Treatment of multiple sclerosis with an anti–interleukin‐2 receptor monoclonal antibody

Abstract

We examined whether treatment with daclizumab, a humanized monoclonal antibody specific for the interleukin-2 receptor alpha chain, was safe and efficacious in relapsing-remitting and secondary progressive multiple sclerosis patients. Nineteen ambulatory patients with clinically active disease were treated for 5 to 25 months. Seventeen patients were not responding to other immunotherapies. Daclizumab was generally well tolerated. Sustained clinical improvement (10 patients) or stabilization (9 patients) was observed. Daclizumab treatment produced significant reduction in magnetic resonance imaging activity.

CNS vasculitis in a patient with MS on daclizumab monotherapy

“…Multiple phase II studies of daclizumab in multiple sclerosis (MS) have reported significant efficacy in reducing contrast-enhancing lesions (CEL) and clinical disability. [1][2][3][4][5][6] Clinical efficacy of daclizumab treatment in MS has been linked to the expansion of CD56 bright NK cells, 3,6,7 which can regulate adaptive immunity by killing activated autologous T cells. 7 We describe a 42-year-old Caucasian woman (ZAP10) with a 5-year history of relapsing-remitting MS (RRMS) who completed a phase II clinical trial of daclizumab monotherapy in MS. 2 METHODS Magnetic resonance images were obtained at the height of the patient's symptoms using described methodology.…”

Monoclonal Antibodies for Multiple Sclerosis Treatment

“…19 IL-2 is secreted by activated lymphocytes and stimulates production of other proinflammatory cytokines while it is also involved in lymphocytic proliferation. Daclizumab was initially approved for the prevention of renal allograft rejection as part of a combination regimen and evidence was progressively accumulated showing that this drug could also be effective in other diseases, such as non-infectious uveitis 30,31 and MS. [32][33][34][35][36][37][38] After demonstrating that the drug could be effective in animal models of the disease, 10 patients diagnosed with RRMS and secondary progressive MS (SPMS) were treated for six months with the combination of intravenous daclizumab (at 1 mg/kg/dose two weeks apart for the first two doses and once every four weeks thereafter for a total of seven infusions) and interferon beta after suboptimal response to the latter alone.…”

Emerging Therapies for Multiple Sclerosis

“…73,74 Two small, open-label (baseline versus treatment) phase II trials of daclizumab in MS have been published. 75,76 Both targeted RR MS patients with inadequate clinical and paraclinical response (i.e., MRI) to IFN-␤ preparations and used daclizumab as add-on therapy at the dose of 1 mg/kg of body weight administered as intravenous monthly infusions.…”

“…75,76 Both the inhibition of brain inflammation by daclizumab and the reappearance of inflammation after cessation of the therapy developed gradually over a period of 2 to 3 months, suggesting that daclizumab induced gradual and prolonged immunomodulatory changes in vivo. A multicenter, randomized, doubleblinded phase II trial of daclizumab (2 mg/kg s.c. every 2 weeks) in 230 RR MS patients with incomplete therapeutic response to IFN-␤ (CHOICE trial) has been recently concluded.…”