Researchers have found that despite apparent disease remission in rheumatoid arthritis (RA), the presence of foot synovitis should prompt escalation of therapy to improve functional outcomes and prevent long-term joint damage, according to findings published in Arthritis Care & Research.
“Our findings emphasize the importance of examining the ankle and foot as a part of the routine management of patients with RA,” wrote Mihir D. Wechalekar, MD, FRACP, PhD, and colleagues from the Repatriation General Hospital, South Australia. “Given the impact of foot synovitis on stability of remission, radiological progression, and independent impact on quality of life, decisions should not be made solely on the basis of disease activity scores (DAS) that omit foot joints.”
In order to (1) investigate correlations between DAS and foot synovitis, (2) analyze the radiographic progression in patients with foot synovitis, and (3) assess functional outcomes of foot synovitis over time, researchers recruited 266 participants above the age of 18 who presented with early RA (<12 months) to the Early Arthritis Clinic at the Royal Adelaide Hospital between 2000-2014. The participants were DMARD-naïve at the start of the study, and were diagnosed with RA according to the 1987 revised American College of Rheumatology (ACR) or the 2010 ACR/EULAR criteria.
The researchers also sought to evaluate the effectiveness of various DAS and remission measures — both those that require a full joint count including ankles and feet (such as the ACR Boolean-based criteria) — and those that omit joint counts of the ankles and feet (including the 28-joint count disease activity score (DAS28), the Clinical Disease Activity Index (CDAI), and the Simplifed Disease Activity Index (SDAI)).
At the beginning of the study, the participants began initial treatment with triple DMARD therapy (methotrexate 10mg weekly, sulfasalazine 500mg twice daily, increased to 1gram twice daily over 3 weeks, and hydroxychloroquine 200mg twice daily).
To achieve DAS28-erythrocyte sedimentation rate (DAS28-ESR) remission, treatment was escalated by increasing methotrexate to a maximum of 25mg weekly followed by addition of leflunomide, another DMARD, or a biologic DMARD according to a predefined algorithm. If deemed necessary, the participants were permitted to take parenteral glucocorticoids (typically 120 mg IM depot methyl prednisolone), but oral corticosteroids and NSAIDs were actively discouraged. If participants were using corticosteroids at the beginning of the study, they were tapered and discontinued whenever possible.
The researchers reviewed the participants’ conditions every 3-6 weeks. The presence of tender and swollen joints, as well as the presence or absence of foot synovitis, was assessed. Foot synovitis was considered to be present if any of the fore-, mid-, or hind-foot joints were tender and swollen.
The researchers defined remission as DAS28-ESR or C-reaction protein (CRP) score of <2.6, CDAI score of ≤ 2.8, or SDAI score of ≤ 3.3. Patients had yearly radiographic assessments, which were scored using the Sharp modified van der Heijde (SvH) method.
The researchers found that in the first 3 years, RA disease activity fluctuated with patients transitioning back and forth between remission and non-remission. They found that the average length of time in remission was substantially shorter for SDAI/CDAI [1.0 years (95% CI 0.6, 1.4) and 1.0 years (95% CI 0.7, 1.5) respectively] than for DAS28 based remission [2.0 years (95% CI 1.35, 2.7)].
“We included foot synovitis as a covariate to determine if [its presence] affected the probability of transitioning from remission to non-remission, and found that foot synovitis significantly influenced the transition intensities. Patients in DAS28(ESR), SDAI, and CDAI remission with foot synovitis were approximately twice as likely to relapse compared to patients in remission without foot synovitis,” the researchers wrote.
“Our study confirms and extends our previous findings concerning the underestimation of disease activity using DA measures that omit foot joints,” the authors stated. “When these criteria are used to define remission, a substantial proportion of patients have ongoing foot synovitis, which predicts relapse of standard disease activity measures, radiographic progression, and worse functional outcomes.”
Summary and Clinical Applicability
Disease activity measures that omit assessment of foot joints are only modestly able to detect foot synovitis over time.
Because foot synovitis in RA patients in remission predicts a relapse into non-remission and worse long-term radiographic and functional outcomes, attention should be paid to the ankles and feet when assessing disease activity in RA patients. If foot synovitis is detected, therapy should promptly be escalated to prevent long-term joint damage and to improve functional outcomes.
Wechalekar M, Lester S, Hill CL, et al. Active Foot Synovitis in Patients with Rheumatoid Arthritis: Patients with Foot Synovitis in Apparent Remission have Unstable Remission Status, Radiographic Progression and Worse Functional Outcomes. Arthritis Care Res. 2016; doi:10.1002/acr.22887.