National Multiple Sclerosis Registry Research Articles

Hospitalisations and humoral COVID-19 vaccine response in vaccinated rituximab-treated multiple sclerosis patients

BackgroundPatients with multiple sclerosis (MS) treated with anti-CD20 therapies such as rituximab may have increased risk of severe COVID-19 disease. Vaccination induces protective immunity, but humoral vaccine response is known to be attenuated in rituximab-treated MS-patients-patients, which has indicated a need for real world data on severe morbidity and mortality from COVID-19 after vaccination. MethodsRituximab-treated patients treated at Haukeland University Hospital were identified through the National MS Registry and invited to participate in the study by giving a consent and providing a blood sample 3 weeks or later after ordinary COVID-19- vaccination, i.e. 2 doses given with a standard interval of 3 weeks. Blood samples were analysed with Enzyme-Linked Immunosorbent assay (ELISA) to evaluate humoral vaccine response with screening test against receptor-binding domain (RBD) and confirmatory Spike IgG-specific ELISA. A haemagglutination test (HAT) was performed as a marker of neutralizing antibodies. Patient serum concentration of rituximab were quantified using liquid chromatography tandem mass spectrometry (LC-MS/MS). Registry data from the Norwegian MS registry and information on hospitalization from patient records were collected and linked to laboratory results. Results111 patients were included in the study. A total of 7 (6.3%) were hospitalized due to COVID-19 disease during the observation period. No patient was admitted to ICU and there were no deaths. 34.2% did not have detectable titre of SARS CoV-2 Spike IgG antibodies, 72.1% did not have a detectable titre of SARS CoV-2 RBD antibodies, and 88.2% did not have a detectable HAT titre. There was a correlation between hospitalisation and the absence of SARS CoV-2 Spike IgG antibody titre, and between hospitalisation and MS disease duration, as well as between spike IgG antibody titre and CD19 B-cell count, time since last rituximab infusion, cumulative rituximab treatment time and total IgG level in the patients. ConclusionA substantial proportion of rituximab-treated MS-patients-patients did not have detectable humoral vaccine responses after 2 doses of COVID-19 vaccination. Despite this, the cumulative percentage of patients hospitalized with COVID-19 disease throughout the observation period of 22 months was low, and no patients required ICU treatment. The results support that vaccinated MS-patients treated with rituximab have a protective effect against serious Covid-19 infection.

A national registry-based study of ethnic differences in people with multiple sclerosis in Iran

ObjectiveThe relationship between MS and ethnicity has been understudied in the Middle East compared to the United States and Europe. As Iran as the highest prevalence of MS in the Middle East, we decided to investigate the demographic and clinical differences in people with MS (pwMS) from major ethnicities Iran. MethodsIn a cross-sectional study using data from National Multiple Sclerosis Registry in Iran. PwMS from six provinces were chosen and interviewed for determining their ethnicity. Persians (Fars), Kurds, Lurs, Azeris and Arabs with a clear ethnic background were included. Recorded data from the registry was used to compare the demographic and clinical features. ResultsA total of 4015 pwMS (74.2% female) were included in the study with an average age of 36.76 ± 9.68 years. Persians and Kurds had the highest percentage of pwMS in youngest and oldest age groups, respectively, with 2.9% and 5.7% (p<0.01). The highest average age of onset was seen in Persians (29.47 ± 8.89) and the lowest observed in Mazandaranis (26.82 ± 7.68, p<0.01). Azeris and Kurds had the highest proportions of pwMS diagnosed <18 and >55, at rates of 12% and 1.6%, respectively (p<0.01). There were statistically significant differences in distribution of phenotypes (p<0.01) and time to progression to secondary progressive MS (p<0.01) such that Persians had the highest rate of clinically isolated syndrome (CIS) at 19.3% and Arabs had highest rates of relapsing-remitting MS (86.2%) and secondary progressive MS (16.4%). Lurs, Azeris and Mazandaranis had significantly more patients progressing to secondary-progressive MS <5 years from diagnosis (p<0.01). There was a significant difference in number of relapses between the ethnicities (p<0.01) with Lurs having the highest proportion of participants reporting >4 relapses with 23.0% and Azeris having the highest percentage of pwMS reporting no relapse (53.0%). Kurds had the highest Expanded Disability Status Scale (EDSS) average at 2.93 ± 1.99 and Lurs had the lowest with 1.28 ± 1.25 (p<0.01). The differences in prevalence of positive family history for the whole cohort between ethnicities were significant (P=0.02), ranging from 12.8% in Kurds to 19.6% in Persians. ConclusionWe found Persians to have higher rates of pediatric MS and higher rates of CIS. Kurds and Lurs had higher and lower EDSS scores, respectively. Lurs and Persian had higher annual relapse rates. We also found lower rates of SPMS among Arabs and earlier progression to SPMS in Lurs, Azeris and Mazandaranis. Such differences highlight the importance of the potential role of ethnicities in diagnosis and prognosis of MS, especially considering their observation within the geographical limits of a single country.

