Importance of early treatment initiation in the clinical course of multiple sclerosis

2016 ◽  
Vol 23 (9) ◽  
pp. 1233-1240 ◽  
Author(s):  
Andrius Kavaliunas ◽  
Ali Manouchehrinia ◽  
Leszek Stawiarz ◽  
Ryan Ramanujam ◽  
Jonas Agholme ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Early Treatment ◽  
Treatment Initiation ◽  
Cox Regression ◽  
Age At Onset ◽  
Hazard Ratio ◽  
Outcome Variable ◽  
Treatment Start ◽  
Disability Status

Objectives: The aim of this study was to identify factors influencing the long-term clinical progression of multiple sclerosis (MS). A special objective was to investigate whether early treatment decisions influence outcome. Methods: We included 639 patients diagnosed with MS from 2001 to 2007. The median follow-up time was 99 months (8.25 years). Cox regression models were applied to identify factors correlating with the outcome variable defined as time from treatment start to irreversible score 4 of the Expanded Disability Status Scale (EDSS). Results: Patients initiated on treatment later had a greater risk of reaching EDSS 4 (hazard ratio of 1.074 (95% confidence interval (CI), 1.048−1.101)), increased by 7.4% for every year of delay in treatment start after MS onset. Patients who started treatment after 3 years from MS onset reached the outcome sooner with hazard ratio of 2.64 (95% CI, 1.71−4.08) compared with the patients who started treatment within 1 year from MS onset. Baseline EDSS and age at onset were found to be predictive factors of disability progression. Conclusion: Early treatment initiation was associated with a better clinical outcome. In addition, we confirmed the well-established prognostic factors of late age at onset and early disability.

scholarly journals Sleep-related hypermotor epilepsy

Neurology ◽  
2016 ◽  
Vol 88 (1) ◽  
pp. 70-77 ◽  
Author(s):  
Laura Licchetta ◽  
Francesca Bisulli ◽  
Luca Vignatelli ◽  
Corrado Zenesini ◽  
Lidia Di Vito ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Age At Onset ◽  
Hazard Ratio ◽  
Seizure Freedom ◽  
Brain Disorder ◽  
Long Term Outcome

Objective:To assess the long-term outcome of sleep-related hypermotor epilepsy (SHE).Methods:We retrospectively reconstructed a representative cohort of patients diagnosed with SHE according to international diagnostic criteria, sleep-related seizures ≥75% and follow-up ≥5 years. Terminal remission (TR) was defined as a period of ≥5 consecutive years of seizure freedom at the last follow-up. We used Kaplan-Meier estimates to calculate the cumulative time-dependent probability of TR and to generate survival curves. Univariate and multivariate Cox regression analyses were performed.Results:We included 139 patients with a 16-year median follow-up (2,414 person-years). The mean age at onset was 13 ± 10 years. SHE was sporadic in 86% of cases and familial in 14%; 16% of patients had underlying brain abnormalities. Forty-five percent of patients had at least 1 seizure in wakefulness lifetime and 55% had seizures only in sleep (typical SHE). At the last assessment, 31 patients achieved TR (TR group, 22.3%), while 108 (NTR group, 77.7%) still had seizures or had been in remission for <5 years. The cumulative TR rate was 20.4%, 23.5%, and 28.4% by 10, 20, and 30 years from inclusion. At univariate analysis, any underlying brain disorder (any combination of intellectual disability, perinatal insult, pathologic neurologic examination, and brain structural abnormalities) and seizures in wakefulness were more frequent among the NTR group (p = 0.028; p = 0.043). Absence of any underlying brain disorder (hazard ratio 4.21, 95% confidence interval 1.26–14.05, p = 0.020) and typical SHE (hazard ratio 2.76, 95% confidence interval 1.31–5.85, p = 0.008) were associated with TR.Conclusions:Our data show a poor prognosis of SHE after a long-term follow-up. Its outcome is primarily a function of the underlying etiology.

