OBJECTIVES: To evaluate clinical prognosis following the introduction of a first targeted therapy (TT) according to the serological profile of rheumatoid arthritis (RA) and to analyze differences in efficacy of TT. METHOD: This single-center retrospective study included patients with RA who received a first TT between 2000 and 2020. Patients were seropositive (IgM and/or IgA rheumatoid factors plus anti-CCP) or seronegative (without autoantibodies). Various data were collected at baseline and during follow-up. The primary endpoint was remission (assessed by DAS28) at one and two years. RESULTS: Among 259 patients, 164 (63.3%) were seropositive and presented higher disease activity and more frequent erosive involvement than seronegative patients at TT introduction. The most prescribed first TTs were etanercept for seronegative RA (47 ([49.5%) versus 41 (25%), p <
0.001) and abatacept for seropositive RA (41 (25%) versus 6 (6.3%), p <
0.001). Remission rates and TT switches were not significantly different between groups. Initial DAS28-CRP and number of painful joints were independent prognostic factors associated with absence of remission at one year (OR 0.46 (0.26, 0.80), p = 0.007) and two years (OR 0.90 (0.82, 0.98), p = 0.027) respectively. Among seropositive patients, the two-year remission rate was not significantly different according to the therapeutic class received (cellular- versus cytokine-targeted). CONCLUSIONS: Patients with seropositive RA showed more active and severe disease than patients with seronegative RA at the introduction of a first TT. Although the choice of the first TT varied according to serological profile and time of analysis, clinical prognosis at one and two years was similar between groups. Key Points • Seropositive versus seronegative RA was more active at start of first targeted therapy. • First-line TTs were etanercept for seronegative RA and abatacept for seropositive RA. • Rate of targeted therapy switches was comparable between both groups. • Remission rates at 1 and 2 years were similar in seropositive and seronegative RA. • Remission rates were similar for cellular and cytokine inhibitors in seropositive RA.