Firenze, Italy
Firenze, Italy

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Diamantopoulos A.,Symmetron Ltd | Benucci M.,Section of Rheumatology | Capri S.,Cattaneo University | Berger W.,Hoffmann-La Roche | And 3 more authors.
Journal of Medical Economics | Year: 2012

Objective: This study was designed to evaluate the cost utility of tocilizumab in rheumatoid arthritis (RA) patients, with inadequate responses to traditional disease-modifying anti-rheumatic drugs (tDMARDs) from a payer's perspective in Italy. Methods: An individual patient simulation model was used to project lifetime medical costs (payer's perspective) and quality-adjusted life-years (QALYs). Treatment sequences starting with tocilizumab or the most commonly prescribed biologics (etanercept, adalimumab, or infliximab) were compared. The addition of tocilizumab to standard of care, without the replacement of anti-tumor necrosis factor (TNF)-α treatments, was also evaluated. Patient characteristics, treatment efficacy, and quality-of-life data were based on three phase 3 tocilizumab clinical trials (TOcilizumab Pivotal Trial in Methotrexate Inadequate respONders [OPTION], Tocilizumab in cOmbination With traditional DMARD therapy [TOWARD], and TociLIzumab Safety and THE Prevention of Structural Joint Damage [LITHE]). Mixed-treatment comparison was used to estimate response probabilities. Resource utilization, treatment acquisition, administration, and monitoring costs were estimated using Italian secondary sources. Uncertainty in model parameters was evaluated by probabilistic sensitivity analysis. Results: Replacement of anti-TNF-α treatments with tocilizumab reduced total costs over a patient's lifetime (base-case analysis: tocilizumab sequence, €141,100 vs standard of care sequence, €143,500). Patients receiving tocilizumab realized more QALYs than patients receiving standard of care (9.8881 vs 9.3502 QALYs). Therefore, according to the base-case analysis, the tocilizumab sequence dominated the standard of care. In a sensitivity analysis, the model base-case result was robust to input changes. When tocilizumab was added to standard of care, without replacing anti-TNF-α treatments, the incremental cost-effectiveness ratio was €17,100 per QALY. Conclusion: The analysis demonstrates that, in Italy, replacing another biologic DMARD with tocilizumab or adding tocilizumab to the current standard of care is a cost-effective strategy in the treatment of RA patients with inadequate responses to tDMARDs. © 2012 Informa UK Ltd All rights reserved.


Stagi S.,University of Florence | Bertini F.,Section of Rheumatology | De Martino M.,University of Florence | Cerinic M.M.,Section of Rheumatology | Falcini F.,Section of Rheumatology
Lupus | Year: 2014

Background: Hypovitaminosis D is common in the general population. Although many studies on 25-hydroxyvitamin D (25(OH)D) are available on systemic lupus erythematosus (SLE), few data are reported in juvenile-onset SLE (JSLE) patients. Design: This study aimed to assess serum 25(OH)D levels in JSLE patients and to identify risk factors for vitamin D deficiency in this population. Methods: Forty-five Caucasian JSLE patients (36 females, nine males; mean age 18.9±6.3 years) and 109 age- and sex-matched healthy controls entered the study. Dualenergy X-ray absorptiometry (DXA) scans of the lumbar spine, serum calcium and phosphate, bone-specific alkaline phosphatase (BSAP), parathyroid hormone (PTH), and 25(OH)D were assessed. The data were compared with an age- and sex-matched control group including 109 Caucasian healthy subjects. Results: JSLE patients exhibited lower 25(OH)D levels than controls (p<0.005), with the lower values observed in patients with active vs. inactive disease (p<0.05). JSLE patients exhibited reduced total calcium levels (p<0.001) and higher phosphate levels (p<0.001), BSAP (p<0.001) and PTH (p<0.001) than controls. In addition, JSLE patients exhibited lower spine bone mineral apparent density (BMAD) SDS values than controls (p<0.001), with higher values in patients with 25(OH)D sufficiency and insufficiency than in those with 25(OH)D deficiency (p<0.001). Conclusions: Patients with JSLE have significantly lower 25(OH)D levels than controls. Therefore, vitamin D supplementation may be useful to normalize bone mass and quality in subjects with JSLE. © The Author(s), 2014.


