Differential Efficacy of TNF Inhibitors with or Without the Immunoglobulin Fragment Crystallizable (fc) Portion in Rheumatoid Arthritis: the ANSWER Cohort Study

Background: Rheumatoid factor (RF) binds to the Fc portion of immunoglobulin and can bind to the Fc portion of anti-TNF monoclonal antibodies (TNFi), attenuating their clinical efficacy. We tried to determine whether the therapeutic efficacy is different between TNFi with or without the immunoglobulin Fc portion in rheumatoid arthritis (RA) patients depending upon the RF titres.Methods: RA patients treated with TNFi were enrolled from an observational multi-centre registry in Japan. TNFi treatments were divided into two groups based on the structural characteristics between TNFi with Fc (infliximab, adalimumab, golimumab, etanercept) and TNFi without Fc (certolizumab-pegol). Patients were classified into 4 groups according to RF titre quartiles. The sequential disease activity score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR) were compared by the Mann-Whitney U test between TNFi with and without the immunoglobulin Fc portion in each RF titre group.Results: A total of 705 RA patients were included and classified into four groups according to quartiles of baseline RF titres (RF1; RF 0-15.0 IU/mL, RF2; 15.0-55.0, RF3; 55.0-166, RF4; 166-7555). In RF4, RA patients treated with TNFi without Fc had a significantly lower DAS28-ESR than those treated with TNFi with Fc (3.2 (2.3-4.2) vs. 2.7 (2.0-3.0)) (median, IQR) after 12 months of follow-up, while there were no significant differences in RF1, RF2, and RF3.Conclusion: TNFi without Fc (certolizumab-pegol) may be more efficacious than TNFi with Fc in RA patients with high RF titres.