TNF and osteoarthritis: In a three-arm osteoarthritis trial (IMPAWS-OA-1), EF-M2 reduced owner-reported pain (least-squares mean ΔCBPI-PSS −2.11 with thrice-weekly dosing vs. −0.54 placebo) and improved force-plate kinetics (+7.08% body-weight peak vertical force), with parallel increases in IL-10 and in the ARG1/iNOS ratio and reductions in TNF-α; adverse events were infrequent, mild, and balanced with placebo [15].