Rheumatoid Arthritis: Zoli A

Cardillo C, Schinzari F, Mores N, Mettimano M, Melina D, Zoli A, Ferraccioli G. · Department of Internal Medicine, Divisione di Terapia Medica, Università Cattolica del Sacro Cuore, Rome, Italy. <> · Clin Pharmacol Ther. · Pubmed #16952494 No free full text.

Abstract: BACKGROUND: Patients with rheumatoid arthritis (RA) have endothelial dysfunction, which may predispose them to the risk of premature atherosclerosis. This study investigated the involvement of tumor necrosis factor (TNF) alpha in the pathophysiologic characteristics of this abnormality by use of the TNF-alpha-neutralizing antibody infliximab. METHODS: Endothelium-dependent and -independent vasodilator responses to intra-arterial infusion of increasing doses of acetylcholine and sodium nitroprusside, respectively, were assessed by strain-gauge plethysmography in patients (n = 10) with early RA during saline solution infusion and after intra-arterial infusion of infliximab (200 microg/min). RESULTS: Circulating markers of systemic inflammation (C-reactive protein and interleukin 6) were higher in patients than in control subjects (n = 10, both P < .05), whereas plasma levels of TNF-alpha and soluble TNF receptor types 1 and 2 were similar in both groups (all P > .05). During saline solution infusion, the vasodilator response to acetylcholine was blunted in patients with RA compared with control subjects (14.2 +/- 9.2 mL . min-(1). dL-(1) versus 23.7 +/- 9.2 mL . min-(1). dL-(1) at the highest dose, P = .004) whereas vasodilation to sodium nitroprusside was not different between groups (P = .10). In patients with RA infliximab did not modify circulating C-reactive protein levels (P = .29, versus saline solution) but did potentiate the vasodilator response to acetylcholine (21.0 +/- 11.1 mL . min-(1). dL-(1); P = .004, versus saline solution). The response to sodium nitroprusside, in contrast, was not modified by infliximab (P = .28 versus saline solution). CONCLUSIONS: Intravascular administration of anti-TNF-alpha antibody ameliorates endothelial function in patients with RA but does not concurrently affect systemic inflammatory changes. Our findings suggest that enhanced TNF-alpha generation within the vessel wall, rather than systemic mechanisms, plays a role in the pathobiologic features of endothelial dysfunction in RA.

Alivernini S, Mazzotta D, Zoli A, Ferraccioli G. · Division of Rheumatology UCSC-Catholic University of Rome, Rome, Italy. · Drugs Aging. · Pubmed #19552491 No free full text.

Abstract: BACKGROUND: Disease-modifying antirheumatic drugs (DMARDs) play a crucial role in the treatment of persistent chronic synovitis, such as active rheumatoid arthritis (RA) and spondyloarthritis, by inducing or maintaining disease remission, reducing the frequency of flares or relapses, and allowing corticosteroids to be tapered while maintaining disease control. OBJECTIVE: The aim of this retrospective study was to evaluate the safety of, and adherence to treatment with, leflunomide in elderly RA and psoriatic arthritis patients compared with younger patients. METHODS: A total of 90 Italian patients (80 with active RA and 10 with psoriatic arthritis) were retrospectively examined at entry and after 24 months' follow-up. Patients were divided into two groups according to age: those aged <or=65 years (n = 50) and those aged >65 years (n = 40). Each patient was analysed for clinical, demographic and laboratory parameters in order to evaluate liver, renal and haematological toxicity. Disease Activity Score including a 28-joint count (DAS28) and physician global assessment of disease activity (MD global) were measured to define disease activity. RESULTS: During the 24-month follow-up period, 30 patients (33.3%) discontinued leflunomide: 17 patients (34.0%) in the group of patients aged <or=65 years and 13 patients (32.5%) in those aged >65 years. There were no differences in treatment withdrawal between the two groups. Overall, 10 patients (11.1%) in the entire study population discontinued leflunomide for lack of efficacy, while 21 (23.3%) discontinued the drug because of adverse effects (one patient withdrew because of both inefficacy and adverse effects). There were no significant differences in efficacy or adverse effects between patients aged <or=65 years and patients aged >65 years. There was also no significant difference in survival rates of leflunomide treatment when patients aged <or=65 years were compared with patients aged >65 years (p = 0.94). There were no significant differences in withdrawal rates in the overall population when leflunomide monotherapy was compared with leflunomide combination therapy. There were also no significant differences in the types of adverse effects associated with monotherapy or combination therapy when the two age groups were compared. CONCLUSIONS: Leflunomide is a useful and well tolerated DMARD for the treatment of RA and psoriatic arthritis in the elderly. The safety profile of, and adherence to, leflunomide is not different in older patients with chronic inflammatory joint diseases such as RA or psoriatic arthritis to that observed in younger patients.

