Development of neutralizing antibodies or treatment-emergent antidrug antibodies (TE-ADAs) is uncommon, transient, and does not affect the clinical efficacy or safety of secukinumab in patients with moderate to severe plaque psoriasis, according to study results published in the Journal of the European Academy of Dermatology and Venereology.
The analysis was based on phase 3 extension studies SCULPTURE and ERASURE, both of which investigated secukinumab in patients with moderate to severe plaque psoriasis for ≤5 years. In the SCULPTURE study, fixed-interval and retreatment-as-needed regimens, consisting of secukinumab 300 mg or 150 mg for maintenance of response, were compared for ≤52 weeks. The ERASURE study compared 300-mg and 150-mg secukinumab doses with placebo for the same period. Patients with serum samples taken at 76 weeks were included in the analysis.
The psoriasis area and severity index (PASI) was used to evaluate disease activity, with PASI response and partial response defined as a ≥75% reduction from baseline score and a ≥50% to <75% reduction from baseline PASI, respectively. The researchers also looked at TE-ADAs, which were defined as post-treatment positive antidrug antibody signals in patients with negative signals at baseline.
Of the 1636 patients who received secukinumab and were subsequently evaluated for antidrug antibodies, a total of 32 developed TE-ADAs. The number of TE-ADAs in the sample translated to cases <1%/y [MT2] over 5 years.
Approximately 28% of patients with TE-ADAs (n=9) had neutralizing antibodies. Up to 5.4% of the 9992 pharmacokinetic samples assessed at the time of immunogenicity determination exhibited secukinumab concentrations higher than the drug tolerance level of 53.8 μg/mL.
The development of TE-ADAs in both studies did not correlate with a loss of secukinumab response. There was also no effect of TE-ADAs on safety or pharmacokinetics of the study therapy.
A limitation of the study was the retrospective nature of the analysis.
“Half of the TE-ADA cases that occurred were transient, had low titers, and were not associated with any particular secukinumab dose or treatment regimen,” the researchers concluded.
Reich K, Blauvelt A, Armstrong A, et al. Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, exhibits low immunogenicity in psoriasis patients treated up to 5 years [published online April 22, 2019]. J Eur Acad Dermatol Venereol. doi:10.1111/jdv.15637