Which patients presenting with arthralgia eventually develop rheumatoid arthritis? The current state of the art

Abstract

Early initiation of treatment in patients with inflammatory arthritis at risk of persistence and/or erosive progression is important because it is associated with a reduced rate of progression of joint damage and functional disability. It has been proposed that a window of opportunity exists, during which disease processes are less matured and disease modification can be more effective. The phase of arthralgia preceding clinical arthritis is likely to be an important part of this window of opportunity, during which treatment might prevent progression to clinical arthritis. Several proof-of-concept trials in individuals with arthralgia are now evaluating this hypothesis. Central to such trials is the ability to identify groups at high risk of rheumatoid arthritis (RA) in whom preventive treatment can be tested. This review describes the relevance of adequate prediction making, as well as the accuracy of different types of predictors (including imaging and serological markers) with their value in predicting the progression of arthralgia to arthritis. Despite promising results, studies have been performed in heterogeneous patient populations and most findings have not been validated in independent studies. Future observational or preventive studies should be conducted with homogeneous patient groups (eg, patients fulfilling the European League Against Rheumatism criteria for arthralgia at risk of RA) in order to increase interstudy comparability and to allow result validation.

Keywords: disease activity; rheumatoid arthritis; treatment.

Figure 1

Adequate risk prediction is crucial for the design of informative preventive trials and for implementation of positive trial results.

Figure 2

Predictors of rheumatoid arthritis development belong to different categories. A predictor of disease might directly reflect the underlying biological process, it can be a biological bystander of disease, or it might have no relation at all with the underlying biology and is a phenotypic marker.

Figure 3

Clinical expertise of GPs and rheumatologists in differentiating patients with arthralgia. This figure is constructed based on the following references: The clinical expertise of GPs and rheumatologists is effective in differentiating patients with arthralgia; of all patients with MSK symptoms visiting their GPs (~300/1000/year13–15), only a small subset is suspected for arthritis (~3/1000/year). Of all patients with any MSK symptoms visiting secondary care (~8/1000/year53), only 7% were identified as CSA. The incidence of any MSK symptom in secondary care is higher than the incidence of patients with suspected arthritis in primary care, as GPs also refer patients with MSK symptoms in whom they did not suspect arthritis to be present. 74% of patients with CSA had a positive EULAR definition. CSA, clinically suspect arthralgia; GP, general practitioner; EULAR, European League Against Rheumatism; RA, rheumatoid arthritis; MSK, musculoskeletal symptoms.

Figure 4

EULAR-defined characteristics describing arthralgia at risk for RA. The reported AUC, sensitivity and specificity were calculated within newly presenting patients with CSA in outpatient clinics of European expert rheumatologists (who were part of the task force who defined arthralgia at risk for RA) with clinical expertise as reference. A sensitive definition requires the presence of at least three items and a specific definition requires the presence of at least four items. AUC, area under the curve; EULAR, European League Against Rheumatism; MCP, metacarpophalangeal; RA, rheumatoid arthritis; sens, sensitivity; spec, specificity; UA, undifferentiated arthritis.