Simonetta Salemi

Influenza vaccine administration in rheumatoid arthritis patients under treatment with TNFα blockers: Safety and immunogenicity

Twenty-eight patients with low-moderate, stable rheumatoid arthritis (RA), under treatment with tumor necrosis factor (TNF) alpha blockers, were immunized at least once with non-adjuvanted trivalent influenza vaccine during three consecutive influenza seasons. Antibodies toward A influenza antigens significantly increased and reached protective levels, still detectable 6 months after vaccination, both in RA patients and healthy controls. Response to B antigen instead was only observed from the second year for healthy controls and in the third year for patients. No significant difference in disease activity and anti-nuclear antibodies was observed as a consequence of vaccine administration, whereas T regulatory cells showed a significant increase 30 days after immunization in RA patients. This study confirms safety of influenza vaccine administration in RA patients treated with TNFalpha blockers. The cohort follow-up revealed the overcoming of poor B vaccine antigen immunogenicity via repeated vaccinations. Finally, protective antibody response was still observed 6 months after vaccination.

Could Autoimmunity Be Induced by Vaccination

Autoimmune reactions to vaccinations may rarely be induced in predisposed individuals by molecular mimicry or bystander activation mechanisms. Autoimmune reactions reliably considered vaccine-associated, include Guillain-Barré syndrome after 1976 swine influenza vaccine, immune thrombocytopenic purpura after measles/mumps/rubella vaccine, and myopericarditis after smallpox vaccination, whereas the suspected association between hepatitis B vaccine and multiple sclerosis has not been further confirmed, even though it has been recently reconsidered, and the one between childhood immunization and type 1 diabetes seems by now to be definitively gone down. Larger epidemiological studies are needed to obtain more reliable data in most suggested associations.

Infection risk in Rheumatoid Arthritis and Spondyloarthropathy patients under treatment with DMARDs, Corticosteroids and TNF-α antagonists

BackgroundInfections which complicate rheumatic diseases such as Rheumatoid Arthritis (RA) and Spondyloarthropathy (SpA) (Psoriatic Arthritis [PA] and Ankylosing Spondylitis [AS]), may cause significant morbidity and mortality. However, among the studies on the incidence rate (IR) of infections in such patients, very few have involved controls and the results have been controversial, probably due to methodological difficulties.To estimate infection rates in RA and SpA patients under disease-modifying anti-rheumatic drugs (DMARDs), corticosteroids (CS) and tumor necrosis factor (TNF)α antagonists, alone or combined, a single-centre retrospective observational cohort study has been performed.Patients and methodsIncidence rates/100 patient-years of any infections were evaluated in RA and SpA outpatients observed in the period November 1, 2003 through December 31, 2009 and stratified according to therapy. Infection incidence rate ratios (IRR) were calculated using Poisson regression models which adjusted for demographic/clinical characteristics of the patients.ResultsThree hundred and thirtyone infections [318 (96.1%) non-serious and 13 (3.9%) serious] have been registered among 176 of the 341 patients (52%). The IR/100 patient-years of all infections was 36.3 ranging from 12.4 (DMARDs + CS) to 62.7 (anti-TNFα + CS). The most frequent infection site was respiratory tract, and bacteria were responsible for three quarters of all infections. In the multivariate analysis, adding anti-TNFα to DMARDs doubled the IRR compared to DMARDs alone, anti-TNFα + CS significantly tripled it, whereas anti-TNFα + CS + DMARDs only increased the risk 2.5 times. The degree of disease activity was strongly and significantly associated with the infection risk (severe or moderate versus mild, IRR = 4). Female sex was significantly associated with increased infection risk, while duration of disease and anti-influenza vaccination were protective, the latter even for cutaneous/soft-tissue (mainly herpetic) infections.ConclusionThe combination anti-TNFα with CS was found to be the most pro-infective treatment, whereas DMARDs alone were relatively safe. Physicians, therefore, should be aware that there may be an increased risk of infection when using anti-TNFα and CS therapy together. Anti-influenza vaccination appears to provide broad protection, adding evidence to support its use in these patients, and deserves further study.

Are Anti-Infectious Vaccinations Safe and Effective in Patients with Autoimmunity?

Vaccinations have been traditionally considered a risk factor for the induction/reactivation of autoimmune diseases. A Medline search through key words “vaccinations and autoimmune diseases” from 1947 through December 2009 was conducted. Until now, vaccination effects in autoimmune diseases have only been studied in over 5000 patients. Vaccinations generally did not induce worsening of disease activity in patients with multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, insulin-dependent-diabetes-mellitus, chronic arthritis in children, vasculitides, and myasthenia gravis, whereas immunogenicity, although protective, was generally lower than in normal controls, depending on disease severity and immunosuppressive therapy. Data are very poor on the efficacy.

Lack of hepatitis B virus reactivation after anti-tumour necrosis factor treatment in potential occult carriers with chronic inflammatory arthropathies

BACKGROUND Hepatitis B virus (HBV) reactivation in patients positive for antibody to HB core antigen (anti-HBc), negative for HB surface antigen (HBsAg) and HBV-DNA (potential occult HBV carriers), treated with anti-tumor necrosis factor (TNF)α, is a debated question. The aim of the study was to evaluate the safety of anti-TNFα therapy in anti-HBc positive/HBsAg negative subjects with rheumatoid arthritis (RA) and spondyloarthropathy (SpA). METHODS All consecutive HBsAg negative RA and SpA outpatients referring to the Immuno-Rheumatology Institute at the S. Andrea hospital, Sapienza, University of Rome who had to undergo anti-TNFα therapy. RESULTS Among the 169 enrolled subjects, 20 (12%) were potential occult HBV carriers (anti-HBc positive, HBsAg and HBV-DNA negative patients with or without anti-HBs). During the follow-up (mean ± SD 45 ± 22 months), aminotransferases and HBV-DNA, tested every two and six months respectively, did not change. CONCLUSION This study confirms the substantial safety of anti-TNFα therapy in potential occult HBV carriers RA and SpA patients.

