scholarly journals Relapse Rate and MRI Activity in Young Adult Patients With Multiple Sclerosis: A Post Hoc Analysis of Phase 3 Fingolimod Trials

2018 ◽  
Vol 4 (2) ◽  
pp. 205521731877861 ◽  
Author(s):  
Jutta Gärtner ◽  
Tanuja Chitnis ◽  
Angelo Ghezzi ◽  
Daniela Pohl ◽  
Wolfgang Brück ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Young Adults ◽  
Disease Activity ◽  
Relapse Rate ◽  
Negative Binomial ◽  
Age Groups ◽  
Young Patients ◽  
Negative Binomial Regression ◽  
Phase 3 ◽  
Double Blind

Background Disease activity differs in young patients with multiple sclerosis (MS) compared with the overall adult MS population. Objective The objective of this paper is to evaluate the effect of fingolimod 0.5 mg on disease activity in young adults with MS from three randomized, double-blind Phase 3 trials. Methods Annualized relapse rate (ARR), number of new/newly enlarging T2 lesions (neT2), and no evidence of disease activity (NEDA-3) were estimated in the intent-to-treat population at age 20 (youngest) and 30 (young) and compared to the overall population. Models used included a negative binomial regression (ARR/neT2) and a logistic regression (NEDA), with age at baseline as a continuous covariate. Results ARRs were higher in younger patients (all p < 0.05), and significantly reduced with fingolimod versus placebo or interferon beta-1a (IFN β-1a), with the percentage reduction inversely proportional to age. Fingolimod was significantly associated with a lower number of neT2 lesions versus placebo/IFN in all age groups except versus IFN in the youngest patients. Regardless of age, fingolimod-treated patients were more likely to achieve NEDA-3 versus placebo/IFN β-1a, with strongest benefits in the youngest patients (all p < 0.05). Conclusions Young adults show higher levels of MS disease activity, and may particularly benefit from fingolimod treatment compared with the overall study population.

scholarly journals Cerebrospinal fluid markers in incident pediatric-onset multiple sclerosis: a nationwide study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kyla A. McKay ◽  
Ronny Wickström ◽  
Jan Hillert ◽  
Virginija Danylaite Karrenbauer
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Relapse Rate ◽  
Negative Binomial ◽  
Negative Binomial Regression ◽  
Expanded Disability Status Scale ◽  
Binomial Regression ◽  
Disability Status ◽  
Igg Index ◽  
Pediatric Onset

AbstractTo investigate whether cerebrospinal fluid (CSF) markers differ between pediatric-onset multiple sclerosis (PoMS, onset < 18 years) and adult-onset (AoMS), and whether these markers are associated with clinical outcomes among PoMS. Prospective nationwide registry study of incident MS, including persons with a CSF sample < 3 years post-MS onset. We compared CSF oligoclonal band (OCB) status, immunoglobulin G (IgG) index levels, and mononuclear cell count between PoMS and AoMS. Within the PoMS cohort we analyzed the association between CSF markers, relapse rate and Expanded Disability Status Scale (EDSS) score, using negative binomial regression and generalized estimating equations, respectively. The cohort consisted of 130 PoMS and 3228 AoMS cases. The PoMS group had higher odds of OCB-positivity (odds ratio: 2.70; 95% CI 1.21–7.67). None of the CSF markers were associated with relapse rate in the PoMS cohort; however, OCB-positivity was associated with higher EDSS scores. This study suggested that PoMS more commonly display CSF evidence for intrathecal IgG production than AoMS. Further, we found evidence of a relationship between OCB-positivity and subsequent disability, suggesting that they could play a role in the prognostication of MS in children.

Smoking is associated with increased disease activity during natalizumab treatment in multiple sclerosis

2018 ◽  
Vol 25 (9) ◽  
pp. 1298-1305 ◽  
Author(s):  
Eva Rosa Petersen ◽  
Helle Bach Søndergaard ◽  
Julie Hejgaard Laursen ◽  
Anna Gabriella Olsson ◽  
Lars Börnsen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Relapse Rate ◽  
Negative Binomial ◽  
Smoking Status ◽  
Human Leukocyte ◽  
Negative Binomial Regression ◽  
Nucleotide Polymorphisms ◽  
Allelic Discrimination ◽  
Smoking Intensity ◽  
Natalizumab Treatment

