Phase 3 Trials of Tapinarof Cream for Plaque Psoriasis

被引:141
作者
Lebwohl, Mark G. [1 ]
Stein Gold, Linda [2 ]
Strober, Bruce [3 ]
Papp, Kim A. [4 ]
Armstrong, April W. [6 ]
Bagel, Jerry [8 ]
Kircik, Leon [1 ,9 ]
Ehst, Benjamin [10 ]
Hong, H. Chih-ho [5 ]
Soung, Jennifer [7 ]
Fromowitz, Jeff [11 ]
Guenthner, Scott [12 ]
Piscitelli, Stephen C. [13 ]
Rubenstein, David S. [13 ]
Brown, Philip M. [13 ]
Tallman, Anna M. [13 ]
Bissonnette, Robert
机构
[1] Icahn Sch Med Mt Sinai, 5 E 98th St,5th Fl, New York, NY 10029 USA
[2] Henry Ford Hlth Syst, Detroit, MI USA
[3] Cent Connecticut Dermatol Res, Cromwell, CT USA
[4] Prob Med Res, Waterloo, ON, Canada
[5] Univ British Columbia, Vancouver, BC, Canada
[6] Univ Southern Calif, Keck Sch Med, Los Angeles, CA USA
[7] Southern Calif Dermatol, Santa Ana, CA USA
[8] Psoriasis Treatment Ctr Cent New Jersey, E Windsor, NJ USA
[9] Skin Sci, Louisville, KY USA
[10] Oregon Med Res Ctr, Portland, OR USA
[11] Dermatol Boca, Boca Raton, FL USA
[12] Indiana Clin Trials Ctr, Plainfield, IN USA
[13] Dermavant Sci, Morrisville, NC USA
关键词
SATISFACTION; ADHERENCE; MILD;
D O I
10.1056/NEJMoa2103629
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BACKGROUND Tapinarof cream is a topical aryl hydrocarbon receptor-modulating agent under investigation for the treatment of psoriasis. Tapinarof modulates the expression of interleukin-17 and the skin-barrier proteins filaggrin and loricrin. METHODS We conducted two identical phase 3 randomized trials of tapinarof in patients with mild-to-severe plaque psoriasis. Adults with a baseline Physician's Global Assessment (PGA) score of 2 (mild) to 4 (severe) (on a scale from 0 to 4, with higher scores indicating more severe psoriasis) and a percent of total body-surface area affected of 3 to 20% were randomly assigned in a 2:1 ratio to use tapinarof 1% cream or vehicle cream once daily for 12 weeks. The primary end point, PGA response, was a PGA score of 0 (clear) or 1 (almost clear) and a decrease from baseline of at least 2 points at week 12. Secondary efficacy end points at week 12 were a reduction of at least 75% in the Psoriasis Area and Severity Index (PASI) score, a PGA score of 0 or 1, the mean change from baseline in the percent of body-surface area affected, and a reduction of at least 90% in the PASI score. Patient-reported outcomes were the mean changes from baseline to week 12 in the proportion of patients who had a decrease of at least 4 points in the Peak Pruritus Numeric Rating Scale (PP-NRS) score (range, 0 [no itch] to 10 [worst imaginable itch]), the PP-NRS total score, the Dermatology Life Quality Index total score, and the Psoriasis Symptom Diary score. Results In trials 1 and 2, a total of 692 and 674 patients, respectively, were screened, with 510 and 515 patients being enrolled. A PGA response occurred in 35.4% of the patients in the tapinarof group and in 6.0% of those in the vehicle group in trial 1 and in 40.2% and 6.3%, respectively, in trial 2 (P<0.001 for both comparisons). RESULTS for secondary end points and patient-reported outcomes were generally in the same direction as those for the primary end point. Adverse events with tapinarof cream included folliculitis, nasopharyngitis, contact dermatitis, headache, upper respiratory tract infection, and pruritus. CONCLUSIONS Tapinarof 1% cream once daily was superior to vehicle control in reducing the severity of plaque psoriasis over a period of 12 weeks but was associated with local adverse events and headache. Larger and longer trials are needed to evaluate the efficacy and safety of tapinarof cream as compared with existing treatments for psoriasis.
引用
收藏
页码:2219 / 2229
页数:11
相关论文
共 17 条
[1]   Adherence, satisfaction and preferences for treatment in patients with psoriasis in the European Union: a systematic review of the literature [J].
Belinchon, I. ;
Rivera, R. ;
Blanch, C. ;
Comellas, M. ;
Lizan, L. .
