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. 2024 Apr 10:16:163-174.
doi: 10.1016/j.jdin.2024.03.025. eCollection 2024 Sep.

Dupilumab improves pruritus and skin lesions in patients with prurigo nodularis: Pooled results from 2 phase 3 trials (LIBERTY-PN PRIME and PRIME2)

Gil Yosipovitch  1 , Brian S Kim  2 , Shawn G Kwatra  3 , Nicholas K Mollanazar  4 , Sonja Ständer  5 , Takahiro Satoh  6 , Pedro Mendes-Bastos  7 , Tsen-Fang Tsai  8 , Elizabeth Laws  9 , Michael C Nivens  10 , Jennifer Maloney  10 , Genming Shi  9 , Ashish Bansal  10 , Ariane Dubost-Brama  11
Affiliations

Dupilumab improves pruritus and skin lesions in patients with prurigo nodularis: Pooled results from 2 phase 3 trials (LIBERTY-PN PRIME and PRIME2)

Gil Yosipovitch et al. JAAD Int. .

Abstract

Background: Phase 3 PRIME/PRIME2 trials independently demonstrated efficacy and an acceptable safety profile of dupilumab adults with moderate-to-severe prurigo nodularis.

Objective: To obtain a more precise estimate of onset and magnitude of treatment effect using PRIME/PRIME2 pooled data.

Methods: In PRIME/PRIME2, patients were randomized to dupilumab or placebo for 24 weeks. Pooled analysis assessed proportion of patients achieving clinically meaningful improvement in itch, clear/almost-clear skin, or both; at weeks 12 and 24; overall and by demographic subgroups and changes from baseline to week 24 in symptoms, signs, and quality of life.

Results: Patients receiving dupilumab (n = 153) vs placebo (n = 158) experienced significant improvements in all tested endpoints. At week 24, 90 (58.8%) dupilumab-treated vs 30 (19.0%) placebo-treated patients achieved clinically meaningful improvement in itch, 71 (46.4%) vs 27 (17.1%) clear/almost clear skin, and 54 (35.3%) vs 14 (8.9%) achieved both (P < .0001 for all). Treatment benefits were independent of baseline demographics. Safety to week 36 was generally consistent with the known dupilumab safety profile.

Limitations: On-treatment data limited to 24 weeks.

Conclusions: Pooled analysis confirmed improvements reported in individual trials and revealed earlier effect onset in itch and skin pain. Dupilumab treatment showed benefits across demographics.

Keywords: Dermatology Life Quality Index (DLQI); Investigator’s Global Assessment for Prurigo Nodularis Stage (IGA PN-S); Worst Itch Numerical Rating Scale (WI-NRS); dupilumab; prurigo nodularis.

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Conflict of interest statement

