Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis.
Author(s): Leonardi C, Matheson R, Zachariae C, Cameron G, Li L, Edson-Heredia E, Braun D,
Banerjee S.
Affiliation(s): Department of Dermatology, Saint Louis University School of Medicine, St. Louis,
MO, USA. leonardi@centralderm.com
Publication date & source: 2012, N Engl J Med. , 366(13):1190-9
BACKGROUND: Type 17 helper T cells have been suggested to play a pathological
role in psoriasis. They secrete several proinflammatory cytokines, including
interleukin-17A (also known as interleukin-17). We evaluated the safety and
efficacy of ixekizumab (LY2439821), a humanized anti-interleukin-17 monoclonal
antibody, for psoriasis treatment.
METHODS: In our phase 2, double-blind, placebo-controlled trial, we randomly
assigned 142 patients with chronic moderate-to-severe plaque psoriasis to receive
subcutaneous injections of 10, 25, 75, or 150 mg of ixekizumab or placebo at 0,
2, 4, 8, 12, and 16 weeks. The primary end point was the proportion of patients
with reduction in the psoriasis area-and-severity index (PASI) score by at least
75% at 12 weeks. Secondary end points included the proportion of patients with
reduction in the PASI score by at least 90% or by 100%.
RESULTS: At 12 weeks, the percentage of patients with a reduction in the PASI
score by at least 75% was significantly greater with ixekizumab (except with the
lowest, 10-mg dose)--150 mg (82.1%), 75 mg (82.8%), and 25 mg (76.7%)--than with
placebo (7.7%, P<0.001 for each comparison), as was the percentage of patients
with a reduction in the PASI score by at least 90%: 150 mg (71.4%), 75 mg
(58.6%), and 25 mg (50.0%) versus placebo (0%, P<0.001 for each comparison).
Similarly, a 100% reduction in the PASI score was achieved in significantly more
patients in the 150-mg group (39.3%) and the 75-mg group (37.9%) than in the
placebo group (0%) (P<0.001 for both comparisons). Significant differences
occurred at as early as 1 week and were sustained through 20 weeks. Adverse
events occurred in 63% of patients in both the combined ixekizumab groups and in
the placebo group. No serious adverse events or major cardiovascular events were
observed.
CONCLUSIONS: Use of a humanized anti-interleukin-17 monoclonal antibody,
ixekizumab, improved the clinical symptoms of psoriasis. Further studies are
needed to establish its long-term safety and efficacy in patients with psoriasis.
(Funded by Eli Lilly; ClinicalTrials.gov number, NCT01107457.).
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