To evaluate the efficacy, safety, and tolerability of combination therapy with intramuscular interferon beta-1a and oral doxycycline, a potent inhibitor of matrix metalloproteinases, in patients with relapsing remitting multiple sclerosis (RRMS) having breakthrough disease activity.

Eligible individuals were evaluated monthly for 3 months while taking intramuscular interferon beta-1a, 30 micrograms weekly, then monthly for 4 months while receiving intramuscular interferon beta-1a, 30 micrograms and oral doxycycline, 100 mg daily.

Inclusion Criteria:

• age 18-55
• Relapsing-Remitting Multiple Sclerosis (RRMS)
• Avonex therapy for 6 months prior continuous
• annualized relapse rate >2 during Avonex therapy
• most recent relapse within 60 days of baseline
• entry Expanded Disability Status Scale (EDSS) 1.5-4.5
• one or more gadolinium (Gd+) MRI lesions on a baseline MRI
• no history of immune modulator or immunosuppressant therapy used in combination with Avonex (other then GSC administer for clinical relapses)
• not participating in any other study of ms therapeutics
• Serum neutralizing antibodies (NABs) titer to Avonex <20

Exclusion Criteria:

• Medical or Psychiatric conditions that will affect patients ability to provide informed consent

• inability to undergo MRI

• clinically serious medical conditions or significantly abnormal labs

• no use of these medications or procedures within six months prior to study:

  *monoclonal antibodies,total lymphoid radiation,systemic steroids,cytotoxic or immunosuppressive medications such as mitoxantrone or cyclophosphamide or any other investigational drugs

• Interferon neutralizing antibody titers >20

• no breast feeding or pregnant

• no patients with any systemic illness,psychiatric condition or other disorder that would concern safety of patient to complete procedures of protocol

• abnormal blood test

• clinically significant abnormality on chest x-ray (CXR)

Adverse event data was collected for 7 months