Exposure to systemic antibiotics in outpatient care and the risk of multiple sclerosis.

BACKGROUND: Infections, early life exposures and the microbiome have been associated with the aetiology of multiple sclerosis (MS). Data on any possible roles of antibiotics is scarce and conflicting. OBJECTIVE: The objective of this study was to investigate associations between outpatient systemic antibiotic exposure and the risk of MS in a nationwide case-control setting. METHODS: Patients with MS were identified from the nation MS registry and their exposure to antibiotics was compared with that of persons without MS, provided by the national census authority. Antibiotic exposure was investigated using the national prescription database and analyzed by Anatomical Therapeutic Chemical (ATC) category. RESULTS: Among the 1830 patients with MS and 12765 control persons, there were no associations between exposure to antibiotics in childhood (5-9 years) or adolescence (10-19 years) and the subsequent risk of MS. There was also no association between antibiotic exposure 1-6 years before disease onset and the risk of MS, save for exposure to fluoroquinolones in women (odds ratio: 1.28; 95% confidence interval: 1.03, 1.60; p = 0.028) which is probably associated with the increased infection burden in the MS prodrome. CONCLUSION: Use of systemic prescription antibiotics was not associated with subsequent MS risk.

Epstein-barr virus and multiple sclerosis risk in the finnish maternity cohort.

OBJECTIVE: To determine whether maternal Epstein-Barr virus (EBV) IgG antibody levels are associated with risk of multiple sclerosis (MS) in the offspring. METHODS: We conducted a prospective nested case-control study in the Finnish Maternity Cohort (FMC) with serum samples from >800,000 women collected during pregnancy since 1983. Cases of MS among offspring born between 1983 and 1991 were identified via hospital and prescription registries; 176 cases were matched to up to 3 controls (n = 326) on region and dates of birth, sample collection, and mother's birth. We used conditional logistic regression to estimate relative risks (RRs) and adjusted models for sex of the child, gestational age at sample collection, and maternal serum 25-hydroxyvitamin D and cotinine levels. Similar analyses were conducted among 1,049 women with MS and 1,867 matched controls in the FMC. RESULTS: Maternal viral capsid antigen IgG levels during pregnancy were associated with an increased MS risk among offspring (RRtop vs bottom quintile = 2.44, 95% confidence interval [CI] = 1.20-5.00, p trend = 0.004); no associations were found between maternal EBV nuclear antigen 1 (EBNA-1), diffuse early antigen, or cytomegalovirus IgG levels and offspring MS risk. Among women in the FMC, those in the highest versus lowest quintile of EBNA-1 IgG levels had a 3-fold higher risk of MS (RR = 3.21, 95% CI = 2.37-4.35, p trend <1.11e-16). These associations were not confounded or modified by 25-hydroxyvitamin D. INTERPRETATION: Offspring of mothers with high viral capsid antigen IgG during pregnancy appear to have an increased risk of MS. The increase in MS risk among women with elevated prediagnostic EBNA-1 IgG levels is consistent with previous results. ANN NEUROL 2019;86:436-442.

Medication adherence/persistence among patients with active multiple sclerosis in Finland.

OBJECTIVES: To explore adherence, persistence, and treatment patterns in patients with multiple sclerosis (MS) in Finland treated with disease-modifying therapies (DMTs) for active MS in 2005-2018. MATERIALS AND METHODS: The study cohort was identified using the Drug Prescription Register of Social Insurance Institute, Finland. All patients had at least one prescription of glatiramer acetate (GA), beta-interferons, teriflunomide, or delayed-release dimethyl fumarate (DMF). Adherence was calculated using proportion of days covered (PDC) (cutoff ≥0.8). Time to non-persistence was calculated by the number of days on index DMT treatment before the first treatment gap (≥90 days) or switch and analyzed with time-to-event methodology. RESULTS: The cohort included 7474 MS patients (72.2% female; mean age 38.9 years). Treatment switches were steady over 2005-2012, peaked in 2015. PDC means (standard deviations) were GA, 0.87 (0.17); beta-interferons, 0.88 (0.15); DMF, 0.89 (0.14); teriflunomide, 0.93 (0.10). Adherence frequencies were GA, 78.4%; beta-interferons, 81.3%; DMF, 86.9%; teriflunomide, 91.7%. Logistic regression showed that age group, DMT and the starting year, sex, and hospital district independently affected adherence. Patients receiving teriflunomide and DMF, males, and older patients were more likely to persist on treatment. There was no difference in persistence between patients prescribed teriflunomide and DMF, or between GA and beta-interferons. CONCLUSIONS: Oral DMTs had greater adherence and persistence than injectable DMTs.

