HSV encephalitis associated with off-label rituximab treatment of multiple sclerosis

2022 ◽  
Author(s):  
Federico Montini ◽  
Bruno Colombo ◽  
Antonino Giordano ◽  
Ingazio Diego Lopez ◽  
Lucia Moiola ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Off Label

scholarly journals Ethical use of off-label disease-modifying therapies for multiple sclerosis

2021 ◽  
pp. 135245852110302
Author(s):  
Joanna Laurson-Doube ◽  
Nick Rijke ◽  
Anne Helme ◽  
Peer Baneke ◽  
Brenda Banwell ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
World Health ◽  
World Federation ◽  
Off Label ◽  
Disease Modifying Therapies ◽  
The World ◽  
Disease Modifying ◽  
Health Organization

Background: Off-label disease-modifying therapies (DMTs) for multiple sclerosis (MS) are used in at least 89 countries. There is a need for structured and transparent evidence-based guidelines to support clinical decision-making, pharmaceutical policies and reimbursement decisions for off-label DMTs. Objectives/Results: The authors put forward general principles for the ethical use of off-label DMTs for treating MS and a process to assess existing evidence and develop recommendations for their use. Conclusion: The principles and process are endorsed by the World Federation of Neurology (WFN), American Academy of Neurology (AAN), European Academy of Neurology (EAN), Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), Middle-East North Africa Committee for Treatment and Research in Multiple Sclerosis (MENACTRIMS) and Pan-Asian Committee for Treatment and Research in Multiple Sclerosis (PACTRIMS), and we have regularly consulted with the Brain Health Unit, Mental Health and Substance Use Department at the World Health Organization (WHO).

Rapidly increasing off-label use of rituximab in multiple sclerosis in Sweden - Outlier or predecessor?

2018 ◽  
Vol 138 (4) ◽  
pp. 327-331 ◽  
Author(s):  
S. G. Berntsson ◽  
A. Kristoffersson ◽  
I. Boström ◽  
A. Feresiadou ◽  
J. Burman ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Off Label Use ◽  
Off Label ◽  
Label Use

Subcutaneous administration of alemtuzumab in patients with highly active multiple sclerosis

2012 ◽  
Vol 18 (8) ◽  
pp. 1197-1199 ◽  
Author(s):  
Jai S Perumal ◽  
Farng Foo ◽  
Perry Cook ◽  
Omar Khan
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Events ◽  
Subcutaneous Administration ◽  
Off Label Use ◽  
Lymphoid Leukemia ◽  
Off Label ◽  
Highly Active ◽  
Highly Active Multiple Sclerosis ◽  
Relapsing Multiple Sclerosis ◽  
Active Multiple Sclerosis

Alemtuzumab is an anti-CD52 monoclonal antibody with remarkable efficacy in relapsing multiple sclerosis (MS). In clinical trials and off-label use in MS, alemtuzumab has been administered intravenously (IV). Alemtuzumab is approved for chronic lymphoid leukemia as IV. Oncology guidelines recommend alemtuzumab subcutaneous (SC) over IV. There is no report of alemtuzumab SC in MS. We report two patients with highly active relapsing MS who were treated with SC alemtuzumab, had significant improvement and tolerated SC alemtuzumab well without the typical infusion-associated adverse events. SC alemtuzumab in MS warrants further studies as this may enhance patient convenience and minimize infusion-associated adverse events.

