Estimates of the risk of inhibitors development after product switch
| Year . | Author/reference . | Design . | Sample . | Follow-up, mo . | Inhibitors . | Rate, × 1000 patient/y . | Notes . |
|---|---|---|---|---|---|---|---|
| 1988 | Giles et al59 * | Prospective | 478 | 12 | 18 | 0.019 | |
| 339 | 24 | 17 | 0.030 | ||||
| 2007 | Singleton et al63 † | Retrospective | 94 | ≤ 20 | 4 | 0.042 | All patients |
| 77 | ≤ 20 | 1 | 0.013 | (−) history | |||
| 2007 | Gouw et al66 ‡ | Retrospective | 316 | (> 50 ED) | NR | ||
| 2008 | Rubinger60 § | Prospective | 225 | 12 | 0 | 0 | |
| 189 | 24 | 0 | 0 | ||||
| 2009 | Rea et al61 ‖ | Retrospective | 33 | > 3 | 1 | 0.033 | |
| 2011 | Siegmund et al65 ¶ | Retrospective# | 118 | NA | 0 | ||
| 2011 | Bacon et al62 # | Retrospective | 113£ | Up to > 100 ED | 1 | 0.009 |
| Year . | Author/reference . | Design . | Sample . | Follow-up, mo . | Inhibitors . | Rate, × 1000 patient/y . | Notes . |
|---|---|---|---|---|---|---|---|
| 1988 | Giles et al59 * | Prospective | 478 | 12 | 18 | 0.019 | |
| 339 | 24 | 17 | 0.030 | ||||
| 2007 | Singleton et al63 † | Retrospective | 94 | ≤ 20 | 4 | 0.042 | All patients |
| 77 | ≤ 20 | 1 | 0.013 | (−) history | |||
| 2007 | Gouw et al66 ‡ | Retrospective | 316 | (> 50 ED) | NR | ||
| 2008 | Rubinger60 § | Prospective | 225 | 12 | 0 | 0 | |
| 189 | 24 | 0 | 0 | ||||
| 2009 | Rea et al61 ‖ | Retrospective | 33 | > 3 | 1 | 0.033 | |
| 2011 | Siegmund et al65 ¶ | Retrospective# | 118 | NA | 0 | ||
| 2011 | Bacon et al62 # | Retrospective | 113£ | Up to > 100 ED | 1 | 0.009 |
BDD indicates B-domain deleted; ED, exposure day; NR, not reported; PTP, previously treated patients; and NA, not available.
Rate of inhibitor positivity before switch was 0.079. When these patients were not excluded, rates were 0.038 at 12 months and 0.050 at 24 months.
A total of 17 patients had history of previous inhibitors, of which 3 of developed a recurrence. All 4 inhibitors were transient, the only 1 de novo was secondary to surgery. At study completion, 51 patients had > 100 ED, and 24 had 20-100 ED.
The study enrolled PTPs and reported the RR for inhibitor development in 54 patients switching versus those not switching. The adjusted RR was 0.9 (95% confidence interval 0.5-1.6).
A total of 274 patients were tested at baseline, of which 4 were positive (0.014).
Cases observed over 8 years and switched from full-length to BDD factor VIII, the observed inhibitor was transient and secondary to surgery.
The cases were observed over 14 years, and switched from plasma-derived to recombinant factor VIII. A total of 101 patients had severe disease.
The observed inhibitor was in a PTP. No recurrent inhibitors were observed after switching 16 patients with a positive inhibitor history.