Dataset Information

Impact of natalizumab on patient-reported outcomes in multiple sclerosis: a longitudinal study.

ABSTRACT:

Background

Natalizumab (Tysabri, Biogen Idec and Elan Pharmaceuticals) significantly reduces the relapse rate and disability progression, and improves health-related quality of life (HRQoL), in patients with relapsing-remitting multiple sclerosis. We investigated the impact of natalizumab on patient-reported outcomes (PROs) in a real-world setting.

Methods

PRO data were collected from patients enrolled in a longitudinal real-world study using validated measures administered as surveys before the patients initiated natalizumab treatment and after the 3rd, 6th, and 12th monthly infusion. HRQoL, ability to carry out daily activities, disability level, and impact on cognitive functioning and fatigue were assessed.

Results

A total of 333 patients completed 12 months of assessments. After 12 months of natalizumab treatment, 69% to 88% of patients reported a positive outcome (either an improvement or no further decline) in all PRO measures assessed. Significant improvements in general and disease-specific HRQoL were observed after three infusions, both with physical (p < .01) and psychological (p < .001) measures, and were sustained after 12 infusions (all p < .001). The impact of multiple sclerosis on cognitive functioning and fatigue was significantly reduced (both p < .001 after 3 and 12 infusions).

Conclusions

PRO measures were improved with natalizumab in a real-world setting. The improvements were observed as early as after 3 months and sustained over a 12-month period. The improvements in PROs show that, in clinical practice, the clinical benefits of natalizumab are translated into patient-reported benefits.

SUBMITTER: Stephenson JJ

PROVIDER: S-EPMC3543243 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Publications

Impact of natalizumab on patient-reported outcomes in multiple sclerosis: a longitudinal study.

Stephenson Judith J JJ Kern David M DM Agarwal Sonalee S SS Zeidman Ruth R Rajagopalan Krithika K Kamat Siddhesh A SA Foley John J

Health and quality of life outcomes 20121227

<h4>Background</h4>Natalizumab (Tysabri, Biogen Idec and Elan Pharmaceuticals) significantly reduces the relapse rate and disability progression, and improves health-related quality of life (HRQoL), in patients with relapsing-remitting multiple sclerosis. We investigated the impact of natalizumab on patient-reported outcomes (PROs) in a real-world setting.<h4>Methods</h4>PRO data were collected from patients enrolled in a longitudinal real-world study using validated measures administered as sur ...[more]

PMID: 23270428

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Project description:BackgroundThere is increasing emphasis on using patient-reported outcomes (PROs) to complement traditional clinical outcomes in medical research, including in multiple sclerosis (MS). Research, particularly in oncology and heart failure, has shown that PROs can be prognostic of hard clinical endpoints such as survival time (time from study entry until death). However, unlike in oncology or cardiology, it is unknown whether PROs are associated with survival time in neurological diseases. The Multiple Sclerosis Impact Scale-29 (MSIS-29) is a PRO sensitive to short-term change in MS, with questions covering both physical and psychological quality of life. This study aimed to investigate whether MSIS-29 scores can be prognostic for survival time in MS, using a large observational cohort of people with MS.Methods and findingsFrom 15 July 2004 onwards, MSIS-29 questionnaires were completed by people with MS registered with the MS Society Tissue Bank (n = 2,126, repeated 1 year later with n = 872 of the original respondents). By 2014, 264 participants (12.4%) had died. Higher baseline MSIS-29 physical (MSIS-29-PHYS) score was associated with reduced survival time (subgroup with highest scores versus subgroup with lowest scores: hazard ratio [HR] 5.7, 95% CI 3.1-10.5, p < 0.001). Higher baseline MSIS-29 psychological score was also associated with reduced survival time (subgroup with highest scores versus subgroup with lowest scores: HR 2.8, 95% CI 1.8-4.4, p < 0.001). In those with high baseline MSIS-29 scores, mortality risk was even greater if the MSIS-29 score worsened over 1 year (HR 2.3, 95% CI 1.2-4.4, p = 0.02). MSIS-29-PHYS scores were associated with survival time independent of age, sex, and patient-reported Expanded Disability Status Scale score in a Cox regression analysis (per 1-SD increase in MSIS-29-PHYS score: HR 1.8, 95% CI 1.1-2.9, p = 0.03). A limitation of the study is that this cohort had high baseline age and disability levels; the prognostic value of MSIS-29 for survival time at earlier disease stages requires further investigation.ConclusionsThis study reports that PROs can be prognostic for hard clinical outcomes in neurological disease, and supports PROs as a meaningful clinical outcome for use in research and clinical settings.

