How Should Rheumatoid Arthritis Disease Activity Be Measured Today and in the Future in Clinical Care?

Quantitative clinical monitoring of musculoskeletal conditions and inflammatory joint diseases is challenging. Traditional measures to assess rheumatoid arthritis (RA), such as joint assessment, laboratory, imaging, and patient self-report measures, have limitations and provide only a reflection of the underlying inflammatory process. A gold standard to define disease activity in RA does not exist and various indices of disease activity must be used. Standard quantitative monitoring with a treatment goal has been shown to be beneficial to patient outcomes in randomized clinical trials. Quantitative monitoring has also contributed to improved long-term outcomes for RA in clinical care. Challenges of the measures need to be recognized and hurdles identified that prevent quantitative monitoring in every-day clinical care concerning disease activity and beyond. These aspects are discussed in this article.

Quantitative clinical monitoring of musculoskeletal conditions and inflammatory joint diseases is challenging compared with quantitative monitoring of conditions such as hypertension or hyperlipidemia, for which single measures can be used as an indicator of disease status and change. Traditional measures to assess rheumatoid arthritis (RA), such as joint assessment, laboratory, imaging, and patient self-report measures, have limitations and provide only a reflection of the underlying inflammatory process. A gold standard to define disease activity in RA does not exist and various indices of disease activity must be used.

Quantitative monitoring of RA as part of daily clinical practice has certainly improved since Dr Wright’s observation in 1983 that “clinicians may all too easily spend years writing ‘doing well’ in the notes of a patient who has become progressively crippled before their eyes….” Standard quantitative monitoring with a treatment goal has been shown to be beneficial to patient outcomes in randomized clinical trials. Quantitative monitoring has also contributed to improved long-term outcomes for RA in clinical care.

One of the earliest proposals for an active monitoring and treatment strategy for RA was expressed by Luukkainen and colleagues in 1978 “… In our opinion gold treatment ought to be started in the early stages of RA, before the development of erosions. We are treating not only the actual inflammation of the joints but also the quality of the patient’s life for many decades in the future.” Although benefits of quantitative monitoring of RA are obvious, challenges of the measures need to be recognized and hurdles identified that prevent quantitative monitoring in every-day clinical care concerning disease activity and beyond. These aspects are discussed in this article.

Measuring of disease activity leads to less disease activity

Most clinical trials are designed to analyze differences between active and control treatments rather than to attain a certain clinical status. A traditional clinical trial involves an extensive battery of measures of disease activity and other measures at study visits, which are simply used to document patient status but not to guide therapies. However, a few trials can be called strategy trials because they involve a treatment goal, and response/disease activity level at each study visit influences treatment doses.

The Finnish Combination Treatment Trial (FIN-RACo) was the first clinical trial with remission as the primary outcome measure. During the 2-year study, treatments had to be adjusted if remission was not met. At the end of the study, disease activity score (DAS28) remission rates were 68% in the combination arm and 41% in the monotherapy arm, and American College of Rheumatology (ACR) remission rates were 42% versus 20% in the 2 groups, among the highest ever seen in clinical trials or clinical care.

The TICORA (Tight Control of RA) study aimed at low disease activity of DAS <2.4 in the strategy arm, with frequent clinical visits and escalation of treatments. At the end of the trial, 65% of patients were in DAS remission of DAS <1.6 in the strategy arm versus 16% in the routine care arm. The Behandelstrategieën voor Reumatoide Artritis (BeSt [Treatment Strategies for RA]) study had a treatment goal of DAS ≤2.4; 38% to 46% of patients in the 4 arms were in DAS remission at the end of the intervention. In the 2-year CAMERA (an open-label strategy trial), 50% of patients were in DAS28 remission in an intensively computer-assisted monitoring group versus 37% in the conventional group. Similarly, in the CIMESTRA (Cyclosporine, Methotrexate, Steroid in RA) trial, 2-year radiographic and clinical results were better in the strategy group versus the control group. Fransen and colleagues compared a strategy group designed with routine disease activity measurements and the aim of DAS28 ≤3.2 with a usual care group with no routine measuring. For 24 weeks, patients in the strategy group received more antirheumatic drugs and had better outcomes than patients in the usual care group.

These clinical trials indicate that the practice of quantitative monitoring of RA leads to better outcomes than routine care without quantitative monitoring. Furthermore, a treatment target and quantitative monitoring have obviously played a role in clinics that have reported favorable long-term outcomes of RA. However, quantitative monitoring of RA involves challenges that may prevent implementation of these measures in routine clinical care ( Table 1 ).

Table 1

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