Rheumatoid Arthritis: Furlan A

Efthimiou P, Flavell RA, Furlan A, Gasbarrini G, Gava A, Koné-Paut I, Manna R, Punzi L, Sutterwala FS, Touitou I, Doria A. · Rheumatology Section, Lincoln Medical and Mental Health Center, New York, USA. · Clin Exp Rheumatol. · Pubmed #18570755 No free full text.

Abstract: The autoinflammatory syndromes are a group of disorders characterized by recurrent episodes of seemingly unprovoked inflammation without significant levels of autoantobodies and antigen specific T cells. Although a direct association between defective innate immune responses to bacterial components and these diseases has not been formally established, much ongoing research is aimed towards confirmation of that hypothesis. This article will review recent advances in the study of a subset of NOD-like receptors (NLRs), which control the activation of caspase-1 through the assembly of a large protein complex called inflammasome. Moreover, we will review recent progresses in understanding of a range of autoinflammatory conditions in humans.

Botsios C, Ostuni P, Sfriso P, Furlan A, Fiocco U, Sgarabotto D, Todesco S. · Dipartimento Scienze Mediche e Chirurgiche, Universitá degli Studi, Padova, Italia. · Reumatismo. · Pubmed #14872221 links to  free full text

Abstract: Different animal studies show that several proinflammatory cytokines are essential for natural resistance to specific infections, particularly versus intracellular organisms. However, uncontrolled overproduction of some proinflammatory cytokines, in diseases such as rheumatoid arthritis, can be just as dangerous to the host as the absence of the same cytokines. Reduction in the production and/or activities of proinflammatory cytokines in rheumatoid arthritis remains a therapeutic objective for many patients. The tumour necrosis factor-alpha (TNF-alpha) blockers infliximab, etanercept and adalimumab and the recombinant interleukin 1 (IL-1) receptor antagonist anakinra are effective in patients with active rheumatoid arthritis. However, there is a growing body of clinical evidence that neutralization of TNF-alpha is associated with an increased risk of opportunistic infections, including mycobacterial diseases. Blockade of IL-1 activity with the IL-1 receptor antagonist (IL-1Ra) appears, at present, to be relatively safe. Postmarketing experience and pharmacovigilance programs are necessary to determine the overall safety profile of the new agents. At this time, treating physicians must weigh carefully the benefits of biologics against their safety, particularly in patients at risk of infection.

Botsios C, Sfriso P, Furlan A, Ostuni P, Biscaro M, Fiocco U, Todesco S, Punzi L. · Cattedra e U.O.C. Reumatologia, Università-Azienda Ospedaliera di Padova, Italia. · Reumatismo. · Pubmed #17435840 links to  free full text

Abstract: OBJECTIVE: We evaluated both the efficacy and safety of anakinra in daily routine rheumatoid arthritis clinical practice. METHODS: We studied 60 cases, including patients with previous anti-TNFalpha exposure, treated with anakinra (100 mg/daily s.c.) in combination with methotrexate (7.5-10 mg/week i.m.) or leflunomide (20 mg/die) in a two year observational study. Efficacy measures were assessed using the American College of Rheumatology (ACR) response criteria. Safety was evaluated according to a modified World Health Organization adverse reaction term dictionary. RESULTS: At week 14, ACR 20% response criteria have been fulfilled by 53 (91.3%) out of 58 patients, 51 (87.9%) of them achieving also an ACR 50%and 15 (25.8%) an ACR 70%response. Thirteen patients touched 102 weeks of treatment: ACR 20% response was achieved in 92.3%, while ACR 50% and ACR 70% were respectively found in 84.6% and 38.4% of the cases. The mean decrease in HAQ score was 0.38, p<0.001. Of the 16 patients who were previously treated with anti-TNFalpha blockers, 81.2% responded to anakinra. There was no significant difference in the ACR response between groups with and without previous anti-TNFalpha exposure. Seventeen patients (28.3%) stopped anakinra because of side-effects (5%) or failure to respond (23.3%). Only 4 cases of pulmonitis, of which 2 have been hospitalised, and 1 case with tuberculosis (previously treated with infliximab) were observed. CONCLUSIONS: Our clinical experience confirms that anakinra is effective and safe in the treatment of rheumatoid arthritis. Anakinra seems also useful in patients with previous anti-TNFalpha blockers failures. Even though major adverse events were rare, clinicians should be aware of such a possibility.

Day D, Furlan A, Irvin E, Bombardier C. · Institute for Work & Health, Toronto, ON, Canada. · J Clin Epidemiol. · Pubmed #16167387 No free full text.

Abstract: BACKGROUND AND OBJECTIVES: Assess the efficacy of simplified search strategies and identify the best electronic bibliographic database for clinical trials in the field of musculoskeletal disorders and pain. METHODS: Clinical trials within selected reviews from the Cochrane Back, Musculoskeletal, and PaPaS Review Groups were searched using MEDLINE, EMBASE, CINAHL, and CENTRAL to identify which database included the highest percentage of trials. Simplified search strategies for each review were devised and compared to the original, more complex strategy for sensitivity, specificity and precision. RESULTS: Individually, MEDLINE, and EMBASE included 90 and 89% of the relevant studies respectively, and 94% when combined. CENTRAL contained 87% and CINAHL 31%. Generally, simplified search strategies (two to four lines) had higher specificity than the original strategies (approximately 27 lines). Sensitivity was also high, but varied according to intervention. Super simple search strategies (one to two lines) proved as sensitive, but were slightly less specific, depending on the intervention. Both simple and super simple search strategies were often more precise than the original. CONCLUSION: Simplified search strategies are an effective, efficient way to search for clinical trials. They work best when the intervention is a pharmaceutical or a well-defined physical treatment. Their sensitivity, however, is not adequate for conducting systematic reviews.