OBJECTIVETo systematically evaluate the safety and efficacy of natalizumab in treating multiple sclerosis (MS) and Crohn's disease(CD).

METHODSLiteratures from 1998 to 2009 were searched in databases including MEDLINE,EMBASE,The Cochrane Library, and CBM for randomized controlled trials (RCTs) and quasi-randomization controlled trials. Quality assessment and data extraction were conducted using the Cochrane Collaboration's RevMan 5.0 software and then a Meta analysis was performed. The main indicators included the rate of adverse reactions, the rate of serious adverse reactions,response rate,and remission rate.

RESULTSThirteen trials entered the final analysis. The main findings in the MS trials included: the rate of serious and general adverse effects were no significantly different among different groups (P>0.05). The new lesions rate was not significantly different within 3 months after treatment [RR=0.99, 95%CI (0.82, 1.18), P=0.87], but was significantly lower in 6 months in the treatment group [RR=0.45, 95%CI (0.33, 0.60), P<0.00001], and such advantage was maintained till 2 years later [RR=0.49, 95%CI (0.45, 0.53), P<0.00001]. The 2-year relapse rate was also significantly lower in the treatment group [RR=0.51, 95%CI (0.38, 0.69), P<0.0001]. The main findings in CD trials were as follows: The incidences between serious reactions and general adverse reactions were not significantly different (P>0.05). The remission rate was not significantly different between treatment group and control group in the 2nd week [RR=4.67, 95%CI (0.65, 33.26), P=0.12], but became significantly higher in the treatment group after 12 weeks [RR=1.46, 95%CI (1.26, 1.70), P<0.00001]. The response rate was significantly higher in the treatment group [RR=1.53, 95%CI (1.15, 2.03), P=0.004].

CONCLUSIONSThe rates of serious and general adverse reactions are not remarkably increased after natalizumab treatment for both MS and CD. The new lesions rate and 2-year relapse rate of MS as well as the response rate and remission rate of CD are all improved after natalizumab treatment,especially after long-term administration. Although severe adverse effect such as progressive multifocal leukoencephalopathy may occur,its clinical application can be further promoted after cautiously balancing the benefits and risks.

Antibodies, Monoclonal, Humanized ; therapeutic use ; Crohn Disease ; drug therapy ; Humans ; Multiple Sclerosis ; drug therapy ; Natalizumab ; Treatment Outcome

OBJECTIVES: John Cunningham virus (JCV) is a polyoma virus that infects humans, mainly in childhood or adolescence, and presents no symptomatic manifestations. JCV can cause progressive multifocal leukoencephalopathy (PML) in immunosuppressed individuals, including those undergoing treatment for multiple sclerosis (MS) and neuromyelitis optica (NMO). PML is a severe and potentially fatal disease of the brain. The prevalence of JCV antibodies in human serum has been reported to be between 50.0 and 90.0%. The aim of the present study was to review worldwide data on populations of patients with MS and NMO in order to establish the rates of JCV seropositivity in these individuals. METHODS: The present review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and used the following search terms: “JCV” OR “JC virus” AND “multiple sclerosis” OR “MS” OR “NMO” OR “neuromyelitis optica” AND “prevalence.” These terms were searched for both in smaller and in larger clusters of words. The databases searched included PubMed, MEDLINE, SciELO, LILACS, Google Scholar, and Embase. RESULTS: After the initial selection, 18 papers were included in the review. These articles reported the prevalence of JCV antibodies in the serum of patients with MS or NMO living in 26 countries. The systematic review identified data on 29,319 patients with MS/NMO and found that 57.1% of them (16,730 individuals) were seropositive for the anti-JCV antibody (range, 40.0 to 69.0%). CONCLUSIONS: The median worldwide prevalence of JCV among adults with MS or NMO was found to be 57.1%.
Adolescent ; Adult ; Antibodies ; Brain ; Humans ; JC Virus* ; Leukoencephalopathy, Progressive Multifocal ; Multiple Sclerosis* ; Natalizumab ; Neuromyelitis Optica* ; Polyomavirus ; Prevalence*

