PracticeUpdate: Dermatology - Winter 2018

IID 2018 29

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 Tou- louse, 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. 59.0% of those treated with ustekinumab (P < .001) • 2% of patients treated with ixekizumab achieved PASI 100 vs 23.5% of those treated with ustekinumab (P = .001) Additionally, 86.6% of patients treated with ixekizumab achieved static Physician’s Global Assessment score 0 or 1 vs 69.3% of those treated with ustekinumab after 24 weeks (P < .001).

The majority of treatment-emergent adverse events were mild or moderate. There were no statistically significant differences between treatment groups in overall treatment-emergent adverse events. The safety profile of ixekizumab was consistent with pre- vious clinical trials. In the present subgroup review, patients were randomized 1:1 to receive approved dosing of ixekizumab (160 mg initial dose, 80 mg every 2 weeks to week 12, and every 4 weeks thereafter, total n=136); or ustekinumab (45 mg in patients weighing ≤100 kg or 90 mg in patients weighing >100 kg at weeks 0 and 4, and every 12 weeks thereafter, n=166). Efficacy at week 52 was measured as the percentage of patients who achieved PASI 90/100 in patient subgroups of prior biologic use and analyzed using nonresponder imputation and Fisher’s exact test: • Prior biologic use: ixekizumab n=18, ustekinumab n=25 • No prior biologic use: ixekizumab n=118, ustekinumab n=141 • Weight ≤100 kg: ixekizumab n=104, ustekinumab n=121 • Weight >100 kg: ixekizumab n=31, ustekinumab n=45 • Baseline disease severity, PASI <20: ixekizumab n=85, usteki- numab n=107 • Baseline disease severity, PASI ≥20: ixekizumab n=51, usteki- numab n=59 Response was significantly greater with ixekizumab than with ustekinumab in: • Biologic-naive patients (PASI 90: 76.3% vs 62.4%, P = .022; PASI 100: 55.1% vs 39.7%, P = .017) • Biologic-experienced patients for PASI 90 (77.8% vs 40.0%, P = .028) • Patients weighing ≤100 kg (PASI 90: 77.9% vs 62.0%, P = .013; PASI 100: 53.8% vs 38.8%, P = .032) • Patients with baseline PASI ≥20 (PASI 90: 90.2% vs 57.6%) • Patients weighing >100 kg (PASI 90: 74.2% vs 51.1%, P = .057; PASI 100: 48.4% vs 26.7%, P = .08) • Patients with baseline PASI <20 (PASI 90: 68.2% vs 59.8%, P = .291; PASI 100: 48.2% vs 37.4%, P = . 143) Response was consistently higher with ixekizumab across patient subgroups at week 52, including in difficult-to-treat patients, for example, biologic-experienced patients or those with more severe disease. www.practiceupdate.com/c/68651

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 Area and Severity Index (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 assess- ment 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: • 2% of patients treated with ixekizumab achieved PASI 75 vs 81.9% of patients treated with ustekinumab (P = .015) • 1% of patients treated with ixekizumab achieved PASI 90 vs

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VOL. 2 • NO. 3 • 2018