ECTRIMS/EAN consensus on vaccination in people with multiple sclerosis: Improving immunization strategies in the era of highly active immunotherapeutic drugs.

BACKGROUND: With the new highly active drugs available for people with multiple sclerosis (pwMS), vaccination becomes an essential part of the risk management strategy. OBJECTIVE: To develop a European evidence-based consensus for the vaccination strategy of pwMS who are candidates for disease-modifying therapies (DMTs). METHODS: This work was conducted by a multidisciplinary working group using formal consensus methodology. Clinical questions (defined as population, interventions, and outcomes) considered all authorized DMTs and vaccines. A systematic literature search was conducted and quality of evidence was defined according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. The recommendations were formulated based on the quality of evidence and the risk-benefit balance. RESULTS: Seven questions, encompassing vaccine safety, vaccine effectiveness, global vaccination strategy and vaccination in sub-populations (pediatric, pregnant women, elderly and international travelers) were considered. A narrative description of the evidence considering published studies, guidelines, and position statements is presented. A total of 53 recommendations were agreed by the working group after three rounds of consensus. CONCLUSION: This first European consensus on vaccination in pwMS proposes the best vaccination strategy according to current evidence and expert knowledge, with the goal of homogenizing the immunization practices in pwMS.

European Committee for Treatment and Research in Multiple Sclerosis and European Academy of Neurology consensus on vaccination in people with multiple sclerosis: Improving immunization strategies in the era of highly active immunotherapeutic drugs.

BACKGROUND AND PURPOSE: With the new highly active drugs available for people with multiple sclerosis (pwMS), vaccination becomes an essential part of the risk management strategy. We aimed to develop a European evidence-based consensus for the vaccination strategy of pwMS who are candidates for disease-modifying therapies (DMTs). METHODS: This work was conducted by a multidisciplinary working group using formal consensus methodology. Clinical questions (defined as population, interventions and outcomes) considered all authorized DMTs and vaccines. A systematic literature search was conducted and quality of evidence was defined according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. The recommendations were formulated based on the quality of evidence and the risk-benefit balance. RESULTS: Seven questions, encompassing vaccine safety, vaccine effectiveness, global vaccination strategy and vaccination in subpopulations (pediatric, pregnant women, elderly and international travelers) were considered. A narrative description of the evidence considering published studies, guidelines and position statements is presented. A total of 53 recommendations were agreed by the working group after three rounds of consensus. CONCLUSION: This first European consensus on vaccination in pwMS proposes the best vaccination strategy according to current evidence and expert knowledge, with the goal of homogenizing the immunization practices in pwMS.

Outcomes in patients with lung cancer treated with crizotinib and erlotinib in routine clinical practice: A post-authorization safety cohort study conducted in Europe and in the United States.

PURPOSE: We examined safety outcomes of interest (SOI) and overall survival (OS) among lung cancer patients initiating crizotinib and erlotinib in routine clinical practice. METHODS: This descriptive cohort study used routinely collected health data in Denmark, Finland, Sweden, the Netherlands, and the United States (US) during 2011-2017, following crizotinib commercial availability in each country. Among crizotinib or erlotinib initiators, we reported baseline characteristics and incidence rates and cumulative incidences of the SOI - hepatotoxicity, pneumonitis/interstitial lung disease, QT interval prolongation-related events, bradycardia, vision disorders, renal cysts, edema, leukopenia, neuropathy, photosensitivity, malignant melanoma, gastrointestinal perforation, cardiac failure and OS. Results from the European Union (EU) countries were combined using meta-analysis; results from the US were reported separately. RESULTS: There were 456 patients in the crizotinib cohort and 2957 patients in the erlotinib cohort. Rates of the SOI per 1000 person-years in the crizotinib cohort ranged from 0 to 65 in the EU and from 0 to 374 in the US. Rates of the SOI per 1000 person-years in the erlotinib cohort ranged from 0 to 91 in the EU and from 3 to 394 in the US. In the crizotinib cohort, 2-year OS was ~50% in both EU and US. In the erlotinib cohort, 2-year OS was 21% in the EU and 35% in the US. CONCLUSIONS: This study describes clinical outcomes among lung cancer patients initiating crizotinib or erlotinib in routine clinical practice. Differences between SOI rates in EU and US may be partially attributable to differences in the underlying databases.

Pregnancy outcomes after exposure to interferon beta: a register-based cohort study among women with MS in Finland and Sweden.

