Two Phase 3, Randomized, Controlled Trials of Ruxolitinib Cream for Vitiligo.

Autor:	Rosmarin D; From Tufts Medical Center, Boston (D.R.); Centre Hospitalier Universitaire de Nice and Centre Méditerranéen de Médecine Moléculaire, Université Côte d'Azur, Nice (T.P.), the Office of Mireille Ruer-Mulard, M.D., Martiques (M.R.-M.), the Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hôpital Saint-André, and Centre National de la Recherche Scientifique Unité Mixte de Recherche 5164, ImmunoConcept, Université de Bordeaux, Bordeaux (J.S.), and Henri Mondor University Hospital and Université Paris-Est Créteil Val de Marne, Paris (K.E.) - all in France; Palo Alto Foundation Medical Group, Sunnyvale (A.G.P.), and the Vitiligo and Pigmentation Institute of Southern California, Los Angeles (P.G.) - both in California; the University of Texas Southwestern Medical Center, Dallas (A.G.P., S.R.D.), and Innovative Dermatology, Plano (S.R.D.) - both in Texas; the University of Massachusetts Chan Medical School, Worcester (J.E.H.); Icahn School of Medicine at Mount Sinai, New York (M.L.); Amsterdam University Medical Center, Amsterdam (A.W.); and Incyte, Wilmington, DE (D.K., K.S., K.B.)., Passeron T; From Tufts Medical Center, Boston (D.R.); Centre Hospitalier Universitaire de Nice and Centre Méditerranéen de Médecine Moléculaire, Université Côte d'Azur, Nice (T.P.), the Office of Mireille Ruer-Mulard, M.D., Martiques (M.R.-M.), the Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hôpital Saint-André, and Centre National de la Recherche Scientifique Unité Mixte de Recherche 5164, ImmunoConcept, Université de Bordeaux, Bordeaux (J.S.), and Henri Mondor University Hospital and Université Paris-Est Créteil Val de Marne, Paris (K.E.) - all in France; Palo Alto Foundation Medical Group, Sunnyvale (A.G.P.), and the Vitiligo and Pigmentation Institute of Southern California, Los Angeles (P.G.) - both in California; the University of Texas Southwestern Medical Center, Dallas (A.G.P., S.R.D.), and Innovative Dermatology, Plano (S.R.D.) - both in Texas; the University of Massachusetts Chan Medical School, Worcester (J.E.H.); Icahn School of Medicine at Mount Sinai, New York (M.L.); Amsterdam University Medical Center, Amsterdam (A.W.); and Incyte, Wilmington, DE (D.K., K.S., K.B.)., Pandya AG; From Tufts Medical Center, Boston (D.R.); Centre Hospitalier Universitaire de Nice and Centre Méditerranéen de Médecine Moléculaire, Université Côte d'Azur, Nice (T.P.), the Office of Mireille Ruer-Mulard, M.D., Martiques (M.R.-M.), the Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hôpital Saint-André, and Centre National de la Recherche Scientifique Unité Mixte de Recherche 5164, ImmunoConcept, Université de Bordeaux, Bordeaux (J.S.), and Henri Mondor University Hospital and Université Paris-Est Créteil Val de Marne, Paris (K.E.) - all in France; Palo Alto Foundation Medical Group, Sunnyvale (A.G.P.), and the Vitiligo and Pigmentation Institute of Southern California, Los Angeles (P.G.) - both in California; the University of Texas Southwestern Medical Center, Dallas (A.G.P., S.R.D.), and Innovative Dermatology, Plano (S.R.D.) - both in Texas; the University of Massachusetts Chan Medical School, Worcester (J.E.H.); Icahn School of Medicine at Mount Sinai, New York (M.L.); Amsterdam University Medical Center, Amsterdam (A.W.); and Incyte, Wilmington, DE (D.K., K.S., K.B.)., Grimes P; From Tufts Medical Center, Boston (D.R.); Centre Hospitalier Universitaire de Nice and Centre Méditerranéen de Médecine Moléculaire, Université Côte d'Azur, Nice (T.P.), the Office of Mireille Ruer-Mulard, M.D., Martiques (M.R.