Table 4

Articles reporting imaging findings alone as risk factors in individuals at risk of RA

Study	Population	Cohort size	Risk factor	Frequency	Outcome
Ultrasound alone
MSK symptoms without arthritis
van de Stadt et al36	Seropositive arthralgia (ACPA and/or RF)	192	US PD signal (joint level)	BL	Development of IA OR=2.9 (95% CI 4.65 to 360)
Nam et al33	Anti-CCP+ with non-specific MSK symptoms	136	US PD signal (patient level) US BE (patient level) USGS ≥2 (patient level)	BL	Development of IA US PD signal: HR 3.7 (95% CI 2.0 to 6.9), p<0.001 US BE: HR 2.9 (95% CI 1.7 to 5.1), p<0.001 US GS ≥2: HR 2.3 (95% CI 1.0 to 4.9), p=0.038
Zufferey et al40	Anti-CCP-negative patients with arthralgia and no synovitis	80	US synovitis (SONAR score)	BL	Progression to RA OR=7.4 (95% CI 1.19 to 42.8), p=0.02
van Beers-Tas et al37	Seropositive arthralgia (ACPA and/or RF)	163	US GS ≥2 (excluding MTP joints) (patient level)	BL	Development of IA HR=3.4 (95% CI 1.6 to 6.8), p<0.01
Pentony et al34	Anti-CCP+ with non-specific MSK symptoms	44	US total PD score in the wrists, MCPJs (1–5) and PIP joints (1–5)	BL Preprogression Progression	Development of IA 54.5% progressors had increased PD signal score longitudinally vs 9.1% non-progressors
Kisten et al38	Anti-CCP+ with non-specific MSK symptoms but no clinical/US inflammation	66	US TSV (patient level)	BL or FU visits	Development of IA RR=3.0 (95% CI 1.8 to 4.8), p=0.001
Hensvold et al39	Anti-CCP+ with non-specific MSK symptoms but no clinical/US inflammation	66	Combined US-TSV on US (patient level) and positive HLA-SE	BL	Development of IA HR=4.9 (95% CI 1.5 to 16), p=0.01
Duquenne et al35	Anti-CCP+ with non-specific MSK symptoms	307	≥1 joint with PD signal	>12M before progression 3–12M before progression <3M before progression	Development of IA in the next 3 months OR=7.52
Early clinical arthritis
Freeston et al41	UA ≤12W of inflammatory arthralgia ±synovitis	50	US GS score ≥3, PD signal ≥1, ≥1 BE	BL	Development of persistent arthritis Probability increased from 34% to 94%
Filer et al42	UA—early synovitis of ≥1 joint and symptom duration ≤3M	58	PD 10 index: summed PD grades of MCP joints 2–3, wrists and MTP joints 2–3	BL	Development of RA PD 10 index combined with Leiden prediction score: AUC 0.962, compared with AUC 0.905 (Leiden score alone), p<0.05
Sahbudin et al43	UA—early synovitis of ≥1 joint and symptom duration ≤3M	107	US digital flexor TSV Positive PD signal in MCP3	BL	Development of RA OR=4.066 (95% CI 1.444 to 11.444), p=0.008 OR=3.078 (95% CI 1.047 to 9.046), p=0.041
MRI±US
MSK symptoms without arthritis
Kleyer et al44	ACPA-positive at-risk individuals	20	MRI TSV at ≥2 sites	BL	Development of RA 5/5 (100%) of individuals who developed RA had MRI TSV at ≥2 sites
Van Steenbergen et al46	CSA	150	Subclinical MRI inflammation	BL	Development of IA HR=5.07 (95% CI 1.77 to 14.50), p=0.002
Boer et al63	Patients with CSA and patients with UA (arthritis <2 years)	225 CSA+201 UA	MRI inflammation ‘corrected’ for MRI abnormalities in healthy individuals	BL	‘Corrected’ versus ‘uncorrected’ MRI inflammation Development of IA at 12 months Accuracy 60% (95% CI 54 to 67) vs 32% (95% CI 26–38) AUC 0.71 vs 0.55 Fulfilment of 1987 RA criteria at 12 months Accuracy 44% (95% CI 38 to 51) vs 22% (95% CI 17 to 29) AUC 0.65 vs 0.52
Hunt et al45	Anti-CCP+ individuals with non-specific MSK symptoms	98	MRI TSV US PD+ ≥2 US GS ≥2	BL	Development of IA HR=4.02 (95% CI 1.91 to 8.44), p=0.002 HR=5.09 (95% CI 1.93 to 13.44), p=0.006 HR=2.69 (95% CI 1.14 to 6.34), p=0.059
Early clinical arthritis
Navalho et al49	Untreated recent onset (<1 year) polyarthritis	32	MRI ECU TSV MRI FT2 TSV MRI synovitis of the radioulnar joint	BL	Development of RA OR=3.21 (95% CI 1.09 to 9.40), p=0.03 OR=9.6 (95% CI 1.17 to 78.93), p=0.03 OR=8.79 (95% CI 1.02 to 75.63), p=0.04
Navalho et al47	Untreated recent onset (<1 year) undifferentiated polyarthritis	4	MRI carpal joint synovitis MRI flexor tendon TSV MRI global joint and tendon count Global MRI and US scores	BL	Development of RA OR=3.64 (95% CI 1.19 to 11.84), p=0.032 OR=5.09 (95% CI 1.62 to 16.05), p=0.005 OR=2.77 (95% CI 1.249 to 6.139), p=0.012 AUC=0.959 and=0.853, respectively, p<0.05
Dakkak et al48	UA (arthritis in ≥1 joint, symptom duration <2 years)	123	MRI TSV in feet adjusted for BME and synovitis of the foot MRI TSV in feet adjusted for CRP and swollen joint count MRI TSV in hands independent of BME and synovitis	BL	Development of RA OR=3.29 (95% CI 1.03 to 10.53) OR=2.14 (95% CI 0.77 to 5.95) OR=3.99 (95% CI 1.64 to 9.69)

HR/OR and CIs have been reported where available.
+, positive; A, abstract only; ACPA, anticyclic citrullinated peptide antibodies; AUC, area under the curve; BE, bone erosions; BL, baseline; BME, bone marrow oedema; CCP, cyclic citrullinated peptide; CRP, C reactive protein; CSA, clinically suspect arthralgia; ECU, extensor carpi ulnaris; FDRs, first-degree relatives; FT, flexor tendons; FU, follow-up; GS, grey scale; IA, inflammatory arthritis; M, months; MCPs, metacarpophalangeal joints; MSK, musculoskeletal; MSUS, musculoskeletal ultrasound; MTPs, metatarsophalangeal joints; PD, power Doppler; PPV, positive predictive value; RA, rheumatoid arthritis; RF, rheumatoid factor; RR, relative risk; TSV, tenosynovitis; UA, unclassified/undifferentiated arthritis; US, ultrasound; W, weeks.