Impact of Biological Therapies on the Immune Response after Pneumococcal Vaccination in Patients with Autoimmune Inflammatory Diseases.

Patients with different autoimmune inflammatory diseases (AIID) on biological therapy are at risk of pneumococcal disease. Adults with inflammatory arthropathies, connective tissue diseases, psoriasis, or inflammatory bowel disease on biological therapy such as anti-TNFα, rituximab, tocilizumab, abatacept, or anakinra were included in this study. Patients completed a protocol combining the pneumococcal vaccines PCV13 and PPV23. Immune response against pneumococcal serotypes 1, 3, 7F, 14, 19A, and 19F were assessed evaluating functional antibodies by an opsonophagocytosis killing assay (OPKA). In this study, 182 patients with AIID completed the sequential vaccination protocol. Patients on etanercept tended to achieve OPKA titers against a larger number of serotypes than the rest of patients on other biological therapies, while adalimumab was associated to a lower number of serotypes with OPKA titers. Rituximab was not associated with a worse response when compared with the rest of biological agents. Not glucocorticoids, nor synthetic disease-modifying antirheumatic drugs, interfered with the immune response. OPKA titers against serotype 3 which is one of the most prevalent, was obtained in 44% of patients, increasing up to 58% in those on etanercept. Hence, almost 50% of patients on biological therapy achieved functional antibodies after the administration of a complete pneumococcal vaccination protocol.

Effect of intravenous iron on functional outcomes in hip fracture: a randomised controlled trial.

OBJECTIVES: to determine the safety and effect of intravenous iron sucrose on functional outcomes, delirium, nosocomial infections and transfusion requirements in older patients with hip fracture. DESIGN: single-centre randomised, double-blind, placebo-controlled clinical trial. SETTING AND PARTICIPANTS: orthogeriatric share care service at an academic tertiary care hospital. A total of 253 patients were recruited: 126 patients were assigned to intravenous iron and 127 to placebo. METHODS: on days 1, 3 and 5 after admission, the iron group received 200 mg Venofer® (iron sucrose) in 100 ml saline and the placebo group 100 ml saline. The primary outcome was absolute functional gain, considered as Barthel index (BI) at discharge minus BI on admission. Secondary outcomes included incidence of postoperative delirium according to the confusion assessment method, proportion of patients recovering prior functional status at 3 months, postoperative transfusion requirements, haemoglobin at 3 months, incidence of nosocomial infections and safety. RESULTS: the median participant age was 87 (interquartile range, 82.5-91.5) years. Most patients were female (72.7%), and the median previous BI was 81(59-95). No significant effect of intravenous iron was observed for the primary outcome: the median AFG score was 17.1 points (4.8-23.3) in the intravenous iron group and 16 points (6-26) in the placebo group (P = 0.369). No significant treatment effects were observed for other functional outcomes or secondary end points. CONCLUSION: while we found no impact of intravenous iron sucrose on functional recovery, incidence of postoperative delirium, transfusion requirements, haemoglobin at 3 months, mortality and nosocomial infections rates in older patients with hip fracture, we did find that the intervention was safe.

Off-label use of inhaled bronchodilators in hospitalised patients in Spain: a multicentre observational study.

BACKGROUND: Off-label prescription of inhaled bronchodilators (IB) is frequent, despite the fact that they can be ineffective and increase avoidable healthcare costs. OBJECTIVE: To analyse the frequency of off-label prescription of IB in hospitalised patients. Indications and level of evidence, involved drugs, medical specialties prescribing off-label IB and patients' adherence to IBs were also evaluated. METHOD: A descriptive, observational, cross-sectional study was performed in four tertiary hospitals in Spain. The main outcome measure was the number of patients prescribed off-label IBs. Prescriptions were checked against the European Medicines Agency-approved indications. The level of evidence supporting off-label prescription of IBs (according to MICROMEDEX 2.0) was also analysed. Patients were interviewed to test differences (off-label vs on-label) in adherence and knowledge about their inhaled therapy. RESULTS: 217 patients were prescribed IBs, 92 of whom were givend off-label IBs (54.7% men, mean age 73.9±12.9 years). The most common off-label prescriptions for IBs were: unspecified dyspnoea (not related to COPD or asthma) (27.2%), respiratory infections (23.9%) and heart failure (22.8%). 76.8% of patients did not have evidence supporting them. Beta2-agonist+corticosteroids and anticholinergics were most commonly prescribed off-label. Internal Medicine was the main medical specialty involved. There were no differences between off-label and on-label users in terms of patients' knowledge about treatment and adherence. CONCLUSION: Off-label indications for IBs are common in hospitalised patients and are generally indicated without scientific support. Dyspnoea not related to COPD or asthma, respiratory infections and heart failure were the main off-label indications, most frequently treated with anticholinergics and beta2-agonists+corticosteroids, for which their efficacy and safety has not been proved. Our results show that prescribing needs to be improved to follow the evidence that exists. Moreover, further research focused on off-label indications is needed to clarify whether they are effective, safe and cost-effective.

