Objective:
To describe a temporal association between COVID-19 vaccine administration and multiple sclerosis (MS) relapses.
Methods:
This case series study was collected in four MS Centres in Central ...Italy, using data from 16 MS patients who received COVID-19 vaccination and presented both clinically and radiologically confirmed relapses between March and June 2021. We collected patients' relevant medical history, including demographics, MS clinical course, disease-modifying treatment (DMT) received (if applicable), and data from MRI scans obtained after the COVID-19 vaccination.
Results:
Three out of 16 patients received a diagnosis of MS with a first episode occurring after COVID-19 vaccination; 13 had already a diagnosis of MS and, among them, 9 were on treatment with DMTs. Ten patients received BNT162b2/Pfizer-BioNTech, 2 patients mRNA-1273/Moderna, and 4 patients ChAdOx1 nCoV-19/AstraZeneca. All MS relapses occurred from 3 days to 3 weeks after receiving the first dose of the COVID-19 vaccination or the booster. All patients had evidence of radiological activity on MRI.
Discussion:
Clinical and radiological findings in these cohort of MS patients confirmed disease re/activation and suggested a temporal association between disease activity and COVID-19 vaccination. The nature of this temporal association, whether causative or incidental, remains to be established.
In patients with Multiple Sclerosis (pwMS) disease-modifying therapies (DMTs) affects immune response to antigens. Therefore, post-vaccination serological assessments are needed to evaluate the ...effect of the vaccine on SARS-CoV-2 antibody response.
We designed a prospective multicenter cohort study enrolling pwMS who were scheduled for SARS-Cov-2 vaccination with mRNA vaccines (BNT162b2, Pfizer/BioNTech,Inc or mRNA-1273, Moderna Tx,Inc). A blood collection before the first vaccine dose and 4 weeks after the second dose was planned, with a centralized serological assessment (electrochemiluminescence immunoassay, ECLIA, Roche-Diagnostics). The log-transform of the antibody levels was analyzed by multivariable linear regression.
780 pwMS (76% BNT162b2 and 24% mRNA-1273) had pre- and 4-week post-vaccination blood assessments. 87 (11·2%) were untreated, 154 (19·7%) on ocrelizumab, 25 (3·2%) on rituximab, 85 (10·9%) on fingolimod, 25 (3·2%) on cladribine and 404 (51·7%) on other DMTs. 677 patients (86·8%) had detectable post-vaccination SARS-CoV-2 antibodies. At multivariable analysis, the antibody levels of patients on ocrelizumab (201-fold decrease (95%CI=128–317), p < 0·001), fingolimod (26-fold decrease (95%CI=16–42), p < 0·001) and rituximab (20-fold decrease (95%CI=10–43), p < 0·001) were significantly reduced as compared to untreated patients. Vaccination with mRNA-1273 resulted in a systematically 3·25-fold higher antibody level (95%CI=2·46–4·27) than with the BNT162b2 vaccine (p < 0·001). The antibody levels on anti-CD20 therapies correlated to the time since last infusion, and rituximab had longer intervals (mean=386 days) than ocrelizumab patients (mean=129 days).
In pwMS, anti-CD20 treatment and fingolimod led to a reduced humoral response to mRNA-based SARS-CoV-2 vaccines. As mRNA-1273 elicits 3·25-higher antibody levels than BNT162b2, this vaccine may be preferentially considered for patients under anti-CD20 treatment or fingolimod. Combining our data with those on the cellular immune response to vaccines, and including clinical follow-up, will contribute to better define the most appropriate SARS-CoV-2 vaccine strategies in the context of DMTs and MS.
FISM2021/Special-Multi/001; Italian Ministry of Health‘Progetto Z844A 5 × 1000′.
Background
This research aimed to investigate the experience of Neuromyelitis Optica Spectrum Disorders (NMOSD) by integrating the perspectives of patients, caregivers and clinicians through ...narrative-based medicine to provide new insights to improve care relationships.
Methods
The research was conducted in the second half of 2022 and involved six Italian centres treating NMOSD and targeted adult patients, their caregivers and healthcare providers to collect the three points of view of living with or caring for this rare disease, still difficult to treat despite the pharmacological options. Narratives followed a structured outline according to the time: yesterday-today-tomorrow, to capture all disease phases.
Results
Twenty-five patients diagnosed with NMOSD, ten caregivers and 13 healthcare providers participated in the research. Patients reported symptoms limiting their daily activities and strongly impacting their social dimension. We noticed improvements across disease duration, whilst the persistence of limitations was recurrent in patients with longer diagnoses.
Caregivers’ narratives mainly share experiences of their daily life changes, the burden of the caregiving role and the solutions identified, if any. Healthcare providers defined their role as a guide.
Conclusion
Limitations in activities are prominent in the lives of people with NMOSD, along with fatigue. Family members are the weakest link in the chain and need information and support. Healthcare professionals are attentive to the helping dimension.
