Safety Of Natalizumab Research Articles

High NEDA and No PIRA in Natalizumab-Treated Patients With Pediatric-Onset Multiple Sclerosis.

Although pediatric-onset multiple sclerosis (POMS) is characterized by a more rapid accumulation of CNS inflammation than adult-onset MS (AOMS), the therapeutic algorithms applied in POMS are usually based on AOMS therapeutic outcomes. To define a high-efficacy treatment (HET)-based strategy to treat POMS, we designed an observational retrospective study aimed at evaluating the efficacy and safety of natalizumab (NTZ) in naïve POMS and AOMS. Starting from 160 patients, we applied a 2:1 (adult:pediatric) matching on propensity scores and obtained 32 patients with NTZ-treated POMS and 64 with AOMS, estimated from a multivariable logistic regression model. All patients were clinically and radiologically followed up every 6 months for a mean period of 46.0 ± 26.9 months. Following re-baseline at month 6, no difference (log-rank test: p = 0.924) in new and enlarging T2 white matter lesions, postcontrast T1 lesions, and relapse rate were observed between POMS and AOMS throughout the study. Progression independent of relapse activity (PIRA) was never observed in POMS, while 9 of 64 patients with AOMS (12.5%) had PIRA events during the follow-up (40.0 ± 25.9 months; log-rank p value 0.0156). JCV seroconversion rate during NTZ infusion did not differ between POMS and AOMS (log-rank test p = 0.3231). Finally, no serious adverse event was observed in both POMS and AOMS. The favorable outcomes observed on clinical, especially in PIRA, and radiologic parameters strongly support the use of NTZ as a first-choice HET in POMS.

The first study of real-world efficacy and safety of Natalizumab (Tysabri®) in Iran

Objectives: Natalizumab is an injectable DMT (disease-modifying therapy) which used for RRMS (relapsing-remitting multiple sclerosis) since 2006. The drug has been available in Iran since 2014. Introduction: This study was aimed to evaluate the real-world effectiveness of Natalizumab in a referral center in Tehran, Iran. This study is the first real world analysis of efficacy and safety of Natalizumab in our country. Methods: In this retrospective study, patients with RRMS were investigated in a high-volume center in Tehran from 2019 to 2021. MS (Multiple Sclerosis) patients under treatment with Natalizumab who have received at least 3 infusions of the drug and had completed follow-up data, have been evaluated for safety and efficacy of Natalizumab. Results: 100 patients were included in the final analysis. The mean follow-up time was 20 months (6–33 months). The median EDSS (Expanded Disability Status Scale) score of patients reached to 2 from 2.5 after the treatment course (P < 0.0001). The annualized relapse rate (ARR) decreased from 0.81 (95% CI: 0.73–0.87) to 0.023 (95% CI 0.009–0.061). The median JCV (John Cunningham virus) index remained unchanged before treatment 0.85 (IQR: 0.21–2.41) compare to after the treatment 0.85 (IQR: 0.21–2.31). The number of patients with active brain and cervical MRI (Magnetic Resonance Imaging) lesions decreased significantly (P = 0.001). NEDA-3 (No evidence of disease activity) was improved from 9% to 87% after the treatment with Natalizumab. No serious adverse events except than one progressive multifocal encephalopathy (PML) case have been found. The main reasons of switching from Natalizumab to the other DMDs (Disease Modifying Drugs) were positive JC index, starting phase, noncompliance, pregnancy, MRI activity and seroconversion after starting the drug. Conclusion: Natalizumab is a safe and effective choice in RRMS patients for reducing relapse rate, disability score, active MRI lesion, and improving the NEDA (No evidence of disease activity).

Efficacy & Safety of Natalizumab's Extended Interval Dosing in Relapsing Remitting Multiple Sclerosis

Efficacy & Safety of Natalizumab's Extended Interval Dosing in Relapsing Remitting Multiple Sclerosis

Practical Clinical Guidelines for Natalizumab Treatment in Patients With Relapsing Multiple Sclerosis.

