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AB0422 Serum Drug Level and Anti-Citrullinated Peptide Antibodies as Biomarkers That Predict Eular Response in Rheumatoid Arthritis - A New Step to Personalized Medicine
  1. D. Opris1,
  2. M. Diana1,
  3. C. Gainaru2,
  4. M. Iliuta2,
  5. L. Groseanu1,
  6. I. Saulescu1,
  7. C. Constantinescu1,
  8. V. Bojinca1,
  9. A. Balanescu1,
  10. D. Predeteanu1,
  11. R. Ionescu1
  1. 1Rheumatology, “Sfanta Maria” Hospital, Bucharest
  2. 2“Carol Davila” University of Medicine, Bucharest, Romania

Abstract

Background Rituximab (RTX) therapy for rheumatoid arthritis (RA) exhibit enhanced effectiveness in patients with positive rheumatoid factor and/or anti-citrullinated peptide antibodies (ACPA). These two findings seem to predict clinical response (1). There are limited data on RTX drug level and its relationship with ACPA status, and their influence on response to treatment.

Objectives To investigate the relationship between patient's ACPA status, their RTX serum level before retreatment and clinical response in RA patients undergoing the B cell depletion therapy.

Methods A prospective cohort study on 25 patients with RA undergoing RTX for a mean time of 41.79 months. Just before a new retreatment course, RTX serum level and RTX-antibodies were measured by sandwich ELISA (Promonitor-RTX Ref.PG-PRTX-12700). Patients were divided according to RTX serum level into detectable versus non-detectable drug level based on assay cut-off. Clinical and pharmacological data were collected at the time of dosing serum RTX level and 6 months later, time of follow-up. The unpaired t-test and Wilcoxon Mann-Whitney test were used for comparisons. Associations between investigated parameters have been assessed by logistic regression and calculating the area under ROC (receiver-operating characteristic) curve (AUC), using STATA SE/11 software.

Results Seven patients (28%) had ACPA negative status. At the time of RTX dosing, their mean DAS28 score was 4.39±1.79, significantly higher compared to 3.27±0.56 score in ACPA positive patients (P=0.0227). ACPA positive status was positively associated with detectable RTX levels (OR=8.75; 95%CI 1.21-63.4; P=0.032), being a moderate predictor with AUC=0.7153; 95%CI: 0.5239 - 0.9067. At the time of follow-up, ACPA positive patients had significantly lower DAS28 score (P=0.0402) and lower SDAI score (P=0.0119) compared to ACPA negative patients. Also, detectable RTX level was associated significantly with good and moderate EULAR response (OR=6.0; 95%CI: 1.01-35.91; P=0.50), but this was a moderate predictor for EULAR response (AUC=0.7000, 95%CI: 0.5087-0.8913). The combination of detectable RTX level and ACPA positivity (multiplicative model) significantly was associated to good and moderate EULAR response at 6 months (OR=16.0; 95%CI: 2.16-118.27; P=0.007), being good predictor with AUC=0.800 (95%CI: 0.6325-0.9675). All patients tested negative for anti-RTX antibodies.

Conclusions This observational study showed that ACPA positivity combined with detectable RTX drug level before retreatment represents a good predictor for good and moderate EULAR response at 6 months. Measuring RTX level can be used to personalize treatment in patients with RA undergoing B cell depletion therapy.

References

  1. Isaacs JD, Cohen SB, Emery P, Tak PP et al. Effect of baseline rheumatoid factor and anticitrullinated peptide antibody serotype on rituximab clinical response: a meta-analysis. Ann. Rheum. Dis. 2012 Jun 11

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.4812

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