Kloppenburg Margreet
Departments of Rheumatology and Clinical Epidemiology, Leiden University Medical Centre, Postbox 9600, Leiden 2300RC, the Netherlands.
Semin Arthritis Rheum. 2024 Feb;64S:152326. doi: 10.1016/j.semarthrit.2023.152326. Epub 2023 Nov 22.
Synovial inflammation is present in osteoarthritis and associated with pain and structural damage, so it is hypothesized that anti-inflammatory drugs might be of use in osteoarthritis. However, nine randomized clinical trials targeting pro-inflammatory cytokines, especially IL-1 and TNFα, did not show an effect on short-term pain relief (as primary end-points). These results were rather disappointing. The questions is whether the results reflect a true lack of effect of anti-inflammatory drugs in osteoarthritis, or whether there are alternative explanations. Currently, we lack insight in the pathobiology of the synovitis-driven endotype and in cross-talk between tissues in the osteoarthritic joint, complicating identification of the appropriate patients for trials and of the best outcome measures. Furthermore we lack classification criteria to define inflammatory osteoarthritis complicating selection of patients. We do know that anti-inflammatory corticosteroids alleviate pain in osteoarthritis, warranting further investigation of other mediators than IL-1 and TNFα. Now, trials are set up with short follow-up aiming for short-term pain alleviation. For investigation of pain alleviation in the context of disease modification, trials with at least one year follow-up should be performed.
骨关节炎存在滑膜炎症，且与疼痛和结构损伤相关，因此推测抗炎药物可能对骨关节炎有用。然而，针对促炎细胞因子，尤其是白细胞介素 -1（IL-1）和肿瘤坏死因子α（TNFα）的九项随机临床试验，并未显示出对短期疼痛缓解（作为主要终点）有效果。这些结果相当令人失望。问题在于这些结果是反映了抗炎药物在骨关节炎中确实无效，还是存在其他解释。目前，我们对滑膜炎驱动的内型的病理生物学以及骨关节炎关节中组织间的相互作用缺乏了解，这使得确定合适的试验患者和最佳结局指标变得复杂。此外，我们缺乏定义炎症性骨关节炎的分类标准，这也使患者的选择变得复杂。我们确实知道抗炎皮质类固醇可减轻骨关节炎的疼痛，这使得对除IL-1和TNFα之外的其他介质进行进一步研究成为必要。现在，已开展了短期随访的试验，旨在实现短期疼痛缓解。为了在疾病改善的背景下研究疼痛缓解情况，应进行至少一年随访的试验。
