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Objective To describe the effectiveness and safety of tocilizumab (TCZ), an interleukin-6 receptor inhibitor, in a cohort of patients with rheumatoid arthritis (RA) recruited in clinical practice. Methods TRUST was an observational study in RA patients who started treatment with TCZ in the 6 months prior to site activation and were still on treatment at start of study; patients were followed up to 12 months after the first TCZ infusion. Results 322 RA patients were enrolled in 59 Italian centres (mean age: 55.8 years; mean disease duration: 120.5 months; baseline DAS28: 5.3). After 6 months of TCZ treatment, patients achieving low disease activity (DAS28 ≤3.2; 57.52%) or disease remission (DAS28 < 2.6; 38.05%) were 216 out of 226 patients with available DAS28 (p < 0.001). No statistically significant differences were found in mean DAS28 and HAQ score changes from baseline (start of TCZ treatment) to study end between patients previously inadequately responding to disease-modifyinganti-rheumatic drugs (DMARD-IR) or to DMARDs plus tumour necrosis factor inhibitors (DMARD +TNFi-IR): both patient populations responded to TCZ. A statistically significant decrease in mean VAS Fatigue score (48.4 vs. 34.7; p=0.0025) at month 6 was observed. In patients treated with TCZ as monotherapy (32.61%), DAS28, VAS fatigue and HAQ scores decreased from baseline to any post-baseline time point. Overall, 62 patients (19.3%) prematurely discontinued TCZ treatment, 24 (7.5%) for safety reasons. Drug-related adverse events occurred in 92 patients (28.6%) (mostly 3 hypercholesterolaemia and leucopenia) and drug-related serious adverse events in 11 patients (3.4%). Conclusion This study confirms the good effectiveness and safety profile of TCZ in real life RA patient care.

A deficiency in calcium intake, is considered an important risk factor for the development of osteoporosis. Since the human body cannot produce calcium, individuals are recommended to maintain an adequate daily intake. The aim of the “Calcium Intake in the Mediterranean Region” Study is to evaluate the mean calcium intake in men and women between 40 and 80 residing in various areas of the Mediterranean basin. Enrolled subjects have been asked to fill out a self-administered questionnaire to evaluate the mean daily calcium intake from food, principle risk factors for osteoporosis were registered. A dual- energy X-ray absorptiometry (DEXA) has also been carried out to evaluate bone mineral density (BMD). During the recruitment period between March 2011 and February 2014, were enrolled 982 subjects. 90% are female, the average age is 60.4±10.0 years.The mean daily calcium intake is 1005 ± 449.9mg. Over the 63% of the sample assume a lower calcium intake compared to the recommended dietary allowance (RDA), there are statistically significant gender differences (p < 0.0001) because men have a greater calcium assumption. There is also a significant decreasing trend of assumption with age (p < 0.0001). Calcium Intake is lower in osteopenic and osteoporotic subjects compared to subjects with normal BMD (p=0.0048). Factors significantly associated with a low calcium intake are: sex, age, body mass index, previous fracture, family fracture history. Our study remarks the importance of calcium for the bone health and at the same time, confirms that Mediterranean women over 60 years of age need more calcium daily intake.

The fundamental role of Vitamin D has been long known in regulating calcium homeostasis and bone metabolism. An increased contribution of Vitamin D was recently described in association with a lower incidence of Rheumatoid Arthritis (RA). This must not be surprising, as the immunomodulating effects of Vitamin D are clear, which have been attributed protective effects in autoimmune disorders such as some chronic inflammatory bowel diseases, multiple sclerosis and type I diabetes. An interaction was suggested between Vitamin D metabolism and inflammation indexes through mediation of TNF-alpha which is also especially involved in osteoclastic resorption and therefore in bone loss processes. Some preliminary data would indicate an association between seasonal changes of Vitamin D serum levels, latitude and disease activity (DAS28) in RA patients. Consequently, the Osteoporosis and Metabolic Bone Diseases Study Group of SIR believes that there are grounded reasons for assessing the Vitamin D status of RA patients in order to investigate whether this is to be related to physiopathological and clinical aspects of disease other than those of bone involvement. Primary end point of the study will be to assess the levels of 25 OH Vitamin D in RA patients. Secondary endpoints will include correlation with dis-ease activity, densitometry values and bone turnover. The cross-sectional study will enroll patients of both sex genders, age ranging between 30 and 75 years according to the 1988 ACR criteria, onset of symptoms at least 2 years prior to study enrollment. Patients will be excluded suffering from osteo-metabolic diseases, liver and kidney insufficiency and those administered Vitamin D boli in the previous 12 months. Disease activity will be evaluated with the HAQ. Hemato-chemical tests and femoral and lumbar bone densitometry will be performed, unless recently undergone by patients. Blood levels of 25 OH C Vitamin D and PHT and of the two bone remodelling markers (bone alkaline phosphatase and serum CTX) will be measured, as well. Patient enrollment will start on February 2007 and will last 4 months. By the end of 2007 the study will be concluded and results will be published.

