Poor treatment adherence is problematic in many therapy areas, including multiple sclerosis (MS). Several immunomodulatory drugs are available for the treatment of MS, all of which require frequent ...parenteral administration. Current first-line therapies are two formulations of interferon (IFN) beta-1a, one of IFN beta-1b, and one of glatiramer acetate. Discontinuation of treatment is common, particularly in the first few months after initiation. Although the true effect of poor adherence to MS therapy is not known, it is likely to lead to a fall in treatment efficacy. Many factors influence a patient's adherence to treatment, including the patient's MS subtype and disability level, cognitive impairment resulting from MS, perceived lack of efficacy of the prescribed medication, and adverse events associated with MS therapy. This article summarizes the barriers to adherence to MS therapies, and discusses patient management strategies that can be employed to encourage adherence. Future advances in the field of MS treatment will be explored, including the development of orally administered drugs, which may enhance adherence.
Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the central nervous system and is associated with autoantibodies to anti-aquaporin-4 (AQP4-IgG) in approximately two thirds ...of patients. Interleukin-6 is involved in the pathogenesis of the disorder. Satralizumab is a humanized monoclonal antibody targeting the interleukin-6 receptor. The efficacy of satralizumab added to immunosuppressant treatment in patients with NMOSD is unclear.
In a phase 3, randomized, double-blind, placebo-controlled trial, we randomly assigned, in a 1:1 ratio, patients with NMOSD who were seropositive or seronegative for AQP4-IgG to receive either satralizumab, at a dose of 120 mg, or placebo, administered subcutaneously at weeks 0, 2, and 4 and every 4 weeks thereafter, added to stable immunosuppressant treatment. The primary end point was the first protocol-defined relapse in a time-to-event analysis. Key secondary end points were the change from baseline to week 24 in the visual-analogue scale (VAS) pain score (range, 0 to 100, with higher scores indicating more pain) and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score (range, 0 to 52, with lower scores indicating more fatigue). Safety was also assessed.
A total of 83 patients were enrolled, with 41 assigned to the satralizumab group and 42 to the placebo group. The median treatment duration with satralizumab in the double-blind period was 107.4 weeks. Relapse occurred in 8 patients (20%) receiving satralizumab and in 18 (43%) receiving placebo (hazard ratio, 0.38; 95% confidence interval CI, 0.16 to 0.88). Multiple imputation for censored data resulted in hazard ratios ranging from 0.34 to 0.44 (with corresponding P values of 0.01 to 0.04). Among 55 AQP4-IgG-seropositive patients, relapse occurred in 11% of those in the satralizumab group and in 43% of those in the placebo group (hazard ratio, 0.21; 95% CI, 0.06 to 0.75); among 28 AQP4-IgG-seronegative patients, relapse occurred in 36% and 43%, respectively (hazard ratio, 0.66; 95% CI, 0.20 to 2.24). The between-group difference in the change in the mean VAS pain score was 4.08 (95% CI, -8.44 to 16.61); the between-group difference in the change in the mean FACIT-F score was -3.10 (95% CI, -8.38 to 2.18). The rates of serious adverse events and infections did not differ between groups.
Among patients with NMOSD, satralizumab added to immunosuppressant treatment led to a lower risk of relapse than placebo but did not differ from placebo in its effect on pain or fatigue. (Funded by Chugai Pharmaceutical; ClinicalTrials.gov number, NCT02028884.).
Cognitive impairment is a common and disabling feature of multiple sclerosis (MS), but a precise characterization of cognitive phenotypes in patients with MS is lacking.
To identify cognitive ...phenotypes in a clinical cohort of patients with MS and to characterize their clinical and magnetic resonance imaging (MRI) features.
This multicenter cross-sectional study consecutively screened clinically stable patients with MS and healthy control individuals at 8 MS centers in Italy from January 1, 2010, to October 31, 2019. Patients with MS and healthy control individuals who were not using psychoactive drugs and had no history of other neurological or medical disorders, learning disability, severe head trauma, and alcohol or drug abuse were enrolled.
Participants underwent a neurological examination and a cognitive evaluation with the Rao Brief Repeatable Battery and Stroop Color and Word Test. A subgroup of participants also underwent a brain MRI examination. Latent profile analysis was used on cognitive test z scores to identify cognitive phenotypes. Linear regression and mixed-effects models were used to define clinical and MRI features of each phenotype.
