Intervention with methotrexate in patients with arthralgia at risk of rheumatoid arthritis to reduce the development of persistent arthritis and its disease burden (TREAT EARLIER): a randomised, double-blind, placebo-controlled, proof-of-concept trial.

BACKGROUND: Rheumatoid arthritis is the most common autoimmune disease worldwide and requires long-term treatment to suppress inflammation. Currently, treatment is started when arthritis is clinically apparent. We aimed to evaluate whether earlier intervention, in the preceding phase of arthralgia and subclinical joint inflammation, could prevent the development of clinical arthritis or reduce the disease burden. METHODS: We conducted a randomised, double-blind, placebo-controlled, proof-of-concept-trial at the Leiden University Medical Centre, Leiden, Netherlands. Adults aged 18 years or older with arthralgia clinically suspected of progressing to rheumatoid arthritis and MRI-detected subclinical joint inflammation were eligible for enrolment across 13 rheumatology outpatient clinics in the southwest region of the Netherlands and randomly assigned (1:1) to a single intramuscular glucocorticoid injection (120 mg) and a 1-year course of oral methotrexate (up to 25 mg/week), or placebo (single injection and tablets for 1 year). Participants and investigators were masked to group assignment. Follow-up continued for 1 year after the end of the 1-year treatment period. The primary endpoint was development of clinical arthritis (fulfilling the 2010 rheumatoid arthritis classification criteria or involving two or more joints) that persisted for at least 2 weeks. Patient-reported physical functioning, symptoms, and work productivity were secondary endpoints, which were measured every 4 months. Additionally, the course of MRI-detected inflammation was studied. All participants entered the intention-to-treat analysis. This trial is registered with EudraCT, 2014-004472-35, and the Netherlands Trial Register, NTR4853-trial-NL4599. FINDINGS: Between April 16, 2015, and Sept 11, 2019, 901 patients were assessed for eligibility and 236 were enrolled and randomly assigned to active treatment (n=119) or placebo (n=117). At 2 years, the frequency of the primary endpoint was similar between the groups (23 [19%] of 119 participants in the treatment group vs 21 [18%] of 117 in the placebo group; hazard ratio 0·81, 95% CI 0·45 to 1·48). Physical functioning improved more in the treatment group during the first 4 months and remained better than in the placebo group (mean between-group difference in Health Assessment Questionnaire disability index over 2 years: -0·09, 95% CI -0·16 to -0·03; p=0·0042). Similarly, pain (on scale 0-100, mean between-group difference: -8, 95% CI -12 to -4; p<0·0001), morning stiffness of joints (-12, -16 to -8; p<0·0001), presenteeism (-8%, -13 to -3; p=0·0007), and MRI-detected joint inflammation (-1·4 points, -2·0 to -0·9; p<0·0001) showed sustained improvement in the treatment group compared with the placebo group. The number of serious adverse events was equal in both groups; adverse events were consistent with the known safety profile for methotrexate. INTERPRETATION: Methotrexate, the cornerstone treatment of rheumatoid arthritis, initiated at the pre-arthritis stage of symptoms and subclinical inflammation, did not prevent the development of clinical arthritis, but modified the disease course as shown by sustained improvement in MRI-detected inflammation, related symptoms, and impairments compared with placebo. FUNDING: Dutch Research Council (NWO; Dutch Arthritis Society).

Evidence for the presence of synovial sheaths surrounding the extensor tendons at the metacarpophalangeal joints: a microscopy study.

MRI-detected inflammation around the extensor tendons of metacarpophalangeal (MCP-) joints is prevalent in RA and poses a markedly increased risk of RA development when present in arthralgia patients. Such inflammation is called 'peritendinitis' since anatomy literature reports no presence of a tenosynovial sheath at these tendons. However, the presence or absence of tenosynovium at these extensor tendons has never been studied. Therefore, an anatomical and histological study of extensor tendons at the MCP-joints of three embalmed human hands was performed. Immunohistochemical staining showed the presence of markers for synovial macrophages and fibroblast-like synoviocytes bordering a natural dorsal space next to the extensor tendon, suggesting the presence of a synovial lining. This implies that contrast-enhancement on MRI around extensor tendons at MCP-joints observed in early RA and pre-RA likely represents tenosynovitis and that inflammation of this synovial tissue is an early feature of RA.