Early treatment delays long-term disability accrual in RRMS: Results from the BMSD network

2021 ◽  
pp. 135245852110101
Author(s):  
Pietro Iaffaldano ◽  
Giuseppe Lucisano ◽  
Helmut Butzkueven ◽  
Jan Hillert ◽  
Robert Hyde ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cox Regression ◽  
Disease Onset ◽  
Optimal Time ◽  
Optimal Timing ◽  
Real World Data ◽  
Treatment Start ◽  
Time To First Treatment ◽  
The Impact

Background: The optimal timing of treatment starts for achieving the best control on the long-term disability accumulation in multiple sclerosis (MS) is still to be defined. Objective: The aim of this study was to estimate the optimal time to start disease-modifying therapies (DMTs) to prevent the long-term disability accumulation in MS, using a pooled dataset from the Big Multiple Sclerosis Data (BMSD) network. Methods: Multivariable Cox regression models adjusted for the time to first treatment start from disease onset (in quintiles) were used. To mitigate the impact of potential biases, a set of pairwise propensity score (PS)-matched analyses were performed. The first quintile, including patients treated within 1.2 years from onset, was used as reference. Results: A cohort of 11,871 patients (median follow-up after treatment start: 13.2 years) was analyzed. A 3- and 12-month confirmed disability worsening event and irreversible Expanded Disability Status Scale (EDSS) 4.0 and 6.0 scores were reached by 7062 (59.5%), 4138 (34.9%), 3209 (31.1%), and 1909 (16.5%) patients, respectively. The risk of reaching all the disability outcomes was significantly lower ( p < 0.0004) for the first quintile patients’ group. Conclusion: Real-world data from the BMSD demonstrate that DMTs should be commenced within 1.2 years from the disease onset to reduce the risk of disability accumulation over the long term.

scholarly journals Early Clinical Features, Time to Secondary Progression, and Disability Milestones in Polish Multiple Sclerosis Patients

Medicina ◽  
2019 ◽  
Vol 55 (6) ◽  
pp. 232 ◽  
Author(s):  
Łukasz Rzepiński ◽  
Monika Zawadka-Kunikowska ◽  
Zdzisław Maciejek ◽  
Julia L. Newton ◽  
Paweł Zalewski
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Features ◽  
Age At Onset ◽  
Disease Onset ◽  
Initial Symptoms ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Disease Variant ◽  
Multiple Sclerosis Patients

Background and Objectives: Determining the clinical course of multiple sclerosis (MS) and prediction of long-term disability can be a big challenge. To determine early clinical features of MS, their influence on long-term disability progression, and time to transition from relapsing-remitting MS (RRMS) to secondary progressive MS (SPMS), a cohort of Polish patients was studied. Materials and Methods: We retrospectively evaluated 375 Polish MS patients based on data from available medical records. We assessed early clinical MS features and the relationship between demographics and time from disease onset to attainment of 4 and 6 points on the Expanded Disability Status Scale (EDSS), as well as time to conversion from RRMS to SPMS. Results: The differences between initial MS variants were significantly associated with gender, age at disease onset, number and type of the first symptoms, and rate of the disability accrual. Mean times from disease onset to attainment of EDSS 4 and 6 were significantly influenced by the disease variant, age at onset, gender, degree of recovery from the initial symptoms, and first inter-bouts interval. The mean time to secondary progression was significantly influenced by the number and type of the first symptoms of RRMS. Conclusions: Early clinical features of MS are important in determining the disease variant, the time to transition from RRMS to SPMS, as well as predicting the disability accumulation of patients. Despite the small differences regarding the first MS symptoms, the disability outcomes in the cohort of Polish patients are similar to other regions of the world.

Pregnancy in multiple sclerosis women with relapses in the year before conception increases the risk of long-term disability worsening

2021 ◽  
pp. 135245852110233
Author(s):  
Emilio Portaccio ◽  
Laura Tudisco ◽  
Luisa Pastò ◽  
Lorenzo Razzolini ◽  
Mattia Fonderico ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Control Group ◽  
Treatment Optimization ◽  
Younger Age ◽  
Disability Status ◽  
Clinical Stability

