In RA, Is Clinical Remission Enough?

Among patients with rheumatoid arthritis (RA) who were in longstanding clinical remission, only a small minority were in strict ultrasound remission, Danish investigators reported.

In a group of 87 patients with RA who had been in clinical remission for at least a year according to the Disease Activity Score in 28 joints based on C-reactive protein (DAS28-CRP), only 7% were found to have scores of 0 on both gray scale and Doppler measurements, according to Lene Terslev, MD, PhD, and colleagues from Copenhagen University Hospital.

As they noted in their study online in Arthritis Research & Therapy, DAS28-CRP score below 2.6 is considered clinical remission, and the median DAS28-CRP score in this group of patients was 1.8.

Yet a Doppler score above 0 in at least one joint was seen in 44% of patients, a gray scale score of 1 or higher in at least one joint was seen in 93%, and a gray scale hypertrophy score of 2 or higher in at least one joint was seen in 54% of patients.

Current recommendations favor a treat-to-target approach in RA, using a DAS28-CRP goal below 2.6 or another endpoint such as the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean remission, which is more stringent and places more emphasis on factors such as comorbidities and work productivity. However, the available recommendations have thus far not required ultrasound confirmation of remission.

Recommendations notwithstanding, the presence of ultrasound-detected subclinical synovitis has been linked with erosion progression and risk of flare in RA.

Ultrasound remission has generally been considered the absence of Doppler activity, while the relevance of gray scale synovial hypertrophy has been unclear.

Therefore, to address questions regarding the adequacy of clinical remission as a treatment goal and the specific contributions of Doppler and gray scale ultrasound findings, Terslev’s group conducted a cross-sectional observational study that included 87 patients with longstanding DAS28-CRP remission.

The ultrasound examination included 24 joints of the elbows, wrists, hands, knees, and feet. Because no formal definition of ultrasound remission has been established, the researchers used three definitions:

• Strict ultrasound remission: gray scale score = 0 and Doppler score = 0

• Semi-strict ultrasound remission: gray scale score ≤ 1 and Doppler score = 0

• Doppler ultrasound remission: Doppler score = 0, irrespective of gray scale score

A total of 45 patients were being treated with conventional disease-modifying antirheumatic drugs (DMARDs) and 42 with biologic therapies, with or without conventional DMARDs.

Patients’ mean age was 61, two-thirds were women, and mean disease duration was 10 years. The strict ACR/EULAR Boolean remission was present in 77%.

“Overall, very little clinical residual disease activity was present, with 79 of the patients (91%) having neither clinically swollen nor tender joints in the 28 joints assessed for DAS28-CRP,” the researchers observed. Only five patients had two swollen joints.

Doppler sum score was 0, but gray scale sum score averaged 6.

Similar ultrasound findings were found, regardless of whether the remission criteria were DAS28-CRP or ACR/EULAR Boolean. Among the 87 patients in DAS28-CRP remission, ultrasound strict remission was present in only 7%, while 37% were in semi-strict remission and 56% were in Doppler remission.

Among the 67 patients meeting the criteria for ACR/EULAR Boolean remission, only 9% were in strict remission, 37% were in semi-strict remission, and 57% were in Doppler remission.

On an additional composite remission score, the Simple Disease Activity Index, the ultrasound scores again were similar, with 9% being strict remission, 40% semi-strict remission, and 59% Doppler remission.

The 7% of patients meeting the criteria for ultrasound strict remission all were receiving biologics.

The importance of gray scale hypertrophy has been debated, where scores of 1, particularly in the joints of the feet, are commonly reported in established RA but also in healthy controls. Yet studies have demonstrated that a gray scale score of 1 is associated with worsening of erosions.

“It therefore appears justified to define true ultrasound remission as strict ultrasound remission with a gray scale score = 0 and a Doppler score = 0, despite that this appears difficult to achieve in routine care,” the researchers wrote.

The observation that subclinical synovitis was common in patients regardless of which clinical composite endpoint was used “challenges the use of clinical composite scores alone for determining a state of remission in established RA patients in routine care,” Terslev and co-authors said.

They added that further studies will be needed to determine whether patients with residual subclinical inflammation might benefit from further adaptations in treatment strategies.

A limitation of the study, the team said, was the cross-sectional design.