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Patient subgroup analyses of the treatment effect of subcutaneous interferon β-1a on development of multiple sclerosis in the randomized controlled REFLEX study.

ABSTRACT: The REFLEX study (NCT00404352) established that subcutaneous (sc) interferon (IFN) β-1a reduced the risks of McDonald MS (2005 criteria) and clinically definite multiple sclerosis (CDMS) in patients with a first clinical demyelinating event suggestive of MS. The aim of this subgroup analysis was to assess the treatment effect of sc IFN β-1a in patient subgroups defined by baseline disease and demographic characteristics (age, sex, use of steroids at the first event, classification of first event as mono- or multifocal, presence/absence of gadolinium-enhancing lesions, count of <9 or ≥9 T2 lesions), and by diagnosis of MS using the revised McDonald 2010 MS criteria. Patients were randomized to the serum-free formulation of IFN β-1a, 44 μg sc three times weekly or once weekly, or placebo, for 24 months or until diagnosis of CDMS. Treatment effects of sc IFN β-1a on McDonald 2005 MS and CDMS in the predefined subgroups were similar to effects found in the intent-to-treat population. McDonald 2010 MS was retrospectively diagnosed in 37.7 % of patients at baseline. Both regimens of sc IFN β-1a significantly reduced the risk versus placebo of McDonald 2005 MS and CDMS, irrespective of McDonald 2010 status at baseline (risk reductions between 29 and 51 %). The effect of sc IFN β-1a was not substantially influenced by baseline patient demographic and disease characteristics, or baseline presence/absence of McDonald 2010 MS.

SUBMITTER: Freedman MS

PROVIDER: S-EPMC3948518 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Patient subgroup analyses of the treatment effect of subcutaneous interferon β-1a on development of multiple sclerosis in the randomized controlled REFLEX study.

Freedman Mark S MS De Stefano Nicola N Barkhof Frederik F Polman Chris H CH Comi Giancarlo G Uitdehaag Bernard M J BM Casset-Semanaz Florence F Hennessy Brian B Lehr Lorenz L Stubinski Bettina B Jack Dominic L DL Kappos Ludwig L

Journal of neurology 20140112 3

The REFLEX study (NCT00404352) established that subcutaneous (sc) interferon (IFN) β-1a reduced the risks of McDonald MS (2005 criteria) and clinically definite multiple sclerosis (CDMS) in patients with a first clinical demyelinating event suggestive of MS. The aim of this subgroup analysis was to assess the treatment effect of sc IFN β-1a in patient subgroups defined by baseline disease and demographic characteristics (age, sex, use of steroids at the first event, classification of first event ...[more]

PMID: 24413638

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Project description:BackgroundPatient adherence to treatment is key to preventing the worsening of neurological disability in multiple sclerosis (MS). The RebiSmart® autoinjector facilitates self-administration of subcutaneous interferon β-1a (sc IFN β-1a) and records objective adherence data. The CORE study was undertaken to evaluate the relationship between subjectively reported and objective adherence of MS patients using RebiSmart® in Switzerland and explore variables associated with objective adherence.MethodsPatients with relapsing-remitting MS who were treated with sc IFN β-1a 44 or 22 μg three times weekly using RebiSmart® for at least 9 months participated in this phase IV non-interventional study. Neurologist questionnaires were used at month 0 to collect patient demographics, medical history and estimates of patients' adherence. Patient questionnaires were used to record subjective patient-reported adherence at month 0 and estimates of variables influencing adherence. Objective adherence data were obtained from the RebiSmart® log-files at months 0 and 6.ResultsOf 56 patients who completed the observation period, 53 had evaluable data. Objective adherence differed significantly between self-reported compliant (n = 33) and non-compliant groups (n = 20) (p = 0.00001). Older age, greater disability, patient's perception of the importance of ease of use and storage, being well informed about RebiSmart® features and neurologists' estimations of adherence were all positively associated with treatment adherence.ConclusionsWe showed for the first time that subjective patient-reported adherence in MS was well in line with objective adherence, suggesting that the frequency of administration is reported accurately by patients to their neurologist. This observation may have implications for future treatment monitoring strategies and strategic medical decisions. Patients, particularly those who are younger and with lower levels of disability, may benefit from being better informed of the importance of being adherent to their treatments and receiving information about their medication and the device they are using.

