Recognizing RA remission: is a new standard needed?

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Jan 9, 2004

Recognizing RA remission: is a new standard needed?

Madrid, Spain and Los Angeles, CA - Remission in rheumatoid arthritis (RA)

should be viewed as 1 end of a spectrum of disease rather than a dichotomous

variable, and a reasonable therapeutic target for remission would be a

Disease Activity Scale (DAS28) score of 3.1, Dr Balsa (Hospital

Universitario La Paz, Madrid, Spain) says in the January 2004 issue of the

Journal of Rheumatology [1].

In work supported by Aventis Pharma, Balsa and colleagues compared the DAS28

and DAS 28-3 (excluding patients' evaluation of disease activity) to

American College of Rheumatology (ACR) preliminary criteria and concluded

that the DAS28 score is more clinically useful than the more restrictive ACR

criteria and that a DAS28 of 2.81 reliably identifies patients who would be

considered in remission by ACR criteria.

" We consider it clinically useful to set a therapeutic goal of <3.1 on the

DAS28 scale. "

" We consider it clinically useful to set a therapeutic goal of <3.1 on the

DAS28 scale. This was found to be related to low disease activity as well as

low disability progression and radiological damage, " Balsa writes.

Study compared 3 ways of judging remission

This study included 788 patients randomly selected from a population of 13

260 patients with RA at 34 participating centers in Spain. The report is

based on 735 patients who had no missing data for the main study variables

(remission criteria and DAS components). Mean disease duration was 10 years,

36.2% of patients had extra-articular involvement, and >70% had some

comorbidity.

The ACR-proposed criteria include 5 or more of the following for at least 2

consecutive months: not more than 15 minutes of morning stiffness, no

fatigue, no joint pain by anamnesis, no joint tenderness or pain on motion,

no soft-tissue swelling in joints or tendon sheaths, and erythrocyte

sedimentation rate (ESR) of <30 mm/h for females or <20 mm/h for males [2].

Balsa argues that the ACR criteria define remission as a yes/no condition,

while defining it as the lower end of a disease continuum would permit

clinicians to use the same tools to judge remission as are used to assess

disease activity in standard clinical practice, specifically the DAS. A

previous study in early-onset RA had concluded that a DAS score of <2.6

would be required to meet the ACR 4-of-5 criteria [3]. Balsa's study showed

a strong correlation between ACR-defined remission and a DAS28 cutoff value

of 2.81. Balsa thinks this difference might be due to his evaluation of

patients with established rather than early disease and because this was

original data rather than an extrapolation from previous data.

" The ACR preliminary criteria for remission have several shortcomings that

hamper their clinical usefulness, " Balsa writes. " The descriptions of the

criteria are not sufficiently detailed, and there are no specifications on

how they are to be measured. Two of the 6 items, 'little morning stiffness'

and 'absence of fatigue,' may duplicate each other, are hard to determine

reliably, and are not included in the core set of measures of RA. . . . The

remission definition obtained using ACR criteria is a dichotomous variable,

which implies that small changes in disease activity may cause a change in

the patient's classification. "

DAS28 and 28-3 scores were calculated for all patients and had a high degree

of correlation. Patients in ACR-defined remission had lower DAS28 and

DAS28-3 scores, tender joint count, swollen joint count, ESR, and C-reactive

protein levels. There was no significant correlation between DAS 28-3 and

patient global assessment of disease activity.

The investigators constructed receiver operating characteristics (ROC)

curves to determine the cutoff value for remission using the DAS28 and DAS

28-3 criteria. " The resulting value for DAS28 was 3.14 (sensitivity 87%,

specificity 67%) when all the ACR criteria were used, and 2.81 (sensitivity

84%, specificity 81%) when fatigue was omitted, " Balsa reports. " The cutoff

values for the DAS 28-3 were 3.52 (sensitivity 84%, specificity 66%) and

2.95 (sensitivity 82%, specificity 83%) with and without fatigue,

respectively. "

More patients judged in remission using DAS 28 criteria

According to ACR criteria, 32 (4.1%) patients were in remission. Without

considering fatigue, which Balsa says is rarely measured in clinical

practice, 62 (7.9%) patients were in remission. Taking the ACR criteria

individually, absence of joint pain had the highest predictive value, while

fatigue, morning stiffness, and ESR had the lowest.

Using a DAS 28 <2.81, 170 patients would have been in remission (sensitivity

81%, specificity 82%). Results with the DAS 28-3 were similar, which

suggests that either could be used to assess disease activity in established

RA, Balsa says.

Balsa also points out that evaluating disease activity in established RA is

different from doing so in early disease, since consideration must be given

to distinguishing the effects of active inflammation from those of

irreversible joint damage.

Is an easier standard needed?

In an editorial that accompanies this study, Dr Harold E us (University

of California, Los Angeles School of Medicine) says that despite the

improvements with early aggressive therapy, relatively few patients satisfy

the ACR criteria of remission for at least 2 months [4].

" Are the ACR criteria too rigorous? " us asks. " Would more attainable

definition(s) hasten the development of new and better drugs and biological

agents? "

us says that the consequences of RA are measurable as signs and symptoms

of inflammation, functional impairment, and structural damage to joints. The

ACR criteria ignore physical function and structural damage to joints.

In Balsa's study, the DAS-28 value that was equivalent to satisfying the

full ACR remission criteria was 3.14 if fatigue were included as a

criterion, 2.81 if fatigue were omitted.

" These cutoff values substantially increase the number of patients who would

be classified in remission, " us points out.

The practical importance of this difference is uncertain. us suggests

that a subjective definition of remission is " probably sufficient for

clinical practice " provided all 3 domains are carefully considered (signs

and symptoms of inflammation, functional impairment, and structural damage

to joints).

" Clearly, remissions can be independent of treatment, although controlled

clinical trials are beginning to indicate that major improvement or 'near

remission' is more frequent with certain DMARD and/or biologic agents than

with control treatments, even in long-standing RA, " us concludes.

Janis