Effects of RANKL inhibition on promoting healing of bone erosion in rheumatoid arthritis using HR-pQCT: a 2-year, randomised, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the effects of denosumab on erosion healing at 2-4 metacarpophalangeal (MCP) head as determined by high-resolution peripheral quantitative CT (HR-pQCT) in patients with rheumatoid arthritis (RA) with stable disease. METHODS: This was a randomised, placebo-controlled, double-blind study. Patients with RA with disease activity score 28 joints (DAS28) ≤5.1 were randomised (1:1) to subcutaneous denosumab 60 mg or placebo once every 6 months for 24 months. The primary outcome was erosion healing at MCP 2-4 on HR-pQCT at 12 months. The effects of denosumab on erosion and joint space parameters on HR-pQCT and radiographs, disease activity and health assessment questionnaire-disability index (HAQ-DI) were also examined. RESULTS: At 24 months, HR-pQCT images were analysed in 98 patients. One-third of the patients achieved sustained low disease activity throughout the study. At 12 months, changes in erosion parameters on HR-pQCT were similar between the two groups. At 24 months, new erosions (19% vs 9%, p=0.009) and erosion progression (18% vs 8%, p=0.019) were more common in the placebo group than the denosumab group. Erosion healing was seen in a significantly higher proportion of patients in the denosumab group (20% vs 6%, p=0.045) at 24 months. No significant changes in joint space parameters on HR-pQCT, van der Heijde-Sharp erosion score, DAS28 and HAQ-DI were observed in the two groups at 12 and 24 months. CONCLUSION: Although no differences in erosion parameters were observed at 12 months, denosumab was more efficacious than placebo in erosion repair on HR-pQCT after 24 months. TRIAL REGISTRATION NUMBER: NCT03239080.

Management of rheumatoid arthritis: 2019 updated consensus recommendations from the Hong Kong Society of Rheumatology.

The expanding range of treatment options for rheumatoid arthritis (RA), from conventional synthetic disease-modifying antirheumatic drugs (DMARDs) to biological DMARDs (bDMARDs), biosimilar bDMARDs, and targeted synthetic DMARDs, has improved patient outcomes but increased the complexity of treatment decisions. These updated consensus recommendations from the Hong Kong Society of Rheumatology provide guidance on the management of RA, with a focus on how to integrate newly available DMARDs into clinical practice. The recommendations were developed based on evidence from the literature along with local expert opinion. Early diagnosis of RA and prompt initiation of effective therapy remain crucial and we suggest a treat-to-target approach to guide optimal sequencing of DMARDs in RA patients to achieve tight disease control. Newly available DMARDs are incorporated in the treatment algorithm, resulting in a greater range of second-line treatment options. In the event of treatment failure or intolerance, switching to another DMARD with a similar or different mode of action may be considered. Given the variety of available treatments and the heterogeneity of patients with RA, treatment decisions should be tailored to the individual patient taking into consideration prognostic factors, medical comorbidities, drug safety, cost of treatment, and patient preference.

Effect of Treat-to-target Strategies Aiming at Remission of Arterial Stiffness in Early Rheumatoid Arthritis: A Randomized Controlled Study.

OBJECTIVE: To determine the efficacy of 2 tight control treatment strategies aiming at Simplified Disease Activity Score (SDAI) remission (SDAI ≤ 3.3) compared to 28-joint count Disease Activity Score (DAS28) remission (DAS28 < 2.6) in the prevention of arterial stiffness in patients with early rheumatoid arthritis (RA). METHODS: This was an open-label study in which 120 patients with early RA were randomized to receive 1 year of tight control treatment. Group 1 (n = 60) aimed to achieve SDAI ≤ 3.3 and Group 2 (n = 60), DAS28 < 2.6. Pulse wave velocity (PWV) and augmentation index (AIx) were measured at baseline and 12 months. A posthoc analysis was also performed to ascertain whether achieving sustained remission could prevent progression in arterial stiffness. RESULTS: The proportions of patients receiving methotrexate monotherapy were significantly lower in Group 1 throughout the study period. At 12 months, the proportions of patients achieving DAS28 and SDAI remission, and the change in PWV and AIx, were comparable between the 2 groups. In view of the lack of differences between the 2 groups, a posthoc analysis was performed at Month 12, including all 110 patients with PWV, to elucidate the independent predictors associated with the change in PWV. Multivariate analysis revealed that achieving sustained DAS28 remission at months 6, 9, and 12 and a shorter disease duration were independent explanatory variables associated with less progression of PWV. CONCLUSION: With limited access to biologic disease-modifying antirheumatic drugs, treatment efforts toward DAS28 and SDAI remission had similar effects in preventing the progression of arterial stiffness at 1 year. However, achieving sustained DAS28 remission was associated with a significantly greater improvement in PWV. [Clinical Trial registration: Clinicaltrial.gov NCT01768923.].