Time interval between the onset of symptoms and diagnosis of multiple sclerosis and the influential factors: A national registry-based study

ObjectiveThe time to diagnosis of multiple sclerosis (MS) is of great importance for early treatment, thereby reducing the disability and burden of the disease. The purpose of this study was to determine the time from the onset of clinical symptoms to the diagnosis of MS and to evaluate the factors associated with a late diagnosis in Iranian MS patients. MethodsThe present cross-sectional study was conducted on patients with MS who were registered in the National MS Registry System of Iran (NMSRI). ResultsOverall, 23291 MS patients registered in 18 provinces of Iran were included in this study. The mean (standard deviation) interval between the onset of the disease and diagnosis of MS was 13.42 (32.40) months, and the median was one month. The diagnostic interval of 41.6% of patients was less than one month, and 14.8% of them had a one-month time to diagnosis. Patients with an age of onset below 18 years and those diagnosed after the age of 50 years had a longer time to diagnosis (P<0.001). Patients with primary progressive MS (PPMS) had the longest time to diagnose and those with relapsing-remitting MS (RRMS) had the shortest time (P<0.001). The results of negative binominal regression showed that the average rate of delay in diagnosis in women was 12% less than that in men. The average delay in diagnosis in patients with a positive family history of MS was 23% more than that in others. The rate of delay in the diagnosis of patients with PPMS and secondary progressive MS was 2.22 and 1.66 times higher, respectively, compared with RRMS. ConclusionThe findings of the present study revealed that more than half of the MS patients were diagnosed within a one-month interval from the symptom onset, which is an acceptable period. More attention should be paid to patients’ access to medical facilities and MS specialists.

Real-life study to assess effectiveness and safety of eculizumab in patients with neuromyelitis optica spectrum disorders in France: protocol for ECUP4, an observational study.

Eculizumab, a humanized monoclonal antibody targeting the C5 complement protein, has been approved for the treatment of neuromyelitis optica spectrum disorders (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive (Ab+). The aim of this study is to evaluate the long-term effectiveness and safety of eculizumab in French adults with NMOSD and to describe patients' characteristics, disability, and quality of life using data collected in a real-world setting. This is the protocol for ECUP4, an ongoing prospective, observational, non-comparative, multicenter study conducted in 32 reference centers in France. Eligible patients must also be enrolled in NOMADMUS, a nested cohort of the French national multiple sclerosis registry (OFSEP). The primary endpoint is the annualized relapse rate. Secondary endpoints include the long-term safety of eculizumab, as well as patients' characteristics, treatment outcomes, disability, pain, visual acuity, and quality of life. Visits and treatments follow routine clinical practice. The case report forms (CRF) comprise data recorded in the context of the NOMADMUS cohort, collected during routine visits. The inclusion period is planned for 3 years, with no limitation on the number of patients enrolled. The maximum follow-up duration will be 5.5 years. The efficacy and safety of eculizumab in patients with AQP4+ NMOSD have been demonstrated in randomized clinical trials that showed a significant reduction in the risk of relapse, with a safety profile consistent with other indications. This study will provide clinical and patient-reported evidence of the benefits of eculizumab, using data from a real-world setting in France. This study is registered at the French public repertory Health data Hub, N° F20211228123801. All information can be accessed at: https://www.health-data-hub.fr/.

Does initial high efficacy therapy in multiple sclerosis surpass escalation treatment strategy? A comparison of patients with relapsing-remitting multiple sclerosis in the Czech and Swedish national multiple sclerosis registries.

