[Recent progress in clinical trials for rheumatic diseases].
Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease that causes significant morbidity and mortality. RA patients should be started with DMARD represented by methotrexate (MTX) as early as possible. However, even use of MTX often fails to control disease activity and to prevent structural damage and, thereby, more effective treatment strategies are needed. Since TNF-alpha and IL-6 play a pivotal role in the pathological processes of RA, biologics targeting these cytokines with MTX, have revolutionized the treatment of RA, producing significant improvement in clinical, radiographic and functional outcomes not seen previously. However, even with these drugs the frequency and degree of responses are restricted. Therefore, new agents targeting cell surface molecules which are involved in cellular interaction and/or signaling on immune cells have been emerging, in order to increase response rates and to achieve high frequencies of remission or even cure. Two biologics abatacept, a CTLA4-Ig fusion protein, and rituximab, an anti-CD20 antibody, were launched in US and EU for the treatment of RA and many biologics are under the clinical trials from the similar concept. Thus, certain biologics have brought about paradigm shift in the treatment of rheumatic diseases, but an economical issue remains unsolved. In order to overcome the concern, low molecular weight chemical products have been rethought. Not a few agents targeting intracellular activation signaling in immune cells such as Jak and Syk are under clinical examinations and some of them appear to show wonderful results, which are comparable to biologics in the context of the treatment of rheumatic diseases. The prospects are here.
Tanaka
Yoshiya
Y
The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health.
D000069594:Abatacept; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents / Q000008:administration & dosage; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000209:etiology; D002986:Clinical Trials as Topic; D015195:Drug Design; D004359:Drug Therapy, Combination; D006801:Humans; D018796:Immunoconjugates; D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; D053616:Janus Kinase 3; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000209:etiology; D008727:Methotrexate / Q000008:administration & dosage; D011505:Protein-Tyrosine Kinases; D012216:Rheumatic Diseases / Q000188:drug therapy* / Q000209:etiology*; D000069283:Rituximab; D015398:Signal Transduction; D000072377:Syk Kinase; D014409:Tumor Necrosis Factor-alpha
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D018796:Immunoconjugates; D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; D014409:Tumor Necrosis Factor-alpha; D000069283:Rituximab; D000069594:Abatacept; D011505:Protein-Tyrosine Kinases; D053616:Janus Kinase 3; C000606896:SYK protein, human; D000072377:Syk Kinase; D008727:Methotrexate