Natalizumab Infusions Research Articles

Cyclophosphamide Pulses Therapy after Natalizumab Discontinuation for Multiple Sclerosis: A Multicentre Study

Importance: Natalizumab discontinuation induces the recurrence of Multiple Sclerosis (MS) disease activity: Currently no therapeutic approach has been found able to abolish disease reactivation. Objective: To collect data from patients with MS switching from natalizumab to cyclophosphamide. Design: Retrospective multicentre study. Setting: Nine Multiple Sclerosis Centers in Italy. Participants: A total of 47 patients with clinically definite RR-MS switched to cyclophosphamide after natalizumab discontinuation. Two patients were excluded from the analysis because received less than 12 natalizumab infusions. The remaining 45 patients were subdivided into two main groups: Early Treatment (period of washout between natalizumab and cyclophosphamide 1 to 3 months), Late Treatment (washout between natalizumab and cyclophosphamide higher than 3 months). Intervention: Cyclophosphamide intravenous pulses after natalizumab discontinuation. Main outcome measure: Number of relapses, Expanded Disability Status Scale scores, number of new T2/fluidattenuated inversion recovery lesions and contrast-enhancing lesions on brain magnetic resonance imaging, rebound effect, adverse events. Results: In the Early Treatment group, only 3/23 patients (13%) experienced a clinical relapse and only 2 out of 13 (15%) patients showed brain Magnetic Resonance Imaging (MRI) activity at 3 months, while none developed MRI activity at 6 months after cyclophosphamide introduction. In the Late Treatment Group 12/22 patients (63%) had relapses during the washout period and 4/22 (40%) after the introduction of cyclophosphamide; MRI disease activity was shown in 5/9 (56%) at 3 months and in 5/14 (36%) at 6 months after cyclophosphamide introduction. Conclusions and relevance: These data show that cyclophosphamide could be able to reduce disease reactivation after natalizumab, in particular with a short washout period after natalizumab discontinuation. It can be suggested that a short period (3-6 months) of cyclophosphamide monthly pulses could be used as “re-induction” treatment in patients discontinuing natalizumab.

Non-Hodgkin Lymphoma of the Stomach in a Patient Treated with Natalizumab

A 61-year-old man with relapsing-remitting multiple sclerosis developed extranodal large B-cell lymphoma of the stomach following monthly natalizumab infusions for 6 years. Development of lymphoproliferative disorders increases with chronic use of immunosuppression. Cases of primary central nervous system lymphoma as well as one case of peripheral T-cell lymphoma have previously been reported with natalizumab use. Given the absence of a known association between multiple sclerosis and extranodal presentations of diffuse large B-cell lymphoma, a causal association with natalizumab administration cannot be excluded.

P047 - Sustained benefit of natalizumab in pediatric multiple sclerosis with breakthrough activity: A case report

Objective Limited data are available on natalizumab in pediatric multiple sclerosis. This is to report the sustained therapeutic benefit of natalizumab over 32 months follow up in a 12-year old child with a breakthrough activity disease. Methods In February 2009, the diagnosis of childhood onset relapsing remitting multiple sclerosis was confirmed at age 9, based on the “International Pediatric Multiple Sclerosis Study Group”. A disease breakthrough activity with suboptimal response was considered after 26 months of a well tolerated treatment with beta-interferon-1b; 6 relapses, rapid neurological deterioration and an increase by 4 new plaques on average per year with at least one showing enhancement after gadolinium injection were observed on MRI follow up. Monthly natalizumab 300 mg intravenous infusion was initiated on February 2012, after written consent. Negative JCV antibodies from serum samples were confirmed using the “STRATIFT JCV” test before treatment initiation and at 6 months intervals; clinical evaluation and biological tests were performed on routine base every 3 months. Results The patient's neurological status improved dramatically with rapid recovery after the second natalizumab infusion. Presently, this 13-year-old patient has received a total of 32 infusions of natalizumab and is still asymptomatic with no occurrence of any clinical relapse or no new lesion. Treatment is still well tolerated. Conclusion This report highlights the tolerability and sustained therapeutic efficacy of natalizumab as second-line therapy in childhood multiple sclerosis with breakthrough disease activity when critical decision of shifting from first-line therapy has to be made in children with potential greater risk in reaching progressive neurological disability at younger age.

