scholarly journals Long-term survival analysis of masitinib in amyotrophic lateral sclerosis

2021 ◽  
Vol 14 ◽  
pp. 175628642110303
Author(s):  
Jesus S. Mora ◽  
Walter G. Bradley ◽  
Delia Chaverri ◽  
María Hernández-Barral ◽  
Javier Mascias ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Survival Analysis ◽  
Phase Iii ◽  
Progression Rate ◽  
Term Survival ◽  
Risk Of Death ◽  
Severe Impairment ◽  
Phase Iii Study ◽  
Lateral Sclerosis

Background: A randomized, placebo-controlled phase III study (AB10015) previously demonstrated that orally administered masitinib (4.5 mg/kg/day) slowed rate of functional decline, with acceptable safety, in amyotrophic lateral sclerosis (ALS) patients having an ALS Functional Rating Scale-revised (ALSFRS-R) progression rate from disease onset to baseline of <1.1 points/month. Here we assess long-term overall survival (OS) data of all participants from study AB10015 and test whether a signal in OS is evident in an enriched patient population similar to that prospectively defined for confirmatory study AB19001. Methods: Survival status of all patients originally randomized in AB10015 was collected from participating investigational sites. Survival analysis (using the multivariate log-rank test and Cox proportional hazards model, with stratification factors as covariates) was performed on the intention-to-treat population and enriched subgroups, which were defined according to initial randomization, baseline ALSFRS-R progression rate and baseline disease severity. Results: A significant survival benefit of 25 months ( p = 0.037) and 47% reduced risk of death ( p = 0.025) was observed for patients receiving 4.5 mg/kg/day masitinib ( n = 45) versus placebo ( n = 62) in an enriched cohort with ⩾2 on each baseline ALSFRS-R individual component score (i.e. prior to any complete loss or severe impairment of functionality) and post-onset ALSFRS-R progression rate <1.1 (i.e. exclusion of very fast progressors) [median OS of 69 versus 44 months, respectively; hazard ratio, 0.53 [95% CI (0.31–0.92)]]. This corresponds to the population enrolled in confirmatory phase III study, AB19001. Conclusions: Analysis of long-term OS (75 months average follow-up from diagnosis) indicates that oral masitinib (4.5 mg/kg/day) could prolong survival by over 2 years as compared with placebo, provided that treatment starts prior to severe impairment of functionality. This trial was registered at www.ClinicalTrials.gov under identifier NCT02588677 (28 October 2015).

scholarly journals Improved Long-Term Survival with Edaravone Therapy in Patients with Amyotrophic Lateral Sclerosis: A Retrospective Single-Center Study in Japan

2021 ◽  
Vol 14 (8) ◽  
pp. 705
Author(s):  
Hideki Houzen ◽  
Takahiro Kano ◽  
Kazuhiro Horiuchi ◽  
Masahiro Wakita ◽  
Azusa Nagai ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Rank Test ◽  
Positive Pressure ◽  
Control Group ◽  
Single Center ◽  
Term Survival ◽  
Long Term Survival ◽  
Kaplan Meier ◽  
Lateral Sclerosis

Reports on the long-term survival effect of edaravone, which was approved for the treatment of amyotrophic lateral sclerosis (ALS) in 2015 in Japan, are rare. Herein, we report our retrospective analysis of 45 consecutive patients with ALS who initially visited our hospital between 2013 and 2018. Of these, 22 patients were treated with edaravone for an average duration of 26.6 (range, 2–64) months, whereas the remaining patients were not treated with edaravone and comprised the control group. There were no differences in baseline demographics between the two groups. The primary endpoint was tracheostomy positive-pressure ventilation (TPPV) or death, and the follow-up period ended in December 2020. The survival rate was significantly better in the edaravone group than in the control group based on the Kaplan–Meier analysis, which revealed that the median survival durations were 49 (9–88) and 25 (8–41) months in the edaravone and control groups, respectively (p = 0.001, log-rank test). There were no serious edaravone-associated adverse effects during the study period. Overall, the findings of this single-center retrospective study suggest that edaravone might prolong survival in patients with ALS.

scholarly journals Role of Blood Neurofilaments in the Prognosis of Amyotrophic Lateral Sclerosis: A Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yan-ni Zhou ◽  
You-hong Chen ◽  
Si-qi Dong ◽  
Wen-bo Yang ◽  
Ting Qian ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Meta Analysis ◽  
Progression Rate ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Risk Of Death ◽  
Disease Progression Rate ◽  
Als Patients ◽  
Lateral Sclerosis

Background: Neurofilaments in cerebrospinal fluid (CSF) and in blood are considered promising biomarkers of amyotrophic lateral sclerosis (ALS) because their levels can be significantly increased in patients with ALS. However, the roles of neurofilaments, especially blood neurofilaments, in the prognosis of ALS are inconsistent. We performed a meta-analysis to explore the prognostic roles of blood neurofilaments in ALS patients.Methods: We searched all relevant studies on the relationship between blood neurofilament levels and the prognosis of ALS patients in PubMed, Embase, Scopus, and Web of Science before February 2, 2021. The quality of the included articles was assessed using the Quality in Prognosis Studies (QUIPS) scale, and R (version 4.02) was used for statistical analysis.Results: Fourteen articles were selected, covering 1,619 ALS patients. The results showed that higher blood neurofilament light chain (NfL) levels in ALS patients were associated with a higher risk of death [medium vs. low NfL level: HR = 2.43, 95% CI (1.34–4.39), p &lt; 0.01; high vs. low NfL level: HR = 4.51, 95% CI (2.45–8.32), p &lt; 0.01]. There was a positive correlation between blood phosphorylated neurofilament heavy chain (pNfH) levels and risk of death in ALS patients [HR = 1.87, 95% CI (1.35–2.59), p &lt; 0.01]. The levels of NfL and pNfH in blood positively correlated with disease progression rate (DPR) of ALS patients [NfL: summary r = 0.53, 95% CI (0.45–0.60), p &lt; 0.01; pNfH: summary r = 0.51, 95% CI (0.24–0.71), p &lt; 0.01].Conclusion: The blood neurofilament levels can predict the prognosis of ALS patients; specifically, higher levels of blood neurofilaments are associated with a greater risk of death.

