Effect Of Disease-modifying Treatment Research Articles

Disease-Modifying Treatments for Multiple Sclerosis Affect Measures of Cellular Immune Responses to EBNA-1 Peptides.

Epstein-Barr virus (EBV) has been strongly implicated in the pathogenesis of multiple sclerosis (MS). Despite this, there are no routinely used tests to measure cellular response to EBV. In this study, we analyzed the cellular response to EBV nuclear antigen-1 (EBNA-1) in people with MS (pwMS) using a whole blood assay. This cross-sectional study took place in a dedicated MS clinic in a university hospital. We recruited healthy controls, people with epilepsy (PWE), and pwMS taking a range of disease-modifying treatments (DMTs) including natalizumab, anti-CD20 monoclonal antibodies (mAbs), dimethyl fumarate (DMF), and also treatment naïve. Whole blood samples were stimulated with commercially available PepTivator EBNA1 peptides and a control virus-cytomegalovirus (CMV) peptide. We recorded the cellular response to stimulation with both interferon gamma (IFN-γ) and interleukin-2 (IL-2). We also compared the cellular responses to EBNA1 with IgG responses to EBNA1, viral capsid antigen (VCA), and EBV viral load. We recruited 86 pwMS, with relapsing remitting MS, in this group, and we observed a higher level of cellular response recorded with IFN-γ (0.79 IU/mL ± 1.36) vs healthy controls (0.29 IU/mL ± 0.90, p = 0.0048) and PWE (0.17 IU/mL ± 0.33, p = 0.0088). Treatment with either anti-CD20 mAbs (0.28 IU/mL ± 0.57) or DMF (0.07 IU/mL ± 0.15) resulted in a cellular response equivalent to control levels or in PWE (p = 0.26). The results of recording IL-2 response were concordant with IFN-γ: with suppression also seen with anti-CD20 mAbs and DMF. By contrast, we did not record any differential effect of DMTs on the levels of IgG to either EBNA-1 or VCA. Nor did we observe differences in cellular response to cytomegalovirus between groups. This study demonstrates how testing and recording the cellular response to EBNA-1 in pwMS may be beneficial. EBNA-1 stimulation of whole blood samples produced higher levels of IFN-γ and IL-2 in pwMS compared with controls and PWE. In addition, we show a differential effect of currently available DMTs on this response. The functional assay deployed uses whole blood samples with minimal preprocessing suggesting that employment as a treatment response measure in clinical trials targeting EBV may be possible.

Glial Activity Load on PET Reveals Persistent "Smoldering" Inflammation in MS Despite Disease-Modifying Treatment: 18 F-PBR06 Study.

18 F-PBR06-PET targeting 18-kDa translocator protein can detect abnormal microglial activation (MA) in multiple sclerosis (MS). The objectives of this study are to develop individualized mapping of MA using 18 F-PBR06, to determine the effect of disease-modifying treatment (DMT) efficacy on reducing MA, and to determine its clinical, radiological, and serological correlates in MS patients. Thirty 18 F-PBR06-PET scans were performed in 22 MS patients (mean age, 46 ± 13 years; 16 females) and 8 healthy controls (HCs). Logarithmically transformed "glial activity load on PET" scores (calculated as the sum of voxel-by-voxel z -scores ≥4), "lnGALP," were compared between MS and HC and between MS subjects on high-efficacy DMTs (H-DMT, n = 13) and those on no or lower-efficacy treatment, and correlated with clinical measures, serum biomarkers, and cortical thickness. Cortical gray matter (CoGM) and white matter (WM) lnGALP scores were higher in MS versus HC (+33% and +48%, P < 0.001). In H-DMT group, CoGM and WM lnGALP scores were significantly lower than lower-efficacy treatment ( P < 0.01) but remained abnormally higher than in HC group ( P = 0.006). Within H-DMT patients, CoGM lnGALP scores correlated positively with physical disability, fatigue and serum glial fibrillary acid protein levels ( r = 0.65-0.79, all P 's < 0.05), and inversely with cortical thickness ( r = -0.66, P < 0.05). High-efficacy DMTs decrease, but do not normalize, CoGM and WM MA in MS patients. Such "residual" MA in CoGM is associated with clinical disability, serum biomarkers, and cortical degeneration. Individualized mapping of translocator protein PET using 18 F-PBR06 is clinically feasible and can potentially serve as an imaging biomarker for evaluating "smoldering" inflammation in MS patients.

