Background

Historically, disease activity diminished during pregnancy in women with relapsing-remitting MS. Today, women with high disease activity are more likely to attempt pregnancy due to the disease control that new therapies offer. But disease activity during pregnancy in the modern day remains understudied.

Objectives

Describe disease activity in a modern pregnancy cohort, grouped by preconception disease-modifying therapy (DMT) class; determine the predictors of relapse during pregnancy.

Methods

Data were obtained from the MSBase Registry. Term/preterm pregnancies conceived from 2011-2019 were included. DMT were classed by low, moderate and high-efficacy. Annualized relapse rates (ARR) were calculated for each pregnancy trimester and 12 months either side. Predictors of relapse during pregnancy were determined using clustered logistic regression.

Results

We included 1640 pregnancies from 1452 women. DMT used in the year before conception were none (n=346), low (n=845), moderate (n=207) and high-efficacy (n=242). Most common DMT in each class was interferon-beta (n=597), fingolimod (n=147) and natalizumab (n=219) for low, moderate and high-efficacy respectively. Conception EDSS ≥2 was more common in higher efficacy DMT groups (high: 41.3%; moderate 28.5%; low 22.4%; none 20.2%). For low-efficacy and no DMT groups, ARR fell through pregnancy. ARR of the moderate-efficacy group increased in the 1^st pregnancy trimester (0.55 [95% CI 0.36-0.80] vs 0.14 [95% CI 0.10-0.21] on low-efficacy), then decreased to a trough in the third. Conversely, ARR steadily increased throughout pregnancy for those on high-efficacy DMT (3^rd trimester: 0.42 [95% CI 0.25-0.66] vs 0.12 [95% CI 0.07-0.19] on low-efficacy). Higher efficacy DMT groups were associated with higher ARR in the early postpartum period (high: 0.84 [95% CI 0.62-1.1]; moderate: 0.90 [95% CI 0.65-1.2]; low: 0.47 [95% CI 0.38-0.58]). Preconception use of high and moderate-efficacy DMT and higher preconception ARR were predictors of relapse in pregnancy. But, continuation of high-efficacy DMT into pregnancy was protective against relapse (odds ratio 0.80 [95% CI 0.68-0.94]). Age ≥35 years was associated with reduced odds of relapse.

Conclusions

Women with RRMS treated with moderate or high-efficacy DMT are at greater risk of relapse during pregnancy. Careful pregnancy management, and use of long-acting high-efficacy DMT preconception, or continuing natalizumab into pregnancy, may prevent relapse in pregnancy.

Background

Multiple Sclerosis (MS) is a chronic disease that requires frequent medical follow-up. COVID-19 pandemic may have changed the way patients accessed Health Care facilities including laboratory and imaging exams as well as urgent or routine medical appointments.

Objectives

To assess differences in health care accessibility from a patient perspective since the announcement of the state of emergency, due to COVID-19 pandemic, by the Portuguese government.

Methods

We performed an online questionnaire-based study; 485 adult patients followed in our tertiary centre with the diagnosis of MS were invited to answer the survey that was accessible from April to June 2020.

Results

We included 195 valid questionnaires from 195 patients. Fifty-four percent had a university degree (53.8%) and approximately half of the patients were professionally active. Most of the patients (69.7%) did not experience any symptom related to MS. Fifty-nine patients (30.3%) had new possible MS- related symptoms of whom 37 (62%) sought health care services: 47% had an appointment with their neurologist through a phone call, 22% contacted the MS nurse, 17% contacted the general practitioner, 8% were seen at the MS clinic (by other neurologist) and 6% at the emergency department. About a third of patients (30.6%) who did not seek a health care appointment admitted that would do it otherwise in a non-pandemic context. Regarding scheduled exams, 37 patients (19%) did not perform a scheduled blood collection and 23 (11.8%) did not perform scheduled imaging, mostly due to medical advice (46% and 44% respectively) or due to patient fear (31% and 19%). Eighteen patients (9.2%) stopped their prescribed medication of which 14 did so on their own volition. Thirteen patients were tested for COVID-19, two were positive. More than half the patients (55.9%) considered that teleconsultation was adequate and were satisfied with the information and recommendations provided (59.5%).

