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ObjectivesKnee osteoarthritis (OA) is a leading cause of health-related disability. In the absence of curative non-operative therapies, treatment goals are limited to symptom relief. Data are limited on how patients and physicians prioritise available treatment options. We assessed patients’ preferences for and physicians’ attitudes towards intra-articular treatments including corticosteroids (IACS), an extended-release corticosteroid (TA-ER) and hyaluronic acids (IAHA).MethodsWe conducted a prospective, IRB-exempt, double-blind survey of patients with and providers who treat knee OA. Respondents were required to have received or prescribed TA-ER in a non-trial setting. We evaluated patients’ OA history, impact of knee OA and treatment preferences, and physicians’ decision-making and prescribing experiences.ResultsOf the 97 patient participants, mean age was 56 years, 70.0% were women, 75.0% had bilateral knee OA and 46.4% were diagnosed over 5 years ago. Of the 50 physician participants, 34.0% were rheumatologists, 42.0% were orthopaedic surgeons and 60.0%, on average, treat 50+ patients with knee OA per month. Treatment selection factors considered ‘very important’ to patients and physicians included disease severity (88.7%, 82.0%), impact on quality of life (88.7%, 72.0%), disease extent (84.5%, 54.0%) and activity level (80.4%, 64.0%). A majority (93.8%) of patients indicated moderate to severe difficulty with their knees. Fewer patients (76.3%) reported shared decision making compared with physicians (92.0%). Half (50.5%) of the patients reported that they experienced months of pain relief with TA-ER, 27.7% with IACS and 18.8% with IAHA. Physician assessments were consistent but estimated a greater duration of treatment effects than that reported by patients across all therapies.ConclusionWhile knee OA has a tremendous impact on patients, there are significant unmet treatment needs. The increasing use of patient-reported outcomes will allow patients and physicians to track pain and functional status over time and across therapies, improving shared decision-making.

Purpose: Resveratrol is a natural plant polyphenol and a free radical scavenger with potent antioxidant properties that influences many biological processes including cell division and inflammation. However, due to its poor water solubility, it can be hardly taken up by the human body. To improve the pharmacological efficacy of Resveratrol, we synthesized the Resveratrol-salicylate hybrid molecule compound 10 (C10). In the present study, we investigated the role of Resveratrol and the Resveratrol derivative C10 on human fibroblast-like synoviocytes (FLS) and chondrocytes. Methods: Primary human FLS or chondrocytes were isolated from synovia or cartilage specimens obtained from patients that underwent knee surgery for the treatment of osteoarthritis (OA) or rheumatoid arthritis (RA). Informed consent was obtained from all patients. 3D micromass cultures of FLS were established. FLS, micromasses and chondrocytes were treated in vitro with Resveratrol or C10, with or without subsequent stimulation with pro-inflammatory cytokines (TNF-a or IL-1b). IL-6 in FLS and 3D culture supernatants was analyzed by ELISA. Gene expression in OA chondrocytes was analyzed by RT-qPCR. Results: Treatment of primary human OA chondrocytes with Resveratrol or C10 led to a decreased expression of IL-1b and matrix metalloproteinase-13 (MMP-13), with C10 being more effective. Furthermore, treatment with both Resveratrol and C10, reduced IL-6 secretion by primary human FLS from OA and RA patients in a concentrationdependent manner. Interestingly, a more pronounced effect on FLS was observed with Resveratrol. This result was verified by IL-6 secretion from RA FLS 3D cultures. Conclusions: Resveratrol and its derivative C10 reduce matrix degrading enzyme expression and cytokine secretion in FLS and chondrocytes from patients with OA and RA. Therefore, C10 has chondroprotective and anti-inflammatory properties, which might be useful for the treatment of degenerative and inflammatory joint diseases in the future.

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