Real-world study of rurioctocog alfa pegol and emicizumab in US clinical practice among patients with hemophilia A

Figures & data

Figure 1. Study design.

*Data for the octocog alfa cohort are excluded from this report because of the limited sample size and lack of pre-/post-switch data for within-group comparison.

Figure 2. Summary of propensity-score matching.

Figure 3. Patient disposition.

Table 1. Patient demographic and characteristics at baseline.

	Emicizumab cohort n = 85	Matched emicizumab cohort* n = 54	Rurioctocog alfa pegol cohort n = 18
Age (SD), years
0–9	18 (21.2)	8 (14.8)	3 (16.7)
10–19	41 (48.2)	23 (42.6)	7 (38.9)
≥20	26 (30.6)	23 (42.6)	8 (44.4)
P value vs rurioctocog alfa pegol cohort	0.526	1.000
Hemophilia severity, n (%)
Moderate: 1–5% FVIII	11 (12.9)	4 (7.4)	1 (5.6)
Severe: <1% FVIII	74 (87.1)	50 (92.6)	17 (94.4)
P value vs rurioctocog alfa pegol cohort	0.687	1.000
Number of target joints, n (%)	n = 64	n = 39	n = 11
0	48 (75.0)	26 (66.7)	4 (36.4)
1	10 (15.6)	7 (17.9)	3 (27.3)
2	4 (6.2)	4 (10.3)	2 (18.2)
≥3	2 (3.1)	2 (5.1)	2 (18.2)
P value vs rurioctocog alfa pegol cohort	0.025	0.368
Pre-index ABR, mean (range)	1.68 (0–9)	2.06 (0–9)	2.19 (0–9)
P value vs rurioctocog alfa pegol cohort	0.160	0.730

*Propensity-score matched to rurioctocog alfa pegol cohort based on age, hemophilia severity, and pre-index ABR; 54 patients from 85 patients in emicizumab cohort.

Baseline defined as ≥6 months before index date.

ABR, annualized bleed rate; FVIII, factor VIII; SD, standard deviation.

Table 2. Total mean weekly consumption of on-demand and prophylactic FVIII and emicizumab.

	Emicizumab n = 85	Matched emicizumab n = 54	Rurioctocog alfa pegol n = 18	Rurioctocog alfa pegol with outlier bleed removed* n = 17
Pre-index
On-demand FVIII medical procedures, IU ± SD	38 ± 185	34 ± 188	19 ± 83	21 ± 85
On-demand FVIII bleed or preventive, IU ± SD	746 ± 1342	960 ± 1524	836 ± 1576	839 ± 1625
FVIII for prophylaxis by standard regimen, IU ± SD	6851 ± 4075	7650 ± 4039	6884 ± 3347	6733 ± 3386
Total weekly total FVIII consumption, IU ± SD	7635 ± 4655	8644 ± 4724	7740 ± 4129	7593 ± 4207
Post-index
On-demand FVIII medical procedures, IU ± SD	18 ± 87	25 ± 107	0 ± 0	0 ± 0
On-demand FVIII bleed or preventive, IU ± SD	94 ± 198	127 ± 232	171 ± 396	81 ± 117
Prophylactic emicizumab (mg/kg) or rurioctocog alfa pegol (IU/kg) consumption ± SD	109 ± 67	124 ± 72	6224 ± 2939	6138 ± 3006
Total weekly total FVIII consumption, IU ± SD	112 ± 221	153 ± 259	6395 ± 2973	6219 ± 2966

*One patient had a bleed that required 92,340 IU to resolve. This patient was removed from this column as a sensitivity analysis.

FVIII, factor VIII; SD, standard deviation.

Table 3. Proportional wastage of FVIII and emicizumab prophylaxis.