Project description:Introduction and backgroundAdherence is a critical factor for optimal clinical outcomes in multiple sclerosis (MS) treatment. This study investigated the adherence and clinical outcomes of MS patients treated with subcutaneous (sc) interferon (IFN) (β)-1a, an established immunomodulatory treatment for relapsing MS. The benefits of a patient support programme (PSP) were also studied.MethodsThis phase-IV prospective, observational multicentre study enrolled patients with relapsing MS who were treated with sc IFN β-1a for 24 months was conducted at 53 centres across 17 countries. The primary endpoint was adherence to sc IFN β-1a treatment, as assessed using Morisky Green Levine Medication Adherence Scale (MGLS) scores at 24 months. The MGLS is a self-reported diagnostic tool to address medication non-adherence, with a score ranging from 0 to 4, with 0 representing high adherence, 1-2 representing medium adherence, and 3-4 representing low adherence. Other endpoints included time to study and treatment discontinuation over 24 months, the proportion of relapse-free patients, and Expanded Disability Status Scale (EDSS) progression (defined as ≥1.0 point increase sustained for 3 months) at 24 months. A subgroup analysis was performed for endpoints based on patients assigned to PSP (yes/no-PSP versus non-PSP subgroup).ResultsOf the 577 patients enrolled, 408 had evaluable MGLS scores at 24 months. A total of 336 (58.2%; 95% confidence interval [CI]: 54.1-62.3%) patients reported high adherence, 57 (9.9%; 95% CIs: 7.6-12.7%) reported medium adherence, and 15 (2.6%; 95% CI: 1.5-4.3%) reported low adherence at 24 months. The PSP subgroup reported higher adherence (n = 206; 65.8%) than the non-PSP subgroup (n = 130; 56.5%). By 24 months, 52.2% of the patients were relapse-free and 17.2% patients experienced ≥1 relapse. Expanded Disability Status Scale progression was observed in 12.3% of patients. Over the 24-month period, 30.8% of the patients discontinued treatment, and the most common reasons for treatment discontinuation were adverse events (AEs, 10.4%), being lost to followup (7.1%), and a lack of efficacy (5.5%). Overall, 39.6% patients experienced ≥1 AE, which ranged from mild to moderate.ConclusionThe study demonstrated high adherence to sc IFN β-1a treatment with an added benefit of PSP participation. More than half of the patients remained relapse-free over a 24-month period. No new safety concerns to sc IFN β-1a treatment were observed.Clinical trial registrationhttps://clinicaltrials.gov/study/NCT02921035, NCT02921035.

Project description:ObjectivesTo compare treatment persistence between two dosages of interferon ?-1a in a large observational multiple sclerosis registry and assess disease outcomes of first line MS treatment at these dosages using propensity scoring to adjust for baseline imbalance in disease characteristics.MethodsTreatment discontinuations were evaluated in all patients within the MSBase registry who commenced interferon ?-1a SC thrice weekly (n?=?4678). Furthermore, we assessed 2-year clinical outcomes in 1220 patients treated with interferon ?-1a in either dosage (22 µg or 44 µg) as their first disease modifying agent, matched on propensity score calculated from pre-treatment demographic and clinical variables. A subgroup analysis was performed on 456 matched patients who also had baseline MRI variables recorded.ResultsOverall, 4054 treatment discontinuations were recorded in 3059 patients. The patients receiving the lower interferon dosage were more likely to discontinue treatment than those with the higher dosage (25% vs. 20% annual probability of discontinuation, respectively). This was seen in discontinuations with reasons recorded as "lack of efficacy" (3.3% vs. 1.7%), "scheduled stop" (2.2% vs. 1.3%) or without the reason recorded (16.7% vs. 13.3% annual discontinuation rate, 22 µg vs. 44 µg dosage, respectively). Propensity score was determined by treating centre and disability (score without MRI parameters) or centre, sex and number of contrast-enhancing lesions (score including MRI parameters). No differences in clinical outcomes at two years (relapse rate, time relapse-free and disability) were observed between the matched patients treated with either of the interferon dosages.ConclusionsTreatment discontinuations were more common in interferon ?-1a 22 µg SC thrice weekly. However, 2-year clinical outcomes did not differ between patients receiving the different dosages, thus replicating in a registry dataset derived from "real-world" database the results of the pivotal randomised trial. Propensity score matching effectively minimised baseline covariate imbalance between two directly compared sub-populations from a large observational registry.

Dataset Information

Patient subgroup analyses of the treatment effect of subcutaneous interferon β-1a on development of multiple sclerosis in the randomized controlled REFLEX study.

Publications

Patient subgroup analyses of the treatment effect of subcutaneous interferon β-1a on development of multiple sclerosis in the randomized controlled REFLEX study.

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