The results of the present study suggests that there is no difference of MRI data (synovitis and oedema bone) between patients ,treated with Tocililizumab, in remission or LDA using composites scores and patients with disease activity state. Thus clinical remission would be different from the imaging remission.
Rheumatoid arthritis is a chronic inflammatory immune-mediated disease characterized by polyarticular synovitis that can lead to joint destruction with impairment of function and quality of life. With recent improvements in the treatment of rheumatoid arthritis, remission has become an achievable goal for a large proportion of RA patients, and remission is now a defined target in current RA guidelines. However, there is concern about whether current criteria reflect true remission characterized by the abrogation of synovitis and consequently, a lack of radiographic progression [5
Different studies have shown that progression of radiographic joint damage may occur in clinical remission, regardless of the choice of remission definition. This may be explained by subclinical inflammation [7
Sub-clinical inflammation detected by modern imaging techniques such as ultrasonography and magnetic resonance imaging is present in the majority of patients in clinical remission, and is associated with progressive joint damage and disease activity flare in these patients [8
Various definitions of remission in rheumatoid arthritis (RA) have been proposed. Different tools for evaluation of RA activity include the disease activity score of 28 joints (DAS 28), simplified disease activity index (SDAI), clinical disease activity index (CDAI), and newer ACR/EULAR remission criteria and cut points for remission according to these indices have been defined. However, all available remission criteria may ignore important aspects of RA, including physical function and radiographic damage [1
The initiative to treat rheumatoid arthritis to achieve remission has impacted clinical practice internationally [5
]. The use of composite disease activity measures has been advocated to assess disease in preference to ‘clinical judgment’. There are several composite measures which correlate well, higher values having poor functional and radiologic outcomes, but there remains disagreement in classifying disease activity states. Disease activity score assessing 28-joint (DAS28) versions using erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) have good correlation but not equivalence but it’s overestimated remission compared to all other criteria [10
]. The American college of rheumatology (ACR) and the European league against rheumatism (EULAR) have defined remission as a simplified disease activity index (SDAI) value of ≤ 3.3 (index-based definition). The SDAI is statistically comparable to DAS28, but comparable DAS28 cutoff scores may need downward revision.
Aletaha et al. suggested that DAS28-ESR 2.4 more suitably reflected remission. Matsui et al. suggested that DAS28-CRP underestimated disease activity. Inoue et al. found DAS28-CRP 2.3 matched DAS28-ESR remission in Japanese patients [10
].The present study suggests that composite scores overestimate remission and patients retain subclinical inflammation found on MRI. Our results join the various studies that have proven the dissociation between clinical remission according different composite scores and remission in imaging either by ultrasound (Ramirez J et al. [11
]) or MRI (Gandjbakhch F et al. [12
]) or both (Foltz V et al. [13
The term remission is still ill-defined, and the various remission criteria allow different degrees of disease activity to be called remission. Nevertheless, remission as a reflection of no, or at the most, minimal disease activity ought to ensure maximal reversal, preferably normalization of functional impairment and minimal progression of joint destruction, ideally halt and even healing of joint destruction [14
However, stringent criteria are needed to define remission status, as some criteria in current use allow for considerable residual disease activity [15
]. In recent years, ultrasound and magnetic resonance imaging techniques have revealed that a significant percentage of patients classified as being in clinical remission exhibit different grades of synovitis, and a subgroup of these patients suffer flares and/or joint damage during follow-up [6
Ultrasound and MRI can detect inflammation that predicts subsequent joint damage, even when clinical remission is present and can be used to assess persistent inflammation. Magnetic resonance imaging (MRI) provides a greater sensitivity than clinical examination and radiography for assessing disease activity [7
]. The role of imaging in the detection of inflammation and subsequent prediction of outcome has been discussed previously. There is good evidence to support the disparity between clinical remission and evidence of ongoing inflammation seen with various imaging modalities. Power doppler activity has been found in 15%-62% of patients in clinical remission according to DAS 28, American college of rheumatology or simplified disease activity index remission criteria, MRI synovitis in 96% and bone oedema in 52%. In one study, 60% of patients in disease activity score remission had increased uptake on scintigraphy. The presence of ultrasound synovial hypertrophy, power doppler activity and MRI synovitis at baseline in clinical remission has been shown to be significantly associated with structural progression at 1 year, even in asymptomatic joints.
Baseline ultrasound inflammatory activity in clinical remission also seems predictive of future disease flare, with 20% of patients experiencing a flare within 12 months in the absence of baseline ultrasound power doppler activity, compared with 47% in patients with baseline power doppler activity (p<0.009). Although radiographic progression can still be seen in clinical remission, individuals with sustained clinical remission show fewer signs of structural progression compared with patients with clinically relapsing disease [18
In summary, sustained remission is seen in a significant proportion of patients under routine clinical care. However, different remission criteria have different stringencies and the SDAI and CDAI criteria appear to be the most stringent ones currently validated, allowing for only minimal residual joint counts and thus reflecting a state of no active disease more closely than other scores [14
In the present study, defining remission by DAS 28 or SDAI or CDAI or ACR EULAR criteria, the RAMRIS bone oedema, as well as RAMRIS synovitis did not differ by level of disease. Although MRI and ultrasound are currently one of the criteria for remission in RA, further studies are needed in particular to determine the threshold definition of remission on MRI and therapeutic threshold intervention.