Efficacy Of Interferon Beta Research Articles

Incidence, characterization, and clinical impact analysis of peginterferon beta1a immunogenicity in patients with multiple sclerosis in the ADVANCE trial.

Efficacy of interferon beta in multiple sclerosis (MS) can be dampened in patients who develop neutralizing antidrug antibodies (NAbs). Peginterferon beta1a is an interferon conjugated with a polyethylene glycol (PEG) moiety. Pegylation increases a drug's half life and exposure, and may also reduce immunogenicity. The objective of this study was to characterize the incidence and impact of immunogenicity to peginterferon beta1a over 2 years in patients with MS. Patients with relapsing-remitting MS (N = 1512) were randomized to subcutaneous peginterferon beta1a 125 μg every 2 or 4 weeks, or placebo, for 1 year; patients in the placebo group were rerandomized to active treatment in year 2. The incidence and titers of binding antibodies (BAbs) and NAbs to interferon and antibodies to PEG (anti-PEG) were assessed in analytically validated assays. The clinical impact of immunogenicity on relapse and magnetic resonance imaging endpoints was evaluated. Over 2 years, 6%, less than 1%, and 7% of patients developed anti-interferon BAbs, NAbs, and anti-PEG antibodies, respectively. There was no discernible clinically meaningful effect of antibody status on the pharmacodynamic, efficacy, or safety parameters evaluated, although these analyses were limited by the low incidence of treatment-emergent antibodies. The treatment effect of peginterferon beta1a in patients with relapsing-remitting MS is not expected to be attenuated by immunogenicity.

Efficacy of interferon-beta plus ribavirin combination treatment on the development of hepatocellular carcinoma in Japanese patients with chronic hepatitis C.

Although there is much evidence of an antitumor effect of pegylated interferon (IFN)-α-based treatment, limited data is available about that of IFN-β-based treatment. Our goal was to evaluate the impact of IFN-β plus ribavirin (RBV) treatment on the suppression of hepatocellular carcinoma (HCC). This retrospective, multicenter study consisted of 124 chronic hepatitis C patients who were treated with IFN-β plus RBV treatment, including 61 with advanced fibrosis and five with pretreatment HCC. All participants were followed for a median of 2.8 years (range, 2.2-3.2) after the end of their antiviral treatment. The data of 112 patients who finished the treatment were available for analysis. Cox proportional hazard analyses were performed to determine factors significantly associated with HCC development. Cumulative incidence curves for HCC were plotted using the Kaplan-Meier method and differences between groups were assessed using the log-rank test. The 2.9% rate of HCC development of patients with sustained virological response (SVR) was significantly lower (P = 0.027) than the 15.9% of non-SVR patients. Interestingly, no significant difference was observed between the rates of HCC development of patients with and without advanced fibrosis (P = 0.733), even though the SVR rate of patients with advanced fibrosis was significantly lower than that of those without advanced fibrosis (P < 0.001). Stepwise multivariable Cox analysis extracted that only SVR was significantly associated with HCC development (hazard ratio, 0.20; 95% confidence interval, 0.03-0.84, P = 0.027). SVR was significantly associated with a lower risk of HCC development after IFN-β plus RBV treatment.

Human herpesvirus 6 and effectiveness of interferon beta 1b in multiple sclerosis patients

Human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV) have been repeatedly associated with multiple sclerosis (MS) pathogenesis. Also, it has been speculated that, besides its immunomodulatory properties, the efficacy of interferon beta (IFN-beta) in treating the disease may be related to its antiviral properties. The objectives of this study were to evaluate the in vivo antiviral effect of IFN-beta-1b over HHV-6 and EBV and to analyze whether such effect could be involved in its effectiveness in MS. A total of 54 patients with MS were included in an observational, multicentric, 24-month study. HHV-6 and EBV were detected by qPCR in blood and serum samples. IFN-beta-1b effectiveness was evaluated by presence, number and severity of relapses, reduction in the relapse rate, disability progression, and response to the treatment. Patients with HHV-6 in blood had a higher risk of severe relapses (P=0.01) and bad response (P=0.03). HHV-6 was detected more frequently during relapses than in remission in blood (P=0.024) and in serum (P=0.0002). Patients with HHV-6 in serum had more relapses (P=0.02), lesser reduction in the relapse rate (P=0.04), and a lower proportion of responders (P=0.02) than those without HHV-6 active replication. However, any association between EBV and clinical parameters could not be found. We concluded that presence of HHV-6 in blood and serum during IFN-beta treatment could be a good marker of poor response.