BACKGROUND: Our aim was to estimate and compare the prevalence of adverse pregnancy outcomes among pregnant women with multiple sclerosis (MS) exposed to interferon beta (IFNB) and among women with MS unexposed to any MS disease-modifying drug (MSDMD). METHODS: This cohort study used Finnish (1996-2014) and Swedish (2005-2014) national register data. Women with MS having IFNB dispensed 6 months before or during pregnancy as the only medication were considered as IFNB exposed (only IFNB-exposed), whereas women with MS unexposed to any MSDMD were considered unexposed (MSDMD-unexposed). Prevalence was described and compared using log-binomial or logistic regression and adjusted for potential confounders including maternal age and comorbidity. RESULTS: Among 2831 pregnancies, 2.2% of the only IFNB-exposed and 4.0% of the MSDMD-unexposed women had serious adverse pregnancy outcomes [elective termination of pregnancy due to foetal anomaly (TOPFA), major congenital anomaly (MCA) in live, or stillbirth]. After adjustments, the prevalence of serious adverse pregnancy outcomes was lower among the only IFNB-exposed compared with the MSDMD-unexposed [relative risk 0.55, 95% confidence interval (CI) 0.31-0.96]. The prevalence of individual outcomes, including MCA, spontaneous abortions, and stillbirths was not increased with IFNB exposure. Women with MS exposed to IFNB appeared more likely to terminate their pregnancy for reasons other than foetal anomaly, compared with MSDMD-unexposed pregnant MS patients (odds ratio 1.71, 95% CI 1.06-2.78). CONCLUSION: In this large cohort study, no increase in the prevalence of adverse pregnancy outcomes was observed in women with MS exposed to IFNB compared with MS patients unexposed to any MSDMDs. This study together with other evidence led to a change in the labels of the IFNB products in September 2019 in the European Union, and IFNB use today may be considered during pregnancy, if clinically needed.

Presence of Giardia lamblia in stools of six- to 18-month old asymptomatic Malawians is associated with children's growth failure.

AIM: Despite high pathogen burden and malnutrition in low-income settings, knowledge on relationship between asymptomatic viral or parasitic infections, nutrition and growth is insufficient. We studied these relationships in a cohort of six-month-old Malawian infants. METHODS: As part of a nutrient supplementation trial for 12 months, we documented disease symptoms of 840 participant daily and anthropometric measurements every three months. Stool specimens were collected every six months and analysed for Giardia lamblia, Cryptosporidium species and enterovirus, rotavirus, norovirus, parechovirus and rhinovirus using polymerase chain reaction (PCR). The prevalence of the microbes was compared to the children's linear growth and the dietary. RESULTS: The prevalence of the microbes was similar in every intervention group. All age groups combined, children negative for G. lamblia had a mean standard deviation (SD) of -0.01 (0.49) change in length-for-age Z-score (LAZ), compared to -0.12 (0.045) among G. lamblia positive children (difference -0.10, 95% CI -0.21 to -0.00, p = 0.047). The LAZ change difference was also statistically significant (p = 0.042) at age of 18-21 months but not at the other time points. CONCLUSION: Asymptomatic G. lamblia infection was mainly associated with growth reduction in certain three-month periods. The result refers to the chronic nature of G. lamblia infection.

High-throughput multiplex quantitative polymerase chain reaction method for Giardia lamblia and Cryptosporidium species detection in stool samples.

Giardia lamblia and Cryptosporidium species belong to a complex group of pathogens that cause diseases hampering development and socioeconomic improvements in the developing countries. Both pathogens are recognized as significant causes of diarrhea and nutritional disorders. However, further studies are needed to clarify the role of parasitic infections, especially asymptomatic infections in malnutrition and stunting. We developed a high-throughput multiplex quantitative polymerase chain reaction (qPCR) method for G. lamblia and Cryptosporidium spp. detection in stool samples. The sensitivity and specificity of the method were ensured by analyzing confirmed positive samples acquired from diagnostics laboratories and participating in an external quality control round. Its capability to detect asymptomatic G. lamblia and Cryptosporidium spp. infections was confirmed by analyzing stool samples collected from 44 asymptomatic 6-month-old infants living in an endemic region in Malawi. Of these, five samples were found to be positive for G. lamblia and two for Cryptosporidium spp. In conclusion, the developed method is suitable for large-scale studies evaluating the occurrence of G. lamblia and Cryptosporidium spp. in endemic regions and for clinical diagnostics of these infections.