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Pain trajectory defines knee osteoarthritis subgroups: a prospective observational study

Pain trajectory defines knee osteoarthritis subgroups: a prospective observational study
Pain trajectory defines knee osteoarthritis subgroups: a prospective observational study

Knee osteoarthritis (OA) is a heterogeneous disease, and identification of its subgroups/phenotypes can improve patient treatment and drug development. We aimed to identify homogeneous OA subgroups/phenotypes using pain development over time; to understand the interplay between pain and functional limitation in time course; and to investigate subgroups' responses to available pharmacological and surgical treatments. We used group-based trajectory modelling to identify pain trajectories in the phase-3 VIDEO trial (n = 474, 3-year follow-up) and also in the Osteoarthritis Initiative cohort study (n = 4796, 9-year follow-up). We extended trajectory models by (1) fitting dual trajectories to investigate the interplay between pain and functional limitation over time, and (2) including analgesic use as a time-varying covariate. Also, we investigated the relationship between trajectory groups and knee replacement in regression models. We identified 4 pain trajectory groups in the trial and 6 in the cohort. These overlapped and led us to define 4 OA phenotypes: low-fluctuating, mild-increasing, moderate-treatment-sensitive, and severe-treatment-insensitive pain. Over time, functional knee limitation followed the same trajectory as pain with almost complete concordance (94.3%) between pain and functional limitation trajectory groups. Notably, we identified a phenotype with severe pain that did not benefit from available treatments, and another one most likely to benefit from knee replacement. Thus, knee OA subgroups/phenotypes can be identified based on patients' pain experiences in studies with long and regular follow-up. We provided a robust approach, reproducible between different study designs, which informs clinicians about symptom development and delivery of treatment options and opens a new avenue toward personalized medicine in OA.

0304-3959
2841-2851
Radojčić, Maja R.
b2003caf-f95c-4cb4-8215-50e2e96873b7
Arden, Nigel K.
de7b1588-3ab8-4ea0-957d-a38eb881a9d8
Yang, Xiaotian
2b8df5be-a284-4f91-b4bf-32d9285f9bd8
Strauss, Victoria Y.
7f805b15-394f-4a91-8dde-eb3cbae3036a
Birrell, Fraser
7b7402b5-fee8-47c2-bdce-0c66c442076c
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Kluzek, Stefan
02edaad0-3ec7-4c71-a5fc-ffae0a870dff
The VIDEO trial investigators
Radojčić, Maja R.
b2003caf-f95c-4cb4-8215-50e2e96873b7
Arden, Nigel K.
de7b1588-3ab8-4ea0-957d-a38eb881a9d8
Yang, Xiaotian
2b8df5be-a284-4f91-b4bf-32d9285f9bd8
Strauss, Victoria Y.
7f805b15-394f-4a91-8dde-eb3cbae3036a
Birrell, Fraser
7b7402b5-fee8-47c2-bdce-0c66c442076c
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Kluzek, Stefan
02edaad0-3ec7-4c71-a5fc-ffae0a870dff

Radojčić, Maja R., Arden, Nigel K., Yang, Xiaotian, Strauss, Victoria Y., Birrell, Fraser, Cooper, Cyrus and Kluzek, Stefan , The VIDEO trial investigators (2020) Pain trajectory defines knee osteoarthritis subgroups: a prospective observational study. Pain, 161 (12), 2841-2851. (doi:10.1097/j.pain.0000000000001975).

Record type: Article

Abstract

Knee osteoarthritis (OA) is a heterogeneous disease, and identification of its subgroups/phenotypes can improve patient treatment and drug development. We aimed to identify homogeneous OA subgroups/phenotypes using pain development over time; to understand the interplay between pain and functional limitation in time course; and to investigate subgroups' responses to available pharmacological and surgical treatments. We used group-based trajectory modelling to identify pain trajectories in the phase-3 VIDEO trial (n = 474, 3-year follow-up) and also in the Osteoarthritis Initiative cohort study (n = 4796, 9-year follow-up). We extended trajectory models by (1) fitting dual trajectories to investigate the interplay between pain and functional limitation over time, and (2) including analgesic use as a time-varying covariate. Also, we investigated the relationship between trajectory groups and knee replacement in regression models. We identified 4 pain trajectory groups in the trial and 6 in the cohort. These overlapped and led us to define 4 OA phenotypes: low-fluctuating, mild-increasing, moderate-treatment-sensitive, and severe-treatment-insensitive pain. Over time, functional knee limitation followed the same trajectory as pain with almost complete concordance (94.3%) between pain and functional limitation trajectory groups. Notably, we identified a phenotype with severe pain that did not benefit from available treatments, and another one most likely to benefit from knee replacement. Thus, knee OA subgroups/phenotypes can be identified based on patients' pain experiences in studies with long and regular follow-up. We provided a robust approach, reproducible between different study designs, which informs clinicians about symptom development and delivery of treatment options and opens a new avenue toward personalized medicine in OA.

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Pain trajectory defines knee osteoarthritis - Accepted Manuscript
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Accepted/In Press date: 24 June 2020
e-pub ahead of print date: 24 June 2020
Published date: 1 December 2020

Identifiers

Local EPrints ID: 442461
URI: http://eprints.soton.ac.uk/id/eprint/442461
ISSN: 0304-3959
PURE UUID: a521068d-ac01-4743-9b2f-b1540b72217e
ORCID for Cyrus Cooper: ORCID iD orcid.org/0000-0003-3510-0709

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Date deposited: 15 Jul 2020 16:42
Last modified: 18 Mar 2024 05:05

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Contributors

Author: Maja R. Radojčić
Author: Nigel K. Arden
Author: Xiaotian Yang
Author: Victoria Y. Strauss
Author: Fraser Birrell
Author: Cyrus Cooper ORCID iD
Author: Stefan Kluzek
Corporate Author: The VIDEO trial investigators

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