Criteria Associated with Treatment Decisions in Juvenile Idiopathic Arthritis with a Focus on Ultrasonography: Results from the JIRECHO Cohort

In this study, we investigated the factors associated with therapeutic modifications in patients with JIA, focusing on ultrasonography. The factors were evaluated in a cohort of patients with JIA who benefited from MSUS in expert centres [21].

The data of 185 visits were analysed. As the cohort was recent, we used the number of visits for our sample instead of the number of patients, which allowed us to have a larger sample. Moreover, when checking the data, we noticed that some important data were missing from the medical visits as the presence of clinical and US synovitis and we excluded them. This explains why not all patients in our study had a follow-up visit.

First, the presence of synovitis in B-mode US was not statistically associated with therapeutic escalation, although the number of joints with synovitis was higher for patients whose treatments were intensified. Moreover, the presence of synovitis in PD-mode US was not significantly higher in the “therapeutic escalation” group. Additionally, the presence of grade 2 or 3 synovitis in B-mode was higher in patients with “therapeutic escalation” compared with patients with “stable therapeutic or de-escalation”, but not statistically significant.

Others factors associated with treatment modification were analysed, and the presence of arthritis on clinical examination of the ten most commonly affected joints in JIA (elbows, wrists, second MCP joints, knees, ankles) was not associated with the intensification of therapy. The major factors associated with therapeutic decisions, especially treatment escalation, were based on patient outcome, disease activity scores and biological activity markers. Indeed, the physician’s and patient’s VAS scores were both significantly higher in patients with therapeutic escalation, as well as the cJADAS and CRP and ESR levels. Secondly, second MCP tenderness was more elevated in patients with stable treatment than in patients with therapeutic intensification. This elevation could suggest that joint tenderness is sometimes considered more as a chronic pain than a sign of disease activity. Overall, the ROC curve analyses showed that the physician’s VAS score, the cJADAS, the inflammatory biological markers and the presence of at least one joint with synovitis in B-mode US had moderate Se and Sp.

Regarding treatment de-escalation, we did not find any association between MSUS, clinical or biological items and treatment decisions except for CRP lower levels. Thus, in our study, we were unable to determine how the physician decided on decreasing treatments. Once again, the presence of synovitis on US was not significantly different in patients with therapeutic de-escalation compared with patients with stable treatment. However, for patients with therapeutic de-escalation, there were fewer joints with grade 2 or 3 synovitis in B-mode US. We hypothesize that there was no significant difference because of the small number of patients in this group.

The role of MSUS in patients with JIA is under investigation [23]. Ultrasound-detected synovitis have been shown to be common in patients with JIA in clinical remission. Rebollo-Polo et al. [24] also demonstrated that patients with JIA who met the criteria for clinical remission showed pathologic findings in B-mode or PD MSUS. However, Nieto-González et al. [25] reported that subclinical synovitis detected by MSUS was not a predictor of flares following TNF inhibitor therapy tapering in a JIA population. Thus, persistent inflammation could be detected by MSUS, but its significance has not yet been elucidated. Therefore, the relevance of these findings in therapeutic decisions is uncertain.

In adults, the role of MSUS is clearer [26]. In patients with RA, it has been demonstrated that MSUS found more synovitis than clinical joint examination, especially in B-mode and for the shoulders, wrists and metatarsophalangeal joints [27]. Naredo et al. [28] showed that, in RA, synovitis on US was better correlated with CRP and ESR than physical examination findings. This study indicates that therapeutic decisions in RA could depend on MSUS complementary to clinical assessment. In a literature review on the evaluation of structural damage related to RA, MSUS appeared to be sensitive in detecting synovitis and erosions [29]. Studies have shown that patients with RA in clinical remission could have subclinical synovitis that could cause structural damage [30, 31]. Thus, MSUS could help therapeutic decisions to achieve remission.

Our study had some limitations. First, the SARS-CoV-2 pandemic led to a delay in patients’ follow-up, which could also explain why the number of visits was lower than expected. Second, the study was not blinded. The clinician was aware of all the patients’ characteristics, and this could have lessened the impact of US in comparison to clinical characteristics. Third, we selected patients who underwent MSUS of the ten most commonly affected joints in JIA: the second MCP joints, wrists, elbows, knees and ankles. Collado et al. [32] have previously shown the pertinence and feasibility of a reduced US ten-joint evaluation. Moreover, it appears difficult to analyse all the joints via US in children. However, in daily practice, this score should be suitable to the JIA subtype, clinical examination and stage of disease. Although we analyses the same joints for clinical tenderness and swelling, it seems difficult for physicians not to consider the other joints when examining patients, which might lower the impact of US. Moreover, with a reduced protocol, we may have missed subclinical synovitis, especially for patients with persistent and extended oligoarthritis, representing most of our patients. Fourth, patients were included during their routine follow-up and not at a specific point such as disease diagnosis or flare-up. This explains the low number patients with therapeutic modification, which might have reduced the impact of MSUS and the absence of a significant difference between groups, although the number of joints with synovitis on US differed.

Our study showed several strengths. This study is the first to evaluate the impact of MSUS examinations on therapeutic modifications in patients with JIA in a cohort. Furthermore, the reliability of the sonographers at the different centres, which was evaluated prior to this study, was found to be good [21]. Finally, our study was a real-life study that represents routine practice, which is naturally associated with some limitations.

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