Efficacy and safety of secukinumab treatment in adults with extensive alopecia areata

Abstract

Alopecia areata (AA) is a common form of non-scarring hair loss. The pathogenesis of AA is believed to involve multiple inflammatory cytokines, including possibly IL-17A. To assess the efficacy and safety of the IL-17A antagonist secukinumab in AA, we conducted a double-blinded, randomized prospective pilot study in which 11 subjects were treated with either secukinumab (n = 7) or placebo (n = 4) subcutaneously at weeks 0, 1, 2, 3, 4 and every 4 weeks thereafter until (inclusive of) week 20. The primary endpoint for the study was the percentage of patients achieving SALT50 at 24 weeks. A total of three subjects out of 11 completed the study through the primary endpoint, and therefore, we used the last observation carried forward method to analyze the missing data. At the primary endpoint or last completed observation, 0% (0/7) of the secukinumab-treated subjects achieved a 50% reduction in SALT score (SALT50), and likewise, 0% (0/4) of the placebo-treated subjects achieved SALT50. In the secukinumab group, one (14.3%) subject had some hair regrowth, one (14.3%) subject had worsening hair loss, and five (71.4%) subjects had no change in response to treatment. No adverse events attributable to the study drug were observed. The lack of a treatment response to most of our treated patients suggests that the T17/IL-17 axis likely has no pathogenic role in AA and an alternative therapeutic approach should be considered for this disease. However, due to the low statistical power of this study, future studies may be required to corroborate these findings.

Alopecia areata is characterized by dysregulation in systemic type 17 and type 2 cytokines, which may contribute to disease‐associated psychological morbidity

“…These data and data from others indicate that type 17 cytokines are altered in AA. Clinically, IL‐17A blockade has failed to demonstrate efficacy in AA . In contrast, therapeutically targeting the IL‐12/‐23 p40 subunit has been reported to be effective in promoting hair regrowth, indicating that these pathways may operate independently in AA.…”

Frontiers in alopecia areata pathobiology research

“…[134][135][136] The question of whether IL-23 antagonism, such as through ustekinumab therapy, can reproducibly promote hair regrowth in patients with AA awaits systemic analysis. 137 Only a mild therapeutic effect was observed after treatment with IL-17, 138 whereas the phosphodiesterase 4 antagonist apremilast had insufficient therapeutic effects in patients with AA 139 and in the humanized AA mouse model, 140 in which apremilast nevertheless inhibited experimental induction of AA lesions in vivo. Collectively, in addition to targeting IFN-g-and JAK/ STAT-mediated signaling in patients with AA, several additional pathways that also deserve therapeutic targeting, at least in selected AA subpopulations/subtypes, deserve systematic exploration.…”

Hair-Growth Potential of Ginseng and Its Major Metabolites: A Review on Its Molecular Mechanisms

“…It would be interesting to investigate whether ginsenoside Rk1 or other ginsenosides can target JAK2 signaling in dermal papilla and diminish activation of NKG2D+ T cells. Moreover, the pathogenesis of alopecia areata is believed to involve inflammatory cytokines IL-17A and monoclonal antibodies against IL-17A secukinumab-caused hair regrowth in human volunteers [ 55 ]. Treatment of Th17 cells with Panax notoginseng saponins diminished the proliferation and differentiation of Th17 cells and decreased IL-17 expression [ 56 ].…”