- Interferon-β 1a Modulates Expression of RAGE but Not S100A12 and Nuclear Factor-κB in Multiple Sclerosis Patients. [Journal Article]
- NNeuroimmunomodulation 2017 Apr 22
- CONCLUSIONS: It appears that S100A12 participates in the pathogenesis of MS, and it seems that IFN-β 1a modulates immune responses in an S100A12-independent manner. Based on the reported anti-inflammatory effects of RAGE, it seems that RAGE may be considered as a mechanism by IFN-β 1a to modulate immune responses. NF-κB is produced permanently in the human cells and is inactive in the cytoplasm; therefore, the effects of IFN-β 1a may be related to its functions rather than expressions.
- Factors associated with adherence to disease modifying therapy in multiple sclerosis: An observational survey from a referral center in Lithuania. [Journal Article]
- MSMult Scler Relat Disord 2017; 13:107-111
- CONCLUSIONS: One third of patients were non-adherent during last three months. Worse adherence rates were associated with higher education and higher alcohol consumption. Education, alcohol consumption and quality of life scores were found to be significant factors for predicting non-adherence. We found no associations between adherence and anxiety, depression, or drugs side effects.
- Correction: Interferon β-1a for the treatment of Ebola virus disease: A historically controlled, single-arm proof-of-concept trial. [Published Erratum]
- PlosPLoS One 2017; 12(4):e0175930
- [This corrects the article DOI: 10.1371/journal.pone.0169255.].
[This corrects the article DOI: 10.1371/journal.pone.0169255.].
- Population-Based Pharmacokinetic and Exposure-Efficacy Analyses of Peginterferon Beta-1a in Patients With Relapsing Multiple Sclerosis. [Journal Article]
- JCJ Clin Pharmacol 2017 Apr 10
- Peginterferon beta-1a reduced annualized relapse rate as compared with placebo and was approved to treat multiple sclerosis patients. A population pharmacokinetic and an exposure-efficacy model were ...
Peginterferon beta-1a reduced annualized relapse rate as compared with placebo and was approved to treat multiple sclerosis patients. A population pharmacokinetic and an exposure-efficacy model were developed to establish the quantitative relationship between pharmacokinetics and annualized relapse rate. The pharmacokinetics was well described by a 1-compartment model with first-order absorption and linear elimination kinetics. Body mass index was the most significant covariate that impacted both clearance and volume of distribution, which in turn impacted area under the curve and maximum serum concentration. Cumulative monthly area under the curve and annualized relapse rate were best described by a Poisson-gamma (negative binomial) model, demonstrating that the improved efficacy of every-2-weeks dosing was driven by greater drug exposure. The results supported the superior efficacy of the every-2-week dosing regimen compared with the every-4-weeks dosing regimen.
- Multiple immune disorders after natalizumab discontinuation: After the CIRIS, the SIRIS? [Journal Article]
- RNRev Neurol (Paris) 2017 Mar 31
- Natalizumab (NTZ) is an effective treatment for patients with highly active relapsing remitting multiple sclerosis (MS). However, when the therapy must be interrupted, it is important to anticipate t...
Natalizumab (NTZ) is an effective treatment for patients with highly active relapsing remitting multiple sclerosis (MS). However, when the therapy must be interrupted, it is important to anticipate the withdrawal to avoid reactivation or disease rebound. Described here is the case of a 35-year-old woman, with a past history of beta thalassemia, bulimia and asthma, who was diagnosed with MS at age 26. She was treated initially with first-line subcutaneous (sc) immunomodulatory treatments. However, due to liver toxicity, interferon beta-1a sc was interrupted and replaced by glatiramer acetate treatment, which was well tolerated and used for several years. Unfortunately, disease progression with numerous relapses and contrast enhancement on brain MRI led to initiation of NTZ treatment. After more than 2 years of treatment, NTZ was interrupted because of pregnancy, and the patient was again put on glatiramer acetate. Eight weeks after interruption of NTZ therapy, the first signs of diabetes were observed, together with an increase in blood levels of hepatic enzymes, skin reactions such as angioedema and giant urticaria, and hypothyroidism requiring hormone supplementation. The patient delivered her baby without complications, and NTZ was reintroduced several months later. At the present time, the patient's hypothyroidism, diabetes and increased blood levels of hepatic enzymes persist, although no new skin reactions have been observed. Withdrawal of NTZ can not only lead to reactivation of the disease or its rebound, but also to autoimmune manifestations within the framework of immune reconstitution inflammatory syndrome (IRIS). This risk needs to be considered when therapy has to be interrupted, especially when a personal and/or familial past history of autoimmune disease is present.
