Anti-Citrullinated Protein-Peptide Antibodies in Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease and is the most frequent form of inflammatory joint disease. The prevalence is between 0.5% and 1%; women are affected about three times more often than men. The prevalence increases to about 2% in the fourth and fifth decades of life. RA is characterized by symmetrical, eroding joint synovitis. The systemic character of the disease is evident in the participation of other organs, including the heart and lung. In most patients, signs of destructive arthritis can even be recognized in the first year of the disease by using modern imaging procedures, such as magnetic resonance imaging and joint sonography). The disease is accompanied by chronic pain and extended periods off work. Moreover, the increasing handicap leads to failure in joint function and to inability to work. The various systemic manifestations and the increased cardiovascular risk decrease life expectancy (1). Since the switch in paradigm—from retarding the start of therapy to early aggressive therapy—and since the introduction of biologicals, the development of the disease can now be effectively delayed or sometimes even be halted. Numerous studies, such as the treatment strategy studies [Behandlungs-Strategie-Studien; BeSt], have shown that if the treatment is started early and continuously adapted to the activity of the disease, this can greatly enhance the chance of success. The initial use of immunosuppressive combination therapies can increase the rate of clinical remissions and more effectively inhibit or prevent progressive joint destruction in many patients. In the BeSt study, the combination MTX + the antiTNF-alpha antibody infliximab was superior to the combination therapy of conventional immunosuppressives (MTX + sulfasalazine + prednisone), with respect to remission rate (28% versus 40% after one year) and attaining a therapy-free remission phase (2). Another very recently published study (COMET study) has confirmed that combination therapy with MTX + the recombinant TNF-alpha receptor/IgG1 fusion protein etanercept is accompanied by a higher remission rate (50% versus 28% after one year) than with MTX monotherapy, if this is initiated in the early stages of RA (early RA, ERA; three to 24 months after the onset of the disease). At the same time, no radiological evidence for joint destruction was found and it was demonstrated that joint function and working ability were maintained (3). In this context, it is particularly important to identify new diagnostic markers which might permit diagnosis of RA as soon as possible. In future, it should be possible to use these markers to improve the predictability of response or failure to conventional monotherapy or combination therapy with immunosuppressives and to facilitate the recognition of the primary necessity of combination therapy with biologicals for patients with more aggressive disease. This sort of risk stratification with prognostic markers would presumably increase the rate of successful therapy, as well as avoiding the risk of overtreating patients with less aggressive disease. In the ideal case, this risk stratification would allow the expected side effects—such as the increased susceptibility to infection under immunosuppressive therapy—to be included in the selection of therapy. The diagnosis and increasingly complex risk stratification necessitate considerable medical effort and could be carried out in specialized early arthritis outpatient clinics. This edition of the Deutsches Arzteblatt International provides an ex-ceptional insight into the value of the measurement of the serum levels of anticitrullinated protein/peptide antibodies (ACPA) in the diagnosis of RA (4).