Natalizumab (TYSABRI®) was the first high-efficacy monoclonal antibody disease-modifying therapy (DMT) approved as a monotherapy for the treatment of adults with relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting MS, and active secondary progressive MS. Because natalizumab is administered by intravenous infusion, infusion nurses play a key role in the care of natalizumab-treated patients. In the 16 years since approval, substantial data have been gathered on the long-term, real-world effectiveness and safety of natalizumab. This article provides a synopsis of this data, as well as practical information for optimizing patient care. This includes information on strategies to mitigate the risk of progressive multifocal leukoencephalopathy in natalizumab-treated patients, natalizumab use during pregnancy, and use with vaccines. It also includes guidance on the preparation and administration of natalizumab and monitoring of natalizumab-treated patients.

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

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). 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). 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. 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.

Real-world use of natalizumab in Austria: data from the Austrian Multiple Sclerosis Treatment Registry (AMSTR)

IntroductionWith the approval of natalizumab in Europe in 2006, the Austrian Multiple Sclerosis Therapy Registry (AMSTR) was established. Here, we present data from this registry about effectiveness and safety of natalizumab in patients treated up to 14 years.Patients/methodsData retrieved from the AMSTR contained baseline characteristics and biannual documentation of annualised relapse rate (ARR) and Expanded Disability Status Scale (EDSS) score as well as adverse events and reasons for discontinuation on follow-up visits.ResultsA total of 1596 natalizumab patients (71% women, n = 1133) were included in the analysis and the observed treatment duration ranged from 0 to 164 months (13.6 years). The mean ARR was 2.0 (SD = 1.13) at baseline, decreasing to 0.16 after 1 year and 0.01 after 10 years. A total of 325 patients (21.6%) converted to secondary progressive multiple sclerosis (SPMS) during the observational period. Of 1502 patients, 1297 (86.4%) reported no adverse events (AE) during follow-up visits. The most common reported AEs were infections and infusion-related reactions. John Cunningham virus (JCV) seropositivity was the most common specified reason for treatment discontinuation (53.7%, n = 607). There were five confirmed cases of Progressive Multifocal Leukoencephalopathy (PML) with 1 death.ConclusionThe effectiveness of natalizumab in patients with active relapsing–remitting multiple sclerosis (RRMS) could be confirmed in our real-world cohort even after follow-up of up to 14 years, though after year 10, there were less than 100 remaining patients. A low number of AE were reported in this nationwide registry study, establishing Natalizumab’s favourable safety profile during long-term use.

Long-Term Effectiveness and Safety of Natalizumab in African American and Hispanic/Latino Patients with Early Relapsing-Remitting Multiple Sclerosis: STRIVE Data Analysis.

In STRIVE, natalizumab treatment demonstrated effectiveness in clinical, magnetic resonance imaging (MRI), and patient-reported outcomes (PROs) in patients with early relapsing-remitting multiple sclerosis (RRMS). This post hoc analysis examined the effectiveness and safety of natalizumab in patients who self-identified as either Black/African American (AA) or Hispanic/Latino. Clinical, MRI, and PROs were assessed for the Black/AA subgroup (n = 40) and compared with the non-Hispanic White subgroup (n = 158). As a result of the very small sample size, outcomes for the Hispanic/Latino subgroup (n = 18) were assessed separately, including a sensitivity analysis with Hispanic/Latino patients who completed the 4-year study on natalizumab. Clinical, MRI, and PROs were comparable between the Black/AA and non-Hispanic White subgroups except for MRI outcomes at year1. A higher proportion of non-Hispanic White than Black/AA patients achieved MRI no evidence of disease activity (NEDA; 75.4% vs. 50.0%, p = 0.0121) and no new or newly enlarging T2 lesions (77.6% vs. 50.0%, p = 0.0031) at year1; these differences were not observed in years2-4 of the study. For the Hispanic/Latino subgroup in the intent-to-treat population, 46.2% and 55.6% achieved NEDA at years1 and 2; 66.7% and 90.0% achieved clinical NEDA at years3 and 4. Annualized relapse rate was reduced by 93.0% at year1 versus the year before natalizumab initiation; this reduction was maintained throughout the study. Over 4years, 37.5-50.0% of patients had a clinically meaningful improvement in their Symbol Digit Modalities Test score, and 81.8-100.0% and 90.9-100.0% had stable/improved Multiple Sclerosis Impact Scale-29 physical and psychological scores, respectively. Similar results were observed in the sensitivity analysis with Hispanic/Latino subgroup of the 4-year natalizumab completers. These results highlight the effectiveness and safety of natalizumab in patients with early RRMS who self-identified as Black/AA or Hispanic/Latino. GOV: NCT01485003.