Yosipovitch G: AbbVie, Arcutis Biotherapeutics, Bellus Health, Celldex, Eli Lilly, Escient Pharmaceuticals, Galderma, GSK, Kiniksa Pharmaceuticals, LEO Pharma, Novartis, Pfizer, Pierre Fabre, Regeneron Pharmaceuticals Inc, Sanofi, Trevi Therapeutics – advisory board member/consultant; Eli Lilly, Kiniksa Pharmaceuticals, LEO Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals Inc, Sanofi – grants/research funding; Regeneron Pharmaceuticals Inc, Sanofi – investigator. Kim BS: Klirna Biotech – co-founder; 23andMe, Abrax Japan, AbbVie, Almirall, Amagma, Amgen, Arcutis Biotherapeutics, Arena Pharmaceuticals, Argenx, AstraZeneca, Bellus Health, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Clexio Biosciences, CymaBay Therapeutics, Eli Lilly, Escient Pharmaceuticals, Evommune, Galderma, Genentech, Granular Therapeutics, GSK, Guidepoint Global, Incyte, Innovaderm Research, Janssen Pharmaceuticals, Kiniksa Pharmaceuticals, LEO Pharma, Medicxi, Micreos, Novartis, OM Pharma, Pfizer, RecensMedical, Regeneron Pharmaceuticals Inc, Sanofi, Septerna, Shaperon, Teva, Third Harmonic Bio, Third Rock Ventures, Trevi Therapeutics, Triveni, Vial, WebMD – consultant; Cara Therapeutics, Celgene, Kiniksa Pharmaceuticals, Menlo Therapeutics, Regeneron Pharmaceuticals Inc, Sanofi, Theravance Biopharma – advisory board member; Abrax Japan, Klirna Biotech, Locus Biosciences, Nuogen Pharma, RecensMedical – stockholder; patent holder for the use of JAK1 inhibitors for chronic pruritus; patent pending for the use of JAK inhibitors for interstitial cystitis; Nuogen Pharma – founder, chief scientific officer; Cara Therapeutics, LEO Pharma – research grants. Kwatra SG: AbbVie, Arcutis Biotherapeutics, Aslan Pharmaceuticals, Celldex Therapeutics, Galderma, Genzada Pharmaceuticals, Incyte, Johnson & Johnson, Kiniksa Pharmaceuticals, Novartis, Pfizer, Regeneron Pharmaceuticals Inc, Sanofi, Trevi Therapeutics – advisory board member/consultant; Galderma, Incyte, Pfizer, Sanofi – investigator. Mollanazar NK: AbbVie, Boehringer Ingelheim, Galderma, Janssen, LEO Pharma, Novartis, Regeneron Pharmaceuticals Inc, Sanofi, Trevi Therapeutics – advisory board member; Regeneron Pharmaceuticals Inc, Sanofi – investigator. Ständer S: Celldex Therapeutics, Clexio Biosciences, Dermasence, Galderma, GSK, Incyte, Kiniksa Pharmaceuticals, Menlo Therapeutics, Novartis, Sanofi, Trevi Therapeutics – investigator; AbbVie, Almirall, Beiersdorf, Bellus Health, BenevolentAI, Bionorica, Bristol Myers Squibb, Cara Therapeutics, Cello Health, Clexio Biosciences, DS Biopharma, Eli Lilly, Escient Pharmaceuticals, Galderma, Incyte, Integrity CE, Grünenthal, Kiniksa Pharmaceuticals, Klinge Pharma, Klirna Biotech, Menlo Therapeutics, Perrigo, Pfizer, Professor Paul Gerson Unna Academy, Sanofi, Siena Biopharmaceuticals, Touch IME, Trevi Therapeutics, Vanda Pharmaceuticals, Vifor Pharma, WebMD – consultant/advisory board; AbbVie, Almirall, Beiersdorf, Bristol Myers Squibb, Eli Lilly, FOMF, Galderma, LEO Pharma, L’Oréal, MEDahead, Menlo Therapeutics, Novartis, Omnicuris, Pfizer, Pierre Fabre, Professor Paul Gerson Unna Academy, Sanofi, UCB, Vifor Pharma – speaker. Satoh T: AbbVie, Asahi Kasei, Bristol Myers Squibb, Eli Lilly, Hisamitsu Pharmaceutical, Kracie, Kyorin Pharmaceutical, Maruho, Mitsubishi Tanabe Pharma, Otsuka Pharmaceutical, Pfizer, Sanofi, Torii Pharmaceutical – speaker; AbbVie, Daiichi Sankyo, Eli Lilly Japan K. K., Kaken Pharmaceutical, Kyowa Hakko Kirin, Nippon Zoki Pharmaceutical, Otsuka Pharmaceutical, Sato Pharmaceutical, Sun Pharma, Taiho Pharmaceutical, Torii Pharmaceutical – research grants; Nankodo – other fees; Sanofi – investigator. Mendes-Bastos P: AbbVie, Bayer, Cantabria Labs, CS Laboratórios, Eli Lilly, Evelo Biosciences, Janssen-Cilag, LEO Pharma, L’Oréal, Novartis, Organon, Pfizer, Pierre Fabre, Sanofi, Teva, Viatris – speaker/advisor/consultant; AbbVie, Janssen-Cilag, Novartis, Pfizer, Sanofi – Principal Investigator in clinical trials. Tsai TF: AbbVie, AnaptysBio, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galderma, GSK, Janssen-Cilag, LEO Pharma, Merck Sharp & Dohme, Novartis, Pfizer, PharmaEssentia, Sanofi, Sun Pharma, UCB Pharma – investigator/consultant. Laws E, Shi G, Dubost-Brama A: Sanofi – employees, may hold stock and/or stock options in the company. Nivens MC, Maloney J, Bansal A: Regeneron Pharmaceuticals Inc – employees and shareholders.

Figures

Fig 1
Fig 1
Prurigo nodularis. Proportion of patients with ≥4-point reduction from baseline in WI-NRS, IGA PN-S score 0 or 1, or both, at week 12 and week 24 in the pooled analysis (top), and comparison with individual trials (bottom). Cochran-Mantel-Haenszel test was performed on the association between the responder status and intervention group, adjusted by documented history of atopy (atopic or nonatopic), stable use of TCS/TCI (yes or no), region, baseline antidepressant use (yes or no), and study indicator (PRIME and PRIME2). ORs were derived from the Mantel-Haenszel estimator. CI, Confidence interval; IGA PN-S, Investigator’s Global Assessment for PN-Stage (range 0-4); OR, odds ratio; q2w, every 2 weeks; RD, raw difference; TCI, topical calcineurin inhibitors; TCS, topical corticosteroids; WI-NRS, Worst Itch Numerical Rating Scale (range 0-10).
Fig 2
Fig 2
Prurigo nodularis. Patient-reported outcomes over time in the pooled analysis (left) and comparison of results at week 24 with individual trials (right). ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001. Each of the imputed complete data were analyzed by fitting an analysis of covariance model with the corresponding baseline value, intervention group, documented history of atopy (atopic or nonatopic), stable use of TCS/TCI (yes or no), region, baseline antidepressant use (yes or no), and the study indicator (PRIME or PRIME2) as covariates. DLQI, Dermatology Life Quality Index; HADS, Hospital Anxiety and Depression Scale; LS, least-squares; NRS, Numerical Rating Scale; TCI, topical calcineurin inhibitors; TCS, topical corticosteroids; WI-NRS, Worst-Itch Numerical Rating Scale.
Fig 3
Fig 3
Prurigo nodularis. Kaplan-Meier curve of time to first use of high potency or superpotent topical corticosteroid rescue medication through week 24. CI, Confidence interval; HR, hazard ratio; q2w, every 2 weeks.
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