Humoral Response to SARS-COV-2 Vaccination in Patients with Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder: A Real-World Study.

The risk of SARS-CoV-2 infection or severe coronavirus disease 2019 (COVID-19) has been shown to increase in patients with multiple sclerosis (MS). Vaccination is recommended in this patient population, and the effect of disease-modifying treatments (DMTs) on response to vaccination should be considered. This prospective, observational, cross-sectional study investigated humoral response after COVID-19 vaccination as well as possible predictors for response in patients with MS and other neuroinflammatory diseases who received DMTs in routine clinical practice in Spain. Responses were compared versus those seen in healthy controls. After vaccination against COVID-19, most patients with MS developed an immune response comparable to that of healthy individuals. However, approximately half of patients receiving a sphingosine-1-phosphate modulator (SP1-M, fingolimod or siponimod) or a B-cell-depleting agent (aCD20, ocrelizumab or rituximab) did not develop protective antibodies, although patients receiving other DMTs had humoral immune responses comparable to healthy controls. Lymphocyte count was not associated with reduced humoral response in patients receiving an SP1-M or aCD20, whereas, in patients receiving an aCD20 or SP1-M, older age was associated with lower anti-SARS-CoV-2 spike protein immunoglobulin G antibody levels. Treatment with aCD20 or SP1-M therapies appears to be associated with a lower humoral response to vaccines against SARS-CoV-2. Vaccination prior to initiation of these DMTs should be recommended whenever possible.

Alternative Endpoints and Models for AD Prevention Trials

AbstractBackgroundThere are several challenges for AD prevention trials. First, the subtle cognitive change in asymptomatic disease stages requires large sample sizes, e.g. 400‐500/arm for two phase 3 confirmatory trials, or 800‐900/arm for a single phase 3 confirmatory trial, using the traditional MMRM. Second, large, international trials may necessitate the use of different tracers for imaging biomarker assessment due to global availability issues, however, statistical models that harmonize tracer differences within clinical trials are still lacking. Third, primary prevention trials using time to event endpoint demands even larger sample sizes, e.g., 1650/arm for TRAILBLAZER‐ALZ 3 with time‐to‐first‐conversion from CDR global 0 to &gt;0 as the outcome. The percentage slowing relative to placebo decline (e.g., lecanemab led to 27% slowing at 18 months) is a popular concept to describe treatment effect. Instead of estimating the absolute difference using MMRM, we proposed to model this percentage treatment effect directly using the percentage or proportional MMRM (pMMRM). pMMRM can harmonize assessments from different tracers by converting the absolute difference into a shared proportional treatment effect across tracers. When using time‐to‐conversion as the primary outcome, instead of using a single event, Cox proportional hazards models for recurrent events can capture the treatment effect after the first event, where a recurrent event is defined as any increment over the previous visit in CDR global.MethodWe first demonstrated that disease modifying treatment effects are essentially proportional retreatment effects. Then, we evaluated the power advantage of pMMRM over MMRM and Cox recurrent events model over single event model through simulations. Finally, we demonstrated how to harmonize data from different tracers using pMMRM.ResultFigure 1 demonstrates that disease modifying treatment effects are like proportional treatment effects, leading to diverged disease progression trajectories and increased absolute differences. Figure 2 shows the power comparison between MMRM and pMMRM. pMMRM led to a power increase up to 30% over MMRM.ConclusionAlternative models such as pMMRM or Cox recurrent event models can yield greater power and pMMRM can harmonize assessment from different tracers, which may help enable global prevention trials in AD with disease modifying drug effects.

Effect of disease-modifying treatment on spinal cord lesion formation in multiple sclerosis: A retrospective observational study.

