Methods of treating inflammatory and autoimmune diseases...

A - Human Necessities – 61 – K

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A61K 39/395 (2006.01)

Patent

CA 2644110

Natalizumab is a safe and efficacious treatment for inflammatory and autoimmune diseases, such as multiple sclerosis, Crohn's Disease, and rheumatoid arthritis. Chain swapping between natalizumab and IgG4 molecules acts to reduce the level of bivalent natalizumab present following administration of natalizumab, and thus to lower the activity of natalizumab in the patient. Differences in IgG4 levels across patients or within a single patient across time may change the pharmacokinetic profile of natalizumab. Patients with lower levels of IgG4 may experience higher nadir levels of natalizumab during a dosing period. Monitoring IgG4 and/or bivalent natalizumab levels, and determining a dose or dosage period based on the monitoring may improve the safety and/or efficacy of natalizumab therapy.

La présente invention concerne le natalizumab qui est utilisé pour le traitement sûr et efficace de maladies inflammatoires et auto-immunes telles que la sclérose en plaques, la maladie de Crohn et la polyarthrite rhumatoïde. L'échange de chaînes entre le natalizumab et les molécules d'IgG4 agit pour réduire la concentration de natalizumab bivalent présent à la suite de l'administration de natalizumab et ainsi réduire l'activité du natalizumab dans le patient. Les différences de concentrations d'IgG4 parmi les patients ou chez un seul patient en fonction du temps modifieront le profil pharmacocinétique du natalizumab. Les patients avec de plus faibles concentrations d'IgG4 peuvent présenter des concentrations nadir supérieures de natalizumab pendant la période de dosage. Le suivi des concentrations d'IgG4 et/ou de natalizumab bivalent ainsi que la détermination d'une dose ou d'une période de dosage basée sur le suivi peuvent améliorer la sûreté et/ou la sécurité d'une thérapie au natalizumab.

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