Background Polymyositis (PM) and dermatomyositis (DM) are chronic inflammatory diseases primarily affecting skeletal muscle leading to muscle weakness. T cells are likely to have a role in the disease process indicated by the predominance of T cells in the inflammatory infiltrates found in affected muscle, and further supported by the associations with certain HLA class II alleles. The role of T cells may be direct as mediators of muscle fiber necrosis and as producers of inflammatory molecules that may have a negative effect on muscle fiber contractility. Objectives To assess the clinical efficacy of Abatacept, an agent blocking T cell co-stimulation, on disease activity in adult DM and PM patients in a trial with randomized treatment delayed-start design. Methods DM and PM patients with persisting signs of inflammatory active disease after treatment with glucocorticoids and ≥1 immunomodulating drug for ≥3 months were randomized to receive either immediate active treatment with Abatacept intravenous (10 mg/kg) infusions or a delayed start after 3 months. The primary endpoint was the number of responders, defined as improved according to the International Myositis Assessment and Clinical Studies (IMACS) Group definition of improvement (DOI), after treatment for 6 months. The secondary endpoint included the number of responders in the delayed onset arm compared to the active treatment arm at 3 months, and the efficacy after 6 months treatment on the individual components of the IMACS core set measures for the disease activity, and health-related quality of life assessed by SF-36. Results Among 20 randomized patients (9 DM, 11 PM; 13 female, 7 male), 17 were included in the analyses and 8 (47%) achieved the DOI after 6 months of active treatment. No differences between DM and PM, or female and male patients could be seen. At 3 months after study start, 5 of the 10 (50%) patients in the active treatment arm were responders achieving the DOI compared to only 1 of the 7 (14%) patients in the delayed onset arm. After active treatment for 6 months (n=17), significant improvement was seen in muscle strength, assessed by the manual muscle test (MMT)-8, from (median) 70 to 73 (p=0.0082), in gastrointestinal disease activity from 3 to 0 (p=0.0156), and in muscle disease activity from 18 to 10 (p=0.0133). SF-36 physical was significantly improved from median 31 at start to 36 at end of treatment (p=0.0054). There were 36 adverse events (AE) reported. Eight AE were judged as related to the drug, of which 4 were mild and 4 were moderate. These included infections, flank pain and dizziness. There were 3 serious AE, none of which was related to the drug. These included hospitalization due to fracture, worsening in muscle weakness and reconstructive surgery. Conclusions In this pilot study, treatment of PM and DM patients with Abatacept resulted in improved muscle performance and health-related quality of life in half of the patients, and warrants further investigation. Acknowledgements This research received funding support from Bristol-Myers Squibb. Disclosure of Interest A. Tjärnlund: None declared, M. Dastmalchi: None declared, H. Mann: None declared, J. Tomasová Studýnková: None declared, R. Chura: None declared, N. Gullick: None declared, R. Salerno: None declared, P. Gordon Paid instructor for: Bristol-Myers Squibb, J. Vencovský Consultant for: Medimmune, Servier, Novartis, I. Lundberg Consultant for: Novartis, Servier, Astra-Zeneca och Bristol-Myers Squibb