Project description:Abstract Registries have the potential to tackle some of the current limitations in determining the long-term impact of multiple sclerosis. Online assessments using patient-reported outcomes can streamline follow-up enabling large-scale, long-term, cost-effective, home-based, and patient-focused data collection. However, registry data are sparsely sampled and the sensitivity of patient-reported outcomes relative to clinician-reported scales is unknown, making it hard to fully leverage their unique scope and scale to derive insights. This retrospective and prospective cohort study over 11 years involved 15 976 patients with multiple sclerosis from the United Kingdom Multiples Sclerosis Register. Primary outcomes were changes in two patient-reported outcomes: Multiple Sclerosis Impact Scale motor component, and Multiple Sclerosis Walking Scale. First, we investigated their validity in measuring the impact of physical disability in multiple sclerosis, by looking at their sensitivity to disease subtype and duration. We grouped the available records (91 351 for Multiple Sclerosis Impact Scale motor and 68 092 for Multiple Sclerosis Walking Scale) by these two factors, and statistically compared the resulting groups using a novel approach based on Monte Carlo permutation analysis that was designed to cope with the intrinsic sparsity of registry data. Next, we used the patient-reported outcomes to draw novel insights into the developmental time course of subtypes; in particular, the period preceding the transition from relapsing to progressive forms. We report a robust main effect of disease subtype on the patient-reported outcomes and interactions of disease subtype with duration (all P < 0.0001). Specifically, patient-reported outcomes worsen with disease duration for all subtypes (all P < 0.0001) apart from benign multiple sclerosis (Multiple Sclerosis Impact Scale motor: P = 0.796; Multiple Sclerosis Walking Scale: P = 0.983). Furthermore, the patient-reported outcomes of each subtype are statistically different from those of the other subtypes at all time bins (Multiple Sclerosis Impact Scale motor: all P < 0.05; Multiple Sclerosis Walking Scale: all P < 0.01) except when comparing relapsing-remitting multiple sclerosis with benign multiple sclerosis and primary progressive multiple sclerosis with secondary progressive multiple sclerosis. Notably, there were statistically significant differences between relapsing-remitting and progressive subtypes at disease onset. Critically, the patient-reported outcomes are sensitive to future transitions to progressive subtypes, with individuals who transition presenting with higher patient-reported outcomes in their relapsing-remitting phase compared to individuals who don’t transition since onset (all P < 0.0001). Patient-reported outcomes capture different patterns of physical worsening over disease length and across subtypes; therefore, they are a valid tool to measure the physical impact of multiple sclerosis over the long-term and cost-effectively. Furthermore, more advanced physical disability manifests years before clinical detection of progressive subtypes, adding evidence to the presence of a multiple sclerosis prodrome. Lerede et al. found patient-reported outcomes to be a useful tool for tracking multiple sclerosis progression across subtypes and identifying early disability differences. They used permutation-based methods to analyse patient registry data, demonstrating the potential of online monitoring technologies to estimate multiple sclerosis progression risk early and support clinical decision-making. Graphical Abstract Graphical abstract

Project description:Abstract Objectives This case trial reports the effects of L-carnosine supplementation on neuromuscular performance, brain metabolism, and various patient- and clinician-reported outcomes in a case series of patients with multiple sclerosis (MS). Methods Two women (aged 37 and 48) and a man (age 48 years) who fulfilled the 2017 McDonald criteria for MS diagnosis, and were free of other major chronic diseases or acute disorders were recruited for this case study. The duration of illness was 4 years in CASE 1 (37-year old women), 5 years in CASE 2 (48-year old men), and 15 years in CASE 3 (48-year old women). L-carnosine (2 g/day) was administered orally during 8 weeks in all MS patients. The trial was registered at ClinicalTrials.gov (ID NCT03995810). Results The intensity of symptoms and signs of MS after L-carnosine administration diminished in 5 out of 7 domains in CASE 1, in 3 out of 7 domains in CASE 2, and one domain in CASE 3; general fatigue has been reduced in all three cases at the follow-up. The Visual Analog Scale scores for numbness, weakness, pain, and depression decreased in all MS patients at post-administration. This was accompanied by an improved walking distance to exhaustion in all patients, with values improved for 51.1% in CASE 1, 19.5% in CASE 2, and 2.1% in CASE 3 at 8-week follow-up. An increase in serum total antioxidant capacity was found at 8-week follow-up in all patients (from 4.6 to 49.6%); this was accompanied by lower blood lactates at follow-up in all cases (23.5% on average). Single-voxel 1.5 T MRS revealed an increased brain choline-contained compounds (18.9% on average), total creatine (21.2%), and myo-inositol levels (12.3%) in girus cinguli at 8-week follow; this was accompanied by a drop in brain glutamate for 22.6% on average. Conclusions This case report suggests the favorable effects of medium-term L-carnosine as a possible adjuvant treatment to improve selected patient- and clinician-reported outcomes in a man and two women suffering from MS. There is a need for larger and more rigorous human intervention studies to corroborate these preliminary findings. Funding Sources This study was funded by the Serbian Ministry of Education, Science and Technological Development (#175,037); the Provincial Secretariat for Higher Education and Scientific Research (#114–451-710); the Faculty of Sport and Physical Education, Novi Sad; and CarnoMed LLC, Novi Sad.