Long-term survival in amyotrophic lateral sclerosis after stem cell transplantation into the frontal motor cortex

Cytotherapy ◽  
2016 ◽  
Vol 18 (6) ◽  
pp. 806-808 ◽  
Author(s):  
Héctor R. Martínez ◽  
María Teresa González-Garza ◽  
Jorge Moreno-Cuevas ◽  
César E. Escamilla-Ocañas ◽  
Juan Miguel Tenorio-Pedraza ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Stem Cell ◽  
Motor Cortex ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Term Survival ◽  
Long Term Survival ◽  
Lateral Sclerosis

scholarly journals Prediction of survival in amyotrophic lateral sclerosis: a nationwide, Danish cohort study

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Anne-Lene Kjældgaard ◽  
Katrine Pilely ◽  
Karsten Skovgaard Olsen ◽  
Anders Hedegaard Jessen ◽  
Anne Øberg Lauritsen ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Survival Analysis ◽  
Prognostic Marker ◽  
Palliative Treatment ◽  
Rating Scale ◽  
Prognostic Markers ◽  
Progression Rate ◽  
Duration Of Symptoms ◽  
Sporadic Als ◽  
Lateral Sclerosis

Abstract Introduction Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease with great heterogeneity. Biological prognostic markers are needed for the patients to plan future supportive treatment, palliative treatment, and end-of-life decisions. In addition, prognostic markers are greatly needed for the randomization in clinical trials. Objective This study aimed to test the ALS Functional Rating Scale-Revised (ALSFRS-R) progression rate (ΔFS) as a prognostic marker of survival in a Danish ALS cohort. Methods The ALSFRS-R score at test date in association with duration of symptoms, from the onset of symptoms until test date, (defined as ΔFS’) was calculated for 90 Danish patients diagnosed with either probable or definite sporadic ALS. Median survival time was then estimated from the onset of symptoms until primary endpoint (either death or tracheostomy). ΔFS’ was subjected to survival analysis using Cox proportional hazards modelling, log-rank test, and Kaplan-Meier survival analysis. Results and conclusions Both ΔFS’ and age was found to be strong predictors of survival of the Danish ALS cohort. Both variables are easily obtained at the time of diagnosis and could be used by clinicians and ALS patients to plan future supportive and palliative treatment. Furthermore, ΔFS’, is a simple, prognostic marker that predicts survival in the early phase of disease as well as at later stages of the disease.

Efficacy of CAB therapy in stage C prostate cancer: Exploratory analyses based on results of a double-blind, randomized, placebo-controlled phase III study of bicalutamide

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5154-5154 ◽  
Author(s):  
H. Akaza ◽  
Y. Arai ◽  
H. Kanetake ◽  
S. Naito ◽  
M. Usami
Keyword(s):  
Prostate Cancer ◽  
Locally Advanced ◽  
Phase Iii ◽  
Double Blind ◽  
Term Survival ◽  
Class Time ◽  
Phase Iii Study ◽  
Better Than ◽  
Observation Period

5154 Background: Although the efficacy of CAB in advanced prostate cancer (PC) has been demonstrated by the PCTCG and others, more evidence is required in locally advanced (Stage C) PC. The results of a Japanese P III study of bicalutamide in Stage C/D PC suggested the efficacy of CAB was better than monotherapy. When time to progression (TTP) was evaluated in Stage C and D separately, CAB had significant benefits in both stages and results in stage D were consistent with PCTCG data. Thus, this exploratory analysis was conducted to evaluate more thoroughly the efficacy of CAB in Stage C. Methods: 205 untreated PC patients with Stage C/D were randomized to CAB (goserelin 3.6 mg/4 weeks or leuprorelin 3.75 mg/4 weeks + bicalutamide 80 mg/day) or LHRHa monotherapy (same LHRHa + placebo). Among these patients, 99 had Stage C (52/47 on CAB/monotherapy). The median of the following parameters were calculated, and log-rank tests performed: TTP in all Stage C patients; TTP in Stage C patients by age, PSA value at diagnosis, and histopathological class; time to PSA normalization when normal level was defined as =4, =1 and =0.2 ng/mL. Results: The median observation period in Stage C patients was 144 weeks. The median TTPs by each parameter in Stage C are shown below. The median times to PSA normalization on CAB and monotherapy were 7 and 16 weeks (p<0.01), 8 and 93 weeks (p<0.01) and 20 weeks and NR (p<0.01) with normal values defined as =4, =1 and =0.2 ng/mL, respectively. Conclusions: These results suggest that CAB with bicalutamide possesses superior efficacy to LHRHa monotherapy in Stage C regardless of age, PSA value at diagnosis, or degree of tumor differentiation. It is suggested that CAB in Stage C could decrease PSA to lower levels in a shorter period than with LHRHa monotherapy. The study is ongoing to assess long term survival outcome. [Table: see text] No significant financial relationships to disclose.

Sign in / Sign up

Export Citation Format

Share Document