Vitamin D deficiency is very common in patients with rheumatoid arthritis (RA). Aim of this study was to evaluate the prevalence of vitamin D deficiency among the different Italian regions and whether these variations are associated with different severity of the disease. The study includes 581 consecutive RA patients (464 women), not taking vitamin D supplements, from 22 Italian rheumatology centres uniformly distributed across Italy. Together with parameters of disease activity (disease activity score 28), functional impairment (activities of daily living and health assessment questionnaire disability index) and mean sun exposure time, all patients had serum 25-hydroxyvitamin D (25OHD) measured in a centralized laboratory. Vitamin D deficiency (25OHD level

Objective : The Western Ontario and McMaster Universities (WOMAC) Osteoarthritis (OA) Index is a tested questionnaire to assess symptoms and physical functional disability in patients with OA of the knee and the hip. We adapted the WOMAC for the Italian language and tested its metric properties in 304 patients with symptomatic OA of the knee. Methods : Three hundred and four consecutive patients, attending 29 rheumatologic outpatient clinic in northern, central, and southern Italy, were asked to answer two disease-specific questionnaires (WOMAC and Lequesne algofunctional index) and one generic instrument (Medical Outcomes Study SF-36 Health Survey—MOS SF-36). A sample of 258 patients was readministered the WOMAC 7–10 days after the first visit and the structured interview, which also assessed demographic and other characteristics. Internal consistency was assessed using Cronbach's alpha, reliability using intraclass correlation coefficients (ICCs), and construct and discriminant validity using Spearman's correlations, Wilcoxon rank sum test, and Kruskal–Wallis test. Results : All WOMAC subscales (pain, stiffness, and physical function) were internally consistent with Cronbach's coefficient alpha of 0.91, 0.81, and 0.84, respectively. Test–retest reliability was satisfactory with ICCs of 0.86, 0.68, and 0.89, respectively. In comparison with the SF-36, the expected correlations were found when comparing items measuring similar constructs, supporting the concepts of convergent construct validity. Very high correlations were also obtained between WOMAC scores and Lequesne OA algofunctional index. WOMAC physical function, but not WOMAC stiffness and pain subscales, was weakly associated with radiological OA severity ( P =0.03). Also, WOMAC pain score was inversely correlated ( P =0.01) with years of formal education. Examination of discriminant validity showed that the scores on the WOMAC and SF-36 followed hypothesized patterns: the WOMAC discriminated better among subjects with varying severity of knee problems, whereas the SF-36 discriminated better among subjects with varying levels of self-reported health status and comorbidity. Conclusion : The Italian version of WOMAC is a reliable and valid instrument for evaluating the severity of OA of the knee, with metric properties in agreement with the original, widely used version.

Disease activity has been operatively defined as presence of urate deposits that lead to acute arthritis and joint damage. Every item of the pool of measures for each core domain recommended by OMERACT for trials in gout was tested for suitability in defining the concept of disease activity through a Delphi exercise. A three-step approach, similar to the methodology used for the disease activity score in rheumatoid arthritis, was applied to derive the gout activity score (GAS). Decision to change treatment was used as surrogate criterion of high disease activity. Baseline and 12-month follow-up data of 446 patients included in the KING cohort (Kick-off of the Italian Network for Gout) were used. Data included measures of all domains identified as important for trials in gout. Construct and criterion-related validity were preliminary tested using risk of flare and cross-sectional and longitudinal health assessment questionnaire score (HAQ).

Glucocorticoid-induced osteoporosis (GIO) is the most frequent cause of secondary osteoporosis. GIO is linked to glucocorticoids (GC) daily assumption with maximum effect within first months of treatment and decreasing to basal levels as the therapy is discontinued. In Italy, primary prevention of GIO is suggested when GC therapy (prednisone5 mg/day or equivalent) is taken for longer than 3 months. Lazio GISMO (Italian Group for Study and Diagnosis of Bone Metabolism Diseases) group organized the GC and Osteoporosis Epidemiology study (EGEO) to evaluate physician's approach in preventing GIO. The study involved 19 osteoporosis centers. Patients taking long-term GC therapy were recruited and information collected: medical history and anthropometric data, GC therapy, primary disease, physician's specialty, osteopororosis screening, and pharmacological intervention. The study included 1334 patients. Mean age was 63 ± 13 yr; 243 (18%) patients had a history of falls from standing position in the previous 12 months, 78 (35%) vertebral fractures, 91 (41%) fractures other than vertebral, 27 (12%) femoral fractures, and 27 (12%) multiple sites fractures. The molecules of GC more often prescribed were prednisone and 6-metil prednisolone. One thousand and forty patients (78%) were taking GC for more than 6 months. GC therapy was prescribed more frequently by rheumatologists (62%). Antiosteoporotic drugs for GIO prevention were prescribed in 431 patients (32%). Among the patients, only 27% (360) received calcium and vitamin D supplements, and 39% (319) treated by rheumatologists received anti-resorptive drugs. In conclusion, our data show that in Italy, as already described elsewhere, only a small subpopulation of GC-treated patients was supported by an anti-osteoporotic therapy, indicating the need to further stimulate awareness of both patients and specialists, prescribing GC therapy, to an appropriate and prompt GIO prevention.

