Rheumatoid factor positivity rather than anti-CCP positivity, a lower disability and a lower number of anti-TNF agents failed are associated with response to rituximab in rheumatoid arthritis

Abstract

Objectives. We explored clinical factors associated with a major response to rituximab (RTX) (e.g. ACR 550, and European League against Rheumatism (EULAR) moderate to good response) in patients with active long-standing RA and inadequate response to anti-TNF agents or traditional DMARDs. Methods. RTX was used in 110 RA patients in six different Italian centres. The mean disease activity score on 28 joints (DAS28) was 6.4 AE 0.99 and the mean HAQ was 1.63 AE 0.68 at baseline. Thirty-two patients (29.1%) underwent RTX after the failure of DMARD therapy, 37 (33.6%) had failed or were intolerant to at least two anti-TNF agents, and 41 (37.3%) had failed or were intolerant to one anti-TNF agent. Univariate and multivariate analyses were performed. Results. The number of previous anti-TNF agents (P ¼ 0.043), HAQ (P ¼ 0.023), RF positivity (P < 0.0001) and anti-cyclic citrullinated peptide (anti-CCP) positivity (P ¼ 0.003) were associated with ACR response 550 between month þ4 and month þ6 after starting RTX by univariate analysis. Multivariate analysis confirmed that a lower HAQ, a lower number of anti-TNF agents failed before RTX and RF positivity, but not anti-CCP positivity, were the selected variables associated with an ACR response 550, with an accuracy of 84% of the model. Only RF positivity correlated with EULAR moderate to good response both in the univariate and in the multivariate analysis, with an accuracy of 79% of the model. Conclusion. RF-positive rather than anti-CCP-positive RA patients with lower baseline disability and a lower number of previously failed TNF blockers may be the best candidates to RTX.

Rituximab treatment induces the expression of genes involved in healing processes in the rheumatoid arthritis synovium

“…Further analyses indicated that baseline serum IgG levels were significantly higher in responders than in nonresponders. This observation is in line with previous reports indicating that the presence of serum rheumatoid factor is associated with response to rituximab therapy in RA (22,23). Although the overlap in baseline synovial and serum immunoglobulin concentrations did not enable adequate discrimination of responders and nonresponders on an individual basis, the difference might still be informative from a physiopathologic point of view.…”

Serum levels of anti-CCP antibodies, anti-MCV antibodies and RF IgA in the follow-up of patients with rheumatoid arthritis treated with rituximab

“…This observation is consistent with recently reported findings regarding the association between a positive response to RTX and RF and/or a-CCP positivity [50][51][52]. It can be assumed that RA patients characterized by greater autoantibody production respond better to therapies directed against B lymphocytes.…”

“…Several authors have shown that the presence of RF, which is associated with more severe disease and a reduced therapeutic response in general, is a marker of a higher degree of response to RTX [50][51][52]. However, changes in RF serum levels in the follow-up after RTX treatment is not predictive of response, as we also found in this study, even focusing on IgA-specific RF.…”

“…The choice of treatment and monitoring of treatment of RA with biological agents is currently a field of major interest, but strong data on biological markers still remain undefined [49][50][51]. Several authors have shown that the presence of RF, which is associated with more severe disease and a reduced therapeutic response in general, is a marker of a higher degree of response to RTX [50][51][52].…”

Effectiveness of Rituximab in Patients with Rheumatoid Arthritis: Observational Study from the British Society for Rheumatology Biologics Register

“…A study of 110 patients (32 anti-TNF-naive and 78 anti-TNF failures) reported that patients with positive RF, lower baseline Health Assessment Questionnaire (HAQ) score, or those who had failed fewer anti-TNF agents were more likely to achieve an ACR ≥ 50 response 21 . In the same study, only RF positivity was found to be associated with a better EULAR response.…”