Which inflamed tissues explain a positive metatarsophalangeal squeeze test? A large imaging study to clarify a common diagnostic procedure.

OBJECTIVES: The squeeze test of MTP joints is frequently used because it is easy and cheap. It is traditionally perceived as a test for synovitis. Besides classic intra-articular synovitis, also tenosynovitis and intermetatarsal bursitis (IMB) represent synovial inflammation, albeit juxta-articularly located. Both are frequently present in RA and occasionally in other arthritides. Therefore we hypothesized that tenosynovitis and IMB contribute to a positive MTP squeeze test. METHODS: A cross-sectional study design was used. A total of 192 early arthritis patients and 693 clinically suspect arthralgia patients underwent the MTP squeeze test and forefoot MRI at first presentation. MRI measurements in age-matched healthy controls were used to define positivity for synovitis, tenosynovitis and IMB. Logistic regression was used. RESULTS: In early arthritis patients, synovitis [odds ratio (OR) 4.8 (95% CI 2.5, 9.5)], tenosynovitis [2.4 (1.2, 4.7)] and IMB [1.7 (1.2, 2.6)] associated with MTP squeeze test positivity. Synovitis [OR 3.2 (95% CI 1.4, 7.2)] and IMB [3.9 (1.7, 8.8)] remained associated in multivariable analyses. Of patients with a positive MTP squeeze test, 79% had synovitis or IMB: 12% synovitis, 15% IMB and 52% both synovitis and IMB. In clinically suspect arthralgia patients, subclinical synovitis [OR 3.0 (95% CI 2.0, 4.7)], tenosynovitis [2.7 (1.6, 4.6)] and IMB [1.7 (1.2, 2.6)] associated with MTP squeeze test positivity, with the strongest association for synovitis in multivariable analysis. Of positive MTP squeeze tests, 39% had synovitis or IMB (10% synovitis, 15% IMB and 13% both synovitis and IMB). CONCLUSION: Besides synovitis, IMB contributes to pain upon compression in early arthritis, presumably due to its location between MTP joints. This is the first evidence showing that MTP squeeze test positivity is not only explained by intra- but also juxta-articular inflammation.

Walking Disabilities in Association With Tenosynovitis at the Metatarsophalangeal Joints: A Longitudinal Magnetic Resonance Imaging Study in Early Arthritis.

OBJECTIVE: The relationship between functional disability and magnetic resonance imaging (MRI) inflammation has been studied for the hands, but has not been well established for the feet, even though walking difficulties are common. Therefore, our objective was to study whether walking difficulties were associated with MRI inflammation at metatarsophalangeal (MTP) joints in early arthritis patients, at diagnosis and during 24 months of follow-up. METHODS: A total of 532 consecutive patients presenting with early arthritis reported on the presence and severity of walking difficulties (Health Assessment Questionnaire question 4a, scale 0-3), and underwent unilateral contrast-enhanced MRI of MTP joints 1-5 at baseline. In total, 107 patients had clinical and MRI data at follow-up (4, 12, and 24 months). MRI inflammation (synovitis, tenosynovitis, and osteitis) was scored in line with the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring system. At baseline, the association of walking disability with MRI inflammation was assessed using regression. Longitudinally, the association between a change in walking disability with a change in MRI inflammation was studied with linear mixed models. RESULTS: At baseline, 81% of patients with walking disabilities had MRI inflammation at MTP joints, versus 68% without walking disabilities (P < 0.001). Total MRI inflammation (i.e., the sum of tenosynovitis, synovitis, and osteitis) was associated with severity of walking disability (ß = 0.023, P < 0.001). Studying the MRI features separately, tenosynovitis, synovitis, and osteitis were all univariably associated with severity of walking disability (P < 0.001, P < 0.001, and P = 0.014, respectively). In multivariable analysis, the association was strongest for tenosynovitis. During follow-up, a decrease in MTP inflammation was associated with a decrease in walking disability (ß = 0.029, P = 0.001); in multivariable analyses only, tenosynovitis was independently associated (ß = 0.073, P = 0.049). CONCLUSION: Of the different inflamed tissues in MTP joints, predominantly MRI-detected tenosynovitis was associated with walking disabilities. Likewise a reduction in tenosynovitis related to a decrease in walking disabilities. These results increase our understanding of the involvement of tenosynovitis in walking disabilities in early arthritis.

