Efficacy of Tildrakizumab Across Different Body Weights in Moderate-to-Severe Psoriasis Over 5 Years: Pooled Analyses from the reSURFACE Pivotal Studies

Diamant Thaçi; Sascha Gerdes; Kristian Gaarn Du Jardin; Jean Luc Perrot; Lluís Puig

doi:10.1007/s13555-022-00793-z

Efficacy of Tildrakizumab Across Different Body Weights in Moderate-to-Severe Psoriasis Over 5 Years: Pooled Analyses from the reSURFACE Pivotal Studies

Diamant Thaçi^*, Sascha Gerdes, Kristian Gaarn Du Jardin, Jean Luc Perrot, Lluís Puig

^*Corresponding author for this work

Institute of Inflammation Medicine

11 Citations (Scopus)

Abstract

Introduction: Tildrakizumab (TIL), a monoclonal antibody that selectively targets interleukin-23p19, has been approved for the treatment of moderate-to-severe plaque psoriasis. According to the European Medicines Agency Summary of Product Characteristics, the recommended dose is 100 mg, but a 200 mg dose can be used in patients with certain characteristics, such as a high disease burden or body weight (BW) ≥ 90 kg. Fixed one-dose biological therapies tend to become less effective in patients with high BW. This post-hoc study describes the long-term efficacy of TIL across different BWs in pivotal clinical trials. Methods: A 5-year pooled analysis of two double-blind, randomised, controlled phase III trials—reSURFACE 1 and 2—was performed. Efficacy measures were the proportions of the patients with an absolute Psoriasis Area and Severity Index (PASI) of < 3 and < 1 and a Dermatology Life Quality Index (DLQI) of 0/1. The study population included patients randomised to TIL 100 mg or TIL 200 mg who received ≥ 1 TIL dose up to week 12 (part 1 of the trial) or up to week 28 (part 2) and patients who were responders (≥ 75% improvement in PASI) to TIL 100 or TIL 200 mg at week 28 and who were maintained on the same dose up to week 244. Efficacy was evaluated by analysing BW subgroups at weeks 28, 52 and 244. Missing data were analysed using multiple imputation. Safety was assessed in the all-patients-as-treated population. Results: The proportions of TIL-treated patients with PASI < 3 and < 1 (up to week 244) and DLQI 0/1 (up to week 52) were similar for patients with BW < 90 or ≥ 90 kg, regardless of dose. Patients ≥ 120 kg had greater efficacy outcomes at the 200 mg dose. Safety outcomes were similar regardless of treatment dose and weight (< 120/≥ 120 kg). Conclusion: In patients with BW ≥ 120 kg, TIL 200 mg is more efficacious than TIL 100 mg, with similar favourable safety profiles obtained regardless of dose and BW group. Trial registration: ClinicalTrials.gov NCT01722331 (reSURFACE 1) and NCT01729754 (reSURFACE 2).

Original language	English
Journal	Dermatology and therapy
Volume	12
Issue number	10
Pages (from-to)	2325-2341
Number of pages	17
ISSN	2193-8210
DOIs	https://doi.org/10.1007/s13555-022-00793-z
Publication status	Published - 10.2022

