Brief Report: Association of Rheumatoid Factor and Anti–Citrullinated Protein Antibody Positivity With Better Effectiveness of Abatacept: Results From the Pan‐European Registry Analysis

Abstract

Objective. To investigate the role of rheumatoid factor (RF) status and anti-citrullinated peptide antibody (ACPA) status as predictors of abatacept (ABA) effectiveness in patients with rheumatoid arthritis (RA).Methods. We conducted a pooled analysis of data from 9 observational RA registries in Europe (ARTIS [Sweden] [Switzerland]). Inclusion criteria were a diagnosis of RA, initiation of ABA treatment, and available information on RF and/or ACPA status. The primary end point was continuation of ABA treatment. Secondary end points were ABA discontinuation for ineffectiveness or adverse events and response rates at 1 year (good or moderate response according to the European League Against Rheumatism criteria with LUNDEX adjustment for treatment continuation). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the study end points in relation to RF and ACPA status were calculated.Results. We identified 2,942 patients with available data on RA-associated autoantibodies; data on RF status were available for 2,787 patients (77.0% of whom were RF positive), and data on ACPA status were available for 1,903 patients (71.3% of whom were ACPA positive). Even after adjustment for sociodemographic and disease-and treatment-related confounders, RF and ACPA positivity were each associated with a lower risk of ABA discontinuation for any reason .90], P < 0.001 and HR 0.78 [95% CI 0.68-0.90], P < 0.001, respectively), compared to RF-negative and ACPA-negative patients. Similar associations with RF and ACPA were observed for discontinuation of ABA treatment due to ineffectiveness, with HRs of 0.72 (95% CI 0.61-0.84) and 0.74 (95% CI 0.62-0.88), respectively (both P < 0.001).Conclusion. Our results strongly suggest that positivity for RF or ACPA is associated with better effectiveness of ABA therapy.

Predictors of abatacept retention over 2 years in patients with rheumatoid arthritis: results from the real-world ACTION study

“…Double positivity for both RF and anti-CCP was associated with a greater likelihood of abatacept retention than either single positivity or double negativity, irrespective of treatment line. Real-world evidence from a pooled analysis of European RA registries has previously shown that RF and anti-CCP positivity were each strongly associated with improved retention of abatacept [34]. A positive association has also been demonstrated between abatacept retention and anti-CCP positivity in patients in clinical trials [35,36] and a registry study [37].…”

Can Synovial Pathobiology Integrate with Current Clinical and Imaging Prediction Models to Achieve Personalized Health Care in Rheumatoid Arthritis?

“…Interestingly, however, it is becoming increasingly clear that seropositivity for RF and/or ACPA does enhance response to rituximab (40–42). Similarly, enhanced retention to abatacept in patients seropositive for RF and/or ACPA has also been observed in two independent cohorts (43, 44). Despite these observations, significant clinical challenges remain in predicting response to rituximab or abatacept with wide variability seen in response rates within the seropositive groups.…”

Functional and Structural Characterization of a Novel HLA-DRB1*04:01-Restricted α-Enolase T Cell Epitope in Rheumatoid Arthritis

“…Ever since the discovery of the genetic association of RA to a subset of HLA-DR alleles (2), CD4 + T cells have been considered as classical effector cells in RA. Furthermore, the importance of CD4 + T cell effector functions in RA pathogenesis is corroborated both by therapeutic interventions affecting adaptive immune responses (3, 4) and by multiple studies of polyclonal T cell cytokine production (5, 6). The identification of RA-associated antibody responses to citrullinated proteins and the genetic link established between the presence of such autoantibodies and certain HLA class II molecules (7) has directed the investigation of novel autoantigens, and thereby promoted a renaissance in CD4 + T cells studies, as T helper cells would be assumed to govern IgG responses (8).…”