Overview: imaging, biomarkers and arthritis

The recent introduction of effective structure-modifying therapies for rheumatoid arthritis (RA) has changed the way that rheumatologists manage patients with RA, and this has created new demands on imaging and biochemical markers both in clinical practice and in clinical research. Among other things, it has shifted therapeutic strategy towards early, aggressive treatment before the onset of erosive joint damage in order to prevent irreversible functional disability. Additionally, it has made it unethical to withhold active therapy and therefore to perform true placebo-controlled clinical trials. This has necessitated using active comparator study designs instead, which require more patients, more clinical sites and longer studies to test the efficacy of putative new therapies. This adds time and cost to drug development, which slows progress and potentially raises the cost of new therapies that do get approved. Enriching study populations with rapidly progressing patients may offset some of this effect, but this necessitates the availability of prognostic markers that can accurately identify which patients are most likely to develop erosive damage and functional disability. This can be challenging in early RA, as 30% or more of the patients in early RA cohorts do not progress. Early prognosticators are also needed by clinical practitioners to determine which patients need aggressive treatment before the narrow window of opportunity for containing erosive disease closes.

Magnetic resonance imaging (MRI) provides greater sensitivity for bone erosions than radiography does, especially in early RA, when radiography is relatively uninformative. This, along with its ability to detect pre-erosive features, such as synovitis and bone edema, allows MRI to identify patients with the aggressive phenotype of RA very early in the course of their disease. Supplementing MRI with specialized molecular markers, such as CTX-I, CTX-II, glucosyl-galactosyl pyridinoline, COMP and others, may provide additional predictive power. These MRI and molecular markers can also be used to monitor disease progression and treatment response in clinical trials with greater statistical power than radiography can offer.

Accordingly, as the introduction of structure-modifying therapy into mainstream clinical practice drives the demand for sensitivity and precision in predicting and monitoring erosive damage in early RA beyond the technical limits of conventional radiography, MRI and specialized molecular markers become increasingly attractive alternatives for evaluating therapeutic efficacy in clinical trials as well as in clinical practice.