Background
Since the incidence of cancer increases with age, in older cancer patients important information may be missed without a Comprehensive Geriatric Assessment (CGA). On the other side, CGA is ...a time-consuming and complex instrument, so that Geriatric 8 (G8) has been proposed as a more feasible screening tool to identify patients who could benefit from a CGA evaluation. G8 consists of 8 questions (patient age + 7 items derived from the Mini Nutritional Assessment questionnaire). A G8 score ≤ 14 is considered associated with frailty and risk of malnutrition. Another screening test is Bioelectrical Impedance Analysis (Bioimpedentiometry, BIA), which enables to evaluate the nutritional status through a specific parameter known as Phase angle (PhA). This study is aimed at assessing the ability of G8 alone or in combination with PhA to detect elderly cancer patients at higher risk for malnutrition who cannot undergo immediate anticancer treatments.
Methods
A total of 289 cancer patients (168 men and 121 women) aged ≥ 70 years old were enrolled and performed both G8 test, body mass index (BMI) and BIA assessments. A concurrent G8 score ≤ 14 and PhA < 5 defined subjects most exposed to the risk of malnutrition.
Results
An association between BMI and G8 (p < 0.001, OR 1.54) and a clinically significant relationship between G8 and PhA (p = 0.013) were observed.
Conclusion
G8 can be used to identify patients at risk for malnutrition who would benefit from comprehensive CGA. The concurrent use of G8 and BIA presents a higher power in discriminating subjects at higher risk of malnutrition than a single test. This study suggests the need for routine assessment of nutritional status in cancer patients using combinations of methods, in order to implement strategies for individually-tailored care before starting any treatment.
Ocrelizumab is a recombinant humanized monoclonal antibody selectively targeting CD20-expressing B cells. The effect of ocrelizumab on primary progressive multiple sclerosis (PPMS) has been evaluated ...during phase 3 trials that enrolled patients under 55 years with a maximum Expanded Disability Status Scale (EDSS) of 6.5. However, little is known on older disabled patients with longer disease duration. We aimed to assess the clinical effectiveness of ocrelizumab in PPMS patients out of the ORATORIO eligibility criteria. This multicenter retrospective study collected data about the effectiveness of ocrelizumab in PPMS patients who received treatment between May 2017 and June 2022 in the Italian MS centers contributing to the Italian MS Registry who adhered to the Compassionate Use Program. The confirmed EDSS worsening (CEW) (defined as either a ≥ 1-point or ≥ 2-point increase in EDSS score from baseline that was confirmed at T12 and T24) was calculated. At the date of data extraction, out of 887 PPMS patients who had received ocrelizumab, 589 (mean age 49.7 ± 10.7 years, 242 (41.1%) females) were enrolled. The mean follow-up period was 41.3 ± 12.3 months. A total of 149 (25.3%) received ocrelizumab according to the ORATORIO criteria (ORATORIO group) and 440 (74.7%) outside the ORATORIO criteria (non-ORATORIO group). No differences in terms of cumulative probabilities of 12 and 24 months of CEW of ≤ 1 point were found between ORATORIO and non-ORATORIO groups. Cox regression analyses showed that age older than 65 years (HR 2.51, 25% CI 1.07–3.65;
p
= 0.01) was associated with higher risk of CEW at 24 months. Patients not responding to ORATORIO criteria for reimbursability may benefit from ocrelizumab treatment, as disease activity, disease duration, and EDSS seem to not impact the disability outcome. Our results may suggest to extend the possible use of this powerful agent in selected patients under the age of 65 years.
Background
ChatGPT is an open-source natural language processing software that replies to users’ queries. We conducted a cross-sectional study to assess people living with Multiple Sclerosis’ (PwMS) ...preferences, satisfaction, and empathy toward two alternate responses to four frequently-asked questions, one authored by a group of neurologists, the other by ChatGPT.
Methods
An online form was sent through digital communication platforms. PwMS were blind to the author of each response and were asked to express their preference for each alternate response to the four questions. The overall satisfaction was assessed using a Likert scale (1–5); the Consultation and Relational Empathy scale was employed to assess perceived empathy.
Results
We included 1133 PwMS (age, 45.26 ± 11.50 years; females, 68.49%). ChatGPT’s responses showed significantly higher empathy scores (Coeff = 1.38; 95% CI = 0.65, 2.11;
p
>
z
< 0.01), when compared with neurologists’ responses. No association was found between ChatGPT’ responses and mean satisfaction (Coeff = 0.03; 95% CI = − 0.01, 0.07;
p
= 0.157). College graduate, when compared with high school education responder, had significantly lower likelihood to prefer ChatGPT response (IRR = 0.87; 95% CI = 0.79, 0.95;
p
< 0.01).
