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 Reducing return of disease activity in patients with relapsing multiple sclerosis transitioned from natalizumab to teriflunomide: 12-month interim results of teriflunomide therapy

2019 ◽  
Vol 5 (1) ◽  
pp. 205521731882461
Author(s):  
Stanley L Cohan ◽  
Keith Edwards ◽  
Lindsay Lucas ◽  
Tiffany Gervasi-Follmar ◽  
Judy O’Connor ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Brain Magnetic Resonance Imaging ◽  
T2 Lesions ◽  
Disability Status ◽  
The Mean ◽  
Multiple Sclerosis Patients ◽  
Mean Time ◽  
Relapsing Multiple Sclerosis

Background Natalizumab is an effective treatment for relapsing multiple sclerosis. Return of disease activity upon natalizumab discontinuance creates the need for follow-up therapeutic strategies. Objective To assess the efficacy of teriflunomide following natalizumab discontinuance in relapsing multiple sclerosis patients. Methods Clinically stable relapsing multiple sclerosis patients completing 12 or more consecutive months of natalizumab, testing positive for anti-John Cunningham virus antibody, started teriflunomide 14 mg/day, 28 ± 7 days after their final natalizumab infusion. Physical examination, Expanded Disability Status Scale, laboratory assessments, and brain magnetic resonance imaging were performed at screening and multiple follow-up visits. Results Fifty-five patients were enrolled in the study. The proportion of patients relapse-free was 0.94, restricted mean time to first gadolinium-enhancing lesion was 10.9 months and time to 3-month sustained disability worsening was 11.8 months. The mean number of new or enlarging T2 lesions per patient at 12 months was 0.42. Exploratory analyses revealed an annualized relapse rate of 0.08, and a proportion of patients with no evidence of disease activity of 0.68. Forty-seven patients (85.5%) reported adverse events, 95% of which were mild to moderate. Conclusions Teriflunomide therapy initiated without natalizumab washout resulted in a low rate of return of disease activity. Clinicians may consider this a worthwhile strategy when transitioning clinically stable patients off natalizumab to another therapy. ClinicalTrials.gov Identifier: NCT01970410

Detecting clinically-relevant changes in progressive multiple sclerosis

2014 ◽  
Vol 21 (2) ◽  
pp. 171-179 ◽  
Author(s):  
LVAE Bosma ◽  
JM Sonder ◽  
JJ Kragt ◽  
CH Polman ◽  
BMJ Uitdehaag
Keyword(s):  
Multiple Sclerosis ◽  
Outcome Measurement ◽  
Progressive Multiple Sclerosis ◽  
Meaningful Change ◽  
Disability Scale ◽  
Impact Scale ◽  
Disability Status ◽  
Disease Impact

Objective: To investigate which changes in different clinical outcome measures contribute most to increased disease impact, as reported by the patient, in progressive multiple sclerosis (MS). Methods: From a cohort of prospectively-followed MS patients, we selected progressive patients with two visits, 4–6 years apart. We assessed long-term changes on the Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT) and Guy’s Neurological Disability Scale (GNDS). We defined the presence or absence of clinically meaningful change by using the Multiple Sclerosis Impact Scale (MSIS-29) as an anchor measure. We also studied change on recently identified sub-scales of GNDS. Results: Change on GNDS (especially the spinal-plus subscale) contributed most to increased disease impact. Also change on the T25FW contributed largely. Specific profiles of change in T25FW and MSIS seemed to exist (generally, a lower increase in disease impact in patients with longer disease duration and higher baseline impact/disability). In some patients a dissociation existed between increased impact, according to the MSIS-29, and objective physical worsening of the T25FW. Conclusion: These results support using GNDS (particularly the spinal-plus domain) and T25FW in outcome measurement in progressive MS. We suggest there is a relation between baseline clinical characteristics and an increased impact at follow-up. This may have implications for patient selection in trials for progressive MS.

