The safety of anti-TNF agents in the elderly.

Rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis are commonly thought of as inflammatory diseases that affect younger individuals. Although the initial presentation of these diseases is common in a patients twenties or thirties, they usually persist for the duration of the patients life. In addition, up to one-third of patients with RA have disease onset after 60 years of age. Anti-TNF-a therapies now have well-recognized safety profiles that have been demonstrated in the usual clinical trial populations for these diseases, but such populations under-represent patients > or =65 years of age. This retrospective study aims to determine the safety profiles for etanercept, infliximab and adalimumab in patients of 65 years or more, undergoing anti-TNF treatment for an active inflammatory disease such as rheumatoid arthritis, ankylosing spondylitis or psoriatic arthritis, or skin disease like psoriasis. Our data show that admitting elderly patients into anti-TNF therapeutic regimens is a safe option and that it grants these patients access to the best current therapeutic option, possibly leading to better disease outcome. Quality of life in elderly patients affected by arthritis or psoriasis, often reduced by comorbidities, is as important as quality of life in younger patients. Applying the recommended screening before using biological treatment helps to reduce adverse events related to the therapy, and the application of the same screening in elderly patients seems to lead to comparable results.

High levels of NK cells in the peripheral blood of patients affected with anti-phospholipid syndrome and recurrent spontaneous abortion: a potential new hypothesis.

OBJECTIVES: No data regarding phenotypic assets of circulating lymphocytes in anti-phospholipid syndrome (APS) are reported in the literature. Role of anti-phospholipid antibodies (aPL) in recurrent spontaneous abortion (RSA) remains uncertain, while natural killer (NK)-cells are involved in RSA pathogenesis. In this study, patients affected with APS without RSA, APS with RSA and RSA without aPL were studied for NK-cell subpopulation to evaluate its role in abortive events typical of APS. METHODS: NK-cell levels in peripheral blood of APS patients without RSA (n = 28) and in APS-RSA patients (n = 25) were evaluated by means of flow cytofluorimetry. NK-cells levels were evaluated also in RSA without aPL associated with either endocrine (n = 86), anatomic (n = 30) or idiopathic (n = 77) conditions and in 42 healthy women. RESULTS: High NK levels were found in 14/25 (56%) APS-RSA patients. Among these patients, all except one aborted before the 10th gestational week (GW), while among the remaining patients all except one aborted after the 10th GW. NK mean levels were significantly higher in APS-RSA than in all the other conditions studied, including healthy subjects, except idiopathic RSA. CONCLUSIONS: Our results demonstrate that the numbers and proportions of NK-cells are significantly higher in patients with RSA with APS than in APS without RSA. Increased numbers of NK-cells correlate with reduced gestational age at abortion in patients with APS-RSA. These data lead to a hypothesis that NK-cells contribute to the development of RSA in patients with APS. NK-cells might precipitate damage initiated by aPL or they might cause pathology in RSA independent of aPL.

[Antiphospholipid antibodies: their prevalence, clinical significance and correlation with cytokine levels in acute myeloid leukemia and non-Hodgkin's lymphoma]. / Anticorpi anti-fosfolipidi: prevalenza, significato clinico e correlazione con i livelli di citochine nella leucemia mieloide acuta e nel linfoma non-Hodgkin.

Forty-five patients with de novo acute myeloid leukemia (AML) and 22 patients with newly-diagnosed non-Hodgkin lymphoma (NHL) were investigated. Tests for antiphospholipid antibodies (APA) included the measurement of anticardiolipin antibodies (aCL) with a solid-phase immunoassay, and the detection of the lupus-like anticoagulant (LA) activity. Fifteen patients with AML (33.3%) and 9 patients with non-Hodgkin lymphoma (40.9%) presented elevated APA at diagnosis, as compared to 3 out of 174 persons of the control group (p < 0.0001). APA titles became normal in all patients responding to treatment, whereas non-responders retained elevated levels. In addition, 2 patients (1 with AML and 1 with NHL) who had normal APA at diagnosis and were either refractory to treatment or in relapse, subsequently developed LA and/or aCL positivity. At presentation, the mean levels of IgG- and IgM-aCL in patients were not significantly different from controls, and concordance between aCL and LA results reached just 12%. With regard to the clinical course, we were not able to detect any statistically significant difference between patients with normal and elevated APA. Pretreatment concentrations of IL-6 and TNF-alpha in AML, and soluble form of the receptor for interleukin-2 (sIL-2r) in NHL were found significantly elevated compared to controls (p < 0.001, p = 0.011 and p = 0.016 respectively). In addition, the levels of these cytokines correlated with IgG-aCL at the different times of laboratory investigations. These results demonstrate that APA may have a role as markers of disease activity and progression in some haematological malignancies.

