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Introduction

Autoimmune rheumatic
diseases: an introduction

About 1 in 20 individuals will develop an autoimmune condition during their lifetime, and autoimmune rheumatic diseases, which this volume of Medicine focuses on, are prominent
amongst them. The burden of these diseases both to the individual and to society cannot be underestimated. In economic
terms, for example, it is estimated that rheumatoid arthritis
costs the UK health system over 1 billion per annum due to
both the costs of looking after the patients per se and the loss of
productivity, as so many of them have been unable to continue
working.

David A Isenberg

Studies in rheumatoid arthritis

Abstract

In the past decade it has become widely acknowledged that


biological therapies which block TNF- have a significant role
to play in patients who fail to improve on conventional drugs,
such as methotrexate and sulphasalazine. A Biologics Register established by the British Society for Rheumatology will
shortly close its books, registering 4,000 patients each treated
with etanercept, infliximab and adalimumab. There are also
4,000 controls who have rheumatoid arthritis but who are not
being treated with the TNF- blockers. From an analysis of
over 13,000 patients already registered it is clear that about
7075% of patients given any TNF- blocker will show a useful clinical and serological response. Intriguingly, a very similar figure is being seen for patients who have failed a single
TNF- blocker (because of lack of effects or presence of side
effects) and are switched to a second such agent. Furthermore,
it is increasingly likely that there is going to be a role for rituximab, which blocks the CD20 antigen present on many B cells,
and CT4LAIg (abatacept) which interferes with a so-called
second signal between the antigen presenting cells and the
T lymphocytes.
Waiting not far behind in the wings are a host of other
potential therapeutic agents including monoclonal antibodies
which block interleukin 6 receptor, interleukin 10 and interleukin 15. It remains to be seen which of these drugs will, in the
end, be the winners or losers but the sense of excitement is truly
palpable.

Recently, diseases of the immune system have become better understood


and immunosuppressive therapy is now available to treat a wider range
of conditions. In addition, the advancement of biological therapy offers
the possibility of treating autoimmune disorders with fewer side effects.
This contribution provides a general introduction to the Medicine issue
dedicated to autoimmune disorders. It summarizes the developments
that have occurred in the area of autoimmune diseases over the past few
years, including advances in the treat.

Keywords autoimmune diseases; biological agents; B cell depletion;


immunosuppressive drugs; TNF- blockers

We are entering a very exciting time in human history as diseases of the immune system which have plagued mankind for
centuries are becoming much better understood and amenable to
more targeted therapies. Although not all autoimmune diseases
require immunosuppressive therapy (autoimmune hypothyroidism is a good example where replacement of the missing hormone, thyroxine, is a safe and effective treatment), a wide range
of conditions from chronic active hepatitis (which affects a single
organ or system) to systemic lupus erythematosus (which affects
virtually all organs or systems) are increasingly being treated by
monoclonal antibodies. This so-called biological therapy offers
the tantalizing prospect of effective treatment with far fewer side
effects. The classic immunosuppressive drugs, from corticosteroids to cyclophosphamide, were a major advance on what went
before (which was virtually nothing!) and have also contributed
significantly to both the morbidity and mortality of the autoimmune diseases. However, the capacity for biological agents to
induce serious side effects, as was observed recently at Northwick Park Hospital, cannot be ignored. It may be that the biological agent used in this case, which aimed to stimulate a T cell (via
the CD28 receptor), will prove highly exceptional but great care
will be needed with new approaches in the future.

Other diseases
The use of B cell depletion, employing rituximab either alone or
together with steroids and cyclophosphamide, has already been
shown to be of value, albeit in open label studies, in patients
with lupus, Wegeners granulomatosus, dermatomyositis and
Sjgrens syndrome. TNF- blockade using infliximab has shown
to be of benefit in patients with lupus and some forms of TNF-
blockade also help patients with Crohns disease. A variety of
agents are being tried in multiple sclerosis and it is possible to
say with confidence that within the next decade, certainly for
patients with more severe autoimmune diseases, major changes
in standard therapy are going to occur.

Clinical trials

David A Isenberg MD FRCP is Arthritis Research Campaign Professor of


Rheumatology at University College London, UK. His research interests
are clinical assessment and the structure, function and origin of
autoantibodies. Competing interests: none declared.

MEDICINE 34:11

In the past few years it has clearly been established that the
prospective double blind placebo controlled clinical trial is an
essential tool in demonstrating the effectiveness of the biological
439

2006 Elsevier Ltd. All rights reserved.

Introduction

These tools are available for use in many autoimmune rheumatic


diseases and are being applied for use in clinical trials.

agents. For many autoimmune diseases international efforts have


focused on developing the three types of essential tools which
are needed to capture the totality of the effect of one of these
diseases on a patient:
a disease activity index (which captures potentially reversible
change)
a damage index (which captures those clinical features that
are permanent)
a health perception index (the SF36 index has been widely
used for this purpose).

MEDICINE 34:11

Conclusion
This volume of Medicine will, I hope, demonstrate that not only
do we have a much better understanding of autoimmune diseases
in general, and autoimmune rheumatic diseases in particular, but
also that more targeted therapy using biological agents has really
arrived at the bedside having escaped from the laboratory!

440

2006 Elsevier Ltd. All rights reserved.