Effectiveness of Interferon Beta 1a, compared to Interferon Beta 1b and the usual therapeutic regimen to treat adults with moderate to severe COVID-19: structured summary of a study protocol for a randomized controlled trial.
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SUBMITTER: Irvani SSN
PROVIDER: S-EPMC7268172 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: Not available
| S-EPMC7303932 | biostudies-literature
Project description:BackgroundBoth interferon beta-1b (IFN-β-1b) and interferon beta-1a (IFN-β-1a) are immunomodulators that require regular subcutaneous self-administration by patients with multiple sclerosis (MS). However, no electronic autoinjector is available for IFN-β-1a in the US.ObjectiveThis retrospective cohort study investigated adherence to two subcutaneous disease-modifying therapies, IFN-β-1b and IFN-β-1a, during two periods (before and after the introduction of the BETACONNECT® autoinjector for IFN-β-1b).Patients and methodsData were evaluated from the MarketScan database for adults in the US with an MS diagnosis and a medical claim for subcutaneous IFN-β-1b or IFN-β-1a, either before (October 2013-September 2015) or after the introduction of BETACONNECT (October 2016-September 2018). Patient populations were propensity-score matched by demographic and clinical characteristics. Persistence was recorded, and adherence was evaluated by medication possession ratio (MPR).ResultsThe study included 196 IFN-β-1b and 365 IFN-β-1a people with MS (PwMS) (pre-BETACONNECT period), and 126 IFN-β-1b and 223 IFN-β-1a PwMS (post-BETACONNECT period). In the pre-BETACONNECT period, the proportion with at least 80% MPR was higher for IFN-β-1a (90%) than for IFN-β-1b (83%), but in the post-BETACONNECT period the proportion with ≥ 80% MPR was higher for IFN-β-1b (92%) than for IFN-β-1a (86%). In the pre-BETACONNECT period, median persistence (in days) was higher for IFN-β-1a (199) than for IFN-β-1b (152), while in post-BETACONNECT period persistence was higher for IFN-β-1b (327) than for IFN-β-1a (229).ConclusionsFollowing the introduction of BETACONNECT, this exploratory study suggested that PwMS taking IFN-β-1b were more adherent compared with those taking IFN-β-1a, with higher persistence, and more than 90% reached 80% MPR, a threshold commonly used to define good adherence.
| S-EPMC8324614 | biostudies-literature
Project description:The first objective was to investigate the transdermal iontophoresis of interferon beta 1b (IFN); the second was to determine whether the addition of 10 Arg residues at the N-terminus, creating a highly charged poly-Arg analogue (Arg10-IFN), increased delivery. Cumulative permeation of IFN and Arg10-IFN after iontophoresis at 0.5 mA/cm2 for 8 h was 6.97 ± 4.82 and 9.55 ± 1.63 ng/cm2, respectively - i.e. >1000-fold less than that of ribonuclease A, cytochrome c and human basic fibroblast growth factor. Co-iontophoresis of acetaminophen showed that, in contrast to lysozyme, neither IFN nor Arg10-IFN interacted with skin to decrease convective solvent flow. Furthermore, there was no statistically significant difference between (i) iontophoretic delivery of IFN across intact or laser porated skin and (ii) passive or iontophoretic delivery of IFN across laser porated skin. Chromatographic characterisation supported the hypothesis that IFN was bound strongly to albumin. The formation of a ~ 86 kDa complex with albumin was probably responsible for the poor cutaneous delivery of IFN/Arg10-IFN despite the use of iontophoresis and/or laser microporation. Biopharmaceuticals might interact with specific proteins during iontophoretic transport and so decrease their (per)cutaneous delivery without affecting electroosmotic solvent flow, which is usually considered as a reliable marker to report on permeant binding during electrotransport across the skin.
| S-EPMC7358383 | biostudies-literature
Project description:ObjectiveTo compare the effectiveness of glatiramer acetate (GA) vs intramuscular interferon beta-1a (IFN-β-1a), we applied a previously published statistical method aimed at identifying patients' profiles associated with efficacy of treatments.MethodsData from 2 independent multiple sclerosis datasets, a randomized study (the Combination Therapy in Patients With Relapsing-Remitting Multiple Sclerosis [CombiRx] trial, evaluating GA vs IFN-β-1a) and an observational cohort extracted from MSBase, were used to build and validate a treatment response score, regressing annualized relapse rates (ARRs) on a set of baseline predictors.ResultsThe overall ARR ratio of GA to IFN-β-1a in the CombiRx trial was 0.72. The response score (made up of a linear combination of age, sex, relapses in the previous year, disease duration, and Expanded Disability Status Scale score) detected differential response of GA vs IFN-β-1a: in the trial, patients with the largest benefit from GA vs IFN-β-1a (lower score quartile) had an ARR ratio of 0.40 (95% confidence interval [CI] 0.25-0.63), those in the 2 middle quartiles of 0.90 (95% CI 0.61-1.34), and those in the upper quartile of 1.14 (95% CI 0.59-2.18) (heterogeneity p = 0.012); this result was validated on MSBase, with the corresponding ARR ratios of 0.58 (95% CI 0.46-0.72), 0.92 (95% CI 0.77-1.09,) and 1.29 (95% CI 0.97-1.71); heterogeneity p < 0.0001).ConclusionsWe demonstrate the possibility of a criterion, based on patients' characteristics, to choose whether to treat with GA or IFN-β-1a. This result, replicated on an independent real-life cohort, may have implications for clinical decisions in everyday clinical practice.
