Background: Rheumatoid arthritis is a systemic inflammatory rheumatic disease that affects, besides joints, other organs and increases the risk of cardiovascular disease. Anti-cyclic citrullinated peptides (anti-CCP) antibodies play an important role in the pathogenesis of the disease in addition to genetic predisposition. Anti-CCP positivity is associated with disease activity, development of joint erosions, contributing to a poorer disease outcome. In this final paper, the association between anti-CCP antibodies and disease activity in patients with rheumatoid arthritis was examined. Furthermore, the authors monitored and compared the outcome and prognosis of the disease in rheumatoid arthritis patients positive for anti-CCP antibodies compared to patients who were not positive over a period of ten years. Patients and methods: The study group consisted of 158 patients (males/females: 37/121) from the Department of Rheumatology, Clinical Immunology and Allergology, University Hospital Centre Osijek. Relevant clinical data were collected from medical histories. Results: There is no significant association between CCP antibodies and the number of treatment lines and disease activity. Although slightly higher values of CRP and DAS28 were shown in subjects who were positive for CCP antibodies, these differences were not significant after biological therapy regardless of whether they have positive or negative antibodies. Monitoring the outcome of the disease in relation to the values of CRP, SE, DAS28 and HAQ, indicated a significant reduction in these values when applying the first, second or third line of biological therapy. Conclusion: In accordance with the results in this paper, the conclusion is that the application of biological therapy significantly contributes to a reduced value of CRP, SE, DAS28 and HAQ, indicating effectiveness of the biological drug in reducing disease activity.