Background: Smoking has been associated with increased multiple sclerosis (MS) risk, disease worsening, and progression in MS patients. Furthermore, interactions between smoking and human leukocyte antigen (HLA) genes have been shown for MS risk. Recently, we found that smoking was associated with an increased relapse rate in interferon-beta-treated relapsing-remitting multiple sclerosis (RRMS) patients. Objectives: We examined the association between smoking and relapses in natalizumab-treated RRMS patients. Second, we investigated if an interaction between smoking and HLA-DRB1*15:01 or HLA-A*02:01 affected the number of relapses during treatment. Methods: In this observational cohort study, 355 natalizumab-treated RRMS patients were assessed. Prespecified criteria excluded 62 patients. Clinical data from the starting of treatment to the two-year follow-up visit were collected. Smoking status was obtained by a questionnaire survey. TaqMan allelic discrimination was used for genotyping of tag single-nucleotide polymorphisms (SNPs) for HLA-DRB1*15:01 and HLA-A*02:01. Negative binomial regression analysis was used to analyze the association between relapse rate and smoking intensity and HLA. Results: One pack of cigarettes (20 cigarettes) per day during natalizumab treatment increased the relapse rate during treatment with 38% (incidence rate ratio (IRR) = 1.38, 95% confidence interval (CI): 1.08–1.77, p = 0.01). No association or interaction was found between smoking and HLA-DRB1*15:01 or HLA-A*02:01, respectively. Conclusion: Smoking intensity was significantly associated with the number of relapses during natalizumab treatment.

scholarly journals Sickness absence and disability pension after carpal tunnel syndrome diagnosis: A register-based study of patients and matched references in Sweden

2021 ◽  
pp. 140349482110027
Author(s):  
Tea Lallukka ◽  
Rahman Shiri ◽  
Kristina Alexanderson ◽  
Jenni Ervasti ◽  
Ellenor Mittendorfer-Rutz ◽  
...  
Keyword(s):  
Health Care ◽  
Carpal Tunnel Syndrome ◽  
Sickness Absence ◽  
Carpal Tunnel ◽  
Disability Pension ◽  
Negative Binomial ◽  
Age Groups ◽  
Negative Binomial Regression ◽  
Sociodemographic Factors ◽  
Tunnel Syndrome

Aims: The aim of this study was to examine sickness absence and disability pension (SA/DP) during working lifespan among individuals diagnosed with carpal tunnel syndrome (CTS) and their matched references, accounting for sociodemographic factors. Methods: We used a register cohort of 78,040 individuals aged 19–60 years when diagnosed with CTS in secondary health care (hospitals and outpatient specialist health care) and their 390,199 matched references from the general population in 2001–2010. Sociodemographic factors and SA/DP net days during a three-year follow-up were included. Negative binomial regression was used. Results: For those not on DP at inclusion, the average number of SA/DP days per person-year was 58 days (95% confidence interval (CI) 56–60 days) among individuals with CTS and 20 days (95% CI 19–21 days) among the matched references. Among both groups, these numbers increased with age and were higher among women than among men. The rate ratio (RR) of SA/DP days was threefold higher among people with CTS than among the matched references (adjusted RR=3.00, 95% CI 2.91–3.10) Moreover, compared to the matched references, the RR for SA/DP was higher among men with CTS (RR=3.86, 95% CI 3.61–4.13) than among women with CTS (RR=2.69, 95% CI 2.59–2.78). The association between CTS and the number of SA/DP days was smaller among older age groups. Sociodemographic factors were similarly associated with SA/DP among people with and without CTS. Conclusions: Numbers of SA/DP days were higher among people with CTS than their matched references in all age groups, particularly among individuals in their early work careers, highlighting public-health relevance of the findings.

scholarly journals Disease-modifying therapy prescription patterns in people with multiple sclerosis by age

2021 ◽  
Vol 14 ◽  
pp. 175628642110064
Author(s):  
Yinan Zhang ◽  
Amber Salter ◽  
Shan Jin ◽  
William J. Culpepper ◽  
Gary R. Cutter ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Age Groups ◽  
The Elderly ◽  
Department Of Veterans Affairs ◽  
Real World Data ◽  
Research Committee ◽  
The North ◽  
Disease Modifying ◽  
Magnetic Resonance Imaging Mri

Background: Disease-modifying therapies (DMTs) for multiple sclerosis (MS) are approved for their ability to reduce disease activity, namely clinical relapses and signal changes on magnetic resonance imaging (MRI). Disease activity appears age dependent. Thus, the greatest benefit would be expected in younger people with MS (PwMS) whereas benefits in the elderly are uncertain. Methods: Real-world data were obtained from PwMS from the North American Research Committee on Multiple Sclerosis (NARCOMS) registry and the US Department of Veterans Affairs Multiple Sclerosis Surveillance Registry (MSSR). Results: 6948 PwMS were surveyed from NARCOMS, and the MSSR had 1719 participants. In younger adult PwMS 40-years old or less, 183 (61.4%) in NARCOMS and 179 (70.5%) in the MSSR were prescribed DMTs. Among PwMS over age 60, 1575 (40.1%) in NARCOMS and 239 (36.3%) in the MSSR were prescribed DMTs. More PwMS in the age group of 31–40 ( p = 0.035) and 41–50 ( p = 0.001) in the MSSR were using DMTs compared with PwMS of the same age groups in NARCOMS. Conclusion: These findings suggest that DMTs are under-utilized in the younger population and continue to be commonly prescribed in the elderly. Broader access may explain the higher prescription rate of DMTs in US veterans.

