Remission in rheumatoid arthritis: is it all the same?

Abstract

Remission is the key treatment goal in rheumatoid arthritis and should provide the optimal state for patients. Clinical remission criteria are based on composite scores of disease activity and are widely used in clinical practice and trials. With the use of biologic therapies and treat to target strategies, rates of clinical remission have significantly improved. Despite achieving this target, many patients demonstrate structural and functional deterioration. This raises the question regarding the validity of clinical criteria, although they have evolved significantly over the years. Imaging modalities such as ultrasound have been described as more accurate methods of assessing the remission state compared with clinical assessment alone. Furthermore, immuno-pathological assessments are gaining significant interest as this would enable assessment of disease activity at the primary site of pathology. Further research is required to develop accurate biomarkers of remission. We aimed to review the evolution of remission criteria in rheumatoid arthritis to date and to evaluate novel concepts in and the future of defining remission.

Keywords:

• biomarkers
• classification criteria
• comprehensive disease control
• disease-modifying anti-rheumatic drugs
• remission
• rheumatoid arthritis
• T-cell immunology
• ultrasound

Financial & competing interests disclosure

This work was supported by the Leeds Institute of Rheumatology and Musculoskeletal Medicine. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Remission is the optimum treatment target in rheumatoid arthritis and should represent the absence of all articular and extra-articular inflammation (and immunologic activity). The European League Against Rheumatism have highlighted the importance of remission as an outcome in their recent recommendations. Rates of clinical remission are increasing with the advent of biologic disease-modifying antirheumatic drug therapies and treat to target strategies.

• Achieving clinical remission may not always be associated with good outcomes, specifically with regard to structural progression and functional deterioration. Current remission criteria/composite disease activity scores are largely subjective and do not consider sub-clinical inflammation. Thus, the validity of these criteria remains questionable. Furthermore, there is no universal definition of remission.

• With the achievement of sustained remission, the reduction and discontinuation of biologic therapies has emerged as an important consideration in order to help minimize drug-induced side effects and maximize cost–effectiveness. Such novel treatment paradigms require robust biomarkers and predictors of sustained remission.

• Power Doppler ultrasonography and MRI are thought to more accurately define the remission state by assessing inflammation and structural progression more specifically compared with clinical assessment alone.

• Immune dysregulation plays a major role in the pathogenesis of rheumatoid arthritis. T-cell subset analysis and multi-biomarker assays as markers of disease activity/remission is a novel concept gaining heightened interest.

• Patient perceived remission is complex and may not directly reflect disease activity. Further work is required to evaluate the psychosocial contribution to disease activity assessment.

• Comprehensive disease control (CDC) has emerged a as a potential method to assist with defining the remission state in rheumatoid arthritis. It describes the principle of the simultaneous control of inflammation, attainment of normal physical function and the absence of radiographic progression.

• Multi-level assessment of remission, for example, clinical, imaging, immunological and functional/patient perception measurements could provide a more comprehensive and accurate definition of remission. This could facilitate risk stratification and more patient-specific treatment strategies. Further research is required to develop and validate biomarkers of remission.

Notes