Ixekizumab safe, effective up to 5 years in moderate-to-severe plaque psoriasis

Treatment with ixekizumab (IXE) for moderate-to-severe plaque psoriasis is consistently safe and effective through 264 weeks in patients using the approved dose, according to the UNCOVER-3 study.

“The results reported here illustrate the consistency of the safety profile for the approved dosing regimen of IXE as well as sustained long-term efficacy through 5 years of treatment in patients with moderate-to-severe plaque psoriasis,” the researchers said.

The multicentre UNCOVER-3 study randomized 1,346 patients 1:2:2:2 to receive subcutaneous injections of placebo, etanercept 50 mg twice weekly, or IXE 80 mg every 2 weeks or 4 weeks after an initial dose of IXE 160 mg, respectively. Patients entered the long-term extension (LTE) period at week 12 with dosing of IXE every 4 weeks, which could escalate to every 2 weeks after week 60.

The researchers then reported efficacy for the every-2/4-weeks IXE group of the intention-to-treat population. They also reported safety for patients who received at least one dose of IXE every 2 or every 4 weeks.

Using modified nonresponder imputation, 78.8 percent, 67.1 percent, and 46.2 percent of patients receiving the approved dose of IXE every 2/4 weeks (n=385) achieved ≥75-percent, ≥90-percent, or 100-percent improvement at week 264 from baseline in the Psoriasis Area and Severity Index, respectively. [J Am Acad Dermatol 2021;85:360-368]

Additionally, static Physician’s Global Assessment score of 0/1 and 0 responses were 69.2 percent and 45.3 percent, respectively. More than half (57.7 percent) of the participants also reported no itch, indicating improvements in patients' quality of life. [J Eur Acad Dermatol Venereol 2017;31:1483-1490]

The most common treatment-emergent adverse event (TEAE) was infection, such as nasopharyngitis and upper respiratory tract infection, occurring in 72.7 percent of patients.

“The safety profile of the approved IXE dosing regimen over 5 years was similar to those of previous reports, with no unexpected safety outcomes and no new adverse events,” the researchers said. [J Am Acad Dermatol 2017;77:855-862; J Eur Acad Dermatol Venereol 2020;34:301-309; J Am Acad Dermatol 2018;79:824-830; Dermatol Ther (Heidelb) 2020;10:431-447]

Most TEAEs were mild to moderate, and overall discontinuation due to AEs was low (incidence rate, 2.2). Infections decreased after 1 year and remained stable. Crohn’s disease and ulcerative colitis events were also low during the LTE period and consistent with background rates. [Lancet 2018;390:2769-2778; J Eur Acad Dermatol Venereol 2019;33:333-339; Dermatol Ther (Heidelb) 2020;10:133-150]

“Similar to prior findings, Candida events remained low during the LTE period, and no severe or systemic Candida events were reported,” the researchers said. “These findings demonstrate the consistency in the safety profile of the approved IXE treatment regimen over time.” [J Dermatol Nurses Assoc 2019;11:250-263]

Of note, the current study was limited by the lack of comparison treatment group after week 12, according to the researchers.

Psoriasis is a chronic immune-mediated disease that usually requires lifelong management. IXE, a high-affinity monoclonal antibody that neutralizes interleukin 17A, has been proven safe and effective up to 4 years in UNCOVER-3 study data for patients with moderate-to-severe plaque psoriasis. [J Am Acad Dermatol 2019;80:1029-1072; J Am Acad Dermatol 2017;77:855-862; Lancet 2015;386:541-551]