High titers of both rheumatoid factor and anti-CCP antibodies at baseline in patients with rheumatoid arthritis are associated with increased circulating baseline TNF level, low drug levels, and reduced clinical responses: a post hoc analysis of the RISING study

Abstract

BackgroundAlthough both rheumatoid factor (RF) and anticyclic citrullinated peptide antibodies (anti-CCP) are useful for diagnosing rheumatoid arthritis (RA), the impact of these autoantibodies on the efficacy of tumor necrosis factor (TNF) inhibitors has been controversial. The aim of this post hoc analysis of a randomized double-blind study (the RISING study) was to investigate the influences of RF and anti-CCP on the clinical response to infliximab in patients with RA.MethodsMethotrexate-refractory patients with RA received 3 mg/kg of infliximab from weeks 0 to 6 and then 3, 6, or 10 mg/kg every 8 weeks from weeks 14 to 46. In this post hoc analysis, patients were stratified into three classes on the basis of baseline RF/anti-CCP titers: “low/low-C” (RF < 55 IU/ml, anti-CCP < 42 U/ml), “high/high-C” (RF ≥ 160 IU/ml, anti-CCP ≥ 100 U/ml), and “middle-C” (neither low/low-C nor high/high-C). Baseline plasma TNF level, serum infliximab level, and disease activity were compared between the three classes.ResultsBaseline RF and anti-CCP titers showed significant correlations with baseline TNF and infliximab levels in weeks 2–14. Comparison of the three classes showed that baseline TNF level was lowest in the low/low-C group and highest in the high/high-C group (median 0.73 versus 1.15 pg/ml), that infliximab levels at week 14 were highest in the low/low-C group and lowest in the high/high-C group (median 1.0 versus 0.1 μg/ml), and that Disease Activity Score in 28 joints based on C-reactive protein at week 14 was lowest in the low/low-C group and highest in the high/high-C group (median 3.17 versus 3.82). A similar correlation was observed at week 54 in the 3 mg/kg dosing group, but not in the 6 or 10 mg/kg group. Significant decreases in both RF and anti-CCP were observed during infliximab treatment.ConclusionsRF/anti-CCP titers correlated with TNF level. This might explain the association of RF/anti-CCP with infliximab level and clinical response in patients with RA. Baseline RF/anti-CCP titers may serve as indices that aid infliximab treatment.Trial registrationClinicalTrials.gov, NCT00691028. Retrospectively registered on 3 June 2008.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1401-2) contains supplementary material, which is available to authorized users.

Using the Immunophenotype to Predict Response to Biologic Drugs in Rheumatoid Arthritis

“…Many groups have investigated rheumatoid factor (RF) and anti-citrullinated peptide antibody (ACPA) positivity to predict response to therapy of all biologics. The reports for anti-TNF therapy are either conflicting [22][23][24]28,29], or did not find a correlation [25,26]. A meta-analysis of 5561 patients also did not find an association between ACPA/RF status and anti-TNF response [27].…”

Association of female sex and positive rheumatoid factor with low serum infliximab and anti-drug antibodies, related to treatment failure in early rheumatoid arthritis: results from the SWEFOT trial population

“…In two previous studies on established RA, there was no significant relationship between RF positivity and ADAs to different biological agents, but the study populations included varied widely (4,13). Meanwhile, Takeuchi et al found in established RA an association between low autoantibody titres at baseline (RF and anti-CCP) and high levels of sIFX at follow-up (14). Although RF may interfere with standard cross-linking ELISA, our assay is an inhibition assay and control sera with high-titre RF do not give false-positive results.…”

Measuring the T‐cell down‐regulation of TCR‐zeta, ZAP‐70 and CD28 in arthritis patients: An old tool for new biomarkers

“…In this regard, a major role for CD4 + CD28 + in SF of non‐RA patients, counterposed to the major role of CD8 + CD28null in SF of seronegative RA patients, may account for the good outcomes observed following treatment with the CD28/B7 modulator abatacept in PsA and even in gout patients, but not in seronegative RA . Moreover, while high titers of autoantibodies would predict a more aggressive disease in seropositive patients , measuring ZETA expression in SF T cells may be particularly useful for predicting arthritis severity in seronegative patients.…”