Natalizumab in pediatric multiple sclerosis: results of a cohort of 55 cases

2013 ◽  
Vol 19 (8) ◽  
pp. 1106-1112 ◽  
Author(s):  
A Ghezzi ◽  
C Pozzilli ◽  
LME Grimaldi ◽  
L Moiola ◽  
V Brescia-Morra ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Median Number ◽  
Limited Information ◽  
Long Term Effects ◽  
Strong Suppression ◽  
Pediatric Multiple Sclerosis ◽  
Disability Status ◽  
Pre Treatment ◽  
Magnetic Resonance Imaging Mri

Background: Limited information is available on the use of natalizumab (NA) in pediatric multiple sclerosis (ped-MS) patients. Objective: The purpose of this study was to describe the long-term effects of NA in a large cohort of active ped-MS patients. Methods: Patients with definite ped-MS were treated with NA if in the previous year they had experienced at least two relapses or a severe relapse with incomplete recovery while on immunomodulating treatment, or at least two relapses and new magnetic resonance imaging (MRI) lesions regardless of any prior treatment. Results: The study included 55 patients (mean age: 14.4 years, mean number of relapses: 4.4, pre-treatment mean disease duration: 25.5 months). They received a median number of 26 infusions. Three relapses occurred during the follow-up, one female patient continued to deteriorate in cognitive functioning. Mean Expanded Disability Status Scale (EDSS) scores decreased from 2.7 to 1.9 at the last visit ( p<0.001). During the follow-up the majority of patients remained free from MRI activity. Transient and mild clinical adverse events occurred in 20 patients. Mild hematological abnormalities occurred in seven patients. Anti-JCV antibodies were detected in 20/51 tested patients. Conclusions: NA was well tolerated in all patients. A strong suppression of disease activity was observed in the majority of patients during the follow-up.

scholarly journals Determinants of therapeutic lag in multiple sclerosis

2021 ◽  
pp. 135245852098130
Author(s):  
Izanne Roos ◽  
Emmanuelle Leray ◽  
Federico Frascoli ◽  
Romain Casey ◽  
J William L Brown ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Expanded Disability Status Scale ◽  
Disability Progression ◽  
Delayed Onset ◽  
Disease Characteristics ◽  
Disability Status ◽  
Male Sex ◽  
Pre Treatment ◽  
Patient Subgroups

Background: A delayed onset of treatment effect, termed therapeutic lag, may influence the assessment of treatment response in some patient subgroups. Objectives: The objective of this study is to explore the associations of patient and disease characteristics with therapeutic lag on relapses and disability accumulation. Methods: Data from MSBase, a multinational multiple sclerosis (MS) registry, and OFSEP, the French MS registry, were used. Patients diagnosed with MS, minimum 1 year of exposure to MS treatment and 3 years of pre-treatment follow-up, were included in the analysis. Studied outcomes were incidence of relapses and disability accumulation. Therapeutic lag was calculated using an objective, validated method in subgroups stratified by patient and disease characteristics. Therapeutic lag under specific circumstances was then estimated in subgroups defined by combinations of clinical and demographic determinants. Results: High baseline disability scores, annualised relapse rate (ARR) ⩾ 1 and male sex were associated with longer therapeutic lag on disability progression in sufficiently populated groups: females with expanded disability status scale (EDSS) < 6 and ARR < 1 had mean lag of 26.6 weeks (95% CI = 18.2–34.9), males with EDSS < 6 and ARR < 1 31.0 weeks (95% CI = 25.3–36.8), females with EDSS < 6 and ARR ⩾ 1 44.8 weeks (95% CI = 24.5–65.1), and females with EDSS ⩾ 6 and ARR < 1 54.3 weeks (95% CI = 47.2–61.5). Conclusions: Pre-treatment EDSS and ARR are the most important determinants of therapeutic lag.

