Article Text

PDF
FRI0288 Immunogenicity is Associated with Lupus-Like Autoimmunity in Rheumatoid Arthritis Patients Treated with Infliximab
  1. Y. Ishikawa1,
  2. T. Fujii1,2,
  3. S. Kondoh-Ishikawa1,
  4. M. Hashimoto2,
  5. M. Furu2,
  6. H. Ito3,
  7. Y. Imura1,
  8. R. Nakashima1,
  9. N. Yukawa1,
  10. H. Yoshifuji1,
  11. K. Ohmura1,
  12. T. Mimori1
  1. 1Department of Rheumatology and Clinical Immunology
  2. 2Department of the Control for Rheumatic Diseases
  3. 3Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

Abstract

Background Immunogenicity, a formation of anti-drug antibodies (ADA) against a biologic agent, has also been reported in patients with rheumatoid arthritis (RA) receiving anti-TNF antibody (Ab) treatment. In case of infliximab (IFX), immunogenicity is strongly linked to subtherapeutic serum drug levels and a lack of clinical response [1]. On the other hand, autoimmune phenomena, such as lupus-like syndrome or auto-Ab productions, are frequently observed in RA patients receiving TNF inhibitors, and some of these patients also show insufficient clinical response [2]. However, the association between immunogenicity and autoimmunity has not been fully elucidated.

Objectives In RA patients treated with IFX, ADA-predicting factors such as patient background and auto Ab production are examined and a better management for ADA-mediated insufficient response is investigated.

Methods Fifty-seven Japanese RA patients (female 79%; 55.2 years old; disease duration 7.2 years) treated with IFX from 2004 to 2013 were retrospectively examined. Serum IFX trough levels and ADA against IFX were measured by ELISA and radioimmunoassay (RIA), respectively [1]. Anti-nuclear antibodies (ANA) and anti-DNA Abs were measured by semi-quantitative indirect fluorescence assay and RIA, respectively. Both anti-single-stranded (ss) and double-stranded (ds) DNA Abs were measured by ELISA.

Results Twenty-one RA patients (36.8%) developed ADA after the IFX administration and their serum IFX trough levels were significantly lower compared to those in ADA-negative group (0.09±0.04 vs. 2.48±0.33 μg/mL, p <0.0001). There were no significant differences in age, sex, disease duration, RA stage, DAS28 score, and concomitant use of oral prednisolone (PSL) and MTX between the groups. Anti-DNA Abs (RIA) were more frequently recognized in ADA-positive group at the last observation (57% vs 22%, p =0.011). In addition, ADA-positive group showed significantly higher serum levels of anti-DNA (1.53±0.43 to 26.5±19.7 IU/mL, p =0.003) and anti-ssDNA Ab (13.6±1.09 to 34.8±12.2 AU/mL, p =0.038) along with the development of ADA. There also was a positive correlation of serum ADA levels with ANA (r =0.273, p =0.0002), anti-DNA (r =0.229, p =0.0014) or anti-ssDNA Ab (r =0.155, p =0.0258) levels. Although ADA-positive patients had a higher cumulative IFX withdrawal rate (p =0.047), preceding intravenous (IV)-PSL administration was significantly associated with higher sustained IFX treatment rate in the group (p =0.0008).

Conclusions The development of ADA against IFX is linked to lupus-like autoimmunity and subsequent insufficient clinical response against IFX. Therefore, it may be useful to monitor serum ANA and anti-DNA Abs as predicting factors of ADA in RA patients treated with IFX. In addition, IV-PSL might be effective to restore the ADA-mediated insufficient response.

References

  1. van Schouwenburg PA, et al. Nat Rev Rheumatol. 2013 Mar; 9:164-172.

  2. Yukawa N, et al. Arthritis Res Ther. 2011; 13:R213.

Acknowledgements The authors thank Dr. D. van der Kleij and Dr. G. J. Wolbink for the measurements of serum levels of IFX and anti-IFX Abs.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.1421

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.