P027 - Severe reactivation of multiple sclerosis after discontinuation of fingolimod: An IRIS-associated phenomenon

Background Data on the mechanism of rebound activity post-withdrawal of fingolimod in multiple sclerosis (MS) patients is scarce. Objectives To describe a patient with multiple sclerosis (MS) who developed severe reactivation after discontinuation of fingolimod. Method Case report and review of literature. Results A 36-year old woman with aggressive MS since 1998 was switched to fingolimod due to JC virus seropositivity after receiving 24 infusions of natalizumab. The 8-week natalizumab washout period was unremarkable. While on fingolimod, she developed severe lymphopenia (0.2×109/L) necessitating withdrawal of fingolimod. Seven weeks later, she presented with dysarthria and right-sided pyramidal weakness, which rapidly progressed to drowsiness and coma within few days. The clinical presentation and radiological features were suspicious for progressive multifocal leukoencephalopathy (PML). CSF JCV DNA was negative. She received plasmapheresis and maintenance corticosteroids afterwards. A clinical improvement was observed within 14 days but she sustained significant hemiparesis requiring extensive rehabilitation. The final diagnosis of severe reactivation of MS post-withdrawal of fingolimod was established. It is postulated that the significant reactivation of MS was due to its association with an Immune Reconstitution Inflammatory Syndrome (IRIS) given the abrupt rise in lymphocyte count after fingolimod withdrawal. Conclusion Our case highlighted the diagnostic dilemma in JC virus seropositive patients who developed relapses after discontinuing potent immunomodulators. Patients who discontinued fingolimod might be at risk of developing IRIS resulting in disease reactivation in the washout period. Data on the mechanism of rebound activity post-withdrawal of fingolimod in multiple sclerosis (MS) patients is scarce. To describe a patient with multiple sclerosis (MS) who developed severe reactivation after discontinuation of fingolimod. Case report and review of literature. A 36-year old woman with aggressive MS since 1998 was switched to fingolimod due to JC virus seropositivity after receiving 24 infusions of natalizumab. The 8-week natalizumab washout period was unremarkable. While on fingolimod, she developed severe lymphopenia (0.2×109/L) necessitating withdrawal of fingolimod. Seven weeks later, she presented with dysarthria and right-sided pyramidal weakness, which rapidly progressed to drowsiness and coma within few days. The clinical presentation and radiological features were suspicious for progressive multifocal leukoencephalopathy (PML). CSF JCV DNA was negative. She received plasmapheresis and maintenance corticosteroids afterwards. A clinical improvement was observed within 14 days but she sustained significant hemiparesis requiring extensive rehabilitation. The final diagnosis of severe reactivation of MS post-withdrawal of fingolimod was established. It is postulated that the significant reactivation of MS was due to its association with an Immune Reconstitution Inflammatory Syndrome (IRIS) given the abrupt rise in lymphocyte count after fingolimod withdrawal. Our case highlighted the diagnostic dilemma in JC virus seropositive patients who developed relapses after discontinuing potent immunomodulators. Patients who discontinued fingolimod might be at risk of developing IRIS resulting in disease reactivation in the washout period.

Multiple sclerosis symptom recrudescence at the end of the natalizumab dosing cycle.

This study was undertaken to determine how frequently patients receiving natalizumab for multiple sclerosis (MS) experience recrudescence of their MS symptoms at the end of the dosing cycle. One hundred consecutive MS patients receiving natalizumab completed a survey evaluating changes in symptoms during the natalizumab dosing cycle. Ninety-one patients also completed questionnaires at two time points: the first week after natalizumab infusion and the last week of the dosing cycle. These included the Multiple Sclerosis Quality of Life-54 (MSQOL-54), Fatigue Visual Analog Scale (VAS), Fatigue Severity Scale (FSS), and Beck Depression Inventory-II (BDI-II). End of dosing interval (EDI) symptoms were reported as currently being experienced by 57% of respondents. An additional 10% reported that they previously experienced that phenomenon, but not currently, and 33% reported never experiencing this. In those with EDI symptoms, they began to occur a median of 21 days after infusion and improved again a median of 1 day after infusion. The most common symptoms reported were fatigue, weakness, walking impairment, and cognitive difficulties. No specific demographic or disease characteristics were associated with this phenomenon. In the subgroup with EDI symptoms, the MSQOL-54, Fatigue VAS, FSS, and BDI-II scores were all significantly worse in the last week of the dosing cycle when compared with the first week. No difference was seen in these scores between first and last week in the subgroup not experiencing symptom recrudescence. Recrudescence of fatigue, weakness, walking impairment, or cognitive difficulties at the end of the dosing cycle occurs in about two-thirds of MS patients receiving natalizumab.

