Daclizumab phase II trial in relapsing and remitting multiple sclerosis: MRI and clinical results.
OBJECTIVE
Daclizumab is an interleukin 2 receptor alpha chain specific humanized monoclonal antibody that has shown promising therapeutic effects in multiple sclerosis (MS). Daclizumab treatment in patients with relapsing and remitting MS was administered to determine effects on MRI and clinical outcomes.


METHODS
Patients with MS on interferon (IFN) therapy but with continuing relapses and contrast enhancing lesions (CEL) were selected. Patients were evaluated with monthly MRI scans and clinical rating scales starting 3 months prior to treatment and then at 0.5 to 27.5 months during treatment. Daclizumab (1 mg/kg IV) was administered twice in the first month (initiated and administered again in 2 weeks), followed by treatments every 4 weeks. IFN was continued until 5.5 months after daclizumab was initiated. Patients were then placed on daclizumab monotherapy. Patients with recurrent CEL were restarted on IFN with daclizumab therapy at (1.5 mg/kg IV) every 28 days.


RESULTS
Nine patients qualified for inclusion and completed the trial. Efficacy measured by both total CEL and new CEL (p < 0.001), relapses, timed ambulation, Expanded Disability Status Scale, and Neurologic Rating Scale (p < 0.05 to p < 0.01) was observed.


CONCLUSIONS
Daclizumab was effective in reducing contrast enhancing lesions and improving clinical scores in patients with relapsing and remitting multiple sclerosis with active disease not controlled by interferon therapy. These results provide evidence for long-term efficacy and support further clinical development of daclizumab.
Rose
J W
JW
Neurovirology Research Laboratory, Veterans Affairs Salt Lake City Health Care System, Salt Lake City, UT 84148, USA. jrose@genetics.utah.edu
Burns
J B
JB
Bjorklund
J
J
Klein
J
J
Watt
H E
HE
Carlson
N G
NG
D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D002490:Central Nervous System / Q000187:drug effects* / Q000473:pathology* / Q000503:physiopathology; D000077561:Daclizumab; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000009:adverse effects; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007262:Infusions, Intravenous; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000627:therapeutic use; D007372:Interferons / Q000627:therapeutic use; D053645:Interleukin-2 Receptor alpha Subunit / Q000037:antagonists & inhibitors / Q000276:immunology; D008206:Lymphatic Diseases / Q000139:chemically induced / Q000276:immunology; D008279:Magnetic Resonance Imaging; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis* / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D000068576:Interferon beta-1b; D016899:Interferon-beta; D007372:Interferons; D000077561:Daclizumab