Funding

Medical writing assistance in the preparation of this manuscript was provided by Mónica Giménez, PhD, and Eva Mateu, PhD, of TFS HealthScience. Support for this assistance was funded by Almirall R&D, Barcelona, Spain. We thank the participants of the study. The post hoc analyses and Rapid Service Fee for this manuscript were sponsored by Almirall R&D, Barcelona, Spain. Medical writing assistance in the preparation of this manuscript was provided by Mónica Giménez, PhD, and Eva Mateu, PhD, of TFS HealthScience. Support for this assistance was funded by Almirall R&D, Barcelona, Spain. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. DT made a significant contribution to the conception and design of the study, the analysis and interpretation, the drafting of the manuscript and the critical review of it for important intellectual content. SG and KGdJ contributed to the conception and study design and critically reviewed the article. JLP and LLP critically reviewed the manuscript. Part of this manuscript is based on work that was previously presented at the 31st Congress of the European Academy of Dermatology and Venereology (EADV), Milan, 7–10 September 2022. Diamant Thaçi has received honoraria as an advisor, speaker and/or investigator from AbbVie, Almirall, Amgen, Biogen-Idec, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Janssen-Cilag, LEO Pharma, Novartis, Pfizer, Regeneron, Roche-Possay, Samsung, Sanofi and UCB; Sascha Gerdes has been an advisor for and/or received speakers’ honoraria from and/or received grants from and/or participated in clinical trials by the following companies: AbbVie, Affibody AB, Akari Therapeutics Plc, Almirall-Hermal, Amgen, Anaptys Bio, Argenx BV, AstraZeneca AB, Biogen Idec, Bioskin, BoehringerIngelheim, Celgene, Dermira, Eli Lilly, Forward Pharma, Galderma, Hexal AG, Incyte Inc., Janssen-Cilag, Johnson & Johnson, Kymab, Leo Pharma, Medac, MSD, Neubourg Skin Care GmbH, Novartis, Pfizer, Principia Biopharma, Regeneron Pharmaceutical, Sandoz Biopharmaceuticals, Sanofi-Aventis, Trevi Therapeutics, and UCB Pharma; Kristian Gaarn Du Jardin is an employee of Almirall; Jean-Luc Perrot has been an advisor for and/or received speakers’ honoraria from and/or received grants from and/or participated in clinical trials by the following companies: Abbott/AbbVie Inc, Amgen, Celgene, Eli Lilly and Company, Galderma, Incyte Corporation, Janssen-Cilag Ltd, Johnson & Johnson, LEO Pharma, Merck Serono, Merck Sharp & Dohme, Novartis, Pierre Fabre, Pfizer, Sanofi-Aventis, Schering-Plough, and UCB Pharma; Lluís Puig has received grants/research support from or participated in clinical trials (paid to the institution) by AbbVie, Almirall, Amgen, Boehringer Ingelheim, Celgene, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Regeneron, Roche, Sanof, and UCB; received honoraria or consultation fees from AbbVie, Almirall, Amgen, Baxalta, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Fresenius-Kabi, Janssen, JS BIOCAD, LEO Pharma, Lilly, Mylan, Novartis, Pfizer, Regeneron, Roche, Sandoz, Samsung-Bioepis, Sanof, and UCB; and participated in company-sponsored speaker’s bureaus for Celgene, Janssen, Lilly, Novartis, and Pfizer. The reSURFACE 1 and reSURFACE 2 trials received approval from local institutional review boards or ethics committees. The studies were performed in accordance with Good Clinical Practice guidelines and the Helsinki Declaration of 1964 and its later amendments. All subjects provided written informed consent to participate in the studies. The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Research Areas and Centers

Academic Focus: Center for Infection and Inflammation Research (ZIEL)
Centers: Center for Research on Inflammation of the Skin (CRIS)

DFG Research Classification Scheme

2.22-19 Dermatology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1007/s13555-022-00793-z

Cite this

@article{31a5072a52d04de1a36925aea66214db,

title = "Efficacy of Tildrakizumab Across Different Body Weights in Moderate-to-Severe Psoriasis Over 5 Years: Pooled Analyses from the reSURFACE Pivotal Studies",

abstract = "Introduction: Tildrakizumab (TIL), a monoclonal antibody that selectively targets interleukin-23p19, has been approved for the treatment of moderate-to-severe plaque psoriasis. According to the European Medicines Agency Summary of Product Characteristics, the recommended dose is 100 mg, but a 200 mg dose can be used in patients with certain characteristics, such as a high disease burden or body weight (BW) ≥ 90 kg. Fixed one-dose biological therapies tend to become less effective in patients with high BW. This post-hoc study describes the long-term efficacy of TIL across different BWs in pivotal clinical trials. Methods: A 5-year pooled analysis of two double-blind, randomised, controlled phase III trials—reSURFACE 1 and 2—was performed. Efficacy measures were the proportions of the patients with an absolute Psoriasis Area and Severity Index (PASI) of < 3 and < 1 and a Dermatology Life Quality Index (DLQI) of 0/1. The study population included patients randomised to TIL 100 mg or TIL 200 mg who received ≥ 1 TIL dose up to week 12 (part 1 of the trial) or up to week 28 (part 2) and patients who were responders (≥ 75\% improvement in PASI) to TIL 100 or TIL 200 mg at week 28 and who were maintained on the same dose up to week 244. Efficacy was evaluated by analysing BW subgroups at weeks 28, 52 and 244. Missing data were analysed using multiple imputation. Safety was assessed in the all-patients-as-treated population. Results: The proportions of TIL-treated patients with PASI < 3 and < 1 (up to week 244) and DLQI 0/1 (up to week 52) were similar for patients with BW < 90 or ≥ 90 kg, regardless of dose. Patients ≥ 120 kg had greater efficacy outcomes at the 200 mg dose. Safety outcomes were similar regardless of treatment dose and weight (< 120/≥ 120 kg). Conclusion: In patients with BW ≥ 120 kg, TIL 200 mg is more efficacious than TIL 100 mg, with similar favourable safety profiles obtained regardless of dose and BW group. Trial registration: ClinicalTrials.gov NCT01722331 (reSURFACE 1) and NCT01729754 (reSURFACE 2).",

author = "Diamant Tha{\c c}i and Sascha Gerdes and \{Du Jardin\}, \{Kristian Gaarn\} and Perrot, \{Jean Luc\} and Llu{\'i}s Puig",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = oct,

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language = "English",

volume = "12",

pages = "2325--2341",

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Efficacy of Tildrakizumab Across Different Body Weights in Moderate-to-Severe Psoriasis Over 5 Years: Pooled Analyses from the reSURFACE Pivotal Studies. / Thaçi, Diamant; Gerdes, Sascha; Du Jardin, Kristian Gaarn et al.
In: Dermatology and therapy, Vol. 12, No. 10, 10.2022, p. 2325-2341.