scholarly journals Impact of Switching to Fingolimod Versus Injectable Disease-Modifying Therapy Cycling on Risk of Multiple Sclerosis–Related Relapses: A Retrospective Analysis

2020 ◽  
pp. 0000-0000
Author(s):  
Maria Cecilia Vieira ◽  
Yunfeng Li ◽  
Xiangyi Meng ◽  
Huanxue Zhou ◽  
Olivia Wenxian Piao ◽  
...  
Keyword(s):  
Retrospective Analysis ◽  
Relapse Rate ◽  
Real World ◽  
Negative Binomial ◽  
Office Visit ◽  
Negative Binomial Regression ◽  
Negative Binomial Regression Model ◽  
Corticosteroid Administration ◽  
Disease Modifying Therapy ◽  
Disease Modifying

Abstract Background: Clinical and real-world studies have shown significant reductions in MS relapses in patients receiving fingolimod versus injectable disease-modifying therapies (iDMTs). The objective was to compare MS relapse rate and incidence in patients switching from an iDMT to fingolimod with those cycling from one iDMT to another or those remaining on their original iDMT. Methods: A retrospective analysis was performed using MarketScan® Commercial and Medicare Supplemental claims data (July-1-2010–June-30-2016). Adult MS patients receiving ≥1 iDMT during the study were included. Relapses were identified from an MS-related hospitalization, outpatient ER or office visit, and corticosteroid administration. Annualized relapse rate ratio was estimated by negative binomial regression model with repeat-measures. Results: Of 16,352 patients, 1,110 were switchers to fingolimod, 908 were iDMT cyclers, and 14,334 were non-switchers. At baseline, rate and incidence of MS relapses were higher in switchers and iDMT cyclers versus non-switchers (P &lt; .001); mean (SD) relapse rates declined from 0.4 (0.7), 0.4 (0.7), and 0.2 (0.5) at baseline to 0.2 (0.5), 0.3 (0.6), and 0.1 (0.4) after follow-up in switchers, iDMT cyclers, and non-switchers, respectively. Relapse incidence also declined in each cohort. The highest reductions in relapse rate and incidence were observed in switchers to fingolimod, where relapse risk was significantly reduced versus iDMT cyclers (22%; P = .0433) and non-switchers (47%; P &lt; .001). Conclusions: This real-world study provides evidence that patients switching from an iDMT to fingolimod have the highest reductions in annualized rate and incidence of MS relapses, and significantly reduced risk of relapse, versus iDMT cyclers and non-switchers.

scholarly journals THE US MIDLIFE MORTALITY CRISIS CONTINUES: INCREASED DEATH RATES FROM CAUSES OTHER THAN COVID-19 DURING 2020

2021 ◽  
Author(s):  
Dana A Glei
Keyword(s):  
Indirect Effect ◽  
Causes Of Death ◽  
Excess Mortality ◽  
Negative Binomial ◽  
National Level ◽  
Age Groups ◽  
Negative Binomial Regression ◽  
Negative Binomial Regression Model ◽  
Age Group ◽  
External Causes

COVID-19 has prematurely ended many lives, particularly among the oldest Americans, but the pandemic has also had an indirect effect on health and non-COVID mortality among the working-age population, who have suffered the brunt of the economic consequences. This analysis quantifies the changes in mortality for selected causes of death during the COVID 19 pandemic up to December 31, 2020, and investigates whether the levels of excess mortality varied by age group. The data comprise national-level monthly death counts by age group and selected causes of death from January 1999 to December 2020 combined with annual mid-year population estimates over the same period. A negative binomial regression model was used to estimate monthly cause-specific excess mortality during 2020 controlling for the pre-pandemic mortality patterns by age, calendar year, and season. To determine whether excess mortality varied by age, we tested interactions between broad age groups and dichotomous indicators for the pre-pandemic (January-February) and the pandemic (March-December) portions of 2020. In relative terms, excess all cause mortality (including COVID-19) peaked in December at ages 25-44 (RR=1.58 relative to 2019, 95% CI=1.50-1.68). Excluding COVID-19, all of the excess mortality occurred between ages 15 and 64, peaking in July among those aged 25-44 (RR=1.45, 95% CI 1.37-1.53). We find notable excess mortality during March-December 2020 for many causes (i.e., influenza/pneumonia, other respiratory diseases, diabetes, heart disease, cerebrovascular disease, kidney disease, and external causes), but almost exclusively among young and midlife (aged 25-74) Americans. For those aged 75 and older, there was little excess mortality from causes other than COVID-19 except from Alzheimer's disease. Excess non-COVID mortality may have resulted, at least partly, from incorrectly classified COVID-19 deaths, but neither misclassification nor an atypical flu season that disproportionately affected younger people is likely to explain the increase in mortality from external causes, which was evident even during January-February 2020. Exploratory analyses suggest that drug-related mortality may be driving the early rise in external mortality. The growth in drug overdoses well before there was any hint of a pandemic suggests it is probably not solely an indirect effect of COVID-19, although the pandemic may have exacerbated the problem.