Comparison of rituximab originator (MabThera®) to biosimilar (Truxima®) in patients with multiple sclerosis

2020 ◽  
pp. 135245852091217 ◽  
Author(s):  
Thomas Perez ◽  
Audrey Rico ◽  
Clémence Boutière ◽  
Adil Maarouf ◽  
Marjorie Roudot ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Events ◽  
Efficacy And Safety ◽  
Middle Income ◽  
Middle Income Countries ◽  
Disability Status ◽  
Baseline Characteristics ◽  
Magnetic Resonance Imaging Mri ◽  
Improve Access

Background: Rituximab’s originator MabThera® or Rituxan® has demonstrated high efficacy in multiple sclerosis (MS). Because of the patent expiration, rituximab biosimilars have been developed. However, because a biosimilar is not the exact copy of the originator, the efficacy and safety of a biosimilar may significantly differ. Objectives: To compare the efficacy and safety of the biosimilar Truxima® and the originator MabThera® in MS. Methods: Consecutive MS patients receiving MabThera® or Truxima® were prospectively followed during 1 year after treatment introduction. Allocation to each treatment depended on the period of introduction and not the physician’s choice. Lymphocyte count, clinical and magnetic resonance imaging (MRI) activity, Expanded Disability Status Scale (EDSS), and adverse events were compared. Results: In total, 105 and 40 patients received MabThera® and Truxima®, respectively. The two groups did not differ in baseline characteristics. Effect on CD19+ lymphocytes and disease activity were similar during follow-up. EDSS remained stable, with no difference between groups. Adverse events were similar between groups. Conclusion: The efficacy and safety of the rituximab biosimilar Truxima® seem equivalent to the originator MabThera® in MS patients. Truxima® could represent a relatively cheap and safe therapeutic alternative to MabThera® and could improve access to highly efficient therapy for MS in low- or middle-income countries.

scholarly journals Short-term outcomes of pediatric multiple sclerosis patients treated with alemtuzumab at a Canadian University multiple sclerosis clinic

2020 ◽  
Vol 6 (2) ◽  
pp. 205521732092661
Author(s):  
David Jure Hunt ◽  
Anthony Traboulsee
Keyword(s):  
Multiple Sclerosis ◽  
Stable Disease ◽  
Expanded Disability Status Scale ◽  
Short Term ◽  
Pediatric Multiple Sclerosis ◽  
Risks And Benefits ◽  
Disability Status ◽  
Infusion Reactions ◽  
Multiple Sclerosis Patients

There is a lack of literature documenting the use of alemtuzumab in pediatric multiple sclerosis (MS) patients. Here we describe a 16-year-old and a 17-year-old patient receiving alemtuzumab and being followed for 37 months and 20 months, respectively. Both patients experienced a 1.0 decrease in Expanded Disability Status Scale since initial alemtuzumab infusion and had stable disease. No serious infusion reactions, infections, or definite relapses were recorded on follow-up. Alemtuzumab has been relatively well-tolerated and effective; however, larger, longer-term studies are necessary to understand the specific risks and benefits of alemtuzumab in pediatric MS.

Characterizing cognitive function during relapse in multiple sclerosis

2014 ◽  
Vol 20 (13) ◽  
pp. 1745-1752 ◽  
Author(s):  
Ralph HB Benedict ◽  
Sarah Morrow ◽  
Jonathan Rodgers ◽  
David Hojnacki ◽  
Margaret A Bucello ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Test Performance ◽  
Clinical Status ◽  
Cognitive Change ◽  
Expanded Disability Status Scale ◽  
Resonance Imaging ◽  
Disability Status ◽  
Magnetic Resonance Imaging Mri ◽  
Meaningful Event

Objective: To characterize neuropsychological (NP) test performance during multiple sclerosis (MS) relapse and recovery. Methods: Clinical status was assessed with NP testing and Expanded Disability Status Scale (EDSS) in 24 relapsing patients, and 24 individually-matched, stable controls. All presented with cognitive symptoms as indicated by patient, clinician or caregiver perceived decline, but were free of optic neuritis, ataxia and upper extremity weakness that could compromise NP testing. The presence of enhancing magnetic resonance imaging (MRI) lesions was considered confirmatory of relapse. Relapsing patients were treated with corticosteroids. NP testing and EDSS were compared to pre-relapse baseline levels, and three-month, post-relapse, follow-up. Results: Analyses revealed significant decline on the Symbol Digit Modalities Test (SDMT) ( p=0.005) and worsening on EDSS ( p=0.019). Impairment was observed at the point of relapse in cases but not controls. The groups were no longer different at three-month follow-up. The increment of decline on SDMT was 3.5 raw score points, or roughly 6%. Conclusions: This is the first study to assess NP status changes during MS relapse using well established, reliable metrics. The presence of a clinically meaningful event is substantiated by decline in NP testing, observed or reported cognitive change, and in a subset of patients, gadolinium-enhancing MRI lesions.