Emicizumab cohort	Proportion wastage FVIII therapy, pre-index				Proportion wastage, emicizumab, post-index
	≥10%, n/N (%)		≥20%, n/N (%)	Mean %	≥10%, n/N (%)	≥20%, n/N (%)	Mean %
All	3/85 (3.5)		1/85 (1.2)	1.00	24/85 (28.2)	11/85 (12.9)	8.40
Matched emicizumab	2/54 (3.7)		1/54 (1.9)	0.38	12/54 (22.2)	5/54 (9.3)	6.00
	Proportion wastage FVIII therapy, pre-index				Proportion wastage, rurioctocog alfa pegol, post-index
Rurioctocog alfa pegol cohort	≥10%, n/N (%)		≥20%, n/N (%)	Mean %	≥10%, n/N (%)	≥20%, n/N (%)	Mean %
All, n/N (%)	0/18 (0)		0/18 (0)	−0.30	0/18 (0)	0/18 (0)	−0.30
Paired t-test for change in wastage, all emicizumab; n = 85
Estimate (95% CI), %		+7.41 (4.28 to 10.15)					P^1<0.001
Paired t-test for change in wastage, matched emicizumab cohort; n = 54
Estimate (95% CI), %		+5.61 (2.87 to 8.36)					P^1<0.001
Paired t-test for change in wastage post switch; rurioctocog alfa pegol; n = 18
Estimate (95% CI), %		+0.00 (−2.87 to 2.87)					P^1 = 0.997
T-test for difference in wastage proportion for emicizumab vs rurioctocog alfa pegol
Estimate (95% CI); difference, %		+8.70 (5.48 to 11.93)					P^2<0.001
T-test for difference in wastage proportion for matched emicizumab vs rurioctocog alfa pegol
Estimate (95% CI); difference, %		+6.30 (3.64 to 8.96)					P^2<0.001

CI, confidence interval.

P¹ Paired t-test; P² t-test.

Table 4. Observed ABR during pre- and post-treatment switch periods and change in ABR after switching.

		ABR pre-index	ABR post-index	Difference in ABR from pre- to post-index
	Bleed type	Mean (95% CI)
Rurioctocog alfa pegol (n = 18)	All	2.19 (1.23–3.36)	0.66 (0.30–1.15)	−1.53 (−2.36 to −0.80)*
Emicizumab (n = 85)		1.68 (1.21–2.20)	0.63 (0.39–0.89)	−1.05 (−1.58 to −0.56)
Matched emicizumab (n = 54)		2.06 (1.39–2.80)	0.69 (0.36–1.09)	−1.36 (−2.15 to −0.62)
Rurioctocog alfa pegol (n = 18)	Joint	1.36 (0.75–2.01)	0.38 (0.16–0.62)	−0.98 (−1.57 to −0.44)
Emicizumab (n = 85)		0.76 (0.53–1.02)	0.37 (0.22–0.54)	−0.40 (−0.67 to −0.13)
Matched emicizumab (n = 54)		0.89 (0.57–1.24)	0.45 (0.23–0.69)	−0.44 (−0.83 to −0.07)
Rurioctocog alfa pegol (n = 18)	Spontaneous	0.58 (0.27–0.89)	0.33 (0.15–0.52)	−0.25 (−0.65 to 0.14)
Emicizumab (n = 85)		0.70 (0.45–1.00)	0.26 (0.13–0.42)	−0.44 (−0.74 to −0.17)
Matched emicizumab (n = 54)		0.86 (0.50–1.28)	0.31 (0.13–0.51)	−0.55 (−1.01 to −0.13)
Rurioctocog alfa pegol (n = 18)	Trauma/injury	1.42 (0.56–2.55)	0.28 (0.04–0.64)	−1.14 (−1.96 to −0.46)
Emicizumab (n = 85)		0.76 (0.47–1.09)	0.33 (0.15–0.55)	−0.43 (−0.78 to −0.10)
Matched emicizumab (n = 54)		0.98 (0.54–1.48)	0.39 (0.11–0.73)	−0.59 (−1.13 to −0.07)
Rurioctocog alfa pegol (n = 18)	Spontaneous joint	0.39 (0.13–0.65)	0.24 (0.08–0.43)	−0.15 (−0.46 to 0.14)
Emicizumab (n = 85)		0.43 (0.27–0.62)	0.19 (0.09–0.31)	−0.24 (−0.43 to −0.07)
Matched emicizumab (n = 54)		0.50 (0.30–0.72)	0.22 (0.09–0.38)	−0.28 (−0.53 to −0.05)

*Versus emicizumab, P = 0.527; versus matched emicizumab, P = 0.738 (treatment × post-index interaction term).

ABR, annualized bleeding rate; CI, confidence interval.