interferon beta 1a [keywords]
- EVASEP: A Noninterventional Study Describing the Perception of Neurologists, Patients, and Caregivers on Caregivers' Role in the Support of Patients Suffering from Multiple Sclerosis Treated with Subcutaneous Interferon Beta 1a. [Journal Article]
- Mult Scler Int 2016.:4986073.
Background.The perception of the role of caregivers for people with multiple sclerosis (MS) is important but poorly studied, particularly in patients with low levels of disability.
Objectives.To describe the perceptions of the role of caregivers from the perspective of the caregiver, the patient, and neurologists. Methods. This observational study was conducted in France on patients with relapsing remitting MS treated with subcutaneous (SC) interferon-β-1a (IFN-β-1a) for more than 24 months.
Results.Caregiver, patients, and neurologists all considered providing moral support and fighting against the disease as the most important role of the care provider. Moral support was considered significantly more important by caregivers than the patients and neurologists (p = 0.002) and caregivers considered their role in helping patients to fight disease more important than did the neurologists (p = 0.006). Knowledge of disease and available treatments were less important among support providers than patients (p = 0.007 and p = 0.001).
Conclusion.There are many unmet needs in the perception of the role of caregivers for people with MS which need to be addressed to deliver the most effective care package for patients and to support the needs of the support provider.
- [Clinical and demographic characteristics of patients with multiple sclerosis]. [English Abstract, Journal Article]
- Rev Med Inst Mex Seguro Soc 2016.:S186-90.
Multiple sclerosis (MS) is a disease whose physiopathogenesis shows a complex interaction of genetic and environmental factors. Given that those factors have not been documented in our country, we describe the clinical and demographic characteristics from a sample of patients with MS.We carried out an observational, descriptive, cross-sectional, and retrolective study in a Center for Demyelinating Diseases. We took the information from the clinical records of a sample of patients with multiple sclerosis, who arrived to the center from April 2014 to July 2015.We obtained data from 313 patients, out of which 65.5 % were women. Mean age was 41 years (SD 11.22). Minimum age of diagnosis was 12 years and maximum, 66 years; mean age of diagnosis was 32 years (SD 9.72). With regards to clinical variables, 3.4 % presented radiologically isolated syndrome (RIS), 82 % relapsing-remitting MS (RRMS), 13.9 % secondary-progressive MS (SPMS), and 0.8 % primary-progressive MS (PPMS). Of all the patients, 10 % had first or second degree relatives with diagnosis of this disease; 16 % had foreign ancestors; 27 % were smokers. Treatment consisted of glatiramer acetate, 28 %; intramuscular interferon beta 1a, 18 %; subcutaneous interferon beta 1a, 16 %; subcutaneous interferon beta 1b, 30 %; fingolimod, 3 %; and others, 5 %.Clinical and demographic characteristics are similar to those reported in international literature. More studies would be needed to typify Mexican population with MS.
- Management Strategies for Flu-Like Symptoms and Injection-Site Reactions Associated with Peginterferon Beta-1a: Obtaining Recommendations Using the Delphi Technique. [Journal Article]
- Int J MS Care 2016 Jul-Aug; 18(4):211-8.
Flu-like symptoms (FLSs) and injection-site reactions (ISRs) have been reported with interferon beta treatments for multiple sclerosis (MS). We sought to obtain consensus on the characteristics/management of FLSs/ISRs in patients with relapsing-remitting MS based on experiences from the randomized, placebo-controlled ADVANCE study of peginterferon beta-1a.ADVANCE investigators with a predefined number of enrolled patients were eligible to participate in a consensus-generating exercise using a modified Delphi method. An independent steering committee oversaw the development of two sequential Delphi questionnaires. An average rating (AR) of 2.7 or more was defined as consensus a priori.Thirty and 29 investigators (ie, responders) completed questionnaires 1 and 2, respectively, representing 374 patients from ADVANCE. Responders reported that the incidence/duration of FLSs/ISRs in their typical patient generally declined after 3 months of treatment. Responders reached consensus that FLSs typically last up to 24 hours (AR = 3.17) and have mild/moderate effects on activities of daily living (AR = 3.34). Patients should initiate acetaminophen/nonsteroidal anti-inflammatory drug treatment on a scheduled basis (AR = 3.31) and change the timing of injection (AR = 3.28) to manage FLSs. Injection-site rotation/cooling and drug administration at room temperature (all AR ≥ 3.10) were recommended for managing ISRs. Patient education on FLSs/ISRs was advocated before treatment initiation.Delphi responders agreed on the management strategies for FLSs/ISRs and agreed that patient education is critical to set treatment expectations and promote adherence.