scholarly journals Real-world effectiveness of dimethyl fumarate versus fingolimod in a cohort of patients with multiple sclerosis using standardized, quantitative outcome metrics

2022 ◽  
Vol 8 (1) ◽  
pp. 205521732110698
Author(s):  
Carrie M Hersh ◽  
Arman Altincatal ◽  
Nicholas Belviso ◽  
Shivani Kapadia ◽  
Carl de Moor ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Sensitivity Analysis ◽  
Real World ◽  
Dimethyl Fumarate ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Brain Volume Loss ◽  
Disability Status ◽  
Magnetic Resonance Imaging Mri

Background Prior studies suggest comparable effectiveness of dimethyl fumarate (DMF) and fingolimod (FTY) in multiple sclerosis (MS) using relapse, Expanded Disability Status Score (EDSS), and magnetic resonance imaging (MRI) lesion metrics. Objective Compare the real-world effectiveness of DMF versus FTY using quantitative, validated neuroperformance tests, MRI, and serum neurofilament light chain (sNfL) outcomes while controlling for between-group differences. Methods Patients were eligible if on DMF or FTY when first enrolled in the MS Partners Advancing Technology and Health Solutions (MS PATHS) network and had ≥1-year follow-up in MS PATHS. Sensitivity analysis included a subgroup who started DMF/FTY ≤2 years from enrolment. After propensity score weighting, differences in means and in mean 1-year change of neuroperformance and MRI outcomes were compared. sNfL levels were assessed. This was a non-randomized comparison. Results In the overall cohort, no significant differences were observed between DMF ( n = 702) and FTY ( n = 600) in neuroperformance or MRI outcomes including brain volume loss; mean time (SD) since treatment initiation was 1.98 (0.68) years for DMF and 2.02 (0.75) years for FTY. A sensitivity analysis controlling for DMF and FTY treatment duration yielded similar results. Conclusion In this study, DMF and FTY demonstrated similar effects on physical and cognitive neuroperformance and MRI outcomes. Direct comparisons to other fumarates and S1P receptor modulators were not conducted.

Pediatric onset multiple sclerosis: McDonald criteria 2010 and the contribution of spinal cord MRI

2013 ◽  
Vol 19 (10) ◽  
pp. 1330-1335 ◽  
Author(s):  
Hannah-Maria Hummel ◽  
Wolfgang Brück ◽  
Steffi Dreha-Kulaczewski ◽  
Jutta Gärtner ◽  
Jens Wuerfel
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Age At Onset ◽  
Regional Distribution ◽  
Pediatric Multiple Sclerosis ◽  
Mcdonald Criteria ◽  
Spinal Mri ◽  
Magnetic Resonance Imaging Mri ◽  
Pediatric Onset

Background: Diagnostic magnetic resonance imaging (MRI) criteria have not been sufficiently validated in pediatric multiple sclerosis (MS) despite differences in epidemiologic data and clinical disease courses between pediatric and adult MS. Objective: The objective of this paper is to evaluate the diagnostic applicability and validity of the revised McDonald diagnostic criteria 2010 in a large cohort of pediatric-onset MS patients (POMS) and compare them to previously recommended MRI-based classifications. Furthermore, we aimed to investigate the contribution of spinal cord lesions to the revised McDonald criteria 2010. Methods: A cohort of 85 patients with definite MS, age at onset 2.8–18 years, was analyzed in a retrospective multicenter study. Number and regional distribution of T2w and contrast-enhancing T1w lesions at initial and follow-up MRIs were main outcome measures. Results: In 62% of POMS the initial MRI within four weeks after symptom onset was sufficient to diagnose MS according to the revised McDonald criteria 2010. In a subcohort of patients with spinal MRI at first presentation, 10% reached the dissemination in space (DIS) and dissemination in time (DIT) criteria only by the inclusion of contrast-enhancing spinal lesions. Conclusions: The revised McDonald criteria 2010 facilitate the diagnosis of POMS already at first presentation. The addition of a spinal cord MRI was helpful only in selected cases.