Spinal cord lesions in multiple sclerosis (MS) are an important contributor to disability. Knowledge on the effect of disease-modifying treatment (DMT) on spinal lesion formation in MS is sparse, as cord outcome measures are seldom included in MS treatment trials. We aim to investigate whether intermediate- or high-efficacy DMTs (i/hDMT) can reduce spinal lesion formation, compared with low-efficacy DMTs (lDMT) and/or no treatment. Relapse-onset MS patients with ≥2 spinal MRIs (interval >3 months and <10 years) were retrospectively identified. The i/hDMT-group was defined as patients who were treated with i/hDMTs during ≥90% of spinal MRI follow-up time. Controls received lDMTs and/or no treatment ≥90% of follow-up duration. In a secondary analysis, only patients using lDMT for ≥90% of follow-up were considered controls. Patients were matched using propensity-scores. Cox proportional hazards models were used to estimate the risk of new spinal lesions. 323 patients had ≥2 spinal cord MRIs. 49 satisfied i/hDMT and 168 control group criteria. 34 i/hDMT patients were matched to 83 controls. Patients in the i/hDMT-group were significantly less likely to develop new cord lesions at follow-up (HR 0.29 [0.12-0.75], p=0.01). When the i/hDMT-group was matched to only controls using lDMT ≥90% of follow-up time (n=17 and n=25, respectively), there was no statistically significant difference (HR 1.01 [0.19-5.24], p=0.99). Treatment with intermediate- or high-efficacy DMTs reduces the risk of new spinal cord lesions compared with matched patients receiving no treatment and/or lDMTs. No conclusions could be drawn on whether i/hDMTs provide a larger risk reduction compared to only lDMTs (control group receiving lDMTs ≥90% of follow-up time).

Using instrumental variables to correct for bias in real-world cohort studies of the effects of disease-modifying treatment in MS

Background: Estimating the effect of disease-modifying treatment of MS in observational studies is impaired by bias from unmeasured confounders, in particular indication bias. Objective: To show how instrumental variables (IVs) reduce bias. Methods: All patients with relapsing onset of MS 1996–2010, identified by the nationwide Danish Multiple Sclerosis Registry, were followed from onset. Exposure was treatment index throughout the first 12 years from onset, defined as a cumulative function of months without and with medium- or high-efficacy treatment, and outcomes were hazard ratios (HRs) per unit treatment index for sustained Expanded Disability Scale Score (EDSS) 4 and 6 adjusted for age at onset and sex, without and with an IV. We used the onset cohort (1996–2000; 2001–2005; 2006–2010) as an IV because treatment index increased across the cohorts. Results: We included 6014 patients. With conventional Cox regression, HRs for EDSS 4 and 6 were 1.15 [95% CI: 1.13–1.18] and 1.17 [1.13–1.20] per unit treatment index. Only with IVs, we confirmed a beneficial effect of treatment with HRs of 0.86 [0.81–0.91] and 0.82 [0.74–0.90]. Conclusion: The use of IVs eliminates indication bias and confirms that treatment is effective in delaying disability. IVs could, under some circumstances, be an alternative to marginal structural models.

Effects of disease-modifying therapies on lipid parameters in patients with multiple sclerosis.

Cholesterol and lipids are essential components of nerve cells. Myelin synthesis and stabilization is a cholesterol-dependent process. It has been shown in several studies that high plasma cholesterol levels may be associated with clinical deterioration in Multiple Sclerosis (MS). There is scarce information about the effects of disease-modifying treatment (DMTs) on lipid profile. In this study, we aimed to investigate the effect of DMTs on plasma lipid profiles in MS patients. The records of 380 MS patients who were still under follow-up were analyzed in terms of age, sex, disease duration, EDSS scores, serum lipid levels, and used DMTs. The data of patients receiving Interferon (n=53), Glatiramer acetate (n=25), Fingolimod (n=44), Teriflunomide (n=24), Dimethyl fumarate (n=7) and Ocrelizumab (n=14) were compared with the data of control group (n=53). A total of 220 patients, 157 women, and 63 men, were included in the study. The average age of the participants in the study was 39.83±10.21 years, mean disease duration was 8.45±6.56 years, and the EDSS score was 2.25±1.97. Although, Lipid parameters were higher in MS patients using Fingolimod the difference cannot reach the statistical significance. No significant relationship was found between the DMTs that MS patients had been using for the last six months and their cholesterol levels.

