Table 4.

Concise summary of papers on the assessment of inflammatory activity at joint level

Papers/design	Diagnostic tests (*: n)	Reference standards (*: n)†	Results	RoB: *
Clinical assessment as reference standard
4 papers (3 CS, 1 CC)21 42 72 88 341 RA patients	Imaging: US (1: 165); OST measure (3: 176)	Clinical evaluation according to physician (2: 132); Clinically swollen joint (2: 109); Clinically tender joint (1: 50)	OST measures as diagnostic test with following types of clinical assessment as reference standard: Clinically swollen: Sens 37%–42% (*1); spec 86%–93% (*1) Clinically swollen and/or tender: PPV: 46%–50% (*1); NPV: 78%–85% (*1) Clinical evaluation according to physician: r=0.63, p<0.0001 (*1) Treatment influenced on the basis of US findings: 51.7% (*1)	H: 4
Imaging as reference standard
14 papers (1 SLR (*14), 9 CS, 2 CC, 1 CS)‡26 31–33 37 41 59 60 67 72 81 83 88 89 RA patients: All patients, n=788 With shoulder pain, n=73	Clinical assessment: Clinically tender joints (2: 102) Clinically swollen joints (3: 163) Biomarkers: IL-2, IL-4, IL-6, IL-10, IL-17, TNF, IFN, VEGF (1: 64) Other imaging measure than reference standard: OST measures (5: 222); US (3: 456); MRI (1: 19); Contrast-enhanced MRI (1: 43); Fluorescence optical imaging (1: 18)	US (8: 526); FolateScan (1: 40); MRI (4: 295)	Clinically swollen joints (*2): Hand and foot joints: NPV 40% (*1) Hand joints: sens 41%, spec 93% (*1) OST measure as diagnostic test with US as reference standard (*5): Hand joints: sens 29%–91%, spec 24%–93% (*4) Wrist: sens 39%, spec 87% (*1) MCP: sens 70%, spec 74% (*1) PIP: sens 29%–83%, spec 64%–89% (*3) US as diagnostic test with MRI as reference standard (*2 of which 1 SLR): sens 64%–91%, spec 60%–94%. SLR concludes: ‘US is a valid and reproducible technique for detecting synovitis in the wrist and finger joints. It may be considered for routine use as part of the standard diagnostic tools in RA.’ None of the other diagnostic tests were replicated using the same diagnostic accuracy measures.	M: 1
				H: 13
Histology as reference standard
1 paper (CS)27 RA patients with at least 1 joint amenable to biopsy, n=15	Imaging: US (GS and PD; 1: 15)	Krenn index of cellular inflammation (1: 15); Krenn lining layer score (1: 15); Inflammatory cell infiltrates (1: 15);	US (GS) as diagnostic test with following histology measures as reference standard: Krenn index of cellular inflammation (r=0.65, p<0.01) Krenn lining layer score (r=0.52, p<0.05) US (PD) as diagnostic test with following histology measures as reference standard: Krenn index of cellular inflammation (r=0.34, s NR) Krenn lining layer score (r=0.48, s NR)	H: 1

*Number of studies.

†For the general established RA population, the clinical assessment of swelling in the joint was deemed as appropriate to assess the presence of inflammatory activity at joint level (ie, in a specific joint). In patients in whom there is explicit doubt about the presence of inflammatory activity, the traditional measures are not trustworthy. Therefore, in studies assessing this population we considered established imaging measures as a more appropriate reference standard.

‡Abstract.

CC, case control; CS, cross-sectional; GS, Grey scale; H, high; IFN, interferon; IL, interleukin; L, low; MCP, metacarpophalangeal; NPV, negative predictive value; NR, not reported; OST, optical spectral transmission; PD, power Doppler; PIP, proximal interphalangeal; PPV, positive predictive value; RA, rheumatoid arthritis; RoB, risk of bias; s, significant; sens, sensitivity; SLR, systematic literature review; spec, specificity; TNF, tumour necrosis factor; US, ultrasonography; VEGF, vascular endothelial growth factor.