Therapy - immunomodulation - Part IIFriday, September 30, 2005, 15:30 - 17:00
Daclizumab phase I/II trial in relapsing and remitting MS: MRI and clinical resultsJ. Rose, J. Burns, J. Bjorklund, J. Klein, H. Watt, N. Carlson (Salt Lake City, USA)
Objective: A phase I/II trial of Daclizumab (Dac) in patients with relapsing and remitting multiple sclerosis (MS) was performed to determine effects on MRI and clinical parameters.
Backgound: Dac is a humanized monoclonal antibody specific for the Interleukin 2 receptor alpha chain. The antibody has shown promising effects either in combination with interferon or as a monotherapy.
Methods: MS patients on interferon therapy but with continuing relapses and contrast enhancing lesions (CEL) were selected for participation. Patients were evaluated with serial monthly MRI scans and clinical rating scales including Timed Ambulation, EDSS and NRS from 3months prior to Treatment (baseline) and then at 0.5 months to 12.5 months during treatment. Dac (1mg/Kg) was initiated at baseline and administered again in 2 weeks followed by every 4 week treatments according to a protocol developed at NIH. Interferon was continued until 5.5 months after Dac was initiated. Patients without continuing CEL were placed on Dac monotherapy and patients with recurrent CEL were continued on interferon with Dac therapy at (1.5mg/Kg) every 28 days per protocol. The primary outcome measure was the number of new CEL with the other MRI and clinical scores as secondary measures.
Results: Eight patients qualified for treatment with Dac. One patient developed a severe relapse prior to Dac initiation and was discontinued therapy after two treatments. Seven patients continued on treatment. The total CEL and new CEL were compared between pretreatment scans subsequent scans in 3-month intervals. A significant four-fold reduction in total CEL was observed in the second and third intervals. New CEL were reduced four-fold at all three intervals after treatment initiation (p<0.05, p<0.01, p<0.01 respectively). Significant reductions in Timed Ambulation, EDSS and NRS were observed. Two patients were observed to have recurrent new CEL and restarted interferon in addition to an increase in Dac dose. Treatment resulted in a significant decrease in the number of relapses (p<0.005). Discussion: Dac is effective in reducing CEL and in improving clinical scores in relapsing-remitting MS patients with active disease not controlled by interferon alone. Optimal therapy for some patients may require combination treatment with interferon. These results provide further evidence for efficacy and support the development of larger phase II and phase III trials.