EDITORIAL - Outcome issues for RA: What do we have and what do we want?

[Guest guest]

Journal of Rheumatology

March 2006

Editorial

Outcome Issues for Rheumatoid Arthritis: What Do We Have and What Do We

Want?

DANIEL A. ALBERT,

5 Maloney Building, Suite 504,

3400 Spruce Street,

Philadelphia, Pennsylvania 19104-4283, USA

Address reprint requests to Dr. Albert. E-mail: albertd@...

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In this issue of The Journal, El Miedany, et al1 have described a study

examining the outcome of patients treated with anti-tumor necrosis factor-a

therapy in terms of the ability of the Disease Activity Score 28 (DAS 28) to

identify patients who have and who have not responded to the therapy. They

examine various permutations of the DAS 282 in order to identify those

aspects of the scoring system that were problematic. The gold standard was

the ability to discriminate responders from nonresponders, and with this

approach they were able to show that C-reactive protein (CRP) was a more

accurate measure of disease activity than erythrocyte sedimentation rate,

and that patient global assessment was inferior to physician global

assessment. This is, in a sense, an internal examination of the validity of

the components of the DAS 28 and doesn't address the larger question of what

are and are not the characteristics of outcome measures that would be

maximally useful to physicians and patients.

Starting from the premise of what do we want, it is self-evident that we

need a scale that adequately discriminates between responders and

nonresponders to a disease modifying drug3. A score should be reproducible,

both by a single evaluator (test-retest reliability; that is, intrarater

reliability) and across evaluators; that is, interrater reliability. It

should be a continuous variable since the response of the individuals to

medications is not an all-or-nothing phenomenon. In this sense the DAS 28 is

a substantial improvement over the American College of Rheumatology response

criteria ACR20, 50, or 70, although there have been many proposals to

reconfigure the components of the ACR criteria as a continuous measure4. It

should be relatively linear in the sense that a distribution of results

falls on a continuum and should not be skewed, for example, if there are

" floor " or " ceiling " effects. The measure should have equal ability to

discriminate in an interventional study such as a randomized controlled

trial or in an effectiveness study such as an observational cohort of

patients. The scoring system ought to correlate, and in a sense predict, an

anatomic outcome such as erosions detected on radiography or magnetic

resonance imaging5. The scoring system should have the usual criteria for

validity such as face validity and convergent validity and so on. Last, we

should be able to aggregate the measures over time and utilize techniques

such as area under the curve to best describe the clinical course of

patients6.

With this preamble in mind, what do we actually want to know about patients

with rheumatoid arthritis? Certainly inflammation of the joints is

paramount, both as a manifestation of the disease and as a target for

therapy. Given the difficulty in performing reliable joint examinations, the

validity of joint counts has been extensively explored. A DAS 28 count joint

examination is probably sufficient for patients with RA. The presence of

inflammatory serum markers is unquestionably a facet of the disease that

gives important clues to the pathogenesis and pathophysiology. In most

studies, CRP performs better than sedimentation rate, but other acute phase

reactants could be used. For the moment, the CRP is probably appropriate.

Less clear are the global measures. Neither the patient nor the physician

global is particularly reliable in either test/retest situations or

interrelater reliability. One might consider substituting a patient based

pain measurement such as the visual analog scale as an albeit qualitative

measure of discomfort associated with the disease. Unfortunately, external

features such as fibromyalgia or neuropathy often contaminate this.

Nonetheless, pain is a major clinical characteristic that motivates

therapeutic intervention and must be included in a measure. For practical

reasons, extensive questionnaires such as the McGill Pain Questionnaire are

not useful as a component of an outcome measure. To this end, a measure of

disability should be included because it correlates with other consequences

of the disease such as employability and economic and financial decline7.

Last, an often ignored but important issue is the practicality of using the

scale for clinical encounters of a routine nature. Most of these scales have

been used in clinical trials, but a practical summary score of disease

activity would be immensely useful in the clinic to quantify a patient's

disease activity and response to therapy longitudinally.

The available measures, predominately the ACR20, 50, and 70 and the DAS 28,

are useful but limited outcome measures for RA. They were designed primarily

to evaluate new therapeutic modalities in a trial scenario and none has

proved very useful in a day to day clinical setting. All the measures are

given at one point in time and judged in a categorical fashion against

pretreatment values. In addition, the ACR20, 50, and 70 are dichotomous

scales, which tend to reduce the power of the continuous measures used as

components for them. It might, however, be reasonable to retain a

dichotomous (categorical) outcome of remission (no tender, swollen joint, AM

stiffness, pain, fatigue, or elevated acute phase reactants) or clinical

remission (no tender swollen joints or acute phase reactants)8. Both these

designations have been proposed as ACR criteria with a rough correlation

with DAS score of between 2.32 and 2.609.

Scale construction is an intricate and time consuming activity. The major

judicial body that examines these outcome measures is OMERACT, which meets

on a yearly basis to discuss potential revision of the available scales10.

In summary, we are part way toward developing a truly useful outcome measure

of RA. I believe that in the future patient and physician global assessment

will be discarded. A pain measurement and the functional disability

component of the ACR scoring system will be retained, but modified, so that

the floor and ceiling effects of the Health Assessment Questionnaire are

eliminated for less severely disabled individuals. There seems to be no

substitute on the horizon for an adequate physical examination, which

relegates assessment to experienced physicians and nurse practitioners. In

addition, CRP test, which is our best choice among acute phase reactants, is

usually not available on a same-day basis, so the score cannot be calculated

" in real time. " Eventually, we will require a " real-time, " reliable, and

valid instrument that can be used in ongoing longitudinal care of patients

with rheumatoid arthritis: a useful instrument in the clinic and in studies

that will permit us to extrapolate directly from studies to our patients. It

may even clarify what clinical characteristics are most likely to be

addressed by which therapeutic modality.

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