Hidradenitis suppurativa treatment with secukinumab linked to low immunogenicity

Treatment-emergent anti-drug antibodies (TE-ADA) were found in under 1% of patients on IL-17A inhibition with secukinumab for hidradenitis suppurativa (HS). On further analysis, the discovered TE-ADA were non-neutralising.

Since anti-drug antibodies may occur as an immune response to treatment with biologics, possibly altering properties such as pharmacokinetics, inducing side effects, and decreasing efficacy, Prof. Martina Porter (Beth Israel Deaconess Medical Center, MA, USA) and colleagues were interested in the immunogenicity of secukinumab in patients with HS [1,2]. The analysis was based on data from the phase 3 SUNSHINE (NCT03713619) and SUNRISE (NCT03713632) trials, in which secukinumab demonstrated positive efficacy and safety results in patients with moderate-to-severe HS [1,3]. Testing for TE-ADA was performed at baseline and study weeks 16, 52, and 60 (i.e. follow-up period). When TE-ADA were identified, they were further evaluated for potential drug-neutralising abilities and influence on, for example, pharmacokinetics.

Overall, low immunogenicity of secukinumab treatment was found, with TE-ADA rates of 0.6% (SUNSHINE) and 0.8% (SUNRISE) in participants who had had no baseline manifestation of ADA. At week 60, 3 participants on a 300 mg every 4 weeks regimen of secukinumab developed TE-ADA in SUNSHINE. In SUNRISE, 2 participants on bi-weekly medication and 2 receiving secukinumab every 4 weeks had TE-ADA. No loss of efficacy was observed, except for 1 of the TE-ADA-positive participants. Furthermore, pharmacokinetics stayed overall normal in the presence of TE-ADA. Aside from 1 participant, serum trough levels were also within the range of participants negative for TE-ADA. Moreover, no association was observed with immunogenicity-related adverse events.

Relevant readings:

• HS: Targeting IL-1 pathway potential option after anti-TNF failure (AAD 2024)
• BTK signalling as a novel target in hidradenitis suppurativa treatment (AAD 2024)

1. 
   
   1. Porter M, et al. Secukinumab demonstrates low immunogenicity in patients with moderate-to-severe hidradenitis suppurativa: Results from placebo-controlled, double-blind, Phase 3 SUNSHINE and SUNRISE trials. P52241, 2024 AAD Annual Meeting, 8–12 March, San Diego, USA.
   2. Jahn EM, Schneider CK. N Biotechnol. 2009;25:280-6.
   3. Kimball AB, et al. Lancet. 2023;401:747-61.

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Posted on 22 April 202417 May 2024