Hyaluronic Acid Eases Joint Damage of Hemophilia, Study Reports

2 injections of supplement over one year aided most adults with ankle arthropathy

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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hyaluronic acid joint supplement | Hemophilia News Today | pilot study of joint damage treatment | illustration of person's lower leg

Adults with hemophilia and ankle joint damage taking part in a yearlong pilot study largely reported that two injections of hyaluronic acid, which acts to lubricate the joint, eased ankle pain and improved movement.

The treatment, given six months apart in this U.K. trial, also enabled most of these people to better participate in physical and social activities.

Because the small trial lacked an untreated control group for comparison, researchers said its findings cannot be used to determine hyaluronic acid’s effectiveness for ankle arthropathy in hemophilia patients. Rather, they support a larger study of the treatment’s safety and efficacy.

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The study, “A single centre, open label, pilot study evaluating the effect of intra-articular hyaluronic acid injection on pain and functionality when injected into the ankle (tibio-talar and sub-talar) joint in patients with haemophilic arthropathy,” was published in the journal Haemophilia.

Hyaluronic acid a supplement for people with joint disease

Arthropathy, or joint disease, is a common complication of hemophilia caused by repeated bleeding episodes in a joint. While arthropathy may impact all large joints, it is often found in the ankle joint.

Injections of hyaluronic acid (HA) — a natural lubricating substance found in joint fluid — have been used to treat other conditions, such as osteoarthritis, a degenerative joint disease. Small studies also suggest benefit with hemophilic arthropathy of the knee joint.

However, limited evidence supports the use of HA in the ankle joint of people with hemophilia.

Researchers at the Nuffield Orthopaedic Centre in Oxfordshire, England, evaluated the impact of two, six-month ankle injections of HA, sold as Ostenil Plus, on easing pain in 21 adults with ankle arthropathy being followed at an Oxford hemophilia care center.

Participants’ mean age was 35.2, and 19 had hemophilia A and two had hemophilia B. MRI scans confirmed the presence of severe ankle arthropathy across the group.

Among them, 19 were on routine preventive replacement therapy, one was receiving on-demand treatment, and another was being treated with Hemlibra (emicizumab) due to the presence of inhibitors, or neutralizing antibodies that reduce the effectiveness of replacement therapies.

HA was injected into a patient’s affected ankle at the study’s start (baseline) and again after six months. In total, 26 joints were given HA injections: 12 left ankles and 14 right ones. For five patients, both ankles were treated. Participants were then followed for an additional six months.

The study’s primary goal was a reduction in self-reported pain at 12 months, as measured by the visual analog scale (VAS) pain score, in which 0 indicates no pain and 10 extreme pain. Secondary measures focused on joint function, quality of life, and safety.

The overall annualized bleeding rate in the year before the study was 2.2. At baseline, the mean hemophilia joint health score (HJHS), a measure of joint function, was 7 for the left ankle and 4.9 for the right ankle. HJHS scores range from 0–20 for each joint, with higher scores reflecting poorer joint function. The hemophilia activity list (HAL) for physical activity was 68.7, “showing moderately affected functional ability,” the team noted.

Findings of pilot study evaluating 21 hemophilia patients

The mean baseline VAS pain score across all affected ankle joints was 5.6. Over the following 12 months, there was a progressive and statistically significant drop in these pain scores. One year later, the mean VAS score was 3.4.

Of the 26 joints injected with HA, 11 had a greater than 30% reduction in VAS scores after three months. After one year, a significant reduction in reported pain was observed in 18 joints.

At one year, lower VAS scores were reported in 22 joints (85%), higher (worse) scores were reported in three joints (11%), and one joint showed no change in pain (4%).

Accordingly, ankle joint function progressively improved over the course of that year, as shown by better scores in the activities of a daily living section of the foot and ankle ability measure (FAAM) assessment. Self-reported, FAAM is a measure of physical abilities in individuals experiencing lower leg, foot, and ankle function impairments. No changes in FAAM sports scores were noted.

HJHS scores for hemophilia ankle health significantly improved, moving from 6.1 to 4.0 after one year. Patients’ annualized bleeding rate also dropped from 2.2 to 1.4, but the difference was not statistically significant. There was no change in health-related quality of life, as assessed with the EQ-5D-5L.

Treatment was considered safe, with one patient reporting a feeling of faintness after receiving the first ankle injection that resolved without treatment.

Participants were asked to provide feedback on the intervention, giving 16 positive responses, four that noted no change, and one holding a negative view of HA treatment.

Positive comments included feelings of lesser ankle pain and stiffness, supporting movement with greater confidence and a greater ability to engage in physical activities, sports, and other social events.

“I felt more confident on my feet. It no longer locked up as frequently or as long as before, and it felt as though I had slightly more movement,” said one participant.

Mobility was certainly more comfortable. Climbing stairs was certainly easier as was walking,” said another. “Can’t say how long the relief lasted although it was longer than the standard steroid injection.”

Another noted a “stable feeling in ankle. Running pace improved. Noticeable improvement in pain, and mood due to pain.”

Among reasons given for “no change” responses were a drop in “general activity” due to the COVID-19 pandemic, “which has probably helped with my ankle. So it’s hard to tell how much difference is due to the injection or due to the reduced activity,”  said one person in this group.

The one patient with worsening symptoms was placed on a waiting list for ankle fusion surgery, the scientists reported.

Although its small size, common in pilot studies, limited the relevance of these findings, the researchers favored further evaluation in larger and placebo-controlled trials.

“This study supports the completion of a future, larger study to evaluate the efficacy of HA,” they wrote. “The ideal design would be a randomised controlled trial with a placebo comparator arm.”