MRI Predicts Flare in Kids With Inactive Arthritis

Two-thirds of children with juvenile idiopathic arthritis (JIA) who had clinically inactive disease were found to have subclinical synovitis on MRI, placing them at risk for disease flare, Italian researchers reported.

In a multivariate analysis, MRI-detected synovitis was the most accurate predictor of active disease among children whose disease was classified as inactive on clinical parameters, with a hazard ratio of 2.45 (95% CI 1.31-4.59, P=0.003), according to Clara Malattia, MD, PhD, of IRCCS Istituto Giannina Gaslini in Genova, and colleagues.

In addition, a high MRI score for bone marrow edema was associated with progression of joint damage, the investigators reported online in Arthritis Care & Research.

As the most common pediatric rheumatic disease, JIA is characterized by ongoing inflammation of the synovium and tendon sheaths. “The primary aim of treatment is to prevent irreversible sequelae by inducing early disease remission that, owing to the significant advances in therapeutic options, has become an attainable goal for most JIA patients,” they wrote.

Currently, disease activity is assessed according to symptoms, clinical examination, and acute phase reactants, although questions have recently been raised as to whether imaging findings should be used to more firmly establish the absence of joint inflammation. It has been shown that persistent synovitis in adults with rheumatoid arthritis is associated with disease flare and joint damage.

To explore the possibility that this might also be the case in JIA, Malattia and colleagues retrospectively reviewed outcomes for 90 JIA patients who had undergone contrast-enhanced MRI from 2012 to 2016. Inactive disease was defined as no arthritis, fever, serositis, rash, splenomegaly, lymphadenopathy, or uveitis; a normal erythrocyte sedimentation rate or C-reactive protein level; physician global assessment indicating no active disease; and duration of morning stiffness no longer than 15 minutes.

Clinical remission on medication was defined as inactive disease for 6 continuous months with treatment, and clinical remission off medication was defined as inactive disease for 12 months following the discontinuation of all anti-arthritis medications.

MRIs were obtained for the wrist and metacarpophalangeal joints, ankle and mid-foot, knee, and hips.

Patients’ median age was 14, and the median disease duration was 8.5 years. Most were girls, and the most common JIA subtype was extended oligoarthritis.

About 17% of patients were in clinical remission off medication, and the remaining 83.3% were on medications, with more than half being treated with biologics.

On MRI, 65.5% of patients had subclinical synovitis and 46.7% had bone marrow edema. Median synovitis and bone marrow edema scores at baseline were 16.7 and 8, respectively.

During a median follow-up of 48 months, 63.3% of patients had a disease flare, at a median time of 1.5 years.

Among the 75 patients who were in clinical remission on medication at baseline, 44% subsequently had discontinued treatment and 36% had reduced the dosage or frequency of use. Among those who had discontinued, 72.7% experienced a flare, as did 53.3% of those who had reduced the dose or maintained the original regimen.

There were no associations between disease flare and disease subtype or duration, patient age, duration of remission, or synovitis on MRI.

Out of 59 patients who had MRI-detected synovitis, 74.6% flared compared with 41.9% of those without synovitis (P=0.002).

Among 54 patients who had radiographs at baseline and follow-up, structural damage progression was observed in 31.5%.

While subclinical synovitis was not associated with damage progression, factors on a multivariate analysis that were associated were age above 17 years (HR 3.51, 95% CI 1.09-11.25, P=0.04) and a bone marrow edema score above 4 (HR 4.40, 95% CI 0.87-22.18, P=0.045). “Histological studies in rheumatoid arthritis patients have shown that bone marrow edema reflects the presence of an inflammatory infiltrate which triggers an osteoclastic response, thus paving the way for bone erosion development,” the researchers observed.

“Our results show that MRI plays an important role in predicting the risk of disease flare and joint deterioration, with potential implications for patients’ management,” they wrote.

“The detection of residual inflammation on MRI may help to identify patients with sustained clinically inactive disease that could more safely undergo treatment reduction or discontinuation,” they concluded.

A limitation of the study was its retrospective design, and longitudinal prospective studies will be required to confirm these results, they noted.