Objectives. Advanced imaging modalities have shown that not only joints but also bones and tendon sheaths can be inflamed at diagnosis of RA. We aimed to better understand the time-order in which... Show moreObjectives. Advanced imaging modalities have shown that not only joints but also bones and tendon sheaths can be inflamed at diagnosis of RA. We aimed to better understand the time-order in which the inflamed tissues respond to DMARD treatment. Also, because ACPA status may reflect a different pathophysiology, differences in time-order of inflammation decrease were hypothesized between these disease types.Methods. A total of 216 consecutive patients presenting with RA (n = 1 7 6) or undifferentiated arthritis (n = 40) , who all started with conventional synthetic DMARD treatment, were studied. 1.5T contrast-enhanced hand and foot MRIs were performed before treatment and after 4, 12 and 24 months. Cross-lagged models evaluated the influence of two time patterns: a simultaneous pattern (`change in one inflammatory feature associated with change in another feature') and a subsequent pattern (`change in one inflammatory feature preceded change in another feature'). ACPA stratification was performed.Results. The median symptom duration at presentation was 13 weeks. Forty-four percent of patients was ACPA-positive. All pairs of inflammatory features decreased simultaneously in all time intervals (0-4/4-12/12-24 months; P< 0.05). Moreover, time-orders were identified: synovitis decrease preceded tenosynovitis decrease (0-4 to >4-12 months; P=0.02 and 4-12 to >12-24 months; P=0.03). Largely similar results were obtained in both ACPA subgroups. Additionally, in ACPA-positive but not ACPA-negative patients, synovitis decrease preceded osteitis decrease (4-12 to >12-24 moths; P= 0.002).Conclusion. This study increased the understanding of the response to treatment on the tissue level. In addition to simultaneous decrease of inflammation, synovitis decrease preceded tenosynovitis decrease. Differences in timeorder of inflammation decrease between ACPA subgroups suggest differences in underlying inflammatory pathways. Show less
Niemantsverdriet, E.; Dakkak, Y.J.; Burgers, L.E.; Bonte-Mineur, F.; Steup-Beekman, G.M.; Kooij, S.M. van der; ... ; Helm-van Mil, A.H.M. van der 2020
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... Show moreBackground: 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. Show less
Boer, A.C.; Wouters, F.; Dakkak, Y.J.; Niemantsverdriet, E.; Helm-van Mil, A.H.M. van der 2020
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... Show moreObjectives. 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. Show less
Matthijssen, X.M.E.; Wouters, F.; Boeters, D.M.; Boer, A.C.; Dakkak, Y.J.; Niemantsverdriet, E.; Helm-van Mil, A.H.M. van der 2019