scholarly journals Fatigue after a first attack of suspected multiple sclerosis

2017 ◽  
Vol 24 (7) ◽  
pp. 974-981 ◽  
Author(s):  
Roos M van der Vuurst de Vries ◽  
Jan JA van den Dorpel ◽  
Julia Y Mescheriakova ◽  
Tessel F Runia ◽  
Naghmeh Jafari ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Depression Scale ◽  
Common Symptom ◽  
Disability Status ◽  
Definite Multiple Sclerosis ◽  
Fatigue Severity ◽  
Clinically Definite Multiple Sclerosis ◽  
In Cis

Background: Fatigue is reported by more than 75% of multiple sclerosis (MS) patients. In an earlier study, we showed that fatigue is not only a common symptom in patients at time of clinically isolated syndrome (CIS; fatigued 46%) but also predicts subsequent diagnosis of clinically definite multiple sclerosis (CDMS). The course of fatigue after CIS is unknown. Objective: We aimed to explore the long-term course of fatigue after CIS. Methods: In this study, 235 CIS patients, aged 18–50 years, were prospectively followed. Patients filled in the Krupp’s Fatigue Severity Scale (FSS) and the Hospital Anxiety and Depression Scale (HADS) at baseline and annually. After reaching CDMS diagnosis, Expanded Disability Status Scale (EDSS) was obtained annually. Mixed-effects models were used to analyse longitudinal FSS measurements. Results: Fatigue at baseline was an independent predictor for CDMS diagnosis (hazard ratio (HR): 2.6, 95% confidence interval (CI): 1.6–4.4). The evolution of FSS was the same in CIS patients who remained monophasic and patients who were diagnosed with CDMS during follow-up. However, FSS increased by 0.86 units after reaching CDMS diagnosis ( p = 0.01). After this increase, the FSS course remained unaltered ( p = 0.44). Conclusion: Fatigue, which is often present at time of CIS, probably persists over time and increases after a second attack.

scholarly journals Brain atrophy at onset and physical disability in multiple sclerosis

2012 ◽  
Vol 70 (10) ◽  
pp. 765-768 ◽  
Author(s):  
Juan Ignacio Rojas ◽  
Liliana Patrucco ◽  
Cristina Besada ◽  
Laura Bengolea ◽  
Edgardo Cristiano
Keyword(s):  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Brain Atrophy ◽  
Physical Disability ◽  
Disease Onset ◽  
First Year ◽  
Expanded Disability Status Scale ◽  
Disability Status

The aim of this study was to investigate if brain atrophy in multiple sclerosis (MS) patients during the disease onset predicts long term disability. METHODS: MS patients with follow-up time of at least 7 years from disease onset and with baseline and second magnetic resonance 12 months later were included to measure brain atrophy. Expanded Disability Status Scale (EDSS) was categorized in three groups, EDSS=0, EDSS=1 and 2.5 and EDSS>2.5, and used as disability measure. RESULTS: Twenty-six patients were included. Mean atrophy during the first year in patients that reached an EDSS≥3 was -0.76±0.45 %, in patients with an EDSS between 1 and 2.5 was -0.59±0.56, while in patients with an EDSS of 0 it was -0.38±0.42 (p=0.003). DISCUSSION: Brain atrophy rates during the first year of disease were predictive of disease progression in our population.

Long-term survival of patients with multiple sclerosis in West France

2007 ◽  
Vol 13 (7) ◽  
pp. 865-874 ◽  
Author(s):  
E. Leray ◽  
SP Morrissey ◽  
J. Yaouanq ◽  
M. Coustans ◽  
E. Le Page ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
General Population ◽  
Fold Increase ◽  
French Population ◽  
Term Survival ◽  
Survival Probabilities ◽  
Clinical Onset ◽  
Disability Status

