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Oliveira do Hospital, Portugal

Putrik P.,Maastricht University | Ramiro S.,Hospital Garcia de Orta | Ramiro S.,University of Amsterdam | Kvien T.K.,Diakonhjemmet Hospital | And 4 more authors.
Annals of the Rheumatic Diseases

Objectives We investigated access to biologic and synthetic disease modifying drugs (bDMARDs and sDMARDs) in patients with rheumatoid arthritis (RA) across Europe. Methods A cross-sectional study at national level was performed in 49 European countries. A questionnaire was sent to one expert, addressing the number of approved and reimbursed bDMARDs and sDMARDs, prices and copayments, as well as acceptability of bDMARDs (barriers). Data on socio-economic welfare (gross domestic product per capita (GDP), health expenditure, income) were retrieved from web-based sources. Data on health status of RA patients were retrieved from an observational study. Dimensions of access (availability, affordability and acceptability) were correlated with the country's welfare and RA health status. Results In total, 46 countries (94%) participated. Six countries did not reimburse any of the five sDMARDs surveyed, and in ten countries no bDMARDs were reimbursed. While the price of annual treatment with an average sDMARD was never higher than GPD, the price of one year treatment with a bDMARD exceeded GPD in 26 countries. Perceived barriers for access to bDMARDs were mainly found among financial and administrative restrictions. All dimensions of access were positively correlated with the country's economic welfare (coefficients 0.69 to 0.86 for overall access scores). Conclusions Patients with RA in lower income European countries have less access to bDMARDs and sDMARDs, with particularly striking unaffordability of bDMARDs in some of these countries. When accepting that sDMARDs and bDMARDs are equally needed across countries to treat RA, our data point to inequities in access to pharmacological treatment for RA in Europe. Source

Garces S.,Instituto Gulbenkian Of Ciencia | Antunes M.,University of Lisbon | Benito-Garcia E.,Clinical and Translational Research Center | Benito-Garcia E.,Assessment Technology Group | And 3 more authors.
Annals of the Rheumatic Diseases

Introduction Clinical remission is today the treatment goal for rheumatoid arthritis (RA), which requires fast and assertive therapeutic decisions for a tight control of disease activity. Few objective parameters are available to guide clinical decisions, particularly in switcher patients. We designed a preliminary algorithm introducing immunogenicity assessment in the current approach to patients with RA receiving tumour necrosis factor inhibitors (TNFi). Objective To evaluate the concordance between the new algorithm and current clinical practice, comparing the effectiveness of 'immunogenicity-based' versus 'empirical-based' switches in a cohort of patients with established RA receiving biologics. Methods: EULAR therapeutic response was evaluated in 105 patients with RA (naive or switchers) over one year, through generalised estimation equation (GEE) analyses. Serum drug trough levels were assessed by ELISA and antidrug antibodies (ADAb) by Bridging ELISA. Results: During follow-up, 48.6% of patients had therapeutic decisions concordant with the proposed algorithm (Group A), and 51.4% had discordant decisions (Group B). One year after the therapeutic decision, patients from Group A had a higher probability of achieving response (OR=7.91, p<0.001, 95% CI 3.27 to 19.13) and low disease activity (OR=9.77, p<0.001, 95% CI 4.69 to 20.37) than patients in Group B. Conclusions: Immunogenicity assessment might help to optimise therapeutic decisions, leading to a better control of disease activity with significantly better clinical outcomes in patients with RA receiving TNFi. Source

Garces S.,Hospital Garcia de Orta | Garces S.,Instituto Gulbenkian Of Ciencia | Demengeot J.,Instituto Gulbenkian Of Ciencia | Benito-Garcia E.,Bio Clinical and Translational Research Center
Annals of the Rheumatic Diseases

Background: Immunogenicity of aTNFs is one of the mechanisms behind treatment failure. Objective: To assess the effect of anti-drug antibodies (ADA) on drug response to infliximab, adalimumab and etanercept, and the effect of immunosuppression on ADA detection, in patients with Rheumatoid Arthritis, Spondyloarthritis, Psoriasis and Inflammatory Bowel Diseases. Data sources: PubMed, EMBASE, Cochrane databases, article reference lists (through August 19 2012). Study selection: Out of 2082 studies, 17 were used in the meta-analysis (1RCT; 16 observational studies). Data extraction: Two reviewers extracted data. Risk ratios (RR), 95% CI, using random-effect models, sensitivity analysis, meta-regressions and Egger's test were calculated. Data synthesis: Of 865 patients, ADA against infliximab or adalimumab reduced drug response rate by 68% (RR=0.68, 95% CI=0.12 to 0.36), an effect attenuated by concomitant methotrexate (MTX): <74% MTX+: RR=0.23, 95% CI=0.15 to 0.36; ≥74% MTX+: RR=0.32, 95% CI=0.22 to 0.48. Anti-etanercept antibodies were not detected. Of 936 patients, concomitant MTX or azathioprine/mercaptopurine reduced ADA frequency by 47% (RR=0.53, 95% CI=0.42 to 0.67), particularly when ADA were assessed by RIA (RR=0.36, 95% CI=0.23 to 0.55) compared with ELISA (RR=0.63, 95% CI=0.53 to 0.74). Conclusions: ADA reduces drug response, an effect that can be attenuated by concomitant immunosuppression, which reduces ADA frequency. Drug immunogenicity should be considered for the management of patients receiving biological therapies. Source

Santos G.,Centro Hospitalar Of Lisbon Central | Goulao J.,Hospital Garcia de Orta
Journal of Dermatological Treatment

Basal cell carcinoma (BCC) is the most frequent cutaneous neoplasm of the periorbital region. After tumor excision, the function of the eyelid has to be preserved, keeping the protection of the eyeball with preservation of damp, avoiding epiphora and ectropion. The authors describe the reconstruction, in a single surgical procedure, of a full-thickness defect of the outer half of the free edge of the lower eyelid through free chondromucosal graft of the septum and Tripier flap. There are very few cases that describe the septal chondromucosal flap in eyelid reconstruction. This case also corroborates the fact that the chondromucosal graft is a valuable surgical option for reconstruction of full-thickness lower eyelid defects. © 2014 Informa Healthcare USA on behalf of Informa UK Ltd. Source

Azevedo P.C.,Hospital Garcia de Orta | Murphy G.,University College London | Isenberg D.A.,University College London
Methods in Molecular Biology

Many studies have explored the pathology of systemic lupus erythematosus (SLE), an autoimmune rheumatic disorder with a striking female predominance. Numerous autoimmune phenomena are present in this disease, which ultimately result in organ damage. However, the specific cellular and humoral mechanisms underlying the immune dysfunction are not yet fully understood. It is postulated that autoimmunity is based on the interaction of genetic predisposition, hormonal and environmental triggers that result in reduced tolerance to self-tissues. These phenomena could occur because of altered antigen presentation, abnormalities in B cell responses, increases in the function of T-helper cells, abnormal cytokine production, exaggerated effector responses, or loss of regulatory T cells or B cells. Abnormalities in all of these components of the immune response have been implicated to varying degrees in the pathogenesis of SLE. This chapter will attempt to provide a "state-of-the- art" review of the evidence about the mechanisms underlying the pathology of SLE. © 2014 Springer Science+Business Media New York. Source

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