Biological Therapies for Rheumatoid Arthritis: Progress to Date

Biologic drugs for the management of rheumatoid arthritis (RA) have revolutionized the therapeutic armamentarium with the development of several novel monoclonal antibodies, which include murine, chimeric, humanized, fully human antibodies and fusion proteins. These biologics bind to their targets with high affinity and specificity. Since 1998, nine different biologics have been approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) for the treatment of RA, and several others are in different stages of clinical trials. This field is in continuous evolution and new biologics are tested every year. Therefore a precise analysis is required in order to have a detailed and updated state of the art of this field. In this review, our main aim is to analyse all available biological therapies that are FDA and EMA approved for the treatment of RA and also those that are in clinical trials for the management of RA patients.

Polyclonal intravenous immunoglobulin: An important additional strategy in sepsis?

Sepsis syndrome is characterized by a systemic inflammatory response to infection potentially leading to acute organ failure and rapid decline to death. Polyclonal intravenous immune globulin, a blood product derived from human donor blood, in addition to antiinfective activities, also exerts a broad antiinflammatory and immunomodulating effect. Intravenous immunoglobulin (IVIg) has been proposed as adjuvant therapy for sepsis even though the clinical studies demonstrating their efficacy and safety are relatively small. Several systematic reviews and meta-analyses of intravenous immunoglobulin treatment in sepsis have been performed. As a result of heterogeneity across studies and inconsistencies in results, the majority have concluded that more evidence, coming from large, well-conducted randomized controlled trials (RCTs), is required. Moreover the appropriate timing of administration and the identification of specific clinical settings represent a key factor to maximizing their beneficial effect. The authors, in this revision, review the basic mechanisms of action of IVIg, the rationale for their use, and their clinical applications.

The Expanding Role of Therapeutic Antibodies

Therapeutic antibodies have been used since the end of nineteenth century, but their use is progressively increased and recently, with the availability of monoclonal antibodies, they are successfully employed in a large disease spectrum, which transversally covers different fields of medicine. Hyperimmune polyclonal immune globulin has been used against infectious diseases, in a period in which anti-microbial drugs were not yet available, and it still maintains a relevant place in prophylaxis/therapy. Although immune globulin should be considered life-saving as replacement therapy in humoral immunodeficiencies, its place in the immune-modulating treatment is not usually first-choice, but it should be considered as support to standard approved treatments. Despite therapeutic monoclonal antibodies have been lastly introduced in therapy, their extreme potentiality is reflected by the large number of approved molecules, addressed toward different immunological targets and able to heavily influence the prognosis and quality of life of a wide range of different diseases.

Could early rheumatoid arthritis resolve after periodontitis treatment only?: case report and review of the literature.

AbstractRheumatoid arthritis (RA) is an immune-mediated polyarthritis; currently no pathogenic agent has been identified as a disease trigger. A patient with RA, presumably caused by periodontal infection, whose remission has been observed after periodontitis treatment in absence of specific RA therapy, is reported here for the first time, to our knowledge.A 61-year-old male patient presented migrant arthritis associated with antibodies against citrullinated protein antigens positivity. The clinical features allowed to make RA diagnosis according to the 2010 European League against Rheumatism/American College of Rheumatology RA classification criteria. X-ray of the second upper molar showed chronic apical periodontitis. After its treatment, arthritis remission has been observed in the absence of specific RA therapy.It has been suggested that periodontitis may have a trigger role in RA pathogenesis. This could be explained by the enzymatic action of Porphyromonas gingivalis, probably leading to break tolerance to collagen. The identification and subsequent treatment of periodontitis should therefore be considered pivotal in RA prophylaxis and management.

Imaging Progression despite Clinical Remission in Early Rheumatoid Arthritis Patients after Etanercept Interruption

The aim of this preliminary study is to evaluate clinical and imaging response in twenty patients with early Rheumatoid Arthritits (eRA) treated with Etanercept (Etn) + Methotrexate (Mtx) and to investigate whether clinical and MRI remission may be maintained after biological therapy interruption. Assessment included: radiography, Visser score and anti-CCP antibodies at baseline; disease activity score in 44 joints (DAS44), rheumatoid factor (RF), Magnetic Resonance Imaging (MRI) of hands and wrists at baseline (T0), 12 (T1), and 24 months (T2). MRI was scored for synovitis, bone oedema and erosions (OMERACT study); patients who reached clinical and imaging remission at T1 were considered eligible for interrupting Etn. At T1 8/20 (40%) patients showed a total remission [DAS44 from 5 (T0) to 1.4 (T1); p<0.02], whereas the other 12/20 (60%) showed an improvement, without complete remission [DAS44 from 4.8 (T0) to 2.8 (T1); p<0.05]. Etn was therefore interrupted in the first group of patients (group A), whereas it was continued in the other group (group B). At T2, group A maintained clinical remission and group B showed further not significant DAS44 reduction from T1. At T1, a significant reduction in synovitis, bone oedema and total score (p<0.01) was observed both in group A and in group B. At T2, group A showed an increase in all the MRI scores that was significant for the synovitis and total score, whereas group B exhibited a further not significant reduction. This preliminary study reports an excellent clinical and imaging response in eRA patients treated with Etn with total remission in 40% of them after a 1-year therapy period. However, it indicates that joint damage may progress, despite a sustained clinical remission, after Etn suspension