Conclusions

We conclude that COVID-19 pandemic markedly impacted Health Care access to MS patients and may change the way MS clinics evaluate and follow their patients as telemedicine emerges as a valuable tool.

Background

Multiple Sclerosis (MS) is a chronic disease that encompasses lifelong symptoms and both physical and psychological disability. The COVID-19 pandemic may have changed the way patients accessed Health Care facilities, with an impact on their perceived health status and psychological well-being.

Objectives

To evaluate physical disability and psychosocial well-being since the announcement of the state of emergency, due to COVID-19 pandemic, by the Portuguese government.

Methods

We performed an online questionnaire-based study; 485 adult patients followed in our tertiary centre with the diagnosis of MS were invited to answer the survey that was accessible from April to June 2020. We analysed data regarding disability (self-reported EDSS), mental status, fatigue and sleep through scales validated for the Portuguese population: suffering thermometer, Depression Anxiety Stress Scales-21 (DASS-21) (answered when suffering thermometer scored more than 5), Modified Fatigue Impact Scale (MFIS-21) and Satisfaction Alerteness Timing Efficiency Duration (SATED) sleep scale.

Results

We included 195 valid questionnaires from 195 patients. Fifty-four percent had a university degree (53.8%) and approximately half of the patients were professionally active. Self-reported EDSS presented a positive correlation with last EDSS measured by the neurologist (p<0.01, R²=0.68). Median (IQR) DASS-21 was 18 (12-25), MFIS-21 was 31 (17-49) and SATED 20 (16-24). Emotional suffering was equal or greater than 5/10 in 31% during the state of emergency and in 53% at the time of survey response. A third of patients reported lower quality of sleep due to COVID-19 and higher fatigue. A quarter of patients reported more pain and 30% reported more spasticity.

Patients who had a self-reported EDSS worse than the last EDSS measured by the neurologist had significantly worse performance in MFIS (p<.001) and SATED (p=.007), while no differences were observed for DASS-21 (p=.36). Patients who said that were feeling worse since COVID-19 pandemics also had worse performance in MFIS-21 (p<.001) and SATED (p=.028), while this was not observed for DASS-21 (p=0.26).

Conclusions

We conclude that the COVID-19 pandemic impacted the physical and psychological well-being of MS patients. Patients who felt more disabled scored significantly higher in fatigue and sleep quality measures. In-person follow-up is needed to confirm the patient-reported disability worsening.

Background

Neuromyelitis optica spectrum disorders (NMOSD) encompasses a group of rare inflammatory diseases which primarily target the optic nerves, spinal cord, and brain. Typically, magnetic resonance imaging (MRI) data from single-center studies comprise 20-50 patients, limiting statistical power for outcomes research. Using retrospective data from the PArallel MRI in NmOsd (PAMRINO) study, a novel prospective NMOSD image repository (NMOsDIR) representing multiple international sites was coordinated by Charité-Universitätsmedizin Berlin and the Medical Image Analysis Center (Basel).

Objectives

The PAMRINO study aimed to investigate and analyze retrospective MRIs collected from NMOSD-specialized centers, potentially for the evaluation of disease-related brain and spinal cord changes. NMOsDIR serves as an international imaging research resource (comprising standardized retinal optical coherence tomography and MRI scans) and clinical data hub for prospective studies in NMOSD. Linking imaging and clinical data, as well as enabling analysis pipelines for each modality, will facilitate multi-centered studies using sufficient data and statistical power to advance outcomes research in this rare disease.

Methods

For clinical data collection in PAMRINO, a Research Electronic Data Capture (REDCap) platform was used, where participating centers entered data relevant for NMOSD patient monitoring. An image database (XNAT) was established for image uploads. This large collection of MRI data is currently being analyzed in a joint international effort of NMOSD clinical neuroradiologists and scientists.

