The added value of musculoskeletal ultrasound to clinical evaluation in the treatment decision of rheumatoid arthritis outpatients: physician experience matters

Disease activity is a central aspect in the evaluation of patients with rheumatoid arthritis (RA) because it comprises signs and symptoms of the disease, impacts patient reported outcomes and is responsible for the progression of joint damage [1, 2]. Disease activity is reversible, and its abolishment or reduction to desirable levels is the major target of any therapeutic intervention. In clinical practice, it is advisable to regularly evaluate disease activity; a core set of clinical measures [3‐5] and pooled indices that combine a variable number of disease activity measures [6] are available and have shown to be beneficial in following RA patients.

In 2013, the EULAR task force on imaging in RA clinical practice [7] developed 10 recommendations on various aspects of imaging in RA using research-based evidence, expert opinions and recommendations aimed to address clinical questions relevant to current practice and stated that ultrasound was a valuable candidate to detect clinical joint inflammation (superior to clinical examination), monitor disease activity, predict progression and therapeutic response and detect damage and persistent inflammation even when clinical remission was achieved. These recommendations summarized the experience gained in routine clinical practice over more than two decades, in which ultrasound was efficiently incorporated as a bedside method to enable clinical evaluation and therapy monitoring with high patient acceptability; novel scores that evaluated a reduced number of joints had been tested and were found to effectively reflect overall joint inflammation in RA, in addition to being less time consuming [8‐12]. In this clinical context, the German Ultrasound 7 Score (GUS-7) combines soft tissue changes as well as erosive bone lesions in a single ultrasound scoring system [12]; the score concentrates on a small number of joint regions and examination time is reduced to approximately 10–20 min, making it a suitable candidate to integrate into daily rheumatologic practice.

It is generally accepted that disease activity is the most important factor that determines treatment consideration during routine evaluation of an outpatient with RA, although additional factors, such as comorbidities [13], costs/availability of DMARDs [14] and treatment related adverse/events, are increasingly recognized [15]. In addition, although maintained disease activity or remission status might prompt the clinician to suggest a medication change, patient’s willingness to change treatment might affect the final proposal [16]. In a study designed to capture patients with moderate to high disease activity that would prompt a discussion of medications, only in 39% of the study visits did the clinician report a medication change [17].

Ultrasound assessment has certainly improved our accuracy to detect (the level of) disease activity in RA patients, although its real impact on the final treatment proposal in real world practice has not been assessed. The primary objective of this study was to define the percentage of routine clinical scenarios in which GUS-7 findings impacted the treatment indicated by the rheumatologist in an ongoing cohort of early (at cohort inclusion) RA outpatients; we were particularly interested in exploring if the impact differed among rheumatologists categorized by experience, senior (SR) vs. trainee (TR). Additional objectives were to describe GUS-7 findings in our cohort of patients, compare GUS-7 usefulness and factors that impact treatment among physicians and explore GUS-7 patient acceptance.

In the present study, we assessed the impact of adding musculoskeletal ultrasound information to the treatment decisions in an ongoing cohort of early RA outpatients and evaluated if the impact differed according to the experience of the rheumatologist involved in the treatment decision, SR vs. TR; we also compared how both physicians rated additional factors that might impact treatment decisions; finally, we explored patient satisfaction with the radiological assessment.

The study was performed in a real clinical setting of an ongoing cohort of early (at cohort inclusion) RA patients who had been treated since the beginning of their enrollment according to a T2 T strategy with traditional DMARDs (with/without corticosteroids) following current recommendations [27]; in addition, up to 49% of the patients had comorbidities. The simultaneous presence of multiple pathological conditions is more a rule than an exception in RA patients and has important academic issues and implications in daily practice [13]. We consider our results contribute to define the impact of ultrasound in RA patients’ clinical care. Additional strengths of the study were the blinding for ultrasound evaluations and for clinical assessments (between the TR and the SR).

Four years ago, the Targeted Ultrasound Initiative (TUI) group stated that targeting therapy to PD activity provided superior outcomes in RA patients compared with treating to clinical targets alone [28] and undertook an international study in 8 countries to determine the added value of musculoskeletal ultrasound to the state-of-the-art management of RA, the Targeted Ultrasound in RA (TURA) study; the results of the TURA study have not been published yet. In the present study, we found that musculoskeletal ultrasound impacted the treatment decision in a limited number of the clinical scenarios, 20%, and the impact was greater for the lesser experienced rheumatologist, the TR, compared to the SR. The role of ultrasound in RA management has been recently revisited [29], and the need to counterbalance the expanded scientific literature on the generalized benefits of ultrasound in RA management with appropriate strategy trials has been addressed. Two recent studies performed in early RA populations [30, 31] highlighted discrepancies between the potential benefits of adding ultrasound information to the treatment decisions in early RA patient management and the actual impact on clinical and imaging outcomes. In addition, although musculoskeletal ultrasound provides a more accurate additional (to clinical assessment) method for assessing disease activity, its incorporation to a T2 T strategy in early RA patients modified only 29% of all DAS-28-based DMARD decisions and did not impact patient outcomes [32]; this percentage is close to that recently reported by Diaz-Torné et al. [33], who assessed RA patients with a longer disease duration (mean follow-up of 15.5 ± 10.7 years), the majority of them treated with conventional DMARDs (68%); in their study, ultrasound information made a change in the therapeutic decision in 32% of the patients. The above mentioned studies are consistent and highlight the complexity of RA patient management that goes far beyond the assessment of disease activity and even in the clinical context of remission; a careful assessment of the risk-benefit of targeting ultrasound remission also needs to be performed. As recently highlighted by van der Heijde D [34], the ultimate target should be better long-term patient-reported outcomes. We also found that the impact was greater in the TR than in the more experienced rheumatologist. This finding could be related to a greater experience of the SR in early RA and a deeper knowledge of the patients from the clinic, so the SR can be more confident in deciding treatment based on a limited number of traditional medical and serological factors. In addition, young rheumatologists have identified training on novel imaging technologies as among the most important educational needs [35]; a more accurate understanding of novel technology might favor a rapid incorporation to routine clinical practice. Nonetheless, it should be emphasized that both clinicians (the TR and the SR) completed a 12-h course of musculoskeletal ultrasound in rheumatic diseases and that in addition to the GUS-7, 3 other factors among 6 were differently rated by the TR and the SR to impact the treatment decision.

