Comparative performance of composite measures from two phase III clinical trials of ixekizumab in psoriatic arthritis

Laura C Coates; Josef S Smolen; Philip J Mease; M Elaine Husni; Joseph F Merola; Eric Lespessailles; Mitsumasa Kishimoto; Lisa Macpherson; Andrew J Bradley; Rebecca Bolce; Philip S Helliwell

doi:10.1136/rmdopen-2022-002457

Comparative performance of composite measures from two phase III clinical trials of ixekizumab in psoriatic arthritis

RMD Open. 2022 Sep;8(2):e002457. doi: 10.1136/rmdopen-2022-002457.

Authors

Affiliations

¹ Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK laura.coates@ndorms.ox.ac.uk.
² Medical University of Vienna, Vienna, Austria.
³ Department of Rheumatology, Swedish Medical Center, Providence St Joseph Health, and School of Medicine, University of Washington, Seattle, Washington, USA.
⁴ Department of Rheumatic and Immunologic Diseases, Cleveland Clinic, Cleveland, Ohio, USA.
⁵ Division of Rheumatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
⁶ University of Orleans, Orleans Hospital, Orleans, France.
⁷ School of Medicine, Kyorin University, Tokyo, Japan.
⁸ Eli Lilly and Company, Indianapolis, Indiana, USA.
⁹ School of Medicine, University of Leeds, Leeds, UK.

Abstract

Background/objective: The aim of this study was to evaluate relative performance of composite measures in psoriatic arthritis and assess the impact of structural damage and functional disability on outcomes during ixekizumab treatment.

Methods: Data from SPIRIT-P1 and SPIRIT-P2 were analysed to evaluate the effect of ixekizumab on achievement of low disease activity (LDA) and remission with the minimal disease activity (MDA) and very low disease activity (VLDA) composite, Disease Activity index for Psoriatic Arthritis (DAPSA), Psoriatic Arthritis Disease Activity Score, GRAppa Composite ScorE and modified Composite Psoriatic Disease Activity Index (mCPDAI). Performance was compared by quantifying residual symptom burden and the impact of structural damage and functional disability.

Results: Significantly more ixekizumab-treated patients achieved treatment targets at week 24 versus placebo assessed with all composites. More patients achieved targets assessed by mCPDAI and DAPSA than other composites. Residual disease activity was similar between composites, but residual high patient-reported outcomes (PROs) and functional disability were more frequent when assessed with mCPDAI and DAPSA. Achievement of treatment targets was reduced by high baseline levels of structural damage and functional disability.

Conclusion: Residual disease activity was similar in patients achieving treatment targets assessed with all composites, but residual high PROs and functional disability were more common when assessed with mCPDAI and DAPSA, most likely due to the absence/attenuated functional assessment in these composites. High baseline levels of structural damage and functional disability attenuated response rates with all composites, affecting MDA/VLDA most prominently; LDA may be the most appropriate target in these patients.

Trial registration number: NCT01695239.

Keywords: autoimmune diseases; patient reported outcome measures; psoriatic arthritis.

Publication types

Clinical Trial, Phase III
Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Monoclonal, Humanized
Antirheumatic Agents* / therapeutic use
Arthritis, Psoriatic* / diagnosis
Arthritis, Psoriatic* / drug therapy
Disease Progression
Humans
Severity of Illness Index
Treatment Outcome

Substances

Antibodies, Monoclonal, Humanized
Antirheumatic Agents
ixekizumab

Associated data

ClinicalTrials.gov/NCT01695239