Background: The influence of pregnancy on long-term disability in multiple sclerosis (MS) is still controversial. Objective: To assess the risk of long-term disability worsening after pregnancy in MS women as compared with a propensity-score (PS) matched group of MS women without pregnancy. Methods: In the setting of the Italian Pregnancy Dataset, MS patients with (pregnancy group (PG)) and without pregnancy (control group (CG)) were recruited. Time to disability worsening on the Expanded Disability Status Scale (EDSS) was assessed through a multivariable Cox regression model. Results: The PS-matching retained 230 PG and 102 CG patients. After a follow-up of 6.5 +/- 3.1 years, disability worsening occurred in 87 (26.2%) women. In the multivariable analysis, disability worsening was associated with pregnancy in women with relapses in the year before conception (adjusted hazard ratio (aHR) = 1.74; 95% confidence interval (CI) 1.06–2.84; p = 0.027), higher EDSS (aHR = 1.39; 95% CI 1.12–1.74; p = 0.003), younger age (aHR = 0.95; 95% CI 0.91–0.99; p = 0.022) and shorter DMD exposure over the follow-up ( p < 0.008). Conclusion: Pregnancy in MS women with relapses in the year before conception increases the risk of long-term disability worsening. Our findings underscore the importance of counselling in MS women facing a pregnancy that should be planned after a period of clinical stability, favouring treatment optimization in patients with recent disease activity.

‘Clinically definite benign multiple sclerosis’, an unwarranted conceptual hodgepodge: evidence from a 30-year observational study

2012 ◽  
Vol 19 (4) ◽  
pp. 458-465 ◽  
Author(s):  
E Leray ◽  
M Coustans ◽  
E Le Page ◽  
J Yaouanq ◽  
J Oger ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Observational Study ◽  
Medical Treatments ◽  
Clinical Onset ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Long Term Follow Up ◽  
Benign Multiple Sclerosis ◽  
New Biomarkers

Background: Benign multiple sclerosis (BMS) is a controversial concept which is still debated. However identification of this kind of patients is crucial to prevent them from unnecessary exposure to aggressive and/or long term medical treatments. Objectives: To assess two definitions of ‘clinically definite benign multiple sclerosis’ (CDBMS) using long-term follow-up data, and to look for prognostic factors of CDBMS. Methods: In 874 patients with definite relapsing–remitting MS, followed up for at least 10 years, disability was assessed using the Disability Status Scale (DSS). CDBMS was defined by either DSS score≤2 (CDBMS1 group) or DSS score≤ 3 (CDBMS2 group) at 10 years. We estimated the proportion of patients who were still benign at 20 and 30 years after clinical onset. Results: CDBMS frequency estimates were 57.7% and 73.9% when using CDBMS1 and CDBMS2 definitions, respectively. In the CDBMS1 group, only 41.7% (105/252) of cases were still benign 10 years later, and 41.1% (23/56) after an additional decade, while there were 53.8% (162/301) and 59.5% (44/74) respectively in the CDBMS2 group. Conclusions: This 30-year observational study, which is one of the largest published series, indicates that favourable 10-year disability scores of DSS 2 or 3 fail to ensure a long-term benign course of multiple sclerosis. After every decade almost half of the CDBMS were no longer benign. CDBMS, as currently defined, is an unwarranted conceptual hodgepodge. Other criteria using new biomarkers (genetic, biologic or MRI) should be found to detect benign cases of MS.

Combined visual and motor evoked potentials predict multiple sclerosis disability after 20 years

2014 ◽  
Vol 20 (10) ◽  
pp. 1348-1354 ◽  
Author(s):  
Regina Schlaeger ◽  
Christian Schindler ◽  
Leticia Grize ◽  
Sophie Dellas ◽  
Ernst W Radue ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Motor Evoked Potentials ◽  
Rank Correlation ◽  
Disease Modifying Therapy ◽  
Disability Status ◽  
Adaptive Processes ◽  
Multivariable Regression ◽  
Predictive Relationships ◽  
Magnetic Resonance Imaging Mri