Intermetatarsal Bursitis, a Novel Feature of Juxtaarticular Inflammation in Early Rheumatoid Arthritis Related to Clinical Signs: Results of a Longitudinal Magnetic Resonance Imaging Study.

OBJECTIVE: Intermetatarsal bursae in the forefeet possess a synovial lining similar to joints and tendon sheaths. Inflammation of these bursae (intermetatarsal bursitis [IMB]) was recently identified as specific for early rheumatoid arthritis (RA). The present study was undertaken to determine if IMB is indeed an RA feature by assessing the following: 1) the association with other local inflammatory measures (synovitis, tenosynovitis, and osteitis), 2) the association with clinical signs, and 3) whether it responds to disease-modifying antirheumatic drug (DMARD) therapy similarly to other local inflammatory measures. METHODS: One hundred fifty-seven consecutive early RA patients underwent unilateral contrast-enhanced 1.5T forefoot magnetic resonance imaging (MRI) at diagnosis. MRIs were evaluated for IMB presence and for synovitis, tenosynovitis, and osteitis in line with the RA MRI Scoring (RAMRIS) system (summed as RAMRIS inflammation). MRIs at 4, 12, and 24 months were evaluated for IMB presence and size in patients who had IMB at baseline and received early DMARD therapy. Logistic regression and generalized estimating equations were used. Anti-citrullinated protein antibody (ACPA) stratification was performed. RESULTS: Sixty-nine percent of RA patients had ≥1 IMB. In multivariable analysis on bursa level, presence of IMB was independently associated with local presence of synovitis and tenosynovitis, with odds ratios (OR) of 1.69 (95% confidence interval [95% CI] 1.12, 2.57) and 2.83 (95% CI 1.80, 4.44), respectively, but not osteitis. On the patient level, IMB presence was most strongly associated with tenosynovitis (OR 2.92 [95% CI 1.62, 5.24]). IMB presence was associated with local joint swelling (OR 2.7 [95% CI 1.3, 5.3]) and tenderness (OR 1.7 [95% CI 1.04, 2.9]) independent of RAMRIS inflammation. During treatment, IMB size decreased between 0 and 12 months. This decrease associated with decrease in RAMRIS inflammation, which was driven by synovitis decrease. Within ACPA-positive and ACPA-negative RA, similar results were obtained. CONCLUSION: IMB particularly accompanies inflammation of the synovial lining of joints and tendon sheaths, showed a similar treatment response after DMARD initiation, and associates with typical clinical signs. These findings suggest that IMB represents a frequently present novel RA feature of juxtaarticular synovial inflammation.

Increased frequency of intermetatarsal and submetatarsal bursitis in early rheumatoid arthritis: a large case-controlled MRI study.

