Efficacy and Safety of Ixekizumab with or Without Methotrexate in Biologic-Naïve Patients with Psoriatic Arthritis: 52-Week Results from SPIRIT-H2H Study

Josef S. Smolen; Anthony Sebba; Eric M. Ruderman; Hendrik Schulze-Koops; Christophe Sapin; Amanda M. Gellett; Aubrey Trevelin Sprabery; Lingnan Li; Inmaculada de la Torre; Gaia Gallo; Soyi Liu-Leage; Sreekumar Pillai; Paulo Reis; Peter Nash

doi:10.1007/s40744-020-00250-3

Efficacy and Safety of Ixekizumab with or Without Methotrexate in Biologic-Naïve Patients with Psoriatic Arthritis: 52-Week Results from SPIRIT-H2H Study

Josef S. Smolen, Anthony Sebba, Eric M. Ruderman, Hendrik Schulze-Koops, Christophe Sapin, Amanda M. Gellett, Aubrey Trevelin Sprabery, Lingnan Li, Inmaculada de la Torre, Gaia Gallo, Soyi Liu-Leage, Sreekumar Pillai, Paulo Reis, Peter Nash^*

^*Corresponding author for this work

Medicine, Rheumatology Division

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

Abstract

Introduction: In the SPIRIT-H2H (ClinicalTrials.gov: NCT03151551) trial in biologic-naïve patients with active psoriatic arthritis (PsA), ixekizumab (IXE) was superior to adalimumab (ADA) at week 24 in terms of achieving a combined endpoint of ≥ 50% improved response in the American College of Rheumatology scale score (ACR50) and 100% improvement in the Psoriasis Areas and Severity Index (PASI100), and was non-inferior in terms of achieving ACR50. IXE resulted in similar improvements of PsA manifestations irrespective of the use of concomitant conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), while ADA response was higher with concomitant csDMARD use. The aim of this study was to determine the efficacy and safety of treatment with IXE and ADA with or without methotrexate (MTX), the most commonly use csDMARD, through week 52 in patients with PsA. Methods: In the open-label, rater-blinded, head-to-head SPIRIT-H2H trial, randomization of patients was stratified by concomitant use of csDMARD and moderate-to-severe plaque psoriasis involvement. In the post-hoc subgroup analysis presented here, subgroups were defined as with/without concomitant MTX use at baseline. Treatment group effects within subgroups were tested using Fisher’s exact test. Missing data were imputed using non-responder imputation. Results: By week 52, IXE provided similar improvements in the combined ACR50 and PASI100 endpoint, ACR50, and other PsA-related domains regardless of whether IXE was used with or without MTX, while ADA efficacy appeared to be improved with concomitant MTX use. When used without concomitant MTX, IXE resulted in significantly higher response versus ADA in terms of the combined ACR50 and PASI100 (p = 0.002) endpoint, minimal disease activity (p = 0.016), and very low disease activity (p = 0.037). The safety of both agents was consistent with their known safety profiles regardless of concomitant MTX use. Conclusion: In PsA patients with inadequate control of the disease, IXE delivers consistent efficacy in several clinical domains of the disease regardless of concomitant MTX use. The efficacy of ADA is increased by the concomitant use of MTX. These findings can inform treatment decisions when considering the need for concomitant MTX use with IXE or ADA at initiation or for long-term maintenance.

Original language	English (US)
Pages (from-to)	1021-1035
Number of pages	15
Journal	Rheumatology and Therapy
Volume	7
Issue number	4
DOIs	https://doi.org/10.1007/s40744-020-00250-3
State	Published - Dec 2020

Funding

The authors thank the study participants, caregivers, and investigators. This study and the journal’s Rapid Service Fee were funded by Eli Lilly and Company, which contributed to study design, data collection, data analysis, data interpretation, manuscript preparation, and publication decisions. Elsa Mevel, PhD and Cynthia R. Abbott who are employees of Eli Lilly provided writing and editorial assistance. Funding for this assistance was provided by Eli Lilly and Company. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, had full access to all the data in this study, take responsibility for the integrity of data and accuracy of the data analysis, and have given their approval for this version to be published. Josef S Smolen reports research grants from AbbVie, Astra-Zeneca, Janssen, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, and Roche; and personal fees from AbbVie, Amgen, Astra-Zeneca, Astro, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Gilead, ILTOO, Janssen, Lilly, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, and UCB. Anthony Sebba is a consultant for Eli Lilly and Company, Genentech, Gilead, Regeneron Pharmaceuticals, Sanofi, and is on the speaker bureau of Eli Lilly and Company, Roche, and Sanofi. Eric M Ruderman is a consultant for AbbVie, Amgen, Bristol-Meyers Squibb, Eli Lilly and Company, Gilead, Janssen, Novartis, and Pfizer. Hendrik Schulze-Koops has research grants from AbbVie, Novartis, and has received honoraria for consultancies and/or speaking engagements from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Gilead, Janssen, Eli Lilly and Company, Merck Sharp & Dohme, Novartis-Sandoz, Pfizer, Roche, Sanofi.

