Background: One of the causes of chronic pain in osteoarthritis (OA) is an inadequate resolution of inflammation causing persistent inflammation ^[1] . The resolution of inflammation is an active biochemical process mainly driven by specialized pro-resolving lipid mediators (SPMs) ^[2] . SPMs, such as 18-HEPE, 17-HDHA, and 14-HDHA, are polyunsaturated fatty acid derivatives that promote macrophage phagocytosis, cease the infiltration of pro-inflammatory immune cells, counter-regulate pro-inflammatory mediators, and increase the production of anti-inflammatory mediators ^[3] . Despite OA’s burden, there is limited treatment. The main treatments are the NSAIDs, but due to the chronic nature of OA and the side effects of long-term NSAIDs intake, new improved treatments are needed ^[4] . Furthermore, the therapeutic arsenal is limited in patients with certain comorbidities, where they are contraindicated, e.g. prolonged NSAIDs in patients with cardiovascular pathology.

Objectives: Promoted by a patient and scientific organization such as OAFI (Osteoarthritis Foundation International) as a primary objective, the aim was to evaluate the effectiveness of SPM supplements in reducing pain in patients with knee OA. As secondary, function, rigidity, health-related quality of life, use of concomitant treatments (including rescue), safety and tolerability were assessed.

Methods: A randomized, multicenter, double-blind, and placebo-controlled parallel-group pilot study was performed in Spain with adults between 18-68 years old diagnosed with knee OA scored 2-3 on the Kellgren and Lawrence radiological scale. The study was conducted for 24 weeks. The SPM group took SPM-enriched oil, and the placebo group took olive oil placebo. The primary endpoint was the change in pain on the Visual Analog Scale (VAS) after 12 weeks of supplementation. Secondary endpoints included: Pain change evaluation, stiffness, and function measured with the WOMAC index; assessment of constant, intermittent, and total pain according to the OMERACT-OARSI score; evaluation of changes in health-related QoL parameters; the use or not of concomitant, rescue, and anti-inflammatory medication; and safety and tolerability assessments.

Results: 85 patients were included, 52 were assigned to the safety population, 23 in the SPM group and 28 in the placebo group. The median age was 62.2 years. 52.17% of patients were female in the SPMs group, and 53.57% were female in the placebo group. Most of the patients had grade 2 OA according to the Kellgren and Lawrence classification. After 8 weeks, we observed a significant reduction in VAS score (p=0.039), and after 12 weeks, we observed a significant decrease in VAS scores (p=0.031) and intermittent pain in the OMERACT-OARSI score (p=0.019). The SPM group also showed improvements in all five aspects of the EUROQoL-5, including a significant improvement in the usual-activities dimension. None of the patients needed rescue medication or showed any adverse events, appearing safe and well tolerated.

Conclusion: The results of this study support the safety and the positive effects of continuous oral SPM supplementation in patients with symptomatic knee OA.

REFERENCES: [1] Walters ET. Adaptive mechanisms driving maladaptive pain: how chronic ongoing activity in primary nociceptors can enhance evolutionary fitness after severe injury. Philos Trans R Soc Lond B Biol Sci. 2019;374(1785):20190277. doi: 10.1098/rstb.2019.0277.

[2] Sugimoto MA, Sousa LP, Pinho V, Perretti M, Teixeira MM. Resolution of inflammation: what controls its onset? Front Immunol. 2016;7:160. doi: 10.3389/fimmu.2016.00160.

[3] Serhan CN, Dalli J, Colas RA, Winkler JW, Chiang N. Protectins and maresins: New pro-resolving families of mediators in acute inflammation and resolution bioactive metabolome. Biochim Biophys Acta. 2015;1851(4):397–413. doi: 10.1016/j.bbalip.2014.08.006.

[4] Krustev E, Rioux D, McDougall JJ. Mechanisms and mediators that drive arthritis pain. Curr Osteoporos Rep. 2015;13(4):216–224. doi: 10.1007/s11914-015-0275-y.

Acknowledgements: NIL.

Disclosure of Interests: None declared.