Evaluation of the immune response to hepatitis B vaccine in patients on biological therapy: results of the RIER cohort study.

To evaluate the response to hepatitis B virus (HBV) vaccine in patients on biological therapy. Adults with autoimmune inflammatory diseases on biological therapy such as anti-TNFα, rituximab, tocilizumab, abatacept, or anakinra were included. Hepatitis B surface antibody (anti-HBs) was measured by ELISA before and after vaccination. Seroconversion was considered when an anti-HBs titer > 10 mIU/mL was achieved. The effect of treatment on the immunoprotective state was studied. The response was compared with that obtained in patients on synthetic disease modifying anti-rheumatic drugs (DMARDs) and healthy controls. A total of 187 patients on biologicals, 48 on synthetic DMARDs, and 49 on healthy controls were analyzed. More than 80% of patients on biologics responded to the vaccine but required more boosters and second vaccine series. Patients who achieved seroconversion were younger than those who did not (47.10 ± 12.99 vs. 53.18 ± 10.54 years, p = 0.012). Being on etanercept or golimumab was associated with seroconversion, while being on rituximab was not. Seroconversion was achieved in 93.75% of patients on synthetic DMARDs and 97.96% of healthy controls. The seroconversion rate in the biologics group was lower than in the synthetic DMARD group (p = 0.043) and tended to be lower than in the healthy group (p = 0.056). In patients on biological therapy, a high rate of HBV vaccine response can be achieved when a complete vaccination schedule is administered. Vaccination while not on biological agents reduces the requirement for boosters and revaccination. Key points: • Patients on biological therapy can achieve high rates of immune response to HBV vaccine when complete vaccination schedules are administered. • However, to achieve such a high seroconversion rate, more boosters and second vaccination series are required. • This supports the proposal already made to provide HBV vaccination to all patients with an autoimmune inflammatory disease after the diagnosis is made and not when the use of a biological treatment is under consideration.

Antibody responses to influenza vaccine in patients on biological therapy: Results of RIER cohort study.

BACKGROUND AND OBJECTIVES: Influenza vaccine is recommended for patients with autoimmune inflammatory rheumatic diseases who receive biological therapy. To evaluate if biological therapy impairs immunization after seasonal influenza vaccine. MATERIAL AND METHODS: Patients with inflammatory arthopathies, psoriasis, inflammatory bowel disease or connective tissue diseases who were receiving or were going to initiate biological therapy were included and vaccinated during 2014-2015 influenza season. ELISA was used to measure influenza antigen A and B antibodies, before and after vaccination. Demographic parameters, diagnosis and kind of treatment were recorded and their influence on the final serological status against influenza was studied. RESULTS: 253 subjects were analyzed. After vaccination, 77% of participants presented detectable antibodies against antigen A and 50.6% of them had detectable antibodies against antigen B. Final seropositivity rate against antigen B antibodies increased from baseline (50.6% vs 43.5%, p<0.001). Anti-TNF drugs were associated with better response and rituximab with the worst (79.2% vs 55.0% for final seropositivity against antigen A, p=0.020). Vaccine response in the rituximab group tended to improve when the interval between the drug administration and the vaccination was at least 12 weeks (seropositivity rate 80.0% in those with the longer interval vs 25.0% in the other group, p=0.054). CONCLUSIONS: Among the patients on biological therapy vaccinated against influenza, anti-TNF therapy was identified as a predictive factor of final seropositivity. Rituximab presented a lower rate of final seropositivity, which could be increased with an accurate administration schedule.