Natalizumab De-escalation to Interferon-beta-1b in Patients With Relapsing-remitting Multiple Sclerosis

Inclusion Criteria:

• Female or male patients with relapsing-remitting forms of multiple sclerosis (according to McDonald's criteria);
• Age between 18 and 70 years;
• Natalizumab-treatment for at least 12 months following the current Swiss guidelines for treatment initiation;
• Treated with a disease-modifying therapy other than interferon beta-1b for at least 12 months before natalizumab was initiated;
• Never treated with interferon beta-1b;
• Eligible patients are clinically stable (free from relapses and 6-month confirmed disability progression for at least 6 months) while on natalizumab-treatment and do not show any Gd-enhancement on their last MRI performed while on Tysabri;

• In eligible patients MRI were performed in the past as following

  • 6-18 months prior to natalizumab-treatment
  • at natalizumab start
  • 12 months after natalizumab initiation;
• Good records with regard to clinical disease activity (relapse rate, EDSS progression) in the year prior to natalizumab and during natalizumab;
• Patients who decide to stop natalizumab treatment after a careful benefit/risk assessment. Risk for PML increases with duration of natalizumab exposure, pre-treatment with an immunosuppressant agent or serological status of anti-JC-virus positivity;
• Patients, who in context with cessation of natalizumab have decided, after a careful benefit/risk assessment, to continue treatment of their MS with Interferon beta-1b;
• Women of potential childbearing with active contraceptive methods;
• Patients who are willing to undergo study procedures;
• Patients who are willing to undergo MRI;
• Patients who are willing and able to sign informed consent.

Exclusion Criteria:

• Patients who have previously entered this study;
• Natalizumab-treatment for less than 12 months following the current Swiss guidelines for treatment initiation;
• Prior treatment with interferon beta-1b (ever interferon beta-1b);
• Sign of clinical disease activity within the 6 months;
• One or more relapses and/or 6-month confirmed disability progression during the 6 months prior to the study;
• Secondary progressive MS;
• Primary progressive MS;
• Pregnancy - Serum pregnancy test at screening visit positive- or breast feeding;
• Uncontrolled, clinically significant heart diseases, such as arrhythmias, angina, or uncompensated congestive heart failure;
• History of severe depression or attempted suicide or current suicidal ideation;
• Medical or psychiatric conditions that compromise the ability to give informed consent, to comply with the protocol, or to complete the study;
• Uncontrolled seizure disorder;
• Myopathy or clinically significant liver disease;
• Inability, in the opinion of the principal investigator or staff, to comply with protocol requirements for the duration of the study;
• Known hypersensitivity to interferon-beta or other human proteins including albumin;
• Any contraindication for MRI or contrast administration;
• A history of drug abuse in the 6 months prior to screening;
• Treatment with any of the following in the 30 days before day 1: systemic corticosteroids, ACTH, or other investigational drugs;
• Participation in any other study involving investigational or marketed products, concomitantly or within 30 days prior to entry in the study;
• Current participation on other clinical trials;
• Treatment with drugs which might interfere with the evaluation of study drugs during the study protocol such as immunomodulants, immunosuppressives other than interferon beta-1b;
• Likelihood of requiring treatment during the study period with drugs not permitted by the study protocol such as immunomodulants, immunosuppressives other than interferon beta-1b.