Changes in multiple sclerosis epidemiology in Finland over five decades.

Finland is a high-risk region for multiple sclerosis (MS) with several epidemiological studies on the subject published since 1964, but these have not been comprehensively scrutinized. The objective of this study was to review previous studies of Finnish MS epidemiology, introduce new data on MS prevalence in western parts of Finland and do further analyses on data from previous studies. We performed a systematic search on articles regarding MS epidemiology in Finland in PubMed database, and all relevant articles were included in this review. MS prevalences in the western hospital districts of Vaasa, South Ostrobothnia and Pirkanmaa were calculated in 1980-2007 by using previously unpublished data obtained from a retrospective search from hospital administrative registries. To enhance comparability of the epidemiological figures, we calculated age-standardized prevalence of MS from the new data from western hospital districts and previous data from North Ostrobothnia, Southwest Finland and North Karelia. Marked regional differences in MS epidemiology were confirmed with concentration of the disease in the western and south-western parts of the country. The highest regional age-standardized MS prevalence of 288/100 000 was reported in South Ostrobothnia in 2007. A clear and stable increase in MS prevalence was observed through the decades, but the only marked increase in incidence happened in 1990s. Methodological differences hampered direct comparisons of different studies, highlighting the importance of common principles of reporting and standardizing the epidemiological figures. More comprehensive studies on MS epidemiology are still warranted to yield important information concerning the aetiology of the disease.

Multiple sclerosis epidemiology in Finland: Regional differences and high incidence.

OBJECTIVES: Studies on the east-west gradient of multiple sclerosis (MS) are scarce. In Finland, epidemiological differences have been only partially elucidated, but the MS risk is high, and it has been claimed that the occurrence follows a longitudinal gradient. In this register-based study, we updated the MS epidemiology in southwest Finland (SwF) and compared it to the easternmost hospital district, North Karelia (NK), for which no previous data exist. MATERIALS AND METHODS: Patients with ICD-10 code G35 were identified from hospital district administrative data. Patient records were reviewed to include only cases with a definitive diagnosis. Incidence period covered 5 years (2012-2016), and the prevalence date was December 31, 2016. Results were standardized using the direct method. RESULTS: A total of 1184 persons had MS in SwF and 253 persons in NK at the end of 2016. The prevalence was 280/100 000 (95% CI 264-296) in SwF and 168/100 000 (95% CI 148-190) in NK (age-standardized for the European standard population 2013). During the incidence period, 211 new MS diagnoses were made in SwF and 49 in NK. The annual age-standardized (ESP 2013) incidence was 12.1/100 000 person-years (95% CI 10.5-13.8) in SwF and 8.6/100 000 person-years (95% CI 6.4-11.2) in NK in the age-group 10-69 years. CONCLUSIONS: There are regional differences in MS epidemiology in Finland, possibly related to demographic, social, and genetic circumstances, but the retrospective nature and limited sample size of this study might introduce some uncertainty to the calculations. SwF is a region with a globally very high risk for MS.

Multiple sclerosis in Finland 2018-Data from the national register.