PATIENT PREFERENCE AND ADHERENCE, 2016, 10 :2357-2367
[2]   Efficacy and safety of topical WBI-1001 in patients with mild to moderate psoriasis: results from a randomized double-blind placebo-controlled, phase II trial [J].
Bissonnette, R. ;
Bolduc, C. ;
Maari, C. ;
Nigen, S. ;
Webster, J. M. ;
Tang, L. ;
Lyle, M. .
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY, 2012, 26 (12) :1516-1521
[3]   Tapinarof-associated folliculitis is generally mild, self-limiting, and rarely interferes with therapy [J].
Bissonnette, Robert ;
Gold, Linda Stein ;
Rubenstein, David S. ;
Tallman, Anna M. ;
Armstrong, April W. .
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, 2021, 85 (01) :E39-E40
[4]   Tapinarof in the treatment of psoriasis: A review of the unique mechanism of action of a novel therapeutic aryl hydrocarbon receptor-modulating agent [J].
Bissonnette, Robert ;
Gold, Linda Stein ;
Rubenstein, David S. ;
Tallman, Anna M. ;
Armstrong, April .
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, 2021, 84 (04) :1059-1067
[5]   Joint AADeNPF Guidelines of care for the management and treatment of psoriasis with topical therapy and alternative medicine modalities for psoriasis severity measures [J].
Elmets, Craig A. ;
Korman, Neil J. ;
Prater, Elizabeth Farley ;
Wong, Emily B. ;
Rupani, Reena N. ;
Kivelevitch, Dario ;
Armstrong, April W. ;
Connor, Cody ;
Cordoro, Kelly M. ;
Davis, Dawn M. R. ;
Elewski, Boni E. ;
Gelfand, Joel M. ;
Gordon, Kenneth B. ;
Gottlieb, Alice B. ;
Kaplan, Daniel H. ;
Kavanaugh, Arthur ;
Kiselica, Matthew ;
Kroshinsky, Daniela ;
Lebwohl, Mark ;
Leonardi, Craig L. ;
Lichten, Jason ;
Lim, Henry W. ;
Mehta, Nehal N. ;
Paller, Amy S. ;
Parra, Sylvia L. ;
Pathy, Arun L. ;
Siegel, Michael ;
Stoff, Benjamin ;
Strober, Bruce ;
Wu, Jashin J. ;
Hariharan, Vidhya ;
Menter, Alan .
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, 2021, 84 (02) :432-470
[6]   Aryl Hydrocarbon Receptor in Atopic Dermatitis and Psoriasis [J].
Furue, Masutaka ;
Hashimoto-Hachiya, Akiko ;
Tsuji, Gaku .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2019, 20 (21)
[7]  
Gold LFS, 2016, SEMIN CUTAN MED SURG, V35, pS36, DOI 10.12788/j.sder.2016.006
[8]   A phase 2b, randomized clinical trial of tapinarof cream for the treatment of plaque psoriasis: Secondary efficacy and patient-reported outcomes [J].
Gold, Linda Stein ;
Bhatia, Neal ;
Tallman, Anna M. ;
Rubenstein, David S. .
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, 2021, 84 (03) :624-631
[9]   Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics [J].
Menter, Alan ;
Strober, Bruce E. ;
Kaplan, Daniel H. ;
Kivelevitch, Dario ;
Prater, Elizabeth Farley ;
Stoff, Benjamin ;
Armstrong, April W. ;
Connor, Cody ;
Cordoro, Kelly M. ;
Davis, Dawn M. R. ;
Elewski, Boni E. ;
Gelfand, Joel M. ;
Gordon, Kenneth B. ;
Gottlieb, Alice B. ;
Kavanaugh, Arthur ;
Kiselica, Matthew ;
Korman, Neil J. ;
Kroshinsky, Daniela ;
Lebwohl, Mark ;
Leonardi, Craig L. ;
Lichten, Jason ;
Lim, Henry W. ;
Mehta, Nehal N. ;
Paller, Amy S. ;
Parra, Sylvia L. ;
Pathy, Arun L. ;
Rupani, Reena N. ;
Siegel, Michael ;
Wong, Emily B. ;
Wu, Jashin J. ;
Hariharan, Vidhya ;
Elmets, Craig A. .
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, 2019, 80 (04) :1029-1072
[10]   Efficacy and patient-reported outcomes from a phase 2b, randomized clinical trial of tapinarof cream for the treatment of adolescents and adults with atopic dermatitis [J].
Paller, Amy S. ;
Gold, Linda Stein ;
Soung, Jennifer ;
Tallman, Anna M. ;
Rubenstein, David S. ;
Gooderham, Melinda .
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, 2021, 84 (03) :632-638