A multicentre, randomized, double-blind, controlled study of long-term treatment with 0·1% tacrolimus ointment in adults with moderate to severe atopic dermatitis
S. Reitamo
Department of Dermatology, Helsinki University Central Hospital, Meilahdentie 2, Helsinki SF-00250, Finland *Service de Dermatologie, Hôpital Archet 2, Nice, France†Department of Dermatology, Bispebjergs Hospital, Copenhagen, Denmark‡Service de Dermatologie, Hôpital Nord, Saint Etienne, France§Dermatologisches Klinikum und Poliklink der Universität Bonn, Bonn, Germany¶Dermatologische Klinik, Universität Kiel, Kiel, Germany**Unità Operativa Dermatologia II, Policlinico Consorziale di Bari, Bari, Italy††Department of Dermatology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands‡‡Clinica Dermosifilopatica II, Università degli Studi di Firenze, Florence, Italy§§Department of Dermatology, Marselisborg Hospital, Aarhus, Denmark¶¶Additional members of the European Tacrolimus Ointment Study Group are listed in Appendix 1
Search for more papers by this authorJ.P. Ortonne
Department of Dermatology, Helsinki University Central Hospital, Meilahdentie 2, Helsinki SF-00250, Finland *Service de Dermatologie, Hôpital Archet 2, Nice, France†Department of Dermatology, Bispebjergs Hospital, Copenhagen, Denmark‡Service de Dermatologie, Hôpital Nord, Saint Etienne, France§Dermatologisches Klinikum und Poliklink der Universität Bonn, Bonn, Germany¶Dermatologische Klinik, Universität Kiel, Kiel, Germany**Unità Operativa Dermatologia II, Policlinico Consorziale di Bari, Bari, Italy††Department of Dermatology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands‡‡Clinica Dermosifilopatica II, Università degli Studi di Firenze, Florence, Italy§§Department of Dermatology, Marselisborg Hospital, Aarhus, Denmark¶¶Additional members of the European Tacrolimus Ointment Study Group are listed in Appendix 1
Search for more papers by this authorC. Sand
Department of Dermatology, Helsinki University Central Hospital, Meilahdentie 2, Helsinki SF-00250, Finland *Service de Dermatologie, Hôpital Archet 2, Nice, France†Department of Dermatology, Bispebjergs Hospital, Copenhagen, Denmark‡Service de Dermatologie, Hôpital Nord, Saint Etienne, France§Dermatologisches Klinikum und Poliklink der Universität Bonn, Bonn, Germany¶Dermatologische Klinik, Universität Kiel, Kiel, Germany**Unità Operativa Dermatologia II, Policlinico Consorziale di Bari, Bari, Italy††Department of Dermatology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands‡‡Clinica Dermosifilopatica II, Università degli Studi di Firenze, Florence, Italy§§Department of Dermatology, Marselisborg Hospital, Aarhus, Denmark¶¶Additional members of the European Tacrolimus Ointment Study Group are listed in Appendix 1
Search for more papers by this authorF. Cambazard
Department of Dermatology, Helsinki University Central Hospital, Meilahdentie 2, Helsinki SF-00250, Finland *Service de Dermatologie, Hôpital Archet 2, Nice, France†Department of Dermatology, Bispebjergs Hospital, Copenhagen, Denmark‡Service de Dermatologie, Hôpital Nord, Saint Etienne, France§Dermatologisches Klinikum und Poliklink der Universität Bonn, Bonn, Germany¶Dermatologische Klinik, Universität Kiel, Kiel, Germany**Unità Operativa Dermatologia II, Policlinico Consorziale di Bari, Bari, Italy††Department of Dermatology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands‡‡Clinica Dermosifilopatica II, Università degli Studi di Firenze, Florence, Italy§§Department of Dermatology, Marselisborg Hospital, Aarhus, Denmark¶¶Additional members of the European Tacrolimus Ointment Study Group are listed in Appendix 1
Search for more papers by this authorT. Bieber
Department of Dermatology, Helsinki University Central Hospital, Meilahdentie 2, Helsinki SF-00250, Finland *Service de Dermatologie, Hôpital Archet 2, Nice, France†Department of Dermatology, Bispebjergs Hospital, Copenhagen, Denmark‡Service de Dermatologie, Hôpital Nord, Saint Etienne, France§Dermatologisches Klinikum und Poliklink der Universität Bonn, Bonn, Germany¶Dermatologische Klinik, Universität Kiel, Kiel, Germany**Unità Operativa Dermatologia II, Policlinico Consorziale di Bari, Bari, Italy††Department of Dermatology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands‡‡Clinica Dermosifilopatica II, Università degli Studi di Firenze, Florence, Italy§§Department of Dermatology, Marselisborg Hospital, Aarhus, Denmark¶¶Additional members of the European Tacrolimus Ointment Study Group are listed in Appendix 1
