Rituximab Infusion Timing, Cumulative Dose, and Hospitalization for COVID-19 in Persons With Multiple Sclerosis in Sweden

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.

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039 Rates of lymphopenia in years 1–4 in patients with relapsing multiple sclerosis treated annually with cladribine tablets

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2018-anzan.38 ◽

2018 ◽

Vol 89 (6) ◽

pp. A16.2-A16 ◽

Cited By ~ 1

Author(s):

Stuart Cook ◽

Giancarlo Comi ◽

Gavin Giovannoni ◽

Peter Rieckmann ◽

Per Soelberg Sorensen ◽

...

Keyword(s):

Multiple Sclerosis ◽

Adverse Event ◽

Mechanism Of Action ◽

Cumulative Dose ◽

Common Adverse Event ◽

Annual Treatment ◽

Grade 3 ◽

Experienced Grade ◽

Relapsing Multiple Sclerosis ◽

Time Point

IntroductionThe CLARITY and CLARITY Extension studies demonstrated the efficacy of cladribine tablets in patients with relapsing multiple sclerosis. The most common adverse event was lymphopenia, consistent with the mechanism of action of cladribine tablets. Objective was to evaluate whether lymphopenia persists following annual treatment with cladribine tablets.MethodsLymphopenia by grade (NCI CTCAE v3.0) for patients randomised to cladribine tablets 3.5 mg/kg in CLARITY and re-randomised to cladribine tablets 3.5 mg/kg in CLARITY Extension (7 mg/kg cumulative dose over 4 years; n=186) are reported. Patients with Grade 0 lymphopenia (≥1.0×109 cells/L) before the first course of cladribine tablets and Grade 0/1 (≥0.8×109 cells/L) prior to administration in Years 2, 3 and 4 were included in the analysis.Results176 patients were Grade 0 at CLARITY baseline and 167 were Grade 0/1 at CLARITY Extension baseline. Grade 3 lymphopenia was observed in 1% of patients at Week 13 in Year 1, and in 7%, 11% and 12% at Week 12 in Years 2, 3 and 4, respectively. By Week 24 in Years 1, 2, 3 and 4, Grade 3 lymphopenia was observed in 1%, 4%, 4% and 4% of patients, respectively. By Week 36 in Years 1, 2, 3 and 4, Grade 3 lymphopenia was observed in 1%, 2%, 2% and 2% of patients, respectively. Grade 3 lymphopenia was only observed in Week 48 of Year 2 (1% of patients). Grade 3 lymphopenia was reported in <18% of patients at any time point. No patients had Grade 4 lymphopenia at the end of any years.ConclusionNo patients included in this analysis experienced Grade 4 lymphopenia at the end of any treatment year. Grade 3 lymphopenia was uncommon. This study demonstrates the effectiveness of lymphocyte-based treatment criteria in minimising the incidence of severe, sustained lymphopenia during treatment with cladribine tablets.

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Frequency and risk factors of mitoxantrone-induced amenorrhea in multiple sclerosis: the FEMIMS study

Multiple Sclerosis Journal ◽

10.1177/1352458508094882 ◽

2008 ◽

Vol 14 (9) ◽

pp. 1225-1233 ◽

Cited By ~ 45

Author(s):

E Cocco ◽

C Sardu ◽

P Gallo ◽

R Capra ◽

MP Amato ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cumulative Dose ◽

Ad Hoc ◽

Immunosuppressive Treatment ◽

Multivariate Logistic Regression Analysis ◽

Reproductive Capacity ◽

Multivariate Logistic Regression ◽

Childbearing Age ◽

The Impact ◽

Age At Exposure

Background Improved prognosis in women with multiple sclerosis (MS) undergoing immunosuppressive treatment with mitoxantrone (MITO) has led to an increased interest in the effect of such treatments on fertility. FErtility and Mitoxantrone In MS (FEMIMS) is a collaborative retrospective study aimed at evaluating the impact of MITO treatment on fertility in women with MS. Methods Occurrence of chemotherapy-induced amenorrhea (CIA) was evaluated in 189 women with MS treated with MITO before the age of 45. An “ad hoc” questionnaire, paying particular attention to onset of CIA either during or post-MITO treatment, was administered to each patient. The probability of CIA was calculated using a multivariate logistic regression analysis taking into account age at exposure, cumulative dose, and use of estroprogestinic (EP) drugs during treatment. Results Forty-eight (26%) patients presented CIA following MITO. The probability of CIA was increased by 2%/mg/m2 of cumulative dose and by 18% for each year of age, whereas it was reduced by administration of EP during treatment. Conclusions MITO treatment may affect reproductive capacity in women with MS. Patients of childbearing age should be properly counseled before MITO treatment and EP therapy should be administered to reduce the risk of CIA.

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Increasing signal intensity within the dentate nucleus and globus pallidus on unenhanced T1W magnetic resonance images in patients with relapsing-remitting multiple sclerosis: correlation with cumulative dose of a macrocyclic gadolinium-based contrast agent, gadobutrol

European Radiology ◽

10.1007/s00330-015-3879-9 ◽

2015 ◽

Vol 26 (3) ◽

pp. 807-815 ◽

Cited By ~ 141

Author(s):

Dragan A. Stojanov ◽

Aleksandra Aracki-Trenkic ◽

Slobodan Vojinovic ◽

Daniela Benedeto-Stojanov ◽

Srdjan Ljubisavljevic

Keyword(s):

Multiple Sclerosis ◽

Magnetic Resonance ◽

Contrast Agent ◽

Globus Pallidus ◽

Cumulative Dose ◽

Signal Intensity ◽

Dentate Nucleus ◽

Magnetic Resonance Images ◽

Relapsing Remitting ◽

Relapsing Remitting Multiple Sclerosis

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Mitoxantrone in secondarily progressive multiple sclerosis: a series of 18 patients

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2005000200007 ◽

2005 ◽

Vol 63 (2a) ◽

pp. 225-227 ◽

Cited By ~ 5

Author(s):

María Belén Montú ◽

Walter Oleschko Arruda ◽

Marcelo de Souza R. de Oliveira ◽

Ricardo Ramina

Keyword(s):

Multiple Sclerosis ◽

Confidence Intervals ◽

Cumulative Dose ◽

Clinical Laboratory ◽

Progressive Multiple Sclerosis ◽

Effective Drug ◽

Long Line ◽

Relapsing Remitting ◽

Duration Of Disease ◽

The Mean

Mitoxantrone hydrochloride (Novantrone®) is an anthracenedione that has been used as one of the latest in a long line of general immunosuppresive agents studied in multiple sclerosis (MS). We reviewed the clinical, laboratory, neuroimaging and echocardiography data of 18 patients from February 2001 to March 2004 out of a total number of 100 patients with definite MS. Fourteen patients were women (77.7%) and four were men. The mean age of the patients was 41.6±10 years old (confidence intervals 95%: 36.4-46.7 years old). The mean duration of disease was 10.5±6.3 years. Fourteen patients had the secondarily progressive form of MS, and four had the relapsing-remitting form. Mitoxantrone is an useful and clinically effective drug in MS and its major limitation is the potencial cardiotoxicity due to cumulative dose (140 mg).

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