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Efficacy and tolerability of three different doses of oral pimecrolimus in the treatment of moderate to severe atopic dermatitis: a randomized controlled trial

Authors

  • K. Wolff,

    1. Department of Dermatology, Medical University of Vienna, Austria
      *Ninewells Hospital and Medical School, Dundee, U.K.
      †Oregon Health and Science University, Portland, OR, U.S.A.
      ‡Probity Medical Research, Waterloo, Ontario, Canada
      §Hospital for Skin and Allergic Disease, Helsinki, Finland
      ¶Royal Free Hospital, London, U.K.
      **University of Toronto and Ventana Clinical Research, Toronto, Canada
      ††Poznań University of Medical Sciences, Poznań, Poland
      ‡‡Case Western Reserve University, University Hospitals of Cleveland, Cleveland, OH, U.S.A.
      §§Clinical Research, Novartis Pharmaceuticals Inc., East Hanover, NJ, U.S.A.
      ¶¶Clinical Research Dermatology, WSJ 210.9.13, Novartis Pharma AG, CH-4002, Basel, Switzerland
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  • C. Fleming,

    1. Department of Dermatology, Medical University of Vienna, Austria
      *Ninewells Hospital and Medical School, Dundee, U.K.
      †Oregon Health and Science University, Portland, OR, U.S.A.
      ‡Probity Medical Research, Waterloo, Ontario, Canada
      §Hospital for Skin and Allergic Disease, Helsinki, Finland
      ¶Royal Free Hospital, London, U.K.
      **University of Toronto and Ventana Clinical Research, Toronto, Canada
      ††Poznań University of Medical Sciences, Poznań, Poland
      ‡‡Case Western Reserve University, University Hospitals of Cleveland, Cleveland, OH, U.S.A.
      §§Clinical Research, Novartis Pharmaceuticals Inc., East Hanover, NJ, U.S.A.
      ¶¶Clinical Research Dermatology, WSJ 210.9.13, Novartis Pharma AG, CH-4002, Basel, Switzerland
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  • J. Hanifin,

    1. Department of Dermatology, Medical University of Vienna, Austria
      *Ninewells Hospital and Medical School, Dundee, U.K.
      †Oregon Health and Science University, Portland, OR, U.S.A.
      ‡Probity Medical Research, Waterloo, Ontario, Canada
      §Hospital for Skin and Allergic Disease, Helsinki, Finland
      ¶Royal Free Hospital, London, U.K.
      **University of Toronto and Ventana Clinical Research, Toronto, Canada
      ††Poznań University of Medical Sciences, Poznań, Poland
      ‡‡Case Western Reserve University, University Hospitals of Cleveland, Cleveland, OH, U.S.A.
      §§Clinical Research, Novartis Pharmaceuticals Inc., East Hanover, NJ, U.S.A.
      ¶¶Clinical Research Dermatology, WSJ 210.9.13, Novartis Pharma AG, CH-4002, Basel, Switzerland
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  • K. Papp,

    1. Department of Dermatology, Medical University of Vienna, Austria
      *Ninewells Hospital and Medical School, Dundee, U.K.
      †Oregon Health and Science University, Portland, OR, U.S.A.
      ‡Probity Medical Research, Waterloo, Ontario, Canada
      §Hospital for Skin and Allergic Disease, Helsinki, Finland
      ¶Royal Free Hospital, London, U.K.
      **University of Toronto and Ventana Clinical Research, Toronto, Canada
      ††Poznań University of Medical Sciences, Poznań, Poland
      ‡‡Case Western Reserve University, University Hospitals of Cleveland, Cleveland, OH, U.S.A.
      §§Clinical Research, Novartis Pharmaceuticals Inc., East Hanover, NJ, U.S.A.
      ¶¶Clinical Research Dermatology, WSJ 210.9.13, Novartis Pharma AG, CH-4002, Basel, Switzerland
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  • S. Reitamo,

    1. Department of Dermatology, Medical University of Vienna, Austria
      *Ninewells Hospital and Medical School, Dundee, U.K.
      †Oregon Health and Science University, Portland, OR, U.S.A.
      ‡Probity Medical Research, Waterloo, Ontario, Canada
      §Hospital for Skin and Allergic Disease, Helsinki, Finland
      ¶Royal Free Hospital, London, U.K.
      **University of Toronto and Ventana Clinical Research, Toronto, Canada
      ††Poznań University of Medical Sciences, Poznań, Poland
      ‡‡Case Western Reserve University, University Hospitals of Cleveland, Cleveland, OH, U.S.A.
      §§Clinical Research, Novartis Pharmaceuticals Inc., East Hanover, NJ, U.S.A.
      ¶¶Clinical Research Dermatology, WSJ 210.9.13, Novartis Pharma AG, CH-4002, Basel, Switzerland
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  • M. Rustin,