Managing MS in a changing treatment landscape

Increasing options are dictating the development of new algorithms to provide guidance in the treatment of people with multiple sclerosis (MS). There is a wealth of evidence on the safety and efficacy of interferon-beta and glatiramer acetate, which have been used in Europe and in the United States for more than 10years. The spectrum of approved indications for these conventional disease modifying therapies includes the treatment of relapsing-remitting MS, secondary progressive MS, and the clinically isolated syndrome. Beyond these therapies we already have the recently introduced antibody natalizumab and, in some countries, the immunosuppressive agent mitoxantrone. Oral therapies are expected in the near future, with the sphingosin-1-phosphate receptor modulator fingolimod approved in the US and the EU and the purine nucleoside analogue cladribine in Australia and Russia. The evidence on all of these conventional and novel therapeutics is reviewed in this paper to provide an overview of the changing landscape of MS treatment.

A Systematic Review on the Efficacy of Interferon Beta in Relapsing Remitting Multiple Sclerosis; Comparison of Different Formulations

A Systematic Review on the Efficacy of Interferon Beta in Relapsing Remitting Multiple Sclerosis; Comparison of Different Formulations

The Efficacy of Interferon Beta in Delaying Conversion to Clinically Definite Multiple Sclerosis

More than half of patients with a clinically isolated syndrome (CIS) develop clinically definite multiple sclerosis (CDMS). Patients at high risk for CDMS often present with asymptomatic lesions characteristic of CDMS on magnetic resonance imaging scans, although an absence of asymptomatic lesions is not atypical. Phase 3 studies of interferon beta in patients with a CIS suggest that this treatment can delay conversion to CDMS and reduce the risk of new asymptomatic white matter lesions. We reviewed phase 3 studies (CHAMPS, BENEFIT, and ETOMS) and post hoc analyses assessing the efficacy of interferon beta in delaying CDMS in patients with a CIS. The evidence supports early initiation of treatment.

A meta-analysis of interferon-beta in the secondary progressive multiple sclerosis

To systematically review the clinical efficacy of interferon-beta in secondary progressive multiple sclerosis. A systematically review of Cochrane were conducted. The authors searched in electronic literatures of Medline (1980. 1-2008. 1), Ovid (1980. 1-2008. 1), Pubmed (1980. 1-2008. 1), CBMdisc (1980. 1-2008. 1), Cochrane Library (2008. 1) and hand-searched the relevant literatures and symposium reports. The randomized controlled trials of interferon-beta were assessed in secondary progressive MS patients. After evaluating the quality of literatures and extracting the valid data, the authors assessed the randomized controlled trials of interferon-beta in secondary progressive MS patients. RevMan 4.2.3 software was used. Based upon the testing result of heterogeneity, fixed or random effect model was employed to calculate the odds ratio (OR) and 95% CI. Six RCTs of 3115 patients were included. The results indicated that interferon-beta could reduce 1 and 2-year progression rate (OR = 0.73, 95% CI = 0.61-0.88 and OR = 0.84, 95% CI = 0.72-0.98) and lower the relapses rate (OR = 0.67, 95% = 0.55-0.82). Subgroup analysis suggested that relapsing women and patients during the two years before the study benefit much more from interferon-beta (OR = 0.69, 95% CI = 0.53-0.92 vs. OR = 0.73, 95% CI = 0.55-0.97). The treatment of interferon-beta in secondary progressive multiple sclerosis could reduce 1 and 2-year progression rate and lower the relapses rate.