Both physicians agreed on the impact on the treatment proposal in 3 factors (the clinical evaluation of disease activity according to DAS28, the presence and type of comorbidities and the patients’ preferences) and disagreed on the other 3 (the DMARD cost/availability, a tendency to see DMARD-related adverse events and DMARD maximum doses), although the physicians had access to the same patient medical information. The management plan for RA might be a relatively simple task if only disease activity is considered but might become more complex when additional factors are considered; in particular, patients from Latin-America share particular sociodemographic and clinical characteristics that impact their access to health care and commitment with treatment that need to be included in the treatment equation during routine clinical practice [36, 37]. In addition, considerable variation has been observed in doctors’ decisions, and these variations are known to depend on a physician’s medical characteristics and medical experience [38].

In accordance to a greater impact of the ultrasound findings in the TR’s treatment decision vs. the SR’s decision, the TR rated the GUS-7 usefulness significantly higher than the SR in the totality of the clinical scenarios and in those where the GUS-7 impacted the final recommendation. Additionally, both physicians agreed on a higher GUS-7 usefulness in those scenarios where ultrasound findings did impact the treatment. These results suggest that the SR did not discard a priori the potential benefits of incorporating musculoskeletal ultrasound findings in the treatment decision; they rather confirmed that ultrasound assessments were among the most important factors included in the final management proposal.

In the present study, the GUS-7 findings were similar to those previously described in RA patients in whom gray-scale synovitis is frequently observed, even in patients with clinical remission, as were the majority of our patients [39]; tenosynovitis was less frequently identified and confirmed previous publications [12, 40]; erosions were identified in 34% of our patients, similar to what was observed in RA patients (43%) with disease duration proxy to that of our patients [12]; erosions were frequently located in the clinically dominant MTP5 (in addition to the MCP2) as previously published [41]. Interestingly, we found that the MTP2 was the joint most frequently scored with gray-scale synovitis and PD activity; we are unaware of similar findings, although erosions have been frequently described as located in the MTP2 head [41], and there is an association between PD ultrasound activity [42], anatomical and biomechanical factors [43], and a higher risk of erosive disease; our population had a (mean ± SD) body mass index of 25.9 ± 1.8, and 22% were obese.

Finally, patients were highly satisfied with the ultrasound assessment, with minimum discomfort, adequate time requirements and agreed to have ultrasound incorporated to routine clinical assessments, although they did not pay for the study; previous studies have also shown that musculoskeletal ultrasound favors patients’ RA knowledge and their adherence to medication [44, 45].

Limitations of the study need to be addressed. First, a 40% difference between the TR and the SR in the percentage of treatment modification after GUS-7 was estimated; the difference between both physicians was 17%, and the 85 pairs of assessments performed could have been underpowered to test the primary objective. With the sample studied, the study had a 78.2 power to detect the primary objective. Second, the majority of the clinical scenarios described corresponded to remission status, some levels of disease activity (such as high DA level) were underrepresented, and the results might not be generalized to patients with such clinical status; nonetheless, in routine clinical practice, RA outpatients are expected to be in remission or to have low disease activity. Third, an important variable of the GUS-7 evaluation to impact the treatment proposal was the identification of DA; there is no consensus on the optimal scoring system for ultrasound in rheumatoid arthritis [46]. Additionally, DA definition was based on PD activity on at least one area, and low-grade PD signal might not necessarily reflect active synovitis [39]. Fourth, the GUS-7 assessed a limited number of joint sets compared to the clinical evaluation, although the existing literature confirms that they perform as well as extended joint sets [10, 47]. Finally, our study does not assess the adequacy of the final treatment in the ultimate terms of better disease and patient-reported outcomes. We are currently performing a study aimed to address the topic (Ultrasound impact in Rheumatoid Arthritis patient-reported outcomes [ULTRAPRO], ClinicalTrials.​gov Identifier: NCT03228342).

Disease activity is important for the treatment decision during RA patient assessment; in routine clinical practice, additional factors also need to be considered. Musculoskeletal ultrasound added to “traditional rheumatic assessments” impacted the treatment proposal in a limited number of RA outpatients, most of them were classified with remission and low disease activity; the impact was greater in the trainee in rheumatology, who also scored better ultrasound usefulness compared to the senior rheumatologist. Both physicians differed in the impact of additional factors in the final treatment proposal.