Treatment Responses and Their Predictors Of Abatacept In Biologic naïve Patients With Rheumatoid Arthritis; Data Form Abroad Study

Yutaka Kawahito¹, Takao Fujii², Akira Yokota³, Hideo Hashimoto⁴, Kiyoshi Matsui⁵, Kenji Miki⁶, Masayasu Kitano⁵, Naoki Shinmyo⁷, Aihiro Yamamoto¹, Koichiro Ohmura⁸, Takanori Kuroiwa⁹, Toshihiko Hidaka¹⁰, Ichiro Yoshii¹¹, Hideko Nakahara¹², Takashi Fujimoto¹³, Kosaku Murakami¹⁴, Satoshi Morita¹⁵, Masahiro Sekiguchi⁵, Norihiro Nishimoto^16,17, Tsuneyo Mimori⁸ and Hajime Sano⁵, ¹Department of Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan, ²Department of the Control for Rheumatic Diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan, ³Yokota Clinic for Rheumatology, Osaka, Japan, ⁴Dept of Orthopedic Surgery, Rinku Hashimoto Rheumatology Orthopaedics, Osaka, Japan, ⁵Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya-city, Japan, ⁶Department of Orthopaedic Surgery, Amagasaki Central Hospital, Amagasaki, Japan, ⁷Kashiba Asahigaoka Hospital, Kashiba, Japan, ⁸Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan, ⁹Department of Rheumatology, Yukioka Hospital, Osaka, Japan, ¹⁰Zenjinkai Shimin-No-Mori Hospital, Miyazaki, Japan, ¹¹Department of Orthopaedic Surgery, Yoshii Hospital, Shimanto, Japan, ¹²Division of Allergy, Rheumatology and Connective Tissue Diseases, Department of Internal Medicine, NTT West Osaka Hospital, Osaka, Japan, ¹³Nara Medical University, Kashihara, Japan, ¹⁴Rheumatology and Clinical Immunology, Osaka Red Cross Hospital, Osaka, Japan, ¹⁵Graduate School of Medicine & Medical Center, Department of Biostatistics and Epidemiology, Yokohama City University, Kanagawa, Japan, ¹⁶Tokyo Medical University, Tokyo, Japan, ¹⁷Osaka Rheumatology Clinic, Osaka, Japan

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: Abatacept and rheumatoid arthritis (RA), ACPA, C-reactive protein (CRP)

Session Information

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

Session Type: Abstract Submissions (ACR)

Background/Purpose: The identification of predictors of good response to biologic therapy is needed in the perspective of personalized medicine.　To determine the predicting factors of efficacy of abatacept (ABT) in biologic naïve rheumatoid arthritis (RA) patients, we conducted the ABROAD study (Abatacept Research Outcomes as a first-line biological Agent in the real worlD) in collaboration with 46 institutions in Japan.

Methods: Patients received 500mg of ABT for patients weighted less than 60kg or 750mg for patients with more than 60kg with or without methotrexate (MTX) for 24 weeks. We measured SDAI, DAS28-CRP (DAS), CRP levels at week 0, 4, and 24 after treatment. To evaluate the response to abatacept, we used validated response definitions (50/70/ 85% improvement) for the simplified disease activity indices (SDAI), which are correlated with ACR (20/50/70 improvement) response and influenced with radiographic progression and function (Aletaha D, et al. Ann Rheum Dis. 71:1190-6, 2012). Predictors of good SDAI response were identified by using univariate followed by multivariate logistic regression analysis.

Results: We examined 179 RA patients with moderate and high disease activity (SDAI >11, female = 85.5 %, mean age = 62.4 years old, mean disease duration =7.9 years, mean dosage of MTX: 7.5 ± 2.6mg/week). SDAI remission (<3.3) at 24 week was achieved in 13% of our patients. SDAI 50%, 70%, and 85% improvement rate at week 24 were 71%, 39%, 16%, respectively. In univariate analyses, very high-positive ACPA (equal or more than 22 times of the ULN, ≧99 U/mL) at baseline was significantly associated with SDAI 50% improvement at week 24 (OR = 3.390, 95% CI = 1,434-8.0, p = 0.005). Short disease duration (＜1 year) was significantly associated with SDAI 85% improvement (OR = 3.191, 95% CI = 1.262-8.072, p = 0.014). In multivariate analyses, very high-positive ACPA, short disease duration (<1 year), 70% improvement of CRP at week 4 were significantly associated with SDAI response.

ACPA titer at baseline influences on SDAI response．　

1.Patients with short disease duration （<1 year)

	SDAI 50% improvement (24wk)	SDAI 70% improvement (24wk)	SDAI 85% improvement (24wk)
ACPA　< 4.5	25.0%	0.0%	0.0%
ACPA　< 99	50.0%	12.5%	12.5%
ACPA　≧ 99	85.7%	71.4%	50.0%

2. Patients with CRP 70 % improvement (at week 4)

	SDAI 50% improvement (24wk)	SDAI 70% improvement (24wk)	SDAI 85% improvement (24wk)
ACPA　< 4.5	44.4%	33.3%	0.0%
ACPA　< 99	58.6%	37.9%	13.8%
ACPA　≧ 99	95.0%	65.0%	30.0%

Conclusion: In this large biologic naïve observational cohort of RA patients treated with ABT, we suggest that very high-positive ACPA at baseline, short disease duration and CRP improvement at week 4, may be predictors for good response to ABT.

Disclosure:

Y. Kawahito,

Bristol-Myers Squibb Japan,

T. Fujii,

Bristol-Myers Squibb Japan,

A. Yokota,
None;

H. Hashimoto,
None;

K. Matsui,

Bristol-Myers Squibb Japan,

K. Miki,
None;

M. Kitano,

Bristol-Myers Squibb Japan,

N. Shinmyo,
None;

A. Yamamoto,

Bristol-Myers Squibb Japan,

K. Ohmura,

Bristol-Myers Squibb Japan,

T. Kuroiwa,
None;

T. Hidaka,
None;

I. Yoshii,
None;

H. Nakahara,
None;

T. Fujimoto,
None;

K. Murakami,
None;

S. Morita,
None;

M. Sekiguchi,

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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