Multiple sclerosis and systemic sclerosis: efficacy of interferon beta on skin lesions

We report the clinical observation of interferon beta-1a effectiveness in the treatment of skin lesions in a patient affected by multiple sclerosis (MS) and systemic sclerosis (SSc),1 suggesting a common...

Comparison of interferon beta products and azathioprine in the treatment of relapsing-remitting multiple sclerosis

We compared the relative efficacy of interferon beta (IFNbeta) products and azathioprine (AZA) in the treatment of relapsing- remitting multiple sclerosis (RRMS). Ninety-four previously untreated patients of short duration with RRMS were randomly allocated to the two treatment groups. The first group received IFNbeta products (Betaferon,Avonex or Rebif); the second group received AZA for 12 months. Response to treatment was assessed at 3, 6, and 12 months after starting therapy. The mean number of relapse during one year of the study was lower in the AZA group than in the IFNbeta products group (0.28 vs. 0.64, P < 0.05). After 12 months, 57.4% of patients receiving IFNbeta products remained relapse free compared with 76.6% of those given AZA. The Expanded Disability Status Scale (EDSS) decreased by 0.30 units in IFNbeta-treated patients (P < 0.05) and 0.46 in AZAtreated patients (P < 0.001). Treatment with IFNbeta products and AZA significantly reduces the relapse rate and EDSS score in patients with RRMS, while AZA is more effective than the IFNbeta formulations.

A randomized study of two interferon- beta treatments in relapsing–remitting multiple sclerosis

To investigate whether the efficacy of interferon-beta (IFNbeta) treatment of relapsing-remitting MS (RR-MS) was influenced by type, dose, and frequency of administration. From June 1996 through October 1997, the authors offered participation to all Danish RR-MS patients who met the following criteria: definite MS, at least two relapses within 2 years, age 18 to 55, and an Expanded Disability Status Scale (EDSS) score of < or = 5.5. The study was multicenter, controlled, open-label, randomized, head-to-head comparing IFNbeta-1a 22 microg once a week (n = 143) with IFNbeta-1b 250 microg every other day (n = 158), both subcutaneously, for 24 months. Patients who declined randomization were offered treatment with IFNbeta-1b 250 microg every other day (n = 120). The primary end-points were the annualized relapse rate, the time to first relapse, and neutralizing antibody formation. The secondary endpoint was time to sustained progression. The annual relapse rates were virtually equal in the two arms of the randomized study (IFNbeta-1a: 0.70; IFNbeta-1b: 0.71); so were the time to first relapse and the time to sustained progression. In the nonrandomized patients (IFNbeta-1b), the annual relapse rate was not significantly different, but the time to progression was shorter. In this study, 250 microg interferon-beta-1b administered every other day did not prove clinically superior to once-a-week administration of 22 microg interferon-beta-1a.

The IFNβ treatment of multiple sclerosis (MS) in clinical practice: the experience at the MS Center of Bari, Italy

This independent, population-based surveillance study monitored, in clinical practice, the efficacy of interferon beta (IFNbeta) products in 1173 patients with multiple sclerosis (MS) from the Department of Neurological and Psychiatric Sciences, University of Bari, Italy. Relapses and Expanded Disability Status Scale (EDSS) scores were evaluated for up to 6 years for Avonex, Betaferon and Rebif 22 groups, and for up to 3 years for the Rebif 44 group. IFNbeta products produced significant reductions from baseline in relapse rates at 2, 4 and >4 years (p<0.0001), with no differences among treatments (p=0.2). A modest significant (p<0.05) increase of EDSS was observed in all treatment groups from baseline to 48 months, followed thereafter by a plateau. The IFNbeta-1b group showed more withdrawals (19%) compared with Avonex (6%) and Rebif (7%) at 6 years.

