Structured benefit-risk assessment for enoxaparin, in the context of its label extension, for the extended treatment of deep vein thrombosis and pulmonary embolism, and prevention of its recurrence in patients with active cancer.

PURPOSE: Guidelines recommend low-molecular-weight heparins (LMWHs) for patients with cancer-associated thrombosis. However, until recently, only dalteparin and tinzaparin were approved in the European Economic Area (EEA) for these patients. This study compares the benefit-risk profile of enoxaparin with dalteparin and tinzaparin for the extended treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrence in adult patients with active cancer. METHODS: A semi-quantitative structured benefit-risk assessment was conducted for the label-extension application of enoxaparin based on the benefit-risk action team descriptive framework: define decision context; determine key benefit and risk outcomes; identify data sources; extract data; interpret results. RESULTS: The key benefits were defined as reduced all-cause mortality and venous thromboembolism (VTE) recurrence (including symptomatic DVT, fatal PE or non-fatal PE); the key risks were major and non-major bleeding of clinical significance, and heparin-induced thrombocytopenia (HIT). Enoxaparin demonstrated comparable effects for the reduction of VTE recurrence and all-cause mortality versus other EEA-approved LMWHs (dalteparin, tinzaparin). There was no evidence of a significant difference between enoxaparin and the comparator groups with regard to incidence of major and non-major bleeding. The data on HIT were too limited to assess the difference between the two groups. CONCLUSIONS: The assessment demonstrated a favourable benefit-risk profile for enoxaparin similar to that of other EEA-approved LMWHs for the treatment of DVT and PE and the prevention of recurrence in patients with active cancer and thus supported the label-extension approval.

Patient and Physician Perspectives on the Use of a Connected Ecosystem for Diabetes Management: International Cross-Sectional Observational Study.

BACKGROUND: Collaboration between people with type 2 diabetes (T2DM) and their health care teams is important for optimal control of the disease and outcomes. Digital technologies could potentially tie together several health care-related devices and platforms into connected ecosystems (CES), but attitudes about CES are unknown. OBJECTIVE: We surveyed convenience samples of patients and physicians to better understand which patient characteristics are associated with higher likelihoods of (1) participating in a potential CES program, as self-reported by patients with T2DM and (2) clinical benefit from participation in a potential CES program, as reported by physicians. METHODS: Adults self-reporting a diagnosis of T2DM and current insulin use (n=197), and 33 physicians whose practices included ≥20% of such patients, were enrolled in the United States, France, and Germany. We surveyed both groups about the likelihood of patient participation in a CES. We then examined the associations between patients' clinical and sociodemographic characteristics and this likelihood. We also described characteristics of patients likely to clinically benefit from CES use, according to physicians. RESULTS: Compared with patients in Germany and France, US patients were younger (mean age 45.3 [SD 11.9] years vs 61.9 [SD 9.2] and 65.8 [SD 9.4] years, respectively), more often female, more highly educated, and more often working full-time. In all, 51 (44.7%) US patients, 16 (36.4%) German patients, and 18 (46.3%) French patients indicated strong interest in a CES program, and 115 (78.7%) reported currently using ≥1 connected device or app. However, physicians believed that only 11.3%-19.2% of their patients were using connected devices or apps to manage their disease. Physicians also reported infrequently recommending or prescribing connected devices to their patients, although ≥80% (n=28) of them thought that a CES could help support their patients in managing their disease. The factors most predictive of patient likelihood of participating in a CES program were cost, inclusion of medication reminders, and linking blood glucose levels to behaviors such as eating and exercise. In all countries, the most common patient expectations for a CES program were that it could help them eat more healthfully, increase their physical activity, increase their understanding of how blood glucose relates to behavior such as exercise and eating, and reduce stress. Physicians thought that newly diagnosed patients, sicker patients-those who had been hospitalized for diabetes, were currently using insulin, or who had any comorbid condition-and patients who were nonadherent to treatment were most likely to benefit from CES use. CONCLUSIONS: In this study, there was a high degree of interest in the future use of CES, although additional education is needed among both patients with T2DM and their physicians to achieve the full potential of such systems to improve self-management and clinical care for the disease.

A preliminary algorithm introducing immunogenicity assessment in the management of patients with RA receiving tumour necrosis factor inhibitor therapies.

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.

The immunogenicity of anti-TNF therapy in immune-mediated inflammatory diseases: a systematic review of the literature with a meta-analysis.

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.

Behavioral and attitudes survey about Lyme disease among a Brazilian population in the endemic area of Martha's Vineyard, Massachusetts.