Results

Brain, spinal cord, and optic nerve MRI scans with associated clinical data were collected from 514 NMOSD patients and 56 healthy controls from 17 international centers. Roughly 20,000 individual MRI scans from patients and healthy controls were collected. Of these, 78% had T1-weighted cerebral MRIs (55% with 3D scans), 80% had T2-weighted cerebral MRIs (54% with 3D scans), 86% had T2-weighted spinal cord MRIs (55% with 3D scans), and 35% had optic nerve MRIs.

Conclusions

We successfully established PAMRINO, an international collaborative retrospective MRI and clinical data repository. The knowledge gained during this process provided important new insights, where the initial analysis of the dataset has underscored the large degree of heterogeneity in image and clinical data collection in NMOSD-specialized centers. Thus, calling for more standardized methods of data acquisition and imaging analysis, as not to limit research opportunities. The new longitudinal, prospective NMOsDIR will help us to answer many pressing - yet open - questions regarding patients seropositive for aquaporin-4-IgG+, myelin oligodendrocyte glycoprotein-IgG+ and other autoimmune-related diseases. In turn, such a strategy will strengthen future capabilities in research, diagnosis, monitoring and improving NMOSD patient care.

Background

Detailed updated records from Multiple Sclerosis (MS) patient cohorts are crucial to obtain information on disease course and prognosis.

Objectives

To characterize the natural history of MS in a cohort from a Portuguese tertiary centre, comparing patients’ characteristics according to the first appointment date throughout 10-year spans (1987-1996; 1997-2006; 2007-2016).

Methods

In this longitudinal retrospective study we collected data about demography, diagnosis (date, EDSS, subtype), follow-up (duration, EDSS, subtype), relapses (initial symptoms, annualized relapse rate-ARR) and disease-modifying therapies (DMT). We conducted descriptive analysis to characterize the cohort and compared data between the three decades using Chi-square test, ANOVA and Kruskal-Wallis test.

Results

548 adult patients with relapsing-remitting MS were included, 73% female. Mean age at diagnosis was 34.0 years and mean disease duration 14.7 years. 5.7% of all patients had family history of MS. Eighteen patients had died. No significant differences were found regarding gender and age at diagnosis in patients from the 3 subgroups. The most common presenting relapses were supratentorial and spinal cord related. The median number of relapses between first and last appointment was 3, significantly higher in subgroups 87-96 and 97-06, although the ARR was significantly higher in the subgroup 07-16. The baseline EDSS was significantly higher in 87-96 decade and the percentage of patients achieving EDSS 3.0 and 6.0 significantly decreased since first decade. The mean time between EDSS 3.0 and 6.0 was 4.28 years, without significant differences in the 3 decades. The percentage of patients who converted to secondary progressive (SP) disease was significantly higher in 87-96 decade; the mean time to reach SP was 15.5 years, similar in all decades. The majority of patients started treatment with a first line DMT. The number of patients under a second line drug was higher for those included in the decades 97-06 and 07-16. Median time from diagnosis to first treatment was considerably higher for patients with first appointment in the 87-96 decade.

Conclusions

We document the natural history of MS in 3 decades, including 87-96 where DMT were not yet available, and found that patient’s demography remains similar. The higher ARR in last decade may reflect a better awareness of disease monitoring and differences in disability progression may be due to the impact of increasing DMTs.

Background

Therapeutic inertia is defined as a failure to initiate or intensify treatments despite clinical and paraclinical evidence of disease activity. Its prevalence and determining factors in Relapsing-Remitting Multiple Sclerosis (RRMS) patients in Portugal are not known.

Objectives

Our primary goal was to determine the frequency of therapeutic inertia in our RRMS patients; our secondary goal was to describe therapeutic inertia predisposing factors.

Methods

A multicentre retrospective observational study was performed. We studied patients with RRMS followed in MS Clinics of six Portuguese hospitals with at least one medical appointment during the study period (January 1^st to December 31^st 2018).

