Rheumatoid Arthritis: Quartuccio L

De Vita S, Quartuccio L. · Rheumatology Clinic, DPMSC, University of Udine, 33100 Udine, Italy. · Autoimmun Rev. · Pubmed #16920570 No free full text.

Abstract: Based on new biologic and clinical insights, the number of drugs blocking different biologic targets in rheumatoid arthritis (RA) [e.g., tumor necrosis factor alpha (TNFalpha), CTLA4, interleukin (IL)-1, IL-6, IL-15, IL-18, B lymphocyte stimulator (BLyS), CD20] has increased considerably over the last decade. Rituximab, a chimeric monoclonal antibody that was developed for the treatment of B-cell lymphomas, has been used in different autoimmune diseases where B-cells are thought to play a pivotal role. However, blinded randomised controlled trials have been completed only for RA so far, indicating the clear efficacy of B-cell blockade in RA and highlighting the pathogenetic B-cell in rheumatoid synovitis. The use of rituximab in RA is herein updated, from early preliminary studies to more recent presentations in International Conferences. Key clinical and biologic issues are discussed, i.e., efficacy and safety of rituximab, role of concomitant therapies, use in the long term and retreatment strategies, differences with anti-TNFalpha therapy. The possible indications in RA are finally discussed, also on the ground of personal experience with rituximab in RA and other rheumatic diseases associated with B-cell lymphoproliferation. Further clinical research should go hand in hand with laboratory research, and tissue studies are now needed.

Quartuccio L, Fabris M, Ferraccioli G. · Clinica di Reumatologia, Università degli Studi di Udine. · Reumatismo. · Pubmed #15470519 links to  free full text

Abstract: Recently, a new member of the TNF family, BLyS, was identified. This protein, synthesized by myeloid cell lines, specifically interacts with B lymphocytes and increases their life-span. BLyS was studied in the murine models of some autoimmune diseases and it was demonstrated that it has a key role in the B lymphocyte system homeostasis and in the relation between chronic inflammation and autoimmunity. Analysis of BLyS plasma levels in Systemic Lupus Erythematosus, Sjogren's Syndrome and Rheumatoid Arthritis (RA) has shown that BLyS is higher in a group of patients than in the controls. In RA, BLyS correlates with the disease activity, in particular, with the swollen joints count; so, at least part of the chronic rheumatoid synovitis could be the epiphenomenon of the B cells activation driven by monocyte-macrophage population. More studies are necessary to understand the role of BLyS in the interaction between the monocyte and the B lymphocyte in some autoimmune disease and the possible usefulness of this cytokine as a diagnostic or prognostic marker and/or therapeutic target.

De Vita S, Quartuccio L, Fabris M. · Rheumatology Clinic, DPMSC, University of Udine, Udine, Italy. · Dig Liver Dis. · Pubmed #17936213 No free full text.

Abstract: Type II mixed cryoglobulinemia syndrome (MCsn) is a systemic vasculitis mainly linked to immune complex deposition in several organs and to hepatitis C virus (HCV) infection. Therapeutic strategies can target either the viral trigger HCV if present, or pathogenic events downstream the triggering infection, e.g, the proliferating B-cells directly. Antiviral therapy should be considered as first-line treatment in many HCV-positive patients. However, it may prove ineffective, contraindicated, or poorly tolerated. On the other hand, the other available treatments (such as cytotoxic agents, plasma exchange and steroids) may lead to life-threatening complications and may be difficult to manage in the long term. Given the good safety profile in lymphomas, rituximab (RTX) has been used off-label for numerous patients suffering from a variety of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis/ polymyositis, and anti-neutrophil cytoplasmic antibody (ANCA)-positive vasculitis. Efficacy and safety of RTX in MCsn and in particular in MCsn-related glomerulonephritis was recently described. Based on these results, a multicentre, controlled, randomised, clinical trial is now ongoing to compare RTX versus the best available treatments in some severe MCsn manifestations (i.e. skin ulcers, sensory and/or motor neuropathy and active glomerulonephritis).

Quartuccio L, Ferraccioli GF, De Vita S. · No affiliation provided · Scand J Rheumatol. · Pubmed #17062445 No free full text.

This publication has no abstract.

Quartuccio L, De Re V, Fabris M, Marzotto A, Franzolini N, Gasparotto D, Caggiari L, Ferraccioli G, Scott CA, De Vita S. · Rheumatology Clinic, DPMSC, University of Udine, Italy. · Haematologica. · Pubmed #16670074 links to  free full text

Abstract: A patient with rheumatoid arthritis (RA) developed an atypical lymphoproliferative disorder (LPD) after methotrexate and cyclosporine A, which regressed after suspension of both drugs. After subsequent treatment with rituximab, the LPD was still undetectable. Anti-tumor necrosis factor a therapy was used when the arthritis relapsed, but an aggressive B-cell non Hodgkin's lymphoma developed. Molecular analyses showed an oligoclonal B-cell expansion at the LPD step. A minor clone with significant sequence homology to B-cell lymphomas arising in Sjogren's syndrome and mixed cryoglobulinemia syndrome, given rise to the non-Hodgkin's lymphoma. Treatment of rheumatoid arthritis associated with lymphoproliferation represents a clinical challenge, and common pathogenetic pathways to lymphoma may occur in different autoimmune diseases.

Quartuccio L, De Vita S. · No affiliation provided · J Rheumatol. · Pubmed #17407250 links to  free full text

This publication has no abstract.