Background/Purpose: In rheumatoid arthritis (RA), little is known about the prognostic relevance of the change in autoantibody (ab) levels. Seroconversion was reported to be associated with a better clinical and radiological outcome in MTX-insufficient responders (IRs) treated with abatacept (1). The ROC randomized study (2)offered the opportunity to investigate changes in RF and anti-CCP levels in 1^st anti-TNF-IR patients treated either with a 2^nd anti-TNF, abatacept, rituximab or tocilizumab.

Objective: To evaluate the effects of bDMARDS on rheumatoid factor (RF) and IgG, A and M anti-CCP ab in RA, and associations between changes in serological status and clinical and radiological responses.

Methods: Ab titres (IgM-RF, IgG, A and M-anti-CCP) were determined by ELISA at baseline and month 6 in respectively 230, 220, 242 and 241 patients enrolled in the ROC randomized trial. The association between changes in ab titers with clinical response was assessed at months 6 and 12. Radiographs of the hands and feet were analyzed at screening and at months 12. The van der Heijde-modified Sharp scoring method was used to assess the mean change from baseline in total Sharp score (TSS) and to determine radiographic progression.

Results: Seroconversion of IgM-RF (patients with IgM-RF present at baseline, and then that became undetectable after treatment) was observed in only 4 patients (2%), of IgG antiCCP in 15 (7%), of IgA in 17 (7%) and of IgM in 16 patients (7%).

No significant difference in the proportion of patients converted to seronegative status was observed between patients treated with a 2^nd anti-TNF or with a non-TNF targeted therapy. In the non anti-TNF group, seroconversion of IgA anti-CCP was significantly more frequent in rituximab (24%) than in abatacept (7%) or tocilizumab-treated patients (4%) (p=0.007). Seroconversion of RF was associated with a significantly more frequent remission (75% of patients with a DAS28-ESR<2.6 at month 6 among seroconverted patients vs 22% in patients who remained RF positive, p=0.01).

IgA anti-CCP seroconversion was associated with a better therapeutic response (good EULAR response in 59% of seroconverted patients at month 12 vs 25% in patients who remained IgA anti-CCP positive, p=0.004). Seroconversions of IgM and IgG anti-CCP were not associated with any clinical or radiological response.

RF levels decreased irrespectively of the biologic used whereas a significant decrease of anti-CCP isotypes was only observed with rituximab. The decrease of RF was correlated with the decrease of polyclonal B-cell activation markers (total IgG, IgA, IgM, kappa and lambda free light chains of immunoglobulins (FLCs), whereas IgG, IgA, IgM-anti-CCP were not correlated with total IgA, G, M or FLCs. Changes in RF or anti-CCP levels were not associated with clinical or radiographic outcome.

Conclusion: Seroconversion of RF and anti-CCP was infrequent. Seroconversion of RF was significantly associated with a more frequent DAS28-remission and seroconversion of IgA anti-CCP with a better EULAR response.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/change-in-rf-and-anti-ccp-isotype-levels-in-ra-patients-treated-with-anti-tnf-abatacept-rituximab-or-tocilizumab-and-correlation-with-clinical-and-radiographic-outcomes-data-from-a-randomized/