Ixekizumab for the Treatment of Plaque Psoriasis

Vancouver, Canada—Data from the UNCOVER-2 study found that ixekizumab, an anti-interleuekin-17A IgG4 monoclonal antibody, was superior to placebo and etanercept at 12 weeks in 1224 psoriasis patients enrolled, according to results presented at the WCD meeting during a poster session titled A Phase 3 Trial Comparing Ixekizumab with Placebo and Etanercept for Moderate-to-Severe Plaque Psoriasis: Results from the 12-week Induction Period of UNCOVER-2.

The phase 3, multicenter, randomized, double-blind UNCOVER-2 study sought to evaluate the efficacy and safety of ixekizumab in the treatment of psoriasis compared to etanercept and placebo through 12 weeks and through 60 weeks. The data presented at the WCD meeting focused only on 12-week outcomes. Patients ≥18 years of age with moderate-to-severe psoriasis (≥10% body surface area, static Global Physician Assessment [sPGA] ≥3, and Psoriasis Area and Severity Index [PASI] ≥12) were randomly assigned 1:2:2:2 to receive subcutaneous placebo (n=168), etanercept 50 mg twice weekly (n=358), or a single injection of 80-mg ixekizumab every 2 weeks (n=351) or every 4 weeks (n=347) following a 160-mg starting dose. Patients with pustular, erythrodermic, and/or guttate psoriasis; history of drug-induced psoriasis; prior use of etanercept or concurrent or recent use of any biologic agent; systemic psoriasis therapy or phototherapy within 4 weeks; or topical therapy within 2 weeks were excluded. The baseline characteristics and clinical demographics were similar across all 4 cohorts. For example, the duration of psoriasis was 19.1 years for the placebo group, 18.9 years for the etanercept group, 18.5 years for the ixekizumab every 4 weeks group, and 18.3 years for ixekizumab every 2 weeks group.

The primary endpoints were superiority to etanercept and placebo at week 12 with respect to ≥75% improvement in PASI from baseline and sPGA (0,1) with at least a 2-point improvement from baseline. Secondary endpoints included PASI 90 and PASI 100 at week 12, improvement in Itch Numeric Rating Scale, and improvement in Dermatology Life Quality Index (DLQI).

Ixekizumab treatment resulted in rapid improvement, and many patients achieved complete or near complete resolution of psoriasis. Significant improvements were observed as early as week 1 with both ixekizumab dosing regimens and approximately 50% of patients achieved PASI 75 by week 4. At week 12, more patients who received ixekizumab every 4 weeks and every 2 weeks achieved PASI 75 from baseline (77.5% and 89.7%, respectively) compared with etanercept (41.3%) and placebo (2.4%). Also at week 12, more patients in the 2 ixekizumab dosing regimens showed improvement in sPGA from baseline (72.9% and 83.2%, respectively) compared with etanercept (36.0%) and placebo (2.4%). A significant, rapid response with ixekizumab was seen as early as week 2 for near complete (PASI 90) and week 4 for complete resolution of psoriasis (PASI 100). In the association between treatment response and improvements in DLQI and itching across all treatment arms, more patients achieving complete resolution of psoriasis plaques (PASI 100) reported their psoriasis had no impact on quality of life (78.1%) and that their itching (59.9%) was resolved.

The safety profile of ixekizumab was comparable to etanercept. Treatment emergent adverse events in ≥5% of patients randomized to etanercept, ixekizumab every 4 weeks, or ixekizumab every 2 weeks included nasopharyngitis (10.1%, 8.4%, and 10.0%, respectively), injection site reaction (10.9%, 5.5%, and 11.1%, respectively), upper respiratory track infection (7.3%, 4.6%, and 5.4%, respectively), headache (5.6%, 5.2%, and 4.9%, respectively), and injection site erythema (5.0%, 2.6%, and 3.4%, respectively). No deaths were reported for the 3 treatment arms.—Eileen Koutnik-Fotopoulos

The study was supported by Eli Lilly and Company.