FRI0121 IMPROVEMENT OF MATRIX METALLOPROTEINASE-3 AT 12 WEEKS IS AN INDEPENDENT PREDICTIVE FACTOR FOR ACHIEVEMENT OF LOW DISEASE ACTIVITY AT 52 WEEKS IN BIO-SWITCH RHEUMATOID ARTHRITIS PATIENTS TREATED WITH ABATACEPT
Authors: Nobunori Takahashi, Toshihisa Kojima, Shuji Asai, Naoki Ishiguro
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Japanese post-marketing surveillance (PMS) data demonstrated that effectiveness of abatacept in rheumatoid arthritis (RA) patients with previous biologics treatment (bio-switch) was significantly lower than that in bio-naïve patients [1]. Useful predictive factors for good clinical response of abatacept is necessary especially in the bio-switch patients. Serum matrix metalloproteinase-3 (MMP-3) is an enzyme produced by synoviocytes which can be used to predict clinical effectiveness and joint destruction in RA patients [2]. However, little is known about the relationship between MMP-3 and effectiveness of abatacept. <h3>Objectives</h3> This study aimed to study whether serum MMP-3 levels can predict good clinical effectiveness of abatacept in the bio-switch RA patients using data from a multicenter cohort. <h3>Methods</h3> Participants were consecutive 423 RA patients treated with abatacept, observed for longer than 52 weeks, and registered in the TBCR, a Japanese multicenter registry system for RA patients treated with biologics. Multivariate logistic regression analysis was used to study predictive factors for achievement of low disease activity at 52 weeks separately in bio-naïve and bio-switch group. <h3>Results</h3> A total of 189 bio-switch and 234 bio-naïve patients were included in this study. ROC analysis revealed that MMP-3 improvement rate at 12 weeks, compared to 4 and 24 weeks, had highest AUC and the best cut-off value was 20.0% at 12 weeks for predicting achievement of low disease activity (LDA) at 52 weeks in the bio-switch group (Figure 1, right panel). We performed multivariate logistic regression analysis to study independent predictive factors for LDA at 52 weeks using patients' background factors as well as 20% improvement of MMP-3 at 12 weeks. In the bio-naïve group, DAS28-CRP score at baseline was the only predictive factor, while the achievement of 20% improvement of MMP-3 at 12 weeks was an independent predictive factor (adjusted OR: 3.550, p=0.005) in addition to DAS28-CRP in the bio-switch group (Table). In the bio-switch group, patients that achieved 20% improvement of MMP-3 at 12 weeks demonstrated significantly higher achievement rate of LDA at 52 weeks compared to those that did not achieved 20% improvement (60.0 vs 33.3%, p=0.001) (Figure 2). <h3>Conclusion</h3> In the bio-switch patients, we sometimes have difficulty to obtain good clinical response of abatacept and it would be even more important to judge whether to continue abatacept or whether to add other anti-rheumatic drugs as early as possible [3]. Our results suggested that the improvement of MMP-3 at 12 weeks would be a key to predict good clinical effectiveness of abatacept at 1 year. We would be better to note not only the major clinical indices such as DAS28 but also the change of MMP-3 to obtain the best clinical results in the bio-switch patients treated with abatacept. <h3>References</h3> [1] Harigai M, et al. Mod Rheumatol 2016;26(4):491. [2] Hattori Y, et al. Mod Rheumatol 2018;28:119. [3] Takahashi N, et al. Mod Rheumatol 2013;23:904. <h3>Disclosure of Interests</h3> Nobunori Takahashi Speakers bureau: AbbVie, Bristol-Myers Squibb, Chugai, Eisai, Mitsubishi Tanabe, and Pfizer. YS has received speakers' fees from Astellas, Bristol-Myers Squibb, and Ono, Toshihisa Kojima Grant/research support from: Chugai Pharmaceutical (Investigator Initiated Study), Novartis, Nippon Kayaku, Eli Lilly, Eisai, Speakers bureau: Chugai Pharmaceutical, Takeda Pharmaceutical, Pfizer, Eli Lilly Japan, Bristol Myers Squibb, Ono Pharmaceutical, Daiichi Sankyo, Astelas, UCB, Janssen Pharmaceutical, Tanabe Mitsubishi, Shuji Asai Speakers bureau: AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Janssen, Takeda, and UCB Japan, Naoki Ishiguro Grant/research support from: AbbVie, Asahi Kasei, Astellas, Chugai, Daiichi-Sankyo, Eisai, Kaken, Mitsubishi Tanabe, Otsuka, Pfizer, Takeda, and Zimmer Biomet, Consultant for: Ono, Speakers bureau: Astellas, Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, Pfizer, and Taisho Toyama