- Retinal measures correlate with cognitive and physical disability in early multiple sclerosis. [JOURNAL ARTICLE]
- J Neurol 2016 Aug 20.
Further studies are needed to determine the role of retinal optical coherence tomography (OCT) in non-optic neuritis (ON) eyes of patients with early MS. The objective of this study is to explore the relationship between retinal layers' thickness and cognitive as well as physical disability in patients with the early RRMS. Participants in this cross-sectional study were adults with early RRMS, stable on interferon beta-1a, or fingolimod therapy, and without a history of ON in one or both eyes. Patients were evaluated clinically, underwent a battery of cognitive tests, and a retinal OCT scan which was also performed on a group of healthy age- and gender-matched controls. We studied 47 patients with RRMS, on interferon beta-1a (N = 32) or fingolimod (N = 15), and 18 healthy controls. Multivariate analyses controlling for age, disease duration, treatment, and education when exploring cognitive function, showed that pRNFL thickness correlated negatively with 9HPT (standardized Beta -0.4, p < 0.0001), and positively with SDMT (standardized Beta 0.72, p = 0.007). In patients with early RRMS without optic neuropathy, retinal thickness measures correlated with physical disability and cognitive disability, supporting their potential as biomarkers of axonal loss.
- Predictors of first-line treatment persistence in a Portuguese cohort of relapsing-remitting multiple sclerosis. [JOURNAL ARTICLE]
- J Clin Neurosci 2016 Aug 16.
Treatment persistence in first-line injectable disease-modifying therapies (DMT) for relapsing-remitting multiple sclerosis (RRMS) is an important indicator of effectiveness. Identifying predictors of treatment discontinuation is important as there are other therapies currently available and a growing range of emerging drugs. We report a retrospective study of RRMS and clinically isolated syndrome patients followed in a University Hospital during a 13-year period with the objective of identifying predictors of treatment persistence. An evaluation of persistence on the first DMT, rates of DMT discontinuation, and reasons and predictors of discontinuation was performed. A total of 410 patients were included, 69% female, with mean disease duration of 37.8months, mean age of 34.2years and mean follow-up time of 6.1years. The first DMT was glatiramer acetate (GA) in 27.56% of patients, interferon (IFN) β-1a intramuscular in 26.34%, IFNβ-1b in 26.10%, IFNβ-1a22 in 13.66% and IFNβ-1a44 in 6.34%. Treatment was discontinued in 16.34% of patients after 1year of treatment and in 50.24% of patients in the total follow-up time, with a mean time for discontinuation of 39.80months. Higher baseline Expanded Disability Status Scale score was an independent predictor of treatment discontinuation (hazard ratio 1.35, p=0.002). After the first year, treatment persistence was 90.74% for IFNβ-1a-IM, 88.46% for IFNβ-1a44, 83.18% for IFNβ-1b, 83.19% for GA and 69.64% for IFNβ-1a22 (p=0.014). Lower frequency of administration was associated with higher persistence rates. The most common reason for treatment discontinuation was lack of efficacy in all DMT subgroups.
- Long-Term Adherence to IFN Beta-1a Treatment when Using RebiSmart® Device in Patients with Relapsing-Remitting Multiple Sclerosis. [Journal Article]
- PLoS One 2016; 11(8):e0160313.
