Preventive Esperoct Plus Surgery Reduces Joint Bleeds, Aids Mobility
Preventive treatment with Esperoct (turoctocog alfa pegol) plus joint surgery significantly decreased annual joint bleeding rates, reduced pain, and improved mobility in hemophilia A patients, according to an analysis of Pathfinder trial data.
“Our results therefore support the notion that patients with haemophilia A being treated with [Esperoct] prophylaxis benefit from surgeries,” the scientists wrote.
The analysis was published in the journal Haemophilia, in the study, “Clinical outcomes after joint surgery in patients on turoctocog alfa pegol (N8-GP) prophylaxis: A post hoc analysis.”
People with hemophilia A often experience regular bleeding in the joints due to the lack of a blood-clotting protein called factor VIII (FVIII). As a result, patients may require surgery to lessen pain, improve mobility, and enhance their quality of life.
Esperoct is an approved treatment for hemophilia A that is used as an on-demand treatment to help stop bleeding episodes, as well as a prophylactic treatment to help prevent bleeds. Its safety and efficacy were evaluated in the Pathfinder clinical trial program, sponsored by Novo Nordisk, the therapy’s developer.
The open-label Phase 3 Pathfinder 2 study (NCT01480180), completed in December 2018, assessed the safety and efficacy of Esperoct when given prophylactically every fourth day, or on an on-demand basis, to 186 patients with severe hemophilia A, ages 12 and older. With prophylactic treatment, patients achieved a median annualized bleeding rate (ABR) of 0.84, and during the sixth year, 64% of participants did not experience bleeds.
The Phase 3 Pathfinder 3 trial (NCT01489111), also completed in 2018, specifically investigated the safety and efficacy of Esperoct in a subgroup of 36 patients from Pathfinder 2 who had needed surgery and received at least five doses of the medication. These patients then returned to Pathfinder 2 to continue Esperoct prophylaxis until the end of the trial.
The aim of this study, conducted by researchers at the University of Sheffield, in the U.K., and their colleagues, was to examine the impact of joint surgery followed by Esperoct prophylaxis on joint ABR. The report also assessed patient responses to questions related to physical health from the Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL).
The team collected patient information from individuals from both Pathfinder 2 and 3. Those who received on-demand treatment and non-joint surgery were excluded from this analysis. A total of 41 joint surgeries in 30 patients — with a mean age of 37.6 — were examined.
Before surgery, patients received Esperoct for a mean of 702 days (almost two years), ranging from 17 to 2,017 days (5.5 years). After surgery, patients received treatment for a mean of 1,180 days (3.2 years), ranging from 54 to 1,938 days (5.3 years).
The analysis revealed that, compared with before surgery, there was a significant decrease in mean joint ABR after such procedures (1.33 vs. 0.37).
Before surgery, the mean joint ABR was significantly higher, over an equivalent period, in patients who had an operation than among those who did not (1.33 vs. 0.33).
Post-surgery, in 27 participants, the joint ABR improved or stayed the same, compared with pre-surgery. Most of these patients had a pre-surgery joint ABR of less than 3, but among the four individuals who improved, the pre-surgery joint ABR was 3 or higher.
Of the 13 individuals whose joint ABR improved with surgery (17 surgeries in total), the reason for the operation included joint disease (arthropathy) and/or pain, as well as bone problems. One patient underwent surgery for two indications: chronic pain and bone abnormalities. In 15 of the 17 surgeries, the joint ABR dropped to 0; in the remaining two surgeries, it dropped to 1.
Most participants with a joint ABR of 0, before and after surgery, were operated on because of arthropathy. Other indications included prosthesis issues and Charcot ankle — a progressive condition characterized by the slow weakening of bones, joints, and soft tissues of the ankle due to nerve damage.
Patients who underwent surgery for arthropathy and whose joint ABR remained 0 had long-term joint disease caused by hemophilia. Only three bleeding episodes were reported at the operation site, and all other bleeds occurred at non-operated sites.
All of those with a stable joint ABR of 1 had arthropathy in multiple joints, and after surgery, bleeds occurred mostly at non-operated sites, which indicated that “surgery may have improved joint pathology [disease] and decreased bleeding in the affected joint,” the team wrote.
In three patients, joint ABR increased from 0 before surgery to between 2 and 3 after the operation. Two of these individuals had surgery for prosthetic pain and trigger thumbs in both digits (thumbs stuck in a bent position).
The other patient had surgery for arthropathy and experienced joint or muscle bleeding in the right knee, calf, and thigh 23 days post-surgery. This was most likely due to “insufficient FVIII substitution,” according to the researchers, who noted that the dose of FVIII was increased.
Following the added treatment, “mobility-related outcomes improved in this patient,” they wrote.
Based on responses to the Haem-A-QoL, in participants whose joint ABR remained at 0 before and after surgery, joint pain often remained the same, while pain and mobility during movement tended to improve.
Similar results were seen in patients whose joint ABR did not improve with surgery. In these individuals, following seven operations, Haem-A-QoL scores associated with joint pain improved, and after four procedures, the scores worsened. Following 11 surgeries, the scores remained the same.
In movement-related pain, following 14 operations, the Haem-A-QoL score improved, while after five surgeries, the scores worsened, and following three surgeries, it stayed the same. Improvements in walking were found after 12 operations; it remained the same after six surgeries and worsened following five procedures.
“Our results provide evidence that [joint] ABR significantly declined post-surgery and, most often, pain and mobility parameters improved in patients whose pre- and post-surgery [joint] ABR was zero,” the investigators wrote.
“It is likely that the beneficial effects observed in our study are a result of both surgery and concurrent treatment with [Esperoct] prophylaxis,” they concluded.