Vitali C.,Section of Rheumatology | Bootsma H.,University of Groningen | Bowman S.J.,University of Birmingham | Dorner T.,Charite University Hospital | And 6 more authors.
Annals of the Rheumatic Diseases | Year: 2013

A new approach for the classification of patients with Sjögren's syndrome (SS) has been recently proposed. Although these new criteria substantially differ from the American European Consensus Group criteria, which have represented the gold standard for the last decade, when compared with each other the two sets show a high statistical degree of agreement. However, the fact that two different criteria to classify patient with SS could be available may introduce some additional difficulties in the scientific communication, making cohorts of patients selected by using different methods less than completely equivalent, and the results of epidemiological studies and therapeutic trials not entirely comparable. Consequently, to reach a consensus agreement on universally accepted classification criteria for SS seems to be a very desirable objective.


Kastbom A.,Karolinska Institutet | Kastbom A.,Linköping University | Forslind K.,Section of Rheumatology | Forslind K.,Skåne University Hospital | And 8 more authors.
Annals of the Rheumatic Diseases | Year: 2016

Objective: To determine the relationship between changes in antibody levels towards citrullinated peptides derived from different candidate autoantigens and therapeutic outcome in early rheumatoid arthritis (RA). Methods: Baseline and 3-month serum samples from 316 patients with early RA enrolled in the Swedish Farmacotherapy (SWEFOT) trial were analysed for antibodies against cyclic citrullinated peptides (CCP) and citrullinated peptides derived from vimentin (cVim), fibrinogen (cFib) and α-enolase (CEP-1). At 3-month follow-up, methotrexate monotherapy-inadequate responders were randomised to add-on therapy with sulfasalazine and hydroxychloroquine or infliximab. In these patients, anticitrullinated peptide antibodies (ACPA) were also assessed at 12 and 24 months. The proportion of antibody-positive patients and relative changes in antibody levels were compared across ACPA specificities and related to therapeutic response and radiographic progression. Results: During the 2-year follow-up, the proportion of patients testing positive declined significantly regarding antibodies to cVim, cFib and CEP-1, while anti-CCP antibody occurrence remained stable over time. Turning anti-cVim antibody negative was most common, and anti-cVim antibody seroreversion during the first three months associated with significantly less 2-year radiographic progression compared with patients who remained positive. Median antibody levels of all tested ACPAs declined uniformly during initial methotrexate therapy and following response to add-on therapy, with no significant relation to treatment regimen or radiographic progression. Conclusions: The influence of early antirheumatic therapy on ACPA seroreversions was markedly different across specificities, and early disappearance of anti-cVim antibodies associated with better radiological outcome. Thus, these data suggest that the disappearance of particular ACPA reactivities may be beneficial in early RA.


Bai F.,Section of Infectious Diseases | Bai F.,L2 Diagnostics, Llc | Kong K.-F.,Section of Rheumatology | Kong K.-F.,La Jolla Institute for Allergy and Immunology | And 7 more authors.
Journal of Infectious Diseases | Year: 2010

Polymorphonuclear leukocytes (PMNs) are key in innate immunity, but their role in viral pathogenesis is incompletely understood. In infection due to West Nile virus (WNV), we found that expression of 2 PMNattracting chemokines, Cxcl1 and Cxcl2, was rapidly and dramatically elevated in macrophages. PMNs are rapidly recruited to the site of WNV infection in mice and support efficient replication of WNV. Mice depleted of PMNs after WNV inoculation developed higher viremia and experienced earlier death, compared with the control group, which suggest a protective role for PMNs. In contrast, when PMNs were depleted prior to infection with WNV, and in mice deficient in Cxcr2 (a chemokine receptor gene), viremia was reduced and survival was enhanced. Collectively, these data suggest that PMNs have a biphasic response to WNV infection, serving as a reservoir for replication and dissemination in early infection and later contributing to viral clearance. © 2010 by the Infectious Diseases Society of America. All rights reserved.


