Improving Outcomes in RA: What Determines Decisions to Change Ineffective Therapy?

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Editorial: Improving Outcomes in Rheumatoid Arthritis: What Determines

Decisions to Change Ineffective Therapy?

Address reprint requests to Dr. Sokka. E-mail: tuulikki_sokka@...

http://www.jrheum.com/subscribers/06/07/1213.html

Treatment of rheumatoid arthritis (RA) has been transformed greatly over the

past decades from a " reactive " strategy of using disease modifying

antirheumatic drugs (DMARD) only when the diagnosis was certain and damage

apparent, to an aggressive strategy of " preventive " use of DMARD to control

inflammation as completely as possible to slow joint damage. The new

strategy has been accompanied by new DMARD, most notably methotrexate, and

considerable evidence indicates that most patients with RA have better

clinical status today compared with earlier periods. Availability of new

biological therapies adds to the rheumatologist's armamentarium, helping

many patients toward a state of low disease activity or remission.

Changes in the treatment of RA have been accompanied by increased awareness

on the part of rheumatologists of a need for quantitative documentation of

patient status in clinical settings. In 1983, Verna pointed out that

" clinicians may write 'doing well' in the notes of a patient who has become

progressively crippled before their eyes " 1. This situation is becoming rarer

in contemporary care of people with RA.

A major advantage in quantitative assessment of RA patient status is the

Disease Activity Score (DAS), which was developed as a composite score for

disease activity in RA2-4. The DAS is a pooled index that includes 4

measures: tender joint count, swollen joint count, erythrocyte sedimentation

rate (ESR), and patient global assessment. " High " disease activity was

defined as the DAS level when a new DMARD was begun or changed from another

due to lack of efficacy, while " low " disease activity was defined as a DAS

level at which a new DMARD was not started or a DMARD was left unchanged for

at least for one year or was stopped because of remission5.

The DAS, which appeared in 1985, classifies patient status according to

levels of " high " and " low " disease activity, reflecting decision-making

concerning treatments for RA at that time. In this issue of The Journal,

Soubrier and colleagues6 present predictors of change of treatments for RA

in the clinic supervised by Dr. Dougados. They report a lower cutoff value

for " high disease activity " according to the DAS28 than has previously been

reported.

Reevaluation of values of well established measures such as the DAS appears

welcome at this time. Lower levels reflect improvements in patient status

compared to previous decades. An improved clinical status of RA patients at

this time compared to previous decades has been documented concerning

disease activity7,8, functional capacity8-11, radiographic scores8,12,13,

and other clinical measures8, including lower mortality rates in patients

who responded to methotrexate14,15. Further, indirect evidence of improved

patient clinical status is provided by observations that only a minority of

patients in routine rheumatology care meet inclusion criteria in clinical

trials16. The French study6 adds indirect evidence of improved care at this

time, indicating lower cutoff levels to modify a DMARD therapy of DAS28esr =

4.2 and DAS28crp = 3.6, compared to disease activity levels in the Nijmegen

early RA cohort in 1985-945, which correspond to DAS28 >= 5.117.

In an ideal world, disease activity as a biological phenomenon would be the

most important, if not the only, determinant of decision-making concerning

treatment of RA. Suppression of current disease activity would prevent

future joint damage and development of functional losses. A focus on disease

activity implies that clinically assessed high disease activity invariably

leads to change in therapy. However, many patients seen in a regular

rheumatology clinic already have developed joint damage and have problems

with physical function. A decision to change RA therapy may therefore be

affected also by these damage variables, in addition to currently high

inflammatory activity. Development of new erosions likely increases

probability of change in therapy for RA if radiographs are used in routine

evaluation of patients. Good function in activities of daily living is

important from the patient's perspective and is reflected in global health,

which is included in the DAS formula. Assessment using the Health Assessment

Questionnaire would have augmented the completeness of the excellent

analyses of the French group6.

From an international approach, many variables beyond DAS scores, including

patient demographics and psychosocial variables, healthcare system

variables, and society-associated variables, may influence a decision to

change RA therapy. In the French clinic, lower age and shorter disease

duration were associated with a higher likelihood of changing therapy6.

Other patient related variables may include number and type of

comorbidities, education level, and ethnic background. Local traditions may

play an important role in rheumatology daily practice. In some advanced

clinics in the US, methotrexate reached popularity in the early 1980s, 10-20

years before it became the drug of choice in early RA in Europe. Enormous

variation was seen in DMARD " ever used " in a cross-sectional study of

consecutive patients with RA from 9 Western European countries18. This

variation likely reflects local traditions concerning the choice and

availability of DMARD. Accordingly, local traditions may also affect

decisions to change RA therapy.

Nowadays, many more DMARD, including biologic agents, are available compared

to when the DAS was developed and definitions of " mild, " " moderate, " and

" high " disease activity were reported. These definitions reflect the

availability of DMARD and the standard of care at that time, which differs

across decades. Moreover, availability of DMARD and especially biologic

agents differs across countries. Further, guidelines on the use of biologic

agents differ between countries and may strongly influence changes in RA

therapy. The French study provides an example of a clinic where biologic

agents are available for those who are regarded to need them.

A consensus statement and national guidelines for prescribing biologic

agents recommend these agents for patients who have currently active disease

and have received treatment with one or 2 DMARD, usually including

methotrexate19. In some countries, guidelines additionally require a certain

level of disease activity. Examples include the UK, where guidelines

recommend restricting biologics to patients who have DAS28 >= 5.120, while

in The Netherlands, the activity requirement to start a biologic agent is

DAS28 >= 3.2. In Denmark, a patient is required to have 6 or more swollen

joints. Databases that reflect clinical practice nationwide indicate that

the median disease activity score ranged from 5.2 to 6.0 on DAS28 in

patients who started a biologic agent in Denmark and Norway in the early

years of this decade21.

In conclusion, the Soubrier report indicates that disease activity drives

changes in therapy for RA, and that lesser disease activity is tolerated

compared to the past. The study raises several important questions

concerning daily rheumatology practice worldwide: Does current practice

regarding changes in therapy for RA reflect disease activity, as well as

patient psychosocial, healthcare system, and society-related variables? What

about traditions and national guidelines? What guidelines should exist for

decisions to change RA therapy? These questions should be examined more

widely to improve standard clinical practice in many countries.