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Ixekizumab treatment and the impact on SF-36: results from three pivotal phase III randomised controlled trials in patients with moderate-to-severe plaque psoriasis

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Abstract

Purpose

To assess improvements in health-related quality of life (HRQoL) with ixekizumab treatment in patients with moderate-to-severe psoriasis.

Methods

Adults with plaque psoriasis were enrolled in phase III, double-blind, randomised, controlled trials (UNCOVER-1, UNCOVER-2, or UNCOVER-3). All 3 protocols included a 12-week, placebo-controlled induction period; UNCOVER-2 and UNCOVER-3 also had an active-control group (50 mg etanercept) during induction. After induction, patients in UNCOVER-1 and UNCOVER-2 entered a 48-week withdrawal (maintenance) period (Weeks 12–60), during which Week-12 sPGA (0,1) responders were rerandomized to receive placebo, or 80 mg ixekizumab every 4 weeks (Q4W) or 12 weeks. As a secondary objective, HRQoL was measured by the generic Medical Outcomes Survey Short Form-36 (SF-36) at baseline and Weeks 12 and 60. Changes in mean SF-36 Physical and Mental Component Summary (PCS and MCS) and domain scores and proportions of patients reporting improvements ≥ minimal important differences in SF-36 scores were compared between groups.

Results

At Week 12, ixekizumab-treated patients (both dose groups in UNCOVER-1, -2, and -3) reported statistically significantly greater improvements in mean SF-36 PCS and MCS and all 8 SF-36 domain scores versus placebo. Further, more ixekizumab-treated patients than placebo-treated patients reported at least minimal treatment responses in SF-36 PCS and MCS scores and domain scores. Overall improvements in SF-36 PCS and MCS scores were maintained through Week 60.

Conclusions

Ixekizumab-treated patients reported statistically significant improvements in HRQoL at 12 weeks that persisted through 1 year.

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Acknowledgements

This study was sponsored by Eli Lilly and Company. We are indebted to the patients and study personnel who participated in UNCOVER-1, UNCOVER-2, and UNCOVER-3. Dr. Richard Warren is supported by the NIHR Manchester Biomedical Research Centre. We thank Lori Kornberg, PhD, Kelly Guerrettaz, and Lydia Morris, PhD, of Syneos Health, Raleigh, NC, who provided writing support on behalf of Eli Lilly and Company. We also thank Vrishali Lopes of Optum Outcomes Insight Consulting, Lincoln, RI, and Regina Rendas-Baum of Optum Quality Metrics, Lincoln, RI, for their data analysis on SF-36 population norms for the USA on behalf of Eli Lilly and Company.

Author information

Authors and Affiliations

  1. Division of Dermatology, Department of Medicine, Dalhousie University, 6054 Coburg Road, Halifax, NS, Canada

    Richard G. B. Langley

  2. Translational Research in Inflammatory Skin Diseases, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, and Skinflammation® Center, Hamburg, Germany

    Kristian Reich

  3. Biopharmaceutical Consultant, Portola Valley, CA, USA

    Vibeke Strand

  4. Wake Forest University Health Sciences, Winston-Salem, NC, USA

    Steven R. Feldman

  5. Toulouse University, Toulouse, France

    Carle Paul

  6. Medical College of Wisconsin, Milwaukee, WI, USA

    Kenneth Gordon

  7. The Dermatology Centre, Salford Royal NHS Foundation Trust, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK

    Richard B. Warren

  8. Probity Medical Research, Windsor, ON, Canada

    Darryl Toth

  9. Eli Lilly Benelux S.A., Brussels, Belgium

    Enkeleida Nikaï & Hilde Carlier

  10. Eli Lilly and Company, Indianapolis, IN, USA

    Baojin Zhu, Orin Goldblum, Emily Edson-Heredia, Russel Burge, Chen-Yen Lin & Kristin Hollister

  11. Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg, Hamburg, Germany

    Matthias Augustin

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  1. Richard G. B. Langley
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Corresponding author

Correspondence to Richard G. B. Langley.