Current Status of Oral Disease-Modifying Treatment Effects on Cognitive Outcomes in Multiple Sclerosis: A Scoping Review.

Cognitive impairment represents one of the most hidden and disabling clinical aspects of multiple sclerosis (MS). In this regard, the major challenges are represented by the need for a comprehensive and standardised cognitive evaluation of each patient, both at disease onset and during follow-up, and by the lack of clear-cut data on the effects of treatments. In the present review, we summarize the current evidence on the effects of the available oral disease-modifying treatments (DMTs) on cognitive outcome measures. In this systematised review, we extract all the studies that reported longitudinally acquired cognitive outcome data on oral DMTs in MS patients. We found 29 studies that evaluated at least one oral DMT, including observational studies, randomised controlled trials, and their extension studies. Most of the studies (n = 20) evaluated sphingosine-1-phosphate (S1P) modulators, while we found seven studies on dimethyl fumarate, six on teriflunomide, and one on cladribine. The most frequently used cognitive outcome measures were SDMT and PASAT. Most of the studies reported substantial stability or mild improvement in cognitive outcomes in a short-time follow-up (duration of most studies ≤2 years). A few studies also reported MRI measures of brain atrophy. Cognitive outcomes were evaluated only in a minority of prospective studies on oral DMTs in MS patients with variable findings. More solid and numerous data are present for the S1P modulators. A standardised cognitive evaluation remains a yet unmet need to better clarify the possible positive effect of oral DMTs on cognition.

Onasemnogene abeparvovec preserves bulbar function in infants with presymptomatic spinal muscular atrophy: a post-hoc analysis of the SPR1NT trial

Bulbar function in spinal muscular atrophy has been defined as the ability to meet nutritional needs by mouth while maintaining airway protection and communicate verbally. The effects of disease-modifying treatment on bulbar function are not clear. A multidisciplinary team conducted post-hoc analyses of phase 3 SPR1NT trial data to evaluate bulbar function of infants at risk for spinal muscular atrophy who received one-time gene replacement therapy (onasemnogene abeparvovec) before symptom onset. Three endpoints represented adequate bulbar function in SPR1NT: (1) absence of physiologic swallowing impairment, (2) full oral nutrition, and (3) absence of adverse events indicating pulmonary instability. Communication was not assessed in SPR1NT. We descriptively assessed numbers/percentages of children who achieved each endpoint and all three collectively. SPR1NT included infants <6 postnatal weeks with two (n = 14) or three (n = 15) copies of the survival motor neuron 2 gene. At study end (18 [two-copy cohort] or 24 [three-copy cohort] months of age), 100% (29/29) of patients swallowed normally, achieved full oral nutrition, maintained pulmonary stability, and achieved the composite endpoint. When administered to infants before clinical symptom onset, onasemnogene abeparvovec allowed children at risk for spinal muscular atrophy to achieve milestones within published normal ranges of development and preserve bulbar function.

CO21 A New View on Quantification of Disease Modification: Two Case Studies from Parkinson’s Disease

Therapies that slow disease progression are a major unmet need in neurodegenerative diseases, such as Parkinson’s disease (PD). Disease-modifying treatment effects are usually reported in terms of differences in outcome measures which can be difficult to interpret, especially by patients. Here we aim to explore an interpretable quantification of time delay of two PD therapies rasagiline (approved symptomatic PD therapy with potential disease-modifying effects) and prasinezumab (investigational anti-α-Synuclein antibody), based on published trial results.