Project description:The objective of this study was to investigate confirmed progression independent of relapse activity in relapsing-remitting multiple sclerosis patients under long-term natalizumab treatment. We performed a retrospective, cross-sectional study of clinical data captured between 1994 and 2019 at two German multiple sclerosis tertiary referral centres. Data files of all relapsing-remitting multiple sclerosis patients treated with natalizumab for ≥24 months were analysed. Confirmed progression independent of relapse activity was defined as ≥12 week confirmed disability progression on a roving Expanded Disability Status Scale reference score by 1 point in patients with an Expanded Disability Status Scale score ≤3 or 0.5 in patients with an Expanded Disability Status Scale score ≥3.5 in the absence of a relapse. Cox proportional hazard models were used to analyse the probability of developing confirmed progression independent of relapse activity depending on both disease and natalizumab treatment duration. Among the 184 patients identified, 44 (24%) developed confirmed progression independent of relapse activity under natalizumab irrespective of the Expanded Disability Status Scale score at natalizumab onset. Time to confirmed progression independent of relapse activity was not affected by Expanded Disability Status Scale at natalizumab onset (categorized by Expanded Disability Status Scale score ≤3.5 versus >3.5) nor by duration of disease nor by duration of therapy. Confirmed progression independent of relapse activity occurred earlier in the disease course in patients with an earlier natalizumab therapy onset with regard to disease duration. A stepwise forward regression analysis revealed disease duration as the main factor for confirmed progression independent of relapse activity development (P = 0.005). Taken together, confirmed progression independent of relapse activity occurs in a substantial proportion of patients on long-term natalizumab treatment and independent of Expanded Disability Status Scale score at natalizumab onset. Our findings suggest that patients who are initiated on natalizumab early during disease course, usually in order to treat an aggressive clinical phenotype, have a higher risk of early confirmed progression independent of relapse activity.

Project description:BackgroundTreatment and monitoring decisions in people with multiple sclerosis (MS) are based commonly on clinician-reported outcomes. These reflect physical and radiological disease activity and are the most relevant endpoints in clinical trials. Over the past few years, the number of studies evaluating so-called patient-reported outcomes (PROs) has been increasing. PROs are reports from patients concerning their own health perception. They are typically obtained by means of questionnaires and aim to quantify symptoms such as fatigue, depression, and sexual dysfunction. The emergence of PROs has made a tremendous contribution to understanding the individual impact of disease in people with MS and their health-related quality of life. However, the assessment of PROs consumes resources, including time and personnel. Thus, useful ways to conveniently introduce PROs into clinical practice are needed.ObjectiveWe aim to provide a rationale and pilot study protocol for a mobile health (mHealth) solution named "haMSter" that allows for remote monitoring of PROs in people with MS.MethodsThe core function of haMSter is to provide three scientifically validated PRO questionnaires relevant to MS for patients to fill out at home once a month. Thereby, longitudinal and remote documentation of PROs is enabled. A scoring algorithm graphically plots PRO scores over time and makes them available at the next visit.ResultsThe pilot study is currently ongoing and will evaluate adherence to this mHealth solution in 50 patients over a period of 6 months. Results from the haMSter pilot study are expected in 2021.ConclusionshaMSter is a novel mHealth-based solution for modern PRO research, which may constitute the first step in achieving the ability to integrate PROs in clinical practice. This allows for a more problem-oriented approach in monitoring visits, which addresses patient needs and ultimately saves time.Trial registrationClinicalTrials.gov NCT04555863; https://clinicaltrials.gov/ct2/show/NCT04555863.International registered report identifier (irrid)DERR1-10.2196/25011.

Dataset Information

Impact of natalizumab on patient-reported outcomes in multiple sclerosis: a longitudinal study.

Background

Methods

Results

Conclusions

Publications

Impact of natalizumab on patient-reported outcomes in multiple sclerosis: a longitudinal study.

Similar Datasets

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