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Rheumatoid Arthritis
Remission and Biologic-free Remission in Rheumatoid Arthritis
a report by
Benazir Saleem
1
and Paul Emery
2
1. Specialist Registrar in Rheumatology; 2. Professor of Rheumatology, Head of the Academic Section of Musculoskeletal Disease, University of Leeds
Rheumatoid arthritis (RA), a chronic inflammatory destructive arthritis, has been described as a more accurate definition for remission as it allows
causes significant mortality and morbidity. The advent of biologic therapies for less residual disease.
9
has enabled levels of disease control previously thought impossible, such
that remission – measured clinically – has become the goal of therapy. Early Problems with Clinical Remission Criteria
aggressive therapy has also improved remission rates, with tight control of All three clinical remission criteria (ACR, DAS and SDAI) are composed
inflammation to prevent structural damage. This is relevant as erosions can of mainly subjective criteria and do not include measures of structural
develop within months of the diagnosis of RA.
1
True remission should deterioration. Fibromyalgia, age and other co-morbidities can affect
represent the absence of inflammation as well as no deterioration of joint self-reporting of pain and global health assessment, and the impact of
damage or function. However, despite achieving clinical remission, some these co-variates must be taken into account when using subjective
patients continue to progress radiographically. As a result, clinical remission measures – such as patient visual analogue scales – to help determine
criteria do not measure inflammation sensitively or correlate with structural whether patients are in remission.
10
damage, and therefore may not represent true remission.
Clinical Remission and Radiographic Damage
This poor sensitivity may explain why, even though clinical remission is A cohort of 191 patients with early RA in sustained clinical remission (DAS
achieved, disease activity can reactivate when therapy is ceased. In <1.6) from four French centres
11
were recruited to determine
consequence, effective therapy is continued indefinitely and ceased only radiographic damage. Radiographic stability was seen in the majority of
for adverse events, with significant health and economic implications. patients, with a clear improvement in functional capacity; however,
There is limited data on whether patients with established RA in clinical 16.7% of patients had significant radiographic progression and 20%
remission can be withdrawn from biologic therapy. It appears that the developed erosions in a previously unaffected joint. Similar results were
withdrawal of disease-modifying antirheumatic drug (DMARD) therapy in observed in 187 patients in clinical remission according to ACR criteria,
patients in remission leads to relapse.
2,3
However, there are more omitting fatigue.
12
For the majority of patients in sustained remission
encouraging data in some patients with early RA, in whom tumour there was no radiographic progression, but 7% had relevant progression
necrosis factor (TNF) antagonists can induce remission that is sustained and 15% developed new erosions. These findings were recently
after withdrawal of the drug. confirmed in 107 patients in DMARD-induced clinical remission as
assessed by their physician.
13
A statistically significant 29% of the total
From these trials, it appears that clinical remission criteria are cohort had worsening of total X-ray score; 15 and 17% of patients who
unsatisfactory outcome measures as not only are they unable to predict fulfilled ACR or DAS remission criteria, respectively, had radiographic
those patients who can safely be withdrawn from biologic therapy, but
they are also unable to predict those patients who will continue to
Benazir Saleem is a Specialist Registrar and Clinical
progress radiographically. This is likely explained by the poor association
Research Fellow in Rheumatology, based at the Academic
between clinical remission criteria and true remission (see below). Unit of Musculoskeletal Disease at the University of Leeds
and the Leeds Teaching Hospitals Trust. Her major research
interest is remission induction and maintenance in
The assessment of true remission appears to require objective criteria
rheumatoid arthritis, allied with a clinical interest in
such as imaging, immunology and duration (sustainability), and should
resistant rheumatoid arthritis and biologic therapies. She
graduated from Leeds University Medical School in 1999.
account for the therapeutic agent used.
Paul Emery is Professor of Rheumatology and Head of the
Clinical Remission Criteria
Academic Section of Musculoskeletal Disease at the Leeds
The available definitions of remission are based on mainly subjective
Institute of Molecular Medicine, University of Leeds, and
clinical parameters. The American College of Rheumatology (ACR) –
Clinical Director of Rheumatology at the Leeds Teaching
Hospitals Trust. He is President-Elect of the European League
formerly the American Rheumatism Association (ARA) – preliminary Against Rheumatism (EULAR) and has served on the editorial
criteria for remission
4
were developed in 1981 and modified more
boards of several journals. Professor Emery’s research
interests centre on the immunopathogenesis of and
recently. The European League Against Rheumatism (EULAR) disease
immunotherapy for rheumatoid arthritis and connective
activity scores (DAS and DAS28) are widely used in research and daily tissue diseases. He has a special interest in the factors leading to persistent inflammation and
clinical practice.
5
Recently, the DAS28 cut-offs for remission have been
has published over 500 peer-reviewed articles in this area. Professor Emery is a recipient of the
Roche Biennial Award for Clinical Rheumatology, the Rheumatology Doctor of the Year Award
criticised for underestimating active disease, and the appropriateness of
in 1999 and the EULAR prize for outstanding contribution to rheumatology research in 2002.
the DAS28 in remission assessment has been questioned.
6–8
The
E:
p.emery@leeds.ac.uk
simplified disease activity index (SDAI), by using more stringent criteria,
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