Search for more papers by this authorR. Fölster-Holst
Department of Dermatology, Helsinki University Central Hospital, Meilahdentie 2, Helsinki SF-00250, Finland *Service de Dermatologie, Hôpital Archet 2, Nice, France†Department of Dermatology, Bispebjergs Hospital, Copenhagen, Denmark‡Service de Dermatologie, Hôpital Nord, Saint Etienne, France§Dermatologisches Klinikum und Poliklink der Universität Bonn, Bonn, Germany¶Dermatologische Klinik, Universität Kiel, Kiel, Germany**Unità Operativa Dermatologia II, Policlinico Consorziale di Bari, Bari, Italy††Department of Dermatology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands‡‡Clinica Dermosifilopatica II, Università degli Studi di Firenze, Florence, Italy§§Department of Dermatology, Marselisborg Hospital, Aarhus, Denmark¶¶Additional members of the European Tacrolimus Ointment Study Group are listed in Appendix 1
Search for more papers by this authorG. Vena
Department of Dermatology, Helsinki University Central Hospital, Meilahdentie 2, Helsinki SF-00250, Finland *Service de Dermatologie, Hôpital Archet 2, Nice, France†Department of Dermatology, Bispebjergs Hospital, Copenhagen, Denmark‡Service de Dermatologie, Hôpital Nord, Saint Etienne, France§Dermatologisches Klinikum und Poliklink der Universität Bonn, Bonn, Germany¶Dermatologische Klinik, Universität Kiel, Kiel, Germany**Unità Operativa Dermatologia II, Policlinico Consorziale di Bari, Bari, Italy††Department of Dermatology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands‡‡Clinica Dermosifilopatica II, Università degli Studi di Firenze, Florence, Italy§§Department of Dermatology, Marselisborg Hospital, Aarhus, Denmark¶¶Additional members of the European Tacrolimus Ointment Study Group are listed in Appendix 1
Search for more papers by this authorJ.D. Bos
Department of Dermatology, Helsinki University Central Hospital, Meilahdentie 2, Helsinki SF-00250, Finland *Service de Dermatologie, Hôpital Archet 2, Nice, France†Department of Dermatology, Bispebjergs Hospital, Copenhagen, Denmark‡Service de Dermatologie, Hôpital Nord, Saint Etienne, France§Dermatologisches Klinikum und Poliklink der Universität Bonn, Bonn, Germany¶Dermatologische Klinik, Universität Kiel, Kiel, Germany**Unità Operativa Dermatologia II, Policlinico Consorziale di Bari, Bari, Italy††Department of Dermatology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands‡‡Clinica Dermosifilopatica II, Università degli Studi di Firenze, Florence, Italy§§Department of Dermatology, Marselisborg Hospital, Aarhus, Denmark¶¶Additional members of the European Tacrolimus Ointment Study Group are listed in Appendix 1
Search for more papers by this authorP. Fabbri
Department of Dermatology, Helsinki University Central Hospital, Meilahdentie 2, Helsinki SF-00250, Finland *Service de Dermatologie, Hôpital Archet 2, Nice, France†Department of Dermatology, Bispebjergs Hospital, Copenhagen, Denmark‡Service de Dermatologie, Hôpital Nord, Saint Etienne, France§Dermatologisches Klinikum und Poliklink der Universität Bonn, Bonn, Germany¶Dermatologische Klinik, Universität Kiel, Kiel, Germany**Unità Operativa Dermatologia II, Policlinico Consorziale di Bari, Bari, Italy††Department of Dermatology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands‡‡Clinica Dermosifilopatica II, Università degli Studi di Firenze, Florence, Italy§§Department of Dermatology, Marselisborg Hospital, Aarhus, Denmark¶¶Additional members of the European Tacrolimus Ointment Study Group are listed in Appendix 1
Search for more papers by this authorC. Groenhoej Larsen
Department of Dermatology, Helsinki University Central Hospital, Meilahdentie 2, Helsinki SF-00250, Finland *Service de Dermatologie, Hôpital Archet 2, Nice, France†Department of Dermatology, Bispebjergs Hospital, Copenhagen, Denmark‡Service de Dermatologie, Hôpital Nord, Saint Etienne, France§Dermatologisches Klinikum und Poliklink der Universität Bonn, Bonn, Germany¶Dermatologische Klinik, Universität Kiel, Kiel, Germany**Unità Operativa Dermatologia II, Policlinico Consorziale di Bari, Bari, Italy††Department of Dermatology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands‡‡Clinica Dermosifilopatica II, Università degli Studi di Firenze, Florence, Italy§§Department of Dermatology, Marselisborg Hospital, Aarhus, Denmark¶¶Additional members of the European Tacrolimus Ointment Study Group are listed in Appendix 1
