Targeting early disease: lessons from rheumatoid arthritis

A problem frequently encountered in RA is the delay in assessment; this has a negative impact on early treatment and subsequent outcomes. A trial by Van Aken et al. with methotrexate in pre-RA showed it somewhat delays the onset vs. placebo, but not significantly [19]. When the (small) study population was separated into two groups (serologic positive and negative), there was, however, a clear difference. Thus, serology might be an indicator for early diagnosis and treatment.

Another question is the role of biologics: does early treatment reduce radiographic progression? The OPTIMA study compared different treatment adjustment strategies (adalimumab plus methotrexate or methotrexate monotherapy) [20]. Treatment to a stable and low disease activity target resulted in improved clinical, functional, and structural outcomes (for both adalimumab continuation and methotrexate monotherapy).

A higher proportion of patients who received initial adalimumab plus methotrexate achieved the low disease activity target compared to those initially treated with methotrexate alone. Timing of the therapy is important, not so much its aggressiveness. However, there are limiting factors to early treatment. Delays in patient presentation (up to six months, which is very long in musculoskeletal disease) may lead to a delayed referral to a rheumatologist. Screening and prevention can be of help here, as can public awareness from general practitioners, so they know what to watch for.

A triage system can aid timely diagnosis of the right patient too. There are no diagnostic criteria for RA yet, but there are classification criteria which can be used. The lessons learned from RA point towards early treatment (the earlier the better), as this leads to less permanent damage in RA. The window of opportunity comes into view here as early treatment may alter the course of the disease. The initial combination of methotrexate and a TNF inhibitor is not superior to methotrexate followed by methotrexate + TNF inhibitor. Thus, step-up therapy is sufficient here. Shortening treatment delay is also essential, with multiple causative factors needing to be addressed by specific strategies [21].