scholarly journals Consistent control of disease activity with fingolimod versus IFN β-1a in paediatric-onset multiple sclerosis: further insights from PARADIGMS

2019 ◽  
pp. jnnp-2019-321124 ◽  
Author(s):  
Kumaran Deiva ◽  
Peter Huppke ◽  
Brenda Banwell ◽  
Tanuja Chitnis ◽  
Jutta Gärtner ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Phase Iii ◽  
Disability Progression ◽  
Double Blind ◽  
Younger Patients ◽  
Treatment Groups ◽  
Registration Number ◽  
Treatment Naïve ◽  
Post Hoc

BackgroundIn PARADIGMS, a double-blind phase III trial in 215 paediatric patients with multiple sclerosis (MS) (10 to <18 years), fingolimod administered for up to 2 years significantly reduced the annualised relapse rate (ARR) and rate of new/newly enlarged T2 (n/neT2) lesions compared with interferon (IFN) β-1a.ObjectivesTo investigate (1) differences between treatment groups across subpopulations (treatment-naïve, younger/prepubertal patients); (2) disability progression.MethodsARRs at 10, 11 and 12 years were estimated based on predefined modelling extrapolations. Changes in Expanded Disability Status Scale (EDSS), and in 3 month (3M) and 6 month (6M) confirmed disability progression (CDP) were evaluated post hoc.ResultsIn the treatment-naïve subpopulation, fingolimod reduced ARR and n/neT2 lesions by 85.8% and 53.4%, respectively versus INF β-1a (both p<0.001), compared with 81.9% and 52.6% in the overall population. Model-based ARR reductions in younger patients (≤12 years) were 91.9%–94.6%. Twice as many IFN β-1a-treated than fingolimod-treated patients had worse EDSS scores at study end (20.6% vs 10.5%, p=0.043). Risk reductions in 3M-CDP and 6M-CDP were 77.2% (p=0.007) and 80.2% (p=0.040), respectively.ConclusionsFingolimod in paediatric MS was associated with consistent control of disease activity versus IFN β-1a (including treatment-naïve and younger patients) and resulted in less disability progression for up to 2 years.Trial registration numberNCT01892722.

scholarly journals Reproductive history of the Danish multiple sclerosis population: A register-based study

2019 ◽  
Vol 26 (8) ◽  
pp. 902-911 ◽  
Author(s):  
Julie Yoon Moberg ◽  
Bjarne Laursen ◽  
Lau Caspar Thygesen ◽  
Melinda Magyari
Keyword(s):  
Multiple Sclerosis ◽  
Regression Model ◽  
Negative Binomial ◽  
Negative Binomial Regression ◽  
Annual Number ◽  
Negative Binomial Regression Model ◽  
Live Births ◽  
Multiple Sclerosis Population ◽  
History Of ◽  
Ectopic Pregnancies

Background: A diagnosis of multiple sclerosis (MS) may impact the choice of parenthood. Objective: To investigate the number of live births, abortions and ectopic pregnancies among persons with MS. Methods: From the Danish Multiple Sclerosis Registry, we extracted data from all persons diagnosed with MS from 1960 to 1996 and matched each MS person with four reference persons. We used a negative binomial regression model for the live births and Poisson regression model for abortions and ectopic pregnancies. The total fertility rate (TFR) during 1960–2016 and the annual number of live births in the MS population were analysed. Results: Persons with MS had fewer children than reference persons. Fewer women with MS had elective abortions after diagnosis (incidence rate ratio (IRR) = 0.88; 95% confidence interval (CI) = 0.78–1.00) than reference persons. There was no difference regarding the number of elective abortions, spontaneous abortions or ectopic pregnancies after onset. The TFR was lower for women with MS than for reference persons, and the number of annual live births by MS persons increased during 1960–2016. Conclusion: MS seems to considerably impact reproductive choices, especially after clinical diagnosis, resulting in the MS population having fewer children than the general population.

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