In relapsing-remitting multiple sclerosis (RRMS) the most common treatment strategy has been to start with low-moderate efficacy disease modifying therapy (LE-DMT) and to escalate to more efficacious treatments in cases of breakthrough disease activity. However, recent evidence suggests a better outcome in patients commencing with moderate-high efficacy DMT (HE-DMT) immediately after clinical onset. The aim of this study is to compare disease activity and disability outcomes in patients treated with the two alternative strategies using the Swedish and Czech national multiple sclerosis registries, taking advantage of the fact that the relative frequency of each strategy differs markedly between these two countries. Adult RRMS patients who initiated their first-ever DMT between 2013 and 2016 and were included in the Swedish MS register were compared with a similar cohort from the MS register of the Czech Republic using propensity score overlap weighting as a balancing method. The main outcomes of interest were time to confirmed disability worsening (CDW), time to achieve an expanded disability status scale (EDSS) value of 4, time to relapse, and time to confirmed disability improvement (CDI). To support the results, a sensitivity analysis focusing solely on patients from Sweden starting with HE-DMT and patients from the Czech Republic starting with LE-DMT was performed. In the Swedish cohort, 42% of patients received HE-DMT as initial therapy compared to 3.8% of patients in the Czech cohort. The time to CDW was not significantly different between the Swedish and Czech cohorts (p-value 0.2764), with hazard ratio (HR) of 0.89 and a 95% confidence interval (CI) of 0.77-1.03. Patients from the Swedish cohort exhibited better outcomes for all remaining variables. The risk of reaching EDSS 4 was reduced by 26% (HR 0.74, 95%CI 0.6-0.91, p-value 0.0327), the risk of relapse was reduced by 66% (HR 0.34, 95%CI 0.3-0.39, p-value <0.001), and the probability of CDI was three times higher (HR 3.04, 95%CI 2.37-3.9, p-value <0.001). The analysis of the Czech and the Swedish RRMS cohorts confirmed a better prognosis for patients in Sweden, where a significant proportion of patients received HE-DMT as initial treatment.

Impact of the first Gulf war on multiple sclerosis risk in Kuwait: a quasi-experimental study

ObjectiveIt has been reasoned that stressful life events tend to alter immune function thereby increasing the susceptibility to autoimmune diseases including multiple sclerosis (MS). Using the database of Kuwait National MS Registry, this quasi-experimental study assessed the impact of the first Gulf War (Iraqi invasion of Kuwait in 1990) on MS risk in Kuwait.MethodsMS incidence data from 1980 to 2019 were obtained from the Kuwait National MS Registry. Annual age-standardized incidence rates (ASIRs) (per 105 person-years) were computed using the World Standard Population as a reference. Interrupted time series analysis with the option of autoregressive order (1) was used to evaluate the impact of the first Gulf War on MS risk by treating 1990 as an intervention year.ResultsEstimated baseline annual ASIR (per 105 person-years) was 0.38 (95% CI: -1.02, 1.78; p = 0.587). MS ASIRs (per 105 person-years) tended to increase significantly every year prior to 1990 by 0.45 (ASIR per 105 person-years = 0.45; 95% CI: 0.15, 0.76; p = 0.005). During the first year of the first Gulf War, there seemed to be a non-significant increase (step change) in ASIRs (per 105 person-years) of MS (ASIR per 105 person-years = 0.85; 95% CI: − 5.16, 6.86; p = 0.775) followed by a non-significant increase in the annual trend in MS ASIRs per 105 person-years (relative to the preintervention trend i.e., the difference between the pre-first Gulf War versus the post-first Gulf War trends) by 0.65 (ASIR per 105 person-years = 0.65; 95% CI: − 0.22, 1.52; p = 0.138). However, a postestimation measure of the post-first Gulf War trend was statistically significant (ASIR per 105 person-years = 1.10; 95% CI: 0.40, 1.80; p = 0.003), which implies that the post-first Gulf War trend in the annual ASIRs (per 105 person-years) inclined to be the same as was the pre-first Gulf War (i.e., counterfactual of the pre-first Gulf War trend in annual ASIRs (per 105 person-years) as if no first Gulf War took place).The Durbin-Watson test statistic (d = 1.89) showed almost non-significant autocorrelations across the time series observations on ASIRs (per 105 person-years).ConclusionsThis study suggests that the first Gulf War was not significantly associated with the increasing trend in MS risk at population level in Kuwait neither with any short-term change nor with secular trend. Future studies may consider confirming the role of conflict-related stress or other stressful life events in potential exacerbation of MS risk along with unraveling biologically plausible mechanistic pathways.

The Czech National MS Registry (ReMuS): Data trends in multiple sclerosis patients whose first disease-modifying therapies were initiated from 2013 to 2021.