-M.), the Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hôpital Saint-André, and Centre National de la Recherche Scientifique Unité Mixte de Recherche 5164, ImmunoConcept, Université de Bordeaux, Bordeaux (J.S.), and Henri Mondor University Hospital and Université Paris-Est Créteil Val de Marne, Paris (K.E.) - all in France; Palo Alto Foundation Medical Group, Sunnyvale (A.G.P.), and the Vitiligo and Pigmentation Institute of Southern California, Los Angeles (P.G.) - both in California; the University of Texas Southwestern Medical Center, Dallas (A.G.P., S.R.D.), and Innovative Dermatology, Plano (S.R.D.) - both in Texas; the University of Massachusetts Chan Medical School, Worcester (J.E.H.); Icahn School of Medicine at Mount Sinai, New York (M.L.); Amsterdam University Medical Center, Amsterdam (A.W.); and Incyte, Wilmington, DE (D.K., K.S., K.B.)., Harris JE; From Tufts Medical Center, Boston (D.R.); Centre Hospitalier Universitaire de Nice and Centre Méditerranéen de Médecine Moléculaire, Université Côte d'Azur, Nice (T.P.), the Office of Mireille Ruer-Mulard, M.D., Martiques (M.R.-M.), the Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hôpital Saint-André, and Centre National de la Recherche Scientifique Unité Mixte de Recherche 5164, ImmunoConcept, Université de Bordeaux, Bordeaux (J.S.), and Henri Mondor University Hospital and Université Paris-Est Créteil Val de Marne, Paris (K.E.) - all in France; Palo Alto Foundation Medical Group, Sunnyvale (A.G.P.), and the Vitiligo and Pigmentation Institute of Southern California, Los Angeles (P.G.) - both in California; the University of Texas Southwestern Medical Center, Dallas (A.G.P., S.R.D.), and Innovative Dermatology, Plano (S.R.D.) - both in Texas; the University of Massachusetts Chan Medical School, Worcester (J.E.H.); Icahn School of Medicine at Mount Sinai, New York (M.L.); Amsterdam University Medical Center, Amsterdam (A.W.); and Incyte, Wilmington, DE (D.K., K.S., K.B.)., Desai SR; From Tufts Medical Center, Boston (D.R.); Centre Hospitalier Universitaire de Nice and Centre Méditerranéen de Médecine Moléculaire, Université Côte d'Azur, Nice (T.P.), the Office of Mireille Ruer-Mulard, M.D., Martiques (M.R.-M.), the Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hôpital Saint-André, and Centre National de la Recherche Scientifique Unité Mixte de Recherche 5164, ImmunoConcept, Université de Bordeaux, Bordeaux (J.S.), and Henri Mondor University Hospital and Université Paris-Est Créteil Val de Marne, Paris (K.E.) - all in France; Palo Alto Foundation Medical Group, Sunnyvale (A.G.P.), and the Vitiligo and Pigmentation Institute of Southern California, Los Angeles (P.G.) - both in California; the University of Texas Southwestern Medical Center, Dallas (A.G.P., S.R.D.), and Innovative Dermatology, Plano (S.R.D.) - both in Texas; the University of Massachusetts Chan Medical School, Worcester (J.E.H.); Icahn School of Medicine at Mount Sinai, New York (M.L.); Amsterdam University Medical Center, Amsterdam (A.W.); and Incyte, Wilmington, DE (D.K., K.S., K.B.)., Lebwohl M; From Tufts Medical Center, Boston (D.R.); Centre Hospitalier Universitaire de Nice and Centre Méditerranéen de Médecine Moléculaire, Université Côte d'Azur, Nice (T.P.), the Office of Mireille Ruer-Mulard, M.D., Martiques (M.R.-M.), the Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hôpital Saint-André, and Centre National de la Recherche Scientifique Unité Mixte de Recherche 5164, ImmunoConcept, Université de Bordeaux, Bordeaux (J.S.), and Henri Mondor University Hospital and Université Paris-Est Créteil Val de Marne, Paris (K.E.) - all in France; Palo Alto Foundation Medical Group, Sunnyvale (A.G.P.), and the Vitiligo and Pigmentation Institute of Southern California, Los Angeles (P.G.) - both in California; the University of Texas Southwestern Medical Center, Dallas (A.G.P., S.R.D.), and Innovative Dermatology, Plano (S.R.D.) - both in Texas; the University of Massachusetts Chan Medical School, Worcester (J.E.H.); Icahn School of Medicine at Mount Sinai, New York (M.L.); Amsterdam University Medical Center, Amsterdam (A.W.); and Incyte, Wilmington, DE (D.K., K.S., K.B.)