Low immunogenicity of emicizumab in persons with haemophilia A.
Haemophilia
; 27(6): 984-992, 2021 Nov.
Article
en En
| MEDLINE
| ID: mdl-34480814
ABSTRACT
INTRODUCTION:
Emicizumab is a humanised, bispecific monoclonal antibody mimicking the cofactor function of activated factor (F)VIII. It is indicated for routine prophylaxis of bleeding episodes in persons with haemophilia A (PwHA) with/without FVIII inhibitors.AIM:
To evaluate the development of anti-emicizumab antibodies and their impact on pharmacokinetics (PK), pharmacodynamics (PD), efficacy and safety in PwHA.METHODS:
Data from seven completed or ongoing phase 3 studies were pooled. The assessment of the immunogenicity profile of emicizumab included anti-drug antibody (ADA) measurement and the association of ADAs with PK, PD, bleeding events, and adverse events.RESULTS:
Of 668 PwHA evaluable for immunogenicity analysis, 34 (5.1%) developed ADAs after exposure to emicizumab. ADAs were transient in 14/34 PwHA (41.2%). ADAs were neutralising in vitro in 18/34 PwHA (52.9%) and associated with decreased emicizumab concentration in 4/668 evaluable PwHA (.6%); of those, one (.1%) discontinued emicizumab due to loss of efficacy. ADAs without decreased exposure did not impact emicizumab efficacy. The proportion of PwHA who had injection-site reactions (ISRs) was higher in ADA-positive PwHA (29.4% vs. 20.8%); however, the safety profile was similar between ADA-positive and ADA-negative PwHA, overall. No cases of anaphylaxis or hypersensitivity were reported in ADA-positive participants.CONCLUSION:
The immunogenicity risk of emicizumab in phase 3 studies was low. ADAs, including in vitro neutralising ADAs, were not associated with a change in safety profile. Routine surveillance is, therefore, not warranted; however, in cases where a loss and/or waning of efficacy are observed, prompt evaluation by a healthcare provider should be sought.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Anticuerpos Biespecíficos
/
Hemofilia A
Límite:
Humans
Idioma:
En
Revista:
Haemophilia
Asunto de la revista:
HEMATOLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Suiza