Recovery of cognitive function after relapse in multiple sclerosis

2020 ◽  
Vol 27 (1) ◽  
pp. 71-78 ◽  
Author(s):  
Ralph HB Benedict ◽  
Jeta Pol ◽  
Faizan Yasin ◽  
David Hojnacki ◽  
Channa Kolb ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Processing ◽  
Verbal Memory ◽  
Patient Reported Outcomes ◽  
Patient Reported ◽  
Disability Status ◽  
Neurological Exam ◽  
Magnetic Resonance Imaging Mri ◽  
Cognitive Processing Speed

Background: Cognitive impairment is common in multiple sclerosis (MS) but its manifestation as acute disease activity is underappreciated. Objective: The aim of this study is to examine recovery after MS relapse on multiple tests of cognitive and motor function and explore correlates of change with Expanded Disability Status Scale (EDSS), magnetic resonance imaging (MRI), and cognitive reserve. Methods: Fifty relapsing group (RG) and matched stable participants were examined at baseline, during relapse, and at 3-month follow-up. Tests of cognitive processing speed (Symbol Digit Modalities Test (SDMT)) and consensus opinion measures of memory, ambulation, and manual dexterity were administered. All RG patients were treated with a 5-day course of Acthar Gel (5 mL/80 IU). Results: In RG patients, SDMT declined from 55.2 to 44.6 at relapse and recovered to 51.7, a slope differing from stable controls ( p = 0.001). A statistical trend ( p = 0.07) for the same effect was observed for verbal memory and was significant for ambulation ( p = 0.03). The Cerebral Function Score from the EDSS also changed in the RG and recovered incompletely relative to controls ( p = 0.006). Conclusion: These results replicate earlier reports of cognitive worsening during relapse in MS. Clinically meaningful improvements followed relapse on SDMT and ambulation. Cognitive decline during relapse can be appreciated on neurological exam but not patient-reported outcomes.

scholarly journals Safety and Efficacy of Rituximab in Multiple Sclerosis: A Retrospective Observational Study

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Bassem I. Yamout ◽  
Nabil K. El-Ayoubi ◽  
Johny Nicolas ◽  
Yehya El Kouzi ◽  
Samia J. Khoury ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Relapse Rate ◽  
Perianal Abscess ◽  
Disability Progression ◽  
Surgical Interventions ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Clinical Practice Setting ◽  
Magnetic Resonance Imaging Mri

Objective. To evaluate the efficacy and safety of rituximab in multiple sclerosis in a clinical practice setting. Methods. Clinical data for all adult patients with multiple sclerosis (MS) treated with off-label rituximab at a single MS center in Lebanon between March 2008 and April 2017 were retrospectively collected from medical charts. The main efficacy outcomes assessed were annualized relapse rate (ARR) and proportion of patients free from relapses, disability progression, or magnetic resonance imaging (MRI) activity. Results. A total of 89 rituximab-treated patients were included: 59 relapsing-remitting MS (RRMS) and 30 progressive MS (PMS). Patients were treated with 1000 or 2000 mg rituximab IV every 6–12 months for a mean duration of 22.2 ± 24.8 months. The subjects were 65.2% females with a mean age of 40.5 ± 12.3 years and a mean disease duration of 7.9 ± 6.2 years. During treatment, the ARR decreased from 1.07 at baseline to 0.11 in RRMS (p<0.0001) and from 0.25 to 0.16 in PMS patients (p=0.593). The mean Expanded Disability Status Scale (EDSS) remained unchanged in both RRMS and PMS patients. Between baseline and the last follow-up, the percent of patients free from any new MRI lesions increased from 18.6% to 92.6% in the RRMS group and from 43.3% to 82% in the PMS group. No evidence of disease activity (NEDA) was achieved in 74% of patients at 1 year of treatment. A total of 64 adverse events (AEs) (71.9%) were recorded with the most common being infusion-related reactions in 25.8% of patients, all mild in nature. Two of our rituximab-treated patients experienced serious AEs requiring surgical interventions: pyoderma gangrenosum vaginalis with perianal abscess and fistula and an increase in the size of a meningioma. No case of progressive multifocal leukoencephalopathy (PML) was detected. Conclusion. In our real-world cohort, rituximab was well-tolerated and effective in reducing relapse rate and disability progression in relapsing-remitting and progressive MS patients.