., Ruer-Mulard M; From Tufts Medical Center, Boston (D.R.); Centre Hospitalier Universitaire de Nice and Centre Méditerranéen de Médecine Moléculaire, Université Côte d'Azur, Nice (T.P.), the Office of Mireille Ruer-Mulard, M.D., Martiques (M.R.-M.), the Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hôpital Saint-André, and Centre National de la Recherche Scientifique Unité Mixte de Recherche 5164, ImmunoConcept, Université de Bordeaux, Bordeaux (J.S.), and Henri Mondor University Hospital and Université Paris-Est Créteil Val de Marne, Paris (K.E.) - all in France; Palo Alto Foundation Medical Group, Sunnyvale (A.G.P.), and the Vitiligo and Pigmentation Institute of Southern California, Los Angeles (P.G.) - both in California; the University of Texas Southwestern Medical Center, Dallas (A.G.P., S.R.D.), and Innovative Dermatology, Plano (S.R.D.) - both in Texas; the University of Massachusetts Chan Medical School, Worcester (J.E.H.); Icahn School of Medicine at Mount Sinai, New York (M.L.); Amsterdam University Medical Center, Amsterdam (A.W.); and Incyte, Wilmington, DE (D.K., K.S., K.B.)., Seneschal J; From Tufts Medical Center, Boston (D.R.); Centre Hospitalier Universitaire de Nice and Centre Méditerranéen de Médecine Moléculaire, Université Côte d'Azur, Nice (T.P.), the Office of Mireille Ruer-Mulard, M.D., Martiques (M.R.-M.), the Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hôpital Saint-André, and Centre National de la Recherche Scientifique Unité Mixte de Recherche 5164, ImmunoConcept, Université de Bordeaux, Bordeaux (J.S.), and Henri Mondor University Hospital and Université Paris-Est Créteil Val de Marne, Paris (K.E.) - all in France; Palo Alto Foundation Medical Group, Sunnyvale (A.G.P.), and the Vitiligo and Pigmentation Institute of Southern California, Los Angeles (P.G.) - both in California; the University of Texas Southwestern Medical Center, Dallas (A.G.P., S.R.D.), and Innovative Dermatology, Plano (S.R.D.) - both in Texas; the University of Massachusetts Chan Medical School, Worcester (J.E.H.); Icahn School of Medicine at Mount Sinai, New York (M.L.); Amsterdam University Medical Center, Amsterdam (A.W.); and Incyte, Wilmington, DE (D.K., K.S., K.B.)., Wolkerstorfer A; From Tufts Medical Center, Boston (D.R.); Centre Hospitalier Universitaire de Nice and Centre Méditerranéen de Médecine Moléculaire, Université Côte d'Azur, Nice (T.P.), the Office of Mireille Ruer-Mulard, M.D., Martiques (M.R.-M.), the Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hôpital Saint-André, and Centre National de la Recherche Scientifique Unité Mixte de Recherche 5164, ImmunoConcept, Université de Bordeaux, Bordeaux (J.S.), and Henri Mondor University Hospital and Université Paris-Est Créteil Val de Marne, Paris (K.E.) - all in France; Palo Alto Foundation Medical Group, Sunnyvale (A.G.P.), and the Vitiligo and Pigmentation Institute of Southern California, Los Angeles (P.G.) - both in California; the University of Texas Southwestern Medical Center, Dallas (A.G.P., S.R.D.), and Innovative Dermatology, Plano (S.R.D.) - both in Texas; the University of Massachusetts Chan Medical School, Worcester (J.E.H.); Icahn School of Medicine at Mount Sinai, New York (M.L.); Amsterdam University Medical Center, Amsterdam (A.W.); and Incyte, Wilmington, DE (D.K., K.S., K.B.)., Kornacki D; From Tufts Medical Center, Boston (D.R.); Centre Hospitalier Universitaire de Nice and Centre Méditerranéen de Médecine Moléculaire, Université Côte d'Azur, Nice (T.P.), the Office of Mireille Ruer-Mulard, M.D., Martiques (M.R.