- Reasons for discontinuation of subcutaneous interferon β-1a three times a week among patients with multiple sclerosis: a real-world cohort study. [Journal Article]
- BNBMC Neurol 2017 Mar 23; 17(1):57
- CONCLUSIONS: Potential drivers of discontinuation change over time. Improved awareness of the drivers of discontinuation could lead to targeted interventions to improve adherence.
- Subcutaneous Interferon β-1a Administration by Electronic Auto-injector is Associated with High Adherence in Patients with Relapsing Remitting Multiple Sclerosis in a Real-life Study. [Journal Article]
- NINeurol Int 2017 Feb 20; 9(1):6957
- The objective was to investigate adherence measured by an electronic auto-injector device, and self-reported adherence and treatment convenience in subjects with relapsing remitting multiple sclerosi...
The objective was to investigate adherence measured by an electronic auto-injector device, and self-reported adherence and treatment convenience in subjects with relapsing remitting multiple sclerosis (RRMS), using an electronic auto-injector Rebismart(®) to self-inject interferon β-1a. Thirty one patients with RRMS using the electronic auto-injector Rebismart(®) for self-injecting interferon β-1a subcutaneously three times weekly were included in a real-life clinical multicenter study for 24 weeks in Finland. Mean adherence reported by the device and mean self-assessment of adherence were studied. Reasons for missing injections and treatment convenience were assessed. Association between adherence and gender and age were studied. The mean adherence calculated from the device data was 93.5%. The mean self-assessment of adherence was 96.6%. The most common reason for missing an injection was forget-fulness. Adherence (measured by the device) was not changed over time. In the high adherence group there were more females and young patients (<30 years of age). The auto-injector was found to substantially ease the treatment by 90% of the patients. The electronic auto-injector was associated with high adherence to treatment. The device was found to ease the patient's treatment and it was perceived as easy to use. It is a convenient tool to assess patient's adherence to treatment.
- Impact of adherence on subcutaneous interferon beta-1a effectiveness administered by Rebismart(®) in patients with multiple sclerosis. [Journal Article]
- PPPatient Prefer Adherence 2017; 11:415-421
- CONCLUSIONS: Patients with multiple sclerosis who self-injected INF β-1a with Rebismart(®) had excellent adherence, correlating with a high proportion of relapse-free patients and very low annualized relapse rate.
- Population Pharmacokinetics of Cladribine in Patients with Multiple Sclerosis. [Journal Article]
- CPClin Pharmacokinet 2017 Mar 02
- CONCLUSIONS: Both CdA and CAde displayed linear PK after intravenous and oral administration of CdA, with CdA renal function depending on CLCR. Trial registration number for study 25643: NCT00213135.
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- Effect of Fingolimod on Brain Volume Loss in Patients with Multiple Sclerosis. [Review]
- CDCNS Drugs 2017; 31(4):289-305
- Brain atrophy occurs at a faster rate in patients with multiple sclerosis (MS) than in healthy individuals. In three randomized, controlled, phase III trials, fingolimod reduced the annual rate of br...
Brain atrophy occurs at a faster rate in patients with multiple sclerosis (MS) than in healthy individuals. In three randomized, controlled, phase III trials, fingolimod reduced the annual rate of brain volume loss (BVL) in patients with relapsing MS (RMS) by approximately one-third relative to that in individuals receiving placebo or intramuscular interferon beta-1a. Analysis of brain volume changes during study extensions has shown that this reduced rate of BVL is sustained in patients with RMS receiving fingolimod continuously. Subgroup analyses of the core phase III and extension studies have shown that reductions in the rate of BVL are observed irrespective of levels of inflammatory lesion activity seen by magnetic resonance imaging at baseline and on study; levels of disability at baseline; and treatment history. The rate of BVL in these studies was predicted independently by T2 lesion and gadolinium-enhancing lesion burdens at baseline, and correlations observed between BVL and increasing levels of disability strengthened over time. In another phase III trial in patients with primary progressive MS (PPMS), fingolimod did not reduce BVL overall relative to placebo; however, consistent with findings in RMS, there was a treatment effect on BVL in patients with PPMS with gadolinium-enhancing lesion activity at baseline. The association between treatment effects on BVL and future accumulation of disability argues in favor of measuring BVL on a more routine basis and with a more structured approach than is generally the case in clinical practice. Despite several practical obstacles, progress is being made in achieving this goal.