A real world multi center study on efficacy and safety of natalizumab in Indian patients with multiple sclerosis

BackgroundNatalizumab (NTZ) is increasingly being used in Indian multiple sclerosis (MS) patients. There are no reports on its safety and efficacy, especially with respect to the occurrence of progressive multifocal leukoencephalopathy (PML). ObjectivesTo describe the patient characteristics, treatment outcomes, and adverse events, especially the occurrence of PML in NTZ-treated patients. MethodsA multicentre ambispective study was conducted across 18 centres, from Jan 2012 to Dec 2021. Patients at and above the age of 18 years treated with NTZ were included. Descriptive and comparative statistics were applied to analyze data. ResultsDuring the study period of 9 years, 116 patients were treated with NTZ. Mean age of the cohort was 35.6 ± 9.7 years; 83/116 (71.6%) were females. Relapse rate for the entire cohort in the year before NTZ was 3.1 ± 1.51 while one year after was 0.20±0.57 (p = 0.001; CI 2.45 -3.35). EDSS of the entire cohort in the year before NTZ was 4.5 ± 1.94 and one year after was 3.8 ± 2.7 (p = 0.013; CI 0.16–1.36). At last follow up (38.3 ± 22.78 months) there were no cases of PML identified. ConclusionsNatalizumab is highly effective and safe in Indian MS patients, with no cases of PML identified at last follow up.

Systematic Review and Meta-Analysis Comparing the Safety of Natalizumab, Ocrelizumab, and Alemtuzumab in Treating Relapsing–Remitting, Primary Progressive, and Secondary Progressive Multiple Sclerosis

Three monoclonal antibodies—natalizumab (NTZ), ocrelizumab (OCR), and alemtuzumab (ALM)—are the mainstays for the treatment of both relapsing and progressive forms of multiple sclerosis (MS). Here, their safety in patients with MS is analyzed and compared for rational use, especially during the COVID-19 pandemic. All clinical studies published between 2016 and 2020 with the primary outcome of the occurrence of adverse events (AEs) with the use of NTZ, OCR, and ALM in the treatment of MS were systematically searched in the PubMed database. In this review, the percentage of patients reporting AEs was calculated and compared. The most common AEs associated with the use of NTZ, OCR, and ALM were infection and infestation. The percentage of patients reporting urinary tract infection, upper respiratory tract infection, and herpes was 16% using natalizumab, 7% using natalizumab and ocrelizumab, and 2% with ocrelizumab, respectively. The most common AEs, such as rashes, pyrexia, and influenza, were reported with ocrelizumab and alemtuzumab. Additionally, alemtuzumab was associated with immune thrombocytopenia (2%), respiratory infections (7%), and thyroid dysfunction (43%). All these data outcomes show that of the three monoclonal antibodies, natalizumab and ocrelizumab were associated with a reduced incidence of adverse events, making them a safer choice for MS.

Effect of natalizumab treatment on the rate of No Evidence of Disease Activity in young adults with multiple sclerosis in relation to pubertal stage

Approximately 40% of young-onset multiple sclerosis (MS) patients experience breakthrough disease, which carries a high risk for long-term disability, and requires using therapies beyond traditional first-line agents. Despite the increasing use of newer disease-modifying treatments (DMTs) in this population, data are not available to guide the need for escalating DMTs and there is a scarcity of data on the effects of natalizumab in children and young adults with active disease. We performed a retrospective analysis of the rate of No Evidence of Disease Activity (NEDA), tolerability, and safety of natalizumab in a multi-center cohort of 36 children and young adults with highly active MS. All patients had active disease and initiated treatment with natalizumab. The primary endpoint was the rate of achieving NEDA-3 status, within two years of natalizumab treatment. To examine a possible effect of age on the outcome of treatment, outcomes were also analyzed by pre-pubertal (n = 13 children aged 9–13 years) and pubertal subgroups (n = 23 young adolescents aged 14–20 years). The NEDA-3 status of the pre-pubertal group was 92% in the first and second year and in the pubertal group - 96% in the first year and 92% in the second year. Natalizumab reduced the number and volume of brain lesions in both pre-pubertal and pubertal groups. Treatment was well-tolerated, only 8 patients (22.2%) had adverse events during the 2-year study period. Our analysis shows that natalizumab is effective and well-tolerated in pre-pubertal and pubertal MS patients.