A total of 1212 patients with MS (mean SD age, 41.1 11.1 years; 784 women 64.7%) and 196 healthy control individuals (mean SD age, 40.4 8.6 years; 130 women 66.3%) were analyzed in this study. Five cognitive phenotypes were identified: preserved cognition (n = 235 patients 19.4%), mild-verbal memory/semantic fluency (n = 362 patients 29.9%), mild-multidomain (n = 236 patients 19.5%), severe-executive/attention (n = 167 patients 13.8%), and severe-multidomain (n = 212 patients 17.5%) involvement. Patients with preserved cognition and mild-verbal memory/semantic fluency were younger (mean SD age, 36.5 9.8 years and 38.2 11.1 years) and had shorter disease duration (mean SD 8.0 7.3 years and 8.3 7.6 years) compared with patients with mild-multidomain (mean SD age, 42.6 11.2 years; mean SD disease duration, 12.8 9.6 years; P < .001), severe-executive/attention (mean SD age, 42.9 11.7 years; mean SD disease duration, 12.2 9.5 years; P < .001), and severe-multidomain (mean SD age, 44.0 11.0 years; mean SD disease duration, 13.3 10.2 years; P < .001) phenotypes. Severe cognitive phenotypes prevailed in patients with progressive MS. At MRI evaluation, compared with those with preserved cognition, patients with mild-verbal memory/semantic fluency exhibited decreased mean (SE) hippocampal volume (5.42 0.68 mL vs 5.13 0.68 mL; P = .04), patients with the mild-multidomain phenotype had decreased mean (SE) cortical gray matter volume (687.69 35.40 mL vs 662.59 35.48 mL; P = .02), patients with severe-executive/attention had higher mean (SE) T2-hyperintense lesion volume (51.33 31.15 mL vs 99.69 34.07 mL; P = .04), and patients with the severe-multidomain phenotype had extensive brain damage, with decreased volume in all the brain structures explored, except for nucleus pallidus, amygdala and caudate nucleus.
This study found that by defining homogeneous and clinically meaningful phenotypes, the limitations of the traditional dichotomous classification in MS can be overcome. These phenotypes can represent a more meaningful measure of the cognitive status of patients with MS and can help define clinical disability, support clinicians in treatment choices, and tailor cognitive rehabilitation strategies.
Ocean acidification has been shown to have highly variable effects, with many negative and some positive responses from individual species, while community level effects are largely unknown. Although ...an overall loss of biodiversity is expected, predicting the effects of ocean acidification on whole assemblages can be problematic as both direct and indirect effects of acidification must be taken into consideration. This study demonstrates how invertebrate assemblages associated with the highly productive seagrass, Posidonia oceanica, respond to natural acidification that occurs at CO2 vents off the coast of Italy. We examined seasonal differences in invertebrate community structure between two distinct pH zones: control (pH8.1) and acidified (pH7.8) and show that many groups of invertebrate taxa were robust to acidification effects. Differences in community structure appeared to be driven by the indirect effects of acidification, such as changes to canopy structure and food availability, rather than physiological intolerance to low pH. The number of invertebrates collected in acidified stations was almost double that of control stations during the study and many heavily calcified species appeared to thrive. These results highlight how positive indirect effects may buffer the ecological impacts of acidification, and provide evidence that this highly productive, nearshore habitat may provide refuge to its associated communities from future ocean acidification.
•Many seagrass-associated taxa appear robust to ocean acidification.•Invertebrate abundance almost doubled in naturally acidified stations.•The increase in invertebrate abundance was only observed in warm water months.•Changes to community structure appeared to be driven by indirect rather than direct effects of acidification.
Using the term of progressive multiple sclerosis (PMS), we considered a combined population of persons with secondary progressive MS (SPMS) and primary progressive MS (PPMS). These forms of MS cannot ...be challenged with efficacy by the licensed therapy. In the last years, several measures of risk estimation were developed for predicting clinical course in MS, but none is specific for the PMS forms. Personalized medicine is a therapeutic approach, based on identifying what might be the best therapy for an individual patient, taking into account the risk profile. We need to achieve more accurate estimates of useful predictors in PMS, including unconventional and qualitative markers which are not yet currently available or practicable routine diagnostics. The evaluation of an individual patient is based on the profile of disease activity.Within the neurology field, PMS is one of the fastest-moving going into the future.
Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease with still unknown etiology. We aimed at investigating the association between environmental and occupational ...factors with ALS risk.
We performed a population-based case-control study in four Italian provinces (Catania, Modena, Novara, and Reggio Emilia) by administration of tailored questionnaires to ALS cases (
= 95) and randomly selected population referents (
= 135). We estimated ALS risk by calculating the odds ratio (OR) with its 95% confidence interval (CI) using an unconditional logistic regression model.
We found a positive association with disease risk for history of occupation in the agricultural sector (OR = 2.09, 95% CI 0.79-7.54), especially for longer than 10 years (OR = 2.72, 95% 1.02-7.20). Overall occupational exposure to solvents also suggested a positive association, especially for thinners (OR = 2.27, 95% CI 1.14-4.54) and paint removers (OR = 2.01, 95% CI 0.90-4.48). Both occupational and environmental exposure to electromagnetic fields show a slightly increased risk with OR = 1.69 (95% CI 0.70-4.09) and 2.41 (95% CI 1.13-5.12), respectively. Occupational but not environmental exposure to pesticides (OR = 1.22, 95% CI 0.63-2.37), particularly fungicides, and exposure to metals (OR = 4.20, 95% CI 1.88-9.38), particularly lead, mercury, and selenium, showed an imprecise but positive association. Finally, there was an indication of increased risk for living in proximity to water bodies.
Despite the caution that needs to be used due to some study limitations, such as the low number of exposed subjects and the possibility of recall bias, these results suggest the potential role of some environmental and occupational factors in ALS etiology.
