Final Results of the Prospective ADVATE^® Immune Tolerance Induction Registry (PAIR) Study with Plasma- and Albumin-Free Recombinant Factor VIII

Figures & data

Figure 1 Flow of patients through the PAIR study. *Within 33 months of treatment. ^†As defined by the protocol.

Abbreviations: CAS, completer analysis set; FAS, full analysis set; ITI, immune tolerance induction; PAIR, Prospective ADVATE Immune Tolerance Induction Registry.

Table 1 Baseline Characteristics of Patients in the PAIR Study

Characteristic	FVIII ≤1% (n = 38)	All Patients (N = 44)
Age at ITI therapy start, months, median (range)	19.0 (1.0–320.0)	23.5 (1.0–676)
Race, n (%)
White	24 (63.2)	29 (65.9)
Asian	1 (2.6)	1 (2.3)
Black	4 (10.5)	4 (9.1)
Hispanic	3 (7.9)	3 (6.8)
Other/missing	6 (15.8)	7 (15.9)
Family history of inhibitor, n (%)
Yes	10 (26.3)	11 (25.0)
No	25 (65.8)	30 (68.2)
Unknown	3 (7.9)	3 (6.8)
Titer, BU, median (mean, range)
At diagnosis	4.9 (19.1, 0.7–173.0)	4.9 (21.2, 0.5–173.0)
Peak before ITI therapy^a	12.5 (44.0, 0.7–225.2)	12.5 (43.0, 0.7–225.2)
Immediately before ITI therapy	4.0 (8.5, 0–60.6)	3.95 (8.0, 0–60.6)

Notes: Results by current classification of severe hemophilia (FVIII <1%) are provided in Supplementary Table 1. ^aIf peak titer before ITI therapy was not reported, the maximum of all titer measurements made before ITI therapy was used.

Abbreviations: BU, Bethesda unit; FVIII, coagulation factor VIII; ITI, immune tolerance induction; PAIR, Prospective ADVATE Immune Tolerance Induction Registry.

Table 2 ITI Therapy Dosage Regimens Utilized in the PAIR Study

Dose in IU/kg/day, n (%)	FVIII ≤1% (n = 38)		All Patients (N = 44)
	High Titer^a,b (n = 26)	Low Titer^a,c (n = 12)	High Titer^a,b (n = 29)	Low Titer^a,c (n = 15)
≥200	4 (15.4)	0	4 (13.8)	0
~131–199	2 (7.7)	0	3 (10.3)	0
90–130	16 (61.5)	6 (50.0)	18 (62.1)	8 (53.3)
<90	4 (15.4)	6 (50.0)	4 (13.8)	7 (46.7)

Notes: Results by current classification of severe hemophilia (FVIII <1%) are provided in Supplementary Table 3. ^aIf peak titer before ITI therapy was not reported, the maximum of all titer measurements made before ITI therapy was used. ^b≥5 BU at baseline. ^c<5 BU at baseline.

Abbreviations: BU, Bethesda unit; FVIII, coagulation factor VIII; ITI, immune tolerance induction; IU, international unit; PAIR, Prospective ADVATE Immune Tolerance Induction Registry.

Table 3 Summary of AEs in the PAIR Study (FAS)

AEs	n (% of Total AEs)
All AEs	284 (100.0)
SAEs
Total	56 (19.7)
Considered treatment-related	0
Nonserious AEs
Total	228 (80.3)
Considered unrelated to treatment	214 (75.4)
Considered treatment-related	14 (4.9)
Discontinuations	n (% of Total Patients) (N = 44)
Patient withdrew	2 (4.5)
Physician decision	1 (2.3)
Lost to follow-up	4 (9.1)
Other	2 (4.5)

Abbreviations: AE, adverse events; FAS, full analysis set; PAIR, Prospective ADVATE Immune Tolerance Induction Registry; SAE, serious adverse event.

Table 4 Outcomes in Patients Who Completed rAHF ITI Therapy (CAS)

Completers, n (%)	Severe Hemophilia (FVIII ≤1%) (n = 31)	Non-Severe Hemophilia (FVIII > 1%) (n = 5)	Total (n = 36)
General success	18 (58.1)	3 (60.0)	21 (58.3)
Partial success	2 (6.5)	0 (0)	2 (5.6)
Failure	7 (22.6)	1 (20.0)	8 (22.2)

Note: Results by current classification of severe hemophilia (FVIII <1%) are provided in Supplementary Table 4.

Abbreviations: CAS, completer analysis set; FVIII, coagulation factor VIII; ITI, immune tolerance induction; NA, not available; PK, pharmacokinetic; rAHF, antihemophilic factor (recombinant).

Figure 2 Kaplan–Meier success curves for achievement of first negative titer.

Abbreviations: CI, confidence interval; ITI, immune tolerance induction.