Role of Natalizumab in Relapsing-Remitting Multiple Sclerosis: A review

Introduction: Multiple sclerosis is a non-traumatic neurological disease caused by an immune-mediated reaction leading to a chronic inflammatory demyelinating disorder of the central nervous system. The treatments for multiple sclerosis are mainly divided into three categories: treatment of exacerbation, slowing disease progression with disease-modifying therapies, and symptomatic therapies. Natalizumab is a monoclonal antibody that works by preventing the adhesion of lymphocytes into the endothelium of the blood-brain barrier, reducing lymphocyte infiltration into the central nervous system. This review aims to study the efficacy and safety of natalizumab in relapsing-remitting multiple sclerosis. Methods: The review was performed using databases like PubMed, Cochrane library, Google scholar from which 48 relevant articles were selected based on the various inclusion criteria. The following keywords were used: “Natalizumab”, “Multiple sclerosis”, “side effects”, “Relapsing-remitting multiple sclerosis”, “progressive multifocal leukoencephalopathy” in different combinations. Results: The literature review suggests that natalizumab reduces the rate of sustained progression of the disease and disability, and was associated with a lower relapse rate in patients with relapsing-remitting multiple sclerosis. However, Progressive multifocal leukoencephalopathy is one of the serious side effects of natalizumab. Conclusion: The literature review suggests that Natalizumab has favorable outcomes in patients with relapsing-remitting multiple sclerosis. Since progressive multifocal leukoencephalopathy is one of the serious side effects of natalizumab, risk stratification should be done.

Real-World Effectiveness of Natalizumab in Korean Patients With Multiple Sclerosis.

Background and Purpose: Natalizumab is a highly efficacious disease-modifying therapy for relapsing-remitting multiple sclerosis (MS). Data on the efficacy and safety profile of natalizumab in Asian patients with MS are limited. This study assessed the efficacy and safety of natalizumab in Korean patients with MS in a real-world setting.Methods: This study enrolled consecutive Korean patients with active relapsing-remitting MS who were treated with natalizumab for at least 6 months between 2015 and 2021. To evaluate the therapeutic outcome of natalizumab, we used the Expanded Disability Status Scale (EDSS) scores and brain magnetic resonance imaging; adverse events were assessed at regular intervals. No evidence of disease activity (NEDA) was defined as no clinical relapse, no worsening of EDSS score, and no radiological activities.Results: Fourteen subjects with MS were included in the study. The mean age at initiation of natalizumab therapy was 32 years. All patients were positive for anti-John Cunningham virus antibodies before natalizumab administration. The mean annual relapse rate was markedly reduced from 2.7 ± 3.2 before natalizumab therapy to 0.1 ± 0.4 during natalizumab therapy (p = 0.001). Disability was either improved or stabilized after natalizumab treatment in 13 patients (93%). During the 1st year and 2 years after initiating natalizumab, NEDA-3 was achieved in 11/12 (92%) and 9/11 (82%) patients, respectively. No progressive multifocal leukoencephalopathy or other serious adverse events leading to the discontinuation of natalizumab were observed.Conclusions: Natalizumab therapy showed high efficacy in treating Korean patients with active MS, without unexpected safety problems.

Patient and treatment characteristics and safety outcomes of patients with relapsing-remitting multiple sclerosis treated with natalizumab in Greece: Results from the multicenter, 5-year prospective observational study 'TOPICS greece'.