Treatment of multiple sclerosis with rituximab: A multicentric Italian–Swiss experience

2019 ◽  
Vol 26 (12) ◽  
pp. 1519-1531 ◽  
Author(s):  
Chiara Zecca ◽  
Francesca Bovis ◽  
Giovanni Novi ◽  
Marco Capobianco ◽  
Roberta Lanzillo ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Relapse Rate ◽  
B Lymphocyte ◽  
Outcome Analysis ◽  
Off Label ◽  
Disability Status ◽  
Relapsing Remitting ◽  
First Relapse ◽  
Anti Cd20

Background: Rituximab, an anti-CD20 monoclonal antibody leading to B lymphocyte depletion, is increasingly used as an off-label treatment option for multiple sclerosis (MS). Objective: To investigate the effectiveness and safety of rituximab in relapsing–remitting (RR) and progressive MS. Methods: This is a multicenter, retrospective study on consecutive MS patients treated off-label with rituximab in 22 Italian and 1 Swiss MS centers. Relapse rate, time to first relapse, Expanded Disability Status Scale (EDSS) progression, incidence of adverse events, and radiological outcomes from 2009 to 2019 were analyzed. Results: A total of 355/451 enrolled subjects had at least one follow-up visit and were included in the outcome analysis. Annualized relapse rate significantly decreases after rituximab initiation versus the pre-rituximab start year in RRMS (from 0.86 to 0.09, p < .0001) and in secondary-progressive (SP) MS (from 0.34 to 0.06, p < .0001) and had a slight decrease in primary-progressive (PP) MS patients (from 0.12 to 0.07, p = 0.45). After 3 years from rituximab start, the proportion of patients with a confirmed EDSS progression was 14.6% in the RRMS group, 24.7% in the SPMS group, and 41.5% in the PPMS group. No major safety concerns arose. Conclusion: Consistently with other observational studies, our data show effectiveness of rituximab in reducing disease activity in patients with MS.

scholarly journals Incidence, management, and outcomes of autoimmune nephropathies following alemtuzumab treatment in patients with multiple sclerosis

2019 ◽  
Vol 25 (9) ◽  
pp. 1273-1288 ◽  
Author(s):  
Richard Phelps ◽  
Jonathan A Winston ◽  
Daniel Wynn ◽  
Mario Habek ◽  
Hans-Peter Hartung ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Development Program ◽  
Disease Diagnosis ◽  
Close Monitoring ◽  
Off Label ◽  
Clinical Development Program ◽  
Appropriate Treatment ◽  
Post Marketing ◽  
End Stage ◽  
Relapsing Remitting Multiple Sclerosis

Background: Autoimmune disorders including nephropathies have been reported more frequently in alemtuzumab-treated multiple sclerosis (MS) patients than in the general population. Objective: Describe instances of autoimmune nephropathy in alemtuzumab-treated MS patients. Methods: Cases were identified from safety monitoring within the alemtuzumab relapsing-remitting multiple sclerosis (RRMS) clinical development program (CDP) or post-marketing, or following off-label use. Results: As of 16 June 2017, 16 autoimmune nephropathies have occurred following alemtuzumab treatment for MS. The incidence of autoimmune nephropathies was 0.34% within the CDP (5/1485 patients). The five CDP cases (one of anti-glomerular basement membrane (anti-GBM) disease, two of membranous glomerulonephropathy, and two of serum anti-GBM antibody without typical anti-GBM disease) were identified early, responded to conventional therapy (where needed), and had favorable outcomes. Three of 11 cases outside the CDP occurred following off-label alemtuzumab use prior to approval for RRMS and were all anti-GBM disease. Diagnosis was delayed in one of these three cases and another did not receive appropriate treatment; all three cases resulted in end-stage renal failure. All anti-GBM disease cases with documented urinalysis demonstrated prior microscopic hematuria. Conclusion: Close monitoring of alemtuzumab-treated MS patients facilitates diagnosis and treatment early in the nephropathy course when preservation of renal function is more likely.

scholarly journals Safety and efficacy of rituximab as first- and second line treatment in multiple sclerosis – A cohort study

2021 ◽  
Vol 7 (1) ◽  
pp. 205521732097304
Author(s):  
Hilde Marie Torgauten ◽  
Kjell-Morten Myhr ◽  
Stig Wergeland ◽  
Lars Bø ◽  
Jan H Aarseth ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Events ◽  
De Novo ◽  
University Hospital ◽  
Drug Discontinuation ◽  
Early Therapy ◽  
Safety And Efficacy ◽  
Off Label ◽  
Disease Modifying Therapy ◽  
Grade 3

