Despite the use of a goal-directed approach in some inflammatory diseases (e.g., lowering serum uric acid to a target of 6.0 mg/dl in patients with gout), surprisingly, rheumatology as a specialty and rheumatologists in particular appear to be slow in adopting the regular use of standardized, objective metrics in rheumatoid arthritis (RA), let alone a goal-directed approach, linking an objective metric of disease activity to therapeutic intervention. The absence of a “target” does not mean that we have not recognized the need to lower disease activity. But what is the evidence that the philosophy of “the lower the better” holds true for RA disease activity?

Reviewing the Evidence

In 2008, an international expert panel comprised primarily of rheumatologists began review of available evidence on goal-directed therapy in RA. The results of this effort became the International Treat to Target Initiative, now endorsed by representatives and patients from over 46 countries, and published in 2010.1 This expert panel agreed on several “Overarching Principles” as well as specific recommendations (see Table 1).

Based on available evidence, the use of an outcome that includes an objective measure to guide therapy will ultimately facilitate patient care.2-4 For example, the Tight Control of Rheumatoid Arthritis (TICORA) study employed an arbitrary therapeutic algorithm that used no biologic agents and advanced therapy according to a structured algorithm every three months if patients did not achieve low disease activity as measured by the Disease Activity Score 28 (DAS28; i.e., DAS28≤3.2).2 Patients in the intensive therapy group achieved lower disease activity than did patients assigned to routine care.

The Computer Assisted Management in Early Rheumatoid Arthritis (CAMERA) study used a computer algorithm to drive escalation of methotrexate therapy and showed that a greater percentage of patients achieved remission when they were treated according to this computer algorithm than when they were treated according to their physician’s intuition.3 The Behandel Strategieen (BeST) study compared four different therapeutic regimens, some of which included biologic therapies, others of which predominantly included traditional disease modifying antirheumatic drug (DMARD) therapies.4 The BeST study also showed that advancing patients every three months along a predefined therapeutic algorithm, if they were not in DAS low disease activity, led to better outcomes with less disease progression and better functional status more rapidly if patients were treated with either a biologic agent or traditional DMARDs.

The questions driven by these studies then become the following: 1) What is the best metric to use when measuring disease activity (e.g., DAS28, CDAI, SDAI)? and 2) What is the most appropriate (or realistic) target (e.g., remission or low disease activity)? To date, only a few small studies have attempted to compare the efficacy of different treatment targets in RA.5 Given the debate in the literature about the relative utility and ease of use of patient-reported and physician-reported outcomes, it is unlikely that this issue will be resolved definitively or that the rheumatology community will reach consensus regarding which objective metric is best to use in setting a patient’s target. Nevertheless, the “treat to target” concept remains essential: set a target, measure progress by a standardized metric, and adjust therapy accordingly.

Treat to Target in Practice

We suggest that in clinical practice, each rheumatologist should select a target that makes the most sense for an individual patient and initiate and then adjust therapeutic strategies in order to reach that target. Whether that outcome measure is a single variable (e.g., joint count) or a composite of multiple variables (e.g., DAS28), the use of an outcome measure is important so that a patient’s progress can be effectively evaluated. The algorithm proposed by the International Treat to Target Initiative for treating RA to target is presented in Figure 1.1