OBJECTIVES: John Cunningham virus (JCV) is a polyoma virus that infects humans, mainly in childhood or adolescence, and presents no symptomatic manifestations. JCV can cause progressive multifocal leukoencephalopathy (PML) in immunosuppressed individuals, including those undergoing treatment for multiple sclerosis (MS) and neuromyelitis optica (NMO). PML is a severe and potentially fatal disease of the brain. The prevalence of JCV antibodies in human serum has been reported to be between 50.0 and 90.0%. The aim of the present study was to review worldwide data on populations of patients with MS and NMO in order to establish the rates of JCV seropositivity in these individuals.METHODS: The present review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and used the following search terms: “JCV” OR “JC virus” AND “multiple sclerosis” OR “MS” OR “NMO” OR “neuromyelitis optica” AND “prevalence.” These terms were searched for both in smaller and in larger clusters of words. The databases searched included PubMed, MEDLINE, SciELO, LILACS, Google Scholar, and Embase.RESULTS: After the initial selection, 18 papers were included in the review. These articles reported the prevalence of JCV antibodies in the serum of patients with MS or NMO living in 26 countries. The systematic review identified data on 29,319 patients with MS/NMO and found that 57.1% of them (16,730 individuals) were seropositive for the anti-JCV antibody (range, 40.0 to 69.0%).CONCLUSIONS: The median worldwide prevalence of JCV among adults with MS or NMO was found to be 57.1%.
Adolescent ; Adult ; Antibodies ; Brain ; Humans ; JC Virus ; Leukoencephalopathy, Progressive Multifocal ; Multiple Sclerosis ; Natalizumab ; Neuromyelitis Optica ; Polyomavirus ; Prevalence

Here we report a case of pediatric multiple sclerosis treated with interferon beta-1b. Interferon beta is widely used in adult patients with multiple sclerosis (MS). However, its effects and safety in pediatric patients have not been well established. Although supporting data are limited, the use of disease modifying therapies (DMTs) such as interferon beta-1b is recommended early in treatment of children with MS. Reports of interferon beta treatment in pediatric MS patients in Korea are rare. In this report, we describe a Korean girl who was effectively treated with interferon beta-1b for three years. There were no relapses or serious side effects. Therefore, this report provides evidence supporting the use of interferon beta in pediatric MS patients in Korea and other Asian countries. We also reviewed current medical treatment of MS, including some DMTs and second-line treatment options such as natalizumab and cyclophosphamide, and several new oral agents such as fingolimod.
Adult ; Antibodies, Monoclonal, Humanized ; Asian Continental Ancestry Group ; Child ; Cyclophosphamide ; Humans ; Interferon-beta ; Interferons ; Korea ; Multiple Sclerosis ; Propylene Glycols ; Recurrence ; Sphingosine ; Fingolimod Hydrochloride ; Interferon beta-1b ; Natalizumab

Multiple sclerosis (MS) is an inflammatory autoimmune disorder of the central nervous system (CNS) and one of the most common disabling neurological diseases of young adults. Although the exact mechanisms involved in MS pathogenesis remain unclear, MS is believed to be caused by interactions between as yet unidentified environmental factors and susceptibility genes. Symptoms commonly occurred in MS include visual disturbance; weakness; spasticity; sensory disturbances; ataxia; bladder, bowel, and sexual dysfunction; fatigue; affective symptoms; and cognitive impairment. Most patients initially undergo a relapsing-remitting course, however, without treatment, the majority of them make a transition to the secondary progressive form. The clinical diagnosis is based on demonstrating neurological lesions, predominantly in the white matter, that are disseminated over space with the lapse of time. The key to the successful MS management is to prevent disability. Although there is no effective cure for MS, therapies are available that mitigate the course of the disease, treat relapses and improve symptoms, all of which place a significant impact on patients' quality of life. Recent clinical trials suggest that early identification and treatment are critical to optimize the treatment benefit. Currently six agents have been specifically approved for mitigating the course of MS. These include three formulations of interferon beta, glatiramer acetate, mitoxantrone, and natalizumab. Recent advances in understanding of immune pathogenesis lead us to new therapeutic approaches focused on precise target mechanisms. Many ongoing clinical trials will provide better treatment protocols in near future.
Antibodies, Monoclonal, Humanized ; Central Nervous System ; Humans ; Hypogonadism ; Interferon-beta ; Mitochondrial Diseases ; Mitoxantrone ; Multiple Sclerosis ; Natalizumab ; Ophthalmoplegia ; Peptides ; Quality of Life ; Recurrence ; Urinary Bladder ; Young Adult

