# Identifying clinically relevant subgroups of patients with knee pain flares for ibuprofen treatment: a secondary analysis

## TL;DR

This study found that higher doses of ibuprofen do not provide more benefit for patients with severe knee inflammation compared to lower doses.

## Contribution

The study challenges the assumption that higher ibuprofen doses are better for severe inflammatory knee symptoms.

## Key findings

- No significant interaction was found between ibuprofen dose and subgroup inflammatory symptoms on pain severity.
- Higher doses of ibuprofen did not show clinical benefit for patients with severe inflammatory knee symptoms.
- Future research should explore potential subgroups among patients with knee osteoarthritis.

## Abstract

We aimed to evaluate whether subgroups with more severe inflammatory symptoms during a knee pain flare benefited more from a high dose ibuprofen treatment than subgroups with less severe inflammatory symptoms.

This secondary analysis included adults with ≥ 1 flares of knee pain in the last year, who experienced a new episode within 24 h and randomized into two treatment groups of daily ibuprofen 1200 mg or 2400 mg for 5 days. A multilevel regression analysis was used to assess interaction effects between intervention groups and pre-defined subgroups, based on osteoarthritis related symptoms (severity of morning stiffness, swelling, and pain). The primary outcome was the difference in treatment effect between subgroups on pain severity (0–10 on the numeric rating scale (NRS)) after 5 days. Differences in treatment effect between subgroups after 3 days (NRS) and 5 days (Western Ontario and McMaster Universities Osteoarthritis (WOMAC) scale) were secondary outcomes.

Participants (N = 308) had a mean age of 52.4 ± 12.9 (SD) years with 41% female subjects. No significant interaction was found between the pre-defined subgroups and intervention groups on pain severity after day 5 (all p-values ≥ 0.28) or on the secondary outcomes (all p-values ≥ 0.38). Given the potential lack of power, the absolute and adjusted mean differences between treatment arms were compared for each subgroup; none of the differences reached clinical significance.

Between subgroups with more and less severe inflammatory symptoms during knee pain flares, no significant nor clinical benefit was found from a higher dose of ibuprofen compared to a lower dose.
Keypoints• Despite the overall superiority of the higher dose, patients with severe inflammatory knee symptoms do not benefit more from an anti-inflammatory dose of ibuprofen than patients with less severe symptoms.• A higher dose of ibuprofen is not indicated for patients with severe inflammatory knee symptoms.• Given the heterogeneity among patients with knee osteoarthritis, potential subgroups should be explored in future research.

Keypoints

• Despite the overall superiority of the higher dose, patients with severe inflammatory knee symptoms do not benefit more from an anti-inflammatory dose of ibuprofen than patients with less severe symptoms.

• A higher dose of ibuprofen is not indicated for patients with severe inflammatory knee symptoms.

• Given the heterogeneity among patients with knee osteoarthritis, potential subgroups should be explored in future research.

The online version contains supplementary material available at 10.1007/s10067-025-07539-0