BACKGROUND: The forefoot is a preferential location for joint and tendon sheath inflammation in rheumatoid arthritis (RA). It also contains bursae, of which the intermetatarsal bursae have a synovial lining. Some small imaging studies suggested that intermetatarsal bursitis (IMB) and submetatarsal bursitis (SMB) are involved in RA, but their association has not been thoroughly explored. Healthy control studies suggested that lesion size might be relevant. We studied the relation between IMB and SMB in early RA, compared to other arthritides and healthy controls, and the relevance of lesion sizes. METHODS: Six hundred and thirty-four participants were studied: 157 consecutive patients presenting with early RA, 284 other arthritides, and 193 healthy controls. All underwent unilateral contrast-enhanced MRI of the forefoot at presentation. Two readers independently scored IMB and SMB and measured transverse and dorsoplantar diameters, blinded to clinical data. Subsequently, consensus was reached. Intra-reader ICC was 0.89. Logistic regression models were used, and test characteristics were calculated. RESULTS: IMB and SMB associated with RA independent of each other (P < 0.001) and independent of age, gender, BMI, RA-MRI inflammation, and anti-CCP-antibodies (P = 0.041). Sensitivity for RA of IMB was 69%, and for SMB 25%. Specificity for IMB was 70% compared to other arthritides, and 84% compared to healthy controls. For SMB, this was 94% and 97% respectively. Regarding lesion size, the groups had considerable overlap: no cut-off size for RA could be distinguished with high sensitivity and specificity. CONCLUSION: Intermetatarsal and submetatarsal bursitis associated with early rheumatoid arthritis, contributing to the emerging evidence that inflammation of juxta-articular soft tissues is an early feature of RA.

TREAT Early Arthralgia to Reverse or Limit Impending Exacerbation to Rheumatoid arthritis (TREAT EARLIER): a randomized, double-blind, placebo-controlled clinical trial protocol.

BACKGROUND: We present a study protocol for a randomized, double-blind, placebo-controlled trial that investigates the hypothesis if intervention in the symptomatic phase preceding clinical arthritis (clinically suspect arthralgia (CSA)) is effective in preventing progression from subclinical inflammation to clinically apparent persistent arthritis. Currently, rheumatoid arthritis (RA) can be recognized and diagnosed when arthritis (joint swelling) has become detectable at physical examination. Importantly, at this time, the immune processes have already matured, chronicity is established, and patients require long-standing treatment with disease-modifying anti-rheumatic drugs. The TREAT EARLIER trial studies the hypothesis that intervention in the symptomatic phase preceding clinical arthritis is more often successful in permanent disease modification because of less matured underlying disease processes. METHODS: A two-level definition to identify patients that are prone to develop RA is used. First, patients should have CSA and recent-onset arthralgia (< 1 year) that is suspect to progress to RA according to the expertise of the treating rheumatologist. Second, patients need to have subclinical inflammation of the hand or foot joints at 1.5 T MRI. The trial aims to recruit 230 participants from secondary care hospital settings across the south-west region of The Netherlands. Intervention will be randomly assigned and includes a single-dose of intramuscular 120 mg methylprednisolon followed by methotrexate (increasing dose to 25 mg/week orally) or placebo (both; injection and tablets) over the course of 1 year. Thereafter, participants are followed for another year. The primary endpoint is the development of clinically detectable arthritis, either fulfilling the 2010 criteria for RA or unclassified clinical arthritis of ≥ 2 joints, which persists for at least 2 weeks. DMARD-free status is a co-primary endpoint. The patient-reported outcomes functioning, along with workability and symptoms, are key secondary endpoints. Participants, caregivers (including those assessing the endpoints), and scientific staff are all blinded to the group assignment. DISCUSSION: This proof-of-concept study is the logical consequence of pre-work on the identification of patients with CSA with MRI-detected subclinical joint inflammation. It will test the hypothesis whether intervention in patients in this early phase with the cornerstone treatment of classified RA (methotrexate) hampers the development of persistent RA and reduce the disease burden of RA. TRIAL REGISTRATION: Dutch Trial Register NL4599 (NTR4853). Registered on 20 October 2014.

The relation between physical joint examination and MRI-depicted inflammation of metatarsophalangeal joints in early arthritis.

