Antidrug antibodies against PCSK9 antibody did not affect efficacy and safety
Antidrug Antibodies in Patients Treated with Alirocumab
Letter to the editorLiterature - Roth EM, Goldberg AC, Catapano AL, et al. - NEJM 2017, Epub ahead of print
- 5.1% of alirocumab-treated patients and 1.0% of control patients presented with antidrug antibodies. This presence was persistent (≥12 weeks in at least 2 consequent samples) in 1.4% and 0.2% of patients, respectively.
- Antidrug antibodies did not interfere with efficacy, as comparable reductions in LDL-c levels were maintained over the course of the studies, regardless of antidrug antibody levels. For patients treated with 150 mg every 2 weeks, the least squares (LS) mean LDL-c level at 78 weeks was 52.2 mg/dL (95% CI 50.0-54.3) in patients that did not develop antidrug antibodies, 58.6 mg/dL (95% CI 47.3-69.9, P=0.2752) for those who had transient antidrug antibodies and 60.1 mg/dL (95% CI 41.9-78.2, P=0.3981) for those who had persistent antidrug antibodies, in which P corresponds to the comparison with the no antidrug antibody group. These numbers were 65.3 (95% CI 61.8-68.9), 56.2 (95% CI 44.1-68.3, P=0.1414) and 65.7 mg/dL (95% CI 47.0-84.5, P=0.9677) respectively, for patients who received 75 mg alirocumab every 2 weeks with possible dose increase to 150 mg.
- Regarding safety, no enhanced frequency of adverse events were observed in patients with or without antidrug antibodies (any treatment-emergent adverse event 79.7, 80.6 and 77.3% for no, transient and persistent), although injection-site reactions were more frequent among patients with antidrug antibodies (11.6% for transient and 15.9% for persistent) compared to without (5.9%).
Although antidrug antibodies were present in some patients treated with alirocumab, this did not affect the magnitude and duration of LDL-lowering. However, it should be noted that the number of patients with immunogenicity was very small.