In France no data have been published about comparing survival in multiple sclerosis (MS) patients with the general French population. We estimated survival probabilities in MS patients from a major centre for MS in West France. We also compared MS survival with the general population and assessed prognostic parameters. All patients with MS onset after January 1976 and classified as dead or alive on 1 January 2004 were included. One thousand eight-hundred and seventy-nine patients (sex ratio W: M 2.3; relapsing/progressive onset 77.4%/22.6%) fulfilled these criteria, disease duration ranged from one to 28 years. By 2004, 68 patients died (51 due to MS) and the 15 and 25-year survival probabilities were 96% and 88%. Male gender, progressive course (either primary or secondary), polysymptomatic onset, and increased annual relapse rate during the first two years of MS were related to a worse prognosis. After a mean follow-up duration of 12.7 years since clinical onset, MS increased the number of deaths compared with the general population. However taking into account disability status, we found that less disabled MS patients had a better survival and highly disabled patients a worse survival (eight-fold increase of mortality) compared with the French population. Multiple Sclerosis 2007; 13: 865—874. http://msj.sagepub.com

scholarly journals Tumefactive demyelination: Clinical outcomes, lesion evolution and treatments

2019 ◽  
Vol 5 (2) ◽  
pp. 205521731985575 ◽  
Author(s):  
Staley A Brod ◽  
J William Lindsey ◽  
Flavia Nelson
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Outcomes ◽  
Demyelinating Disease ◽  
Mass Effect ◽  
Disability Status ◽  
Demyelinating Lesions ◽  
Lesion Regression ◽  
The Relationship

Objective Large demyelinating lesions with possible mass effect (tumefactive multiple sclerosis or tumefactive demyelination) can be mistaken for tumour-like space-occupying lesions suggesting a malignant outcome. Methods We reviewed our own experience of multiple sclerosis subjects ( n = 28) with tumefactive demyelination to determine the relationship between clinical outcomes and lesion evolution, clinical outcomes and their relationship to different therapies. Patients with central nervous system demyelinating disease were identified from our database over the last 10 years. Results No patient increased in extended disability status scale (EDSS). Overall, lesion regression was associated with improved EDSS. Lesion regression was also associated with therapy versus no therapy. No specific therapy or corticosteroid infusions improved EDSS over the long term. The absence of enhancement on follow up on magnetic resonance imaging portended lesion regression. Conclusion Tumefactive demyelination may predict a more benign overall course and is susceptible to traditional immunomodulatory treatments.

scholarly journals Subcutaneous cladribine to treat multiple sclerosis: experience in 208 patients

2021 ◽  
Vol 14 ◽  
pp. 175628642110576
Author(s):  
Kimberley Allen-Philbey ◽  
Stefania De Trane ◽  
Zhifeng Mao ◽  
Cesar Álvarez-González ◽  
Joela Mathews ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Stage ◽  
Neurofilament Light Chain ◽  
Skin Reactions ◽  
Neurofilament Light ◽  
Disability Status ◽  
Walking Tests ◽  
Grade 3

Objective: To report on safety and effectiveness of subcutaneous cladribine (Litak®) in multiple sclerosis (MS) patients. Methods: Litak® was offered to MS-patients irrespective of disease course. Litak® 10 mg was administered for 3–4 days during week 1. Based on lymphocyte count at week 4, patients received another 0–3 doses at week 5. A second course was administered 11 months later. Follow-up included adverse events, relapses, expanded disability status scale (EDSS), 9-hole-peg and Timed-25-foot-walking tests, no-evidence-of-disease-activity (NEDA), no-evidence-of-progression-or-active-disease (NEPAD), MRI, cerebrospinal fluid (CSF) neurofilament light chain (NfL), and lymphocyte counts. Results: In all, 208 patients received at least one course of treatment. Age at baseline was 44 (17–72) years and EDSS 0–8.5. Cladribine was generally well tolerated. One myocardial infarction, one breast cancer, and three severe skin reactions occurred without long-term sequelae. Two patients died (one pneumonia, one encephalitis). Lymphopenia grade 3 occurred in 5% and grade 4 in 0.5%. In 94 out of 116 pwMS with baseline and follow-up (BaFU) data after two treatment courses, EDSS remained stable or improved. At 18 months, 64% of patients with relapsing MS and BaFU data ( n = 39) had NEDA. At 19 months, 62% of patients with progressive MS and BaFU data ( n = 13) had NEPAD. Of n = 13 patients whose CSF-NfL at baseline was elevated, 77% were normalised within 12 months. Conclusions: Litak® was well tolerated. Effectiveness in relapsing MS appeared similar to cladribine tablets and was encouraging in progressive MS. Our data suggest cladribine may be safe and effective in MS-patients irrespective of their disease stage.

