and men with severe hemophilia A who were seen at their center. They also evaluated the impact of age, treatment delay — the interval between diagnosis and treatment initiation — prophylaxis, and adherence to treatment on patients’ joint health.

Patients’ demographic, clinical, and treatment information was collected, as well as their self-reported joint status. The health of six joints — both elbows, knees, and ankles — also was assessed through two validated measures.

The Hemophilia Early Arthropathy Detection with UltraSound in China (HEAD-US-C) was used to evaluate joint structure, while the Hemophilia Joint Health Score (HJHS) was used to assess function. Higher scores on both measures indicate worse joint health.

Treatment adherence was evaluated using the Validated Hemophilia Regimen Treatment Adherence Scale-Prophylaxis.

The patients’ ages ranged from 4 to 41, with a median age of 22. They had been diagnosed at a median age of 1 and had started treatment at a median age of 5, reflecting a median treatment delay of 2.75 years. Nearly half (48%) began treatment more than a year after diagnosis.

While all patients were on FVIII replacement treatment, a large proportion (45%) were treated on-demand, and only four (13%) were on continuous prophylaxis.

Results showed that the total number of patient-reported affected joints was similar to that detected through HEAD-US-C, but lower than that reported through HJHS, suggesting that joint impairment may occur earlier than structural changes and clinical symptoms.

As such, “objective assessments were vital for discovering early joint impairment,” the researchers wrote, adding that such measurements “should be considered in addition to bleeding episodes when treatment regimens are adjusted.”

Scores of both measures were the highest for the knee, suggesting that it was “the joint with the worst condition,” according to the investigators.

Consistent with previous studies, higher HEAD-US-C scores were significantly associated with higher HJHS scores, highlighting a link between joint structure and function.

In addition, older age was significantly associated with higher scores on both joint measures, suggesting that joint damage accumulates with increasing age.

Patients with more than one year of treatment delay showed worse joint structure and function than those whose treatment began within one year of diagnosis, but this difference only reached statistical significance for HJHS.

Notably, when adjusted for potential influencing factors, older age at treatment initiation, but not longer treatment delay, was significantly associated with higher HEAD-US-C and HJHS scores.

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These results highlight the importance of starting treatment at younger ages and as soon as possible after diagnosis to prevent joint impairment in severe hemophilia A patients.

Moreover, no significant differences in joint health were detected between patients on on-demand treatment, intermittent prophylaxis, and continuous prophylaxis.

The team noted that this may be related to the small number of patients on continuous preventive treatment and the fact that those on intermittent prophylaxis were relatively older (median age of 30) and likely to have greater joint damage.

Also, among the 17 patients on prophylaxis, poor treatment adherence was significantly associated with worse joint structure and function, “suggesting that better adherence to prophylaxis was beneficial for joint protection,” the researchers wrote.

These findings indicate that arthropathy was common in this group of boys and men with severe hemophilia A and that “prompt treatment and adherence improvement may reduce severity,” the team wrote.

“Treatment delay is a specific situation in China, especially in financially limited areas,” the researchers wrote, adding that the leading cause of insufficient treatment in these patients was “financial burden.” While most patients (74%) had health insurance, it only covered the cost of on-demand treatment.

Larger, multi-center studies following patients over time are needed to confirm these findings, the team said, noting the relatively small number of individuals treated at this center.