Search for more papers by this authorthe European Tacrolimus Ointment Study Group
Department of Dermatology, Helsinki University Central Hospital, Meilahdentie 2, Helsinki SF-00250, Finland *Service de Dermatologie, Hôpital Archet 2, Nice, France†Department of Dermatology, Bispebjergs Hospital, Copenhagen, Denmark‡Service de Dermatologie, Hôpital Nord, Saint Etienne, France§Dermatologisches Klinikum und Poliklink der Universität Bonn, Bonn, Germany¶Dermatologische Klinik, Universität Kiel, Kiel, Germany**Unità Operativa Dermatologia II, Policlinico Consorziale di Bari, Bari, Italy††Department of Dermatology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands‡‡Clinica Dermosifilopatica II, Università degli Studi di Firenze, Florence, Italy§§Department of Dermatology, Marselisborg Hospital, Aarhus, Denmark¶¶Additional members of the European Tacrolimus Ointment Study Group are listed in Appendix 1
Search for more papers by this authorS. Reitamo
Department of Dermatology, Helsinki University Central Hospital, Meilahdentie 2, Helsinki SF-00250, Finland *Service de Dermatologie, Hôpital Archet 2, Nice, France†Department of Dermatology, Bispebjergs Hospital, Copenhagen, Denmark‡Service de Dermatologie, Hôpital Nord, Saint Etienne, France§Dermatologisches Klinikum und Poliklink der Universität Bonn, Bonn, Germany¶Dermatologische Klinik, Universität Kiel, Kiel, Germany**Unità Operativa Dermatologia II, Policlinico Consorziale di Bari, Bari, Italy††Department of Dermatology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands‡‡Clinica Dermosifilopatica II, Università degli Studi di Firenze, Florence, Italy§§Department of Dermatology, Marselisborg Hospital, Aarhus, Denmark¶¶Additional members of the European Tacrolimus Ointment Study Group are listed in Appendix 1
Search for more papers by this authorJ.P. Ortonne
Department of Dermatology, Helsinki University Central Hospital, Meilahdentie 2, Helsinki SF-00250, Finland *Service de Dermatologie, Hôpital Archet 2, Nice, France†Department of Dermatology, Bispebjergs Hospital, Copenhagen, Denmark‡Service de Dermatologie, Hôpital Nord, Saint Etienne, France§Dermatologisches Klinikum und Poliklink der Universität Bonn, Bonn, Germany¶Dermatologische Klinik, Universität Kiel, Kiel, Germany**Unità Operativa Dermatologia II, Policlinico Consorziale di Bari, Bari, Italy††Department of Dermatology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands‡‡Clinica Dermosifilopatica II, Università degli Studi di Firenze, Florence, Italy§§Department of Dermatology, Marselisborg Hospital, Aarhus, Denmark¶¶Additional members of the European Tacrolimus Ointment Study Group are listed in Appendix 1
Search for more papers by this authorC. Sand
Department of Dermatology, Helsinki University Central Hospital, Meilahdentie 2, Helsinki SF-00250, Finland *Service de Dermatologie, Hôpital Archet 2, Nice, France†Department of Dermatology, Bispebjergs Hospital, Copenhagen, Denmark‡Service de Dermatologie, Hôpital Nord, Saint Etienne, France§Dermatologisches Klinikum und Poliklink der Universität Bonn, Bonn, Germany¶Dermatologische Klinik, Universität Kiel, Kiel, Germany**Unità Operativa Dermatologia II, Policlinico Consorziale di Bari, Bari, Italy††Department of Dermatology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands‡‡Clinica Dermosifilopatica II, Università degli Studi di Firenze, Florence, Italy§§Department of Dermatology, Marselisborg Hospital, Aarhus, Denmark¶¶Additional members of the European Tacrolimus Ointment Study Group are listed in Appendix 1
Search for more papers by this authorF. Cambazard
Department of Dermatology, Helsinki University Central Hospital, Meilahdentie 2, Helsinki SF-00250, Finland *Service de Dermatologie, Hôpital Archet 2, Nice, France†Department of Dermatology, Bispebjergs Hospital, Copenhagen, Denmark‡Service de Dermatologie, Hôpital Nord, Saint Etienne, France§Dermatologisches Klinikum und Poliklink der Universität Bonn, Bonn, Germany¶Dermatologische Klinik, Universität Kiel, Kiel, Germany**Unità Operativa Dermatologia II, Policlinico Consorziale di Bari, Bari, Italy††Department of Dermatology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands‡‡Clinica Dermosifilopatica II, Università degli Studi di Firenze, Florence, Italy§§Department of Dermatology, Marselisborg Hospital, Aarhus, Denmark¶¶Additional members of the European Tacrolimus Ointment Study Group are listed in Appendix 1
