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Clinical Trial
. 2017 Nov 15;19(1):250.
doi: 10.1186/s13075-017-1449-z.

Matrix metalloproteinase-3 and the 7-joint ultrasound score in the assessment of disease activity and therapeutic efficacy in patients with moderate to severe rheumatoid arthritis

Ling Zhou  1 , Geng Wang  1 , Xin Liu  1 , Jing Song  1 , Ling Chen  1 , Huji Xu  2
Affiliations
Clinical Trial

Matrix metalloproteinase-3 and the 7-joint ultrasound score in the assessment of disease activity and therapeutic efficacy in patients with moderate to severe rheumatoid arthritis

Ling Zhou et al. Arthritis Res Ther. .

Abstract

Background: This study aimed to investigate the reliability and validity of serum matrix metalloproteinase-3 (MMP-3) levels and articular ultrasound (US) scores in assessing disease activity and therapeutic response in rheumatoid arthritis (RA) patients.

Methods: A total of 151 RA patients were enrolled, of whom 22 were treated with certolizumab pegol (Cimzia, CZP). The RA patients were divided into the following four subgroups according to their disease activity score in 28 joints (DAS28): stable, mild activity, moderate activity, and high activity. Forty-three healthy controls were simultaneously studied. The serum MMP-3 levels and 7-joint US (US7) scores of all subjects were determined. The patients who were treated with CZP were subsequently followed for 6 months.

Results: The serum MMP-3 levels of all the RA patients were significantly higher than those of healthy controls, and those of patients with moderate and severe RA were significantly higher than those of patients with stable RA. The US7 scores of patients with severe RA were significantly higher than those of patients in other groups. Using the DAS28 as a reference standard, the corresponding cutoff value of MMP-3 was 70.5 ng/ml. After CZP treatment, the MMP-3 levels and US7 scores were significantly decreased at week 2, and the mean changes in US7 scores at weeks 12 and 24 were significantly higher in both groups with American College of Rheumatology 50% positive response (ACR50) and ACR 70% positive response (ACR70) than in the negative groups.

Conclusion: Serum MMP-3 and the US7 scores could both effectively reflect disease activity and therapeutic responses in patients with moderate to severe RA.

Trial registration: CTR20140405 (RA0044), CTR20140405: A phase 3, Multicenter, Double-blind, Placebo Controlled, Parallel Group, Randomized, 24-Week Study to Evaluate the Safety and Efficacy of Certolizumab Pegol as Additional Medication to Methotrexate in Chinese Subjects With Active Rheumatoid Arthritis Who Have an Incomplete Response to Methotrexate, Registered on 13 June 2014. CTR20140412 (RA0078), CTR20140412: A phase 3, Multicenter, Open-label Extension Study to Assess the Safety and Efficacy of Certolizumab Pegol as Additional Medication to Methotrexate in Chinese Subjects With Active Rheumatoid Arthritis Who Participated in RA0044, Registered on 02 July 2014.

Keywords: Articular ultrasonography; Matrix metalloproteinase-3; Rheumatoid arthritis.

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Conflict of interest statement

Ethics approval and consent to participate

All the recruited subjects who participated in the study had provided informed consent. The study protocol has been approved by the Medical Ethics Committee of Shanghai Changzheng Hospital (Reference number: 2014 (Ethics)-34; 2014(Ethics)-35).

Consent for publication

All authors gave final approval of the version to be published. We have obtained consent to publish from all participants to report individual patient data.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Serum matrix metalloproteinase-3 (MMP-3) levels (a) and 7-joint ultrasound (US7) scores (b) in the different groups of patients with active rheumatoid arthritis (RA). a MMP-3 in patients with RA with moderate and severe disease activity were significantly higher than in patients with stable RA (105.10 vs 33.40, p < 0.001; 363.11 vs 33.40, p < 0.001). No significant differences were found between the group with mild RA and the group with stable RA or the normal control group (54.25 vs 33.40, p > 0.05; 54.25 vs 35.20, p > 0.05). b The US7 scores in patients with severe active RA were significantly higher than those in patients in the stable, mild, and moderate RA groups (7.8 vs 0.8 p < 0.001; 7.8 vs 2.2 p < 0.05; 7.8 vs 3.2 p < 0.05). No significant differences were found between patients with mild or moderate RA activity and those with stable activity (p > 0.05)
Fig. 2
Fig. 2
Receiver operating characteristic (ROC) curve of matrix metalloproteinase-3 (MMP-3) for classification of disease activity in rheumatoid arthritis (RA). Setting the disease activity score in 28 joints (DAS28) as the reference standard, the sensitivity of MMP-3 in classifying the disease activity of RA was determined using a ROC curve. The corresponding cutoff value in the ROC curve of MMP-3 is 70.5 ng/ml (area under the curve 0.8538, p < 0.0001)
Fig. 3
Fig. 3
Matrix metalloproteinase-3 (MMP-3) and 7-joint ultrasound (US7) scores in 22 patients with rheumatoid arthritis (RA) after treatment with certolizumab pegol (CZP). US7 scores were compared between the MMP-3-positive and the MMP-3-negative groups. Patients’ MMP-3 levels and US7 scores were significantly decreased at week 2 compared with baseline levels
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