BACKGROUND: The relationship between physical joint examination (PE) and MRI-detected inflammation in early inflammatory arthritis has mostly been studied in the hands. Physical examination of MTP joints is considered difficult, and for these joints, this relationship is unknown. Therefore, we studied the concordance of PE with MRI inflammation in MTP joints. Metacarpophalangeal (MCP) joints were included for comparison. METHODS: One thousand seven hundred fifty-nine MTP(2-5) and 1750 MCP(2-5) joints of 441 consecutive patients with early arthritis underwent PE (for joint swelling) and MRI, all evaluated by two assessors. MRI was scored for synovitis, tenosynovitis, and osteitis (summed MRI inflammation). Synovial intermetatarsal bursae may enlarge upon inflammation and become palpable and were therefore also assessed. Analyses (frequencies, GEE) were performed on joint level. RESULTS: PE and MRI were concordant in 79% of MTP joints. Of 1606 non-swollen MTP joints, 83% showed no MRI inflammation and 17% showed subclinical MRI inflammation. Of 153 swollen MTP joints, 48% had MRI inflammation and 52% (79 MTP joints) did not. Of these 79 swollen MTP joints without MRI inflammation, 31 showed intermetatarsal bursitis and 48 joints had none of these MRI abnormalities (this concerned 31% of swollen MTP joints). MTP swelling was statistically independently associated with tenosynovitis (OR 2.21, 95% CI 1.1-4.3) and intermetatarsal bursitis (OR 2.91, 95% CI 1.8-4.8). MTP joints showed subclinical inflammation less often than MCP joints (17% vs. 34%, P < 0.001). Swollen MTP joints showed MRI inflammation less often than swollen MCP joints (48% vs. 88%, P < 0.001). CONCLUSIONS: The absence of swelling of MTP joints in early arthritis is mostly accompanied by the absence of MRI-detected inflammation. Swollen MTP joints are, in addition to synovitis, also explained by tenosynovitis and intermetatarsal bursitis and partly unexplained by MRI. Their clinical relevance must be determined in longitudinal studies.

Rheumatoid Arthritis and Tenosynovitis at the Metatarsophalangeal Joints: An Anatomic and MRI Study of the Forefoot Tendon Sheaths.

Background Although tenosynovitis in the hands is associated with rheumatoid arthritis (RA), it is unknown whether tenosynovitis of the forefoot is associated with RA. Purpose To determine the anatomy of tendon sheaths of the forefoot and the relationship between MRI-detected tenosynovitis at metatarsophalangeal (MTP) joints and RA. Materials and Methods Fourteen forefeet of donated bodies were examined at flexor tendons and extensor tendons for the presence and course of tendon sheaths. In the prospective study between June 2013 and March 2016, newly presenting patients with RA, patients with other early arthritides, and healthy control participants all underwent MRI of unilateral MTP joints 1-5. MRI studies were scored by two independent readers for tenosynovitis, synovitis, and bone marrow edema. The association between the presence of these features and RA was examined by using logistic regression. Results Macroscopically, all extensor and flexor tendons crossing MTP joints demonstrated sheaths surrounding tendons. Microscopically, a synovial sheath was present. MRI evaluation was performed in 634 participants: 157 newly presenting patients with RA (109 women; mean age, 59 years ± 11 [standard deviation]), 284 patients with other early arthritides (158 women; mean age, 56 years ± 17), and 193 healthy control participants (136 women; mean age, 50 years ± 16). MRI-detected tenosynovitis was associated with RA, both when compared with patients with other arthritides (odds ratio [OR], 2.5; 95% confidence interval [CI]: 1.7, 3.9; P < .001) and healthy control participants (OR, 46; 95% CI: 14, 151; P < .001). The association was OR of 2.4 (95% CI: 1.5, 3.8; P < .001) for flexor tendons and OR of 3.1 (95% CI: 1.9, 5.2; P < .001) for extensor tendons. The sensitivity of tenosynovitis in RA was 65 of 157 (41%; 95% CI: 35%, 50%). The specificity for RA was 63 of 284 (78%; 95% CI: 72%, 82%) compared with other arthritides, and three of 193 (98%; 95% CI: 96%, 99%) compared with healthy control participants. Conclusion Tendons at metatarsophalangeal joints are surrounded by tenosynovium. MRI-detected tenosynovitis at metatarsophalangeal joints was specific for rheumatoid arthritis when compared with findings in patients with other arthritides and findings in healthy control participants. © RSNA, 2020 Online supplemental material is available for this article.

