Patients without obvious symptoms still at risk of progressive joint damage

Two new studies presented at the European League Against Rheumatism Annual Congress (EULAR 2015) have shown the importance of using ultrasound to identify those Rheumatoid Arthritis (RA) patients in clinical remission who would benefit from more intensive treatment.

Many patients deemed to be in clinical remission still have active joint disease without any obvious symptoms or physical signs, but with risk of further progression of joint damage. Using ultrasound to predict the risk of flare and exacerbation of symptoms will allow these patients to receive additional treatment, preventing further joint damage and subsequent disability. The two studies highlight:

  • For the first time, an association has been demonstrated between ultrasound diagnosis of tenosynovitis (inflammation of the tendon lining) and patient-related flare and symptom exacerbation in symptom-free patients
  • Using high resolution ultrasound to diagnose active subclinical synovitis (inflammation of the joint lining) in RA patients in clinical remission identifies patients who will benefit from more intensive treatment, preventing further joint damage

EULAR recommendations state that remission (absent disease activity) is the target of treatment in patients with RA, and with modern therapeutic strategies, this target can be achieved more frequently. However, around one half of RA patients in clinical remission experiences a disease flare within 24 months.

Ultrasound diagnosis of tenosynovitis a reliable predictor of flare and symptom exacerbation

"Although the role of ultrasound-diagnosed synovitis is well-known in the literature, no data are available for tenosynovitis," said lead investigator Dr. Emanuela Bellis of the Ospedale Mauriziano, Italy. "We have shown, for the first time, that an ultrasound diagnosis of tenosynovitis provides additional valuable information to the established use of ultrasound-diagnosed subclinical synovitis; it should therefore be routinely included in the management of RA patients in clinical remission," Dr Bellis concluded.

The STARTER study, conducted by the Musculoskeletal Ultrasound Study Group of the Italian Society of Rheumatology, evaluated the association between ultrasound-diagnosed synovitis and ultrasound-diagnosed tenosynovitis with the occurrence of flare over a 6-month period in RA patients in clinical remission.

Results confirmed the value of ultrasound-diagnosed synovitis in predicting flare, defined according to the patients' DAS28 score. However, ultrasound-diagnosed tenosynovitis was more specifically associated with flare as defined by symptom exacerbation, and the need to increase treatment.

A total of 427 consecutive patients with RA and clinical remission underwent a full clinical evaluation and ultrasound examination (assessing synovitis and tenosynovitis) at the wrists, hand and finger joints, and extensor/flexor tendon sheets. A flare was defined by an increase either in the DAS28 score >1.2 (or >0.6 if DAS28 '3.2 at baseline), an increase in treatment, or a change of >4 points in the flare questionnaire if FQ<4 at baseline.

Identification and treatment of subclinical active synovitis prevents joint damage progression

"Although the latest recommendations for the treatment of RA focus on the achievement of clinical remission, we have demonstrated that patients with subclinical synovitis as demonstrated by positive power Doppler signals on an ultrasound, should be treated more intensively to reduce the risk of further joint destruction, even when the patient is currently symptom-free," said study investigator Dr. Tadashi Okano, Department of Orthopedic Surgery, Osaka City University Graduate School of Medicine, Japan.

To evaluate the potential benefit of prescribing additional intensive treatment to RA patients in clinical remission, patients in the SCRUM study with ultrasound-diagnosed subclinical synovitis were randomised to receive either an increased dose of methotrexate (MTX) or to stay on their current MTX dose.

Of 134 patients in clinical remission, ultrasound-positive synovitis was found in 101 patients (75.4%) at baseline. After randomisation, 51 patients were assigned to the MTX increasing group and 50 patients to the MTX stable group.

Initial results from the SCRUM study showed that progression of joint damage was significantly suppressed in the MTX increasing group compared to the MTX stable group at week 24 (p=0.007) and week 52 (p=0.038).