MMP-3 may already be elevated in the early stages of RA (symptoms < 1 year) and shows an upward trend as the disease progresses. It has been shown that MMP-3 levels can

predict a poorer prognosis and correlate with the Larsen score in patients with non-erosive joint. In a study by Martina et al., MMP-3 levels in RA patients were significantly higher than in the healthy control group and correlated positively with erythrocyte sedimentation rate (ESR), CRP, DAS28 and anti-CCP. Hu and colleagues also confirmed that in patients with early RA who had normal CRP and/or ESR, the serum MMP-3 positivity rate was higher than that of CRP and ESR, and this correlated positively with CRP levels.

In a 2022 study involving 145 patients, Liang and colleagues investigated differences in lymphocyte and CD4+ T-cell subtypes between ACPA-positive and ACPA-negative RA patients, and assessed the diagnostic and disease activity monitoring role of MMP-3 in ACPA-negative RA patients. ACPA negativity may occur in up to 30% of patients. Delays in diagnosis can lead to delays in initiating treatment, which may result in irreversible joint damage. It has been demonstrated that monitoring MMP-3 levels is of paramount importance in these patients, thereby facilitating early diagnosis. It has also been established that in ACPA-negative patients, MMP-3 was an important marker for predicting clinical status, stratification and disease progression.

As early as 2000, it was reported that serum MMP-3 levels serve as an indicator of the development of radiological damage in patients with early RA and predict cartilage damage. This has since been supported by several studies.

Rajalingham and colleagues found that the mean serum MMP level in RA patients with radiographic joint erosion was significantly higher than in patients without erosion. Similarly, patients with significant functional impairment (HAQ-DI ≥1) had significantly higher mean MMP-3 levels compared with RA patients without significant disability. Serum MMP-3 is a potential biomarker and prognostic factor for radiographic joint damage and functional disability in RA.

A study conducted in 2012 demonstrated that measuring baseline serum MMP-3 levels enhances the predictive value of anti-CCP in determining long-term radiological outcomes in patients with rheumatoid arthritis. The results suggested that MMP-3 also influences pathological processes that are independent of anti-CCP but are fundamental to the assessment of radiological progression. Hattori and colleagues concluded that measuring baseline MMP-3 levels, in conjunction with other serological markers and clinical measurements, may provide important prognostic information for patients with early RA.

Predicting remission and the likelihood of therapeutic success is just as important in clinical practice as assessing a poor prognosis. Numerous clinical trials have been conducted and have confirmed the usefulness of MMP-3 as a supplement to routine tests.

Hattori and his team analysed data from over 1,300 patients in clinical practice and investigated the utility of serum MMP-3 compared with other markers. They found that MMP-3 measurement was a more effective predictive marker for clinical remission (SDAI ≤ 3.3) and maintenance of normal function (HAQDI ≤ 0.5) than CRP levels. They concluded that MMP-3 measurement should be used in combination with CRP or other parameters of disease activity to assess clinical remission.

Houseman and colleagues demonstrated an association between specific baseline biomarkers/clinical characteristics, including MMP-3, and 2-year radiographic progression in patients with RA. This study was extended to 8 years to further investigate the predictive potential. The combined assessment of biomarkers reflecting joint damage, such as baseline MMP-3 levels, existing serological markers and clinical measures, may provide important prognostic information for patients with early RA. This finding is consistent with the conclusions of other studies.

In the field of personalised medicine, the most effective therapy is tailoring the treatment that is most effective for the individual patient. Furthermore, based on the principle of cost-effectiveness, it is no less important to assess whether to discontinue or switch therapy in the event of treatment failure. In this regard, several studies have explored the role of MMP-3 in monitoring. In 2018, Lerner and colleagues concluded in their review that reduced serum MMP-3 levels, as well as mRNA MMP-3 expression in synovial fibroblasts and peripheral mononuclear cells, reflect the therapeutic response, and low levels predict therapeutic success.

According to Takemoto, “our results suggest that improvements in MMP-3 levels are key to predicting the expected efficacy of therapy. If we focus not only on the usual key indicators, but also on changes in MMP-3 levels, this may help to optimise clinical outcomes”.