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

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.