Conclusions
ChatGPT-authored responses provided higher empathy than neurologists. Although AI holds potential, physicians should prepare to interact with increasingly digitized patients and guide them on responsible AI use. Future development should consider tailoring AIs’ responses to individual characteristics. Within the progressive digitalization of the population, ChatGPT could emerge as a helpful support in healthcare management rather than an alternative.
In this prospective post-marketing study, 21 patients with multiple sclerosis treated with natalizumab for 24 consecutive months elected a trial of treatment interruption (90–180 days). During a mean ...duration of treatment interruption of 111.5 days 4 patients (19.0%) experienced a relapse and 9 out of 19 (47.4%) had MRI activity. Number of contrast-enhancing lesions at baseline was lower than during treatment interruption, but the difference was not significant. These findings suggest that disease activity may return after the last infusion of natalizumab. Patients should have regular MRI assessment during treatment interruption to rapidly identify any return of disease activity. The aim of this study was to determine the optimal duration for temporary interruption of natalizumab therapy in patients who have received continuous therapy with natalizumab for 24 months.
Cognitive impairment is a disabling symptom in multiple sclerosis (MS). While its management remains challenging, beneficial effects on cognition of interferon beta (IFN-β) have been reported and a ...positive effect from estroprogestins has been hypothesised, suggesting that the combination of the two medications in women with MS could offer a promising treatment strategy.
We investigated whether a combination of estroprogestins and IFN-β can improve cognition in women with MS.
Women with relapsing-remitting (RR) MS were randomly assigned (1:1:1) to receive subcutaneous IFN-β-1a (Rebif
, Merck Serono, Geneva, Switzerland) 44 mcg three times a week (tiw) (group 1), subcutaneous IFN-β-1a 44 mcg tiw plus ethinyl estradiol 20 mcg and desogestrel 150 mcg (Mercilon
, MSD Italia SRL, Rome, Italy) (group 2) or subcutaneous IFN-β-1a 44 mcg tiw plus ethinyl estradiol 40 mcg and desogestrel 125 mcg (Gracial
, Organon Italia S.p.A., Rome, Italy) (group 3) in a randomised controlled trial, for which we report the analysis of secondary outcomes. At baseline and at 24 months, all patients underwent magnetic resonance imaging (MRI) and a comprehensive cognitive assessment, including Rao's Brief Repeatable Battery (RBRB) and questionnaires for depression, fatigue and quality of life. Failure in at least two of the RBRB tests defined 'cognitive impairment'.
At baseline, there was no difference in the proportion of cognitively impaired patients. At month 24, the proportion of patients with cognitive impairment was lower in group 3 (34.8%) than in group 1 (47.6%) (p = 0.03). The risk of developing cognitive impairment over 24 months was lower in group 3 (p = 0.02). Mood and fatigue scores were comparable across the groups over time at both time points. However, at month 24, group 3 showed worsening on the sexual function subscale of the 54-item MS quality-of-life questionnaire (p = 0.03).
This study suggests that the combination of high-dose estroprogestins and IFN-β may have positive effects on cognition. However, the effect of this treatment on sexual function requires caution to be exercised. Protocol Number NCT00151801, registered in ClinicalTrials.gov.
OBJECTIVE:To test the effect of oral contraceptives (OCs) in combination with interferon β (IFN-β) on disease activity in patients with relapsing-remitting multiple sclerosis (RRMS).
METHODS:One ...hundred fifty women with RRMS were randomized in a 1:1:1 ratio to receive IFN-β-1a subcutaneously (SC) only (group 1), IFN-β-1a SC plus ethinylstradiol 20 μg and desogestrel 150 μg (group 2), or IFN-β-1a SC plus ethinylestradiol 40 μg and desogestrel 125 μg (group 3). The primary endpoint was the cumulative number of combined unique active (CUA) lesions on brain MRI at week 96. Secondary endpoints included MRI and clinical and safety measures.
RESULTS:The estimated number of cumulative CUA lesions at week 96 was 0.98 (95% confidence interval CI 0.81–1.14) in group 1, 0.84 (95% CI 0.66–1.02) in group 2, and 0.72 (95% CI 0.53–0.91) in group 3, with a decrease of 14.1% (p = 0.24) and 26.5% (p = 0.04) when comparing group 1 with groups 2 and 3, respectively. The number of patients with no gadolinium-enhancing lesions was greater in group 3 than in group 1 (p = 0.03). No significant differences were detected in other secondary endpoints. IFN-β or OC discontinuations were equally distributed across groups.
CONCLUSIONS:Our results translate the observations derived from experimental models to patients, supporting the anti-inflammatory effects of OCs with high-dose estrogens, and suggest possible directions for future research.
CLASSIFICATION OF EVIDENCE:This study provides Class II evidence that in women with RRMS, IFN-β plus ethinylstradiol and desogestrel decreases the cumulative number of active brain MRI lesions compared with IFN-β alone.
PDF
