Higher Titer Of Anti-Citrullinated Protein Antibodies In Biologic-Naïve Rheumatoid Arthritis Patients Are Candidate Biomarkers To Predict Sensitivity Leading To Clinical Remission With Abatacept; Data From The Abroad Study

Takao Fujii¹, Masahiro Sekiguchi², Kiyoshi Matsui², Masayasu Kitano², Motomu Hashimoto³, Koichiro Ohmura⁴, Aihiro Yamamoto⁵, Hideko Nakahara⁶, Keiji Maeda⁷, Akira Yokota⁸, Kenji Miki⁹, Naoki Shimmyo¹⁰, Takanori Kuroiwa¹¹, Kosaku Murakami¹², Yoshio Ozaki¹³, Kenshi Higami¹⁴, Ichiro Yoshii¹⁵, Yuji Nozaki¹⁶, Takashi Ikawa¹⁷, Satoshi Morita¹⁸, Yutaka Kawahito⁵, Norihiro Nishimoto¹⁹, Tsuneyo Mimori⁴ and Hajime Sano², ¹Department of the Control for Rheumatic Diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan, ²Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya-city, Japan, ³The Control for Rheumatic Diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan, ⁴Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan, ⁵Department of Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan, ⁶Division of Allergy, Rheumatology and Connective Tissue Diseases, Department of Internal Medicine, NTT West Osaka Hospital, Osaka, Japan, ⁷Allergy, Rheumatology and Connective Tissue Diseases, Department of Internal Medicine, NTT West Osaka Hospital, Osaka, Japan, ⁸Yokota Clinic for Rheumatology, Osaka, Japan, ⁹Department of Orthopaedic Surgery, Amagasaki Central Hospital, Amagasaki, Japan, ¹⁰Kashiba Asahigaoka Hospital, Kashiba, Japan, ¹¹Department of Rheumatology, Yukioka Hospital, Osaka, Japan, ¹²Dept of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan, ¹³Kansai Medical University Hirakata Hospital, Hirakata, Japan, ¹⁴Department of Rheumatology, Higami Hospital, Nara, Japan, ¹⁵Department of Orthopaedic Surgery, Yoshii Hospital, Shimanto, Japan, ¹⁶Kinki University Faculty of Medicine, Sayama, Japan, ¹⁷Osaka Rehabilitation Hospital, Hannan, Japan, ¹⁸Graduate School of Medicine & Medical Center, Department of Biostatistics and Epidemiology, Yokohama City University, Kanagawa, Japan, ¹⁹Osaka Rheumatology Clinic, Osaka, Japan

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: Abatacept, ACPA, remission and rheumatoid arthritis, treatment

Session Information

Title: Rheumatoid Arthritis Treatment - Small Molecules, Biologics and Gene Therapy I

Session Type: Abstract Submissions (ACR)

Background/Purpose: Biomarkers to predict each rheumatoid arthritis (RA) patient’s sensitivity for biologic disease modifying anti-rheumatic diseases, especially for the only T cell modulator abatacept (ABT), is of high interest from the points of view of medication and medical economy. The purpose of this study is to determine the predicting factors of clinical remission by ABT in biologic-naïve RA patients.

Methods: Efficacy and safety of ABT are being investigated with Japanese biologic-naïve RA patients (N=155) in the ABROAD study (ABatacept Research Outcomes as a first-line biological Agent in the real worlD, an ongoing, prospective, multicenter cohort study in the west side of Japan, female = 83.2%, mean age at the ABT initiation = 61.3 years old, and disease duration = 8.1 years). In this study, simplified disease activity index (SDAI) remission (≦3.3) rate at 24 wks is defined as a goal of treatment and a merkmal of patient’s sensitivity to ABT. Correlation between the SDAI remission rate and other clinical indexes before ABT treatment were analyzed by the univariate analysis method. During the analysis, anti-citrullinated protein antibodies (ACPA) titer values before treatment were classified into 4 groups; negative (less than the upper limit of normal [ULN], <4.5 U/mL), low-positive (less than 3 times of the ULN, 4.5-13.5 U/mL), high-positive (less than 22 times of the ULN, 13.6-99 U/mL), and very high-positive (equal or more than 22 times of the ULN, ≧99 U/mL), and each group was studied independently.

Results: SDAI remission at 24 wks was achieved in 16% of the patients. Very high-positive ACPA (Odds ratio [OR] = 4.44, 95% confidence interval [CI] = 1.28-15.38, p = 0.019) were significantly associated with the SDAI remission. High-positive group was slightly inclinable but insignificant. Low-positive and negative groups had no correlations. As the reference, short disease duration (<1 year) (OR =2.79, 95% CI = 1.02-7.61, p = 0.045 vs. ≧1 year) and moderate disease activity at baseline defined by DAS28-CRP (OR = 4.39, 95% CI = 1.55-12.5, p = 0.005 vs. high disease activity) were also significantly associated with the SDAI remission at 24 wks, and male gender (OR = 2.76, 95% CI = 0.91- 8.40, p = 0.072 vs. female) appeared to be linked. While age at ABT initiation, concomitant use of methotrexate, CRP level at baseline, and the 1987 ACR criteria fulfillment were not statistically associated with the SDAI remission. ACPA positivity association with a better response to ABT observed in this study sustained French report of the ORA registry (Gottenberg JE, et al, ARD 2012;71:1815).

Conclusion: Higher titer of ACPA in biologic-naïve RA patients, in whom T and B lymphocytes are possibly activated, could be a candidate biomarker to predict sensitivity for ABT.

Disclosure:

T. Fujii,

Bristol-Myers Squibb Japan,

M. Sekiguchi,

Bristol-Myers Squibb Japan,

K. Matsui,

Bristol-Myers Squibb Japan,

M. Kitano,

Bristol-Myers Squibb Japan,

M. Hashimoto,

Bristol-Myers Squibb Japan,

K. Ohmura,

Bristol-Myers Squibb Japan,

A. Yamamoto,

Bristol-Myers Squibb Japan,

H. Nakahara,
None;

K. Maeda,
None;

A. Yokota,
None;

K. Miki,
None;

N. Shimmyo,
None;

T. Kuroiwa,
None;

K. Murakami,
None;

Y. Ozaki,
None;

K. Higami,
None;

I. Yoshii,
None;

Y. Nozaki,

Bristol-Myers Squibb Japan,

T. Ikawa,
None;

S. Morita,
None;

Y. Kawahito,

Bristol-Myers Squibb Japan,

N. Nishimoto,

Bristol-Myers Squibb Japan,

T. Mimori,

Bristol-Myers Squibb Japan,

H. Sano,

Bristol-Myers Squibb Japan,

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