Keywords

Adalimumab
Ixekizumab
Methotrexate
Psoriatic arthritis
csDMARD

ASJC Scopus subject areas

Rheumatology
Immunology and Allergy

Access to Document

10.1007/s40744-020-00250-3

Cite this

Smolen, J. S., Sebba, A., Ruderman, E. M., Schulze-Koops, H., Sapin, C., Gellett, A. M., Sprabery, A. T., Li, L., de la Torre, I., Gallo, G., Liu-Leage, S., Pillai, S., Reis, P., & Nash, P. (2020). Efficacy and Safety of Ixekizumab with or Without Methotrexate in Biologic-Naïve Patients with Psoriatic Arthritis: 52-Week Results from SPIRIT-H2H Study. Rheumatology and Therapy, 7(4), 1021-1035. https://doi.org/10.1007/s40744-020-00250-3

@article{c60580d1a8394fcdacebad30dd7fd8a0,

title = "Efficacy and Safety of Ixekizumab with or Without Methotrexate in Biologic-Na{\"i}ve Patients with Psoriatic Arthritis: 52-Week Results from SPIRIT-H2H Study",

abstract = "Introduction: In the SPIRIT-H2H (ClinicalTrials.gov: NCT03151551) trial in biologic-na{\"i}ve patients with active psoriatic arthritis (PsA), ixekizumab (IXE) was superior to adalimumab (ADA) at week 24 in terms of achieving a combined endpoint of ≥ 50% improved response in the American College of Rheumatology scale score (ACR50) and 100% improvement in the Psoriasis Areas and Severity Index (PASI100), and was non-inferior in terms of achieving ACR50. IXE resulted in similar improvements of PsA manifestations irrespective of the use of concomitant conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), while ADA response was higher with concomitant csDMARD use. The aim of this study was to determine the efficacy and safety of treatment with IXE and ADA with or without methotrexate (MTX), the most commonly use csDMARD, through week 52 in patients with PsA. Methods: In the open-label, rater-blinded, head-to-head SPIRIT-H2H trial, randomization of patients was stratified by concomitant use of csDMARD and moderate-to-severe plaque psoriasis involvement. In the post-hoc subgroup analysis presented here, subgroups were defined as with/without concomitant MTX use at baseline. Treatment group effects within subgroups were tested using Fisher{\textquoteright}s exact test. Missing data were imputed using non-responder imputation. Results: By week 52, IXE provided similar improvements in the combined ACR50 and PASI100 endpoint, ACR50, and other PsA-related domains regardless of whether IXE was used with or without MTX, while ADA efficacy appeared to be improved with concomitant MTX use. When used without concomitant MTX, IXE resulted in significantly higher response versus ADA in terms of the combined ACR50 and PASI100 (p = 0.002) endpoint, minimal disease activity (p = 0.016), and very low disease activity (p = 0.037). The safety of both agents was consistent with their known safety profiles regardless of concomitant MTX use. Conclusion: In PsA patients with inadequate control of the disease, IXE delivers consistent efficacy in several clinical domains of the disease regardless of concomitant MTX use. The efficacy of ADA is increased by the concomitant use of MTX. These findings can inform treatment decisions when considering the need for concomitant MTX use with IXE or ADA at initiation or for long-term maintenance.",

keywords = "Adalimumab, Ixekizumab, Methotrexate, Psoriatic arthritis, csDMARD",

author = "Smolen, {Josef S.} and Anthony Sebba and Ruderman, {Eric M.} and Hendrik Schulze-Koops and Christophe Sapin and Gellett, {Amanda M.} and Sprabery, {Aubrey Trevelin} and Lingnan Li and {de la Torre}, Inmaculada and Gaia Gallo and Soyi Liu-Leage and Sreekumar Pillai and Paulo Reis and Peter Nash",

