Anti-TNF therapy: what have we learned in 12 years?

not eff ective for many persons with rheumatoid arthritis (RA) and other infl ammatory rheumatic diseases. At this time RA patients had a signifi cantly decreased life expectancy due to a relatively incontrolled infl ammatory activity of RA combined with an increased incidence of comorbidities and severe treatment-related side eff ects. After 5 years of disease duration, a considerable percentage of patients became unemployed. Th e available disease-modifying anti rheu matic drugs were able to slow disease progression, but they could not stop it. Th is unsatisfying situation changed signifi cantly at the beginning of the 1990s, when treat ment options for RA patients expanded to include TNF blockers. Th ese blockers were shown to signifi cantly decrease not only the infl ammatory activity of RA, but also the radiographic progression. Th is breakthrough in therapeutic options was fostered by the pioneering research of Prof. Sir Ravinder Maini and Prof. Sir Marc Feldman working at the Kennedy Institute in London, who introduced a chimeric monoclonal antibody against TNFα in the treatment of RA patients. Since these early clinical trials, TNF inhibitors have radically changed the entire therapeutic approach, not only for RA but also for ankylosing spondylitis (AS) and for psoriatic arthritis (PsA). While the focus once was symptom mitigation, rheumatologists now seek control of disease progression. Today, TNF inhibitors eff ectively suppress and control the infl ammation driving these diseases, and thereby prevent irreversible tissue damage and disability. Radiographic studies are showing that progressive joint damage can be halted under certain conditions in some patients. Th ese conditions and patients are currently being elucidated. New frontiers include early diagnosis and referral; optimizing treatment regimens; identifying patients at risk of rapidly progressing disease; and instituting early, rapid TNF blockade in these patients. Using combination therapy with TNF inhibitors and disease-modifying antirheumatic drugs – specifi cally methotrexate – at an early stage of RA, disease progression can be stopped or at least signifi cantly retarded. Th e four articles in this supplement present up-to-date information, current data, and the best thinking on antiTNF therapy in RA, AS, and PsA. Since research over the past decade revealed that these three disorders share an infl ammatory mechanism fueled especially by TNF, eff orts to produce viable TNF inhibitors have accelerated. Josef S Smolen and Paul Emery, in their article ‘Infl iximab: 12 Years of Experience’, expound upon the record of effi cacy and safety amassed for this TNF inhibitor. Research on infl iximab, which began with the fi rst randomized controlled study in a rheumatic disease, stimulated most of the development of TNF neutralizing therapies. Th e authors summarize the major trials in RA, AS, and PsA that contributed to this body of evidence. In the second article, ‘Understanding Emerging Treatment Paradigms in Rheumatoid Arthritis’, Ferdinand C Breedveld and Bernard Combe assert that most patients with RA are undertreated. Th ey outline accumulating data showing that intensive treatment in the early stages of RA can slow or stop disease progression, and they describe alternatives to traditional step-up approaches and to sequential monotherapy with disease-modifying antirheumatic drugs. Next, Georg Schett and colleagues focus on bone and cartilage injury in all three diseases, with an emphasis on key knowledge arising from TNF research and how it has paved the way for future advances. Th eir article, ‘Structural Damage in Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis: Traditional Views, Novel Insights Gained from TNF Blockade, and Concepts for the Future’, explores the diff erent pathologies as well as radiographic data for the interaction between infl ammation and structural progression. Lastly, Paul P Tak and I discuss innovative approaches – with TNF inhibitors but also with other biologic agents – to infl ammatory arthritides, including new targets within the infl ammatory cascade, agents designed to aff ect associated pathways, and improved management strategies involving early diagnosis and referral. In the article © 2010 BioMed Central Ltd Anti-TNF therapy: what have we learned in 12 years?