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Conflict of interest

Ms Nikaï and Edson-Heredia, and Drs Zhu, Goldblum, Carlier, Burge, Lin, and Hollister are employees of Eli Lilly and Company and own stock. Professor Langley is a consultant for AbbVie, Amgen, Celgene, Pfizer, Janssen, Boehringer Ingleheim, LEO Pharma, and Valeant. He has received grants/has pending grants, has received honoraria, has received payment for development of educational programs including speaker bureau service, and received expenses covered or reimbursed for travel from AbbVie, Amgen, Celgene, Pfizer, Janssen, Boehringer Ingleheim, and LEO Pharma. Professor Reich has served as advisor and/or paid speaker for and/or participated in clinical trials sponsored by AbbVie, Affibody, Almirall, Amgen, Avillion, Biogen, Boehringer Ingelheim Pharma, Celgene, Centocor, Covagen, Forward Pharma, Fresenius Medical Care, Galapagos, GlaxoSmithKline, Janssen-Cilag, Kyowa Kirin, LEO Pharma, Eli Lilly and Company, Medac, Merck Sharp & Dohme Corp., Novartis, Miltenyi Biotec, Ocean Pharma, Pfizer, Regeneron, Samsung Bioepis, Sanofi, Sun Pharma, Takeda, UCB, Valeant, and XenoPort. Dr Feldman reports that a third party that was supported by Eli Lilly and Company assisted with manuscript preparation. He is a consultant for Eli Lilly and Company, Novartis, Janssen, and Celgene. He received Honoria from Eli Lilly and Company, AbbVie, Celgene, Janssen, and Novartis. He reports grant support or pending grant support from Eli Lilly and Company, Novartis, Janssen, AbbVie, and Celgene (support paid to institution). Dr. Strand reports consulting fees from Eli Lilly and Company, AbbVie, Amgen, Anthera, AstraZeneca, BMS, Boehringer Ingelheim, Celltrion, EMD Serono, Genentech/Roche, GSK, Janssen, Novartis, Pfizer, Regeneron, Sanofi, UCB, outside the submitted work. Dr Paul has received grant support from ADERMI. He reports honoria and reimbursed travel expenses from AbbVie, Boerhinger, Celgene, Eli Lilly and Company, Janssen Cilag, Almirall, Regeneron, Sanofi, Novartis, Pfizer, LEO Pharma, and Pierre Fabre. Dr Gordon received research support from AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly and Company, Novartis, and Jannsen. He has received consulting fees or honoraria from AbbVie, Amgen, Boehringer Ingelheim, Celgene, Dermira, Novartis, Janssen, and Eli Lilly and Company. Dr Richard Warren has actively consulted for AbbVie, Almiral, Amgen, Boehringer Ingelheim, Celgene, Pfizer, Novartis, Janssen, LEO Pharma, XenPort, Eli Lilly and Company, and UCB. Dr Warren’s institution has grants/grants pending from LEO Pharma, AbbVie, Novartis, and Eli Lilly and Company. Dr Warren has received an honorarium from AbbVie, Almiral, Amgen, Boehringer Ingelheim, Celgene, Pfizer, Novartis, Janssen, LEO Pharma, XenPort, Eli Lilly and Company, and UCB. Dr Toth has served as an investigator or speaker for Abbvie, Amgen, BMS, Boehringer Ingelheim, Celgene, Elli Lilly and Company, Incyte, Janssen, Leo Pharma, Novartis, Pfizer, Regeneron, Sanofi-Genzyme, and UCB. M. Augustin has served as a consultant and/or paid speaker for and/or has received research grants and/or honoraries for consulting and/or scientific lectures for and/or received travel expense reimbursement and/or participated in clinical trials sponsored by companies that manufacture drugs used for treatment of psoriasis including AbbVie, Almirall, Amgen, Biogen (Biogen Idec), Boehringer Ingelheim, Celgene, Centocor, Eli Lilly and Company, Janssen-Cilag, LEO Pharma, Medac, MSD (formerly Essex, Schering-Plough), Mundipharma, Novartis, Pfizer, (formerly Wyeth), Pohl Boskamp, Sandoz, and XenoPort.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committees and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Langley, R.G.B., Reich, K., Strand, V. et al. Ixekizumab treatment and the impact on SF-36: results from three pivotal phase III randomised controlled trials in patients with moderate-to-severe plaque psoriasis. Qual Life Res 29, 369–380 (2020). https://doi.org/10.1007/s11136-019-02296-5

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