OBJECTIVES: Finland is a high-risk multiple sclerosis (MS) region, but a national MS register has not existed until 2014. In this paper, we present the Finnish MS register variables and data collected by 31 December 2018. MATERIALS AND METHODS: Numbers and data counts of MS patients in the register (ICD-10 code G35) are presented. The disease types and proportion of patients receiving disease-modifying treatments (DMTs) were analysed in five hospital districts with most complete data sets. MS prevalence in Finland was estimated using administrative hospital discharge data as an additional resource. RESULTS: There were a total of 8722 MS patients in the Finnish MS register by 31 December 2018 (71.5% females). Mean age at MS diagnosis was 38.7 years and peak prevalence was at age 50-54 years. Disease course was relapsing remitting (RRMS) in 66.7%, secondary progressive (SPMS) in 13.5%, and primary progressive (PPMS) in 7.9% of the 5365 MS patients in the selected districts with most complete data. A total of 66.0% of RRMS patients, 19.6% of SPMS patients and 9.9% of PPMS patients were receiving DMTs. By combining MS register data with databases of those hospitals that had not joined the register, the nationwide prevalence estimate was between 10 and 11 thousand patients (corresponding to crude prevalence 180-200/100 000). CONCLUSIONS: The Finnish MS register is currently used in 15/21 Finnish hospital districts. By register integration into the electronic patient files, the coverage of the register has increased to approximately 80% of the estimated Finnish MS population.

Epidemiology of Guillain-Barré syndrome in Finland 2004-2014.

At total mean incidence of 0.84-1.1/100,000 the occurrence of Guillain-Barré syndrome (GBS) is reported to be low in Finland compared to other Caucasian populations. However, a recent study from Southwestern Finland reported an incidence of 1.82/100,000 which is comparable to other Caucasian populations. We analyzed discharge data covering the years 2004 through 2014 on all neurological admissions in all Finnish university and central hospitals with a primary diagnosis of GBS. A total of 989 admissions due to GBS (917 individuals) were identified. The standardized (European population) annual incidence rate was 1.70/100,000 person-years (95% confidence interval 1.60-1.81). GBS incidence had an increasing trend with age. The likelihood of GBS was higher among girls and adolescent women than boys and men of same age (male:female incidence rate ratio [IRR] 0.56), while in the older age groups (>19 years) the occurrence of GBS was higher among males than females (male:female IRR 1.59). The incidence of GBS remained stable during the study period. There was no seasonal variation in GBS admission frequencies (p = 0.28). No significant effect of the 2009-2010 H1N1 influenza or vaccination against it for GBS occurrence was observed. We suggest that GBS is as common, and has similar age-distribution in Finland as in other European countries. Sex-associated susceptibility for GBS appears to be different in children-adolescents and adults.

Admission sodium level and prognosis in adult Guillain-Barré syndrome.

PURPOSE: Guillain-Barré syndrome (GBS) varies in severity and outcome. Hyponatremia predicts poor outcome but previous studies have used divergent methodology and (pseudo)hyponatremia caused by intravenous immunoglobulin administration may confound analysis. We studied if the plasma sodium level at admission was associated with GBS outcome. METHODS: All 69 patients at least 16 years of age treated for GBS in Turku University Hospital in 2004-2013 were included in the study. Clinical information was obtained from patient charts. RESULTS: Women had lower sodium levels at admission (138; IQR 135, 140) compared to men (140; IQR 138, 142; p = 0.0116) but no association of sodium levels with demographics, pre-hospital variables or basic GBS characteristics was found. Multivariate analyses showed lower admission sodium levels to be associated with worse functional status at one year from disease onset (OR 1.37; 95% CI 1.07-1.76; p = 0.0136) and probability of being discharged to another care facility from the hospital (OR 1.31; 95% CI 1.05-1.64; p = 0.0180) but not associated with need of intensive care unit care (p = 0.09) or mechanical ventilation (p = 0.45), length of hospital stay (p =0.48) or functional status at six months (p = 0.07). CONCLUSIONS: Low plasma sodium level at admission is associated with a more severe disease course and a worse outcome in GBS independently of previously identified prognostic factors. Hyponatremia does not, however, appear to be caused by disease-specific factors.