Prevalence and clinical significance of elevated antiphospholipid antibodies in patients with idiopathic thrombocytopenic purpura.

Antibodies against phospholipid antigens (APA) have been demonstrated in idiopathic thrombocytopenic purpura (ITP), but their clinical and pathogenetic significance has remained elusive. In this study we analyzed the prevalence and clinical features of ITP patients with elevated APA. In addition, we prospectively evaluated APA levels after treatment with corticosteroids and compared them with platelet-associated immunoglobulin (PAIgG) titers. We studied 149 patients with newly diagnosed ITP. Of these, 78 had a platelet count less than 50 x 10(9)/L and received an initial treatment with oral prednisone (PDN). In 71 asymptomatic cases with platelet counts between 50 x 10(9)/L and 120 x 10(9)/L, no therapy was scheduled. However, in five of them, the platelet count fell below 50 x 10(9)/L after more than 12 months; these patients were treated with PDN. Tests for APA included the measurement of anticardiolipin antibodies (ACA) with a solid-phase immunoassay and the detection of the lupus-like anticoagulant (LA) activity with coagulation tests that included kaolin-clotting time, dilute Russel's Viper venom time, activated partial thromboplastin time (aPTT), and dilute aPTT. Controls consisted of 174 apparently healthy subjects. Either LA or elevated ACA was seen in 69 patients (46.3%) at diagnosis. LA and ACA were both elevated in 24 cases (16.1% of the overall patient population and 34.8% of patients with high APA concentrations). No correlation was found between LA ratio values and ACA-IgG or -IgM titers, or between ACA-IgG and ACA-IgM levels. The presence of these antibodies was not associated with sex, age, platelet count, or the severity of hemorrhages. PAIgG was detected in 106 of 127 cases (83%). Again, no relationship was observed with clinical parameters or with APA levels. However, all cases with elevated APA also had increased PAIgG. With regard to the clinical course, we were not able to detect any significant difference between patients with normal and elevated APA. An initial complete response to prednisone treatment was observed in 43 of 83 cases (51.8%), with 13 (15.7%) achieving a prolonged complete remission. APA levels were not significantly modified after PDN therapy and on relapse. We conclude that APA positivity is a common finding in patients with ITP and does not select a category with different clinical features. APA levels are not influenced by immunosuppressive therapy with steroids and are not related to the activity of the disease. Therefore, we do not support a role for APA in the pathogenesis of ITP.

Migrainous stroke and the antiphospholipid antibodies.

The pathogenesis of migrainous stroke is controversial. The possibility that a number of migraine-related strokes is associated with the presence of antiphospholipid antibodies, a condition predisposing to coagulopathy, has been suggested. We investigated the prevalence of lupus anticoagulant and anticardiolipin antibodies in patients with migrainous stroke. In 6 out of 16 patients with migrainous cerebral infarction, the presence of antiphospholipids antibodies was detected. In such patients, the presence of other risk factors for stroke was significantly lower (chi 2 = 5.6; p = 0.01) with respect to patients with negative results for antiphospholipid antibodies. These results suggest that antiphospholipid antibodies associated with migraine may be an important marker for ischemic stroke.

Antiphospholipid antibodies: prevalence, clinical significance and correlation to cytokine levels in acute myeloid leukemia and non-Hodgkin's lymphoma.

This study was designed to explore the prevalence and clinical significance of elevated antiphospholipid antibodies (APA) titres in patients affected by acute myeloid leukemia (AML) and high-grade non-Hodgkin's lymphoma (NHL). We also analyzed possible correlations with circulating levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and the soluble form of the receptor for interleukin-2 (sIL-2r). Nineteen patients with de novo AML and 14 patients with newly-diagnosed NHL were investigated. Tests for APA included the measurement of anticardiolipin antibodies (ACA) with a solid-phase immunoassay, and the detection of the lupus-like anticoagulant (LA) activity. Five patients with AML (26.3%) and 5 patients with NHL (35.7%) presented elevated APA at diagnosis, as compared to 3 of 174 persons of the control group (p < 0.0001). APA titres became normal in all patients responding to treatment, whereas non-responders retained elevated levels. In addition, 6 patients (4 with AML and 2 with NHL), who had normal APA at diagnosis and were either refractory to treatment or in relapse, subsequently developed LA and/or ACA positivity. At presentation, the mean levels of IgG- and IgM-ACA in patients were not significantly different from controls, and concordance between ACA and LA results reached just 30%. With regard to the clinical course, we were not able to detect any statistically significant difference between patients with normal and elevated APA. Pretreatment concentrations of IL-6 and TNF-alpha in AML, and sIL-2r in NHL were found significantly elevated compared to controls (p = 0.003, p = 0.009 and p = 0.024 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)