Association between seropositivity and remission in rheumatoid arthritis patients receiving disease-modifying antirheumatic drugs: a retrospective analysis of 5 phase III randomized clinical trials of tocilizumab

Introduction. Rheumatoid arthritis (RA) is an autoimmune chronic inflammatory disease that is often classified according to the presence of anti-cyclic citrullinated peptide antibodies (ACPA) and/or rheumatoid factor (RF) into seropositive or seronegative RA. RF and/or ACPA can be found in up to 75% of RA patients, and seropositivity may indicate higher disease activity and poorer prognosis. There is growing evidence towards using RF and ACPA in combination as a more effective diagnostic tool rather than using each one separately because of their moderate sensitivity when used individually. It has been suggested that combination seropositivity can be used as a more accurate early predictor of structural damage than using them individually.

Aim: To examine the association between RF and/or ACPA seropositivity and remission in RA patients treated with tocilizumab (TCZ) and/or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).

Methods. Data were pooled from 5 phase III randomized clinical trials of RA patients assigned to treatment with the TCZ ± csDMARDs. Available data included baseline RF and ACPA status, age, sex, weight, race, RA disease duration, number of previous DMARDs, and baseline disease activity (measured using the Clinical Disease Activity Index (CDAI)). Serotype’ subgroups were: ACPA positive (+) and RF +, ACPA +/RF negative (-), ACPA-/RF+ and ACPA-/RF-. Remission outcomes were set according to CDAI. Cox proportional analysis was used to assess the association between baseline characteristics and time to the first remission.

Results. The analysis included data from a total of 5502 RA patients treated with TCZ and/or csDMARDs, of which 4108 (74.6%) were ACPA+/RF+, 816 (14.8%) were ACPA+/RF-,  219 (4%) were ACPA-/RF+, and 298 (5.4%) were ACPA-/RF-. In the pooled analysis, RF and ACPA status were associated with significantly higher remission rate using both univariable and adjusted analyses (univariable (HR 1.15 (95%CI 1.01-1.30, P=0.035) and adjusted  (HR 1.17 (95%CI 1.03-1.33, P=0.015)) and (univariable (HR 1.27 (95%CI 1.08-1.49, P=0.004)) and adjusted (HR 1.28 (95%CI1.09-1.51, P=0.003)), respectively. Patients who were ACPA+/RF+ were more likely to achieve CDAI remission compared with ACPA-/RF- on univariable (HR 1.25 (95%CI 1.01-1.55, P=0.016)) and adjusted (HR 1.30 (95%CI 1.04-1.61, P=0.002)) analyses.  There was no difference  in remission rates between either  ACPA-/RF+ and ACPA+/RF- groups compared to the ACPA-/RF- and ACPA-/RF+ groups. The association of the seropositivity status of ACPA and/or RF with remission was independent of the type of RA therapy used (interaction P>0.05).

Conclusion. Seropositivity of both RF and ACPA was independently associated with more frequent remission in RA patients regardless of the type of DMARD used. Seropositivity of both RF and ACPA in combination may increase the ability to predict RA treatment outcome