Abstract
Background
Despite trends towards the increased age of patients living with multiple sclerosis (MS), little is known about the response of older adults with MS to disease-modifying therapies ...(DMTs). Thus, a
post-hoc
analysis was undertaken using data from a 2-year, international, non-interventional, prospective cohort study (NCT00787657; BEACON: BEtaferon prospective study on Adherence, COping and Nurse support) of patients above the age of 40 years with MS and starting interferon beta-1b (IFNB-1b) treatment within 6 months before study entry.
Methods
Middle-aged and older patients with MS were divided into two sub-groups: 41–50 years and > 50 years. Treatment with IFNB-1b started within 6 months before study entry. Patients were followed-up for a 2-year observation period. Assessments included disease history and course, annualised relapse rate (ARR), Expanded Disability Scale Score (EDSS), treatment adherence, Hospital Anxiety and Depression Scale (HADS), and adverse events (AE).
Results
At baseline, the intention-to-treat (ITT) population (
n
= 481) aged 41–50 years (
n
= 327) and > 50 years (
n
= 154), had mean (standard deviation SD) ages of 45.1 (2.8) and 56.2 (4.2) years, maximum age of 72 years, and duration of MS since onset of symptoms of 3.9 (5.2) and 5.9 (7.1) years, respectively. At baseline, the proportion of patients with relapsing–remitting MS (RRMS) was 96.3 and 94.9 %, and secondary progressive MS (SPMS) was 3.7 and 5.1 %, in the 41–50 and > 50 years sub-groups, respectively. The ARR in the 2 years before study start was 0.93 (0.48) and 0.86 (0.54) for the 41–50 and > 50 years groups, respectively, and decreased since study start to 0.20 (1.09) and 0.07 (0.37), respectively. The percentage of patients with anxiety and depression, as measured by HADS, were stable over the study period. Polypharmacy (five or more medications) was seen in 32.3 and 41.2 % of patients aged 41–50 and > 50 years. No unexpected AEs were reported.
Conclusions
This study provides observational data on patients between 40 and 72 years of age, suggesting that IFNB-1b can be an effective and well-tolerated treatment option in MS patients of advanced age.
Trial registration
ClinicalTrials.gov, NCT00787657.
Composition, density and specimen sizes of pelagic polychaete assemblages were analyzed in the Southern Adriatic Sea. The study was based on finely stratified vertical (0-1100 m) and spatial sampling ...(17 stations) representing spring conditions. Holoplanktonic polychaetes were distributed in both neritic and pelagic waters, although the highest densities were observed along the Otranto Channel. Analysis of the size frequency distribution revealed a trend with depth only for some species. Spatial distribution of holoplanktonic polychaete density was not related to bottom depth, being the organisms mainly concentrated in the epipelagic layer (0-100 m). The most abundant species showed maximum values below or within the thermocline and within the Deep Chlorophyll Maximum or just above it. Relations between polychaete presence and the underlying oceanographic mechanisms regulating the circulation in the Otranto Channel were discussed. The presence of several non-determined polychaete larvae (e.g. Syllidae) in the pelagic waters at 800-1100 m depths suggests the importance of the role of Levantine waters as main actual and potential carrier of species in the area, though a relevant contribution comes also from North Adriatic dense waters through deep spilling and cascading in the Southern Adriatic pit. These findings increase the knowledge on holoplanktonic polychaetes ecology within the South Adriatic Sea, and represent significant data in the monitoring of changes in biodiversity.
Data on pregnancy long-term effects on multiple sclerosis (MS) course are still controversial; whether experiencing more than one pregnancy exposes one to risk of the disability's accrual is still ...unknown. We investigated differences existing in terms of disability progression among women with MS (wwMS) who had one or more children after their MS onset.
Monoparous and multiparous wwMS were enrolled from the Catania MS Center, Italy, in a monocenter retrospective study. A Cox proportional hazards model was used to examine the effect of the number of parities on time from MS disease onset to EDSS 4.0 and 6.0. The study protocol was approved by the local Ethical Committee.
During the seven years of observation, 32.1% and 23.2% of the monoparous group reached expanded disability disease status (EDSS) 4.0 and 6.0 respectively, compared to 13.3% and 3.3% of the multiparous group (p = 0.057 and p = 0.017; respectively). The Kaplan-Meier curve analysis showed no statistically-significant differences between the two groups in reaching the two milestones. The multiparous group showed a longer time to reach the EDSS 4.0 (3.5 vs. 2.6 years, log-rank 0.57, p = 0.45). The Cox regression analysis showed that the EDSS at the time of first pregnancy (Exp(B) 9.4, CI 4.5-19.7, p< 0.001) and the time from MS onset to first pregnancy (Exp(B) 0.96, CI = 0.93-0.98, p < 0.05) were significant predictors of reaching the EDSS 4.0, whereas a model including only the EDSS one year after the first pregnancy significantly predicted (Exp(B) value of 6.4, CI 2.6-15.4, p < 0.001) the reaching of EDSS 6.0.
Our results suggest that experiencing more than one pregnancy could not convey a different clinical outcome in wwMS. Further research is needed to confirm our results.
PDF