Preliminary Results of the “Sovet” Observational Program for Use of Natalizumab in the Treatment of Patients with Remitting Multiple Sclerosis

The “Sovet” post-marketing observational program was started in 2011. A total of 69 patients with the remitting form of multiple sclerosis (MS) treated with the second-generation DMD natalizumab (NZ) were studied. NZ infusions were given over 1 h every four weeks for 12 months. Treatment produced significant reductions in the frequency of exacerbations of disease, from 2.22 ± 0.98 to 0.18 ± 0.42 per year, along with a tendency to decreased EDSS scores, from 3.69 ± 1.0 to 3.37 ± 1.17. Adverse events occurred during treatment in 11 patients, each reaction being seen in no more than one person; treatment withdrawal was required in only one case, because of a generalized allergic reaction. The data presented here supplement published data on the positive effects of NZ on the course and signs of MS. These results lead to the conclusion that strict selection of patients and correct management during NZ treatment can provide a positive balance between the benefits of this treatment and its potential risks.

JC Virus in CD34+and CD19+Cells in Patients With Multiple Sclerosis Treated With Natalizumab

Infection with JC virus (JCV) may lead to development of demyelinating progressive multifocal leukoencephalopathy in patients with multiple sclerosis (MS) who are treated with natalizumab. To determine whether mononuclear cells in circulation from MS patients treated with natalizumab harbor JCV DNA. In this prospective investigation, we enrolled 49 MS patients from the Clinical Center for Multiple Sclerosis at The University of Texas Southwestern Medical Center and 18 healthy volunteers. We drew 120-mL blood samples from 26 MS patients at baseline and at approximately 3-month intervals to 10 months during the course of natalizumab infusions. One blood sample was drawn from 23 MS patients receiving natalizumab for more than 24 months and from 18 healthy volunteers. Natalizumab treatment of MS. The blood samples were separated using flow cytometry into CD34+, CD19+, and CD3+ cell subsets; DNA templates were prepared using quantitative polymerase chain reaction for JCV DNA identification. Plasma samples were tested for anti-JCV antibodies by enzyme-linked immunosorbent assays performed at the Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological and Communicative Diseases and Stroke. Thirteen of the 26 patients (50%) with baseline and follow-up blood samples had detectable viral DNA in at least 1 cell compartment at 1 or more points. Ten of the 23 patients (44%) receiving treatment for more than 24 months and 3 of the 18 healthy volunteers (17%) also had detectable viral DNA in 1 or more cell compartment. Fifteen of the 49 MS patients (31%) were confirmed to harbor JCV in CD34+ cells and 12 of 49 (24%) in CD19+ cells. Only 1 of 18 healthy volunteers were viremic in CD34+ cells and none in CD19+ cells. Nine patients and 1 healthy volunteer were viremic but had seronegative test results for JCV antibodies. JC virus DNA was detectable within cell compartments of natalizumab-treated MS patients after treatment inception and longer. JC virus DNA may harbor in CD34+ cells in bone marrow that mobilize into the peripheral circulation at high concentrations. Latently infected cells initiate differentiation to CD19+ cells that favors growth of JCV. These data link the mechanism of natalizumab treatment with progressive multifocal leukoencephalopathy.