Current advances in the pharmacological prevention and management of cognitive dysfunction in multiple sclerosis

ABSTRACT Introduction Cognitive impairment (CI) is a core feature of Multiple Sclerosis (MS), being detectable in up to 65% of subjects. Treatment of CI can be considered of paramount importance. However, no standardized strategies are available to date to define the best treatment approach, especially for the pharmacological management. Areas covered In this narrative review, the authors outline the latest advances in pharmacological management of CI in MS, including Disease Modifying Treatments (DMTs) which indirectly may or may not influence CI and symptomatic drugs. Selected publications were restricted to those written in English, reporting on an adult relapsing-remitting MS or progressive MS sample, assessing the effects of (at least) 1 DMT or treatment in a longitudinal design, reporting data on (at least) one standardized cognitive test performed at baseline and follow-up, and published between January 2018 and May 2022. Expert opinion Recent data can be considered encouraging and inspiring for future studies. Overall, there is preliminary evidence of a beneficial effect of DMTs on cognition, particularly for high-efficacy DMTs. As for symptomatic treatments, dalfampridine appears to be the only medication with robust evidence of a positive effect on cognition. However, the definition of clinically meaningful change/improvement in cognitive functions remains an unmet need. Future studies should assess the role of other patient-related factors that can be associated with a better cognitive response to treatments and investigate the possible positive effect of multimodal interventions on cognition.

Immune responses following COVID-19 infection in multiple sclerosis patients using immunomodulatory therapy.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2), has quickly become a global pandemic. Most multiple sclerosis (MS) patients use disease-modifying treatments (DMTs), such as immunomodulators or immunosuppressants. By targeting different types of immune cells, DMTs affect cellular and/or humoral immunity. The potential effects of DMTs on the long-term immune response to COVID-19 is not fully known. Between 16.04.2020 and 15.07.2020, a total of 34 people, 17 of whom were diagnosed with MS according to the 2010 McDonald diagnostic criteria and a control group of 17 individuals who did not have a known systemic disease who were matched according to age, gender, and COVID-19 disease severity, where all received COVID-19 diagnosis with SARS-CoV-2 PCR positivity in nasopharyngeal swab test and immune responses were measured (SARS-CoV-2 IgM and IgG antibody levels COVID 19 ELISA kit), were included in our study. Demographic data of MS patients and the control group, SARS-CoV-2 immune responses, antibody titers and disease year of MS patients, EDSS scores, disease type, and disease duration were determined. All patients were symptomatic for COVID-19. COVID-19 disease severity was divided into three groups as mild, moderate, and severe according to the clinical condition of the patient. Demographic data of MS patients and the control group, SARS-CoV-2 immune responses, antibody titers and disease year of MS patients, EDSS scores, disease type, and disease duration were determined. All patients were symptomatic for COVID-19. COVID-19 disease severity was divided into three groups as mild, moderate, and severe according to the clinical condition of the patient. According to our study results, IgG-type long-term immune responses were lower in MS patients using DMTs than in the healthy population. We hope that our study will provide insight into the COVID-19 vaccine immune responses.

Progression models for repeated measures: Estimating novel treatment effects in progressive diseases.

Mixed models for repeated measures (MMRMs) are ubiquitous when analyzing outcomes of clinical trials. However, the linearity of the fixed-effect structure in these models largely restrict their use to estimating treatment effects that are defined as linear combinations of effects on the outcome scale. In some situations, alternative quantifications of treatment effects may be more appropriate. In progressive diseases, for example, one may want to estimate if a drug has cumulative effects resulting in increasing efficacy over time or whether it slows the time progression of disease. This article introduces a class of nonlinear mixed-effects models called progression models for repeated measures (PMRMs) that, based on a continuous-time extension of the categorical-time parametrization of MMRMs, enables estimation of novel types of treatment effects, including measures of slowing or delay of the time progression of disease. Compared to conventional estimates of treatment effects where the unit matches that of the outcome scale (eg, 2 points benefit on a cognitive scale), the time-based treatment effects can offer better interpretability and clinical meaningfulness (eg, 6months delay in progression of cognitive decline). The PMRM class includes conventionally used MMRMs and related models for longitudinal data analysis, as well as variants of previously proposed disease progression models as special cases. The potential of the PMRM framework is illustrated using both simulated and historical data from clinical trials in Alzheimer's disease with different types of artificially simulated treatment effects. Compared to conventional models it is shown that PMRMs can offer substantially increased power to detect disease-modifying treatment effects where the benefit is increasing with treatment duration.

Time to rethink the reported disease-modifying treatment effects on cognitive outcomes: Methods and interpretative caveats.