Research output: Journal Articles › Journal articles › Research › peer-review

TY - JOUR

T1 - Efficacy of Tildrakizumab Across Different Body Weights in Moderate-to-Severe Psoriasis Over 5 Years

T2 - Pooled Analyses from the reSURFACE Pivotal Studies

AU - Thaçi, Diamant

AU - Gerdes, Sascha

AU - Du Jardin, Kristian Gaarn

AU - Perrot, Jean Luc

AU - Puig, Lluís

PY - 2022/10

Y1 - 2022/10

N2 - Introduction: Tildrakizumab (TIL), a monoclonal antibody that selectively targets interleukin-23p19, has been approved for the treatment of moderate-to-severe plaque psoriasis. According to the European Medicines Agency Summary of Product Characteristics, the recommended dose is 100 mg, but a 200 mg dose can be used in patients with certain characteristics, such as a high disease burden or body weight (BW) ≥ 90 kg. Fixed one-dose biological therapies tend to become less effective in patients with high BW. This post-hoc study describes the long-term efficacy of TIL across different BWs in pivotal clinical trials. Methods: A 5-year pooled analysis of two double-blind, randomised, controlled phase III trials—reSURFACE 1 and 2—was performed. Efficacy measures were the proportions of the patients with an absolute Psoriasis Area and Severity Index (PASI) of < 3 and < 1 and a Dermatology Life Quality Index (DLQI) of 0/1. The study population included patients randomised to TIL 100 mg or TIL 200 mg who received ≥ 1 TIL dose up to week 12 (part 1 of the trial) or up to week 28 (part 2) and patients who were responders (≥ 75% improvement in PASI) to TIL 100 or TIL 200 mg at week 28 and who were maintained on the same dose up to week 244. Efficacy was evaluated by analysing BW subgroups at weeks 28, 52 and 244. Missing data were analysed using multiple imputation. Safety was assessed in the all-patients-as-treated population. Results: The proportions of TIL-treated patients with PASI < 3 and < 1 (up to week 244) and DLQI 0/1 (up to week 52) were similar for patients with BW < 90 or ≥ 90 kg, regardless of dose. Patients ≥ 120 kg had greater efficacy outcomes at the 200 mg dose. Safety outcomes were similar regardless of treatment dose and weight (< 120/≥ 120 kg). Conclusion: In patients with BW ≥ 120 kg, TIL 200 mg is more efficacious than TIL 100 mg, with similar favourable safety profiles obtained regardless of dose and BW group. Trial registration: ClinicalTrials.gov NCT01722331 (reSURFACE 1) and NCT01729754 (reSURFACE 2).

AB - Introduction: Tildrakizumab (TIL), a monoclonal antibody that selectively targets interleukin-23p19, has been approved for the treatment of moderate-to-severe plaque psoriasis. According to the European Medicines Agency Summary of Product Characteristics, the recommended dose is 100 mg, but a 200 mg dose can be used in patients with certain characteristics, such as a high disease burden or body weight (BW) ≥ 90 kg. Fixed one-dose biological therapies tend to become less effective in patients with high BW. This post-hoc study describes the long-term efficacy of TIL across different BWs in pivotal clinical trials. Methods: A 5-year pooled analysis of two double-blind, randomised, controlled phase III trials—reSURFACE 1 and 2—was performed. Efficacy measures were the proportions of the patients with an absolute Psoriasis Area and Severity Index (PASI) of < 3 and < 1 and a Dermatology Life Quality Index (DLQI) of 0/1. The study population included patients randomised to TIL 100 mg or TIL 200 mg who received ≥ 1 TIL dose up to week 12 (part 1 of the trial) or up to week 28 (part 2) and patients who were responders (≥ 75% improvement in PASI) to TIL 100 or TIL 200 mg at week 28 and who were maintained on the same dose up to week 244. Efficacy was evaluated by analysing BW subgroups at weeks 28, 52 and 244. Missing data were analysed using multiple imputation. Safety was assessed in the all-patients-as-treated population. Results: The proportions of TIL-treated patients with PASI < 3 and < 1 (up to week 244) and DLQI 0/1 (up to week 52) were similar for patients with BW < 90 or ≥ 90 kg, regardless of dose. Patients ≥ 120 kg had greater efficacy outcomes at the 200 mg dose. Safety outcomes were similar regardless of treatment dose and weight (< 120/≥ 120 kg). Conclusion: In patients with BW ≥ 120 kg, TIL 200 mg is more efficacious than TIL 100 mg, with similar favourable safety profiles obtained regardless of dose and BW group. Trial registration: ClinicalTrials.gov NCT01722331 (reSURFACE 1) and NCT01729754 (reSURFACE 2).

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U2 - 10.1007/s13555-022-00793-z

DO - 10.1007/s13555-022-00793-z

M3 - Journal articles

AN - SCOPUS:85138081696

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