Silent progression in patients with rheumatoid arthritis: is DAS28 remission an insufficient goal in RA? Results from the German Remission-plus cohort

Remission is the ultimate goal in RA-therapy. This has been underscored by successful applications of the Treat-to-Target (T2T)-strategies in studies and clinical practice in the last few years [2]. Interestingly, MRI does not always reflect clinical improvement, but on the contrary, does show persisting or progressive joint pathologies in a considerable number of cases in most studies [25, 26]. However, the presence of erosions is associated with a high risk of progression of the disease, while this was only shown for erosions in conventional x-rays, yet [27, 28]. Up until now, therapy response criteria like the well-established EULAR response criteria are based on different constellations of clinical data, while matching MRI criteria are not available. In our study, a high number of 94% of patients showed erosions on MRI in at least one region. Importantly, roughly 40% of all patients who improved in DAS28 or who were in EULAR-defined remission, showed an increase of MR-detectable erosions after 12 months. Approximately 72% of these patients who worsened in ERO-subscore showed a subscore-deterioration of at least 2 points, so that an inaccuracy of the measurement is unlikely and a veritable increase of the MR-detectable erosivness must be assumed. Moreover, there was no relevant distinction between early and late RA, as even patients with a short disease-duration (less than 6 months) progressed.

The course of erosive changes depended on EULAR response in the current study: patients showing DAS28 improvement but EULAR non-response presented an increase of erosiveness in almost 72% of the patients, while only 31% of patients with good EULAR response had progressive erosions in MRI. Thus, our data is in accordance with a study by Van Gestel et al. who demonstrated that the improvement regarding the EULAR-response criteria is associated with less disease progression considering the clinical and conventional radiological course (highly sensitive imaging tools like MRI were not considered in this study) [8]. In contrast, it has been demonstrated that up to 20–30% of patients reaching clinical remission showed progressive erosive joint damage (silent progression) [9, 29]. Regarding the presented data, the proximal MCP-2 joints were most frequently affected by worsening in the ERO-subscore followed by the trapezoid bone and the proximal MCP-joints 3 and 4. The PIP joints were almost not affected (1/29). Regarding our additional analyses for possible predictive markers for silent progression (age, sex, antibody status, systemic inflammation (CRP) and RAMRIS-subscores), there were no statistical significant associations. However, we note that the study was not powered for specific subgroup analysis. It is known that erosive changes and BME detected by MRI lead to bone erosions which can be depict by conventional x-rays later on [16]. There is a lot of evidence that erosive progression in conventional x-rays is related to functional loss in the course of disease [30‐32], while there is a lack of long term MRI data investigating the functional meaning of MR-detectable erosions, yet. Regarding that, long-term studies focused on this question are urgently needed.

Due to these issues, supplementary use of MRI scans could be of additional value to evaluate the therapy response, for example by using a smaller field of view to achieve a shorter examination time. In summary, MRI data in clinical routine confirm a high rate of silent progression despite DAS28 improvement or remission.

This study has some limitations. First, low-field MRI is used which is known to have a poorer local resolution in comparison to high-field MRI. Moreover, this multicentre study was a “real life” study without a static protocol, so that some patients were lost to follow-up or were excluded due to incomplete data. The study is not controlled for confounders such as RF, CCP-status, smoking or ethnicity. Moreover, we cannot completely exclude that progressive erosiveness detected by low-field MRI overestimates the risk of progression. In addition to that, it must be recognized that erosions were scored by MRI which is known as a very sensitive tool and could lead to occasionally over-interpretation. Hence, some sequences (for example STIR-sequences) are not fully comparable to high-field MR-scans due to the poorer resolution. To solve this last issue, both compound scores, such as the DAS28 and MRI based scores (e.g. RAMRIS), should be evaluated against gold standards such as functional or conventional radiological outcome measures in the long term in future studies.