Severe meningo-/encephalitis after daclizumab therapy for multiple sclerosis

2019 ◽  
Vol 25 (12) ◽  
pp. 1618-1632 ◽  
Author(s):  
Lidia Stork ◽  
Wolfgang Brück ◽  
Phillip von Gottberg ◽  
Ulrich Pulkowski ◽  
Florian Kirsten ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Plasma Cells ◽  
Clinical Laboratory ◽  
Interleukin 2 ◽  
Gastrointestinal Symptoms ◽  
Blood Analysis ◽  
Disability Status ◽  
Magnetic Resonance Imaging Mri ◽  
Systemic Symptoms

Background: Daclizumab is a monoclonal antibody that binds the high-affinity interleukin-2 receptor and was approved for the treatment of relapsing multiple sclerosis. Due to severe inflammatory brain disorders, the approval was suspended in March 2018. Objective and Methods: This retrospective cohort study summarizes clinical, laboratory, radiological, and histological findings of seven patients who developed meningo-/encephalitis after daclizumab therapy. Results: Patients presented with encephalitis and/or meningitis and suffered from systemic symptoms such as fever (5/7), exanthema (5/7), or gastrointestinal symptoms (4/7). Secondary autoimmune diseases developed. Blood analysis revealed an increase in eosinophils (5/7). Six patients fulfilled the diagnostic criteria for a drug reaction with eosinophilia and systemic symptoms (DRESS). Magnetic resonance imaging (MRI) showed multiple contrast-enhancing lesions, and enhancement of the ependyma (6/7), meninges (5/7), cranial or spinal nerves (2/7), and a vasculitic pattern (3/7). Histology revealed a pronounced inflammatory infiltrate consisting of lymphocytes, plasma cells and eosinophils, and densely infiltrated vessels. Most patients showed an insufficient therapeutic response and a high disability at last follow-up (median Expanded Disability Status Scale (EDSS) 8). Two patients died. Conclusion: Meningoencephalitis and DRESS may occur with daclizumab therapy. This potential lethal side effect is characterized by a dysregulated immune response. Our findings underline the importance of postmarketing drug surveillance.

De-escalating rituximab dose results in stability of clinical, radiological, and serum neurofilament levels in multiple sclerosis

2020 ◽  
pp. 135245852095203
Author(s):  
Giulio Disanto ◽  
Paolo Ripellino ◽  
Gianna C Riccitelli ◽  
Rosaria Sacco ◽  
Barbara Scotti ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Comparable Efficacy ◽  
High Dose ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
T2 Lesions ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Magnetic Resonance Imaging Mri

Background: Phase II and observational studies support the use of rituximab in multiple sclerosis. Standard protocols are lacking, but studies suggest comparable efficacy between low- and high-dose regimens. Objective: To evaluate effectiveness and safety of de-escalating rituximab dose from 1000 to 500 mg/6 months in multiple sclerosis. Methods: Patients were switched from rituximab 1000 to 500 mg/6 months and prospectively followed for 12 months. Relapses, disability, occurrence of brain/spinal magnetic resonance imaging (MRI) lesions, serum neurofilament light chain (NfL), CD19+ B cell, and IgG concentrations were analyzed. Results: Fifty-nine patients were included (37 relapsing-remitting, 22 secondary progressive). No relapses occurred, with no difference in expanded disability status scale (EDSS) between baseline (4 (2.5–4.5) and 12 months (3.5 (2.5–5.5) p = 0.284). Overall, three new T2 lesions appeared during follow-up. NfL concentration was stable between baseline (7.9 (5.9–45.2) pg/mL) and 12 months (9.1 (5.9–21.3) pg/mL, p = 0.120). IgG concentrations decreased with greater rituximab load (coefficient = −0.439, p = 0.041). IgG deficient patients had greater risk of infections (OR = 6.27, 95% CI = 1.71–22.9, p = 0.005). Conclusion: De-escalating rituximab dose from 1000 to 500 mg/6 months is safe, results in clinical and radiological stability, and does not affect serum NfL over 12 months. Rituximab load negatively influences IgG concentrations, and IgG deficient patients are at higher risk of infections.

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