Bosello S, Santoliquido A, Zoli A, Di Campli C, Flore R, Tondi P, Ferraccioli G. · Division of Rheumatology, Department of Internal Medicine, Catholic University of the Sacred Heart, via G. Moscati, 31-00168 Rome, Italy. · Clin Rheumatol. · Pubmed #18075712 No free full text.

Abstract: Considerable evidence indicates that patients with rheumatoid arthritis (RA) are at greater risk of developing atherosclerosis and cardiovascular disease. Recent studies support the predictive ability of endothelial function measures for subsequent atherosclerotic events. We have investigated the effects of infliximab, a chimeric monoclonal anti-tumor necrosis factor (TNF) antibody, on endothelial vasodilation, measured by brachial ultrasonography and on the levels of inflammatory biomarkers and adhesion molecules in ten consecutive patients with severe long-standing RA, despite methotrexate therapy, during the loading phase of infliximab therapy. Flow-mediated dilation (FMD) in RA patients at baseline was significantly impaired compared with healthy controls (7.71 +/- 2.78% vs 14.91 +/- 6.41%; p = 0.008) and improved significantly after infliximab infusion (12.63 +/- 1.63% vs 7.71 +/- 2.78%; p = 0.005). At baseline, a statistically significant correlation between C-reactive protein levels and FMD was found (r = -0.69, p = 0.026). However, this improvement was transitory, as FMD values returned to baseline values before each infliximab infusion at weeks 2, 6 and 14. There were no significant differences in baseline brachial artery diameter between visits, although at each time, the diameter was increased. According to European League Against Rheumatism response criteria, all ten patients were good responders. No significant differences were observed in intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1, vascular endothelial growth factor and E-selectin plasma levels before and after each infusions. This study demonstrates that endothelial dysfunction is a reversible phenomenon in RA. The addition of anti-TNFalpha treatment reduces inflammatory symptoms in patients with severe RA. The improvement of endothelial function during the loading phase of therapy is transitory, suggesting an enhanced and persistent TNF-alpha generation within the arterial wall.

Ferraccioli G, Zoli A, Alivernini S, De Santis M, Verrillo A, Loperfido F. · Rheumatology Division, Catholic University of the Sacred Heart-Association Columbus, Rome, Italy. · Nat Clin Pract Cardiovasc Med. · Pubmed #16729012 No free full text.

Abstract: BACKGROUND: A 49-year-old man presented at a hospital with an arthritic flare-up and stress dyspnea with a cough. He had a 5-year history of symmetrical polyarthritis, for which he was prescribed 5-15 mg prednisolone daily. He was subsequently diagnosed with rheumatoid arthritis and prescribed 20 mg methotrexate weekly, 3 mg/kg ciclosporin daily and 5 mg prednisolone daily. Infliximab therapy was initiated after 3 months because of persistent joint pain and inflammation. Six months later, however, the patient was readmitted to hospital with a new arthritic flare-up, acute retrosternal chest pain and stress dyspnea. INVESTIGATIONS: Laboratory analyses, electrocardiography, chest radiography, high-resolution CT, echocardiography, technetium-99m-labeled (99mTc)-methoxyisobutyl-isonitrile stress myocardial scintigraphy and coronary angiography. DIAGNOSIS: Lupus anticoagulant and ischemic myocardial microangiopathy. MANAGEMENT: Drug therapy with prednisolone, methotrexate, anakinra, aspirin and clopidogrel.

Scuderi F, Convertino R, Molino N, Provenzano C, Marino M, Zoli A, Bartoccioni E. · Institute of General Pathology, Catholic University, Largo Franesco Vito, 1, 00168 Rome, Italy. · Autoimmunity. · Pubmed #12820688 No free full text.

Abstract: We studied a well-selected population of patients with active rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) without immunosuppressive therapy. Control and patient peripheral blood mononuclear cells (PBMC) were incubated with IL-1beta, IL-10, TGF-beta or LPS for 20 h and the in vitro basal and stimulated secretions of IL-6, TNF-alpha, IL-1beta and IL-1ra were measured by ELISA. We found that in the SLE patients the basal secretion of IL-6 was significantly lower and that of IL-1ra significantly higher than in control subjects, while in the RA group the basal IL-1ra secretion was higher than in healthy subjects. SLE and RA PBMC responded to LPS and IL-1beta reaching higher cytokine secretion values than controls. The in vitro response of SLE and RA PBMC to TGFbeta was normal, while that to IL-10 was defective: IL-10 was able to stimulate the production of IL-6 and IL-1ra in PBMC from normal subjects, but it was unable to enhance IL-6 secretion in RA cells and it was also completely ineffective in inducing IL-1ra secretion in both SLE and RA PBMC. Our work add new data useful for the evaluation of IL-10 and IL-1ra as therapeutic agents in rheumatic diseases.

