Background

The satisfactory bleeding prevention and favorable safety of emicizumab had been reported in severe hemophilia A children with inhibitors (SHAcwI). However, the real-world experience of emicizumab prophylaxis and especially for inhibitor process for SHAcwI is unclear.

Objective

To evaluate the inhibitor status and process of SHAcwI who achieved ITI success, interrupt ITI or not receive ITI and transitioned from Factor (F)VIII to emicizumab.

Methods and materials

This is a single-institution, retrospective review of SHAcwI who received emicizumab.

Results

Total 14 SHAcwI were included with the median historical peak inhibitor titer of 71.2 (range, 9.6 -391.4 Bethesda Unit [BU]/mL). The baseline clinical variants were shown in Table 1. Their inhibitors were diagnosed initially at age of 2.0 (0.09 - 8.43) years. Their F8 genotypes were displayed in Figure 1. Half of patients had intron 22 inversion.

Among the 14 patients, 12 (85.7%) had received ITI treatment before emicizumab, with 66.7% for FVIII 50 IU/kg every other day. Recombinant FVIII and plasm-derived FVIII each account for half. The duration on ITI was 5.7 (0.3 - 74.8) months because of most patients transitioned from early ITI treatment to emicizumab. Total 4 (33.3%) patients achieved ITI success, then transitioned from FVIII to emicizumab immediately (<1 month) without FVIII prophylaxis, and similarly for other patients (12 on ITI, 2 has not yet started). All patients started emicizumab at 4.1 (1.6 - 15.0) years, with loading regimen of 2.3 (1.5 - 3.2) mg/kg/week, and maintenance regimen of 5.4 (3.2 - 6.8) mg/kg/month. Their pre-emicizumab inhibitor titer was 4.9 (0, 416) BU/mL.

During emicizumab prophylaxis, inhibitors were monitored at 5.3 (0.2 - 31.2) months after initial emicizumab. The Figure 2 shown the inhibitors process of 13 patients. Among them, 4 (30.8%) patients experienced an upward trend of inhibitor temporarily at 1.3 (0.8 - 2.9) months after initial emicizumab. Pt-04 experienced the bleeding events and received FVIII exposure. Notably, the four patients (Pt-4/9/13/14) had relatively higher peak inhibitor titer of 226.4 (29.8 - 391.4) BU/mL. And 5 (38.5%) patients (Pt-1/7/10/11/12) had negative inhibitor titer before emicizumab treatment. Among the five patients, 3 patients kept negative inhibitor, 1 patient (Pt-11) occurred inhibitor titer of 1.2 BU/ml at 1 month post-emicizumab then turned to negative again at 7.7 months of emicizumab treatment, and 1 patient (Pt-10) occurred inhibitor titer of 6.3 BU/ml at 1.4 month post-emicizumab. Interestingly, no breakthrough bleeding event was documented for the Pt-11 and Pt-10. Additionally, the steady downward trend was discovered in other 4 patients (Pt-2/3/5/6).

After switching to emicizumab, significantly reduced annualized bleeding rate (0 [0 - 1.0] vs. 0.4 [0 - 4.0], p = 0.06) and annualized joint bleeding rate (0 [0 - 0.2] vs. 0 [0 - 3.0], p = 0.018) were observed (Figure 3).

Conclusions

Emicizumab prophylaxis was an efficacious option to control bleedings for SHAcwI. Inhibitor levels demonstrate a transient upward trend during the initial phase of emicizumab treatment. This phenomenon appears to be independent of breakthrough bleeding or exposure to FVIII.

Disclosures

No relevant conflicts of interest to declare.

This content is only available as a PDF.
2024
Sign in via your Institution