Synovial inflammation in osteoarthritis. A treatable target?

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.