Comorbid epilepsy in Finnish patients with adult-onset Huntington's disease.

BACKGROUND: Seizures are common in juvenile Huntington's disease (HD), but considered to be rare in adult-onset HD. We studied the occurrence of epilepsy and seizures in a nationwide cohort of Finnish patients with adult-onset HD. METHODS: Patients with HD and their diagnoses of epilepsy or seizures were identified by a search into a nationwide registry. Cases were verified in a subsequent review of patient charts. RESULTS: Three out of 114 HD patients alive on prevalence date had been diagnosed with epilepsy giving a prevalence of 2.6% (95% CI, 0.6-7.5). In addition, one patient with a single unprovoked seizure, one patient with a medication-induced seizure and two patients with transient nonspecific attacks were identified. Epilepsy was not associated with clinical severity of HD and seizures were controlled with antiepileptic medications (AEDs). Generalized tonic-clonic seizures (GTCs) were the most common seizure type. CONCLUSIONS: Prevalence of epilepsy is similar in patients with adult-onset HD compared to general population. Seizures are easily controlled with AEDs.

[Respiratory disturbance during sleep induced by vagus nerve stimulator]. / Vagusstimulaattorin aiheuttama unenaikainen hengityshäiriö.

Vagus nerve stimulation can be used in parallel with drug therapy as adjuvant therapy for severe epilepsy. In approximately half of the patients the number of seizures decreases by at least 50%. The most common adverse effects reported for the therapy include mild laryngeal and upper respiratory tract symptoms and dysfunctions, and in some cases, also development of respiratory disturbances during sleep. We describe two patients in whom vagus nerve stimulation induced sleep apnea. The problem was resolved by changing the settings of the stimulator. Sleep apnea syndrome should be kept in mind when planning vagus nerve stimulation therapy and monitoring the response to therapy.

[Magnetic resonance imaging of the brain in the monitoring of immune therapy of multiple sclerosis]. / Aivojen magneettikuvaus MS-taudin immunologisen hoidon seurannassa.

Magnetic resonance imaging of the brain is currently the most sensitive method in detecting the lesions caused by multiple sclerosis. Assessment of the immunological treatment response used in the treatment of multiple sclerosis should be based on the clinical picture and brain MRI. T2-, flair- and T1-biased images, gadolinium enhancement and assessment of atrophy are required for MRI monitoring. In the first-line immune therapy MRI is taken at 6 to 12 months after starting the drug therapy, in fingolimod therapy after 6 to 12 months and 1 to 2 years, respectively, and in alemtuzumab and natalizumab therapy after one and two years.

[Cerebral nocardiosis as surprising cause of a convulsive seizure]. / Aivonokardioosi kouristuskohtauksen yllättävänä aiheuttajana.

Underlying a convulsive seizure of an adult patient many different types of cause can be detected, such as alcohol withdrawal, disturbance of the cerebral circulation, cerebral hemorrhage, brain tumor, metabolic disturbances, drugs or infection. In connection with severe central nervous system infections, such as brain abscesses, convulsive seizures occur in approximately one out of five patients. A patient with brain abscess may be nonfebrile and have normal values of inflammatory markers. The diagnosis is based on contrast-enhanced CT scanning or magnetic resonance imaging of the brain. Even surgical sampling is often necessary. In our patient, a rare nocardia-induced brain abscess turned out to be the cause of recurrent convulsive seizures.

[Progressive multifocal leukoencephalopathy as a complication of natalizumab therapy]. / Progressiivinen multifokaalinen leukoenkefalopatia natalitsumabihoidon komplikaationa.