Multiple sclerosis treatment strategies are changing in the Czech Republic. According to data from 2013-2021, the proportion of patients starting high-efficacy disease-modifying therapies is increasing. In this survey, we describe the actual data trends in multiple sclerosis (MS) patients beginning their first disease‑modifying therapies (DMTs) from 2013 to 2021. The secondary objective was to present the history, data collection, and scientific potential of the Czech National MS registry (ReMuS). First, using descriptive statistics, we analysed the data for patients starting their first DMTs, either platform (including dimethyl fumarate) or high-efficacy DMTs (HE-DMTs), for each successive year. Second, a detailed description of the history, data collection, completeness, quality optimising procedures, and legal policies of ReMuS is provided. Based on the dataset from December 31, 2021, the total number of monitored patients with MS in ReMuS increased from 9,019 in 2013 (referred from 7 of 15 MS centres) to 12,940 in 2016 (referred from all 15 Czech MS centres) to 17,478 in 2021. In these years, the percentage of patients treated with DMTs in the registry ranged from 76 to 83%, but the proportion of patients treated with HE-DMTs changed from 16.2% in 2013 to 37.1% in 2021. During the follow-up period, a total of 8,491 treatment-naive patients received DMTs. The proportion of patients (all MS phenotypes) starting HE-DMTs increased from 2.1% in 2013 to 18.5% in 2021. Patient registries, including ReMuS, provide an essential quality data source, especially in light of the increasing percentage of patients on HE-DMTs. Although early initiation of HE-DMT can provide considerable benefits, it also carries greater potential risks. Consistent long-term follow-up of patients in real‑world clinical practice, which only registries allow, is therefore crucial to evaluate the efficacy and safety of therapeutic strategies, for epidemiological research and to assist decision making by healthcare providers and regulatory bodies.

Headache registry in Szeged: Experiences regarding to migraine patients

<p>Using patient registries is essential both in clinical research and in medical practice. Headaches, more specifically migraines are one of the most common complaints that can detract the quality of a patient&rsquo;s life and these complaints also have a significant socio-econo&shy;mic effect. Our goal is to create a national Headache Registry and to also provide the pre-analysis of the registry&rsquo;s database.</p>. <p>Our research is based on the national Multiple Sclerosis Registry, which we modified using the latest version of diagnostic criteria published by the International Headache Society. This clinical study contains data collected from patients suffering from migraines and currently receiving care at the Headache Outpatient Department at the Neurologic Clinic of the University of Szeged.</p>. <p>The data of 412 patients (363 wo&shy;men and 49 men) suffering from migraine (migraine without aura: n = 313 and migraine with aura: n = 99) were added to the Headache Registry. The average age of participants was 44.1 &plusmn; 12.5 SD years. Regarding the attributes of migraine headaches we examined the following characteristics: localization, quality and intensity (based on the Visual Analogue Scale) of the pain, frequency (the number of headache days per month), medications (acute or prophylactic), comorbidities (depression, anxiety, hypertension, asthma, epilepsy and others), family history and the occurrence of stroke among patients.</p>. <p>Based on international expe&shy;rience, patient registries are the most optimal systems for structured patient mo&shy;nitoring. For high level management and long-term follow up of the patients the application of registries is essential. The registries include the detailed medical history and the diagnostic and therapeutic data of the patients, and they trace the changes during the follow up medical visits. Registries are able to record the entire course of the disease in digital way. The numerous data can be set out any time from the digital database. Extensive spread of patients&rsquo; registries is fundamental not only in every day clinical practice, but also in clinical research.</p>.

Characteristics and management of multiple sclerosis patients during the Omicron era: is there a concern about the MS course in the face of the new variant of COVID-19?

IntroductionThe Omicron variant of COVID-19 is highly transmissible, triggering unprecedented infection rates. The present study aimed to investigate the course of multiple sclerosis (MS) in the Omicron era among Iranian patients with MS. MethodsThis observational study was designed on MS patients of the national MS registry of Iran through a self-designed online questionnaire. A questionnaire was prepared as a Google Form for MS patients during the Omicron outbreak from 1 March to 30 April 2022.ResultsOne hundred seventy-four patients with a mean age of 37.3 ± 9.04 were enrolled. Of the patients, 95.97% used DMT, the most common of which were rituximab and fingolimod. Of the patients, 77.58% were fully vaccinated for COVID-19. Regardless of the COVID-19 vaccination status, 76 patients developed COVID-19, which was mild to moderate. Except for recent corticosteroid therapy and secondary progressive MS (SPMS), other demographic and MS characteristics were not significantly associated with the severity of COVID-19. There was also a marginal association between the Expanded Disability Status Scale (EDSS) and the severity of COVID-19. In addition, 17.10% of patients reported MS relapse following COVID-19 leading to escalation therapy in eight patients.ConclusionOur study demonstrated that in the Omicron era, most patients developed mild COVID-19. Although the predominant COVID-19 variant in this period was Omicron, we could not separate the pathogenic variants. The risk factors for COVID-19 during the Omicron era were not different from other pandemic waves. Our preliminary results revealed that the MS relapse following COVID-19 was higher than in previous waves.

Clinical Profile and the Extent of Disability in Multiple Sclerosis Patients in Madinah, Saudi Arabia.