Disease prevention models have shown individuals are more likely to engage in precautionary behavior if they have confidence in their ability to identify disease symptoms and understand health risks. In immigrant populations, communicating the risks poses greater challenges since linguistic and cultural barriers may impede acceptance of the new behavior. The Brazilian population on Martha's Vineyard, Massachusetts, is at high risk for Lyme disease (LD), the most common vector-borne illness in the United States largely preventable by limiting tick exposure. We surveyed 103 Brazilians on MV about their health beliefs and perceptions of LD risk and assessed their level of precautionary behaviors and the cultural factors influencing them. The population had only a moderate perception of risk and little understanding of LD. Forty-one percent did not think LD posed a risk, while 79% were not sure they could recognize symptoms. Accordingly, the population as a whole reported taking few precautions.

The effect of low-dose aspirin on the decreased risk of development of dyspepsia and gastrointestinal ulcers associated to cyclooxygenase-2 selective inhibitors.

OBJECTIVE: To evaluate the risk of gastrointestinal (GI) symptoms and ulcers associated to the use of low-dose aspirin (ASA) among patients with rheumatoid arthritis (RA) and osteoarthritis (OA) treated with cyclooxygenase-2 (COX-2) drugs, to clarify the controversy in the literature. METHODS: Using a longitudinal databank, a prospective study using Cox proportional hazards models was performed in patients receiving COX-2 therapy for RA or OA to examine the effect of ASA on GI events. In 4 separate analyses patients reported dyspeptic symptoms and GI ulcers at semiannual intervals for up to 3 years. Ulcers were validated by review of medical records. RESULTS: Among 4240 patients taking COX-2-specific inhibitors, with no ulcer at study start, the age- and sex-adjusted hazard ratios for the effect of ASA on the development of epigastric pain, heartburn, nausea, and ulcers, without these previous events, were 1.11 (95% CI 0.97-1.29), 1.00 (95% CI 0.88-1.15), 1.32 (95% CI 1.13-1.54), and 1.27 (95% CI 0.78-2.05). The use of a propensity score to account for the risk of ASA prescription showed an even lower effect of ASA among all GI variables. This risk occurs within the setting of no prior GI symptoms or GI events, and independently of the use of proton pump inhibitors, other GI drugs, other nonsteroidal antiinflammatory drugs, prednisone, or methotrexate. CONCLUSION: In actual practice, the use of low-dose ASA has a small effect on the risk of developing dyspeptic symptoms in a group of patients with rheumatic disease.

Protein, iron, and meat consumption and risk for rheumatoid arthritis: a prospective cohort study.

A recent prospective study showed that higher consumption of red meat and total protein was associated with increased risk for inflammatory polyarthritis. We therefore prospectively examined the relationship between diet (in particular, protein, iron, and corresponding food sources) and incident rheumatoid arthritis (RA) among 82,063 women in the Nurses' Health Study. From 1980 to 2002, 546 incident cases of RA were confirmed by a connective tissue disease screening questionnaire and medical record review for American College of Rheumatology criteria for RA. Diet was assessed at baseline in 1980 and five additional times during follow up. We conducted Cox proportional hazards analyses to calculate the rate ratio of RA associated with intakes of protein (total, animal, and vegetable) and iron (total, dietary, from supplements, and heme iron) and their primary food sources, adjusting for age, smoking, body mass index, and reproductive factors. The multivariate models revealed no association between RA and any measure of protein or iron intake. In comparisons of highest with lowest quintiles of intake, the rate ratio for total protein was 1.17 (95% confidence interval 0.89-1.54; P for trend = 0.11) and for total iron it was 1.04 (95% confidence interval 0.77-1.41; P for trend = 0.82). Red meat, poultry, and fish were also not associated with RA risk. We were unable to confirm that there is an association between protein or meat and risk for RA in this large female cohort. Iron was also not associated with RA in this cohort.

Dietary caffeine intake does not affect methotrexate efficacy in patients with rheumatoid arthritis.

OBJECTIVE: Methylxanthines, like caffeine, have been thought to reverse the antiinflammatory effects of methotrexate (MTX) in rheumatoid arthritis (RA). We investigated whether patients with RA taking MTX with a higher dietary caffeine intake have a worse clinical response to MTX than those with a lower intake. METHODS: Patients with RA enrolled in a prospective cohort study and currently taking MTX were divided equally into low, moderate, and high caffeine consumers. MTX clinical response was defined by the Disease Activity Score (DAS)28, Multidimensional Health Assessment Questionnaire (MDHAQ) score, and duration of morning stiffness. Regression models were used to study the relationship between caffeine intake and MTX response adjusting for age, sex, and other relevant variables at study enrollment. RESULTS: Two hundred and sixty-four patients with RA taking MTX had an average caffeine intake of 211.7 mg and average MTX dose of 16.0 mg/wk. The low caffeine group comprised 87 patients, the moderate 86, and the high 91. In 3 multivariate models, there was no statistical difference in MTX efficacy between groups, as measured by DAS28 score, MDHAQ score, and duration of morning stiffness at study enrollment. Moderate and high caffeine group had higher DAS28 scores, physician's global assessment, and swollen joint counts, but differences were not significant. CONCLUSION: Caffeine intake among patients taking high doses of MTX for RA did not affect MTX efficacy and RA disease activity over time.