Natalizumab medication used in the treatment of active relapsing-remitting multiple sclerosis is associated with a risk of contracting progressive multifocal leukoencephalopathy (PML). Current risk of the PML disease in connection with natalizumab therapy in multiple sclerosis patients is 2.77/1,000. By December 2012, more than 108,000 multiple sclerosis patients worldwide have received natalizumab therapy. There are 350 multiple sclerosis patients receiving natalizumab in Finland. We describe the first one of the two Finnish multiple sclerosis patients having so far been diagnosed with PML disease as a complication of natalizumab therapy.

Real-world treatment outcomes and safety of natalizumab in Finnish multiple sclerosis patients.

Objectives: The primary objective was to evaluate long-term treatment persistence and safety of natalizumab in Finnish multiple sclerosis patients. The secondary objectives were to assess patient characteristics, use of natalizumab-related safety protocol, and treatment persistence in patients with different anti-John Cunningham virus antibody statuses (John Cunningham virus status). Materials & Methods: All adult multiple sclerosis patients in the Finnish multiple sclerosis register who started natalizumab between 1/2006 and 12/2018 were included in this study and followed retrospectively until treatment discontinuation or end of follow-up (12/2019). Results: In total, 850 patients were included. Median duration of natalizumab treatment was 7.8 years in John Cunningham virus negative (n = 229) and 2.1 years in John Cunningham virus positive patients (n = 115; p < 0.001). The most common cause for treatment discontinuation was John Cunningham virus positivity. After natalizumab discontinuation, patients who had a washout duration of less than 6 weeks had fewer relapses during the first 6 months (p = 0.012) and 12 months (p = 0.005) compared with patients who had a washout duration of over 6 weeks. During the median follow-up of 3.6 years, 76% of patients remained stable or improved on their Expanded Disability Status Scale. Conclusions: Treatment persistence was very high among John Cunningham virus negative patients. The study supports long-term effectiveness of natalizumab and a washout duration of less than 6 weeks after discontinuation.

The CLARION study: first report on safety findings in patients newly initiating treatment with cladribine tablets or fingolimod for multiple sclerosis.

OBJECTIVES: As part of the CLARION study: (1) characterize the incidence of severe infections, herpes zoster, and malignancies in patients newly initiating cladribine or fingolimod for relapsing multiple sclerosis (MS); (2) estimate the incidence of severe lymphopenia among cladribine users; and (3) describe prior/subsequent disease-modifying therapy (DMT) in both cohorts. METHODS: Patients were identified from seven participating MS registries/data sources. The incidence rate (IR) of each outcome per 1000 patient-years and its 95% confidence interval (95%CI) were estimated for cohorts using Poisson regression. RESULTS: By cut-off date (01-April-2020), 742 cladribine and 867 fingolimod users were included. Mean follow-up was ∼1 year. The IR for severe infections from all contributing sources (except Denmark) was: cladribine, 7.37 (2.76,19.6); fingolimod, 6.55 (2.46,17.4). The corresponding IR for herpes zoster was 5.51 (1.78,17.1) and 3.27 (0.82,13.1), respectively, while values for opportunistic infections were 0 (0,6.76) and 1.63 (0.23,11.6), respectively. There were no events of progressive multifocal leukoencephalopathy in either cohort. The IR of severe lymphopenia was 63.9 (40.7,100.1) in 349 cladribine users from contributing sources. The IR of malignancies (cut-off date 01-April-2022) was 3.55 (1.59,7.90) for the cladribine cohort (n = 1035) and 3.55 (1.48,8.52) for the fingolimod cohort (n = 843) from three MS registries/data sources. In the combined data sources, 36.8% of cladribine and 27.4% of fingolimod users were DMT-naïve; after initiation of study treatment, 2.5% and 20.2% switched to another DMT, respectively. CONCLUSION: No new safety signal was observed in patients treated with cladribine tablets, although results are limited by a relatively short duration of follow-up.

Proportion and characteristics of secondary progressive multiple sclerosis in five European registries using objective classifiers.

