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Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis.
N Engl J Med. 2012 Mar 29; 366(13):1190-9.NEJM

Abstract

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.).

Links

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Authors+Show Affiliations

Leonardi C
Department of Dermatology, Saint Louis University School of Medicine, St. Louis, MO, USA. leonardi@centralderm.com
Matheson R
No affiliation info available
Zachariae C
No affiliation info available
Cameron G
No affiliation info available
Li L
No affiliation info available
Edson-Heredia E
No affiliation info available
Braun D
No affiliation info available
Banerjee S
No affiliation info available

MeSH

AdultAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedDose-Response Relationship, DrugDouble-Blind MethodFemaleHumansInjections, SubcutaneousInterleukin-17MaleMiddle AgedPsoriasisSeverity of Illness IndexTreatment Outcome

Pub Type(s)

Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22455413

Clinical Trial Links

Clinical trial which this article describes

Citation

Leonardi, Craig, et al. "Anti-interleukin-17 Monoclonal Antibody Ixekizumab in Chronic Plaque Psoriasis." The New England Journal of Medicine, vol. 366, no. 13, 2012, pp. 1190-9.
Leonardi C, Matheson R, Zachariae C, et al. Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis. N Engl J Med. 2012;366(13):1190-9.
Leonardi, C., Matheson, R., Zachariae, C., Cameron, G., Li, L., Edson-Heredia, E., Braun, D., & Banerjee, S. (2012). Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis. The New England Journal of Medicine, 366(13), 1190-9. https://doi.org/10.1056/NEJMoa1109997
Leonardi C, et al. Anti-interleukin-17 Monoclonal Antibody Ixekizumab in Chronic Plaque Psoriasis. N Engl J Med. 2012 Mar 29;366(13):1190-9. PubMed PMID: 22455413.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis. AU - Leonardi,Craig, AU - Matheson,Robert, AU - Zachariae,Claus, AU - Cameron,Gregory, AU - Li,Linda, AU - Edson-Heredia,Emily, AU - Braun,Daniel, AU - Banerjee,Subhashis, PY - 2012/3/30/entrez PY - 2012/3/30/pubmed PY - 2012/4/11/medline SP - 1190 EP - 9 JF - The New England journal of medicine JO - N Engl J Med VL - 366 IS - 13 N2 - 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.). SN - 1533-4406 UR - https://www.unboundmedicine.com/medline/citation/22455413/Anti_interleukin_17_monoclonal_antibody_ixekizumab_in_chronic_plaque_psoriasis_ L2 - https://www.nejm.org/doi/10.1056/NEJMoa1109997?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -