Observations during an elective interruption of natalizumab treatment: a post-marketing study

2010 ◽  
Vol 17 (3) ◽  
pp. 372-375 ◽  
Author(s):  
Giovanna Borriello ◽  
Luca Prosperini ◽  
Fabiana Marinelli ◽  
Federica Fubelli ◽  
Carlo Pozzilli
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Treatment Interruption ◽  
Duration Of Treatment ◽  
Continuous Therapy ◽  
Optimal Duration ◽  
Natalizumab Treatment ◽  
Post Marketing ◽  
The Difference

In this prospective post-marketing study, 21 patients with multiple sclerosis treated with natalizumab for 24 consecutive months elected a trial of treatment interruption (90–180 days). During a mean duration of treatment interruption of 111.5 days 4 patients (19.0%) experienced a relapse and 9 out of 19 (47.4%) had MRI activity. Number of contrast-enhancing lesions at baseline was lower than during treatment interruption, but the difference was not significant. These findings suggest that disease activity may return after the last infusion of natalizumab. Patients should have regular MRI assessment during treatment interruption to rapidly identify any return of disease activity. The aim of this study was to determine the optimal duration for temporary interruption of natalizumab therapy in patients who have received continuous therapy with natalizumab for 24 months.

Disease activity return during natalizumab treatment interruption in patients with multiple sclerosis

Neurology ◽  
2011 ◽  
Vol 76 (22) ◽  
pp. 1858-1865 ◽  
Author(s):  
P. W. O'Connor ◽  
A. Goodman ◽  
L. Kappos ◽  
F. D. Lublin ◽  
D. H. Miller ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Treatment Interruption ◽  
Natalizumab Treatment

scholarly journals Disease activity return during natalizumab treatment interruption in patients with multiple sclerosis

Neurology ◽  
2011 ◽  
Vol 77 (21) ◽  
pp. 1930-1931 ◽  
Author(s):  
K. W. Rammohan ◽  
M. R. Ortega ◽  
S. R. Delgado ◽  
L. Tornes ◽  
P. W. O'Connor
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Treatment Interruption ◽  
Natalizumab Treatment

scholarly journals The majority of natalizumab-treated MS patients have high natalizumab concentrations at time of re-dosing

2017 ◽  
Vol 24 (6) ◽  
pp. 805-810 ◽  
Author(s):  
Zoé LE van Kempen ◽  
Cyra E Leurs ◽  
Birgit I Witte ◽  
Annick de Vries ◽  
Mike P Wattjes ◽  
...  
Keyword(s):  
Body Weight ◽  
Disease Activity ◽  
Brain Magnetic Resonance Imaging ◽  
Serum Concentrations ◽  
Duration Of Treatment ◽  
Treatment Regimens ◽  
Trough Serum ◽  
Natalizumab Treatment ◽  
Magnetic Resonance Imaging Mri ◽  
Relapsing Remitting Multiple Sclerosis

Background: Natalizumab is efficacious in the treatment of relapsing-remitting multiple sclerosis. All patients receive the same treatment regimen of 300 mg every 4 weeks, despite differences in pharmacokinetics between individual patients. Objective: To give neurologists insight into natalizumab concentrations at time of re-dosing, we investigated longitudinal natalizumab concentrations in 80 patients in relation to disease activity, with possible influencing factors. Methods: In a prospective observational cohort study, natalizumab trough serum concentrations were measured in 80 patients. Data on demographics, duration of treatment, Expanded Disability Status Scale, clinical exacerbations, brain magnetic resonance imaging (MRI), and body weight were collected. Results: We measured high (≥10 µg/mL) natalizumab trough concentrations in 94% of patients. Intra-individual concentrations were stable. The spread in concentrations was substantial and did not correlate with disease activity. We found a negative association between natalizumab concentration and body weight (β = −0.30, p = 0.010). Interpretation: The majority of patients showed high natalizumab serum concentrations at time of re-dosing. Alternative treatment regimens could lead to more efficient use of natalizumab, but caution is warranted regarding the possibility of recurrence of disease activity. Prospective clinical trials are needed to establish the safety of extended dose intervals in natalizumab treatment.

A Swedish national post-marketing surveillance study of natalizumab treatment in multiple sclerosis

2011 ◽  
Vol 17 (6) ◽  
pp. 708-719 ◽  
Author(s):  
Carolina Holmén ◽  
Fredrik Piehl ◽  
Jan Hillert ◽  
Anna Fogdell-Hahn ◽  
Malin Lundkvist ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Events ◽  
Drug Effects ◽  
Surveillance Study ◽  
Serious Adverse Events ◽  
Web Based ◽  
Quality Registry ◽  
Post Marketing Surveillance ◽  
Natalizumab Treatment ◽  
Post Marketing

Background: A post marketing surveillance study was conducted to evaluate safety and efficacy of natalizumab in Swedish multiple sclerosis (MS) patients since its introduction in August 2006 until March 2010. Methods: Patients were registered in the web-based Swedish MS-registry at 40 locations and evaluated every 6 months. Adverse events and clinical outcomes were recorded. Results: One thousand one hundred and fifty-two patients were included (71.4% female) and 149 patients stopped treatment; the main reason was planned pregnancy. Anti-natalizumab antibodies were found in 4.5% (52 patients) of which 1.6% displayed persistent antibodies. Serious adverse events were rare, but included three cases with progressive multifocal leukoencephalopathy (PML). There were seven fatal cases, probably unrelated to the natalizumab treatment. For relapsing–remitting MS patients ( n = 901), mean Expanded Disability Status Scale (EDSS, −10.7%), Multiple Sclerosis Severity Scale (MSSS, −20.4%), Multiple Sclerosis Impact Scale (MSIS-29, physical −9.9%, psychological −13.3%) and Symbol Digit Modalities Test (SDMT, +10.7%) all showed significant improvements during 24 months of treatment with natalizumab. The Swedish web-based MS quality registry proved to function as a platform for post-marketing MS drug surveillance, providing long-term data regarding drug effects and adverse events beyond clinical trials. Conclusions: Our results indicate that natalizumab is generally well tolerated and has sustained efficacy for patients with active MS, though the risk of PML is still an important concern.

scholarly journals MS disease activity in RESTORE: A randomized 24-week natalizumab treatment interruption study

Neurology ◽  
2014 ◽  
Vol 83 (22) ◽  
pp. 2099-2100 ◽  
Author(s):  
A. Svenningsson ◽  
P. Sundstrom ◽  
J. Salzer ◽  
M. Vagberg ◽  
R. J. Fox
Keyword(s):  
Disease Activity ◽  
Treatment Interruption ◽  
Natalizumab Treatment

scholarly journals Curing Mycobacterium ulcerans Infection in Mice with a Combination of Rifampin-Streptomycin or Rifampin-Amikacin

2006 ◽  
Vol 51 (2) ◽  
pp. 645-650 ◽  
Author(s):  
Sébastien Lefrançois ◽  
Jérôme Robert ◽  
Aurélie Chauffour ◽  
Baohong Ji ◽  
Vincent Jarlier
Keyword(s):  
Murine Model ◽  
Buruli Ulcer ◽  
Mycobacterium Ulcerans ◽  
Cure Rate ◽  
Duration Of Treatment ◽  
Inflammatory Lesions ◽  
Optimal Duration ◽  
Bactericidal Activities ◽  
The Difference ◽  
Cure Rates

ABSTRACT The curing activities of various durations of treatment with a combination of rifampin (RIF) and either streptomycin (STR) or amikacin (AMK) in murine Mycobacterium ulcerans infection were compared in two experiments. In the first experiment, treatment was begun 1 week after infection, when the inflammatory footpad lesion had not yet occurred (preventive model), and in the second experiment, treatment was begun 6 weeks after infection, when inflammatory footpad lesions were established (curative model). In the first experiment, 4 weeks of treatment with daily RIF-STR or RIF-AMK was able to postpone the occurrence of footpad lesion by 12 weeks (RIF-STR) or 17 weeks (RIF-AMK), thus demonstrating their promising bactericidal activities, but neither treatment was able to prevent the late occurrence of footpad lesions. In the second experiment, the overall cure rates, as assessed by the lack of rebound of inflammatory lesions or remultiplication of M. ulcerans, were only 62% after 2 weeks of treatment with RIF and an aminoglycoside and 85% after 4 weeks; but the cure rate reached 100% after 8 or 12 weeks of treatment. The cure rates were slightly higher with the AMK-containing combination than with the STR-containing combination, but the difference was at the limit of significance (P = 0.07). These results show that in the murine model of Buruli ulcer, 8 weeks is the optimal duration of treatment with a combination of RIF and an aminoglycoside.