Results

We included 427 patients with RRMS, 69.6% females, with a mean age of 41.66 years-old and a mean age at diagnosis of 33.17 years-old. The average number of years since diagnosis was 8.72. MS relapses were reported on 54 patients. Median EDSS score was 1.5 (IQR=1.5). Among the 365 patients who underwent MRI during the study period, 23.8% had new T2 lesions and 7.4% had lesions with contrast enhancement. Therapeutic inertia was present in 80 patients, representing 18.7% of the total sample and 54.8% of the patients with potential to inertia (indication for treatment escalation). Patients with no more than one new T2 lesion, no gadolinium-enhancing lesions, already on a DMT, without adverse events from their current DMT and who were followed in higher care level centres were more likely to have therapeutic inertia (p<0.05). In a binary logistic regression model, the current treatment with DMT (p=0.050), the absence of adverse events (p<0.001), the higher care level (p=0.015) as defined in the Hospital Referral Network in Neurology, and the absence of relapses (p=0.021) or the presence of mild relapses (p=0.027) had an independent effect in therapeutic inertia.

Conclusions

Therapeutic inertia was present in about 1 in 5 patients, exceeding half of the population when considering all the patients with potential to inertia. The subgroup of patients with indication for therapeutic escalation and which also have less active radiological disease was associated with more therapeutic inertia, although these results were not confirmed in a multivariate analysis. Attending a higher care level center, being under DMT, absence of adverse events, and having none or mild relapses, were determining factors for therapeutic inertia.

We believe this study raises awareness to therapeutic inertia as an important problem, providing further knowledge on predisposing factors that may be adressed in MS care.

Background

Disease activity has been investigated in pregnant women with RRMS treated with low-efficacy or no therapy. How newer, more efficacious therapies affect relapse and disability progression risk after pregnancy remains understudied.

Objectives

To describe disease activity in a modern pregnancy cohort contrasted with historical cohorts. To determine the predictors of postpartum relapse and the predictors of six-month confirmed disability progression events in a contemporary pregnancy cohort.

Methods

Data were obtained from the MSBase Registry. Term/preterm pregnancies conceived from 2011-2019 (modern cohort) were compared with those conceived between 2005-2010 and pre-2005. Annualised relapse rates (ARR) were calculated for each pregnancy trimester and 12 months either side. Predictors of time-to-relapse postpartum (1^st 3 months) and time to 6-month confirmed disability progression event were determined with clustered Cox regression analyses. Breastfeeding duration and time to DMT reinitiation were modelled as time-varying covariates.

Results

We included 1640 pregnancies from 1452 women (modern cohort). Disease-modifying therapy (DMT) used in the year before conception included interferon-beta (n=597), natalizumab (n=219) and fingolimod (n=147). Continuation of DMT up to conception increased over time (31% pre-2005 vs 54% modern cohort). Preconception ARR decreased across epochs (pre-2005: 0·58 [95% CI 0·49-0·70]; 2005-2010: 0·40 [95% CI 0·36-0·45]; modern: 0·29 [95% CI 0·27-0·32]). In all epochs, ARR decreased during pregnancy to reach similar troughs in the 3^rd trimester, and rebounded in the 1^st 3-months postpartum. Preconception use of high-efficacy DMT predicted early postpartum relapse (hazard ratio (HR) 2.1 [1.4-3.1]); although those on no DMT were also at risk of postpartum relapse, relative to women on low-efficacy DMT (HR 2.7 [1.2-5.9]). Conception EDSS ≥2, higher preconception and in-pregnancy ARR were also risk factors. DMT reinitiation, particularly of high-efficacy DMT (HR 0.17 [0.07-0.38]), was protective against postpartum relapse. Women who breastfed were less likely to relapse (HR 0.63 [0.42-0.94]). 4.5% of modern pregnancies had confirmed disability progression after delivery. This was predicted by higher pregnancy and postpartum ARR, with postpartum ARR remaining independently predictive in multivariable analysis (HR 1.5 [1.2-2.0]).

Conclusions

The early postpartum period remains a period of vulnerability for disease rebound in women with MS in the modern era. Early DMT reinitiation, particularly with high-efficacy treatment, is protective against postpartum relapse. Confirmed disability progression events after pregnnacy are uncommon in the modern era. Relapse activity is the key driver of these events.