Objectives: The objective is to study the demographics and clinical characteristics of Saudi multiple sclerosis (MS) patients in Madinah, Saudi Arabia, and assess their extent of disability using the Expanded Disability Status Scale (EDSS).Methods: This hospital-based study intended to address the population of all MS-diagnosed patients registered between 2018 and 2021 in the Neurology Department of King Fahad Hospital in the Madinah region. Data were gathered from medical records and by interviewing participants in the Neurology Clinic. The chi-square test and linear and logistic regression were applied to draw inferences.Results: A total of 195 MS-diagnosed patients were included in the analysis. Of these, 72.3% were female. The mean age of the total sample was 34.9±9.2 years, and 7.7% reported a positive family history. Of all patients, 17.9% (n=35) had comorbidities. The mean age at diagnosis was 29.3±8.2 years. The majority (85.6%) were diagnosed with relapsing-remitting multiple sclerosis (RRMS); 77.9% had an EDSS score between 0.0 and 1.5, showing little or no disability. A statistical significance existed between EDSS and the current age of the patients (p=0.004), age at onset (p=0.007), type of MS (p=0.000), presence of muscle weakness (p=0.044), bladder or bowel difficulties at onset (p=0.043), and the duration of MS (p=0.000). Of the patients, 23.6% were not using disease-modifying therapy (DMT). The most commonly used drug was interferon beta 1-b.Conclusion: A lower EDSS was associated with younger age, diagnosis at a younger age, RRMS, duration less than five years, and lower body mass index (BMI). To increase the generalizability of findings, a national MS registry system and further prospective analytical epidemiological research studies are recommended.

Implementing coronavirus disease 2019 scale-up registry protocol in national multiple sclerosis registry system of Iran

Background: The national multiple sclerosis (MS) registry is aimed at monitoring and improving quality of care and providing feedback to improve health outcomes by systematic recording of data. In 2018, the nationwide MS registry of Iran (NMSRI) was initiated for collecting epidemiological data and information on health care provision for patients with MS. The aim of the current study was to introduce the role of implementing coronavirus disease 2019 (COVID-19) scale-up registry protocol in NMSRI and arrange the national MS generality with information obtained during the COVID-19 pandemic. Methods: The NMSRI group set up a program with crucial elements to collect the data of patients with MS who developed COVID-19. All MS cases with confirmed diagnosis of COVID-19 were enrolled in this study. New elements were considered to be added into the dataset, including demographic characteristics, definite diagnosis of COVID-19 and its symptoms, history of comorbidities, history of medications and hospitalization, changes in magnetic resonance imaging (MRI), and infection outcomes. Results: The COVID-19 data collection program was designed in NMSRI to collect data of MS cases with COVID-19 infection. The data collection protocol was explained to neurologists through an online training workshop. To the date of the study, 21 centers from 17 provinces of Iran were involved in the COVID-19 databases promoting NMSRI and 612 participants were registered successfully. Conclusion: We extended an agreement on data collection and developed it in NMSRI with various contributors to discover a critical need for COVID-19 awareness and monitor clinical training in MS.

К ПРОБЛЕМЕ СВЯЗИ ИММУНОТЕРАПИИ У ПАЦИЕНТОВ, СТРАДАЮЩИХ РЕЦИДИВИРУЮЩИМ РАССЕЯННЫМ СКЛЕРОЗОМ, С РИСКОМ ТЯЖЕЛОГО ТЕЧЕНИЯ COVID-19

Immunomodulatory drugs are important to control disease activity in relapsing-remitting multiple sclerosis (MS). Anti-CD 20-therapy is one of such medications. In Sweden, extensive off label prescription of rituximab (RTX) in MS has been documented; it is presently prescribed for more than half of all treated MS patients. The rationale for the increasing prescription of RTX was previous data from phase II and observational studies supporting high efficacy and safety, in addi- tion to the financial aspect. We report national data on usage of disease modifying therapies in MS patients and risk of se- vere COVID-19 in association with RTX exposure within this group. The Swedish National MS Registry (SMSreg) aims to cover all patients with MS in the country, (n=approximately 18,000). After COVID-19 pandemic started in Sweden, a new section was established in it to register clinical and demo- graphic parameters in COVID-19-infected patients. Data presented in the current report were obtained from the SMSreg. A total of 85 out of approximately 6,000 RTX-treated Swedish MS patients had been hospitalized with COVID-19 (as re- ported from the SMSreg, June 16, 2021) and adjusted analyses showed a 2–3 fold increase in a risk (OR = 2.89; p = 0.001) of hospitalization for anti-CD20 treated patients. A change of praxis was introduced in Sweden in spring 2020, resulting in a ma- jority of patients receiving RTX infusions with extended intervals in order to reduce the risk of severe COVID-19 infection. Current Swedish registry data suggest that exposure to RTX in MS may affect the clinical outcome of COVID-19 infec- tion. These observations have rapidly impacted use of immunomodulatory drugs in Swedish MS patients.