Time to rethink the reported disease-modifying treatment effects on cognitive outcomes: Methods and interpretative caveats.

Sodium selenate as a therapeutic for tauopathies: A hypothesis paper.

In a large proportion of individuals with fronto-temporal lobar degeneration (FTLD), the underlying pathology is associated with the misfolding and aggregation of the microtubule associated protein tau (FTLD-tau). With disease progression, widespread protein accumulation throughout cortical and subcortical brain regions may be responsible for neurodegeneration. One of the syndromes of FTLD is the behavioral variant of frontotemporal dementia (bvFTD), in which the underlying pathology is heterogenous, with half of the cases being related to FTLD-tau. Currently, there are no approved disease-modifying treatments for FTLD-tau, therefore representing a major unmet therapeutic need. These descriptive, preliminary findings of the phase 1 open-label trial provide data to support the potential of sodium selenate to halt the cognitive and behavioral decline, as well as to reduce tau levels in a small group of participants with bvFTD (N = 11). All participants were treated with sodium selenate over a period of 52 weeks. Cognition was assessed with the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG, total scores), social cognition with the Revised Self-Monitoring Scale (RSMS, total scores), behavior with the Cambridge Behavioral Inventory (CBI), and carer burden with the Caregiver Buden Scale (CBS). Fluid biomarker measures include cerebrospinal fluid of total tau (t-tau), phosphorylated tau (p-tau181), NfL, p-tau181/t-tau, t-tau/Aβ1–42, and p-tau181/Aβ1–42 levels. After treatment at follow-up, cognition and behavior showed further negative change (based on a reliable change criterion cut-off of annual NUCOG decline) in the “progressors,” but not in the “non-progressors.” “Non-progressors” also showed elevated baseline CSF tau levels and no increase after treatment, indicating underlying tau pathology and a positive response to sodium selenate treatment. Significant changes in MRI were not observed. The findings provide useful information for future clinical trials to systematically assess the disease-modifying treatment effects of sodium selenate in randomized controlled designs for bvFTD and FTLD-tau pathologies.

CO86 Effect of Disease Modifying Treatments on Quality of Life in Patients with Multiple Sclerosis. Systematic Review and Network Meta-Analysis

Due to lack of information in head-to-head trials that compare the effect of disease modifying treatments (DMT) in the health related quality of life (HRQoL) of patients with remittent recurrent multiple sclerosis (RRMS), the objective of this study was to perform a network meta-analysis that estimates the treatment effect between different approved DMTs.

039 Disease modifying treatments and cancer monitoring in MS; the need for a nation-wide disease registry

The immune system is inextricably linked to both cancer and Multiple Sclerosis (MS). National population- based cohort studies in Denmark and Norway have attempted to elucidate the relationship between cancer and MS, but results are conflicting. The advent of highly-efficacious disease modifying treatments (DMTs) in recent years revolutionised MS treatment, but the effect of their immunomodulating mechanism on cancer risk is unclear. Studies thus far have been limited by lack of cancer risk factor data and statistical power. In this pilot study, we identified the relevant data, including patient and cancer characteristics, DMT use, and important risk factors that may confound treatment effects. These data was collected for MS patients with cancer under the care of Salford Royal Foundation Trust. This highlighted the incomplete- ness of records, and the need for a framework for data collection. Moreover, data collection relied on multiple sources. Integration of the resultant question proforma into patient records will be a simple tool to enable reliable, homogeneous data collection. Deepening understanding of the effect of DMTs on cancer risk will improve risk-benefit treatment analysis in MS, thus improving care. Indeed, the institution of a nation-wide patient registry for such data in the UK will facilitate necessary future research.j.das@doctors.org.uk

Effect of disease-modifying treatments on antibody-mediated response to anti-COVID19 vaccination in people with multiple sclerosis.