Sayiner Z.A.,Section of Gastroenterology and Hepatology | Haque U.,Section of Rheumatology | Malik M.U.,Section of Gastroenterology and Hepatology | Gurakar A.,Liver Transplant Program
Gastroenterology and Hepatology | Year: 2014

Extrahepatic manifestations are frequently encountered among patients with chronic hepatitis C virus (HCV) infection. Many of these manifestations are autoimmune disorders, with added mortality and morbidity due to involvement of multiple organ systems. Symptoms of HCV infection and rheumatic diseases may be similar and include arthralgia, myalgia, arthritis, and vasculitis. Also, serologic abnormalities may be found in both cases. Some treatment modalities for HCV infection, including interferon therapy, may aggravate the symptoms of rheumatic diseases, thus confounding clinical presentation. It is imperative to distinguish whether symptoms such as arthralgia, myalgia, and arthritis occur in patients with HCV infection due to primary chronic HCV infection or to a newly developed rheumatologic disease process.


Svensson B.,Lund University | Andersson M.L.E.,Spenshult Hospital | Bala S.-V.,Section of Rheumatology | Forslind K.,Lund University | Hafstrom I.,Karolinska University Hospital
BMJ Open | Year: 2013

Objectives: Remission is a widely accepted goal for treatment of rheumatoid arthritis (RA) but has to be sustained to arrest joint damage and disability. However, appropriate criteria for the assessment of sustained remission in long-term studies are not established. Therefore, we have compared the disease activity score calculated on 28 joints (DAS28) remission criterion, the Simplified Disease Activity Index less than 3.3 remission criterion (SDAI Cr) and the new Boolean-based set of criteria (Boolean Cr), and assessed the association of these criteria with radiographic and functional outcome. Design: Prospective, long-term observational study of patients with early RA. Setting: Secondary level of care; six participating centres from southern Sweden; both urban and rural populations. Participants: 698 patients were consecutively included in the study and 527 remained at the 8-year follow-up visit. Almost all patients were Caucasians, of which 64% were women. To be included, a patient, 18 years or older, had to fulfil the 1987 American College of Rheumatology criteria for RA and have a disease duration of no more than 1 year. Results: Sustained remission was most common by the DAS28 Cr (14%), while 3% met the Boolean Cr and 5% the SDAI Cr, the latter figures increasing to 9% and 8%, respectively, when the patient's global assessment was excluded. Radiographic joint damage was common but least pronounced in patients in sustained remission by all criteria. Sustained remission was associated with rapid and lasting improvement in function assessed by the Health Assessment questionnaire, irrespective of criteria. Conclusions: The DAS28 Cr acquired more patients in sustained remission compared with the other criteria. In spite of that, radiographic damage and disability were not worse than that seen by other criteria and the patients' perspective was preserved. The DAS28 Cr may therefore still be used in long-term observational studies until more accurate criteria are available.


Wortmann R.L.,Section of Rheumatology | MacDonald P.A.,Takeda Global Research and Development Center Inc | Hunt B.,Takeda Global Research and Development Center Inc | Jackson R.L.,Takeda Global Research and Development Center Inc
Clinical Therapeutics | Year: 2010