Background: To assign a course of secondary progressive multiple sclerosis (MS) (SPMS) may be difficult and the proportion of persons with SPMS varies between reports. An objective method for disease course classification may give a better estimation of the relative proportions of relapsing-remitting MS (RRMS) and SPMS and may identify situations where SPMS is under reported. Materials and methods: Data were obtained for 61,900 MS patients from MS registries in the Czech Republic, Denmark, Germany, Sweden, and the United Kingdom (UK), including date of birth, sex, SP conversion year, visits with an Expanded Disability Status Scale (EDSS) score, MS onset and diagnosis date, relapses, and disease-modifying treatment (DMT) use. We included RRMS or SPMS patients with at least one visit between January 2017 and December 2019 if ≥ 18 years of age. We applied three objective methods: A set of SPMS clinical trial inclusion criteria ("EXPAND criteria") modified for a real-world evidence setting, a modified version of the MSBase algorithm, and a decision tree-based algorithm recently published. Results: The clinically assigned proportion of SPMS varied from 8.7% (Czechia) to 34.3% (UK). Objective classifiers estimated the proportion of SPMS from 15.1% (Germany by the EXPAND criteria) to 58.0% (UK by the decision tree method). Due to different requirements of number of EDSS scores, classifiers varied in the proportion they were able to classify; from 18% (UK by the MSBase algorithm) to 100% (the decision tree algorithm for all registries). Objectively classified SPMS patients were older, converted to SPMS later, had higher EDSS at index date and higher EDSS at conversion. More objectively classified SPMS were on DMTs compared to the clinically assigned. Conclusion: SPMS appears to be systematically underdiagnosed in MS registries. Reclassified patients were more commonly on DMTs.

A randomised, double blind, placebo controlled trial with vitamin D3 as an add on treatment to interferon ß-1b in patients with multiple sclerosis.

OBJECTIVES: To study the safety and efficacy of vitamin D3 as an add on therapy to interferon ß-1b (IFNB) in patients with multiple sclerosis (MS). METHODS: 1 year, double blind, placebo controlled, randomised study in 66 MS patients. The primary outcomes were T2 burden of disease (BOD) on MRI scans, proportion of patients with serum levels of 25-hydroxyvitamin D (25(OH)D) ≥85 nmol/l or intact parathyroid hormone (PTH) ≤20 ng/l, and number of adverse events. Secondary outcomes were number of MRI enhancing T1 lesions and new T2 lesions, annual relapse rate, changes in the Expanded Disability Status Scale score, timed 25 foot walk test and timed 10 foot tandem walk tests. RESULTS: Median change in BOD was 287 mm(3) in the placebo group and 83 mm(3) in the vitamin D group (p=0.105). Serum levels of 25(OH)D increased from a mean of 54 (range 19-82) nmol/l to 110 (range 67-163) nmol/l in the vitamin D group. 84% of patients reached a serum 25(OH)D level >85 nmol/l in the vitamin D group and 3% in the placebo group (p<0.0001). Patients in the vitamin D group showed fewer new T2 lesions (p=0.286) and a significantly lower number of T1 enhancing lesions (p=0.004), as well as a tendency to reduced disability accumulation (p=0.071) and to improved timed tandem walk (p=0.076). There were no significant differences in adverse events or in the annual relapse rate. CONCLUSION: Vitamin D3 add on treatment to IFNB reduces MRI disease activity in MS. TRIAL REGISTRATION NUMBER: EudraCT number 2007-001958-99 and ClinicalTrialsGov number NCT01339676.

C-reactive protein and seizures in focal epilepsy: a video-electroencephalographic study.

