Long-term efficacy and safety of tildrakizumab for moderate-to-severe psoriasis: pooled analyses of two randomized phase III clinical trials (reSURFACE 1 and reSURFACE 2) through 148 weeks

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

DOI

  • K Reich, Dermatologikum Berlin and SCIderm Research Institute, Hamburg, Germany.
  • ,
  • R B Warren, Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester NIHR Biomedical Research Centre, The University of Manchester, Manchester, U.K.
  • ,
  • L Iversen
  • L Puig, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
  • ,
  • I Pau-Charles, Almirall R&D, Barcelona, Spain.
  • ,
  • A Igarashi, NTT Medical Center Tokyo, Tokyo, Japan.
  • ,
  • M Ohtsuki, Department of Dermatology, Jichi Medical University, Tochigi, Japan.
  • ,
  • M Falqués, Almirall R&D, Barcelona, Spain.
  • ,
  • M Harmut, Almirall R&D, Barcelona, Spain.
  • ,
  • S Rozzo, Sun Pharmaceuticals, Princeton, NJ, U.S.A.
  • ,
  • M G Lebwohl, Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, U.S.A
  • ,
  • W Cantrell, Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, U.S.A.
  • ,
  • A Blauvelt, Oregon Medical Research Center, Portland, OR, U.S.A.
  • ,
  • D Thaçi, Institute and Comprehensive Centre for Inflammation Medicine, University of Lübeck, Lübeck, Germany.

BACKGROUND: Tildrakizumab is a specific anti-interleukin-23p19 monoclonal antibody approved for the treatment of plaque psoriasis.

OBJECTIVES: To evaluate the long-term efficacy and safety of tildrakizumab treatment for patients with moderate-to-severe psoriasis for up to 148 weeks.

METHODS: Pooled analysis from two double-blind, randomized controlled trials: reSURFACE 1 and reSURFACE 2. Efficacy was assessed for responders (≥ 75% improvement in Psoriasis Area and Severity Index; PASI 75) and partial responders (PASI 50-75) to tildrakizumab 100 mg and 200 mg at week 28 who were maintained on the same dose (administered every 12 weeks), and for partial responders or nonresponders (PASI < 50) to etanercept 50 mg at week 28 who, after a 4-week washout, were switched to tildrakizumab 200 mg (administered at weeks 32 and 36, and every 12 weeks thereafter). Safety was assessed in the all-patients-as-treated population. Three different methods of imputing missing data were used: nonresponder imputation (NRI), multiple imputation and observed cases. The Clinicaltrials.gov numbers are NCT01722331 (reSURFACE 1) and NCT01729754 (reSURFACE 2).

RESULTS: At week 148 (NRI), 72·6%, 53·8% and 28·9% of tildrakizumab 100-mg responders and 80·2%, 59·9% and 32·6% of tildrakizumab 200-mg responders had PASI 75, 90 and 100 responses, respectively. For partial responders to tildrakizumab 100 mg and 200 mg, the proportions of patients achieving PASI 75, 90 and 100 responses were 32·5%, 25·0% and 10·0%; and 47·1%, 27·5% and 12·8%, respectively. For patients who were partial responders or nonresponders to etanercept, the proportions of patients achieving PASI 75, 90 and 100 responses were 66·9%, 43·8% and 14·9% at week 148. Rates of discontinuations due to adverse events [tildrakizumab 100 mg: 1·7 per 100 patient-years (PYs); tildrakizumab 200 mg: 1·2 per 100 PYs] and exposure-adjusted rates of serious adverse events (5·9 per 100 PYs; 5·5 per 100 PYs), severe infections (1·1 per 100 PYs; 1·1 per 100 PYs), malignancies (0·6 per 100 PYs; 0·4 per 100 PYs) and major adverse cardiovascular events (0·4 per 100 PYs; 0·5 per 100 PYs) were low.

CONCLUSIONS: Tildrakizumab was well tolerated and efficacy was well maintained in week 28 responders who continued tildrakizumab treatment through 3 years, or improved among etanercept partial responders or nonresponders who switched to tildrakizumab.

OriginalsprogEngelsk
TidsskriftBritish Journal of Dermatology
ISSN0007-0963
DOI
StatusE-pub ahead of print - 19 jun. 2019

Bibliografisk note

© 2019 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

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