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Abstract
Background Serum matrix metalloproteinase-3 (MMP-3) is a specific inflammatory marker of the synovium in patients with rheumatoid arthritis (RA).
Objectives Our aim in this study is to investigate whether serum MMP-3 is the predictor for continuation rate in treatment for RA patients with biologics.
Methods We analyzed 220 patients with adalimumab (ADA) therapy in the multicenter study group (Tsurumai Biologics Communication Registry; TBCR). We divided into 2 groups based on the improvement of serum level of MMP-3 and CRP: high rate of improvement (MMP-HR group) and low rate of improvement (MMP-LR group) in serum MMP-3 levels at 4 weeks (Fig.1a), and: high rate of improvement (CRP-HR group) and low rate of improvement (CRP-LR group) in serum CRP levels at 4 weeks (Fig.1c). We also divided into 2 groups based on the serum level of MMP-3 and CRP: high value (MMP-H group) and low value (MMP-L group) in serum MMP-3 levels at 4 weeks (Fig.2a), and: high value (CRP-H group) and low value (CRP-L group) in serum CRP levels at 4 weeks (Fig.2c). We evaluated the continuation rate at 3 years in 2 groups, respectively. Kaplan-Meier curves were generated to estimate the continuation rate. The sensitivity and specificity for the best cut-off lebel was analyzed by a receiver-operated characteristic (ROC) curve.
Results The continuation rate of ADA therapy was 54% at 3 years. The rate of continuation in MMP-HR group (63%) is significantly higher than in MMP-LR group (45%) (Fig.1b). The rate of continuation in CRP-HR group (61%) is significantly higher than in CRP-LR group (47%) (Fig.1d). The rate of continuation in MMP-H group (46%) is significantly lower than in MMP-L group (62%) (Fig.2b). The rate of continuation in CRP-H group (41%) is significantly lower than in CRP-L group (71%) (Fig.2d). Moreover, the rate of continuation in (MMP and CRP)-HR group (65%) (Fig.3a) and (MMP and CRP)-L group (71%) (Fig.3b) is high. The best cut-off rate determined by ROC analysis of improvement of serum MMP-3 and CRP level at 4 weeks for determining continuation at 3 years was 5.5% (sensitivity: 69%, specificity: 51%) and 59.0% (sensitivity: 63%, specificity: 57%), respectively. The best cut-off value determined by ROC analysis of serum MMP-3 and CRP level at 4 weeks for determining continuation at 3 years was 118.8 (ng/mL) (sensitivity: 62%, specificity: 55%) and 0.23 (mg/dL) (sensitivity: 66%, specificity: 62%), respectively.
MMP-HR group: high rate of improvement in serum MMP-3 levels at 4 weeks. MMP-LR group: low rate of improvement in serum MMP-3 levels at 4 weeks. CRP-HR group: high rate of improvement in serum CRP levels at 4 weeks. CRP-LR group: low rate of improvement in serum CRP levels at 4 weeks. MMP-H-group: high value in serum MMP-3 levels at 4 weeks. MMP-L group: low value in serum MMP-3 levels at 4 weeks. CRP-H group: high value in serum CRP levels at 4 weeks. CRP-L group: low value in serum CRP levels at 4 weeks.
Conclusions High rate of improvement and low value in serum MMP-3 at 4 weeks yield better continuation for the treatment of RA patients. We considered that the combination of serum MMP-3 and CRP at 4 weeks can be useful for predicting the rate of continuation in RA patients with ADA therapy.
Disclosure of Interest Y. Hattori Grant/research support from: Chugai Pharma Corporation, Pfizer, Abbvie, UCB, Bristol-Myers Squibb, Janssen Pharma, and Nichi-Iko Pharmaceutical Corporation., A. Kaneko Grant/research support from: Chugai Pharma Corporation, Pfizer, Abbvie, UCB, Bristol-Myers Squibb, Janssen Pharma, and Nichi-Iko Pharmaceutical Corporation., D. Kida Grant/research support from: Chugai Pharma Corporation, Pfizer, Abbvie, UCB, Bristol-Myers Squibb, Janssen Pharma, and Nichi-Iko Pharmaceutical Corporation., N. Takahashi Speakers bureau: Abbvie, Eisai Corporation, Mitsubishi Tanabe Pharma Corporation, Takeda Pharma Corporation, Pfizer, Chugai Pharma Corporation, and Bristol-Myers Squibb., H. Kanda Grant/research support from: Chugai Pharma Corporation, Pfizer, Abbvie, UCB, Bristol-Myers Squibb, Janssen Pharma, and Nichi-Iko Pharmaceutical Corporation., T. Kojima Speakers bureau: Takeda Pharma Corporation, Janssen Pharmaceutical, Astellas Pharma Corporation, Mitsubishi Tanabe Pharma Corporation, Takeda Pharma Corporation, Eisai Pharma Corporation, Abbvie, Bristol-Myers Squibb, Pfizer, and Chugai Pharma Corporation., N. Ishiguro Speakers bureau: AbbVie, Chugai Pharma Corporation, Mitsubishi Tanabe Pharma Corporation, Daiichi-Sankyo, Eisai Pharma Corporation, Pfizer, and Takeda Pharma Corporation.