In general, RIX is contraindicated in the presence of serious and opportunistic infections. and we might soon witness the transition from today’s abatement to tomorrow’s remedy with regard to the quality of disease remission in the field of rheumatic conditions, with rheumatoid arthritis (RA) as one of the most frequent entities. At present, achieving complete remission is the ultimate aim, at least for patients with recently diagnosed, early RA. The reduction of clinical disease activity below a disease activity score of 2.6 when evaluating the 28 relevant joints (DAS28), as well as the exclusion of still remaining clinically silent synovial inflammation, are considered to be the principal goals of current rheumatologic treatment concepts [1]. In cases with longer histories and at later stages of disease, however, the cutoff level for individually acceptable residual disease activity might have to be further defined together with the patient, and on the basis of this, individual stage -adapted medication evaluated constantly in close agreement with the patient [1,2]. Past pharmacologic options used to induce remission from RA included chrysotherapy, which became the first established ‘gold’ standard. In 1928, Jacques Forestier had already started to use gold salts therapeutically in France, assuming an infectious factor in RA, which was in the tradition of Robert Koch’s evaluation of gold compounds against real cultures of em Mycobacterium tuberculosis /em [3]. Gold salts, however, were just one drug amongst a growing number of long-acting, remission-inducing agents Gestrinone showing only slow action in decreasing the inflammatory activity of RA. Owing to this mode of action, they have been termed ‘second-line’ medication, also known as disease-modifying anti-rheumatic drugs (DMARDs); apart from gold salts, these also include medications such as azathioprine, chloroquine and hydroxychloroquine (HQ), cyclosporin A (CsA), cyclophosphamide, lefluno-mide (LEF), methotrexate (MTX), and sulfasalazine (SSZ). The mechanisms of action of some of these drugs are still not fully defined, but they are likely to involve an overlap between anti-inflammatory, immunosuppressive and cytotoxic properties. Nonetheless, only DMARDs may significantly slow, stop or even reverse the damage arising from chronic inflammation in cartilage or bone, as shown in an em in vitro /em study on human chondrocytes in alginate cultures [4], for example, as well as in clinical trials implementing radiographic follow-up of patients (see ‘Current repertoire, profiles and clinical evidence for biologics in RA’ below). However, although DMARDs may slow radiographic progression, data also illustrate that progression can continue despite clinical disease control or remission [5]. First-line non-steroidal anti-inflammatory drugs (NSAIDs) and steroids, in contrast, more rapidly inhibit local inflammatory symptoms but have only little to no long-lasting effects on the systemic aspects of RA, as reflected by increased erythrocyte sedimentation rates or elevated levels of C-reactive protein. Therefore, systemic signs of inflammatory rheumatic conditions that patients may complain of – for example, loss of efficiency, lassitude or weight reduction – are not improved by non-selective cyclooxygenase inhibitors, such as diclofenac, ibuprofen, naproxen, piroxicam, meloxicam, indometacin or ace-metacin, nor by the selective cyclooxygenase-2 inhibitors celecoxib or etoricoxib. Members of the so-called biologics, formally classified as a distinct subgroup within the DMARDs, form part of a specific therapeutic strategy targeting pro-inflammatory key cytokines and cellular functions that have deleterious effects during the course of RA. Current options include not only several Gestrinone agents against TNF-, but also Rabbit Polyclonal to Tip60 (phospho-Ser90) compounds directed against IL-1 or IL-6 and modulators of B-cell or T-cell activity. Since biologics are known for their potential to abolish disease progression and persistent residual activity, it is not unreasonable to alternatively call them disease-controlling anti-rheumatic drugs [6]. Most importantly, the ongoing developments in this field require a thorough knowledge of the properties and Gestrinone effects the currently available repertoire of target-specific biological agents may display in the treatment of RA. This review refers to the recent clinical evidence for the use of different biological therapies in.
Categories:Ubiquitin/Proteasome System