Natalizumab (Tysabri®) - Re-defining Efficacy in Multiple Sclerosis - Data from Clinical Trials to Post-marketing Experience

2009 ◽  
Vol 4 (2) ◽  
pp. 58
Author(s):  
David Bates ◽  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Disease Progression ◽  
Large Scale ◽  
Rare Event ◽  
Management Plan ◽  
Social Consequences ◽  
Substantial Impact ◽  
Natalizumab Treatment ◽  
Post Marketing

Multiple sclerosis (MS) is a chronic, disabling condition with severe clinical and social consequences. Current first-line disease-modifying treatments have limited efficacy and do not halt long-term disease progression in the majority of patients. Natalizumab (Tysabri®) is the only monoclonal antibody licensed for use in relapsing–remitting MS (RRMS). It is regarded by many neurologists as the most effective MS drug on the market today, and has the potential to re-define successful MS therapy. Its efficacy has been demonstrated both in large-scale clinical trials and in post-marketing settings. Beneficial effects include reduction of relapse rates and disease progression and magnetic resonance imaging (MRI) measures of disease activity. Natalizumab treatment has a substantial impact on patient quality of life. Moreover, patients have shown significant improvement following natalizumab treatment, making continuing clinical remission a realistic goal in MS for the first time. However, the benefits of natalizumab must be balanced against risk. Progressive multifocal leukoencephalopathy (PML) is a rare event associated with natalizumab treatment that may be minimised with a risk management plan to educate physicians on patient selection and management.

Course of relapsing–remitting multiple sclerosis before, during and after natalizumab

2010 ◽  
Vol 17 (4) ◽  
pp. 490-494 ◽  
Author(s):  
Michael D Kaufman ◽  
R Lee ◽  
HJ Norton
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Relapse Rate ◽  
Generalized Estimating Equations ◽  
Chart Review ◽  
Relapsing Remitting ◽  
Annualized Relapse Rate ◽  
Natalizumab Treatment ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Relapse Rates

The consequences of interruption of natalizumab treatment are incompletely known. The objective was to assess the confirmed annualized relapse rates for patients preceding initiation, during and following suspension of natalizumab therapy. A chart review was conducted and data were analyzed using the Generalized Estimating Equations. During natalizumab therapy the confirmed annualized relapse rate was 0.08, compared to 0.52 ( p = 0.0003) during the prior 12 months and to 0.35 ( p = 0.0032) during the following 3 to 24 months. Similar results were found when confirmed and unconfirmed were analyzed. To conclude, following cessation of natalizumab therapy disease activity rapidly returned to pre-natalizumab levels.

scholarly journals The Toronto Observational Study of Natalizumab in Multiple Sclerosis

2011 ◽  
Vol 38 (3) ◽  
pp. 422-428 ◽  
Author(s):  
Kristen M. Krysko ◽  
Paul W. O'Connor
Keyword(s):  
Multiple Sclerosis ◽  
Observational Study ◽  
Relapse Rate ◽  
Self Report ◽  
Duration Of Treatment ◽  
Disease Modifying Therapy ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Natalizumab Treatment ◽  
Insufficient Response

Background:Natalizumab is indicated for the treatment of relapsing multiple sclerosis (MS) with insufficient response to first-line disease-modifying therapy (DMT). We studied the efficacy of natalizumab for treatment of MS in a single centre observational design.Methods:A retrospective observational study of 146 patients [66% female; mean age 37.4; 72% relapsing remitting MS (RRMS), 28% secondary progressive MS (SPMS)] referred for natalizumab treatment at St. Michael's Hospital MS Clinic between 2007 and August 2009. Data included demographic, clinical (Expanded Disability Status Scale (EDSS) and annualized relapse rate (ARR)) and patient self-report measures.Results:The mean duration of treatment was 20 months in those treated with natalizumab and 97% had received prior DMTs. Eighty-three patients (57%) received at least 12 months of natalizumab treatment. In those who received at least 12 months of treatment, baseline ARR and EDSS were 1.6 and 2.7 in RRMS patients versus 1.0 and 5.4 in SPMS with relapses. The ARR decreased with natalizumab treatment to 0.38 (76% reduction, p<0.001) in RRMS versus 0.32 in SPMS patients (68% reduction, p=0.01). There was a treatment associated 11% reduction in EDSS to 2.4 (p=0.04) in RRMS, but no significant change in SPMS. Eighty-five percent of patients reported improved overall quality of life (QOL) and 62% indicated improved energy.Conclusions:There was a major reduction in relapse rate, stabilization in EDSS and improvement in QOL and energy in some patients on natalizumab, all similar to treatment effects in the pivotal trial.

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