THE RISK OF COVID-19 SEVERITY IN PATIENTS WITH MS APPEARS TO BE ASSOCIATED WITH IMMUNOTHERAPY

Immunomodulatory drugs are important to control disease activity in relapsing-remitting multiple sclerosis (MS). Anti-CD 20-therapy is one of such medications. In Sweden, extensive off label prescription of rituximab (RTX) in MS has been documented; it is presently prescribed for more than half of all treated MS patients. The rationale for the increasing prescription of RTX was previous data from phase II and observational studies supporting high efficacy and safety, in addi- tion to the financial aspect. We report national data on usage of disease modifying therapies in MS patients and risk of se- vere COVID-19 in association with RTX exposure within this group. The Swedish National MS Registry (SMSreg) aims to cover all patients with MS in the country, (n=approximately 18,000). After COVID-19 pandemic started in Sweden, a new section was established in it to register clinical and demo- graphic parameters in COVID-19-infected patients. Data presented in the current report were obtained from the SMSreg. A total of 85 out of approximately 6,000 RTX-treated Swedish MS patients had been hospitalized with COVID-19 (as re- ported from the SMSreg, June 16, 2021) and adjusted analyses showed a 2–3 fold increase in a risk (OR = 2.89; p = 0.001) of hospitalization for anti-CD20 treated patients. A change of praxis was introduced in Sweden in spring 2020, resulting in a ma- jority of patients receiving RTX infusions with extended intervals in order to reduce the risk of severe COVID-19 infection. Current Swedish registry data suggest that exposure to RTX in MS may affect the clinical outcome of COVID-19 infec- tion. These observations have rapidly impacted use of immunomodulatory drugs in Swedish MS patients.

Joinpoint Regression Analysis of Trends in Multiple Sclerosis Incidence in Kuwait: 1980–2019

Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system with unknown precise etiology. Temporally, a tendency for increasing MS incidence has been recorded worldwide. This cross-sectional cohort study sought to quantify trends in the age-standardized incidence rates (ASIRs) (per million person-years) of MS in Kuwait from 1980 to 2019, overall and by subcohorts defined by age at MS onset, sex, and nationality. Methods: MS incidence data from 1980 to 2019 were obtained from the Kuwait National MS Registry (KNMSR). Using midyear relevant Kuwait population as denominator and the World Standard Population as a reference, MS ASIRs overall and by subcohorts defined by age at onset (0–19, 20–39, and 40+ years), sex (male and female), and nationality (Kuwaiti and non-Kuwaiti) were computed. Joinpoint regression analysis was conducted to estimate average annual percent change (AAPC) and its 95% confidence interval (CI) overall and by subcohorts. Results: During 1980–2019, a total of 1,764 MS incident cases of 95.6 million person-years at-risk were diagnosed and registered in KNMSR. The overall MS ASIR (per million person-years) during the study period was 34.1 (95% CI: 16.1, 52.1). Between 1980 and 2010, in the total cohort, ASIRs of MS significantly increased by 13% (AAPC = 13.0; 95% CI: 10.8, 15.3; p < 0.001), followed by statistically nonsignificant declining trend during the ensuing period (AAPC = −3.8; 95% CI: −14.8, 8.8; p = 0.522). Joinpoint regression analysis revealed that 2 subcohorts of Kuwaiti females each with one joinpoint had significant increasing trends in MS ASIRs (0- to 19-year-old Kuwaiti females, AAPC: 1980–2009, 81.0; 95% CI: 58.2, 107.0; p = 0.001; 20- to 39-year-old Kuwaiti females, AAPC: 1980–1999, 131.7; 95% CI: 26.9, 322.8; p = 0.021). Additionally, of remaining 10, 6 subcohorts had significantly (p < 0.05) increasing trends in MS ASIRs from 1980 to 2019. Conclusions: From 1980 to 2010, Kuwait has an overall significantly increasing trend in MS ASIRs followed by a nonsignificant declining drift in the ensuing period. The increasing trend in MS risk appeared to be driven by increased risk among Kuwaiti females younger than 40 years. The underlying factors modulating MS risk in Kuwait need further studies.

