Pain trajectory defines knee osteoarthritis subgroups: a prospective observational study

Radoj?i?, Maja R.; Arden, Nigel K.; Yang, Xiaotian; Strauss, Victoria Y.; Birrell, Fraser; Cooper, Cyrus; Kluzek, Stefan; VIDEO Trial Investigators

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-three VIDEO trial (n=474, three-year follow-up) and also in the Osteoarthritis Initiative cohort study (n=4796, nine-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 four pain trajectory-groups in the trial and six in the cohort. These overlapped and led us to define four 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 that informs clinicians about symptom development and delivery of treatment options and opens a new avenue toward personalized medicine in OA.

• Journal Article Type: Article
• Acceptance Date: Jun 2, 2020
• Online Publication Date: Jun 24, 2020
• Publication Date: Dec 1, 2020
• Deposit Date: Jul 13, 2020
• Publicly Available Date: Jul 14, 2020
• Journal: Pain
• Print ISSN: 0304-3959
• Electronic ISSN: 1872-6623
• Publisher: Lippincott, Williams & Wilkins
• Peer Reviewed: Peer Reviewed
• Volume: 161
• Issue: 12
• Pages: 2841-2851
• DOI: https://doi.org/10.1097/j.pain.0000000000001975
• Keywords: Anesthesiology and Pain Medicine; Neurology; Clinical Neurology
• Public URL: https://nottingham-repository.worktribe.com/output/4766366
• Publisher URL: https://journals.lww.com/pain/Fulltext/2020/12000/Pain_trajectory_defines_knee_osteoarthritis.19.aspx