Several single nucleotide polymorphisms (SNPs) have been associated with rheumatoid arthritis (RA) such as peptidylarginine deiminase-4 (PADI4), osteopontin (OPN), and perforin (PRF1) genes. Thus, we aimed at analysing the influence of eight SNPs in these candidate genes on RA susceptibility and their association with laboratory and clinical features in terms of response to anti-TNF therapy.We performed a case-control study on 377 Caucasian RA patients and 391 healthy, ethnicity-matched, population-based controls. All subjects were genotyped for PADI4_89/94, PADI4_92, PADI4_104, PADI4_100 in PADI4; -156G/GG and +1239A/C in OPN and A91V and N252S in PRF1 genes. The patients were stratified for shared epitope (SE) HLA-DRB1. rheumatoid factor (RF) and anti-citrullinated protein/peptide antibodies (ACPA) were analysed. The patients started anti-TNF treatment and they were evaluated at baseline and after 12 weeks. Disease activity was evaluated with DAS28 and response to treatment with EULAR criteria.A statistically significant association between RA and OPN -156G/GG was found (p=0.023). SE was firmly confirmed to be associated with RA (OR=3.68; p10-10). No other statistically significant association with clinical and laboratory features were observed.For the first time, in an Italian cohort, we report the association between -156G/GG in OPN gene and RA susceptibility. Short-term response to anti-TNF therapy was not influenced by the genetic variants studied.

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Objective. To identify the determinants of anti-TNF-naive patients’ preferences for the route of administration of anti-TNF agents. Methods. The study was carried out in 50 Italian rheumatology centres (802 patients). All patients completed a 31-item questionnaire addressing their perceptions of current treatment and the preferences for treatment with anti-TNF agents. Statistical methods included analysis of variance (ANOVA), t-test and chi-square test. Results. The response rate to the questionnaire was 97.6%. At the time of the survey, 310 (39.9%) patients were dissatisfied with current treatments, owing to inefficacy, side effects and inconvenience of administration. The i.v. and s.c. routes of administration were preferred by 50.2 and 49.8%, respectively. No significant difference was found in patients by gender, age, RA duration or number of drugs used. Reasons for the choice of i.v. administration were the safety of treatment at the hospital and the reassuring effect of physician presence. The s.c. administration was chosen for the convenience of treatment and in particular for home treatment. Patients dissatisfied with current therapy due to side effects preferred s.c. administration (P ¼ 0.029), whereas patients choosing the i.v. route had slightly higher scores on ‘today pain’ (P ¼ 0.047) and ‘articular pain’ (P ¼ 0.023) of the Rheumatoid Arthritis Disease Activity Index (RADAI). Conclusions. Both i.v. and s.c. treatments were well accepted by patients. However, treatment choice has to be discussed with patients, as individual preference seems to be determined by personal attitudes towards safety and convenience, by past experience and by the perception of current disease status.

Osteoporotic fractures remain a major public health problem for their correlated morbidity and mortality. The primary aim of therapy must be the prevention of the first fragility fracture and avoiding subsequent fractures in patients who already have an existing fracture. There are evidences from randomized controlled trials (RCTs) about the efficacy of antiresorptives, such as bisphosphonates in reducing the risk of fracture, but none of these agents completely abolish the fracture risk. The reduction of RRR by different therapies in RCTs is relatively constant but it is important to note that the proportion of inadequate-responders (i.e.: patients fracturing despite adequate pharmacological treatment) is increasing with the severity of the disease: the higher the risk of fracture the higher the proportion of inadequate-responders. Thus, the proportion of non responders across different trials is directly related to the fracture incidence observed in the control group of RCTs which is the most proximate indicator of osteoporosis severity.Teriparatide (TPTD) demonstrate a real increases of both trabecular and cortical bone volume, which are associated with a true reduction of fracture risk, as many RCTs confirm. The beneficial effect of introducing a treatment with antiresorptives after the treatment course with TPTD has been clearly demonstrated with the prevention of the reabsorption of the new bone tissue built during TPTD therapy and rapidly lowers cortical porosity, which leads to further increases in BMD. For these results, the introduction of an anti-resorptive after the treatment course with TPTD is strongly recommended and taken into account.In Italy TPTD is fully reimbursed in patients incurring in a new vertebral or hip fracture while on chronic treatment with antiresorptive or in naive patients with 3 or more vertebral or hip fractures. In conclusion, since patients with severe osteoporosis are at very high risk of new fractures with worsening of quality of life and life expectancy, antiresorptives represent a sub-optimal treatment in these patients, werehas, since TPTD demonstrated real and substantial improvements in bone mass and reduction of fracture risk independently of initial risk, TPTD represents the only therapeutic option able to reverse at least in part this disabling disease.