| S-EPMC7905777 | biostudies-literature
Project description:AimSubcutaneous (s.c.) peginterferon beta-1a injected once every 2 weeks and s.c. interferon beta-1a injected three times per week (Rebif®) have demonstrated efficacy in relapsing-remitting multiple sclerosis, but direct comparisons of pharmacological activity and tolerability between the two products are lacking. COMPARE was an open label, crossover, pharmacokinetic (PK) study evaluating drug exposure and the safety and tolerability of s.c. peginterferon beta-1a and s.c. interferon beta-1a, over 2 weeks in healthy subjects.MethodsThirty healthy subjects received one dose of peginterferon beta-1a (125 μg s.c.) or six doses of interferon beta-1a (44 μg s.c.) over 2 weeks, followed by the alternate treatment after a 2 week washout period. Drug concentrations were measured using an enzyme-linked immunosorbent assay (ELISA) and PK parameters including cumulative area under the concentration-time curve (AUC0-336h ) over 2 weeks and maximum observed serum concentrations (Cmax ) were estimated using a non-compartmental analysis.ResultsThe PK analysis population comprised 26 subjects for each treatment. Drug exposure (AUC0-336h ) was 60% higher with s.c. peginterferon than with s.c. interferon beta-1a (117.4 ng ml(-1) h, 95% confidence interval 95.6, 144.3 vs. 73.1 ng ml(-1) h, 95% confidence interval 61.2, 87.3, respectively; P < 0.0001). Injection-site reactions (ISRs) were the most common adverse events (AEs) observed with both treatments. Numerically lower frequencies and incidence rates of ISRs, headache, myalgia and chills were observed with s.c. peginterferon beta-1a.ConclusionsOne dose of s.c. peginterferon delivered significantly greater drug exposure than s.c. interferon beta-1a three times a week over 2 weeks, and a lower frequency of AEs.
| S-EPMC4972154 | biostudies-literature
Project description: Not available
| S-EPMC8413691 | biostudies-literature
Project description:IntroductionMultiple sclerosis (MS) typically requires life-long management with disease-modifying therapies (DMTs). Many DMTs require regular self-injection, and can be associated with injection site reactions, pain, and needle/injection phobia-but these can be addressed by improvements in autoinjector design. The aim of this study was to investigate patient satisfaction and preference for BETACONNECT™ (Bayer Pharma AG), a novel interferon beta-1b autoinjector.MethodsPatients in Germany performing self-injections using BETACONNECT took part in the study. Data were collected through an online 15-min structured survey. Participants rated their experience with BETACONNECT on a 6-point scale and those satisfied with BETACONNECT were asked to describe the reason using a free-text box.ResultsOne-hundred and eighteen patients with MS completed the survey. Ninety percent preferred BETACONNECT to their previous injection method (only 4% previously used manual injections, so most had previously used other autoinjectors). Ninety-two percent were very confident/confident in their ability to perform an injection using BETACONNECT. The most common free-text responses to "Why are you satisfied with the BETACONNECT™ autoinjector?" were ease of use (46%), less irritation/pain at the injection site (33%), and smoother injections (24%). Features considered most useful were automated injections (98%), adjustable injection speed (98%), and adjustable injection depth (98%). Ninety-seven percent thought it was easy to know when an injection was complete and 95% agreed/strongly agreed it was easy to learn to use the autoinjector. Seventy-three percent agreed that the quietness and effortlessness of the BETACONNECT reduced their level of injection anxiety, 92% that its size and shape makes it easy to handle during injections, and 67% that it decreases injection site pain. Eighty percent of those using the reminder function thought they were less likely to miss an injection.ConclusionPatients with MS self-injecting interferon beta-1b expressed a high level of satisfaction and preference for BETACONNECT. Thus, BETACONNECT represents a valid option to improve patients' overall injection experience.FundingBayer HealthCare Pharmaceuticals.
