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An Evaluation of the Effectiveness of Risk Minimization Measures for Tigecycline in the European Union

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Abstract

Background

Risk minimization measures (RMM) were implemented from February 2011 in the European Union to address risks of superinfection, off-label use and lack of efficacy associated with tigecycline. The objective of this study was to evaluate RMM effectiveness by describing prescription patterns among adults and children treated with any dose of tigecycline for any indication pre- and post-RMM implementation; incidence proportions of superinfection and lack of efficacy among adults treated with approved doses of tigecycline for complicated intra-abdominal infection and complicated skin and soft tissue infection were also evaluated.

Methods

This was an observational, retrospective chart-abstraction study, including charts from 777 patients (399 pre-RMM, 378 post-RMM) at 13 sites across Austria, Germany, Italy, Greece and the United Kingdom (UK). Potential superinfection and lack of efficacy cases among those using tigecycline for on-label indication, age, dose, and duration were adjudicated. The distribution of indications for tigecycline was analyzed overall (i.e. across both study periods) and stratified by study period. Numbers and incidence proportions of superinfection and lack of efficacy cases (potential and adjudicated) were calculated overall and by study period.

Results

Off-label use (indication or age) decreased from 54.2% [95% confidence interval (95% CI): 49.0, 59.3%] pre-RMM to 35.7% (95% CI 30.4, 41.2%) post-RMM. Overall, 45.7% (95% CI 41.9, 49.5%) of patients were prescribed tigecycline off-label; the most commonly reported off-label indications were characterized as “other” (25.5%), hospital acquired pneumonia (8.2%), other pneumonia (6.3%), bacteremia (5.2%) and diabetic foot infection (1.5%). Across study periods, incidence proportions of definite or probable superinfection and lack of efficacy in adults treated for approved indications, authorized treatment doses and duration were 4.5% (95% CI 2.1, 8.4%) and 5.5% (95% CI 2.8, 9.7%), respectively.

Conclusions

Off-label use of tigecycline decreased following RMM implementation. Overall incidence proportions of definite or probable superinfection and lack of efficacy were low. EU PAS register number: EUPAS3674

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Acknowledgements

The authors acknowledge the critical role of Nataliya Volkova, Kevin Sweetland, and Elisa Baelen, Dairin Peret, Ankit Shah, Kathryn Starzyk and other Quintiles, Inc staff in the successful conduct of this study. Further acknowledgement and thanks are due to the in-country investigators (Florian Thalhammer, Guenter Weiss, Stefan Utzolino, Claudia D. Spies, Achim Jorres, Christian Lojewski, George Petrikkos, Panagiotis Kakolyris Gargalianos, Ercole Concia, Elda Righi, Pierluigi Viale, Andrew Kirby and Khalid Mehdi Khalaf Alshafi) and sub-investigators, without whom this study would not have been possible.

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Authors and Affiliations

  1. Pfizer, Inc., New York, NY, 10017, USA

    Vera Frajzyngier, Alvaro Quintana, Hal Tucker, Michele Wible, Anne Hickman, Nathalie Baillon-Plot, Rebecca Lundin & Scott Rottinghaus

  2. APHP, Centre Hospitalier Universitaire Bichat-Claude Bernard, Paris Diderot Sorbonne Cite University, Paris, France

    Philippe Montravers

  3. Santa Maria Della Misericordia University Hospital, Udine, Italy

    Matteo Bassetti

  4. Klinikum Peine Academic Hospital of Medical University Hannover, Peine, Germany

    Christian Eckmann

Authors
  1. Vera Frajzyngier
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  2. Alvaro Quintana
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  3. Hal Tucker
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  4. Michele Wible
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  5. Anne Hickman
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  6. Nathalie Baillon-Plot
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  7. Rebecca Lundin
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  8. Philippe Montravers
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  9. Matteo Bassetti
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  10. Christian Eckmann
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  11. Scott Rottinghaus
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Corresponding author

Correspondence to Vera Frajzyngier.

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Funding

This study was sponsored by Pfizer Inc.

Conflict of interest

Vera Frajzyngier, Alvaro Quintana, Hal Tucker, Michele Wible, Anne Hickman, Nathalie Baillon-Plot, Rebecca Lundin and Scott Rottinghaus are or have been employees at Pfizer, Inc. Philippe Montravers, Matteo Bassetti, Christian Eckmann have been paid consultants for Pfizer, Inc., and received remuneration from Pfizer for their services in connection with this study.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this study, formal consent was not required in the countries included as part of the primary analysis.

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Frajzyngier, V., Quintana, A., Tucker, H. et al. An Evaluation of the Effectiveness of Risk Minimization Measures for Tigecycline in the European Union. Pharm Med 31, 89–99 (2017). https://doi.org/10.1007/s40290-017-0180-z

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  • DOI: https://doi.org/10.1007/s40290-017-0180-z

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