Italian multiple sclerosis register as the basis for post-authorization safety studies

Abstract While the safety and efficacy of Disease Modifying Therapy (DMT) in multiple sclerosis (MS) are assessed in clinical trials, these are of relatively short duration and always confined to highly selected patient groups. The evaluation of real-world data such as patient registries, is vital as it offers long-term data collection and is patient rather than product-focused during the lifetime of MS, and allows to document a patient's treatment history throughout the disease course. Patient registries can play an important role in monitoring the safety of drus. Regulators and the pharmaceutical industry have shown interest in complementing or even replacing phase 4 clinical studies with data from MS registries. The Italian MS Register (IMSR), in collaboration with the Big MS Data initiative, that also includes the national MS registries of Denmark, France, and Sweden and the international database network MSBase, came together with industry to conduct studies on post-authorization safety (PASS) and treatment effectiveness. The IMSR includes the clinical history of approximately 55,000 patients, or approximatively 45% of the estimated cases of MS in Italy. More than 10,000 patients have a follow-up duration of over 10 years. A Core Protocol outlining principles of PASS projects was created in which aggregated results made available to sponsors and health authorities. The Core Protocol specifies variables, emphasizes improved capture of adverse events, in particular cancer, non-melanoma skin cancers and immunosuppression-related infections, all MedDRA-coded. EUROCAT codes for pregnancy outcomes are also documented. Regulators, the pharmaceutical industry and national-level registries have jointly identified a format of collaboration on PASS for DMT in MS to benefit patients and the larger society. In this way, we hope to contribute to a framework that will include emerging and existing registries with the common goal of contributing to the advancement of knowledge in MS. Key messages The real-world data can contribute to understanding of the impact of disease-modifying therapy on long term. A format of collaboration among clinical research, regulators and pharmaceutical industry could be a winning framework to improve the knowledge on safety and treatment effectiveness in MS.

Initiation of first disease-modifying treatment for multiple sclerosis patients in the Czech republic from 2013 to 2016: Data from the national registry ReMuS

Background: Proper management of multiple sclerosis (MS) requires feedback from clinical practice via registries. Objective: To introduce the Czech national multiple sclerosis registry, ReMuS, and explore the availability and use of disease-modifying drugs (DMD). Methods: The analysis focused on patients who started their first DMD, either with first-line or second-line medication and was based on reimbursement criteria set by Czech regulators. Baseline information was used to predict relapses after DMD initiation and to compare patients that started DMD in different years. Results: A total of 3,328 patients started DMD treatment for MS between 2013 and 2016; 3,203 on first-line and 125 on second-line medication. The proportion of patients starting on second-line drugs increased from 1.8% in 2013 to 4.7% in 2016. The occurrence of a relapse within one year of DMD initiation was significantly related to (1) the Expanded Disability Status Scale (EDSS) score immediately prior to starting DMD and (2) the number of previous relapses. Both parameters were significantly lower in patients starting in later years of the explored interval. Conclusion: Data from the ReMuS registry highlights improvements made in the management of MS in the Czech Republic. However, a relatively low percentage of patients started treatment using second-line drugs, in contrast to trends in other countries.

Multiple sclerosis national registry system in Iran: Validity and reliability of a minimum data set

BackgroundAs the prevalence and incidence of Multiple Sclerosis (MS) are increasing remarkably in Iran, gathering standardized information regarding the individual's diagnosis, care, and outcomes through a uniform registry system would enable policy-makers to systematically plan for care quality improvements. ObjectiveTo design a valid and reliable Persian version of a minimum data set to be utilized and integrated into the national MS registry system of Iran. MethodThe minimum data set consisted of six domains including patient identification, family history of MS, diagnosis, disease course, disability status, and medications. The content validity was assessed based on 27 experts’ opinions. Item-Content Validity Index (I-CVI) and Scale-Content Validity Index (S-CVI) were used to assess the questions and their validities. Reliability was evaluated using the intra-class correlation coefficient (ICC) of the test-retest results. ResultsFor validity appraisal, 27 experts reviewed the developed minimum data set. All the items had I-CVI values higher than the critical value of 0.78 in terms of relevance, clarity, and simplicity, except for “medication start date” and “medication end date” in relevance (I-CVI = 0.75 and 0.73, respectively) and “MS type” in simplicity (I-CVI = 0.76). The total S-CVI scores for relevance, clarity, and simplicity were higher than 0.9. In reliability assessment, 27 patients (out of 74 interviewed patients) were re-interviewed to assess the test-retest reliability. All ICCs were higher than the critical value of 0.7 (in 14 items out of 16), except for “progression to secondary-progressive MS” with the ICC = 0.68 and “the reason for medication discontinuance” with the ICC = 0.64. ConclusionThe use of standardized validated minimum data set has the potential to enable the researchers and policy-makers to systematically compare and analyze patient information. The Persian version of the minimum data set found to be valid and reliable in Iran.