| S-EPMC4685867 | biostudies-literature
Project description:The purpose of this study was to develop a biobetter version of recombinant human interferon-β 1a (rhIFN-β 1a) to improve its biophysical properties, such as aggregation, production and stability, and pharmacokinetic properties without jeopardizing its activity. To achieve this, we introduced additional glycosylation into rhIFN-β 1a via site-directed mutagenesis. Glycoengineering of rhIFN-β 1a resulted in a new molecular entity, termed R27T, which was defined as a rhIFN-β mutein with two N-glycosylation sites at 80th (original site) and at an additional 25th amino acid due to a mutation of Thr for Arg at position 27th of rhIFN-β 1a. Glycoengineering had no effect on rhIFN-β ligand-receptor binding, as no loss of specific activity was observed. R27T showed improved stability and had a reduced propensity for aggregation and an increased half-life. Therefore, hyperglycosylated rhIFN-β could be a biobetter version of rhIFN-β 1a with a potential for use as a drug against multiple sclerosis.
| S-EPMC4032242 | biostudies-literature
Project description:BackgroundPharmacological therapies of proven efficacy in coronavirus disease 2019 (COVID-19) are still lacking. We have identified IFNβ-1a as the most promising drug to be repurposed for COVID-19. The rationale relies on the evidence of IFNβ anti-viral activity in vitro against SARS-CoV-2 and animal models resembling SARS-CoV-2 infection and on a recent clinical trial where IFNβ was indicated as the key component of a successful therapeutic combination.MethodsThis is a randomized, controlled, open-label, monocentric, phase II trial (INTERCOP trial). One hundred twenty-six patients with positive swab detection of SARS-CoV-2, radiological signs of pneumonia, and mild-to-moderate disease will be randomized 2:1 to IFNβ-1a in addition to standard of care vs standard of care alone. No other anti-viral drugs will be used as part of the regimens, both in the control and the intervention arms. IFNβ-1a will be administered subcutaneously at the dose of 44 mcg (equivalent to 12 million international units) three times per week, at least 48 h apart, for a total of 2 weeks. The primary outcome is the time to negative conversion of SARS-CoV-2 nasopharyngeal swabs. Secondary outcomes include improvement or worsening in a clinical severity score measured on a 7-point ordinal scale (including transfer to intensive care unit and death), oxygen- and ventilator-free days, mortality, changes in pulmonary computed tomography severity score, hospital stay duration, reduction of viral load measured on nasopharyngeal swabs, number of serious adverse events, and changes in biochemical markers of organ dysfunction. Exploratory outcomes include blood cell counts, cytokine and inflammatory profile, peripheral mRNA expression profiles of interferon-stimulated genes, and antibodies to SARS-CoV-2 and to IFNβ-1a. INTERCOP is the first study to specifically investigate the clinical benefits of IFNβ-1a in COVID-19 patients.DiscussionPotential implications of this trial are multifaceted: should the primary outcome be fulfilled and the treatment be safe, one may envisage that IFNβ-1a be used to reduce the infectivity of patients with mild-to moderate disease. In case IFNβ-1a reduced the duration of hospital stay and/or ameliorated the clinical status, it may become a cornerstone of COVID-19 treatment.Trial registrationEudraCT 2020-002458-25. Registered on May 11, 2020 ClinicalTrials.gov Identifier: NCT04449380.
| S-EPMC7681191 | biostudies-literature
Project description:Natalizumab (NTZ) discontinuation leads to multiple sclerosis reactivation.The objective of this study is to compare disease activity in MS patients who continued on NTZ treatment to those who were switched to subcutaneous interferon 1b (IFNB) treatment.1-year randomized, rater-blinded, parallel-group, pilot study (ClinicalTrial.gov ID: NCT01144052). Relapsing remitting MS patients on NTZ for ?12 months who had been free of disease activity on this therapy (no relapses and disability progression for ?6 months, no gadolinium-enhancing lesions on baseline MRI) were randomized to NTZ or IFNB. Primary endpoint was time to first on-study relapse. Additional clinical, MRI and safety parameters were assessed. Analysis was based on intention to treat.19 patients (NTZ n=10; IFNB n=9) with similar baseline characteristics were included. 78% of IFNB treated patients remained relapse free (NTZ group: 100%), and 25% remained free of new T2 lesions (NTZ group: 62.5%). While time to first on-study relapse was not significantly different between groups (p=0.125), many secondary clinical and radiological endpoints (number of relapses, proportion of relapse free patients, number of new T2 lesions) showed a trend, or were significant (new T2 lesions at month 6) in favoring NTZ.De-escalation therapy from NTZ to IFNB over 1 year was associated with some clinical and radiological disease recurrence. Overall no major safety concerns were observed.
| S-EPMC3750382 | biostudies-literature