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

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December 28, 2003

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

Associate Attending Rheumatologist

Hospital for Special Surgery

Associate Professor of Clinical Medicine

Weill Medical College of Cornell University

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 TICORA

(Tight Control of Rheumatoid Arthritis) study1. (To read this Abstract, go

to the ACR site and select Abstract #515.)

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.

TICORA 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 Europe2. 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 TICORA 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; for DAS 28, see

http://www.das-score.nl/www.das-score.nl/DAS28calc.htm).

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.

--------------------------------------------------------------------------------

1Porter 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)

23.7 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. " http://www.rheumatologycme.org/index.asp?show=features

http://www.hss.edu/Conditions/Rheumatoid-Arthritis/Tight-Control-Of-Early-RA---P\

atient

Not an MD

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org