Psoriasis Retreatment Efficacy: Is Immunogenicity A Threat?

Abstract

Introduction Although biologic therapy has revolutionized psoriasis treatment by enabling potential disease remission, there is a risk of immunogenicity and antidrug antibody (ADA) formation, especially with intermittent therapy. Although clinically unproven, formation of ADAs, specifically neutralizing antibodies (NAbs), may reduce treatment efficacy. Here, we summarize and compare ADA and Nab incidences, as well as retreatment efficacy, of plaque psoriasis−indicated monoclonal antibodies (mAbs).

Methods Evaluated compounds included anti–tumor necrosis factor α (anti-TNFα; infliximab, adalimumab, certolizumab pegol), anti–interleukin-12/-23 (anti–IL-12/-23; ustekinumab), anti–IL-23 (guselkumab, tildrakizumab, risankizumab), and anti–IL-17 (secukinumab, ixekizumab, brodalumab, bimekizumab) mAbs. Prescribing information and published literature were leveraged for ADA/NAb incidence and retreatment data, respectively. ADA incidences represent the percentage of patients with ADAs among all patients who received each mAb. NAb incidences represent the percentage of patients with NAbs among all patients who were positive for ADAs. These incidences are reported for the population of interest (ie, those treated for plaque psoriasis) except for secukinumab and ustekinumab, for which ADA/NAb rates are reported for several indications, including plaque psoriasis.

Results Fully human antibodies (adalimumab, ustekinumab, guselkumab, secukinumab, brodalumab) had lower ADA incidences (range, <1%-12%) than humanized (tildrakizumab, risankizumab, ixekizumab, bimekizumab), humanized Fab' fragment (certolizumab pegol), or chimeric (infliximab) antibodies (range, 6%-51%). The anti-TNFα mAb infliximab had the highest ADA incidence (20%-51%) across all target classes. Although the anti–IL-17 class (range, <1%-45%) had fairly similar ADA incidences to anti–IL-12/-23 and anti–IL-23 classes (range, 6%-24%), the anti–IL-17 class had lower NAb incidences (ranges, 0%-16% vs 6%-57%, respectively). The lowest incidences of ADAs and NAbs were observed for secukinumab, brodalumab, and guselkumab (ADAs: range, <1%-9%; NAbs: range, 0%-8%). Therapies with low ADA/NAb rates tended to exhibit high levels of retreatment efficacy: among patients re-randomized to treatment after experiencing relapse during treatment withdrawal, ≥85% of patients receiving brodalumab (ADAs, 3%; NAbs, 0%) achieved ≥90% improvement from baseline in psoriasis area and severity index (PASI 90) after 8 weeks of retreatment, whereas only 31% of patients receiving tildrakizumab (ADAs, 6%; NAbs, 40%) achieved PASI 90 after ≤36 weeks of retreatment.

Conclusions Of mAbs assessed, anti–IL-17 and anti–IL-23 classes (secukinumab, brodalumab, guselkumab) had the lowest ADA and NAb incidences. Only brodalumab had no NAbs detected. Although direct comparisons between biologics cannot be made due to differences in ADA assays and clinical trial designs, there is a trend of improved efficacy upon retreatment among mAbs with low ADA and NAb incidences.