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Slowing the Progression of Moderate to Severe Rheumatois Arthritis
is started and the radiographic damage progression is another important
Figure 1: Disease Duration, Physical Function and Radiographic
consideration. Once more, the evidence points to the advantages of early
Damage of Patients with Rheumatoid Arthritis
therapy aimed at reducing the radiographic damage. The initial benefits
are still evident five years after treatment, as shown in Figure 1.
25
50
Correlation coef
0.6
Another early treatment benefit is the possibility of remission.
40
0.5
Fortunately, in RA this outcome is an important aim today. Clinical
0.4
30
ficient
remission with no or very low rates of activity is achieved more frequently
0.3
in the early stages of the disease. Many rheumatologists consider that
20
radiographic remission is also possible and must be another important
0.2
Percent max disability/damage
goal in the management of RA. This fact is worth remarking on since
10
0.1
radiographic progression can be evident in some patients with clinically HAQ
controlled disease.
00
Larsen
061218 24 30 42 60
In conclusion, rheumatologists can now reliably measure joint damage Disease duration (months)
with radiographic indexes of joint damage in plain films of hands and
Figure adapted from reference 6.
feet, and this measurement is a necessary outcome measure. New
achievements in USG-Doppler and magnetic resonance imaging are
Figure 2: Representation of Effect in Radiographic Progression
developing. Early treatment, sufficient treatment and especially – but
of Early versus Delayed Disease-modifying Anti-rheumatic
not limited to – biological agents have a major effect in slowing
Drugs (DMARD).
damage progression. So, the ‘window of opportunity’ for treatment
can be extended to radiographic control. Finally, evidence supports that
remission is not complete if radiographic progression is not included in
the criteria.
Delayed Delayed
DMARD DMARD
Improvements in Physical Function
X-ray damage
Early Early
The gold standard of physical function instruments in RA is the Health DMARD DMARD
Assessment Questionnaire (HAQ). It is a simple, self-reported
} }
questionnaire that evaluates the performance of patients in simple daily- Delay
Time Time
Relative
life activities. This instrument was developed at Stanford University
period
delay
period
almost 30 years ago.
26
Many data have been accumulated about physical
(-RCT duration)
function and the HAQ.
AB
An important issue is the fact that physical function is influenced by
Representation of delayed disease-modifying antirheumatic drugs (DMARDs) initiation by study type. A: In
several variables. Some – such as age, gender, co-morbid conditions
cohort studies of patients with early rheumatoid arthritis, long-term radiographic progression is contrasted
and psychosocial factors – are not directly related to RA; and others,
between subsets with early versus delayed initiations of DMARD therapy. B: In a randomised controlled trial
(RCT) effective DMARD regimens are compared with placebo or a less effective DMARD regimen. At the end of
such as pain or joint damage, are disease-dependent.
27
The correlation the RCT period, blinding is removed and patients are free to receive any DMARD. In follow-up studies of these
between the HAQ and radiographic damage is clear, but poor, as
RCTs, delayed DMARD initiation is conceptualised as a relative delay to effective DMARD therapies in the
comparator arm compared with the active treatment arm. Studies that did not receive comparable DMARDs
shown in Figure 2. On the other hand, disease activity and some during the follow-up period were excluded so that long-term radiographic progression could be compared with
respect to the initial therapeutic strategy. Shaded circle = DMARD initiation.
markers of inflammation, like C-reactive protein, correlate weakly with
Figure adapted from reference 25.
the HAQ. However, the correlation between the HAQ, mortality and
co-morbidity is not questionable. with drug combinations and the early use of biological agents are
modifying the clinical course of physical function. HAQ-measured
Two components of the HAQ have been identified. The first is a physical function improves as early as one month after starting therapy
reversible one, possibly related to acute inflammation and disease and reaches maximum improvement between the second and third
activity. It is predominant in the early stages of the disease. The second months and is sustained over 24 months.
29
These facts support the
component is chronic and irreversible, with little ability, if any, to be concept that the use of more potent therapeutic strategies for
modified and possibly related to the structural damage. It accounts for decreasing disease activity has the potential for a more efficient
most of the HAQ score in the late stages of disease.
28
With these physical-function improvement.
considerations – and recognising the many problems related to the
HAQ as a physical-function gold standard – its value as a clinimetric In early RA, conventional DMARD monotherapy induces remission in a
instrument with demonstrated proprieties of truth, discrimination considerable number of RA patients, slowing the physical-function
and feasibility is clearly stated and has been validated in different trials deterioration rates, but the results become more relevant when combined
and languages.
3
therapy is used.
11,30
Once more, this underscores the importance of also
using potent treatment in the early stages of the disease.
Until only a few years ago, the only therapy that significantly improved
the HAQ was surgical joint replacement. Now, an optimised use of Biological agents are effective in improving physical function. Even in
methotrexate, new DMARDs and early, more aggressive strategies patients with long-standing disease, in a clinical environment the use
EUROPEAN MUSCULOSKELETAL REVIEW 2007 17
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