Anti‐tumour necrosis factor‐α: the dawn of a new era in the treatment of rheumatoid arthritis

Abstract

The reports from the Kennedy Institute in London in 1993 and 1994 that monoclonal antibodies to the cytokine tumour necrosis factor-α could significantly suppress symptoms and signs of rheumatoid arthritis (RA) will go down in history as one of the events that has changed the face of rheumatology.1, 2 It has changed not only the lives of patients with RA, ankylosing spondylitis (AS) and other chronic rheumatic diseases, but also the way physicians practise in the management of these conditions. American College of Rheumatology ACR50 and ACR70 responses are now readily achievable and in some patients full remission is being reported. As these drugs are used earlier in the onset of RA there is some data to suggest even higher remission rates. The three most commonly used agents, infliximab, etanercept and adalimumab, are now being joined by others, and the pharmaceutical industry is not only producing more TNF inhibitors, but stimulating research into other cytokine inhibitors. The appropriate dose, what drugs to combine with TNF-α inhibitors and a range of other questions still need to be addressed. In an editorial on the first decade of use of TNF-α inhibitors, Kavanaugh et al.3 raise a number of important issues relating to TNF inhibitors: there is synergy between methotrexate and TNF inhibitors; switching from one agent to another may be effective; and; treatment not only improves signs and symptoms and quality of life, but also slows radiological progression. They also raise important issues in relation to such things as toxicity, what is the best strategy for treating partial responders and pose the question as to whether TNF-α inhibitors should be used as initial therapy in early RA. These compounds are still very expensive and this in itself has raised the profile of rheumatologists within the healthcare system (almost to the level of the oncologist) in terms of their interaction with healthcare funders and hospital administrators. The issue of safety of TNF inhibitors is a particularly important one and very relevant to the Asia-Pacific region. There remain concerns about the association of TNF inhibitor use and infections, particularly tuberculosis (TB),4 and this needs to be considered carefully given that the early trials of these drugs were carried out in countries where the incidence of community tuberculosis is much lower than in any of the countries where these drugs are now being used (for example in the south-east Asia-Pacific region). This has led to the development of a number of guidelines5 that need to be considered when using these drugs in such areas. Interest in this topic has stimulated our Journal to provide this supplement which explores the Asia-Pacific experience in biologic therapies. These data and experiences are most important as we cover over half the world's population and the outcomes, both positive and negative, may be quite different to those seen in clinical trials or clinics carried out in Europe or the Americas. We have been able to call upon many prominent rheumatologists from this region to contribute their experience on the use of TNF inhibitors in the management of RA, various spondyloarthropathies, notably AS, and other chronic inflammatory rheumatic disorders. Important questions related to their use include the following. (i) When are these therapies indicated in APLAR patients? (ii) Are there ethnic differences in patients’ clinical responses? (iii) Can APLAR, where a large number of members are developing countries, afford these high-cost therapies? And can patients be maintained on a lower-dose regimen? (iv) While on cost, how pharmaco-economical are these agents? At which point should these novel biologics be considered? And how do they compare with conventional disease-modifying anti-inflammatory drugs (DMARDs)? (v) Are APLAR patients more susceptible to the various possible side-effects of TNF inhibitor agents, particularly chronic infections such as TB? (vi) If TB is a concern, what is (are) the best way(s) to avoid the development of this potentially serious complication? (vii) How should we educate our patients on the use of TNF inhibitors? (viii) What if these therapies fail? Are there alternatives on the horizon? (ix) Finally, what are the clinical effects of anti-TNF-α agents on other immune-mediated rheumatic conditions? We believe that this special issue will add a new and important perspective to data on TNF inhibitors and allow us to understand their use in our region.