    1. Department of Dermatology, Medical University of Vienna, Austria
      *Ninewells Hospital and Medical School, Dundee, U.K.
      †Oregon Health and Science University, Portland, OR, U.S.A.
      ‡Probity Medical Research, Waterloo, Ontario, Canada
      §Hospital for Skin and Allergic Disease, Helsinki, Finland
      ¶Royal Free Hospital, London, U.K.
      **University of Toronto and Ventana Clinical Research, Toronto, Canada
      ††Poznań University of Medical Sciences, Poznań, Poland
      ‡‡Case Western Reserve University, University Hospitals of Cleveland, Cleveland, OH, U.S.A.
      §§Clinical Research, Novartis Pharmaceuticals Inc., East Hanover, NJ, U.S.A.
      ¶¶Clinical Research Dermatology, WSJ 210.9.13, Novartis Pharma AG, CH-4002, Basel, Switzerland
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  • N. Shear,

    1. Department of Dermatology, Medical University of Vienna, Austria
      *Ninewells Hospital and Medical School, Dundee, U.K.
      †Oregon Health and Science University, Portland, OR, U.S.A.
      ‡Probity Medical Research, Waterloo, Ontario, Canada
      §Hospital for Skin and Allergic Disease, Helsinki, Finland
      ¶Royal Free Hospital, London, U.K.
      **University of Toronto and Ventana Clinical Research, Toronto, Canada
      ††Poznań University of Medical Sciences, Poznań, Poland
      ‡‡Case Western Reserve University, University Hospitals of Cleveland, Cleveland, OH, U.S.A.
      §§Clinical Research, Novartis Pharmaceuticals Inc., East Hanover, NJ, U.S.A.
      ¶¶Clinical Research Dermatology, WSJ 210.9.13, Novartis Pharma AG, CH-4002, Basel, Switzerland
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  • W. Silny,

    1. Department of Dermatology, Medical University of Vienna, Austria
      *Ninewells Hospital and Medical School, Dundee, U.K.
      †Oregon Health and Science University, Portland, OR, U.S.A.
      ‡Probity Medical Research, Waterloo, Ontario, Canada
      §Hospital for Skin and Allergic Disease, Helsinki, Finland
      ¶Royal Free Hospital, London, U.K.
      **University of Toronto and Ventana Clinical Research, Toronto, Canada
      ††Poznań University of Medical Sciences, Poznań, Poland
      ‡‡Case Western Reserve University, University Hospitals of Cleveland, Cleveland, OH, U.S.A.
      §§Clinical Research, Novartis Pharmaceuticals Inc., East Hanover, NJ, U.S.A.
      ¶¶Clinical Research Dermatology, WSJ 210.9.13, Novartis Pharma AG, CH-4002, Basel, Switzerland
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  • N. Korman,

    1. Department of Dermatology, Medical University of Vienna, Austria
      *Ninewells Hospital and Medical School, Dundee, U.K.
      †Oregon Health and Science University, Portland, OR, U.S.A.
      ‡Probity Medical Research, Waterloo, Ontario, Canada
      §Hospital for Skin and Allergic Disease, Helsinki, Finland
      ¶Royal Free Hospital, London, U.K.
      **University of Toronto and Ventana Clinical Research, Toronto, Canada
      ††Poznań University of Medical Sciences, Poznań, Poland
      ‡‡Case Western Reserve University, University Hospitals of Cleveland, Cleveland, OH, U.S.A.
      §§Clinical Research, Novartis Pharmaceuticals Inc., East Hanover, NJ, U.S.A.
      ¶¶Clinical Research Dermatology, WSJ 210.9.13, Novartis Pharma AG, CH-4002, Basel, Switzerland
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  • I. Marks,

    1. Department of Dermatology, Medical University of Vienna, Austria
      *Ninewells Hospital and Medical School, Dundee, U.K.
      †Oregon Health and Science University, Portland, OR, U.S.A.
      ‡Probity Medical Research, Waterloo, Ontario, Canada
      §Hospital for Skin and Allergic Disease, Helsinki, Finland
      ¶Royal Free Hospital, London, U.K.
      **University of Toronto and Ventana Clinical Research, Toronto, Canada
      ††Poznań University of Medical Sciences, Poznań, Poland
      ‡‡Case Western Reserve University, University Hospitals of Cleveland, Cleveland, OH, U.S.A.
      §§Clinical Research, Novartis Pharmaceuticals Inc., East Hanover, NJ, U.S.A.
      ¶¶Clinical Research Dermatology, WSJ 210.9.13, Novartis Pharma AG, CH-4002, Basel, Switzerland
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  • R. Cherill,