PURPOSE: C-reactive protein (CRP) has been studied extensively in many noninflammatory neurologic conditions, but there has been little study of CRP in the context of seizures or epilepsy. The purpose of this study was to examine CRP concentrations in patients with refractory focal epilepsy who were undergoing video-electroencephalography (EEG) monitoring compared with healthy controls, and CRP change during 24 h after a seizure. METHODS: CRP levels were measured in serum at the onset of video-EEG recording (CRP-0h) and at 3, 6, 12, and 24 h after index seizure (the first verified localized-onset seizure) in 31 patients during inpatient video-EEG monitoring by using high sensitivity measurement of CRP concentration. The patients were categorized into two groups: temporal lobe epilepsy (TLE; n = 15) and extratemporal lobe epilepsy (XLE; n = 16). Eighty healthy volunteers served as controls. KEY FINDINGS: CRP-0h concentration was significantly higher in patients with refractory focal epilepsy than in controls (3.5 vs. 0.7 mg/ml, p < 0.001). All five patients with elevated CRP-0h (>mean + 2 standard deviations in controls) had TLE (vs. none in XLE; p = 0.018). Index seizure type was associated with CRP increase from baseline to maximum level after index seizure (p = 0.005). The most important predictor of increase in CRP level was secondarily generalized tonic-clonic seizure (SGTCS; p = 0.030). SIGNIFICANCE: The higher baseline levels in patients with epilepsy compared with healthy controls demonstrates that CRP concentrations are also affected in refractory epilepsy. Our data suggest that SGTCS stimulates CRP production. These results emphasize the association between inflammation and refractory epilepsy.

[Paroxysmal feeling of suffocation during sleep--a diagnostic challenge]. / Unenaikainen kohtauksellinen tukehtumisen tunne--diagnostinen haaste.

Our patient suffered from nocturnal awakenings due to paroxysmal feelings of suffocation for three years. He was extensively examined at the community health centre and at the departments of neurology, psychiatry, oral diseases and respiratory medicine of the district hospital and the university hospital. The clinical hunch of the night nurses of the department of respiratory medicine and video EEG monitoring recommended by the sleep disorders team eventually revealed the real cause of the patient's symptoms.

Finnish multiple sclerosis patients treated with cladribine tablets: a nationwide registry study.

BACKGROUND: Cladribine tablets for adult patients with highly active relapsing multiple sclerosis (MS) have been available in Finland since 2018. Real-world data from different genetic and geographical backgrounds are needed to complement data from clinical trials. METHODS: We investigated the use of cladribine tablets in Finland in a non-interventional cohort study, based on real-world data from the nationwide Finnish MS registry. All eligible patients who had initiated treatment with cladribine tablets in 2018-2020 were included. Descriptive analyses for outcomes were conducted using summary statistics. Time-dependent endpoints were analyzed using cumulated events analysis based on 1-Kaplan-Meier estimates and curves. Subgroups were analyzed separately according to the number of previous disease-modifying therapies (DMTs) and the most common last preceding therapies. RESULTS: Data of 179 patients were analyzed. Median follow-up time was 19.0 months (interquartile range [IQR] 12.0-26.2). Of the 134 patients who were followed for at least 12 months, 112 patients (83.6%) remained relapse-free during follow-up. Mean annualized relapse rate (ARR) was 1.0 (standard deviation [SD] 0.89) at baseline, and 0.1 (SD 0.30) at follow-up. Patients with two or more previous DMTs had shorter time to first relapse (median 2.5 months, IQR 0.6-9.3) when compared to patients with 0-1 previous DMTs (median 11.4 months, IQR 8.7-13.1) (p=0.013). After excluding patients switching from fingolimod (n=33), a statistically significant difference in time to first relapse was no longer observed between the two groups (p=0.252). Adverse events (AEs) were reported in 30 patients (16.8%). The most frequent AE was headache (n=14, 7.8%). One patient (0.6%) died of cardiac arrest. Discontinuation of cladribine tablets was reported in nine patients (5.0%). CONCLUSION: The mean ARR observed in this cohort was similar to what has been reported in clinical trials. Approximately half of the patients had used two or more previous DMTs before cladribine tablets. These patients had a shorter time to first relapse when compared to patients with 0-1 previous DMTs, mostly driven by early relapses in patients switching from fingolimod.