Ixekizumab (IXE) is a high-affinity monoclonal antibody that selectively targets interleukin-17A, and which has been approved for treatment of moderate-to-severe plaque psoriasis in adult patients. [1] There is an unmet medical need for effective and safe therapies for children and adolescents with moderate-to-severe plaque psoriasis.

• This randomised, double-blind phase III study (NCT03073200) evaluated the efficacy and safety of IXE in paediatric patients with moderate-to-severe plaque psoriasis.

Type of study, patients, and inclusion criteria

• Patients (6 to <18 years of age) with moderate-to-severe plaque psoriasis (Psoriasis Area and Severity Index (PASI) ≥12, static Physician’s Global Assessment (sPGA) ≥3, and body surface area involvement ≥10%) were randomised (2:1) to IXE every 4 weeks (Q4W) (N=115) or placebo (PBO) (N=56).
• Patients randomised to IXE received 40 mg (<25 kg), 80 mg (25 to 50 kg), or 160 mg (>50 kg) starting doses (based on body weight), then 20 mg, 40 mg, or 80 mg (respectively) IXE Q4W through week 12
• An active reference arm, etanercept (ETN), was also used.

Primary outcome measure

• Co-primary endpoints were the proportion of patients achieving 75% improvement from baseline in PASI (PASI 75) and sPGA of clear or almost clear skin (sPGA 0,1) at week 12.

• Overall, 98% (IXE), 97% (ETN) and 95% (PBO) of patients completed week 12 assessments; thus, the co-primary endpoints were achieved.
• At week 12, IXE was superior to PBO for PASI 75/90/100 (IXE: 89%/78%/50%, PBO: 25%/5%/2%, P <0.001), sPGA 0,1 (IXE: 81%, PBO: 11%, P <0.001) and sPGA 0 (IXE: 52%, PBO: 2%, P <0.001) responses. At week 4, IXE was superior to PBO for PASI 75 (IXE: 54%, PBO: 9%, P <0.001) and sPGA 0,1 (IXE: 46%, PBO: 6%, P <0.001) (Figure).
• IXE resulted in significantly (P <0.001) greater responses at week 12 for both Itch NRS ≥4 (IXE: 71%, PBO: 20%) and CLDQI/DLQI 0,1 (IXE: 64%, PBO: 23%).
• Among patients receiving ETN, PASI 75/90/100 responses were 63%/40%/17%; sPGA (0,1) response was 53%; and sPGA (0) response was 17%.
• Treatment-emergent adverse events (TEAEs) occurred in 45% (PBO) and 56% (IXE) of patients; none were severe.
• The most common TEAEs in the IXE group (occurring in ≥10% of IXE-treated patients) were nasopharyngitis (11.3%) and headache (10.4%).

• Significantly more patients treated with ixekizumab versus placebo achieved PASI 75 and sPGA (0,1) as early as week 4.
• Most adverse events were mild or moderate in severity and the safety profile was generally consistent with that seen in adults with moderate-to-severe plaque psoriasis.