What is the added value of ultrasound joint examination for monitoring synovitis in rheumatoid arthritis and can it be used to guide treatment decisions? A systematic review and cost-effectiveness analysis

Background

Synovitis (inflamed joint synovial lining), in rheumatoid arthritis (RA) can be assessed by clinical examination (CE) or ultrasound (US).

Objective

To investigate the added value of US, compared to CE alone, in RA synovitis, to clinical and cost-effectiveness.

Data sources

Electronic databases, inception-October 2015, including MEDLINE, EMBASE and Cochrane Databases.

Review methods

A systematic review sought RA studies, comparing additional US with CE. Heterogeneity in intervention, comparators and outcomes precluded meta-analyses. Systematic searches of costeffectiveness and US, and treatment-tapering studies (not necessarily including US) were undertaken.

Mathematical model

A model was constructed that estimated, for patients in whom drug tapering was considered, the reduction in costs of disease modifying drugs (DMARDs) and serious infections, at which the addition of US had a cost per quality adjusted life year (QALY) gained of £20,000 and £30,000. Further, the reduction in the costs of DMARDs at which US become cost-neutral was also estimated.

For patients in whom dose escalation was being considered, the reduction in patients not escalating treatment and in serious infections at which the addition of US had a cost per QALY gained of £20,000 and £30,000 was estimated. The reduction in patients escalating treatment for US to become cost-neutral was also estimated.

Results

Fifty-eight studies were included. Two RCTs compared adding US to a DAS-based treat-to-target strategy for early RA patients. The addition of PDUS to DAS28 based treat-to-target strategy in TaSER reported no significant between group difference for change in DAS44. This study found the PDUS group had significantly more patients attaining DAS44 remission (p=0.03). ARCTIC found the addition of PDUS and GSUS to a DAS based strategy did not produce a significant between group difference in the primary endpoint: composite DAS<1.6, no swollen joints, and no progression in van der Heijde-modified total Sharp Score (vdHSS). ARCTIC did find the erosion score of vdHS had a significant advantage for US group (p=0.04). Erosion in the TaSER study did not find a significant group difference. Other studies suggested PDUS was significantly associated with radiographic progression, and that US had added value for wrist and hand joints rather than foot and ankle joints. Heterogenity between trials made conclusions uncertain. No papers were identified reporting cost-effectiveness of US in monitoring synovitis. The model estimated an average reduction of 2.5% in costs of biological disease-modifying anti-rheumatic drug (bDMARDs) would be sufficient to offset the costs of three-monthly US. The money could not be recouped if oral methotrexate was the only drug used.

Limitations

Heterogeneity of trials precluded meta-analysis. Therefore, no summary estimates of effect were available. Additional costs, and health related quality of life decrement, relating to a flare following tapering or disease progression have not been included. The feasibility of increased US monitoring has not been assessed.

Conclusion

Limited evidence suggests US monitoring of synovitis could provide a cost effective approach to selecting RA patients for treatment tapering or escalation-avoidance. Considerable uncertainty exists for all conclusions. Future research priorities include evaluating US monitoring of RA synovitis in longitudinal clinical studies.