note = "Funding Information: The authors thank the study participants, caregivers, and investigators. This study and the journal{\textquoteright}s Rapid Service Fee were funded by Eli Lilly and Company, which contributed to study design, data collection, data analysis, data interpretation, manuscript preparation, and publication decisions. Elsa Mevel, PhD and Cynthia R. Abbott who are employees of Eli Lilly provided writing and editorial assistance. Funding for this assistance was provided by Eli Lilly and Company. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, had full access to all the data in this study, take responsibility for the integrity of data and accuracy of the data analysis, and have given their approval for this version to be published. Josef S Smolen reports research grants from AbbVie, Astra-Zeneca, Janssen, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, and Roche; and personal fees from AbbVie, Amgen, Astra-Zeneca, Astro, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Gilead, ILTOO, Janssen, Lilly, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, and UCB. Anthony Sebba is a consultant for Eli Lilly and Company, Genentech, Gilead, Regeneron Pharmaceuticals, Sanofi, and is on the speaker bureau of Eli Lilly and Company, Roche, and Sanofi. Eric M Ruderman is a consultant for AbbVie, Amgen, Bristol-Meyers Squibb, Eli Lilly and Company, Gilead, Janssen, Novartis, and Pfizer. Hendrik Schulze-Koops has research grants from AbbVie, Novartis, and has received honoraria for consultancies and/or speaking engagements from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Gilead, Janssen, Eli Lilly and Company, Merck Sharp & Dohme, Novartis-Sandoz, Pfizer, Roche, Sanofi. Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = dec,

doi = "10.1007/s40744-020-00250-3",

language = "English (US)",

volume = "7",

pages = "1021--1035",

journal = "Rheumatology and Therapy",

issn = "2198-6576",

publisher = "Adis International Ltd",

number = "4",

}

Smolen, JS, Sebba, A, Ruderman, EM, Schulze-Koops, H, Sapin, C, Gellett, AM, Sprabery, AT, Li, L, de la Torre, I, Gallo, G, Liu-Leage, S, Pillai, S, Reis, P & Nash, P 2020, 'Efficacy and Safety of Ixekizumab with or Without Methotrexate in Biologic-Naïve Patients with Psoriatic Arthritis: 52-Week Results from SPIRIT-H2H Study', Rheumatology and Therapy, vol. 7, no. 4, pp. 1021-1035. https://doi.org/10.1007/s40744-020-00250-3

TY - JOUR

T1 - Efficacy and Safety of Ixekizumab with or Without Methotrexate in Biologic-Naïve Patients with Psoriatic Arthritis

T2 - 52-Week Results from SPIRIT-H2H Study

AU - Smolen, Josef S.

AU - Sebba, Anthony

AU - Ruderman, Eric M.

AU - Schulze-Koops, Hendrik

AU - Sapin, Christophe

AU - Gellett, Amanda M.

AU - Sprabery, Aubrey Trevelin

AU - Li, Lingnan

AU - de la Torre, Inmaculada

AU - Gallo, Gaia

AU - Liu-Leage, Soyi

AU - Pillai, Sreekumar

AU - Reis, Paulo

AU - Nash, Peter

N1 - Funding Information: The authors thank the study participants, caregivers, and investigators. This study and the journal’s Rapid Service Fee were funded by Eli Lilly and Company, which contributed to study design, data collection, data analysis, data interpretation, manuscript preparation, and publication decisions. Elsa Mevel, PhD and Cynthia R. Abbott who are employees of Eli Lilly provided writing and editorial assistance. Funding for this assistance was provided by Eli Lilly and Company. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, had full access to all the data in this study, take responsibility for the integrity of data and accuracy of the data analysis, and have given their approval for this version to be published. Josef S Smolen reports research grants from AbbVie, Astra-Zeneca, Janssen, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, and Roche; and personal fees from AbbVie, Amgen, Astra-Zeneca, Astro, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Gilead, ILTOO, Janssen, Lilly, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, and UCB. Anthony Sebba is a consultant for Eli Lilly and Company, Genentech, Gilead, Regeneron Pharmaceuticals, Sanofi, and is on the speaker bureau of Eli Lilly and Company, Roche, and Sanofi. Eric M Ruderman is a consultant for AbbVie, Amgen, Bristol-Meyers Squibb, Eli Lilly and Company, Gilead, Janssen, Novartis, and Pfizer. Hendrik Schulze-Koops has research grants from AbbVie, Novartis, and has received honoraria for consultancies and/or speaking engagements from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Gilead, Janssen, Eli Lilly and Company, Merck Sharp & Dohme, Novartis-Sandoz, Pfizer, Roche, Sanofi. Publisher Copyright: © 2020, The Author(s).