Western vs optic-spinal MS

In the current issue of Neurology , Saida et al.1 report the results of a randomized, controlled study of two doses of interferon beta-1b in Japanese patients with multiple sclerosis (MS). The study demonstrated superiority of the higher dose, consistent with the results seen in the North American study.2 Unlike the North American study, the study was not placebo-controlled. However, it was conducted between 1995 and 1999, well after the positive results of the North American interferon beta-1b study were announced, and the investigators believed that it would be unethical to conduct a placebo-controlled study. The efficacy of interferon beta in relapsing remitting patients with MS is well established. What does the current study add? This is the first study of interferon beta treatment from Asia. Ethnic differences are often associated with genetic variations; pharmacogenetic studies addressing responsiveness to interferon beta therapy are in their infancy, but …

Optimising MS disease-modifying therapies: antibodies in perspective

A proportion of people with multiple sclerosis (MS) treated with interferon (IFN) a develop neutralising anti-IFN beta antibodies (NABs). The immunogenicity of the available commercial compounds relates to the genetic structure of the IFN beta molecule, its mode of production, glycosylation status, aggregate formation, commercial formulation, potency, dose, frequency and, possibly, route of administration. At present, it is not possible to predict who will develop NABs usually appear within the first 2 years of starting therapy. In patients treated with IFN beta in whom NABs persist for a significant period of time, their presence is associated with a reduction in both the biological effects and clinical efficacy. Approximately one third of NAB-positive patients with a titre > 20 NU/mL will revert to NAB-negative status with long-term follow-up. The persistence of NABs appears to be linked to the type of IFN beta treatment as well as the titre of antibodies. The overall efficacy of IFN beta and, hence, of any biological disease-modifying treatment (DMT) would be substantially improved if the development of NABs could be prevented or reversed. Although the overall efficacy of IFN beta in MS is relatively modest, the efficacy in individuals who remain NAB-negative is considerably better than in those who become persistently NAB-positive. One could argue that when comparing the 'true' clinical efficacy of different IFN beta products, the comparisons should be limited to the cohorts that remain NAB-negative. As a corollary, the therapeutic efficacy of IFN beta could be maximised if patients who tolerate higher-dose preparations could be prevented from developing persistent NABs. Strategies employed to prevent or reverse the development of NABs with other biological compounds (e. g. insulin, factor VIII, IFN beta, recombinant human erythropoietin) include improvements in the manufacturing process, immunosuppression, induction of tolerance and deimmunisation, and these should be considered in relation to biological DMT therapy as part of future clinical studies.

Treatment of inflammatory and paraproteinemic neuropathies.

Acquired demyelinating and inflammatory neuropathies encompass a number of acute and chronic autoimmune conditions characterized by variable degrees of clinical involvement. These disorders, including Guillain-Barre syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN), and paraprotein-associated neuropathy, have an overall annual incidence of 2-4/100,000 worldwide and are potentially treatable. Over the last few years, several investigations have helped clarify the pathogenesis of immune neuropathies and the definition of molecular targets involved in these diseases, thus providing firmer grounds for treatment with classical immunosuppressive drugs and new biological agents. In GBS and related variants, which are characterized by cellular inflammation and alterations of the blood-nerve barrier, randomized clinical trials show that plasma exchange (PE) and intravenous immunoglobulin (IVIg) are equally effective as disease-modifying treatments, although IVIg has been adopted as the favourite treatment in most centres. In CIDP, controlled clinical trials have established the efficacy of oral prednisone, PE and IVIg, with intermittent IVIg treatment or corticosteroids being usually preferred. Adding azathioprine can help keep lower the required dose of prednisone, while other immunosuppressive agents, such as cyclophosphamide and cyclosporin A may have side effects, limiting their use to selected cases. Currently, the efficacy of interferon beta and alfa is under evaluation. Controlled trials support the view that IVIg is the treatment of choice in MMN. Patients resistant to IVIg administration may benefit of treatments which deplete B cells, such as cyclophosphamide and rituximab. Demyelinating neuropathies associated with circulating paraproteins are clinically heterogeneous, depending on the reactivity and type of the monoclonal (M) protein. In many cases, neuropathies associated with IgM M proteins are not treated because of their slow progression. In patients with a disabling or rapid progression, small trials have shown short-term benefits from IVIg or PE. Recently, fludarabine and rituximab have been reported as beneficial in selected cases.