BackgroundNatalizumab is a highly efficacious treatment for relapsing-remitting multiple sclerosis (RRMS).ObjectiveTo assess the real-world long-term safety of natalizumab in RRMS.MethodsThis multicenter, 5-year prospective observational study, included adults with RRMS newly initiated on natalizumab as per the approved product label in the routine care in Greece. Safety was evaluated by collecting serious adverse events (SAEs) following study enrollment.ResultsBetween 19-Apr-2012 and 18-Dec-2014, 304 eligible patients (median age at natalizumab initiation: 38.0 years; median disease duration: 6.2 years) were enrolled by 20 hospital-based neurologists. Over a median treatment duration period of 58.7 months, 50.7% of the patients discontinued natalizumab, mainly due to anti-JCV antibody detection (59.1%). The adverse event treatment discontinuation rate was 5.2%. The SAE incidence rate during the safety data collection period (median: 48.7 months) was 4.6%. The most common SAEs were infections (1.0%), including 2 cases (0.7%) of progressive multifocal leukoencephalopathy (PML), and no other opportunistic infections. PML diagnoses occurred 6.2-6.7 years after natalizumab initiation, and approximately 2 years after first detection of anti-JCV antibody for both patients. The incidence rate of malignancies was 0.7%.ConclusionIn real-world settings in Greece, natalizumab displayed an acceptable safety profile, with no new safety signals emerging.

Is natalizumab a safe treatment for patients with multiple sclerosis in the COVID-19 pandemic? Data from the first year of the pandemic

BackgroundPatients with MS have increased risk of infections, especially those with highly active treatments. We studied the safety of natalizumab in patients with MS during the COVID-19 pandemic.MethodsDemographic features, time on natalizumab, dose interval and COVID-19 symptoms were evaluated in a prospective study of patients with MS receiving natalizumab during the pandemic. RT-PCR COVID-19 tests from nasopharyngeal samples were performed before natalizumab treatment.ResultsWe analyzed 69 patients: 71% women, mean age 43 years. Mean treatment duration was 68 months (range: 2–141). In 32% of patients, natalizumab regimen was changed from every 4 to every 6 weeks to decrease number of hospital visits. From March to April 2020, 5 patients had COVID-19, 4 showed mild symptoms and 1 a multi-lobar pneumonia. On May 2020, we started COVID-19 screening before natalizumab infusion. From May 2020 to March 2021, tests were performed on 553 nasopharyngeal swabs. Fourteen patients had a positive result and natalizumab was stopped; tests were repeated 1–2 weeks later, with negative results, and natalizumab was restarted. In summary: 19 patients had COVID-19, 10 asymptomatic, 7 mild symptoms, 2 pneumonia (1 of whom hospitalized without mechanical ventilation). There were no statistically significant differences in age (mean±standard deviation, 35.7±11.5 vs 43.4±7.8 years; p=0.158), dose interval (5.33 vs 5.32 weeks; p=0.962) or treatment duration (5.8 vs 5.6 years; p=0.298) between patients with and without COVID-19.ConclusionNatalizumab treatment in MS seems to be safe during the pandemic. Most patients were asymptomatic, and no patient required mechanical ventilation.

Does Extended Interval Dosing Natalizumab Preserve Effectiveness in Multiple Sclerosis? A 7 Year-Retrospective Observational Study

The extended interval dosing (EID) of natalizumab has been suggested to be associated with a reduced risk of progressive multifocal leukoencephalopathy (PML) and short-term preservation of efficacy but its long-term effectiveness remain unknown. We aimed to determine the long-term effectiveness and safety of natalizumab in an EID setting in a cohort of patients with multiple sclerosis (MS) treated for more than 7 years. We conducted an observational retrospective cohort study, including 39 (34 female, 5 male) patients with clinically definite relapsing-MS, initially treated with standard interval dosing (SID) of natalizumab (mean time 54 months [SD29]) who were then switched to EID, every 8 weeks (mean time 76 months [SD13]). The main outcome measures included the following: i) annualized relapse rate (ARR), ii) radiological activity, iii) disability progression, and iv) NEDA-3 no evidence of disease activity index. EID preserved ARR, radiological activity, and prevented disability worsening during follow-up. The proportion of patients maintaining their NEDA-3 status after 24, 48, and 72 months of natalizumab administration in EID was 94%, 73%, and 70%, respectively. Stratified analysis according to history of drug therapy showed that the EID of natalizumab was slightly more effective in naïve patients than in those previously treated with other immunosuppressive drugs. No cases of PML or other severe adverse reactions were reported. In conclusion, long-term therapy with natalizumab in an EID setting following an SID regimen maintained its disease-modifying activity, and was safe and well tolerated for over 7 years. These encouraging observational results need to be confirmed in controlled clinical trials.

