A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis.

@article{Polman2006ARP,
  title={A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis.},
  author={Chris H. Polman and P. W. O'Connor and Eva Kubala Havrdov{\'a} and M. Hutchinson and Ludwig Kappos and David H. Miller and J. Theodore Phillips and Fred D Lublin and Gavin Giovannoni and Andrzej Wajgt and Martin J Toal and Frances Lynn and Michael A. Panzara and Alfred W. Sandrock},
  journal={The New England journal of medicine},
  year={2006},
  volume={354 9},
  pages={
          899-910
        }
}
BACKGROUND Natalizumab is the first alpha4 integrin antagonist in a new class of selective adhesion-molecule inhibitors. We report the results of a two-year phase 3 trial of natalizumab in patients with relapsing multiple sclerosis. METHODS Of a total of 942 patients, 627 were randomly assigned to receive natalizumab (at a dose of 300 mg) and 315 to receive placebo by intravenous infusion every four weeks for more than two years. The primary end points were the rate of clinical relapse at one… 

Figures and Tables from this paper

The role of natalizumab in the treatment of multiple sclerosis: benefits and risks
  • B. Singer
  • Medicine, Psychology
    Therapeutic advances in neurological disorders
  • 2017
TLDR
To optimize appropriate selection of natalizumab for patients with relapsing MS, however, a thorough understanding of individual patient risk factors for PML or other adverse events is also required.
Natalizumab and the role of α4-integrin antagonism in the treatment of multiple sclerosis
TLDR
Natalizumab monotherapy 300 mg intravenous every 4 weeks reduced the risk of sustained disability progression by 42% and annualized relapse rate by 68% over 2 years (both p < 0.001 versus placebo).
Natalizumab: A new treatment for relapsing remitting multiple sclerosis
  • M. Hutchinson
  • Medicine, Biology
    Therapeutics and clinical risk management
  • 2007
TLDR
The benefits and risks of natalizumab support its use as monotherapy for RRMS with high disease activity despite treatment with IFNβ, and for patients with rapidly evolving severe RRMS.
Clinical efficacy and benefit of natalizumab
TLDR
The purpose of this paper is to review evidence for the efficacy of natalizumab, and put its use in MS into perspective.
Natalizumab plus interferon beta-1a for relapsing multiple sclerosis.
TLDR
Natalizumab added to interferon beta-1a was significantly more effective in patients with relapsing multiple sclerosis, and additional research is needed to elucidate the benefits and risks of this combination treatment.
Natalizumab for the treatment of relapsing multiple sclerosis
TLDR
The robust clinical benefits of natalizumab, including benefits on patient-reported quality of life, make it an important addition to disease-modifying therapies available to patients with relapsing MS.
Natalizumab in the treatment of multiple sclerosis
TLDR
Natalizumab is now considered second-line therapy for patients who have failed first-line agents such as interferon or glatiramer acetate, and patients and providers must work together to carefully decide if potential benefits outweigh these rare but potentially devastating complications.
Randomized trial of oral teriflunomide for relapsing multiple sclerosis.
TLDR
Teriflunomide significantly reduced relapse rates, disability progression (at the higher dose), and MRI evidence of disease activity, as compared with placebo.
Natalizumab Risk Stratification: Role of a Two- Step Anti-JCV Antibody Assay
  • P. O'Connor
  • Medicine, Biology
    Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques
  • 2012
TLDR
The mortality rate of natalizumab-associated PMl is considerably lower than the mortality rate that has been reported for PMl in general and may be accounted for, at least in part, by the use of plasma exchange (PleX) in most patients who developed PMl.
Review: Natalizumab in the treatment of multiple sclerosis
Natalizumab reduced the rate of clinical relapse at one year by 68% and the risk of sustained progression of disability by 42—54% over 2 years in its pivotal phase III trial (AFFIRM) in
...
...

References

SHOWING 1-10 OF 37 REFERENCES
Natalizumab plus interferon beta-1a for relapsing multiple sclerosis.
TLDR
Natalizumab added to interferon beta-1a was significantly more effective in patients with relapsing multiple sclerosis, and additional research is needed to elucidate the benefits and risks of this combination treatment.
A controlled trial of natalizumab for relapsing multiple sclerosis.
TLDR
In a placebo-controlled trial, treatment with natalizumab led to fewer inflammatory brain lesions and fewer relapses over a six-month period in patients with relapsing multiple sclerosis.
Interferon beta‐1b is effective in relapsing‐remitting multiple sclerosis
TLDR
The MRI results demonstrate that IFNB has made a significant impact on the natural history of MS in these patients and support the clinical results in showing a significant reduction in disease activity as measured by numbers of active scans and appearance of new lesions.
Intramuscular interferon beta‐1a for disease progression in relapsing multiple sclerosis
TLDR
Interferon beta‐ la had a significant beneficial impact in relapsing multiple sclerosis patients by reducing the accumulation of permanent physical disability, exacerbation frequency, and disease activity measured by gadolinium‐enhanced lesions on brain magnetic resonance images.
Copolymer 1 reduces relapse rate and improves disability in relapsing‐remitting multiple sclerosis
TLDR
It is demonstrated that copolymer 1 treatment can significantly and beneficially alter the course of relapsing-remitting multiple sclerosis in a well-tolerated fashion.
Interferon beta-1a for early multiple sclerosis: CHAMPS trial subgroup analyses.
TLDR
Interferon beta-1a is beneficial when initiated at the first clinical demyelinating event in patients with brain magnetic resonance imaging evidence of subclinical demYelination and the beneficial effect is present for optic neuritis, brainstem-cerebellar syndromes, and spinal cord syndrome.
Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group.
TLDR
Starting treatment with interferon beta-1a at the time of a first demyelinating event is beneficial for patients with brain lesions on MRI that indicate a high risk of clinically definite multiple sclerosis.
Interferon β‐1a for early multiple sclerosis: CHAMPS trial subgroup analyses
TLDR
Interferon β‐1a is beneficial when initiated at the first clinical demyelinating event in patients with brain magnetic resonance imaging evidence of subclinical demYelination and the beneficial effect is present for optic neuritis, brainstem–cerebellar syndromes, and spinal cord syndrome.
Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy.
TLDR
A detailed review of possible cases ofPML in patients exposed to natalizumab found no new cases and suggested a risk of PML of roughly 1 in 1000 patients treated with natalIZumab for a mean of 17.9 months.
...
...