Ixekizumab delivers long-term efficacy in moderate-to-severe plaque psoriasis
Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin 17A, is safe and effective in moderate-to-severe plaque psoriasis, providing a persistent and long-term clinical response through 108 weeks of treatment, reports a recent study.
Researchers randomized 1,346 patients 2:2:2:1 to 80 mg ixekizumab every 2 or 4 weeks, 50 mg etanercept twice weekly, or placebo to assess the efficacy and safety of ixekizumab through 108 weeks of treatment in a phase III clinical trial (UNCOVER-3). Patients switched to ixekizumab every 4 weeks during a long-term extension (LTE) period at week 12. As-observed, multiple imputation (MI) and modified MI (mMI) methods were used to summarize the efficacy data.
Among participants (n=385) receiving the recommended dose (ixekizumab every 2 weeks on weeks 0 to 12 and every 4 weeks during LTE), the 108-week as-observed response rate was 93.4 percent, MI 88.3 percent and mMI 83.6 percent for those achieving ≥75-percent improvement from baseline in the Psoriasis Area and Severity Index. For patients with a Static Physician’s Global Assessment score of 0 or 1, the 108-week as observed, MI and mMI response rates were 82.6, 78.3 and 74.1 percent, respectively. [J Am Acad Dermatol 2017;77:855–862]
“Ixekizumab was well tolerated and no unexpected safety outcomes were reported in the LTE period of UNCOVER-3,” researchers said. “The overall safety profile for ixekizumab during LTE was similar to previously reported shorter treatment periods.” [N Engl J Med 2016;375:345–356]
Furthermore, “[i]t was uncommon for patients to increase their dose frequency following week 60, and this cohort of patients had little effect on overall efficacy profiles,” they added.
A total of 1,077 (84.5 percent) patients reported at least one treatment-emergent adverse event (AE) during LTE, and the most commonly reported AE was nasopharyngitis. Of these, 85 percent were mild or moderate in severity. Discontinuation of treatment due to AE was low at 6.4 percent. A total of five deaths occurred during the LTE, and in all cases, the cause of death was unrelated to ixekizumab exposure, according to researchers.
Several AEs are of special interest for therapeutic agents targeting IL-17A, which plays a key role in regulating both inflammation and neutrophil homeostasis. Aberrant IL-17A signaling is also believed to be associated with inflammatory bowel disease (IBD), cardiovascular disease (CVD) and tumorigenesis. [Trends Mol Med 2016;22:230–241; J Immunol 2008;181:5183–5188; Eur Heart J 2013;34:570–577; Nat Rev Immunol 2010;10:248–256]
Moreover, patients with psoriasis are at an increased risk of incident IBD, CVD and malignancies, making these events of special interest, according to researchers. [Br J Dermatol 2016;175:487–492; Eur J Dermatol 2014;24:305–311; Br J Dermatol 2014;170:366–373; J Invest Dermatol 2009;129:2604–2612; J Invest Dermatol 2006;126:2194–2201]
The current study is limited by the open-label LTE period, lacking long-term head-to-head efficacy and safety comparisons to placebo or etanercept, which were included during the first 12 weeks of UNCOVER-3.
“A more comprehensive analysis of integrated long-term safety data will be provided in later publications,” researchers said.