Clinically relevant improvements in hemophilia joint health scores (HJHS) were reported with emicizumab prophylaxis therapy in certain subgroups of patients in a study examining its use in patients with hemophilia A (PwHA) who did not have factor VIII (FVIII) inhibitors. The study findings were published in the journal Haemophilia.
In an exploratory analysis of the phase 3 HAVEN 3 study (ClinicalTrials.gov Identifier: NCT02847637), PwHA were evaluated for joint health using the HJHS version 2.1 tool at baseline and at multiple time points; a higher score with this scale suggests more severe symptoms. Biomarker analyses related to bone and joint health were also performed at various time points.
Patients with prior episodic FVIII treatment were randomized into 3 study arms (arms A, B, and C). In arms A and B, patients received emicizumab prophylaxis with a weekly loading dose (3.0 mg/kg) for 4 weeks, and then a maintenance dose of 1.5 mg/kg given weekly for arm A (36 patients) or 3.0 mg/kg every 2 weeks for arm B (35 patients). Arm C (18 patients) did not receive prophylaxis for the first 24 weeks but could switch to receiving emicizumab (3.0 mg/kg) every 2 weeks after that point.
A fourth arm, arm D, included 63 PwHA who previously received prophylactic FVIII. These patients received emicizumab dosed at 3.0 mg/kg weekly for 4 weeks, after which they received a 1.5-mg/kg weekly maintenance dose.
The mean patient age overall was 38.3 years (range, 13-77). Baseline HJHS scores tended to be lower in patients who had previously received prophylactic FVIII, who were younger than 40 years of age, or who did not have target joints at baseline.
Across the total population, the mean improvement in total HJHS was -1.86 (95% CI, -3.53 to -0.20) from baseline to week 49. Patients with 1 or more target joints at baseline had a mean improvement in total HJHS of -2.28 (95% CI, -4.15 to -0.42) from baseline to week 49.
Patients with 1 or more target joints at baseline had a mean improvement of -2.13 (95% CI, -3.96 to -0.29) in the HJHS joint-specific domain at week 49, compared with baseline. Improvements for patients with target joints were reportedly maintained through week 97. Patients in the age group of 12 to 39 years also showed HJHS improvements in comparison with baseline.
A total of 117 patients in the study had biomarker data available for analysis. There were not significant differences through week 73, compared with baseline, in most biomarkers with emicizumab prophylaxis. Compared with adults, however, adolescents showed higher levels of certain biomarkers related to bone formation and bone resorption across the study period. These included N-terminal pro-peptide of type I procollagen, osteocalcin, and C-terminal telopeptide of type I collagen.
“Clinically relevant improvements in HJHS were observed in adolescents and younger adults and in those with target joints after 48 weeks of emicizumab in HAVEN 3; this effect was maintained through 96 weeks of emicizumab prophylaxis,” the study investigators wrote in their report.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Kiialainen A, Niggli M, Kempton CL, et al. Effect of emicizumab prophylaxis on bone and joint health markers in people with haemophilia A without factor VIII inhibitors in the HAVEN 3 study. Haemophilia. Published online July 29, 2022. doi:10.1111/hae.14642