Background: Use of urate-lowering therapy (ULT), such as febuxostat or allopurinol, is recommended for the long-term management of hyperuricemia in patients with gout to reduce the incidence of acute flares. Because of the paradoxical relationship between early use of ULT and the increased incidence of gout flares, prophylaxis with either low-dose colchicine or NSAIDs has been recommended, although there have been concerns about the long-term prophylactic use of these agents. Objectives: The present analysis examined flare rates during the 3 Phase III trials of febuxostat based on mean postbaseline serum urate (sUA) concentrations and duration of prophylaxis. Adverse events (AEs) were assessed by prophylaxis with colchicine or naproxen. Methods: This investigator-initiated, post hoc reanalysis of data on gout flares from the 3 randomized, placebo-controlled, Phase III trials evaluated the proportion of patients requiring treatment for gout flares at 4-week intervals based on mean postbaseline sUA concentrations <6.0 and ≥6.0 mg/dL. The 3 trials enrolled males or females aged 18-85 years who had a diagnosis of gout and a baseline sUA concentration ≥8.0 mg/dL. Patients received ULT (febuxostat or allopurinol) or placebo for 6 months or 1 year and flare prophylaxis with colchicine 0.6 mg/d or naproxen 250 mg BID for 8 weeks or 6 months. The prophylactic regimen was chosen at the discretion of the investigator, based on renal function and known intolerance to either drug. Patients with an estimated creatinine clearance <50 mL/min were not to receive naproxen. AEs were summarized based on prophylaxis with colchicine or naproxen. Results: The 3 trials enrolled a total of 4101 patients with gout. The majority were white (80.1%), male (94.5%), and obese (body mass index ≥30 kg/m 2) (62.8%). The mean duration of gout ranged from 10.9-11.9 years, and the mean baseline sUA concentration ranged from 9.6-9.9 mg/dL. Flare rates increased sharply (up to 40%) at the end of 8 weeks of prophylaxis and then declined gradually, whereas flare rates were consistently low (range, 3%-5%) at the end of 6 months of prophylaxis. Mean postbaseline sUA concentrations were correlated with flare rates; by the end of each study, patients with a mean postbaseline sUA concentration <6.0 mg/dL had fewer flares than did those with a mean postbaseline sUA concentration ≥6.0 mg/dL. There were differences in rates of AEs between prophylaxis groups, but the rates did not increase with increased duration of prophylaxis. Conclusion: This analysis of gout flare data from the 3 Phase III trials of febuxostat found that flare prophylaxis for up to 6 months during the initiation of ULT appeared to provide greater benefit than flare prophylaxis for 8 weeks, with no increase in AEs. © 2010 Elsevier HS Journals, Inc.


Choi H.K.,Section of Rheumatology | Zhu Y.,Boston University | Mount D.B.,Harvard University
Current Opinion in Rheumatology | Year: 2010

Purpose of Review: This review provides an update on Recent Findings with regards to the genetics of hyperuricemia and gout, including recent data from genome-wide association studies (GWAS). Recent Findings: Five GWAS around the same time reported that genetic variants of SLC2A9/GLUT9 were associated with lower serum uric acid (SUA) levels and the effects were stronger among women (e.g. SUA level difference per copy of a minor allele,-0.46 mg/dl in women vs.-0.22 mg/dl in men). One study involving four cohorts and one meta-analysis of 14 genome-wide scans found that genetic variants of ABCG2 were associated with higher SUA concentrations and these effects were stronger among men (e.g. uric acid level difference per copy of the minor allele, 0.32 mg/dl in men vs. 0.18 mg/dl in women). Limited data indicate that these associations likely translate into those with the risk of gout. Functional determination that GLUT9 and ABCG2 can transport urate at the apical border of proximal tubules implicates them as substantial players in the renal excretion of urate. Furthermore, five novel genetic loci have been reported in the meta-analysis of 14 genome-wide scans. Summary: Combined with their activities as urate transporters and their strong associations with serum uric acid concentrations, GLUT9 and ABCG2 appeared to be important modulators of uric acid levels and likely of the risk of gout. Together with a growing list of environmental risk factors, these genetic data add considerably to our understanding of the pathogenesis of hyperuricemia and gout. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Doghramji P.P.,Ursinus College | Wortmann R.L.,Section of Rheumatology
Postgraduate Medicine | Year: 2012

Gout is a chronic, progressive condition for which hyperuricemia is the primary risk factor. The initial episodes of gout may be brief, only lasting for 3 to 5 days, and patients may experience pain-free intercritical periods that last from months to years. However, as the disease progresses, acute gout fares become more frequent and prolonged (typically lasting $ 5-10 days). Chronic gouty arthritis develops, with shorter pain-free intervals; tophi become visible and interarticular joint damage occurs. Patients with advanced gout experience chronic pain and a decreased quality of life. Gout prevalence has increased significantly over time. Despite the increase in the number of gout cases, the disease is often mismanaged, especially in primary care. Hyperuricemia is inadequately controlled as a result of suboptimal dosing with urate-lowering drugs, intolerance to therapy, or poor patient compliance. This review article provides a comprehensive discussion of gout pathophysiology, risk factors, and approaches to treatment that encourage the clinician to appreciate hyperuricemia as a multifaceted disorder and manage the condition optimally. © Postgraduate Medicine.

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