Long-term benefits of early and high doses of interferon β-1a treatment in relapsing–remitting multiple sclerosis

The efficacy of interferon beta (IFN b) in the treatment of relapsing /remitting multiple sclerosis (RRMS) is now well established. This agent has been shown to reduce the frequency and severity of relapses and to slow progression of neurological disability [1 /5]. In addition, magnetic resonance imaging (MRI) studies have demonstrated that IFN b reduces the number of active lesions and the accumulation of total MRI lesion load over time [6 /8]. Three IFN b products are currently available and licensed for use in MS, but at different doses and with different dosing frequencies and routes of administration. For many clinicians this raises questions about whether the products differ in their efficacy, which dose is optimal, and whether the route of administration is important. In addition, they may be unsure of when during the disease course they should initiate therapy with this agent. Evidence has accumulated during the last several years indicating that, in order to achieve maximum benefit, therapy with IFN b should be with as high a dose as possible and begin early after diagnosis of the disease. The aim of the present paper is to show why early treatment of RRMS with IFN b is likely to be beneficial and to provide evidence for a dose-response. It also describes recently published results with IFN b1a, which confirm the long-term benefits of early and high-dose treatment. 2. Why IFN b therapy should start early

Interferon for acute hepatitis C.

Acute hepatitis C virus (HCV) infection progresses to chronicity in the majority of patients. In order to prevent the progression to chronic disease, several studies have assessed interferon in patients with acute hepatitis C. The aim of this review was to assess the efficacy of interferon in acute HCV infection. We searched MEDLINE, the Cochrane Controlled Trials Register, and the abstracts of the American Association for the Study of Liver Diseases (June 2001). We also contacted pharmaceutical companies to obtain unpublished trials. Randomised clinical trials comparing interferon with placebo or no treatment, and published as an article, abstract, or letter were selected. No language limitations were used. Two reviewers independently assessed trial quality and extracted data. The following endpoints were analysed: normalization of alanine aminotransferase (ALT) activity at the end of treatment (biochemical ETR); sustained ALT normalization at the end follow-up (biochemical SR); disappearance of serum HCV RNA by polymerase chain reaction assay at the end of treatment (virologic ETR) and at the end of follow-up (virologic SR). Histologic data and adverse events were also recorded. Assessment of drug efficacy used the methods of Peto and Der Simonian and Laird. Six randomised trials involving 206 patients with acute hepatitis C met the inclusion criteria. Four trials assessing interferon alfa-2b in 141 patients, all with transfusion-acquired acute hepatitis C, were included. They demonstrated no significant heterogeneity in the outcomes assessed. When compared with no treatment, interferon alfa-2b was associated with an increase in the rates of virologic ETR and SR by 45% (95% CI 31-59%, P < 0.00001) and 29% (95% CI 14-44%, P = 0.0002), respectively. The virologic ETR was 42% (95% CI: 30-56%) in the interferon alfa-2b group versus 4% (95% CI 0-13%, P < 0.00001) in the control group. At the end of follow-up, a virologic SR was seen in 32% (95% CI 21-46%) of interferon-treated patients versus only 4% (95% CI 0-13%, P = 0.00007) of controls. The tolerability of therapy, or the impact of interferon alfa-2b on hepatic histology, was not reported. Two trials assessed interferon beta in a total 65 patients. The efficacy of interferon beta could not be assessed, however, due to heterogeneity of these trials. Interferon alfa is effective in improving biochemical outcomes and achieving sustained virologic clearance in patients with transfusion-acquired acute hepatitis C. The effect on long-term clinical outcomes could not be assessed due to limitations in the current data.