Background: The development of predictors of multiple sclerosis (MS) disability is difficult due to the complex interplay of pathophysiological and adaptive processes. Objective: The purpose of this study was to investigate whether combined evoked potential (EP)-measures allow prediction of MS disability after 20 years. Methods: We examined 28 patients with clinically definite MS according to Poser’s criteria with Expanded Disability Status Scale (EDSS) scores, combined visual and motor EPs at entry (T0), 6 (T1), 12 (T2) and 24 (T3) months, and a cranial magnetic resonance imaging (MRI) scan at T0 and T2. EDSS testing was repeated at year 14 (T4) and year 20 (T5). Spearman rank correlation was used. We performed a multivariable regression analysis to examine predictive relationships of the sum of z-transformed EP latencies ( s-EPT0) and other baseline variables with EDSST5. Results: We found that s-EPT0 correlated with EDSST5 (rho=0.72, p<0.0001) and ΔEDSST5-T0 (rho=0.50, p=0.006). Backward selection resulted in the prediction model: E (EDSST5)=3.91–2.22×therapy+0.079×age+0.057× s-EPT0 (Model 1, R2=0.58) with therapy as binary variable (1=any disease-modifying therapy between T3 and T5, 0=no therapy). Neither EDSST0 nor T2-lesion or gadolinium (Gd)-enhancing lesion quantities at T0 improved prediction of EDSST5. The area under the receiver operating characteristic (ROC) curve was 0.89 for model 1. Conclusions: These results further support a role for combined EP-measures as predictors of long-term disability in MS.

scholarly journals Long-Term Safety and Efficacy of Subcutaneous Cladribine Used in Increased Dosage in Patients with Relapsing Multiple Sclerosis: 20-Year Observational Study

2021 ◽  
Vol 10 (21) ◽  
pp. 5207
Author(s):  
Konrad Rejdak ◽  
Adriana Zasybska ◽  
Aleksandra Pietruczuk ◽  
Dariusz Baranowski ◽  
Sebastian Szklener ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cumulative Dose ◽  
Induction Dose ◽  
Disability Status ◽  
Risk Of Progression ◽  
Dosing Regimens ◽  
Favorable Safety ◽  
Relapsing Multiple Sclerosis

Cladribine is currently registered as a 10-milligram tablet formulation with a fixed cumulative dosage of 3.5 mg/kg over 2 years. It is important to investigate if an increased dosage may lead to further clinical stability with preserved safety. This study used an off-label subcutaneous (s.c.) formulation of cladribine and compared outcomes (Expanded Disability Status Scale (EDSS) scores and disease progression) between 52 relapsing multiple sclerosis (RMS) patients receiving different s.c. dosing regimens with up to 20 years of follow-up. The study group received induction therapy with s.c. cladribine (1.8 mg/kg cumulative dose; consistent with 3.5 mg/kg of cladribine tablets). Patients were subsequently offered maintenance therapy (repeated courses of 0.3 mg/kg s.c. cladribine during 5–20-year follow-up). Forty-one patients received an increased cumulative dose (higher than the induction dose of 1.8 mg/kg); 11 received the standard induction dose. Risk of progression on the EDSS correlated with lower cumulative dose (p < 0.05) and more advanced disability at treatment initiation (p < 0.05) as assessed by EDSS change between year 1 and years 5 and 10 as the last follow-up. Maintenance treatment was safe and well-tolerated, based on limited source data. Subcutaneous cladribine with increased cumulative maintenance dosage was associated with disease stability and favorable safety over a prolonged period of follow-up (up to 20 years) in RMS patients.

scholarly journals Tumor Necrosis Factor Inhibition and Parkinson Disease

Neurology ◽  
2021 ◽  
Vol 96 (12) ◽  
pp. e1672-e1679
Author(s):  
Xiaoying Kang ◽  
Alexander Ploner ◽  
Nancy L. Pedersen ◽  
Sara Bandres-Ciga ◽  
Alastair J. Noyce ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Ulcerative Colitis ◽  
Tumor Necrosis Factor ◽  
Crohn Disease ◽  
Tumor Necrosis ◽  
Mendelian Randomization ◽  
Age At Onset ◽  
Multiple Sclerosis Risk ◽  
Necrosis Factor

