Risankizumab versus Ustekinumab for Moderate-to-Severe Plaque Psoriasis

被引:414
作者
Papp, Kim A. [1 ]
Blauvelt, Andrew [4 ]
Bukhalo, Michael [5 ]
Gooderham, Melinda [2 ,3 ]
Krueger, James [6 ]
Lacour, Jean-Philippe [7 ]
Menter, Alan [8 ]
Philipp, Sandra [9 ]
Sofen, Howard [13 ]
Tyring, Stephen [12 ]
Berner, Beate R. [10 ]
Visvanathan, Sudha [14 ]
Pamulapati, Chandrasena [14 ]
Bennett, Nathan [14 ]
Flack, Mary [14 ]
Scholl, Paul [14 ]
Padula, Steven J. [11 ]
机构
[1] K Papp Clin Res & Prob Med Res, Waterloo, ON, Canada
[2] Queens Univ, Sch Med, Kingston, ON, Canada
[3] Ctr Dermatol & Prob Med Res, Peterborough, ON, Canada
[4] Oregon Med Res Ctr, Portland, OR USA
[5] Altman Dermatol Associates, Arlington Hts, IL USA
[6] Rockefeller Univ, 1230 York Ave, New York, NY 10021 USA
[7] Univ Nice Sophia Antipolis, Hop lArchet, Nice, France
[8] Baylor Res Inst, Dallas, TX USA
[9] Charite, Berlin, Germany
[10] Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany
[11] Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany
[12] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA
[13] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA
[14] Boehringer Ingelheim Pharmaceut, Ridgefield, CT USA
关键词
PLACEBO-CONTROLLED TRIAL; CLINICAL-TRIALS; DOUBLE-BLIND; MECHANISMS; SAFETY; POPULATION; EFFICACY; COMMON; IL-23;
D O I
10.1056/NEJMoa1607017
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BACKGROUND Interleukin-23 is thought to be critical to the pathogenesis of psoriasis. We compared risankizumab (BI 655066), a humanized IgG1 monoclonal antibody that inhibits interleukin-23 by specifically targeting the p19 subunit and thus prevents interleukin-23 signaling, and ustekinumab, an interleukin-12 and interleukin-23 inhibitor, in patients with moderate-to-severe plaque psoriasis. METHODS We randomly assigned a total of 166 patients to receive subcutaneous injections of risankizumab (a single 18-mg dose at week 0 or 90-mg or 180-mg doses at weeks 0, 4, and 16) or ustekinumab (45 or 90 mg, according to body weight, at weeks 0, 4, and 16). The primary end point was a 90% or greater reduction from baseline in the Psoriasis Area and Severity Index (PASI) score at week 12. RESULTS At week 12, the percentage of patients with a 90% or greater reduction in the PASI score was 77% (64 of 83 patients) for risankizumab (90-mg and 180-mg groups, pooled), as compared with 40% (16 of 40 patients) for ustekinumab (P<0.001); the percentage of patients with a 100% reduction in the PASI score was 45% in the pooled 90-mg and 180-mg risankizumab groups, as compared with 18% in the ustekinumab group. Efficacy was generally maintained up to 20 weeks after the final dose of 90 or 180 mg of risankizumab. In the 18-mg and 90-mg risankizumab groups and the ustekinumab group, 5 patients (12%), 6 patients (15%), and 3 patients (8%), respectively, had serious adverse events, including two basal-cell carcinomas and one major cardiovascular adverse event; there were no serious adverse events in the 180-mg risankizumab group. CONCLUSIONS In this phase 2 trial, selective blockade of interleukin-23 with risankizumab was associated with clinical responses superior to those associated with ustekinumab. This trial was not large enough or of long enough duration to draw conclusions about safety.
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收藏
页码:1551 / 1560
页数:10
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