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In the 1980s there were the fi rst observations of lefl unomide’s disease modifying properties in animal models of arthritis and autoimmunity. Lefl unomide showed to inhibit the infl ammatory response in adjiuvant arthritic rats. At the dosage of 35 mg/kg/day lefl unomide is able to signifi cantly reduce the severity of arthritis induced by fetal human proteoglycan in mice (Glant et al. 1994). Moreover it induces a reduction in circulating antibodies to fetal human proteoglycan as well as of antibodies to mouse proteoglycan. However, a recurrence of the synovitis 2-3 weeks after discontinuation of the drug was found. Analysing the possible difference in mice between two drug’s doses of oral lefl unomide, 10 mg/kg/day was clinically as effective as 5 mg/kg/day of intraperitoneal ciclosporin in the treatment of rats with antigen-induced arthritis with a reduction also in the severity of histological lesions compared to placebo.