Natalizumab safety in paediatric-onset multiple sclerosis at the time of SARS-Cov-2 pandemic.

Natalizumab safety in paediatric-onset multiple sclerosis at the time of SARS-Cov-2 pandemic.

Natalizumab for induction of remission in Crohn's disease.

Natalizumab for induction of remission in Crohn's disease.

Efficacy and safety of natalizumab extended interval dosing

ObjectiveIt is postulated that extending the dosing interval of natalizumab (NTZ) from 4 to 5–8 weeks might decrease the risk of progressive multifocal leukoencephalopathy (PML). The aim of this study was to assess the effect of extended interval dosing (EID) on the therapeutic efficacy of natalizumab. MethodsWe reviewed 85 patients treated at two MS centers in the Middle East with natalizumab for at least 6 months using EID. Patients were shifted after an initial treatment period at standard interval dosing (SID) to an EID ranging from 5–8 weeks. ResultsThe mean treatment duration on SID and EID was 15.4 ± 11.9 and 11.8 ± 7.0 months, respectively. By the end of SID and EID treatment 95.3% and 93.9% of patients were free of relapses (P = 0.41) with an annualized relapse rate (ARR) of 0.0006 and 0.001 respectively (P = 0.42). The mean EDSS at the end of SID and EID periods was 2.56 ± 1.62 and 2.59 ± 1.61 respectively (P = 0.84). A total of 97.6% and 94.7% of patients had no enhancing lesions on MRI during the SID and EID periods respectively (P = 0.18). There were no cases of PML and the rate of infections was lower during the EID period. ConclusionIn patients treated with natalizumab, shifting from SID to EID has no negative effect on efficacy as evidenced by relapse rate, disability progression and MRI activity.

Long-term safety evaluation of natalizumab for the treatment of multiple sclerosis

ABSTRACTIntroduction: Natalizumab is a humanized monoclonal antibody highly effective in relapsing-remitting multiple sclerosis (MS). Important concerns about its safety have been pointed out mainly because of the risk of progressive multifocal leukoencephalopathy (PML), caused by the opportunistic John-Cunningham virus (JCV).Areas covered: This review analyzes all the safety aspects related to the use and safety of natalizumab in MS patients. Other than PML, post-marketing, safety red-flags have been reported, as liver or haematological serious adverse events. Pregnancy evidences will be pointed out.The risk of PML depends on: concomitant or previous immunosuppression, exposure duration, anti–JCV antibody level. In natalizumab-related PML the average survival is 77%; prognostic features and information for the earliest identification of PML have been identified to maximally reduce its incidence, mortality and morbidity.Expert opinion: Natalizumab is a highly effective drug for MS patients but its safety issues represent a relevant limitation and impose strict clinical surveillance of treated patients. Some post-marketing safety red-flags have been pointed out, with higher attention to severe liver failures and limphoma cases. If PML and its consequences are considered the most relevant issues, a continuous surveillance must be maintained also regarding other possible SAEs like liver diseases and malignancies.

Long-term effectiveness and safety of natalizumab in a Portuguese population

ObjectivesNatalizumab long-term effectiveness data in real-world relapsing­remitting multiple sclerosis (RRMS) is needed. Our objective is to report the long­term effectiveness and safety of natalizumab in a cohort of RRMS patients. MethodsThis is a retrospective study of natalizumab treatment for two years or longer in RRMS. Annualized relapse rate, Expanded Disability Status Scale (EDSS), brain magnetic resonance imaging T2 lesion volume, JC virus antibody status, previous treatments and adverse events were analysed. ResultsSeventy-one patients were included with a mean treatment duration of 44.86±17.39months. Over the treatment duration there was a significant decrease in annualized relapse rate (88.37%) and EDSS (28.57%); no evidence of clinical disease activity in 73.24% and 61.97% after one and two-years respectively; and brain magnetic resonance imaging T2 lesion volume remained stable. Forty patients suspended natalizumab, in 85% due to high risk of developing progressive multifocal leukoencephalopathy (PML). The major complication was PML (n=3). ConclusionsNatalizumab showed effectiveness in the long-term follow up period of our cohort, with reduction of ARR, EDSS, and MRI lesion load stabilization. PML was the major complication.