    1. Department of Dermatology, Medical University of Vienna, Austria
      *Ninewells Hospital and Medical School, Dundee, U.K.
      †Oregon Health and Science University, Portland, OR, U.S.A.
      ‡Probity Medical Research, Waterloo, Ontario, Canada
      §Hospital for Skin and Allergic Disease, Helsinki, Finland
      ¶Royal Free Hospital, London, U.K.
      **University of Toronto and Ventana Clinical Research, Toronto, Canada
      ††Poznań University of Medical Sciences, Poznań, Poland
      ‡‡Case Western Reserve University, University Hospitals of Cleveland, Cleveland, OH, U.S.A.
      §§Clinical Research, Novartis Pharmaceuticals Inc., East Hanover, NJ, U.S.A.
      ¶¶Clinical Research Dermatology, WSJ 210.9.13, Novartis Pharma AG, CH-4002, Basel, Switzerland
    Search for more papers by this author
  • S. Emady-Azar,

    1. Department of Dermatology, Medical University of Vienna, Austria
      *Ninewells Hospital and Medical School, Dundee, U.K.
      †Oregon Health and Science University, Portland, OR, U.S.A.
      ‡Probity Medical Research, Waterloo, Ontario, Canada
      §Hospital for Skin and Allergic Disease, Helsinki, Finland
      ¶Royal Free Hospital, London, U.K.
      **University of Toronto and Ventana Clinical Research, Toronto, Canada
      ††Poznań University of Medical Sciences, Poznań, Poland
      ‡‡Case Western Reserve University, University Hospitals of Cleveland, Cleveland, OH, U.S.A.
      §§Clinical Research, Novartis Pharmaceuticals Inc., East Hanover, NJ, U.S.A.
      ¶¶Clinical Research Dermatology, WSJ 210.9.13, Novartis Pharma AG, CH-4002, Basel, Switzerland
    Search for more papers by this author
  • C. Paul,

    1. Department of Dermatology, Medical University of Vienna, Austria
      *Ninewells Hospital and Medical School, Dundee, U.K.
      †Oregon Health and Science University, Portland, OR, U.S.A.
      ‡Probity Medical Research, Waterloo, Ontario, Canada
      §Hospital for Skin and Allergic Disease, Helsinki, Finland
      ¶Royal Free Hospital, London, U.K.
      **University of Toronto and Ventana Clinical Research, Toronto, Canada
      ††Poznań University of Medical Sciences, Poznań, Poland
      ‡‡Case Western Reserve University, University Hospitals of Cleveland, Cleveland, OH, U.S.A.
      §§Clinical Research, Novartis Pharmaceuticals Inc., East Hanover, NJ, U.S.A.
      ¶¶Clinical Research Dermatology, WSJ 210.9.13, Novartis Pharma AG, CH-4002, Basel, Switzerland
    Search for more papers by this author
  • the Multicentre Investigator Group

    1. Department of Dermatology, Medical University of Vienna, Austria
      *Ninewells Hospital and Medical School, Dundee, U.K.
      †Oregon Health and Science University, Portland, OR, U.S.A.
      ‡Probity Medical Research, Waterloo, Ontario, Canada
      §Hospital for Skin and Allergic Disease, Helsinki, Finland
      ¶Royal Free Hospital, London, U.K.
      **University of Toronto and Ventana Clinical Research, Toronto, Canada
      ††Poznań University of Medical Sciences, Poznań, Poland
      ‡‡Case Western Reserve University, University Hospitals of Cleveland, Cleveland, OH, U.S.A.
      §§Clinical Research, Novartis Pharmaceuticals Inc., East Hanover, NJ, U.S.A.
      ¶¶Clinical Research Dermatology, WSJ 210.9.13, Novartis Pharma AG, CH-4002, Basel, Switzerland
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  • Conflicts of interest: K.W. has received research grants from Novartis but holds no personal or financial interest in the company; S.R. has participated in clinical studies for Novartis Pharma and Fujisawa GmbH; R.C., I.M., S.E-A. and C.P. are employees of Novartis.

Carle Paul.
E-mail: carle.paul@pharma.novartis.com

Summary

Background  Adult atopic dermatitis (AD) can seriously affect quality of life of patients and their families, and patients' disease is frequently not satisfactorily controlled with topical therapy. There is a need for alternatives to topical treatment in patients with moderate to severe AD.

Objectives  To investigate the efficacy and safety of oral pimecrolimus, and to determine the response to three different doses in the treatment of AD.

Methods  In a double-blind, placebo-controlled, parallel-group, dose-finding study, patients with moderate to severe AD were randomized to receive either placebo, or oral pimecrolimus 10, 20 or 30 mg twice daily. The study consisted of a pretreatment phase, a 12-week double-blind treatment phase, and a 12-week post-treatment phase.

Results  In total, 103 patients were randomized. A clear, dose-dependent therapeutic effect of pimecrolimus treatment was observed, with a statistically significant onset of efficacy at week 2 and the greatest reduction from baseline of the Eczema Area and Severity Index of 66·6% at week 7 in the 30 mg twice daily dose group. Oral pimecrolimus was well tolerated and there were no signs of nephrotoxicity or the induction of hypertension.

Conclusions  These data demonstrate the clinically relevant efficacy and short-term safety of oral pimecrolimus in adults with moderate to severe AD. Longer-term studies in larger cohorts are now required.

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