Background Rituximab is increasingly used as off-label therapy in multiple sclerosis (MS). More data are needed on safety and efficacy of rituximab, particularly in cohorts of de novo patients and patients in early therapy escalation. Objective To investigate the safety and efficacy of off-label treatment with rituximab in an MS-cohort of predominantly de novo patients or as therapy escalation. Methods We retrieved safety and efficacy data from the Norwegian MS-registry and biobank for all MS-patients treated with rituximab at Haukeland University Hospital, Bergen, Norway, during a four year period. Results In the 365 MS-patients (320 relapsing-remitting MS (RRMS), 23 secondary progressive MS (SPMS), and 22 primary progressive MS (PPMS)), the overall annualized relapse rate (ARR) was 0.03 and annualized drug discontinuation rate (ADDR) was 0.05. NEDA-3 was achived in 79% of patients with available data (n=351). Sixty-one patients experienced infusion-related adverse events of which two were serious (CTCAE grade 3–4). Eighteen patients experienced serious non-infusion related adverse events, of which 16 were infections. Infections (n = 34; 9.3%, CTCAE grade 2-5), hypogammaglobulinemia (n = 19, 5.2%) and neutropenia (n = 16; 4.4%) were the most common non-infusion-related adverse events. Conclusion Rituximab was a safe and highly efficient disease modifying therapy in this cohort of MS-patients; however, infections and neutropenia need to be monitored.

scholarly journals Metastatic calcinosis cutis due to refractory hypercalcaemia responsive to denosumab in a patient with multiple sclerosis

2019 ◽  
Vol 12 (2) ◽  
pp. e223992 ◽  
Author(s):  
Ahmed Jorge ◽  
Robert Szulawski ◽  
Fnu Abhishek
Keyword(s):  
Multiple Sclerosis ◽  
Reference Range ◽  
Subcutaneous Tissue ◽  
Off Label Use ◽  
Calcinosis Cutis ◽  
Off Label ◽  
Hydroxyvitamin D ◽  
Ionised Calcium ◽  
25 Hydroxyvitamin D ◽  
Label Use

Metastatic calcinosis cutis results from abnormal calcium levels leading to the precipitation of insoluble calcium salts in the skin and subcutaneous tissue. Here, we present the case of a 67-year-old man with multiple sclerosis on chronic dexamethasone and concurrent supplementation of calcium and daily cholecalciferol presenting with painful calcified lesions. During initial presentation, corrected calcium was 13.8 mg/dL (reference range: 8.5–10.1 mg/dL), ionised calcium was 1.70 mg/dL (reference range: 1.13–1.32 mg/dL) and 25-hydroxyvitamin D was 41.6 ng/mL (reference range 30–100 ng/mL). Normocalcaemia was restored with the off-label use of denosumab, usually reserved for hypercalcaemia of malignancy and intractable osteoporosis. We discuss potential aetiologies of this patient’s hypercalcaemia, calcinosis cutis diagnosis and management and the off-label use of denosumab.

Relapses, Immunosuppressive and Novel Therapies

2016 ◽  
Author(s):  
Barbara S. Giesser
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Progressive Disease ◽  
Immunosuppressive Agents ◽  
Novel Therapies ◽  
Precipitating Factors ◽  
Off Label ◽  
Disease Modifying Therapies ◽  
Disease Modifying ◽  
Acute Attacks

This chapter presents information about treatment of acute attacks of multiple sclerosis and identification of precipitating factors. Additionally, it includes a detailed discussion of immunosuppressive agents that are used (largely off label) as disease-modifying therapies and data that support their use. Many clinical trials are currently focused on testing agents for use in progressive disease as well as agents that may be neuroprotective or neurorestorative. Results of recent trials of several of these various new and experimental agents are also reviewed.

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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