PracticeUpdate Conference Series: IID 2018

Results of Two Studies Point to Janus Kinase Inhibition for Alopecia Areata

The Janus kinase 1/3 inhibitor ATI-50002 and tofacitinib show promise as therapies for alopecia areata, results of a preclinical and a clinical study show. Z hengpeng Dai, PhD, of Columbia University in New York, explained that alopecia areata is an autoimmune disease caused by cell-mediated destruction of the hair follicle. Approaches that halt the pathogenic T cell response, therefore, are predicted to benefit affected patients. To develop, activate, and maintain homeostasis, T cells rely on a duality of T cell receptor and γ chain cytokine signals. ATI-5002 is a potent, selective next-generation Janus kinase 1/3 inhibitor, predicted to disrupt γ chain cytokine signaling. Dr. Dai and colleagues found that C3H/HeJ mice with alopecia areata that were fed ATI-50002 exhibited robust, dose-dependent hair regrowth even after a short 5-week course of treatment. Immunohistochemical analysis of treated skin revealed significantly decreased alopecia areata-associated inflammation. CD8-positive, natural killer G2D-positive T cells and CD8-positive, CD44-positive, CD62L- negative effector/memory T cells, known to be associated with the pathogenesis of alopecia areata, were markedly reduced in treated mice. Since disruption of the γ chain cytokine network in T cells has been shown to induced T cell exhaustion in the setting of chronic viral infection, Dr. Dai’s team postulated that a potential mechanism of action of Janus kinase inhibitors in alopecia areata could be via selective induction of T cell exhaustion.

After 52Weeks, Ixekizumab Is Linked to Consistently Higher Responses Than Ustekinumab Across Patient SubgroupsWith Moderate to Severe Plaque Psoriasis After 52 weeks of therapy, ixekizumab has been associated with consistently higher responses than ustekinumab across patient subgroups with moderate to severe plaque psoriasis, results of a review of prespecified patient subgroups in the phase III, double-blind, head-to-head IXORA-S trial show.

C arle F. Paul, MD, PhD, of Larrey University Hospital in Toulouse, France, explained that ixekizumab is a high-affinity monoclonal antibody that selectively targets interleukin 17A. Ixekizumab is approved for moderate to severe plaque psoriasis. Dr. Paul and colleagues set out to evaluate ixekizumab vs usteki- numab in commonly reported, prespecified patients subgroups in IXORA-S. In IXORA-S, patients were randomized to either ustekinumb (45 or 90 mg weight-based dosing per label) or ixekizumab (80 mg every 2 weeks for 12 weeks followed by 80 mg every 4 weeks), following a 160-mg starting dose, for a total of 52 weeks. IXORA-S also evaluated Psoriasis Affected Surface Area (PASI) 75 and 100, as well as static Physician’s Global Assessment score 0 or 1 with at least a 2-point improvement from baseline.

PASI measures the extent and severity of psoriasis by assessing average redness, thickness, and scaliness of skin lesions (each graded 0–4), weighted by body surface area of involved skin. The static Physician’s Global Assessment is the physician’s assessment of severity of a patient’s psoriasis lesions overall at a specific point in time. At 24 weeks, patients treated with ixekizumab achieved signifi- cantly higher response rates vs those treated with ustekinumab, as demonstrated by: ƒ ƒ 2% of patients treated with ixekizumab achieved PASI 75 vs 81.9% of patients treated with ustekinumab (P = .015) ƒ ƒ 1% of patients treated with ixekizumab achieved PASI 90 vs 59.0% of those treated with ustekinumab (P < .001)

PRACTICEUPDATE CONFERENCE SERIES • IID 2018 18