Sharma R U, Runhaar J, Bos P K, Dorleijn D M J, Bindels P J E, Bierma-Zeinstra S M A
Department of General Practice, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
Department of Orthopedics & Sports Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
Clin Rheumatol. 2025 Jun 25. doi: 10.1007/s10067-025-07539-0.
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.
我们旨在评估在膝关节疼痛发作期间炎症症状更严重的亚组是否比炎症症状较轻的亚组从高剂量布洛芬治疗中获益更多。
这项二次分析纳入了去年膝关节疼痛发作≥1次、在24小时内经历新发作且被随机分为每日服用1200毫克或2400毫克布洛芬治疗组、为期5天的成年人。基于骨关节炎相关症状（晨僵严重程度、肿胀和疼痛），采用多水平回归分析来评估干预组与预先定义的亚组之间的交互作用。主要结局是5天后各亚组在疼痛严重程度（数字评分量表（NRS）上为0至10分）方面的治疗效果差异。3天后（NRS）和5天后（西安大略和麦克马斯特大学骨关节炎（WOMAC）量表）各亚组治疗效果的差异为次要结局。
参与者（N = 308）的平均年龄为52.4±12.9（标准差）岁，女性受试者占41%。在第5天后，预先定义的亚组与干预组在疼痛严重程度方面（所有p值≥0.28）以及在次要结局方面（所有p值≥0.38）均未发现显著交互作用。鉴于可能存在检验效能不足的情况，对每个亚组比较了治疗组之间的绝对和调整后平均差异；这些差异均未达到临床显著性。
在膝关节疼痛发作期间炎症症状严重程度不同的亚组之间，与低剂量相比，高剂量布洛芬未显示出显著的临床益处。要点 • 尽管高剂量总体上具有优势，但炎症性膝关节症状严重的患者从抗炎剂量布洛芬中获得的益处并不比症状较轻的患者更多。 • 对于炎症性膝关节症状严重的患者，不建议使用高剂量布洛芬。 • 鉴于膝关节骨关节炎患者之间存在异质性，未来研究应探索潜在的亚组。
