A majority of studies of patients with rheumatoid arthritis that have collected data on rheumatoid factor status and response to treatment indicate that positivity for the autoantibody predicts response to rituximab and tocilizumab but not abatacept, according to a systematic review and meta-analysis.
The association of rheumatoid factor (RF) and response to certain biologics is disputed, and the findings have been contradictory. Meanwhile, there’s considerable heterogeneity in patient response to biologics: While some don’t benefit from a certain biologic, they do well on a different one, Dr. Jose Ramon Maneiro of Complejo Hospitalario Universitario de Santiago de Compostela, Santiago, Spain, and his colleagues wrote in their report.
The investigators set out to summarize the available evidence for how well RF positivity predicts response to rituximab, tocilizumab, and abatacept. They searched Medline, Embase, and the Cochrane Library for studies published between 2000 and 2011 in English, Spanish, French, Italian, or Portuguese, as well as online abstracts from the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) congresses from the same time period. The search resulted in more than 3,600 references and abstracts, from which they carefully selected 23 studies representing data from more than 5,800 patients (Semin. Arthritis Rheum. 2013 Jan. 3 [doi: 10.1016/j.semarthrit.2012.11.007]).
The researchers identified 14 studies on rituximab involving about 2,100 patients. In 11 studies that analyzed IgM RF status, 6 reported a significant association between IgM RF positivity and clinical response, including 1 that found a significant association with a titer greater than 30 IU/L but not greater than 20 IU/L. IgA RF status was significantly associated with clinical response in one study, while two other studies reported that IgG RF and IgA RF titers were significantly associated with clinical response. In six studies that used EULAR response criteria, patients with IgM RF positivity had significantly greater odds for meeting the response criteria than did those who were IgM RF negative (odds ratio, 3.52). Assessments of ACR response criteria found that RF positivity resulted in greater odds for an ACR20 response to rituximab in three studies (OR, 1.95) and an ACR50 response in three studies (OR, 5.38).
In four studies on tocilizumab, two indicated no relationship between RF status and response to the drug, whereas one report that analyzed data from three clinical trials found a significant association between RF status and ACR20 response. Another study found that the titer of IgM RF could predict Clinical Disease Activity Index. Overall, a meta-analysis of three studies found that RF positivity was significantly associated with greater odds for an ACR20 response (OR, 1.51).
A post hoc analysis of efficacy data from three clinical trials of abatacept showed no association between RF positivity and response to the drug. However, one observational study reported an association.
The review had several limitations, the authors noted. The meta-analysis aggregated results from clinical trials and observational studies, but none of the clinical trials was designed to test the studied association. Also, in observational studies there is a potential for bias from unmeasured confounding factors. In addition, the quality of the studies was low, the authors reported.
The study was partially supported by the Instituto de Salud Carlos III. The currently available version of the report, a corrected proof, did not note any financial disclosures for the authors.
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