scholarly journals Decreasing impact of late relapses on disability worsening in secondary progressive multiple sclerosis

2019 ◽  
Vol 26 (8) ◽  
pp. 924-935
Author(s):  
Kevin Ahrweiller ◽  
Chloé Rousseau ◽  
Emmanuelle Le Page ◽  
Emma Bajeux ◽  
Emmanuelle Leray ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Short Term ◽  
Secondary Progressive ◽  
Increased Risk ◽  
Disability Status ◽  
Long Term Follow Up

Background: Changes in relapse activity during secondary progressive multiple sclerosis (SPMS) need to be accurately characterized in order to identify patients who might benefit from continuing disease-modifying therapies. Objective: To describe relapse occurrence in patients with SPMS during long-term follow-up and assess its impact on disability worsening. Methods: This retrospective cohort study included 506 patients. We assessed the influence of relapses on time from SPMS onset to an Expanded Disability Status Scale score of 6 (EDSS 6), and on irreversible worsening of EDSS scores across different periods. Results: The annualized relapse rate (ARR) decreased with patient’s age (mean reduction of 43% per decade) and SPMS duration (mean reduction of 46% every 5 years). Post-progression relapses were associated with shorter time from secondary progressive (SP) phase onset to EDSS 6 (hazard ratio (HR) = 1.29, 95% confidence interval (CI) = (1.01, 1.64)). Relapse occurrence during the first 3 years and 3–5 years after SP onset was associated with an increased risk of irreversible EDSS worsening (OR = 3.12 (1.54, 6.31) and 2.04 (1.16, 3.58)). This association was no longer significant after 5 years. Conclusion: The occurrence of relapses was a marker of short-term disability progression during early SPMS, but did not have decisive impact in later SPMS.

scholarly journals Rituximab versus mitoxantrone: comparing effectiveness and safety in advanced relapsing multiple sclerosis

2021 ◽  
Vol 12 ◽  
pp. 204062232110243
Author(s):  
Zrzavy Tobias ◽  
Daniels Esther ◽  
Stuka Niklas ◽  
Weber Dennis ◽  
Winkelmann Alexander ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Propensity Score ◽  
Adverse Events ◽  
Lower Probability ◽  
Disability Progression ◽  
Treatment Groups ◽  
Off Label ◽  
Favorable Safety ◽  
Relapsing Multiple Sclerosis

Background: Rituximab (RTX), a CD20 depleting agent, is a frequently used off-label treatment for multiple sclerosis (MS), while mitoxantrone (MTX) is approved, albeit rarely used for active relapsing MS (RMS). However, observational data comparing RTX and MTX effectiveness and safety are scarce. Objective: We aimed to compare effectiveness and safety of MTX and RTX in patients with active RMS. Methods: From combined retrospective clinical data of three MS centers, we selected patients who had received at least one infusion of RTX or MTX and had at least a 6-month clinical follow-up available. Treatment groups were compared by propensity score (PS)-adjusted regression and inverse PS-weighted generalized estimated equation models regarding disability progression, relapse activity, and adverse events (AEs). Results: We included 292 RMS patients (mean age 41.8 years, 71.6% female) who received RTX (119 patients, mean age 36.8 years, 74.8% female) or MTX (173 patients mean age 45.3 years, 69.4% female). Using both PS methods, we did not find a significant effect favoring RTX or MTX treatment regarding the probability of disability worsening or relapse occurrence. However, RTX treatment was associated with a significantly lower probability of severe AEs and AEs. Conclusions: RTX shows comparable effectiveness but a favorable safety profile compared with MTX in active RMS.

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