-M.), the Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hôpital Saint-André, and Centre National de la Recherche Scientifique Unité Mixte de Recherche 5164, ImmunoConcept, Université de Bordeaux, Bordeaux (J.S.), and Henri Mondor University Hospital and Université Paris-Est Créteil Val de Marne, Paris (K.E.) - all in France; Palo Alto Foundation Medical Group, Sunnyvale (A.G.P.), and the Vitiligo and Pigmentation Institute of Southern California, Los Angeles (P.G.) - both in California; the University of Texas Southwestern Medical Center, Dallas (A.G.P., S.R.D.), and Innovative Dermatology, Plano (S.R.D.) - both in Texas; the University of Massachusetts Chan Medical School, Worcester (J.E.H.); Icahn School of Medicine at Mount Sinai, New York (M.L.); Amsterdam University Medical Center, Amsterdam (A.W.); and Incyte, Wilmington, DE (D.K., K.S., K.B.)., Sun K; From Tufts Medical Center, Boston (D.R.); Centre Hospitalier Universitaire de Nice and Centre Méditerranéen de Médecine Moléculaire, Université Côte d'Azur, Nice (T.P.), the Office of Mireille Ruer-Mulard, M.D., Martiques (M.R.-M.), the Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hôpital Saint-André, and Centre National de la Recherche Scientifique Unité Mixte de Recherche 5164, ImmunoConcept, Université de Bordeaux, Bordeaux (J.S.), and Henri Mondor University Hospital and Université Paris-Est Créteil Val de Marne, Paris (K.E.) - all in France; Palo Alto Foundation Medical Group, Sunnyvale (A.G.P.), and the Vitiligo and Pigmentation Institute of Southern California, Los Angeles (P.G.) - both in California; the University of Texas Southwestern Medical Center, Dallas (A.G.P., S.R.D.), and Innovative Dermatology, Plano (S.R.D.) - both in Texas; the University of Massachusetts Chan Medical School, Worcester (J.E.H.); Icahn School of Medicine at Mount Sinai, New York (M.L.); Amsterdam University Medical Center, Amsterdam (A.W.); and Incyte, Wilmington, DE (D.K., K.S., K.B.)., Butler K; From Tufts Medical Center, Boston (D.R.); Centre Hospitalier Universitaire de Nice and Centre Méditerranéen de Médecine Moléculaire, Université Côte d'Azur, Nice (T.P.), the Office of Mireille Ruer-Mulard, M.D., Martiques (M.R.-M.), the Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hôpital Saint-André, and Centre National de la Recherche Scientifique Unité Mixte de Recherche 5164, ImmunoConcept, Université de Bordeaux, Bordeaux (J.S.), and Henri Mondor University Hospital and Université Paris-Est Créteil Val de Marne, Paris (K.E.) - all in France; Palo Alto Foundation Medical Group, Sunnyvale (A.G.P.), and the Vitiligo and Pigmentation Institute of Southern California, Los Angeles (P.G.) - both in California; the University of Texas Southwestern Medical Center, Dallas (A.G.P., S.R.D.), and Innovative Dermatology, Plano (S.R.D.) - both in Texas; the University of Massachusetts Chan Medical School, Worcester (J.E.H.); Icahn School of Medicine at Mount Sinai, New York (M.L.); Amsterdam University Medical Center, Amsterdam (A.W.); and Incyte, Wilmington, DE (D.K., K.S., K.B.)., Ezzedine K; From Tufts Medical Center, Boston (D.R.); Centre Hospitalier Universitaire de Nice and Centre Méditerranéen de Médecine Moléculaire, Université Côte d'Azur, Nice (T.P.), the Office of Mireille Ruer-Mulard, M.D., Martiques (M.R.-M.), the Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hôpital Saint-André, and Centre National de la Recherche Scientifique Unité Mixte de Recherche 5164, ImmunoConcept, Université de Bordeaux, Bordeaux (J.S.), and Henri Mondor University Hospital and Université Paris-Est Créteil Val de Marne, Paris (K.E.) - all in France; Palo Alto Foundation Medical Group, Sunnyvale (A.G.P.), and the Vitiligo and Pigmentation Institute of Southern California, Los Angeles (P.G.) - both in California; the University of Texas Southwestern Medical Center, Dallas (A.G.P., S.R.D.), and Innovative Dermatology, Plano (S.R.D.) - both in Texas; the University of Massachusetts Chan Medical School, Worcester (J.E.H.); Icahn School of Medicine at Mount Sinai, New York (M.L.); Amsterdam University Medical Center, Amsterdam (A.W.); and Incyte, Wilmington, DE (D.K., K.S., K.B.).