Multiple sclerosis (MS) is an inflammatory autoimmune disorder of the central nervous system (CNS) and one of the most common disabling neurological diseases of young adults. Although the exact mechanisms involved in MS pathogenesis remain unclear, MS is believed to be caused by interactions between as yet unidentified environmental factors and susceptibility genes. Symptoms commonly occurred in MS include visual disturbance; weakness; spasticity; sensory disturbances; ataxia; bladder, bowel, and sexual dysfunction; fatigue; affective symptoms; and cognitive impairment. Most patients initially undergo a relapsing-remitting course, however, without treatment, the majority of them make a transition to the secondary progressive form. The clinical diagnosis is based on demonstrating neurological lesions, predominantly in the white matter, that are disseminated over space with the lapse of time. The key to the successful MS management is to prevent disability. Although there is no effective cure for MS, therapies are available that mitigate the course of the disease, treat relapses and improve symptoms, all of which place a significant impact on patients' quality of life. Recent clinical trials suggest that early identification and treatment are critical to optimize the treatment benefit. Currently six agents have been specifically approved for mitigating the course of MS. These include three formulations of interferon beta, glatiramer acetate, mitoxantrone, and natalizumab. Recent advances in understanding of immune pathogenesis lead us to new therapeutic approaches focused on precise target mechanisms. Many ongoing clinical trials will provide better treatment protocols in near future.
Antibodies, Monoclonal, Humanized ; Central Nervous System ; Humans ; Hypogonadism ; Interferon-beta ; Mitochondrial Diseases ; Mitoxantrone ; Multiple Sclerosis ; Natalizumab ; Ophthalmoplegia ; Peptides ; Quality of Life ; Recurrence ; Urinary Bladder ; Young Adult

BACKGROUND AND PURPOSE: The anti-John-Cunningham virus (JCV)-antibody serostatus and index are used in the risk stratification of progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS) patients treated with natalizumab. However, little information on these parameters is available for Asian countries. The purpose of this study was to determine the rate of seropositivity, index, and longitudinal index evolution in Korean patients with MS. METHODS: The antibody seroprevalence was analyzed in 355 samples from 187 patients with clinically isolated syndrome or MS using a second-generation, two-step, enzyme-linked immunosorbent assay. A 4-year longitudinal evaluation was applied to 66 patients. RESULTS: The overall antibody seroprevalence was 80% (n=149). Among antibody-positive patients, the index had a median value of 3.27 (interquartile range, 1.52–4.18), with 77% (n=114) and 56% (n=83) of patients having indices >1.5 and >3.0, respectively. The serostatus of 59 (89%) of the 66 patients did not change during the longitudinal analysis, while 3 (6%) of the 53 patients who were initially seropositive reverted to seronegativity, and 2 (15%) of the 13 patients who were initially seronegative converted to seropositivity. All patients with a baseline index >0.9 maintained seropositivity, and 92% of patients with a baseline index >1.5 maintained this index over 4 years. No patients developed PML (median disease duration, 8 years). CONCLUSIONS: The seroprevalence and index of anti-JCV antibodies in Korean patients with MS may be higher than those in Western countries.
Antibodies ; Asia ; Asian Continental Ancestry Group ; Enzyme-Linked Immunosorbent Assay ; Humans ; JC Virus ; Leukoencephalopathy, Progressive Multifocal ; Multiple Sclerosis ; Natalizumab ; Seroepidemiologic Studies

Novel biologic agents that selectively target specific molecules and pathways have been developed recently for the management of inflammatory bowel disease (IBD). Anti-TNF-alpha, an antibody to TNF-alpha is one of the first newly developed drugs to dramatically improve the symptoms of patients with IBD. Therapy with anti-TNF-alpha demonstrates a new paradigm for management of IBD and early treatment with these drugs has demonstrated increased benefit. However, more than one-third of the patients have lost response to the drug. Also, there is the problem of antibody formation. Therefore, enormous efforts to develop novel drugs as an alternatives to anti-TNF-alpha are underway. Anti CD4+ T cell cytokine including IL-12/23 and IL-17 blockers, selective anti-adhesion molecules known as natalizumab, vedolizumab and alicaforsen, T-cell proliferation inhibitors, anti-inflammatory cytokines, immune stimulators, growth factors and mitogen activated protein kinase (MAPK) inhibitors are among the novel therapeutic agents that are currently being investigated for efficacy and safety in the management of IBD. The aim of this paper is to review current knowledge concerning the mechanism of action, the short and long term efficacy, and the safety of these novel biologic therapies, as well as that of anti-TNF-alpha, in IBD.
Antibodies, Monoclonal, Humanized ; Antibody Formation ; Biological Agents ; Biological Therapy ; Cytokines ; Humans ; Inflammatory Bowel Diseases ; Intercellular Signaling Peptides and Proteins ; Interleukin-17 ; Phosphorothioate Oligonucleotides ; Protein Kinases ; T-Lymphocytes ; Tumor Necrosis Factor-alpha ; Natalizumab