The effectiveness of disease-modifying drugs in the treatment of multiple sclerosis is associated with adherence. RebiSmart® electronic device provides useful information about adherence to the treatment with subcutaneous (sc) interferon (IFN) β-1a (Rebif®). The aim of the study was to determine long-term adherence to this treatment in patients with relapsing-remitting multiple sclerosis (RRMS). This retrospective multicentre observational study analysed 258 patients with RRMS who were receiving sc IFN β-1a (Rebif®) treatment by using RebiSmart® until replacement (36 months maximum lifetime) or treatment discontinuation. Adherence was calculated with data (injection dosage, time, and date) automatically recorded by RebiSmart®. Patients in the study had a mean age of 41 years with a female proportion of 68%. Mean EDSS score at start of treatment was 1.8 (95% CI, 1.6-1.9). Overall adherence was 92.6% (95% CI, 90.6-94.5%). A total of 30.2% of patients achieved an adherence rate of 100%, 80.6% at least 90%, and only 13.2% of patients showed a suboptimal adherence (<80%). A total of 59.9% of subjects were relapse-free after treatment initiation. Among 106 subjects (41.1%) who experienced, on average, 1.4 relapses, the majority were mild (40.6%) or moderate (47.2%). Having experienced relapses from the beginning of the treatment was the only variable significantly related to achieving an adherence of at least 80% (OR = 3.06, 1.28-7.31). Results of this study indicate that sc IFN β-1a administration facilitated by RebiSmart® could lead to high rates of adherence to a prescribed dose regimen over 36 months.
- Capillary Zone Electrophoresis-Mass Spectrometry of Intact Proteins. [Journal Article]
- Methods Mol Biol 2016.:25-41.
Capillary electrophoresis (CE) coupled with mass spectrometry (MS) has proven to be a powerful analytical tool for the characterization of intact proteins. It combines the high separation efficiency, short analysis time, and versatility of CE with the mass selectivity and sensitivity offered by MS detection. This chapter focuses on important practical considerations when applying CE-MS for the analysis of intact proteins. Technological aspects with respect to the use of CE-MS interfaces and application of noncovalent capillary coatings preventing protein adsorption are treated. Critical factors for successful protein analysis are discussed and four typical CE-MS systems are described demonstrating the characterization of different types of intact proteins by CE-MS. These methodologies comprise the use of sheath-liquid and sheathless CE-MS interfaces, and various types of noncovalent capillary coatings allowing efficient and reproducible protein separations. The discussion includes the analysis of lysozyme-drug conjugates and the therapeutic proteins human growth hormone, human interferon-β-1a, and human erythropoietin.
- Relapse rates in patients with multiple sclerosis treated with fingolimod: Subgroup analyses of pooled data from three phase 3 trials. [Journal Article]
- Mult Scler Relat Disord 2016 Jul.:124-30.
Fingolimod is a once-daily, orally administered therapy for relapsing forms of MS. It has been shown to reduce relapse rates significantly in all phase II and phase III clinical trials when compared with placebo and intramuscular interferon β-1a (IFNβ-1a IM).This study compared annualized relapse rates (ARRs) associated with fingolimod, placebo and IFNβ-1a IM, in patient subgroups from the pooled FREEDOMS, FREEDOMS II, and TRANSFORMS populations. This provided a large data set in which the efficacy of fingolimod could be assessed across a range of patient subgroups, including clinically relevant subgroups not previously analysed.Compared with placebo, fingolimod was associated with significantly lower ARRs across all patient subgroups with relative reductions in ARRs ranging from 35% (patients who had previously received treatment for their MS for up to 1 year; P<0.05) to 69% (patients with symptoms for less than 3 years before study entry; P<0.001). Other relative reductions in ARR compared with placebo included 64% in patients aged 40 years or younger and 63% in those naïve to treatment (P<0.001 for both). Compared with IFNβ-1a IM, the greatest benefits to ARR were seen in patients aged 40 years or younger (55% relative ARR reduction, P<0.001) and in a small subgroup of patients who had previously received IFNβ and glatiramer acetate (55% relative ARR reduction; P<0.05). Reductions in ARR compared with IFNβ-1a IM were not statistically significant in men (33%, P=0.081), in patients aged over 40 years (23%, P=0.230) and in those who had received treatment prior to the study for 1 year or less (35%, P=0.108). Fingolimod was associated with significantly lower ARRs compared with placebo and with IFNβ-1a IM irrespective of treatment status (treatment-naïve and previously treated for MS), and regardless of type of previous therapy.Fingolimod provided consistent efficacy benefits over placebo and IFNβ-1a IM across a range of subgroups of patients with relapsing MS. The magnitude of the beneficial effect of fingolimod over IFNβ-1a IM may depend on age, sex, and duration of previous treatment. These findings suggest that most benefit will be gained by patients who start fingolimod early in the disease course, but the findings also suggest that fingolimod treatment will benefit patients later in the disease course when they have already accrued disability.