Switching From Natalizumab to Fingolimod in Multiple Sclerosis

The safety and efficacy of switching from natalizumab to fingolimod have not yet been evaluated in a large cohort of patients with multiple sclerosis (MS) to our knowledge. To collect data from patients with MS switching from natalizumab to fingolimod. The Enquête Nationale sur l'Introduction du Fingolimod en Relais au Natalizumab (ENIGM) study, a survey-based, observational multicenter cohort study among MS tertiary referral centers. Participants were patients for whom a switch from natalizumab to fingolimod was planned. Clinical data were collected on natalizumab treatment, duration and management of the washout period (WP), and relapse or adverse events during the WP and after the initiation of fingolimod. Occurrence of MS relapse during the WP or during a 6-month follow-up period after the initiation of fingolimod. Thirty-six French MS tertiary referral centers participated. In total, 333 patients with MS switched from natalizumab to fingolimod after a mean of 31 natalizumab infusions (female to male ratio, 2.36; mean age, 41 years; and Expanded Disability Status Scale score at the initiation of natalizumab, 3.6). Seventy-one percent were seropositive for the JC polyomavirus. The Expanded Disability Status Scale score remained stable for patients receiving natalizumab. Twenty-seven percent of patients relapsed during the WP. A WP shorter than 3 months was associated with a lower risk of relapse (odds ratio, 0.23; P = .001) and with less disease activity before natalizumab initiation (P = .03). Patients who stopped natalizumab because of poor tolerance or lack of efficacy also had a higher risk of relapse (odds ratio, 3.20; P = .004). Twenty percent of patients relapsed during the first 6 months of fingolimod therapy. Three percent stopped fingolimod for efficacy, tolerance, or compliance issues. In the multivariate analysis, the occurrence of relapse during the WP was the only significant prognostic factor for relapse during fingolimod therapy (odds ratio, 3.80; P = .05). In this study, switching from natalizumab to fingolimod was associated with a risk of MS reactivation during the WP or shortly after fingolimod initiation. The WP should be shorter than 3 months.

Efficacy and safety of natalizumab in multiple sclerosis: interim observational programme results

BackgroundClinical trials established the efficacy and safety of natalizumab. Data are needed over longer periods of time and in the clinical practice setting.ObjectiveTo evaluate long-term safety of natalizumab and its...

Prevalence of Anti-JC Virus Antibody in Multiple Sclerosis Patients in Kuwait

Background. Multiple sclerosis (MS) therapeutics entered a new era after the development of anti-JC virus (anti-JCV) antibody assay that assesses the risk of development of progressive multifocal leukoencephalopathy (PML) in patients treated with natalizumab. Objective. To determine the prevalence of anti-JCV antibody among MS patients in Kuwait. Methods. Using the national MS registry, demographics and disease characteristics of MS patients who were screened for anti-JC virus antibody were collected. The prevalence of anti-JCV antibody seropositivity and its association with demographic and disease characteristics were evaluated. Results. Out of 110 screened MS patients for anti-JCV antibodies, 65.5% were females. Mean age and disease duration were 29.23 ± 8.55 and 5.39 ± 5.04 years, respectively. 47.3% of patients were already on natalizumab and 52.7% of patients were screened for stratification to either natalizumab or a different Disease Modifying Therapy (DMT). The overall prevalence of anti-JC virus antibody was 40%. Gender (P = 0.69), disease duration (P = 0.11), and number of natalizumab infusions (P = 0.64) were not associated with seropositivity. Patients aged ≥30 years were more likely to be seropositive (P = 0.01). Conclusion. The prevalence of anti-JCV antibody is slightly lower than what is reported in published studies. Seropositivity was associated with an increasing age of MS patients.

We know how to prescribe natalizumab for multiple sclerosis, but do we know how to withdraw it?

Natalizumab is a potent immunosuppressive monoclonal antibody used for the treatment of multiple sclerosis (MS). While definite guidelines for the safety of natalizumab prescriptions are available in all countries, there are no specific recommendations on how to withdraw the drug if the need arises. There are reports describing MS complications after natalizumab infusions were stopped. Most neurologists seem to stop natalizumab treatment according to their idea on how to best carry out the withdrawal. The present study shows the very different manners in which expert neurologists from 14 MS units in Brazil stopped natalizumab in their patients. The authors concluded that pharmacovigilance on natalizumab must persist after the drug is withdrawn in order to have enough data for adequate recommendations.

EFFICACY AND SAFETY OF NATALIZUMAB TREATMENT FOR RELAPSING–REMITTING MULTIPLE SCLEROSIS: INTERIM RESULTS OF THE TYSABRI® OBSERVATIONAL PROGRAMME IN THE UK

IntroductionThe natalizumab (TYSABRI®) Observational Program (TOP) is an ongoing, open–label, 10–year prospective study of relapsing–remitting Multiple Sclerosis (RRMS) patients in European, Australian, and Canadian clinical settings. Patients must be naïve...

