Preventing progression from arthralgia to arthritis: targeting the right patients

• Published in: Nature reviews. Rheumatology Vol. 14; no. 1; pp. 32 - 41
• Main Authors: van Steenbergen, Hanna W., da Silva, José A. Pereira, Huizinga, Tom W. J., van der Helm-van Mil, Annette H. M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-01-2018; Nature Publishing Group
• Subjects: 692/1807/410; 692/308/2779; 692/4023/1670/498; 692/700/139; 692/700/459/1748; Animals; Anti-Citrullinated Protein Antibodies - drug effects; Anti-Citrullinated Protein Antibodies - immunology; Arthralgia; Arthralgia - complications; Arthralgia - diagnosis; Arthritis; Arthritis - complications; Arthritis - diagnosis; Arthritis - drug therapy; Arthritis - prevention & control; Arthritis, Rheumatoid - diagnosis; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - immunology; Autoantibodies; Autoantibodies - immunology; Autoimmunity - drug effects; Biomarkers - metabolism; Care and treatment; Clinical trials; Complications and side effects; Disease Progression; Humans; Immune response; Immunosuppressive Agents - therapeutic use; Inflammation - drug therapy; Medicine & Public Health; Mice; Patients; Predictive Value of Tests; Prevention; review-article; Rheumatoid arthritis; Rheumatology; Risk Factors; Secondary Prevention - methods
• ISSN: 1759-4790; 1759-4804
• DOI: 10.1038/nrrheum.2017.185

Key Points
Early treatment initiation in patients with clinically manifest rheumatoid arthritis (RA) is associated with improved disease outcomes; hence, disease modulation in pre-arthritis phases might prevent the occurrence of clinical arthritis
The inclusion of patients with a low risk of developing RA might dilute possible preventive effects and result in false-negative results in preventive trials
Although a symptomatic phase typically precedes clinical arthritis in patients who develop RA, arthralgia is common and is not specific enough to identify patients at risk of developing RA
The EULAR definition of 'arthralgia suspicious for progression to RA', which identifies patients with arthralgia at risk of developing RA, is a good starting position for preventive trial participant selection
Adequate stratification of patients with arthralgia at risk of developing RA requires a combination of clinical, serological and imaging markers
The symptomatic pre-arthritis phase of rheumatoid arthritis (RA) is hypothesized to be part of a 'window of opportunity' for preventive treatment. This Review discusses the methodological considerations when designing and interpreting preventive trials, and translating findings into clinical practice.
Early treatment is associated with improved outcomes in patients with rheumatoid arthritis (RA), suggesting that a 'window of opportunity', in which the disease is most susceptible to disease-modifying treatment, exists. Autoantibodies and markers of systemic inflammation can be present long before clinical arthritis, and maturation of the immune response seems to coincide with the development of RA. The pre-arthritis phase associated with symptoms such as as joint pain without clinical arthritis (athralgia) is now hypothesized to fall within the aforementioned window of opportunity. Consequently, disease modulation in this phase might prevent the occurrence of clinically apparent arthritis, which would result in a persistent disease course if untreated. Several ongoing proof-of-concept trials are now testing this hypothesis. This Review highlights the importance of adequate risk prediction for the correct design, execution and interpretation of results of these prevention trials, as well as considerations when translating these findings into clinical practice. The patients' perspectives are discussed, and the accuracy with which RA development can be predicted in patients presenting with arthralgia is evaluated. Currently, the best starting position for preventive studies is proposed to be the inclusion of patients with an increased risk of RA, such as those identified as fulfilling the EULAR definition of 'arthralgia suspicious for progression to RA'.