- Rationale, design, and methods of a non-interventional study to establish safety, effectiveness, quality of life, cognition, health-related and work capacity data on Alemtuzumab in multiple sclerosis patients in Germany (TREAT-MS). [Journal Article]
- BMC Neurol 2016.:109.
Alemtuzumab, a humanized monoclonal antibody directed against the cell surface glycoprotein CD52, is licensed in Europe since October 2013 as treatment for adult patients with active relapsing-remitting multiple sclerosis (RRMS). In three randomized, rater-blinded active comparator clinical trials studies, alemtuzumab administered in two annual courses, had superior efficacy as compared to subcutaneous interferon beta-1a, and durable efficacy over 5 years in an extension study with a manageable safety profile in RRMS patients. Data on the utilization and the outcomes of alemtuzumab under clinical practice conditions are limited.Here we describe the rationale, design and methods of the TREAT-MS study (non-interventional long-Term study foR obsErvAtion of Treatment with alemtuzumab in active relapsing-remitting MS).TREAT-MS is a prospective, multicenter, non-interventional, long-term study to collect data on safety, effectiveness, quality of life, cognition and other aspects from 3200 RRMS patients treated with alemtuzumab under the conditions of real-world clinical practice in Germany.As non-interventional trial in Germany.
- Biases affecting injected doses of an experimental drug during clinical trials. [Journal Article]
- Trials 2016; 17(1):321.
During clinical trials, researchers rarely question nominal doses specified on labels of investigational products, overlooking the potential for inaccuracies that may result when calculating pharmacokinetic and pharmacodynamic parameters. This study evaluated the disparity between nominal doses and the doses actually administered in two Phase I trials of a biosimilar drug.In Trial A, 12 healthy volunteers received various doses of an interferon β-1a biosimilar via either subcutaneous or intravenous injection, prepared by partially emptying 0.53 ml syringes supplied by the manufacturer. In Trial B, 12 volunteers received three different formulations of the drug via intravenous injection (biosimilar with and without albumin and a comparator), followed by multiple subcutaneous injections. In both trials, the dose administered was calculated as D = C × V - losses, where C is the drug concentration assessed using ELISA, V is the volume administered calculated using syringe weighing and losses are deduced from in-vitro experiments. Interferon binding to added albumin and infusion lines was evaluated using a (125)I-interferon tracer with gel-filtration chromatography.In Trial A, measured concentrations were close to the nominal strength indicated by the manufacturer (median bias: -6 %), whereas in Trial B they differed significantly for all three formulations (median biases: +67 %, +73 % and +31 % for the biosimilar with albumin, the biosimilar without albumin and the comparator, respectively). In Trial A, the doses actually administered showed large variability and biases, especially at the lowest doses. Indeed, actually injected volumes differed by as much as 74 % from theoretical volumes - a phenomenon mainly attributed to unnoticed fluid re-aspiration through the syringe needle. This was corrected in Trial B. Interferon was not significantly adsorbed on the infusion lines used for intravenous administration. Its binding to albumin was slow, reaching 50 % after a 16 h incubation.These examples illustrate the importance of assessing the actual doses administered in clinical trials, to ensure accuracy in the determination of clearance, distribution volume, bioavailability and dose-response relationships.Clinicaltrials.gov NCT02515695 (Trial A) and NCT02517788 (Trial B). Registered on 24 July and 5 August 2015, respectively.