Natalizumab-related progressive multifocal leukoencephalopathy in Greece

Background & objectivesProgressive multifocal leukoencephalopathy (PML) may complicate natalizumab treatment in multiple sclerosis patients. We sought to characterize the clinical and laboratory features of natalizumab-related PML (NR-PML) cases from Greece. MethodsPharmaceutical industry, national drug authorities and all neurology departments within the Greek territory were asked to provide data for cases of NR-PML until October 2012. Collected cases were classified according to their level of diagnostic certainty using the five-level system introduced by Mentzer et al. (2012). ResultsThirteen NR-PML cases were identified by the neurology departments. Data were provided for only 9 cases. PML manifestations appeared after a median number of 40 (21–52) natalizumab infusions. All but two patients were treated with plasma exchange and some were treated adjunctively with mirtazapine while the others were treated with mefloquine. IRIS developed in 6 cases after a median time of 6 (2–10) weeks from PML presentation and were treated with different regimens of corticosteroids. PML was fatal in 3 cases. The median EDSS after a median follow-up time of 12 (8–23) months in the surviving cases was 4.75 (2–8.5). ConclusionsOutcomes for collected NR-PML cases varied from death to returning to baseline. Close surveillance is essential for early diagnosis and treatment of NR-PML patients.

Presymptomatic Diagnosis with MRI and Adequate Treatment Ameliorate the Outcome after Natalizumab-Associated Progressive Multifocal Leukoencephalopathy

Natalizumab (Tysabri®) is a monoclonal antibody that prevents inflammatory cells from binding to brain endothelial cells and passing into the brain parenchyma. Natalizumab is a highly effective treatment for relapsing-remitting multiple sclerosis (MS). Progressive multifocal leukoencephalopathy (PML) is an opportunistic brain JC virus infection that has been shown to be associated with natalizumab treatment. We describe PML in a patient with MS after 44 monthly infusions of natalizumab. With the aid of a routine Magnetic resonance imaging (MRI) scan, PML was detected before any unambiguous clinical manifestations had emerged. PML was treated with plasma exchange to accelerate removal of natalizumab. Mirtazapine and mefloquine was promptly added and approximately 1 month after plasma exchange, when an immune-reconstitution-inflammatory-syndrome appeared, steroid treatment was initiated. Steroid treatment was then continued until no virus could be detected in the cerebrospinal fluid. The outcome was favorable. We believe that this case clearly illustrates the importance of an early, presymptomatic, detection of PML, and an adequate treatment. We also propose that surveillance with MRI scans, every 3 months after 24 months of treatment, should be performed in JC virus antibody positive natalizumab-treated MS patients in order to detect PML in an early phase.

Bridging, switching or drug holidays – how to treat a patient who stops natalizumab?

Natalizumab (NAT) was the first monoclonal antibody to be approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). While pivotal and postmarketing studies have showed considerable and sustained efficacy of NAT in RRMS, the increasing incidence of therapy-associated progressive multifocal leukoencephalopathy (PML), a brain infection caused by the John Cunningham virus (JCV), is a risk associated with long-term therapy. The risk for therapy-associated PML is highest in so-called “triple risk” patients. Therefore, long-term NAT-treated, immunosuppressive-pretreated, and JCV antibody-positive patients often discontinue NAT therapy. However, until now, it is not known which treatment strategy should be followed after NAT cessation. Since disease activity returns to pretreatment levels, or even above, within 4–7 months from the last infusion of NAT, patients who stop NAT are at considerable risk of relapse and worsening of multiple sclerosis (MS)-related disability. Several strategies have been applied to prevent the recurrence of disease activity after discontinuation of NAT. Of these, bridging with intravenous methylprednisolone, and switching to glatiramer acetate or interferon beta (IFN-beta) do not seem to be effective enough. More promising results have been obtained in retrospective studies and case series with fingolimod (FTY), an alternative escalation therapy for RRMS, although some patients have showed a severe disease rebound after starting FTY treatment. The time interval between the discontinuation of NAT and the start of FTY might affect the recurrence of disease activity. Long-term data about the efficacy and safety of FTY treatment after cessation of NAT are urgently needed and should be further investigated. Prospective studies are warranted, to optimize treatment strategies for RRMS patients who discontinue NAT, especially because new therapies will be available in the very near future.