The Saudi Arabian National Multiple Sclerosis Registry (NMSR): Initial Results Saudi MS Registry Study Group* (P2.390)

The Saudi Arabian National Multiple Sclerosis Registry (NMSR): Initial Results Saudi MS Registry Study Group* (P2.390)

Age-Period-Cohort Modeling of Multiple Sclerosis Incidence Rates in Kuwait: 1980–2014

Background: Multiple sclerosis (MS) is a complex immune-mediated disorder of the central nervous system with undefined etiology. Genetic predisposition and environmental factors play an imperative role in MS causation and its sustained increasing burden worldwide. This study examined the age, period, and cohort effects on MS incidence rates in Kuwait. Methods: In this retrospective cohort study, data on MS cases diagnosed between January 1, 1980 and December 31, 2014 and registered in National MS Registry and reference population were obtained. Age-period-cohort (APC) analysis was conducted using a loglinear Poisson regression model to supplement the descriptive and graphical presentation. Descriptive statistics were complemented with APC parameters’ estimates including net drift, local drift, age at onset curve, and longitudinal age trend. Age effect was presented as incidence rates (per 10⁵ person-years), whereas period and cohort effects were presented as adjusted relative rates. Results: A total of 1,131 cases were diagnosed in 1,385,923 person-years. Overall age-standardized MS incidence rate was 64.5 (95% CI 52.4–79.8). An estimated annual percentage change revealed 7.4% annual increase in MS incidence rate during the study period (Net drift = 7.4%; 95% CI 4.1–10.8%). APC “fitted” age-at-onset curve showed a bimodal pattern with peaked incidence rates at 20–24 years and 45–49 years of age. Compared with the referent period (1980–1984) and cohort (1970–1974), MS incidence rates progressively and significantly (p < 0.001) increased during subsequent time periods and in successive cohorts. Results of APC analysis are descriptive in nature and specific etiological hypotheses were not evaluated. However, the findings of this study substantiated the notion of multiplicity of genetic and/or environmental risk factors’ contributions. Conclusion: A substantial increase in MS incidence rates was recorded, which significantly varied in all 3 temporal dimensions during the study period. Future studies may contemplate biological basis for recorded temporal increase in MS risk.

Effectiveness and Safety of Dimethyl Fumarate Treatment in Relapsing Multiple Sclerosis Patients: Real-World Evidence.

IntroductionDimethyl fumarate (DMF) has been recently approved as a disease-modifying therapy for the treatment of multiple sclerosis (MS). Post-marketing studies are important to confirm what was established in clinical trials.ObjectiveTo evaluate effectiveness and safety of DMF and to measure the occurrence of lymphopenia in a cohort of MS patients in a clinical setting.MethodsUsing the national MS registry, we prospectively assessed relapsing MS patients who had been prescribed DMF for at least 6 months. Primary outcome measure was the proportion of relapse-free patients at last follow-up visit. Secondary outcome measures were the mean change in expanded disability status scale (EDSS) and the proportion of patients with radiological activity (gadolinium-enhancing or new T2 lesions) at the last follow-up visit. Absolute lymphocyte count (ALC) was assessed at baseline (within 6 months prior to DMF initiation) and at one or more times during DMF treatment 3 months post-initiation.ResultsOf 134 patients identified, 119 were eligible and included in the analysis. Women represented 59.7% of the studied cohort. Mean age and mean disease duration were 33.5 ± 11.1 and 8.3 ± 7 years, respectively. A total of 75.6% of the patients received prior disease-modifying therapies. Mean duration of DMF exposure was 20.5 ± 9.5 months. The proportion of relapse-free patients increased significantly from 51.2% to 89.9% (p < 0.0001), while the mean EDSS score decreased from 2.8 ± 1.8 at baseline to 2.3 ± 1.7 (p < 0.058) at last follow-up visit. The proportion of patients with MRI activity decreased significantly from 61.1% to 15.1% (p < 0.0001). The mean ALCs decreased from 2170 to 1430 cells/μl (34% decrease). Lymphopenia was seen in 13 (10.9%) patients, of whom 3 (2.5%) patients had grade 3 lymphopenia necessitating discontinuation of DMF. Although no serious adverse events were reported, 19.3% of patients discontinued DMF.ConclusionIn clinical practice, DMF appeared to be effective in reducing disease activity and progression of disability throughout the observational period. DMF was well tolerated with no serious adverse events. ALC profiles in DMF-treated patients were generally stable throughout the observational period. The proportion of patients who developed severe lymphopenia was similar to figures in clinical trials.