BackgroundFew data are available so far on the antibody-mediated immune response to anti-SARS-Cov2 vaccination in people with multiple sclerosis (pwMS) treated with disease-modifying treatments (DMTs), therefore this issue was explored in a real-life cohort of pwMS.Materials and methodsRetrospective monocentric study on anti-spike protein antibody response in pwMS who had received vaccination for Sars-Cov2. Adverse events following vaccination were also recorded.ResultsOne hundred and twenty pwMS were included: 83 females (69%); median age at vaccination 42 years (range 21–73); 112/120 patients (93%) were receiving DMTs at vaccination. Anti-spike protein IgG antibodies were detectable in 102/120 (85%) cases overall, being the proportion lower in pwMS receiving anti-CD20 antibodies (14/31, 45%) compared to non-depletive treatments (77/78, 99%), p < 0.0001. Median anti-spike titre was lower in anti-CD20 antibodies and fingolimod-treated pwMS compared to those receiving other DMTs, and it correlated with anti-CD20 treatment duration (R − 0.93, p < 0.0001) and with age at vaccination in pwMS not receiving depletive treatments (R − 0.25, p = 0.028). Baseline CD19+ cell count (where available) was higher in the responder group than in non-responders, p < 0.0001. Two symptomatic COVID-19 infections were diagnosed over a median follow-up of 5 months (range 2–7); adverse events were aligned with the published literature.ConclusionAntibody response to anti-COVID-19 vaccines was detected in most of the pwMS analysed, but frequency of responders was reduced in those receiving CD20 depleting therapies compared to other DMTs-treated pwMS. Investigations on cell-mediated immune response are needed to assess whether a protective immune response is elicited also in non-antibody responders.

A clinical effect of disease-modifying treatment on alloimmunisation in transfused patients with myelodysplastic syndromes: data from a population-based study.

Alloimmunisation against blood products is an adverse event, causing time-consuming compatibility testing. Current literature has not yet identified the influence of treatment on the risk of alloimmunisation in patients with myelodysplastic syndromes (MDS). An observational, population-based study, using the HemoBase registry, was performed including all transfused patients who were diagnosed with MDS between 2005 and 2017 in Friesland, a province in the Netherlands. Information about transfusion dates, types, and treatment regimens was collected from the health records. Blood products were matched for ABO and Rhesus D. The effect of disease-modifying treatment was estimated with incidence rates and a Cox time-dependent analysis. 233 patients were included in this study, with a median follow-up of 13.0 months. Alloimmunisation occurred in 21 patients (9.0%) and predominantly occurred early in follow-up. Three (5%) and 18 (11%) alloimmunisation events occurred in patients with and without disease-modifying treatment, respectively. The hazard ratio for alloimmunisation without treatment compared to during treatment was 2.7 (95% CI: 0.35-20.0), with incidence rates of 7.18 and 2.41 per 100 patient-years, respectively. In a non-selected real-world population of MDS patients receiving blood transfusions, the percentage of patients with alloimmunisation was below 10%. The results of this study support the hypothesis that disease-modifying treatment affects the ability of the immune system to mount an antibody response to non-self blood group antigens.

The Turkish experience of COVID-19 infection in people with NMOSD and MOGAD: A milder course?

BackgroundCOVID-19 is a multisystemic infection with variables consequences depending on individual and comorbid conditions. The course and outcomes of COVID-19 during neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) are not clearly known. Objective/methodsThe aim of this study was to examine the features and outcomes of COVID-19 infection in NMOSD and MOGAD patients. The patients' demographic and clinical factors, disease modifying treatment (DMT) used and disease information of COVID-19 infection were recorded. Conditions leading to hospitalization and severe exposure to COVID-19 infection were also analyzed. ResultsThe study included 63 patients from 25 centers. Thirty-two patients (50.8%) belong to AQP-4 seropositive group, 13 (20.6%) and 18 (28.6%) were in MOG-positive and double-seronegative groups, respectively. Risk factors for severe COVID-19 infection and hospitalization were advanced age, high disability level and the presence of comorbid disease. Disease severity was found to be high in double-seronegative NMOSD and low in MOGAD patients. No statistically significant effect of DMTs on disease severity and hospitalization was found. ConclusionIn NMOSD and MOGAD patients, advanced age, high disability and presence of comorbid disease pose risks for severe COVID-19 infection. There was no direct significant effect of DMTs for COVID-19 infection.