Use of Natalizumab in Patients with Active Relapsing-Remitting Multiple Sclerosis in Kuwait

Objective: To evaluate the outcomes of patients with multiple sclerosis (MS) who were treated with natalizumab in Kuwait. Materials and Methods: A retrospective study using the MS registry to identify patients who were treated with natalizumab was conducted. Patients' demographics, clinical characteristics and treatment parameters were collected at baseline and last follow-up visit. Primary outcome was the proportion of relapse-free patients at the last follow-up while secondary outcomes were the change in the mean annual relapse rate, Expanded Disability Status Scale (EDSS) and the proportion of patients with magnetic resonance imaging (MRI) activity at the last follow-up visit. Forty-four patients were included in the study. Results: Of the 44 patients, 27 (61.4%) were females and the remaining 17 (38.6%) males. Mean age of patients and mean disease duration were 29.05 ± 7.25 and 5.71 ± 3.37 years, respectively. The mean number of natalizumab infusions was 18.14. The proportion of relapse-free patients significantly increased from 11.36 to 90.91% (p < 0.0001). The EDSS significantly improved from 4.76 to 3.15 (p < 0.0001) over the observational period. There was no significant difference between patients with EDSS <3 compared to those with EDSS ≥3 (p < 0.67). The proportion of patients with MRI activity was significantly reduced from 95.5 to 18.2% (p < 0.0001) at their last visit. Six patients discontinued the drug, 5 due to positive JC virus and 1 due to pregnancy. Conclusions: Natalizumab induced a suppression of disease activity and was responsible for a significant improvement in disability status in highly active MS patients.

Cost-minimization analysis of fingolimod compared with natalizumab for the treatment of relapsing–remitting multiple sclerosis in Sweden

Background:Fingolimod and natalizumab have the same European Union licence for the treatment of relapsing multiple sclerosis, and are considered by the Committee for Medicinal Products for Human Use (CHMP) to have broadly similar efficacy.Objective:A cost-minimization analysis was performed to compare differences in treatment costs between fingolimod and natalizumab from a societal perspective in Sweden.Methods:This analysis included costs associated with initiating and following treatment (physician visits and monitoring), continuing therapy (drugs and administration), and lost patient productivity and leisure time. Unit costs (in Swedish krona [SEK]) were based on regional data (median prices for physician visits and monitoring sessions). Natalizumab infusion costs were obtained from the national cost-per-patient database. Drug costs for both therapies were 15,651 SEK/28 days.Results:After 3 years, fingolimod use was associated with savings of 124,823 SEK/patient compared with natalizumab (total cost/patient: 566,718 SEK vs 691,542 SEK). Cost savings with fingolimod were 40,402 SEK/patient after 1 year and 301,730 SEK/patient after 10 years. Treatment with natalizumab was 18% more expensive than fingolimod therapy after 1 year and 23% more expensive after 10 years.Limitations:Based on the CHMP assessment, it was assumed that fingolimod and natalizumab have similar efficacy. The analysis was conducted for Sweden, and caution is needed in extrapolating the results to other countries.Conclusion:Fingolimod is cost-saving compared with natalizumab for the treatment of relapsing–remitting multiple sclerosis in Sweden.

Natalizumab Use in Patients With Crohnʼs Disease (CD) and Relapsing Multiple Sclerosis (MS): Updated Utilization and Safety Results