Jazyk:	angličtina
Zdroj:	The New England journal of medicine [N Engl J Med] 2022 Oct 20; Vol. 387 (16), pp. 1445-1455.
DOI:	10.1056/NEJMoa2118828
Abstrakt:	Background: Vitiligo is a chronic autoimmune disease that causes skin depigmentation. A cream formulation of ruxolitinib (an inhibitor of Janus kinase 1 and 2) resulted in repigmentation in a phase 2 trial involving adults with vitiligo. Methods: We conducted two phase 3, double-blind, vehicle-controlled trials (Topical Ruxolitinib Evaluation in Vitiligo Study 1 [TRuE-V1] and 2 [TRuE-V2]) in North America and Europe that involved patients 12 years of age or older who had nonsegmental vitiligo with depigmentation covering 10% or less of total body-surface area. Patients were randomly assigned in a 2:1 ratio to apply 1.5% ruxolitinib cream or vehicle control twice daily for 24 weeks to all vitiligo areas on the face and body, after which all patients could apply 1.5% ruxolitinib cream through week 52. The primary end point was a decrease (improvement) of at least 75% from baseline in the facial Vitiligo Area Scoring Index (F-VASI; range, 0 to 3, with higher scores indicating a greater area of facial depigmentation), or F-VASI75 response, at week 24. There were five key secondary end points, including improved responses on the Vitiligo Noticeability Scale. Results: A total of 674 patients were enrolled, 330 in TRuE-V1 and 344 in TRuE-V2. In TRuE-V1, the percentage of patients with an F-VASI75 response at week 24 was 29.8% in the ruxolitinib-cream group and 7.4% in the vehicle group (relative risk, 4.0; 95% confidence interval [CI], 1.9 to 8.4; P<0.001). In TRuE-V2, the percentages were 30.9% and 11.4%, respectively (relative risk, 2.7; 95% CI, 1.5 to 4.9; P<0.001). The results for key secondary end points showed superiority of ruxolitinib cream over vehicle control. Among patients who applied ruxolitinib cream throughout 52 weeks, adverse events occurred in 54.8% in TRuE-V1 and 62.3% in TRuE-V2; the most common adverse events were application-site acne (6.3% and 6.6%, respectively), nasopharyngitis (5.4% and 6.1%), and application-site pruritus (5.4% and 5.3%). Conclusions: In two phase 3 trials, application of ruxolitinib cream resulted in greater repigmentation of vitiligo lesions than vehicle control through 52 weeks, but it was associated with acne and pruritus at the application site. Larger and longer trials are required to determine the effect and safety of ruxolitinib cream in patients with vitiligo. (Funded by Incyte; TRuE-V1 and TRuE-V2 ClinicalTrials.gov numbers, NCT04052425 and NCT04057573.). (Copyright © 2022 Massachusetts Medical Society.)
Databáze:	MEDLINE
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