Improving the feasibility of MRI in clinically suspect arthralgia for prediction of rheumatoid arthritis by omitting scanning of the feet.

OBJECTIVES: The use of MR-imaging is recommended for the early detection of RA. Next to the small joints of the hands, foot-joints are often involved. Therefore, imaging inflammation of the feet in addition to hands may be informative, but prolongs scan-time and leads to additional costs. We studied the value of MRI of the feet alone and complementary to MRI of the hands in patients with clinically suspect arthralgia (CSA). METHODS: 357 consecutively included CSA patients underwent contrast-enhanced 1.5 T-MRI of hand (MCP2-5 and wrist) and foot (MTP1-5) joints at baseline. Scans were scored for synovitis, osteitis and tenosynovitis. After ⩾1 year follow-up, the development of clinically apparent inflammatory arthritis (IA) was studied. Cox regression was performed and test characteristics were evaluated. Sensitivity analyses were performed for the outcome RA-development (2010-criteria). RESULTS: MRI-detected tenosynovitis of the feet was associated with IA-development, independently from synovitis and osteitis hazard ratio (HR) (95%CI) 4.75 (2.38; 9.49), and independently from ACPA and CRP, HR 3.13 (1.48; 6.64). From all CSA patients, 11% had inflammation in hands and feet, 29% only in hands and 3% only in feet. In line with this finding, the addition of MRI-feet to MRI-hands did not increase the predictive accuracy; the sensitivity remained 77%, while the specificity decreased from 66% to 62%. Sensitivity analyses with RA development as outcome showed similar results. CONCLUSION: Tenosynovitis at the forefeet in CSA predicted IA and RA development. Addition of foot MRI to hand MRI did not increase the accuracy. Foot MRI can be omitted to reduce scan time and costs and increase the feasibility.

Reliability of Magnetic Resonance Imaging (MRI) Scoring of the Metatarsophalangeal Joints of the Foot according to the Rheumatoid Arthritis MRI Score.

OBJECTIVE: The Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) is validated for hand MRI. Its reliability applied to metatarsophalangeal (MTP 1-5) joints is unknown and was studied in early arthritis and clinically suspect arthralgia. METHODS: Patients underwent 1.5 Tesla MRI of MTP, metacarpophalangeal (MCP 2-5), and wrist joints. Two paired readers scored bone marrow edema (BME), synovitis, tenosynovitis, and erosions. Interreader reliability was assessed of 441 consecutive early arthritis patients at baseline, 215 by 2 readers, and the remaining 226 by 2 different readers. Two readers scored baseline MRI of 82 consecutive patients with clinically suspect arthralgia, and 40 randomly selected patients by 9 readers. Intrareader reliability was determined on a random set of 15 early arthritis patients, scored twice by 2 readers. For change scores, 30 early arthritis patients with baseline and 1-year followup MRI were scored by 2 readers. Intraclass correlation coefficients (ICC), Bland-Altman (BA) plots, and smallest detectable change (SDC) were determined. MRI data of MTP joints were compared to wrist and MCP joints. RESULTS: Interreader ICC and mean scores in early arthritis were BME ICC 0.91-0.92 (mean 1.5 ± SD 2.6), synovitis 0.90-0.92 (1.3 ± 1.7), tenosynovitis 0.80-0.85 (1.1 ± 1.8), and erosions 0.88-0.89 (0.7 ± 1.0). In patients with clinically suspect arthralgia, ICC were comparable. Intrareader ICC for inflammatory MRI features were 0.84-0.98, for erosions 0.71 (reader 1), and 0.92 (reader 2). Change score ICC were ≥ 0.90, except erosions (0.77). SDC were ≤ 1.0. BA plots showed no systematic bias. Reliability scores of MTP joints were similar to MCP and wrist joints. CONCLUSION: Status and change MRI scores of BME, synovitis, tenosynovitis, and erosions of MTP joints can be assessed reliably by RAMRIS.

