Background/Purpose

Clinical remission is now an achievable goal in patients with rheumatoid arthritis (RA). Much has been done in order to better understand and define the concept of remission; in the field of ultrasonography (US) some studies have focused on joint synovitis and its significance in terms of prognosis. In the literature, data on the prevalence of tenosynovitis in patients in clinical remission are scarce and its clinical and prognostic significance has not been studied yet. The objective of this study is to assess whether the US tenosynovitis is associated with a decreased risk of flare.

Methods

Sonographic Tenosynovitis Assessment in RheumaToid arthritis patiEnts in Remission (STARTER) is a multicentre cohort study promoted by the Italian Society for Rheumatology (SIR) that includes 26 rheumatology centres recruited across Italy between Oct 2013 and Jun 2014. Ultrasonographers were trained and selected by an inter-reader reliability exercise against a reference standard using static images, setting to 0.7 one ad hoc weighted kappa as entry criterion. Only high level US machines and high frequency probes were allowed. Patients with RA and clinical remission (DAS28 or SDAI or CDAI) were eligible. All patients underwent full clinical evaluation and US examination (synovitis (-S) and tenosynovitis (-T). A 0-3 semiquantitaive score of Grey Scale (GS-) and Power Doppler (PD-) was calculated for wrists, metacarpophalangeal, interphalageal joints and extensor and flexor tendon sheets. Flare was assessed using the flare questionnaire score ranging from 0 (no flare) to 10 (definite flare) [1], dichotomized at the median value (=3). The cross-sectional relationship between presence of GS-T/-S, PD-T/-S were evaluated by logistic models, and presented as odds ratios (OR) and 95%CI, both crude and adjusted for pre-specified confounders. 

Results

A total of 408 RA patients in clinical remission were included in the analyses: 103(25.4%) men, mean(SD) age 56.4(13.5), median(IQR) disease duration 7.1(3.7-13.5) years, median(IQR) remission duration 12 (8-28) months, RF positive 249/360 (69.2%), mean(SD) DAS28 2.1 (0.8), median(IQR) HAQ 0.125(0-0.375), on DMARDs 300 (73.5%), on biologics 161 (39.5%), on glucocorticoids 170 (43.8%).

GS-T was present in 198/373 (53.1%) patients,  PD-T in 88/372 (23.7%),  while GS-S was present in 270/368 (73.4%) patients and PD-S in 171/372 (46.5%). The association between US variables and flare is reported in the Table.

Outcome: flare questionnaire >3	Crude OR (95%CI)	Adjusted* OR  (95%CI)
Grey Scale Tenosynovitis	1.05 (0.69, 1.58)	1.09 (0.68, 1.75)
Power Doppler Tenosynovitis	2.11 (1.29, 3.45)	2.29 (1.29, 4.07)
Grey Scale Synovitis	1.09 (0.68, 1.74)	0.88 (0.50, 1.56)
Power Doppler Synovitis	1.60 (1.05, 2.43)	1.48 (0.91, 2.40)
*age, sex, disease duration, remission duration, musculoskeletal comorbidities, RF, ACPA, DMARDs, biologics, glucocorticoids (oral and injections), NSAIDs.

Using absence of PD-T and PD-S as reference, PD-S alone showed an adjusted OR(95%CI) of 1.45(0.82, 2.58), PD-T alone 3.84(1.33, 11.08) and both PD-S and PD-T 2.55(1.27, 5.10). 

Conclusion

Power Dopper tenosynovitis is independently associated with patient reported flare more strongly than synovial indexes. US-tenosynovitis is new promising feature to identify patients in remission at higher risk of flare. 

[1]. Berthelot JM et al. Ann Rheum Dis 2012;71:1110–1116.

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