Search for more papers by this authorT. Bieber
Department of Dermatology, Helsinki University Central Hospital, Meilahdentie 2, Helsinki SF-00250, Finland *Service de Dermatologie, Hôpital Archet 2, Nice, France†Department of Dermatology, Bispebjergs Hospital, Copenhagen, Denmark‡Service de Dermatologie, Hôpital Nord, Saint Etienne, France§Dermatologisches Klinikum und Poliklink der Universität Bonn, Bonn, Germany¶Dermatologische Klinik, Universität Kiel, Kiel, Germany**Unità Operativa Dermatologia II, Policlinico Consorziale di Bari, Bari, Italy††Department of Dermatology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands‡‡Clinica Dermosifilopatica II, Università degli Studi di Firenze, Florence, Italy§§Department of Dermatology, Marselisborg Hospital, Aarhus, Denmark¶¶Additional members of the European Tacrolimus Ointment Study Group are listed in Appendix 1
Search for more papers by this authorR. Fölster-Holst
Department of Dermatology, Helsinki University Central Hospital, Meilahdentie 2, Helsinki SF-00250, Finland *Service de Dermatologie, Hôpital Archet 2, Nice, France†Department of Dermatology, Bispebjergs Hospital, Copenhagen, Denmark‡Service de Dermatologie, Hôpital Nord, Saint Etienne, France§Dermatologisches Klinikum und Poliklink der Universität Bonn, Bonn, Germany¶Dermatologische Klinik, Universität Kiel, Kiel, Germany**Unità Operativa Dermatologia II, Policlinico Consorziale di Bari, Bari, Italy††Department of Dermatology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands‡‡Clinica Dermosifilopatica II, Università degli Studi di Firenze, Florence, Italy§§Department of Dermatology, Marselisborg Hospital, Aarhus, Denmark¶¶Additional members of the European Tacrolimus Ointment Study Group are listed in Appendix 1
Search for more papers by this authorG. Vena
Department of Dermatology, Helsinki University Central Hospital, Meilahdentie 2, Helsinki SF-00250, Finland *Service de Dermatologie, Hôpital Archet 2, Nice, France†Department of Dermatology, Bispebjergs Hospital, Copenhagen, Denmark‡Service de Dermatologie, Hôpital Nord, Saint Etienne, France§Dermatologisches Klinikum und Poliklink der Universität Bonn, Bonn, Germany¶Dermatologische Klinik, Universität Kiel, Kiel, Germany**Unità Operativa Dermatologia II, Policlinico Consorziale di Bari, Bari, Italy††Department of Dermatology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands‡‡Clinica Dermosifilopatica II, Università degli Studi di Firenze, Florence, Italy§§Department of Dermatology, Marselisborg Hospital, Aarhus, Denmark¶¶Additional members of the European Tacrolimus Ointment Study Group are listed in Appendix 1
Search for more papers by this authorJ.D. Bos
Department of Dermatology, Helsinki University Central Hospital, Meilahdentie 2, Helsinki SF-00250, Finland *Service de Dermatologie, Hôpital Archet 2, Nice, France†Department of Dermatology, Bispebjergs Hospital, Copenhagen, Denmark‡Service de Dermatologie, Hôpital Nord, Saint Etienne, France§Dermatologisches Klinikum und Poliklink der Universität Bonn, Bonn, Germany¶Dermatologische Klinik, Universität Kiel, Kiel, Germany**Unità Operativa Dermatologia II, Policlinico Consorziale di Bari, Bari, Italy††Department of Dermatology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands‡‡Clinica Dermosifilopatica II, Università degli Studi di Firenze, Florence, Italy§§Department of Dermatology, Marselisborg Hospital, Aarhus, Denmark¶¶Additional members of the European Tacrolimus Ointment Study Group are listed in Appendix 1
Search for more papers by this authorP. Fabbri
Department of Dermatology, Helsinki University Central Hospital, Meilahdentie 2, Helsinki SF-00250, Finland *Service de Dermatologie, Hôpital Archet 2, Nice, France†Department of Dermatology, Bispebjergs Hospital, Copenhagen, Denmark‡Service de Dermatologie, Hôpital Nord, Saint Etienne, France§Dermatologisches Klinikum und Poliklink der Universität Bonn, Bonn, Germany¶Dermatologische Klinik, Universität Kiel, Kiel, Germany**Unità Operativa Dermatologia II, Policlinico Consorziale di Bari, Bari, Italy††Department of Dermatology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands‡‡Clinica Dermosifilopatica II, Università degli Studi di Firenze, Florence, Italy§§Department of Dermatology, Marselisborg Hospital, Aarhus, Denmark¶¶Additional members of the European Tacrolimus Ointment Study Group are listed in Appendix 1