Natalizumab was approved by the FDA in 2008 for adult patients with moderately to severely active CD with evidence of inflammation who have had an inadequate response to, or are unable to tolerate, conventional CD therapies and inhibitors of TNF-α. The TYSABRI Outreach: Unified Commitment to Health (TOUCH®) Prescribing Program, Crohn's Disease: Investigating Natalizumab through Further Observational Research & Monitoring (CD INFORM), TYSABRI Global Observation Program In Safety (TYGRIS), and TYSABRI® Pregnancy Exposure Registry (TPER) are ongoing risk management activities designed to further evaluate the safety of natalizumab. This report summarizes recent data on natalizumab utilization and safety in patients with Crohn's disease (CD) and relapsing multiple sclerosis (MS). TOUCH® is a mandatory prescribing program for all patients, prescribers, pharmacies and infusion centers in the US using natalizumab. TOUCH® is designed to inform about the risk of progressive multifocal leukoencephalopathy (PML); warn against concurrent use with antineoplastic, immunosuppressant, or immunomodulating agents, and in patients who are immunocompromised; and promote early diagnosis of PML and timely discontinuation of natalizumab in the event of suspected PML. CD INFORM, a post-marketing commitment, collects patient history, efficacy as assessed by the Harvey Bradshaw Index (HBI), Health Related Quality of Life outcomes, and serious adverse events (SAE) in CD patients on natalizumab therapy. TYGRIS, also a post-marketing commitment, is evaluating the long-term safety of natalizumab in MS. Post-marketing surveillance data are also collected. TPER evaluates the outcomes of pregnancy in women with CD and MS exposed to natalizumab. As of 30 June 2012, ˜104,300 patients have been exposed to natalizumab in the post-marketing setting (103,259 MS; 1,041 CD),. As of 01 August 2012, 271 cases of PML have been confirmed (270 MS, 1 CD). Of the 271 natalizumabtreated patients who developed PML, 212 (78%) had survived, exhibiting varying levels of disability and there were 59 (22%) deaths. Presence of anti-JCV antibodies, prior treatment with immunosuppressants and longer treatment duration with natalizumab, especially beyond 2 years, are identified risk factors for potential development of PML. As of 07 August 2012, 163 patients were enrolled in CD INFORM with the number of natalizumab infusions ranging from 1-56, with a mean and median of 14.6 and 10, respectively. The average HBI at time of entry for these patients was 8.2 (range 0 to 28). Of the 99 CD patients with an HBI assessment after receiving 6 months of natalizumab therapy, the average total score was 4.8, a mean decrease of 2.8 points from baseline. Cumulatively, as of 07 August 2012, there were 93 SAEs occurring in 51 patients reported in CD INFORM, 4 patients experienced 8 SAEs that were considered treatment related. As of 23 May 2012, 375 women (7 with CD) were prospectively enrolled in the TPER with372 outcomes reported, including 8 twin pregnancies resulting in 2 outcomes for each pregnancy. Current exposure and safety data from patients receiving natalizumab in both indications will be presented. Cumulative data from both indications suggest a safety profile consistent with natalizumab product labeling.

DOES NATALIZUMAB TREATMENT INCREASE THE RISK OF HERPES SIMPLEX ENCEPHALITIS IN MULTIPLE SCLEROSIS? CASE AND DISCUSSION

This report presents the 4th documented case worldwide of herpes simplex encephalitis in multiple sclerosis (MS) patients on natalizumab and the first case in the UK. Natalizumab is indicated for...

Natalizumab use in pediatric patients with relapsing-remitting multiple sclerosis

BackgroundNot all pediatric patients with relapsing-remitting multiple sclerosis (MS) may respond to traditional disease-modifying therapies. Natalizumab has been shown to be effective but is currently only approved in adults. ObjectiveTo analyze the safety and efficacy of natalizumab in patients under 18 years of age diagnosed with MS. MethodData for pediatric patients with MS treated with natalizumab in a compassionate use setting were retrospectively collected and analyzed. ResultsValid data were obtained for nine patients under 18 years from seven different centers (mean age, 15 years 4 months [range 9.8–17.7]; 5 were boys). Patients received a median of 17 infusions of natalizumab (range, 2–31) and eight received at least 12 infusions. For these 8 patients, the median score on the Expanded Disability Status Scale decreased from 3.0 to 1.0 and the median annualized relapse rate decreased from 3.0 to 0. After 12 months, no patients reported gadolinium-enhancing lesions compared to seven at baseline. Four post-baseline adverse events occurred and one patient discontinued due to hypersensitivity reaction. ConclusionNatalizumab is a highly effective treatment as a second-line option in pediatric patients. In as far as the limited numbers allowed comparisons, the safety and efficacy of natalizumab in children was in line with the experience published in adult populations.