Elsevier

The Lancet

Volume 358, Issue 9285, 15 September 2001, Pages 903-911
The Lancet

Review
Rheumatoid arthritis

https://doi.org/10.1016/S0140-6736(01)06075-5Get rights and content

Summary

Rheumatoid arthritis is a systemic inflammatory disorder that mainly affects the diarthrodial joint. It is the most common form of inflammatory arthritis, and has a substantial societal effect in terms of cost, disability, and lost productivity. Although the pathogenesis of rheumatoid arthritis remains incompletely understood, much insight into the cellular and molecular mechanisms involved has been gained in the past decade. On the basis of these insights, new therapies have been developed, and clinical trials have shown the efficacy of aggressive treatment of patients with active disease. In this review, we discuss improvements in our understanding of the pathophysiology of inflammatory synovitis in rheumatoid arthritis, and improvements in therapy for patients with the disorder. The past decade has seen substantial advances in these areas. Future studies will be directed at improving methods for early diagnosis and identification of patients with progressive disease, and at improving methods to identify candidates for subclasses of disease-modifying antirheumatic drugs (DMARDs). Long-term safety and efficacy data for the new DMARD agents and combination regimens will also further delineate efficacy and toxicity and thus the appropriate clinical context for use of these therapeutic approaches. The continuing elucidation of pathophysiological pathways relevant in rheumatoid arthritis, coupled with continuing advances in biotechnology and rational drug design, offer substantial hope for the continued development of increasingly potent and specific pharmacotherapy for treatment of rheumatoid arthritis.

Section snippets

Clinical features

The range of presentations of rheumatoid arthritis is broad, but disease onset is insidious in most cases, and several months can elapse before a firm diagnosis can be ascertained. The predominant symptoms are pain, stiffness, and swelling of peripheral joints (Panel 1). The clinical course of the disorder is extremely variable, ranging from mild, self-limiting arthritis to rapidly progressive multisystem inflammation with profound morbidity and mortality (Panel 2). Analyses of the clinical

Genetic data

The results of several studies have shown a higher disease concordance among monozygotic twins (12–15%) than dizygotic twins (4%), implying the influence of genetic factors.6, 7 Heritability analysis of these studies suggests that about 60% of a population's predisposition to rheumatoid arthritis can be accounted for by genetic factors,8 although on analysis of twin pairs concordant for rheumatoid arthritis, striking diversity in disease severity was noted.8, 9

Analysis of genetic markers has

Paradigm shift

The past decade has seen a major transformation in the treatment of rheumatoid arthritis in terms of approach and choice of drugs. The previous therapeutic approach, termed the therapeutic pyramid, generally involved initial conservative management with non-steroidal anti- inflammatory drugs (NSAIDs) for several years; disease- modifying antirheumatic drugs (DMARDs) were withheld until clear evidence of erosions was seen. DMARDs were then added individually in slow succession as the disease

Conclusions

The ability of the new anti-TNF-α biological response modifiers to intervene in the disease process has generated enthusiasm for therapeutic interventions and for the possibility of future drugs that target individual inflammatory pathways. However, this excitement is tempered by the potential for long-term side-effects and toxicity. Rare events that have now been seen with anti- TNF therapy include infections (Mycobacterium tuberculosis, fungal and bacterial sepsis), a lupus-like syndrome, and

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