Search for more papers by this authorC. Groenhoej Larsen
Department of Dermatology, Helsinki University Central Hospital, Meilahdentie 2, Helsinki SF-00250, Finland *Service de Dermatologie, Hôpital Archet 2, Nice, France†Department of Dermatology, Bispebjergs Hospital, Copenhagen, Denmark‡Service de Dermatologie, Hôpital Nord, Saint Etienne, France§Dermatologisches Klinikum und Poliklink der Universität Bonn, Bonn, Germany¶Dermatologische Klinik, Universität Kiel, Kiel, Germany**Unità Operativa Dermatologia II, Policlinico Consorziale di Bari, Bari, Italy††Department of Dermatology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands‡‡Clinica Dermosifilopatica II, Università degli Studi di Firenze, Florence, Italy§§Department of Dermatology, Marselisborg Hospital, Aarhus, Denmark¶¶Additional members of the European Tacrolimus Ointment Study Group are listed in Appendix 1
Search for more papers by this authorthe European Tacrolimus Ointment Study Group
Department of Dermatology, Helsinki University Central Hospital, Meilahdentie 2, Helsinki SF-00250, Finland *Service de Dermatologie, Hôpital Archet 2, Nice, France†Department of Dermatology, Bispebjergs Hospital, Copenhagen, Denmark‡Service de Dermatologie, Hôpital Nord, Saint Etienne, France§Dermatologisches Klinikum und Poliklink der Universität Bonn, Bonn, Germany¶Dermatologische Klinik, Universität Kiel, Kiel, Germany**Unità Operativa Dermatologia II, Policlinico Consorziale di Bari, Bari, Italy††Department of Dermatology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands‡‡Clinica Dermosifilopatica II, Università degli Studi di Firenze, Florence, Italy§§Department of Dermatology, Marselisborg Hospital, Aarhus, Denmark¶¶Additional members of the European Tacrolimus Ointment Study Group are listed in Appendix 1
Search for more papers by this authorConflicts of interest: The authors received study grants from Fujisawa GmbH, Munich, Germany, to perform the study. There were no conflicts of interest.
Summary
Background Atopic dermatis (AD) is a chronic disease that often requires long-term treatment. Topical corticosteroids are the usual therapy for patients with AD, but prolonged usage can result in skin atrophy and other side-effects.
Objectives In a randomized, double-blind, comparative study, to compare the efficacy and safety of a 6-month treatment period with 0·1% tacrolimus ointment vs. a corticosteroid ointment regimen in adults with moderate to severe AD.
Methods Treatment was applied twice daily for a maximum of 6 months. Patients in the tacrolimus treatment group (n = 487) applied 0·1% tacrolimus ointment to all affected areas over the whole body. The patients treated with the corticosteroid regimen (n = 485) applied 0·1% hydrocortisone butyrate ointment to affected areas on the trunk and extremities and 1% hydrocortisone acetate ointment to affected areas on the face and neck. The study primary endpoint was the response rate, i.e. the proportion of patients with at least 60% improvement in the modified Eczema Area and Severity Index (mEASI) between baseline and month 3.
Results By month 3, more patients in the 0·1% tacrolimus group responded to treatment (72·6% vs. 52·3% in the corticosteroid group, P < 0·001). The patients treated with 0·1% tacrolimus also showed greater improvement in mEASI, EASI, affected body surface area and physician and patient assessments of global response. Patients applying 0·1% tacrolimus ointment experienced more skin burning (52·4% vs. 13·8% in the corticosteroid group; P < 0·001). In most patients, skin burning was mild to moderate in severity and decreased rapidly after the first week of treatment. There was no increase in the incidence of infections or malignancies over time in either treatment group.
Conclusions Long-term treatment with 0·1% tacrolimus ointment is significantly more efficacious than a corticosteroid ointment regimen in adults with moderate to severe AD.
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