Zoli A, Lizzio MM, Ferlisi EM, Massafra V, Mirone L, Barini A, Scuderi F, Bartolozzi F, Magaró M. · Istituto di Medicina Interna e Geriatria, Divisione di Reumatologia, Università Cattolica del Sacro Cuore A Gemelli, Rome, Italy. · Clin Rheumatol. · Pubmed #12189455 No free full text.

Abstract: Prolactin (PRL) and glucocorticoids are hormones involved in the regulation of the immune system. Rheumatoid arthritis (RA) is an inflammatory condition that presents a diurnal rhythm of disease activity. ACTH, PRL, cortisol, IL-1 beta and TNF-alpha circadian rhythms have been studied in active RA (aRA) to evaluate a possible relationship between the neuroendocrine system and immunological activity in rheumatoid patients. ACTH, PRL, cortisol, PRL/cortisol ratio and IL-1 beta and TNF-alpha levels were determined in aRA patients and in control subjects at 6.00, 10.00, 14.00, 18.00, 22.00 and 02.00 h. In aRA patients we observed lower ACTH and cortisol levels at 22.00 h and 2.00 h, respectively and higher PRL and PRL/cortisol ratio at 2.00 h when compared to controls. IL-1 beta and TNF-alpha reached their highest serum levels in aRA patients at 2.00 and 6.00 h. This study provides evidence that in aRA there could be a temporary and probably causal relationship between diurnal disease activity, hormonal disequilibrium and cytokine secretion. An imbalance in favour of proinflammatory hormones (PRL and cytokines) as opposed to levels of anti-inflammatory hormones could be responsible for the diurnal rhythm of activity disease observed in aRA patients.

Zoli A, Ferlisi EM, Lizzio M, Altomonte L, Mirone L, Barini A, Scuderi F, Bartolozzi F, Magaro M. · Istituto di Medicina Interna e Geriatria, Università Cattolica del Sacro Cuore A. Gemelli, Rome, Italy. · Ann N Y Acad Sci. · Pubmed #12114312 No free full text.

Abstract: Prolactin (PRL) and glucocorticoids are hormones involved in the regulation of the immune system. Rheumatoid arthritis (RA) is an inflammatory condition that presents a diurnal rhythm of disease activity. PRL/cortisol ratio, and IL-1beta and TNF-alpha levels were determined in patients with RA and in control subjects at 0600, 1000, 1400, 1800, 2200, and 0200 hours. In patients with RA we observed higher PRL/cortisol ratio at 0200 hours, whereas IL-1beta and TNF-alpha reached their highest serum levels at 0200 and 0600 hours. In patients with RA we observed an imbalance in favor of proinflammatory hormones as opposed to levels of antiinflammatory hormones during nocturnal hours together with increased levels of IL-1beta and TNF-alpha of the diurnal rhythm of disease activity.

Zoli A, Priolo F, Galossi A, Altomonte L, Di Gregorio F, Cerase A, Mirone L, Magarò M. · Division of Rheumatology, Institute of Internal Medicine and Geriatrics, Catholic University of the Sacred Heart, Rome, Italy. · J Rheumatol. · Pubmed #10813284 No free full text.

Abstract: OBJECTIVE: To make a comparative evaluation of different imaging techniques for studying the craniocervical junction involvement in patients with rheumatoid arthritis (RA). Upper cervical spine involvement was compared with clinical and immunological data. METHODS: Patients (n = 47) underwent plain radiographs and computerized tomography (CT) and magnetic resonance (MR) study of the craniocervical junction. Neurological examination following clinical signs of possible atlantoaxial involvement was performed in all patients following the Ranawat classification. RESULTS: Radiographic and MR images showed craniocervical involvement in 41.3% and 61% of the patients, respectively. Immunological data were not correlated with imaging findings, whereas Ranawat class II and III of neurological involvement seem to be predictive of atlantoaxial alteration. CONCLUSION: Conventional radiography allowed us to detect 41.3% of patients with craniocervical involvement, but only in advanced stages of the disease. MR imaging had the unique potential of direct and detailed synovial visualization, especially in the gadolinium enhanced axial images, resulting in the early diagnosis of craniocervical RA.

De Leo ME, Tranghese A, Passantino M, Mordente A, Lizzio MM, Galeotti T, Zoli A. · No affiliation provided · J Rheumatol. · Pubmed #12375348 links to  free full text

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