Can tight control of early RA - with a target - help you feel a lot better and reduce joint damage?

Special Report

Theodore R. Fields, MD, FACP
Theodore R. Fields, MD, FACP
Attending Physician, Hospital for Special Surgery
Professor of Clinical Medicine, Weill Cornell Medical College

Certainly we assume your doctor is doing his or her best to treat your rheumatoid arthritis (RA) according to current standards of medical care. But over time - in many diseases - new standards of care gradually arise. For a long time, there has been debate about how aggressively rheumatoid arthritis should be treated. Is it time to define a new standard?

The issue: what should be the goals of therapy in RA? Should we be more aggressive? Some doctors say yes, hoping to help their patients feel even better and to prevent joint damage. Others worry that more aggressive use of medications will produce more side effects - problems doctors call adverse events. Here's the range of possibilities under discussion:

  • aiming for what appears to be the best for each individual patient - without specific targets (which is the traditional approach to RA);
  • aiming for specific targets that measure disease activity or its disappearance - (and if so, what targets) - and raising drug doses or adding/changing drugs until those targets are achieved;
  • aiming for no evidence of disease (NED) - and raising drug doses or adding/changing drugs you reach full remission.

At the recent American College of Rheumatology scientific sessions, the case for targets was made by Duncan Porter, MD, in his report on the TACORA (Tight Control of Rheumatoid Arthritis) study1. Dr. Porter pointed out the similarities between RA and diabetes:

  • both are chronic disorders;
  • both can lead to serious complications that develop over the course of a lifetime;
  • such complications often cause serious illness and premature death.

In diabetes, targets have helped. Doctors don't just aim to "improve" control of blood sugar. They aim for a specific number, based on HbA1c - a blood test that measures your blood sugar control over the prior 2 to 3 months. Medications and dosages are changed to aim for a specific HbA1c target. The target gets blood sugar levels as close to normal as possible. This is called tight control. Research has proven that reaching that target - and staying there - reduces the risk of the serious complications of diabetes.

TACORA sought to determine whether tight control of early RA could provide significantly better outcomes - patients who feel better and had less damage to their joints.

The target they used is based on the Disease Activity Score (DAS) - a way of measuring RA problems developed in Europe. It is based on points for: how many tender and swollen joints you have, your sedimentation rate (a blood test), and your report of how you feel (scored 1-100) - plus some complex math to come up with a number. A DAS score of more than 3.7 indicates high disease activity; a score equal or lower than 2.4 indicates low disease activity. A score of less than 1.6 indicates that you are in remission.

The TACORA target was less than 2.4 for this experiment. The study enrolled 110 patients who had had active RA for less than 5 years. They were randomly assigned to two groups and participated for 18 months.

The "intensive care" group saw their rheumatologist every month. Their DAS was calculated at every visit. If it had not reached 2.4 or lower, therapy was changed to higher doses or new drugs - every month, if needed - to reach that goal. Drugs used included sulfasalazine, prednisolone, methotrexate, cyclosporine, and other disease-modifying anti-rheumatic drugs (DMARDs). Sometimes a persistently painful joint was injected with steroids. All of this was done based on a written plan - called a protocol - for the experimental group.

The "routine care" group saw their rheumatologist every three months. Their doctors aiming for the best for each individual patient - without specific targets. They increased or changed drugs as they thought appropriate.

At the end of 18 months, a physician who did not know who was in which group evaluated all the patients - looked at their test scores for disease activity, quality of life and physical function, and at the X-ray scores of joint damage.

The more aggressive therapy led to significant improvements on every measure. And, overall, the intensive group achieved a DAS of 1.4 - they were in remission.

The routine care group, which had received excellent but traditional care, only achieved a DAS of 2.7.

Another measure of how well RA patients are doing is the ACR 70. What percent of the patients in the group had achieved a 70% improvement in their RA over the course of 18 months? Only 18% of the routine group compared to 67% of the intensive group.

But did this aggressive approach cause any problems? Did those extra drugs cause more side effects? Interestingly, adverse events were less frequent in the intensive group than in the routine group.

It is also interesting that the latest drugs for RA - the anti-TNF agents such as etanercept (Enbrel), infliximab (Remicade) and adalimumab (Humira) - were not used in this study. It is not known how the use of anti-TNF agents might have changed the results of the study. They might have led to further improved outcomes - in both groups of patients.

The researchers concluded that "patients with early RA should be treated intensively using standard DMARDs according to a protocol that targets persistent disease activity." Thus, this study joins many others that support aggressive early treatment of RA.

Is a DAS of less than 2.4 the right target? Should we be even more aggressive? For the moment, the message of this article is that we should be more rather than less aggressive with each patient. But individualization - taking the individual patient into consideration rather than just a number on a chart - is essential.  (See footnote 2 for 2 resources for online DAS calculator)

The case for pushing further -- to "no evidence of disease" in all patients -- is provocative. It does not seem possible in all patients at this time. But it remains a valuable goal as research moves forward - and requires further study.

Porter DR, Grigor C, Stirling A, Capell HA. A Randomised Controlled Trial of a Strategy of Tight Control of Disease Activity in Rheumatoid Arthritis- outcome Over 18 Months. Arthritis Rheum. 2003 Sep;48(9):S232. (Abstract #515)|3.7 indicates high disease activity; a score of <2.4 indicates low disease activity; and a score <1.6 indicates that the patient is in remission. Based on the DAS28, a score >5.1 indicates high disease activity; a score <3.2 indicates low disease activity; and a score <2.6 indicates the patient is in remission."


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