ObjectiveTo evaluate the effects of long-term tumor necrosis factor (TNF) inhibition on the risk and age at onset of Parkinson disease (PD), we performed a 2-sample Mendelian randomization study using genome-wide association studies (GWAS) summary statistics.MethodsGenetic variants in the vicinity of TNFRSF1A, the gene encoding TNF receptor 1 (TNFR1), were identified as predictive of pharmacologic blockade of TNFR1 signaling by anti-TNF therapy, based on genetic associations with lower circulating C-reactive protein (CRP; GWAS n = 204,402). The effects of TNF-TNFR1 inhibition were estimated for PD risk (ncases/controls = 37,688/981,372) and age at PD onset (n = 28,568) using GWAS data from the International Parkinson's Disease Genomics Consortium and 23andMe, Inc. To validate variants as proxies of long-term anti-TNF treatment, we also assessed whether variant associations reflected anticipated effects of TNFR1 inhibition on Crohn disease, ulcerative colitis, and multiple sclerosis risk (n = 38,589-45,975).ResultsTNF-TNFR1 signaling inhibition was not estimated to affect PD risk (odds ratio [OR] per 10% lower circulating CRP = 0.99; 95% confidence interval [CI] 0.91–1.08) or age at onset (0.13 years later onset; 95% CI −0.66 to 0.92). In contrast, genetically indexed TNF-TNFR1 signaling blockade predicted reduced risk of Crohn disease (OR 0.75; 95% CI 0.65–0.86) and ulcerative colitis (OR 0.84; 95% CI 0.74–0.97) and increased multiple sclerosis risk (OR 1.57; 95% CI 1.36–1.81). Findings were consistent across models using different genetic instruments and Mendelian randomization estimators.ConclusionsOur findings do not imply that TNF-TNFR1 signaling inhibition will prevent or delay PD onset.Classification of EvidenceThis study provides Class II evidence that TNF-TNFR1 signaling inhibition is not associated with the risk or age at onset of PD.

124Impact of intimal tracking for recanalization of CTO lesions on long-term clinical outcomes

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Kano ◽  
K Nasu ◽  
M Habara ◽  
T Shimura ◽  
M Yamamoto ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Cox Regression ◽  
Target Lesion ◽  
Hazard Ratio ◽  
Rank Test ◽  
Total Occlusion ◽  
Significant Difference ◽  
The Impact

Abstract Background For recanalization of coronary chronic total occlusion (CTO) lesions, subintimal guidewire tracking in both antegrade and retrograde approaches are commonly used. Purpose This study aimed to assess the impact of subintimal tracking on long-term clinical outcomes after recanalization of CTO lesions. Methods Between January 2009 and December 2016, 474 CTO lesions (434patients) were successfully recanalized in our center. After guidewire crossing in a CTO lesion, those lesions were divided into intimal tracking group (84.6%, n=401) and subintimal tracking group (15.4%, n=73) according to intravascular ultrasound (IVUS) findings. Long-term clinical outcomes including death, target lesion revascularization (TLR), target vessel revascularization (TVR) were compared between the two groups. In addition, the rate of re-occlusion after successful revascularization was also evaluated. Results The median follow-up period was 4.7 years (interquartile range, 2.8–6.1). There was no significant difference of the rate of cardiac death between the two groups (intimal tracking vs. subintimal tracking: 7.0% vs. 4.1%; hazard ratio, 0.61; 95% confidence interval [CI], 0.19 to 2.00; p=0.41), TLR (14.3% vs. 16.2%; hazard ratio, 1.34; 95% CI, 0.71 to 2.53; p=0.37), and TVR (17.5% vs. 20.3%; hazard ratio, 1.27; 95% CI, 0.72 to 2.23; p=0.42). However, the rate of re-occlusion was significantly higher in the subintimal tracking group than intimal tracking group at 3-years re-occlusion (4.2% vs. 14.5%; log-rank test, p=0.002, Figure). In the multivariate COX regression, subintimal guidewire tracking was an independent predictor of re-occlusion after CTO recanalization (HR: 5.40; 95% CI: 2.11–13.80; p<0.001). Figure 1 Conclusions Subintimal guidewire tracking for recanalization of coronary CTO was associated with significantly higher incidence of target lesion re-occlusion during long-term follow-up period.

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