A search to the target tissue in which RA-specific inflammation starts: a detailed MRI study to improve identification of RA-specific features in the phase of clinically suspect arthralgia.

OBJECTIVE: Based on a unique cohort of clinically suspect arthralgia (CSA) patients, we analysed which combinations of MRI features at onset were predictive for rheumatoid arthritis (RA) development. This was done to increase our comprehension of locations of RA onset and improve the predictive accuracy of MRI in CSA. METHODS: In the discovery cohort, 225 CSA patients were followed on clinical arthritis development. Contrast-enhanced 1.5 T MRIs were made of unilateral metacarpophalangeal (MCP) (2-5), wrist, and metatarsophalangeal (1-5) joints at baseline and scored for synovitis, tenosynovitis, and bone marrow edema. Severity, number, and combinations of locations (joint/tendon/bone) with subclinical inflammation were determined, with symptom-free controls of similar age category as reference. Cox regression was used for predictor selection. Predictive values were determined at 1 year follow-up. Results were validated in 209 CSA patients. RESULTS: In both cohorts, 15% developed arthritis < 1 year. The multivariable Cox model selected presence of MCP-extensor peritendinitis (HR 4.38 (2.07-9.25)) and the number of locations with subclinical inflammation (1-2 locations HR 2.54 (1.11-5.82); ≥ 3 locations HR 3.75 (1.49-9.48)) as predictors. Severity and combinations of inflammatory lesions were not selected. Based on these variables, five risk categories were defined: no subclinical inflammation, 1-2 locations, or ≥ 3 locations, with or without MCP-extensor peritendinitis. Positive predictive values (PPVs) ranged 5% (lowest category; NPV 95%) to 67% (highest category). Similar findings were obtained in the validation cohort; PPVs ranged 4% (lowest category; NPV 96%) to 63% (highest category). CONCLUSION: Tenosynovitis, particularly MCP-extensor peritendinitis, is among the first tissues affected by RA. Incorporating this feature and number of locations with subclinical inflammation improved prediction making with PPVs up to 63-67%.

Validity of the rheumatoid arthritis MRI score applied to the forefeet using the OMERACT filter: a systematic literature review.

OBJECTIVE: MRI depicts inflammation and structural damage in rheumatoid arthritis (RA). The validity of MRI-scoring of wrist-joints and metacarpophalangeal-joints according to the RA MRI score(RAMRIS) has been demonstrated. The Outcomes in Rheumatology Clinical Trials (OMERACT) RAMRIS Working Group recently called for validation of the RAMRIS of the metatarsophalangeal (MTP)-joints. Therefore, a systematic literature review was performed to test if the RAMRIS applied to the MTP-joints meets the OMERACT Filter of Truth, Discrimination and Feasibility. METHODS: Medical literature databases up to January 2018 were systematically reviewed for studies reporting on RAMRIS applied to MRI of the MTP-joints in RA. To be included, an article had to contain at least one MRI-feature (synovitis, bone marrow oedema (BME), tenosynovitis, erosion, joint space narrowing (JSN)) and one item from the OMERACT Filter: Truth (face, content and construct validity), Discrimination (test-retest reliability, ability to discriminate in trials, longitudinal construct validity and thresholds of meaning) and Feasibility. RESULTS: Of the 749 retrieved studies, 13 were included, of which 9 provided data on construct validity, 4 on discrimination (3 on reliability, 2 on longitudinal construct validity and 1 on ability to discriminate in trials) and none on feasibility. Construct validity was suggested for BME and erosions, but lacking for synovitis, tenosynovitis and JSN. Data for discrimination remain to be developed for all outcomes. CONCLUSION: According to the OMERACT Filter, the validity of the RAMRIS of the forefeet is insufficient in different aspects. A research agenda was determined.