Knee Osteoarthritis Phenotypes With Distinct Pain Trajectories Identified

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A set of 4 phenotypes for knee osteoarthritis with distinct pain trajectories which may be used to personalize treatment strategies were identified.

A set of 4 phenotypes for knee osteoarthritis with distinct pain trajectories which may be used to personalize treatment strategies were identified, according to study results published in Pain.

Osteoarthritis is a heterogeneous disease which requires a personalized approach to treatment. Using data from the phase 3 Vitamin D Effect on Osteoarthritis trial (VIDEO; Identifier: NCT01176344) and the Osteoarthritis Initiative study (OAI; Identifier: NCT00080171), investigators aimed to identify pain trajectories in patients with knee osteoarthritis that could be used to describe pain, function, and response to treatment over time.

The study’s primary outcome was pain which was assessed using the 0 to 100 pain subscale of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 6-month and 1-year intervals in the VIDEO an OAI studies, respectively. Secondary outcomes of interest included results from the functional limitation subscale of WOMAC and surgical outcomes. Pain trajectories were identified using group-based trajectory modeling. Data were obtained for 474 participants from the VIDEO trial (61.0% women) and 4796 participants from the OAI study (58.5% women).

In the VIDEO trial, 4 pain trajectories and 4 functional limitation trajectories were identified. In a dual model, the functional limitation trajectories were found to minimally affect the classification of pain trajectories. Analgesic use significantly reduced pain in 2 trajectory groups but minimally affected pain classification.

In the OAI study, 6 pain trajectories and 6 functional limitation trajectories were identified. Use of analgesics had a significant positive effect in 5 of 6 trajectory groups and affected classification of 2 pain groups. The concordance between pain and functional trajectory groups was 94.3% over time.

None of the pain trajectory groups in the VIDEO trial were associated with knee replacement over the course of the 3-year follow-up. In the OAI cohort, the third, fourth, and fifth, but not the sixth, pain trajectory groups were at higher risk for knee replacement during the 9 years of follow-up when compared with the second pain trajectory group. The risk was highest in the fourth pain trajectory group (hazard ratio, 4.6; 95% CI, 3.4-6.4). All groups were at increased risk for knee replacement when compared with the first pain trajectory group.

In the VIDEO trial, lower quality of life was associated with all pain trajectories compared with the no pain group. In the OAI study, female sex, depression, Kellgren-Lawrence grade ≥2, and the use of pain medication were all associated with any painful group compared with the no pain group. Older age, lower body mass index, lower depression score, and use of supplements were associated with the fourth and fifth pain groups compared with the sixth pain group.

From these results, the investigators identified 4 osteoarthritis pain phenotypes: low-fluctuating, mild-increasing, moderate-treatment-sensitive, and severe-treatment-insensitive.

“[O]ur approach provided robust results regarding pain experience for [the phenotyping of patients with osteoarthritis] with clinical, research and trial-design relevance,” the study authors concluded. “To improve phenotype differentiation beyond this report, we suggest employing molecular and genetic tools that should provide insight into dysregulated molecular pathways to target.”

Disclosures: Dr Arden and Dr Cooper reported affiliations with the pharmaceutical industry. Please see the original reference for a full list of disclosures.


Radojčić MR, Arden NK, Yang X, et al. Pain trajectory defines knee osteoarthritis subgroups: a prospective observational study. Published online June 24, 2020. Pain. doi:10.1097/j.pain.0000000000001975