PY - 2020/12

Y1 - 2020/12

N2 - Introduction: In the SPIRIT-H2H (ClinicalTrials.gov: NCT03151551) trial in biologic-naïve patients with active psoriatic arthritis (PsA), ixekizumab (IXE) was superior to adalimumab (ADA) at week 24 in terms of achieving a combined endpoint of ≥ 50% improved response in the American College of Rheumatology scale score (ACR50) and 100% improvement in the Psoriasis Areas and Severity Index (PASI100), and was non-inferior in terms of achieving ACR50. IXE resulted in similar improvements of PsA manifestations irrespective of the use of concomitant conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), while ADA response was higher with concomitant csDMARD use. The aim of this study was to determine the efficacy and safety of treatment with IXE and ADA with or without methotrexate (MTX), the most commonly use csDMARD, through week 52 in patients with PsA. Methods: In the open-label, rater-blinded, head-to-head SPIRIT-H2H trial, randomization of patients was stratified by concomitant use of csDMARD and moderate-to-severe plaque psoriasis involvement. In the post-hoc subgroup analysis presented here, subgroups were defined as with/without concomitant MTX use at baseline. Treatment group effects within subgroups were tested using Fisher’s exact test. Missing data were imputed using non-responder imputation. Results: By week 52, IXE provided similar improvements in the combined ACR50 and PASI100 endpoint, ACR50, and other PsA-related domains regardless of whether IXE was used with or without MTX, while ADA efficacy appeared to be improved with concomitant MTX use. When used without concomitant MTX, IXE resulted in significantly higher response versus ADA in terms of the combined ACR50 and PASI100 (p = 0.002) endpoint, minimal disease activity (p = 0.016), and very low disease activity (p = 0.037). The safety of both agents was consistent with their known safety profiles regardless of concomitant MTX use. Conclusion: In PsA patients with inadequate control of the disease, IXE delivers consistent efficacy in several clinical domains of the disease regardless of concomitant MTX use. The efficacy of ADA is increased by the concomitant use of MTX. These findings can inform treatment decisions when considering the need for concomitant MTX use with IXE or ADA at initiation or for long-term maintenance.

AB - Introduction: In the SPIRIT-H2H (ClinicalTrials.gov: NCT03151551) trial in biologic-naïve patients with active psoriatic arthritis (PsA), ixekizumab (IXE) was superior to adalimumab (ADA) at week 24 in terms of achieving a combined endpoint of ≥ 50% improved response in the American College of Rheumatology scale score (ACR50) and 100% improvement in the Psoriasis Areas and Severity Index (PASI100), and was non-inferior in terms of achieving ACR50. IXE resulted in similar improvements of PsA manifestations irrespective of the use of concomitant conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), while ADA response was higher with concomitant csDMARD use. The aim of this study was to determine the efficacy and safety of treatment with IXE and ADA with or without methotrexate (MTX), the most commonly use csDMARD, through week 52 in patients with PsA. Methods: In the open-label, rater-blinded, head-to-head SPIRIT-H2H trial, randomization of patients was stratified by concomitant use of csDMARD and moderate-to-severe plaque psoriasis involvement. In the post-hoc subgroup analysis presented here, subgroups were defined as with/without concomitant MTX use at baseline. Treatment group effects within subgroups were tested using Fisher’s exact test. Missing data were imputed using non-responder imputation. Results: By week 52, IXE provided similar improvements in the combined ACR50 and PASI100 endpoint, ACR50, and other PsA-related domains regardless of whether IXE was used with or without MTX, while ADA efficacy appeared to be improved with concomitant MTX use. When used without concomitant MTX, IXE resulted in significantly higher response versus ADA in terms of the combined ACR50 and PASI100 (p = 0.002) endpoint, minimal disease activity (p = 0.016), and very low disease activity (p = 0.037). The safety of both agents was consistent with their known safety profiles regardless of concomitant MTX use. Conclusion: In PsA patients with inadequate control of the disease, IXE delivers consistent efficacy in several clinical domains of the disease regardless of concomitant MTX use. The efficacy of ADA is increased by the concomitant use of MTX. These findings can inform treatment decisions when considering the need for concomitant MTX use with IXE or ADA at initiation or for long-term maintenance.

KW - Adalimumab

KW - Ixekizumab

KW - Methotrexate

KW - Psoriatic arthritis

KW - csDMARD

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UR - http://www.scopus.com/inward/citedby.url?scp=85111361372&partnerID=8YFLogxK

U2 - 10.1007/s40744-020-00250-3

DO - 10.1007/s40744-020-00250-3

M3 - Article

C2 - 33200394

AN - SCOPUS:85111361372

SN - 2198-6576

VL - 7

SP - 1021

EP - 1035

JO - Rheumatology and Therapy

JF - Rheumatology and Therapy

IS - 4

ER -

Efficacy and Safety of Ixekizumab with or Without Methotrexate in Biologic-Naïve Patients with Psoriatic Arthritis: 52-Week Results from SPIRIT-H2H Study

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