Rheumatoid Arthritis: Streit G

Toussirot E, Streit G, Wendling D. · Department of Rheumatology, University Hospital Jean Minjoz, Bd. Fleming, F-25030 Besancon Cedex, France. · Recent Pat Inflamm Allergy Drug Discov. · Pubmed #19075965 No free full text.

Abstract: TNFalpha plays a pivotal role not only in the inflammatory process but also in the normal response against pathogens and therefore, interfering with this cytokine may increase the risk of infection. TNFalpha antagonists are commonly used in daily clinical practice for the treatment of inflammatory rheumatic diseases including rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and juvenile idiopathic arthritis since the beginning of 2000. The spectrum of pathogens giving infectious disease in patients under anti-TNFalpha therapies ranges from common bacteria to more opportunistic organisms such as Mycobacterium tuberculosis. The infections which were described with TNFalpha inhibitors may have a benign course or may be a serious, life threatening disease, and may be localized or disseminated. These TNFalpha inhibitors related infections were described in the randomized clinical trials, and were then declared to post-marketing surveillance systems and special registries. Tuberculosis (TB) is the most frequent opportunistic infection which has been reported with TNFalpha antagonists and the highest risk appears to be associated with infliximab, and at a lesser extent with etanercept. Currently available data and recent patents on the risk of TB with adalimumab are not sufficient to conclude, but TB cases were also reported with this agent. The description of TB infections with TNFalpha inhibitors led to the establishment of new guidelines for screening patients at high risk of developing TB. These data highlight the importance of post-marketing surveillance and special registries for accurately evaluating the safety profile and particularly the infectious risk of this very effective class of drug in inflammatory rheumatic diseases.

Toussirot E, Streit G, Wendling D. · Department of Rheumatology, Jean Minjoz University Hospital, Bd Fleming, F-25030 Besançon Cedex, France. · Curr Med Chem. · Pubmed #17456023 No free full text.

Abstract: Adipokines are proteins produced by white adipose tissue, which is an active secretory organ. Regulation of immune and inflammatory responses is among the multiple physiological processes involving adipokines. Leptin, adiponectin and resistin are the most extensively studied adipokines. Leptin may promote inflammation by inducing Th1 phenotype development, whereas adiponectin may combat inflammation by reducing the production of pro-inflammatory cytokines. Resistin belongs to a family of proteins found in foci of inflammation, where they contribute to the inflammatory response. All three adipokines have been detected in synovial fluid from joints affected with the inflammatory disease rheumatoid arthritis (RA) or the degenerative disease osteoarthritis (OA). Recent evidence points to involvement of leptin in RA and OA and indicates that adiponectin and/or resistin mediate inflammation in arthritis. Thus, fat tissue is an active organ whose products contribute to inflammatory and degenerative processes underlying common joint diseases.

Wendling D, Streit G, Toussirot E, Prati C. · Service de Rhumatologie, CHU Minjoz et Université de Franche-Comté, 25030 Besançon, France. · Joint Bone Spine. · Pubmed #18674945 No free full text.

Abstract: OBJECTIVE: To assess the rate of occurrence and outcomes of herpes zoster in patients taking TNFalpha antagonists. METHODS: Retrospective review of the medical records of 300 patients who received TNFalpha antagonists to treat chronic inflammatory joint disease. RESULTS: We identified 9 (9/300, 3%) patients who experienced herpes zoster, 6 women and 3 men, with rheumatoid arthritis (n=7) or ankylosing spondylitis (n=2). The drug was infliximab in 4 patients, adalimumab in 2 patients, and etanercept in 3 patients, including 2 patients with a prior history of infliximab therapy (for 12 and 36 months, respectively). Mean treatment duration at the occurrence of herpes zoster was 27 months (range, 6-42 months). DISCUSSION: Glucocorticoid therapy (n=7) and methotrexate therapy (n=6) were the only risk factors identified in our study. Mean follow-up was 26 months. All 9 patients achieved a full recovery with antiviral treatment and interruption of the TNFalpha antagonist. One patient experienced a recurrence after resuming TNFalpha antagonist therapy. CONCLUSION: The scant data in the literature suggest a higher risk of herpes zoster with anti-TNFalpha antibodies than with the soluble receptor. The role for concomitant treatments (glucocorticoids and methotrexate) should be taken into account.