An Interim Analysis of the Efficacy of Abatacept in Japanese Biologics-naïve Rheumatoid Arthritis Patients (results from ABROAD study): Comparison of CRP and MMP-3 Level After Treatment with Abatacept Versus Anti-TNF Agents

Masahiro Sekiguchi¹, Kiyoshi Matsui¹, Masayasu Kitano¹, Mitsuo Namiki¹, Koichiro Ohmura², Takao Fujii³, Hideko Nakahara⁴, Keiji Maeda⁴, Hideo Hashimoto⁵, Takanori Kuroiwa⁶, Kenji Miki⁷, Masanori Funauchi⁸, Kazuhiro Hatta⁹, Kenshi Higami¹⁰, Shunzo Namiuchi¹¹, Ichiro Yoshii¹², Teruyuki Nakatani¹³, Takashi Ikawa¹⁴, Takaji Matsutani¹⁵, Kosaku Murakami¹⁶, Satoshi Morita¹⁷, Yutaka Kawahito¹⁸, Norihiro Nishimoto¹⁵, Tsuneyo Mimori¹⁹ and Hajime Sano¹, ¹Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan, ²Department of Rheumatology & Clin Immunology, Kyoto University, Kyoto, Japan, ³Dept of Rheum/Clinical Immun, Graduate School of Medicine,, Kyoto University, Kyoto, Japan, ⁴Division of Allergy, Rheumatology and Connective Tissue Diseases, Department of Internal Medicine, NTT West Osaka Hospital, Osaka, Japan, ⁵Dept of Orthopedic Surgery, Rinku Hashimoto Rheumatology Orthopaedics, Osaka, Japan, ⁶Department of Rheumatology, Yukioka Hospital, Osaka, Japan, ⁷Department of Orthopaedic Surgery, Amagasaki Central Hospital, Amagasaki, Japan, ⁸Division of Hematology and Rheumatology, Department of Medicine, Kinki University Faculty of Medicine, Osaka, Japan, ⁹Department of Internal Medicine, Tenri Yorozu Sodansyo Hospital, Nara, ¹⁰Department of Rheumatology, Higami Hospital, Nara, Japan, ¹¹Department of Rheumatology, Saiseikai Nakatsu Hospital, Osaka, Japan, ¹²Department of Orthopaedic Surgery, Yoshii Hospital, Shimanto, Japan, ¹³Department of Orthopaedic Surgery, Kishiwada City Hospital, Osaka, Japan, ¹⁴Osaka Rehabilitation Hospital, Hannan, Japan, ¹⁵Laboratory of Immune Regulation, Wakayama Medical University, Ibaraki, Japan, ¹⁶Rheumatology and Clinical Immunology, Osaka Red Cross Hospital, Osaka, Japan, ¹⁷Graduate School of Medicine & Medical Center, Department of Biostatistics and Epidemiology, Yokohama City University, Kanagawa, Japan, ¹⁸Department of Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan, ¹⁹Dept of Rheum & Clinical Immun, Kyoto University, Kyoto, Japan

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: Abatacept, C-reactive protein (CRP), matrix metalloproteinase (MMP), rheumatoid arthritis (RA) and tumor necrosis factor (TNF)

Session Information

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

Session Type: Abstract Submissions (ACR)

Background/Purpose: Abatacept (ABA) is a recombinant fusion protein consisting of the extracellular domain of human CTLA-4, binding to CD80/86 on antigen presenting cells (APCs) and thereby inhibits the interaction between these molecules and CD28 on T cells. ABA suppresses T cell activation and has been reported to have the therapeutic benefit for patients with rheumatoid arthritis (RA). However, there are limited data to compare the efficacy of ABA and anti-TNF agents. We conducted the ABROAD study (Abatacept Research Outcomes as a first-line biological Agent in the real worlD) in collaboration with 37 institutions in Japan. In this study, we confirmed the efficacy of ABA and compared CRP and MMP-3 levels after treatment with ABA versus anti-TNF agents in Japanese biologics-naïve RA patients.

Methods: We analyzed multicenter 100 biologics-naïve RA patients treated with ABA (ABROAD study) from January 2010 to May 2012. Patients received 500mg of abatacept for patients weighted less than 60kg or 750mg for patients with more than 60kg with or without MTX (mean dosage:6.0±3.7mg/week) for 24 weeks. To evaluate the efficacy of the treatment, we measured SDAI, DAS28-CRP (DAS), CRP and MMP-3 levels at week 0, 4, and 24 after treatment. We also compared CRP and MMP-3 levels after treatment with ABA versus anti-TNF agents using propensity score matching of sex, age and duration of the disease in 48 biologic-naïve RA patients, respectively.

Results: At week 0, 4, and 24 after ABA treatment, the mean SDAI /DAS score and CRP/ MMP-3 levels were SDAI (26.2±14.9→16.6±11.1→10.4±9.6), DAS (4.5±1.3→3.5±1.2→2.8±1.2), CRP (2.1±2.2→1.1±1.6→0.8±1.8 mg/dl), and MMP-3 (219.1±202.5→169.7±140.3→114.1±117.0ng/dl), respectively. We observed statistically significant reduction of SDAI/DAS/CRP/MMP-3 levels at week 4 compared to those of the baseline. The proportions of patients who achieved low disease activity or remission at week 24 were 65.7 % and 17.2 % based on SDAI score, and 49.0 % and 39.2 % based on DAS, respectively. In the comparison of propensity score matching 96 biologics-naïve RA patients (48 patients received ABA : ABROAD group; 48 patients received anti-TNF agents : anti-TNF group), the mean CRP levels at week 0, 4 and 24 after treatment were (1.75±1.99→ 0.71±0.88→0.39±0.67 mg/dl) in ABROAD group and (1.60±1.78→0.52±1.24→0.45±0.78 mg/dl) in anti-TNF group, respectively. The mean MMP-3 levels at week 0, 4 and 24 after treatment were (217.4±194.5→166.3±124.7→90.7±64.0 ng/dl) in ABROAD group and (225.9±163.8→164.4±177.2→127.9±128.2 ng/dl) in anti-TNF group, respectively. Although statistically not significant, CRP and MMP-3 levels in ABROAD group were lower than those in anti-TNF group at week 24 after treatment.

Conclusion: We observed the efficacy of ABA at week 4 after treatment of biologic-naïve RA patients. We also observed that CRP and MMP-3 levels in ABROAD group were lower than those in anti-TNF group at week 24 after treatment. These results indicate the possibility that ABA could become as a first-line biologic for the treatment of RA patients.

Disclosure:

M. Sekiguchi,

Bristol-Myers Squibb,

K. Matsui,

Bristol-Myers Squibb,

M. Kitano,

Bristol-Myers Squibb,

M. Namiki,

Bristol-Myers Squibb,

K. Ohmura,

Bristol-Myers Squibb,

T. Fujii,

Bristol-Myers Squibb,

H. Nakahara,
None;

K. Maeda,
None;

H. Hashimoto,
None;

T. Kuroiwa,
None;

K. Miki,
None;

M. Funauchi,

Bristol-Myers Squibb,

K. Hatta,
None;

K. Higami,
None;

S. Namiuchi,
None;

I. Yoshii,
None;

T. Nakatani,
None;

T. Ikawa,
None;

T. Matsutani,

Bristol-Myers Squibb,

K. Murakami,
None;

S. Morita,

Bristol-Myers Squibb,

Y. Kawahito,

Bristol-Myers Squibb,

N. Nishimoto,

Bristol-Myers Squibb,

T. Mimori,

Bristol-Myers Squibb,

H. Sano,

Bristol-Myers Squibb,

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